Review              95        Strategies for examining dynamic cardiomyoplasty
                                     WP Santamore, B Chiang, MA Kashem and RW Stremel     [Full text pdf 28.1Kb]

Articles            101        Optimization of programming in dynamic cardiomyoplasty: enhancin synchronization
                                      of muscle wrap and ventricular contractions
                                     CM Li, C-Y Luo, J Libman, D Francischelli and RC-J Chiu     [Full text pdf 121Kb]

                        107        Maximum cardiac assistance by Latissimus Dorsi muscle stimulation by optimization
                                      of delays, frequencies and pulse
                                      MA Kashem, WP Santamore, BBY Chiang and AD Slater   [Full text pdf 243Kb]

                         113        Effect of variable and constant-frequency train in Latissimus Dorsi muscle stimulati
                                       MA Kashem, WP Santamore, BBY Chiang and AD Slater     [Full text pdf 1.40Mb]
 

                         117        Use of a mathematical model to identify optimal activation patterns  for skeletal muscle
                                       during cardiomyoplasty
                                       SA Binder-Macleod, J Ding, BC Mandigma and AS Wexler     [Full text pdf 82.9Kb]
 

                          125       Response of old skeletal muscle to 8 weeks of electrical stimulation (should we change
                                       the conventional electrical stimulation protocol for cardiomyoplasty?)
                                       VS Chekanov, M Maternowski, G Zander and P Karakozov      [Full text pdf 70.7Kb]
 
 
 
 

MYOLOGY NEWS   131    Abstracts of the International Workshop "Cardiac-Bio-Assist", Paris

October 4-5, 1999
 
 
 

Strategies for Examining Dynamic Cardiomyoplasty

William P. Santamore, Ben Chiang⁽¹⁾, M. Abul Kashem and Richard W. Stremel⁽²⁾

Cardiology Section, Temple University School of Medicine, Philadelphia, PA, (1) Department of Surgery and (2) Department of Physiology and Biophysics, University of Louisville, Louisville, KY

Typically, in cardiomyoplasty (CMP) experimental studies, a new intervention is examined only after 3 months of latissimus dorsi muscle (LDM) training. We believe that this has been a major mistake. In our approach, we sequentially measured the effects of LDM stimulation in CMP. Our experimental results showed that the effects of LDM stimulation were variable, and that this variability was present shortly after surgery.

Accordingly, we tried a number of approaches (LDM training before surgery, LDM stimulation early after surgery, wrapping the LDM in a Gore-Tex membrane, etc.), all of which failed. Our last approach was to try vascular delay, and to evaluate LV function in a terminal study 2 weeks after CMP surgery. Preconditioning the LDM with vascular delay resulted in improving performance of the LDM with consistent increases in LV hemodynamics.

Key words: review, cardiomyoplasty, latissimus dorsi muscle.

Basic Appl. Myol. 9 (3): 95-99, 1999

Address correspondence to:

William P. Santamore, PhD, Cardiology Section, Temple University School of Medicine, Philadelphia, PA, phone (215) 707 4239, fax (215) 707 5737, Email wsantamo@unix.temple.edu.

Optimization of Programming in Dynamic Cardiomyoplasty: Enhancing Synchronization of Muscle Wrap and Ventricular Contractions

Carlos M. Li, Chwan-Yau Luo⁽¹⁾, Jamie Libman, David Francischelli⁽²⁾ and Ray C.-J. Chiu

Division of Cardiothoracic Surgery, McGill University, Montreal, Canada, (1) Division of Cardiothoracic Surgery, National Cheng-Kung University, Taiwan and (2) Division of Cardiac Assist Research, Medtronic, Inc., Minneapolis, USA

Introduction: To obtain maximal benefit from dynamic cardiomyoplasty, stimulation parameters of the cardiomyostimulator need to be optimized. The two components for optimization include the muscle channel and the synchronization channel. This study looks at the issue of timing muscle contraction to ventricular contraction. Specifically, we compared 2 methods of obtaining optimal synchronization delay, 1) using the current clinical method of echocardiographic assessment of mitral valve closure with onset of burst stimulation, and 2) simultaneous open measurements of muscle and ventricular pressure generation.

Methods: A left latissimus dorsi (LD) cardiomyoplasty was performed in 4 dogs. Using a previously established protocol for muscle transformation, the LD muscle was continuously stimulated over 4 weeks with an epineural cuff and the Itrel II myostimulator. After the training period, a Cardiomyostimulator (model #4710) was used for assist, and optimal synchronization timing was assessed. First, m-mode echocardiography was used to optimize timing of burst stimulation spikes with closure of mitral valve. Secondly, a median sternotomy was performed, and Millar pressure measuring catheters were inserted into the left ventricle (LV) and the LD muscle. Optimization of synchronization delay was again assessed with simultaneous measurement of ventricular pressure and the LD intramuscular pressure. Optimal delay for the open method was determined by best overlap of peak pressures of muscle and ventricle. Comparison was made between optimal synchronization obtained by echocardiography and the open method.

Results: All dogs survived the surgery without complication, and underwent the full period of muscle transformation, followed by optimization studies. One dog (#4) appeared to be in heart failure during the optimization study. In all dogs, optimal stimulation delay as measured by the catheter technique was shorter than that determined through m-mode echocardiography. Of note, 1) peak pressure (PMax) generation of muscle occurred 70-100 msec after LV PMax in 3 of 4 dogs (in one dog with failure, muscle PMax occurred 10 msec after LV PMax), and 2) in 3 of 4 dogs, duration of muscle contraction exceeded ventricular contraction, making diastolic impairment difficult to avoid.

Conclusions: From our results, we conclude that optimal synchronization delay occurs at a shorter delay than as determined by the echocardiographic method. In chronically stimulated muscle, Pmax occurs later than LV Pmax, and duration of muscle contraction is longer than LV contraction. A dilemma exists for optimizing timing of muscle contraction where maximal systolic assist is achieved with minimal diastolic interference. Because peak LV wall stress occurs early in systole, and most LV filling occurs early in diastole, we suggest that muscle contraction should occur as early as possible even at the cost of some late diastolic interference.

Key words: cardiomyoplasty, biomechanical assist, optimization of stimulation parameters in dynamic cardiomyoplasty.

Basic Appl. Myol. 9 (3): 101-106, 1999

Address correspondence to:

Carlos M. Li, VA Hospital (CT-111), 3495 Bailey Ave., Buffalo, NY 14215, phone (716) 862 6075, fax (716) 862 6076, Email carlosli@acsu.buffalo.edu.

Maximum Cardiac Assistance by Latissimus Dorsi Muscle Stimulation by Optimization of Delays, Frequencies and Pulses

M. Abul Kashem, William P. Santamore, Benjamin B.Y. Chiang⁽¹⁾ and A. David Slater⁽¹⁾

Division of Cardiovascular Research, Temple University HSC, Philadelphia, USA and (1) Jewish Cardiovascular Research Institute, University of Louisville, Kentucky, USA

To determine optimal parameters for vascular delayed latissimus dorsi muscle (LDM) stimulation, we hypothesized that appropriate pattern of synchronization delay, frequency and number of pulses per burst would improve benefits in cardiomyoplasty. In six dogs, vascular delay of left LDM and induction of myocardial dysfunction were performed 2 weeks before standard cardiomyoplasty. LDM was progressively conditioned for 9 weeks. The interventions were divided into 3 groups of Delay (25, 50, 75, 100 ms; between QRS and muscle stimulation), Frequency (20, 30, 40, 50, 60 Hz; each examined at 6 pulses), and number of Pulses (4, 6, 8, 10 burst-pulses at 50 Hz). With LDM stimulation, pressures and flows were significantly increased in all except 100 ms delay group. 25 ms synchronization delay at 50 Hz and 6-10 pulses, LDM stimulation caused the highest increases in peak aortic pressure (18.3±1.4 mmHg), peak left ventricular pressure (22.4±2.4 mmHg), LV +dP/dt (276.3±166.4 mmHg/sec), stroke volume (8.0±3.3 ml), stroke work (13.0±2.8 gm× m), stroke power (135.0±17.8 gm× m/sec), and peak aortic flow (4.5±0.8 l/min) when assisted beats were compared to unassisted beats. At prolonged synchronization delay and highest burst pulses, the diastolic properties are compromised and at a relative shorter delay, higher frequency and bursts pulses showed maximum systolic improvements.

Key words: cardiomyoplasty, chronic stimulation, delay, frequency, pulses.

Basic Appl. Myol. 9 (3): 107-112, 1999

Address correspondence to:

M. Abul Kashem, MD, Division of Cardiovascular Research, Temple University HSC, 3420 North Broad St., MRB, Rm. #800A, Philadelphia, PA 19140, USA, phone 215 707 2006, fax 215 707 5737, Email mkashem@unix.temple.edu

Effect of Variable and Constant-Frequency Train in Latissimus Dorsi Muscle Stimulation
M. Abul Kashem, William P. Santamore, Benjamin B.Y. Chiang⁽¹⁾ and A. David Slater⁽¹⁾

Division of Cardiovascular Research, Temple University HSC, Philadelphia, USA and (1) Jewish Cardiovascular Research Institute, University of Louisville, Kentucky, USA

We tested the hypothesis that increased hemodynamic augmentation and mechanical performance could be achieved by using a variable frequency pulse train (VFT) to stimulate the latissimus dorsi muscle (LDM), compared to the conventional constant frequency pulse train (CFT) used in cardiomyoplasty. In dogs (n = 6), a vascular delayed LDM was wrapped posteriorly around the heart. LDM was conditioned for 9 weeks using implantable cardiomyostimulator. The hemodynamic parameters were recorded using VFT and CFT LDM stimulation with 7, 6 and 5-pulses, and compared to non-stimulated beats (NS). Both CFT and VFT LDM stimulation significantly increased pressures, flow, and stroke work. However, compared to CFT, VFT stimulation resulted in significant stroke power (20.6%), maximum peak aortic flow (20.1%) and maximum LV dP/dt (14.6%). These results suggested that stimulation of the LDM using VFTs is potentially greater beneficiary for application in cardiomyoplasty.

Key words: cardiomyoplasty, variable frequency, constant frequency, latissimus dorsi muscle.
Basic Appl. Myol. 9 (3): 113-116, 1999

Address correspondence to:

M. Abul Kashem, MD, Division of Cardiovascular Research, Temple University HSC, 3420 North Broad St., MRB, Rm. #800A, Philadelphia, PA 19140, USA, phone 215 707 2006, fax 215 707 5737, Emailmkashem@unix.temple.edu.

Use of a Mathematical Model to Identify Optimal Activation Patterns for Skeletal Muscle During
Cardiomyoplasty

Stuart A. Binder-Macleod, Jun Ding⁽¹⁾, Beverlyn C. Mandigma and Anthony S. Wexler⁽²⁾

Department of Physical Therapy, (1) Interdisciplinary Graduate Program in Biomechanics & Movement Science and (2) Department of Mechanical Engineering, University of Delaware, Newark, Delaware

In cardiomyoplasty the latissimus dorsi muscle is electrical stimulated in synchrony with the heartbeat to enhance ventricular function. Current clinical stimulation protocols use 6-pulse trains with pulses within the train equally spaced by 33.3 ms (CFTs). Recent studies, however, have shown that variable-frequency trains (VFTs), which take advantage of the catchlike property of skeletal muscle, can produce more force than traditionally used CFTs. The purpose of this study was to systematically explore the effects of the number and distribution of pulses within the train on muscle contractile output. With the aid of a mathematical model that we developed, a new stimulation pattern was identified that produced the greatest impulse per pulse for fatigued muscles. Experiments were conducted to compare muscle contractile performance by the new stimulation pattern (DFTs) with the traditionally used CFTs and with previously studied VFTs. The 6-pulse DFTs produced a 49% augmentation over the traditionally used 6-pulse CFT and a 23% augmentation over the 6-pulse VFT. DFTs thus show potential for improving muscle contractile performance in assisting cardiac function. This study illustrates the potential for using mathematical models to predict skeletal muscle forces and help to identify the optimal pattern of activation for each patient.

Key words: variable-frequency train, doublet stimulation, functional electrical stimulation, force optimization.
Basic Appl. Myol. 9 (3): 117-123, 1999

Address correspondence to:

Stuart A. Binder-Macleod, 315 McKinly Laboratory, University of Delaware, Newark, DE 19716, phone (302) 831 8046, fax (302) 831 4234, Email sbinder@udel.edu.

Response of Old Skeletal Muscle to 8 Weeks of Electrical Stimulation (Should We Change the Conventional Electrical Stimulation Protocol for Cardiomyoplasty?)

Valeri S. Chekanov, Michelle Maternowski, Gary Zander and Pavel Karakozov⁽¹⁾

Milwaukee Heart Institute, Wisconsin, USA and (1) Vakhidov Research Center of Surgery, Tashkent, Uzbekistan

We hypothesized that the conditioned muscles of elderly organisms have different responses to electrical stimulation than that of young adult organisms. One-year-old sheep and eight-year-old elderly sheep were used for this investigation.

Results. The latissimus dorsi muscle (LDM) of old sheep has less fatigue resistance than LDM of younger animals. In all animals, LDH-5 fractions decreased after eight weeks ES; LDH-1+2 fractions increased. After a two week delay, the data completely returned to baseline values in old adult animals. The percent area occupied by mitochondria in old sheep was less after ES than in younger animals. In all animals, the mitochondrial area increased after ES and reverted to baseline values after the delay. The number of nuclei and fibers considerably increased after ES.

Conclusions. Young skeletal muscle obtains more plasticity than adult muscle during ES. Elderly skeletal muscle does not convert to a fatigue resistant state as completely as adult skeletal muscle during a conventional eight week ES protocol. It is necessary to change and prolong the ES protocol for elderly patients.

Key words: ageing, dynamic cardyomyoplasty, electrical stimulation protocol, muscle, sheep.
Basic Appl. Myol. 9 (2): 125-130, 1999

Address correspondence to:

Valeri S. Chekanov, M.D., Ph.D., Sinai Samaritan Medical Center, P.O. Box 342, Rm. W419, Milwaukee, WI USA 53201-0342, phone 414 219 7899, fax 414 219 6266.

Workshop on Cardiac-Bio-Assist

Chairmen

Alain Carpentier and Juan C. Chachques

Department of Cardiovascular Surgery
and Laboratory of the Study of Cardiac Prostheses

Broussais Hospital - University of Paris

Paris (France), October 4-5, 1999

PROGRAM

October 4, 1999
9.00 Introduction A. Carpentier

9.10  Session 1: Basic science. New electrostimulation protocols.
         Chairmen: S. Salmons (UK), U. Carraro (Italy)

Break

11.00 Session 2: Cardiomyoplasty: clinical results.
          Chairmen: A. Carpentier (Paris), T. Mesana (Marseille)
Lunch

14.30 Research laboratory activitie
          Presentation of a new pulse generator for cardiomyoplasty (in vivo model).

October 5, 1999

9.00   Session 3: Aortomyoplasty. Skeletal muscle ventricles.
Chairmen: N. Guldner (Germany), R. Lorusso (Italy)

Break

11.00  Session 4: New developments in cardiac bioassist. Cellular cardiomyoplasty.
          Chairmen: J.C. Chachques (Paris), V. Chekanov (USA)

Lunch

14.30  Research laboratory activities: Cellular biology. Equipment and procedures for cell culture.
           Closing remarks

Oral Presentations

October 4, 1999

9.10    am Basic Science
          Chairmen: S. Salmons, U. Carraro

           S Salmons, EB Woo, AT Tang, TL Hooper, JC Jarvis.
           British Heart Foundation, Liverpool, U.K..

Cardiac assistance from skeletal muscle: preserving the graft.

U Carraro, M Barbiero, G Docali, A Cotogni, D Casarotto, C Muneretto.
Padova, Italy

Demand dynamic cardiomyoplasty: mechanographic analyses in patients.

R Scelsi, L Scelsi, AH El Messlemani, U Carraro. Pavia and Padova, Italy.

Morphological findings of LDM graft after short and long-term cardiomyoplasty.

NW Guldner, P Klapproth, M Grossherr, M Stephan, E Rumpel, R Noel, HH Sievers.

Lübeck, Germany.

Clenbuterol supported dynamic training of SM ventricles against systemic load.

V Chekanov, F Brum, J Arzuaga, 0 Fiandra, V Melamed.
Milwaukee, USA; Uruguay.

A new cardiomyostimulator with new functions for cardiac bioassist.

Break

11.00 am Cardiomyoplasty

Chairmen: A. Carpentier, T. Mesana

A Carpentier, JC Chachques, JP Marino, A Berrebi, P Meimoun.

Broussais Hospital, Paris, France.

Dynamic cardiomyoplasty: present and future. Video: mini invasive CMP.

Y Glock, D Roux, P Concina, M Salvador-Mazencq, P Massabuauet, G Foumial.

Toulouse, France.

Dynamic cardiomyoplasty: clinical experience from Toulouse.

T Mesana, JR Monties, et al.

Marseille, France.

Cardiomyoplasty and aortomyoplasty: experimental and clinical experience.

V Bors, R Dorent, G Jondeau, A Delcourt, I Gandjbakhch.

La Pitié Hospital, Paris.

Dynamic cardiomyoplasty: 7 years experience at La Pitié Hospital.

C Werling, C Jungheim, W Saggau.

Ludwigshafen, Germany.

Dynamic cardiomyoplasty: long-term results after seven years.

Dar-Ching Wu.

Singapore.

Cardiomyoplasty as an option in the treatment of heart failure - the Singapore experience.

N D’Attellis, D Bensasson, JP Kieffer, D Meleard, P Guibourt, D Tournay, MH A Armengaud.

Broussais Hospital, Paris, France.

Anesthesia and intensive care management of patients undergoing cardiomyoplasty.

October 5, 1999

9.00 Aortomyoplasty, Skeletal Muscle Ventricles.

Chairmen: N. Guldner, R. Lorusso

FA Baciewiez, GA Thomas, KA Greer, RL Hammond, LW Stephenson.

Detroit, USA.

Skeletal muscle ventricles in circulation: progress towards clinical application.

JC Trainini.

Buenos Aires, Argentine.

Dynamic cardiomyoplasty and aortomyoplasty.

NW Guldner, P Klapproth, M Grossherr, M Stephan, HH Sievers.

Lübeck, Germany.

Biomechanical hearts in descending aorta position - Video presentation.

G Bolotin, R Lorusso, T Wolf, R Sbofti, FH van der Veen, JJ Schreuder, M Smink, Y Rubin, G Uretzky.

Haifa, Israel - Brescia, Italy - Maastricht, NL.

Comparative study between aortomyoplasty and intra-aortic balloon counterpulsation.

E Monnet, EC Orton, G Child, D Getzy, G Jacobs, L Metelman.

Colorado State University, USA.

Neuromuscular function of the latissimus dorsi muscle in goats after cardiomyoplasty.

V Chekanov, M Maternowski, V Nikolaychik.

Milwaukee, USA.

Influence of electrical stimulation on subtotally mobilized latissimus dorsi muscle.

JC Chachques, T Lavergne, JF Toussaint, P Kolar, N Lila, JN Fabiani, A Carpentier.

Broussais Hospital, Paris, France.

Cardiac-bio-assist: a true alternative?

Break

1l.00 am New developments.

Chairmen: J.C. Chachques, V. Chekanov

R Lorusso, V Borghetti, E Tulumello, F Bianchetti, A Marchini.

Brescia, Italy.

Association of cardiomyoplasty and implantable defibrillator: the optimal binomium?

V Chekanov, M Matemowski, P Karakozov.

Milwaukee, USA.

Skeletal muscle age must be considered prior to use in cardiac assist.

E Monnet, EC Orton.

Colorado State University, USA.

Myocardial oxygen consumption and cardiac efficiency after dynamic cardiomyoplasty in dogs with adriamycin induced cardiomyopathy.

G Zakine, JC Chachques, E Martinod, P Fomes, M Sapoval, F Chaussende, D Barritault, J Plouet, A Carpentier.

Broussais Hospital, Paris.

Locally administered growth factors improve latissimus dorsi muscle vascularisation and trophicity following cardiomyoplasty.

C Rajnoch, N Borenstein, JC Chachques, M Shen, N Goussef, JF Toussaint, A Carpentier.

Broussais Hospital, Paris, France.

Cellular cardiomyoplasty: technical approach and experimental models.

A Berrebi, JC Chachques, C Rajnoch, JN Fabiani, A Carpentier.

Broussais Hospital, Paris, France.

Improvement of ventricular function following myoblast implantation.

CARDIAC ASSISTANCE FROM SKELETAL MUSCLE: PRESERVING THE GRAFT

S. Salmons, C. Woo1, A.T.M. Tang¹, T.L. Hooper¹
and J.C. Jarvis

British Heart Foundation Skeletal Muscle Assist Group, Department of Human Anatomy and Cell Biology, University of Liverpool, L69 3GE and (1) Department of Cardiothoracic Surgery, Wythenshawe Hospital, Southmoor Road, Manchester - A123 9LT, U.K.

Deterioration of the latissimus dorsi (LD) muscle wrap after cardiomyoplasty has been demonstrated in both animals and man. It is probably the consequence of several factors, of which the most important is the combination of ischaemia with the increased metabolic demands imposed by electrical stimulation [1]. Delaying simulation for 2-3 weeks after reconfiguring the muscle is not entirely effective and delays the benefit that the patient could otherwise derive from the operation.

Our recent experimental studies have confirmed the presence in the LD muscle of anastomotic channels connecting the vascular trees of the thoracodorsal artery and the perforating arteries [2]. The perforating arteries have to be divided during mobilization of the graft, but the distal region of the muscle is still perfused by the thoracodorsal artery via the arterial anastomoses. Stimulation of the muscle prior to mobilization (prestimulation) appeared to enhance flow through these anastomotic channels, since it abolished the characteristic proximodistal gradients in flow. Associated with these changes, there was an increased resistance to surgical intervention. When untreated muscles were lifted, handled, cooled and replaced at reduced tension, the usual signs of distal ischaemia were observed, and these had not recovered to a significant extent 5 days later. When prestimulated muscles were subjected to the same manipulations there was a smaller reduction in blood flow, the distal region was no longer selectively affected, and any initial ischaemia was completely reversed by 5 days [3, 4]. These findings make a substantial case for stimulating the LD muscle before raising it as a graft, as this can both improve the viability of the muscle and enable cardiac assistance to be delivered to the patient at an earlier postoperative stage.

We are currently seeking to establish formally that these more favourable patterns of blood flow are associated with an increased resistance to stimulation-induced damage. We are also comparing the effects of prestimulation with those of the more invasive true vascular delay procedure, in which the collateral vessels are divided but the LD muscle is left in situ for 10 d before elevating it as a graft.

Progress in these studies will be reported.

Improved preparation of the LD muscle prior to mobilization, in combination with new stimulation protocols, should yield a graft of greater viability and working capacity.

We thank the British Heart Foundation for support, including a Junior Fellowship (E.B.-C. Woo).

References

1. El Oakley RM, et al. Journal of Heart and Lung Transplantation 1995; 14: 359-365.

2. Salmons S, et al. Journal of Anatomy 1998; 193: 93-104.

3. Tang ATM, Jarvis JC, Hooper TL, Salmons S. Annals of Thoracic Surgery 1999; 67, in press.

4. Tang ATM, Jarvis JC, Hooper TL, Salmons S. Cardiovascular Research 1998; 40: 131-137.
 
 

DEMAND DYNAMIC CARDIOMYOPLASTY:
TUNING OF FAST-TO-SLOW HUMAN LD WRAP TRANSFORMATION BY ACTIVITY-REST STIMULATION AND MECHANOGRAPHIC ANALYSES IN ITALIAN SUBJECTS

U. Carraro, M. Barbiero¹, G. Docali¹, A. Cotogni¹, D. Casarotto², C. Muneretto³

C.N.R. Unit for Muscle Biology and Physiopathology and Department of Biomedical Sciences, University of Padova; (1) Division of Cardiology, Legnago General Hospital (Verona); (2) Cardiovascular Surgery, University of Padova; (3) Cardiovascular Surgery, University of Brescia, Italy

In Dynamic Cardiomyoplasty (DC) the standard clinical protocol for Latissimus Dorsi (LD) stimulation produces a highly fatigue-resistant muscle but results in undesirable dynamic characteristics. We developed a noninvasive diagnostic tool (LD wrap "mechanogram") to determine LD contractile characteristics by a standard polygraph previously used for monitoring cardiac apical motion. Based on experimental results obtained with intermittent stimulation in animals [1], and on clinical results of the heart/wrap synchronization obtained with LD wrap mechanogram [2, 3], we implemented in six patients a light regime of LD activity-rest stimulation (demand stimulation).

Dynamic cardiomyoplasty surgery is according to the Carpentier procedure. LD wrap mechanogram is performed as we previously described [2]. By mechanogram and echo Doppler imaging we determine: 1) optimal synchronization delay between the contraction of the LD wrap and cardiac events; and 2) the dynamic contractile characteristics of the LD flap based on tetanic fusion frequency (TFF).

The extent of fast-to-slow transformation of contractile characteristics of the LD flap is shown to be related to the stimulation protocols used, and reversed after months of daily stimulation by an activity-rest protocol (TFF of 12±6 Hz after standard clinical protocol, and 33±7, p < 0.0001 with demand stimulation). After Dernand Dynamic Cardiomyoplasty (DDC) in six patients, there are no deaths. Quality of life is substantially improved with significant reduction of heart failure symptoms (NYAH class: pre-op 3.0, post-DDC 1.5, p < 0.0001), and exercise capacity is increased or at least not significantly decreased (V02 max: pre-op 12.0±1.3 v.s. 14.8±4.4 post-DDC, p = 0.14).

In conclusion, the results suggest that activity-rest stimulation could offer long-term the benefits of Dynamic Cardiomyoplasty to patients with advanced heart failure.

Supported by Italian Ministero per l’Università e la Ricerca Scientifíca e Tecnologica (M.U.R.S.T.) "Cofinanziamento 98 - Programmi di Rilevante Interesse Nazionale: Trial Italiano di Cardiomioplastica Dinamica a Domanda (TiCCD)".

References

1. Arpesella G, Carraro U, Mikus PM, Dozza F, Lombardi P, Marinelli G, Zampieri S, El Messlemani AH, Rossini K, Pierangeli A: Activity-rest stimulation of Latissimus Dorsi for Cardiomyoplasty: 1-year results in sheep. Ann Thorac Surg. 1998; 66: 1983-1990.

2. Carraro U, Barbiero M, Docali G, Brunazzi C, Lorusso R, Rinaldi M, Gazzoli F, Vigano M, Gerometta PS, Barbier P, Biglioli P, Casarotto D, Muneretto C: Dynamic Cardiomyoplasty. Long-term viabilità demonstrated by non-invasive on-line analysis of dynamic contractile characteristics of human LD flap in Italian subjects. J Cardiovasc Diagn P. 1998; 15: 115-125.

3. Carraro U, Docali G, Barbiero M, Brunazzi C, Gealow K, Casarotto D, Muneretto C: Demand Dynamic Cardiomyoplasty: improved clinical benefits by non-invasive monitoring of LD flap and long-term tuning of its dynamic contractile characteristics by activity-rest regime. Basic Appl Myol. 1998; 8: 11-15.
 
 

MORPHOLOGICAL FINDINGS OF LATISSIMUS DORSI MUSCLE GRAFT AFTER SHORT AND LONG-TERM DYNAMIC CARDIOMYOPLASTY. REVIEW OF PUBLISHED AUTOPSIES AND A NEW POST-MORTEM STUDY OF AN UNCONDITIONED GRAFT

Roberto Scelsi, Laura Scelsi¹, Abdul Hassib El Messlemani² and Ugo Carraro²

Departments of Human Pathology and (1) Cardiology, University of Pavia and (2) Department of Biomedical Sciences, University of Padova, Italy

Morphological findings of the Latissimus Dorsi Muscle (LDM) in 12 published post-mortem cases surviving for 1 month to 8 years in which the LDM graft was used for Dynamic Cardiomyoplasty (CD), are reported. The patients suffered from end-stage heart failure due to dilated and ischaemic cardiomyopathy or valvular pathology. Moreover the analysis of muscle fibres and microvasculature of an unconditioned LDM from a patient suddenly died one month after CD is reported. One month after CD, post-operative changes as interstitial edema and extensive fibrous and fatty infiltration were seen. The epicardial-muscle interface showed signs of the recent surgery with inflammation and fibrinous adhesions. Numerical reduction and necrosis of capillaries was detected mainly in the distal part of the LDM graft. At 5 and 7 months after CD, no evident muscular changes were seen and incomplete fibre type transformation was evident, with the fraction of type 1 fiber in the LDM wrap ranging from 55% to 60%. In the patient died at 18 months after operation, the electric stimulation induced an almost complete transformation of fibres into type 1 fatigue-resistant fibres. In the patient died at 15 months after CD, fibre degeneration and atrophy was confined in the region near the electrodes. Four cases were studied after 2 years CD. The LDM graft structure was preserved and fibrous and fatty infiltration of muscle was seen mainly in the distal muscle. In one case, LDM fibre atrophy with internal nuclei was present at the periphery of muscle and fibre degeneration and moderate fibrosis was confined in the region between the electrodes. In another case, the study of LDM vasculature showed a number of arteries about four times larger than in stimulated LDM in the unstimulated one. In the long-term CD (5-8 years following CD), the LDM appeared to be thinner compared with that observed at the time of the surgery, and it showed some changes as fibre atrophy and internal nuclei. In all cases variable fatty infiltration and connective tissue ingrowth was observed. These changes were not related to the distance from the electrodes. In the checked case, transformation of fibre types of LDM was consistent, with marked increase of type 1 fibres. The authors conclude that surgical differentiation of LDM mainly supporting the distal part of muscle may cause ischemic muscular changes, and that the long-term electric stimulation appeared not to be the direct cause of muscular changes, but may be occasionally occurred in the region near to the inserction of the electrodes.
 
 

CLENBUTEROL SUPPORTED DYNAMIC TRAINING OF SKELETAL MUSCLE VENTRICLES AGAINST SYSTEMIC LOAD - A KEY FOR POWERFUL CIRCULATORY ASSIST?

N.W. Guldner, P. Klapproth, M. Grossherr¹, M. Stephan, E. Rumpel, R. Noel and H.-H. Sievers

Clinic of Cardiac Surgery and (1) Clinic of Anaesthesiology, Medical University of Lubeck, Germany

Desirable properties of skeletal muscle for cardiac assistance include fatigue resistance and powerful mechanical performance. Currently clinical application of skeletal muscle was limited due to profound power loss after electrical conditioning. This study investigates a threefold approach for chronic conditioning of skeletal muscle ventricles (SMVs) by electrical transformation, dynamic training against systemic load as well as pharmacological support with clenbuterol.

In 10 adult male goats SMVs were constructed from latissimus dorsi muscle, wrapped around a barrel-shaped intrathoracic training device with windkessel characteristics. SMVs were stimulated electrically and trained dynamically shifting volume into two compliant side bladders against a simulated systemic load. Group I were controls (n = 5) and group II (n = 5) were supported with clenbuterol (150 mg/3 times a week, orally). SMV dynamics were acquired weekly over 5-8 months: peak pressure (p MAX), stroke volume (SV), volume displacement per minute (VD), stroke work per day (SW/d), maximal rate of pressure generation +dp/dt MAX and decay - dp/dt MAX. In group I after 149.5±3.1 days (n = 4), data were: p MAX = 71±5 mmHg, SV = 3.2±1.3 ml, VD = 61.8±4.5 ml/min, SW/d = 0.8±0.4 kJ, +dp/dt MAX = 64.4±15.1 mmHg/s, -dp/dt MAX = 155.8±36.8 mmHg/s. These parameters were significantly improved (p < 0.007) in the clenbuterol treated group II after a training period of 151±3 days: with increased p_max = 196±20 mmHg, SV = 23.3±6.8 ml, VD = 488±186 ml/min, SW/d = 9.1±2.4 kJ, +dP/dt_max = 1134±298 mmHg/s, -dP/dt_max = 1028±102 mmHg/s. In two SMVs of group II VD increased to 1090 and 1235 ml/min after 202 and 246 days of training. At termination myosin heavy chains were totally transformed into MHCI in all SMVs.

In conclusion, this clenbuterol supported dynamic training provides powerful SMVs that may have important clinical implications for the treatment of end-stage heart failure by muscular blood pumps.
 
 

LD-PACE II

A NEW CARDIOMYOSTIMULATOR
WITH NEW FUNCTIONS FOR CARDIAC BIOASSIST

V. Chekanov, F. Brum¹, J. Arzuaga¹, O. Fiandra¹
and V. Melamed²

Heart Care Associates, Milwaukee, WI,
(1) CCC del Uruguay SA, Montevideo, Uruguay
and (2) Illini Group, Chicago, IL

LD-PACE II, a new cardiomyostimulator was manufactured by CCC del Uruguay with the support of the Illini Group, Chicago, Illinois. The LD-PACE II was designed for use in cardiomyoplasty, aortomyoplasty, and skeletal muscle ventricle. In the case of bradycardia or atrio-ventricular blockage, it will act as a pacemaker with a basic pacing rate between 36 and 120 BPM, amplitude of pacing pulse in the range of 0.7-5.5 V, and a width of pacing pulse in the range of 0.122-1.5 ms. Its ventricular sense amplified sensitivity for cardiomyoplasty is programmable from 1-8 mV. It has a blanking period (39-62.5 ms) when all sensing is inhibited. In order to prevent the stimulator from inappropriately sensing events, there is a ventricular refractory period (195-480 ms). Hysteresis (0-20%) allows the patients heart rate to temporarily fall below the lower rate without inducing immediate pacing.

Synchronization delay (2-350 ms) obtains the optimal time of muscle contraction. Adaptive delay allows the automatic change in the delay time with a change of heart rate. The cardiosynchronization ratio is programmed from 1:1-1:16. Muscle output is inhibited if the heart rate is higher than the synchronization upper rate (120-226 BPM). The adaptive ratio allows for the automatic change of the cardiosynchronization ratio with an increase in heart rate. The work- rest regimen allows for the delivery of a muscle stimulus (0-120 min) and then the inhibition of it (0-120 min) according to programmed values. The response in the presence of a PVC inhibits the delivery of a muscle stimulus. Using the magnet device, it is possible to slow down (1:8-1:16) the synchronization ratio during the night, and then to restore it back to a base ratio (1:2-1:4) in the morning.

Delivery of a muscle pulse train is triggered by paced or sensed ventricular events. Characteristics of the pulse train are changes in pulse amplitude (0.44-0.75 V), pulse width (0.061-0.076 ms), pulses per burst (1-8), and pulse interval (15.6-132.8 ms). The adaptive pulse train duration will automatically decrease the train duration with an increase in heart rate and inhibit muscle contraction during the diastolic phase.

All parameters specified as programmable can be done in a noninvasive manner using a programming interface wand connected to a computer using the Windows 95/98 environment.
 
 

DYNAMIC CARDIOMYOPLASTY:
PRESENT AND FUTURE

A. Carpentier, J.C. Chachques, J.P. Marino, A. Berrebi
and P. Meimoun

Department of Cardiovascular Surgery, Broussais Hospital, Paris, France

The management of patients with end stage heart failure (HF) is a daily challenge in cardiac surgery. Cardiac transplantation and mechanical assist devices do not cover all the needs. Since 1985, cardiomyoplasty has been used in our institution in 111 patients. We report the longest follow-up of this technique and the improvements introduced in recent years.

Between 1985 and 1999, 111 patients aged 15 to 72 years (mean 51 years) were operated on; 85 were in NYA class III and 26 in class IV. Ejection fraction (EF) averaged 17%, EDLV volume 178±31 ml/m2. The cause of HF was ischemia in 59 patients, dilated cardiomyopathy in 45 patients and ventricular tumor in 7 patients. Associated pathology (pulmonary hypertension, diabetes, etc.) was present in 60%. The technique has evolved from "open fixation" (58 patients), to "non-suture wrapping" (40 patients), to "mini-invasive technique" (13 patients). Two-stage operations in high risk patients with mitral valve insufficiency or severe arrhythmia were performed in 6 patients. Associated procedures were necessary in 24 patients (CABG = I4, valve = 10).

Hospital mortality was 53% between 1985-1987, 13% between 1988-1997, and 8% since the introduction of mini-invasive techniques. Actuarial survival at 10 years was 70% for preop class III patients and 28% for class IV patients. Average NYHA class was 3.3 preop and 1.4 postop. Nine patients required transplantation. Hemodynamic investigations in the survivors showed significant improvement in EF (21% to 31%) and cardiac index (1.9 to 2.8 L/mn/m2).

In conclusion, Cardiomyoplasty has been associated with better results due to technical improvements, the most significant being mini-invasive techniques, the latest the use of growth factors to enhance muscle vascularisation. Risk factors have been identified resulting in more precise indications, a lower hospital mortality and a wider use of this operation.
 
 

DYNAMIC CARDIOMYOPLASTY:
CLINICAL EXPERIENCE FROM TOULOUSE

Y. Glock, D. Roux, P. Concina, M. Salvador-Mazencq,
P. Massabuau and G. Fournial

Rangueil Hospital, Toulouse, France

From 1993 to january 1999 we have carried out 20 cardiomyoplasty (CMP) procedures in 3 women and 17 men, with an average age of 55.7 years old (44-74 years).

Most of the patients selected for cardiomyoplasty presented contraindications for heart transplantation. Half of the patients could not be grafted due to their age (9 > 60 years old) or due to a contra-indication (1 toxic cardiopathy due to chemotherapy). On the contrary, 2 patients underwent a CMP after having been selected from the waiting list. The etiology of myocardial disease was as follows: 12 had idiopathic dilated cardiomyopathy, 7 ischemic cardiomyopathy and 1 a toxic cardiopathy. The average pre-operative NYHA functional class was 3.2 (16 in class III and 4 in class IV). The average pre-operative ejection fraction was 23.5% (19 to 29%). No patient presented atrial fibrillation. One patient had mitral insufficiency grade 3/4, requiring mitral valve repair before CMP. Two patients underwent CABGs prior to CMP, and in one case an abdominal aortic aneurysm was surgically repair before CMP.

In all patients cardiomyoplasty was performed through a sternotomy. In 4 patients an additional surgical procedure was associated: mitral annuplasty in 1 case, and coronary artery bypass graft (venous) in 3 patients (performed in beating hearts). In I case an IABP was used in the postoperative period.

There were no postoperative bleeding and no perioperative mortality. The in-hospital mortality (30 days) was 25% (5 cases). The causes of in-hospital mortality were: i) Chronic respiratory insufficiency with no possibility to wean from the ventilator at 1 month; ii) Pulmonary embolism on the 8th day; iii) Sudden ventricular fibrillation during the second postoperative week; iv) Respiratory failure due to axonal neuropathy during the ICU stay.

Long term follow-up: Fifteen patients underwent postoperative latissimus dorsi muscle electrostimulation, according to the classic protocol. Follow-up was 100%. The average time of follow-up was 34.7 months (3 to 72 months). At long-term 2 patients died due to: i) sudden death during the 13th month; ii) cardiac decompensation during the 12th month.

The long-term NYHA functional class was 2.4 (mean), including 1 patient in class IV, 6 pts in class III, and 8 pts in class II. The average post-operative ejection fraction was 27.8%. Actuarial survival at 3 years was 59% (including operative mortality). Until now, no patient required heart transplantation after CMP. However, one patient is on the waiting list.

In conclusion, Cardiomyoplasty improves at long-term the quality of life of the majority of patients discharged from the hospital. Technically is a simple surgical procedure but harmful to the respiratory system. It was observed a relative frequency of sudden deaths (2 cases), probably due to malignant ventricular arrhythmias. Concerning patients selection, it is difficult to find a suitable heart failure candidate having a sinus rhythm, no mitral regurgitation, moderate heart dilatation, and normal respiratory function. In our experience, about 60% of patients proposed for cardiomyoplasty presented contra-indications for the procedure.
 
 

CARDIOMYOPLASTY AND AORTMYOPLASTY: EXPERIMENTAL AND CLINICAL EXPERIENCE

T. Mesana, J.R. Monties et al.

Service of Cardiac Surgery. La Timone Hospital, Marseille, France

Cardiomyoplasty (CMP) and aortomyoplasty (AMP) are promising techniques in the treatment of heart failure, however, patient selection has restricted the range of indication of CMP, and, AMP has been performed in a very selected number of centers. We reviewed our clinical and experimental work of these procedures to emphasize the necessity to reorient surgical technique towards new directions and particularly less invasive thoracoscopic approach.

Since January 1993, 18 patients underwent CMP for ischemic, idiopathic or congenital cardiomyopathy. 84% achieved a complete training of the latissimus dorsi muscle and follow-up was complete in all patients up to 4 years. In addition, a clinical pilot study on dynamic descending AMP started in June 1995 and included 5 patients. Three of them could benefit from latissimus dorsi counter-pulsation, surviving 6, 18 and 24 months.

We also investigated on an animal model minimally invasive thoracoscopic surgery for both procedures. Eight goats underwent endoscopic harvest of latissimus dorsi muscle and thorascocopic aortic or cardiac wrap, and studied after surgical recovery.

CMP patients achieved 11.2% hospital mortality and 70.6% actuarial survival at 48 months, though post-operative course was often critical (70% low output syndrome), particularly in ischemic etiology. Long term follow-up and on-off study efficacy analysis favors passive mechanisms but questions latissimus dorsi muscle atrophy related to initial surgical trauma.

Clinical AMP was feasible and provided extra-aortic counter-pulsation. However, surgical technique and patient selection need improvement. Minimally invasive thoracoscopic surgery was applicable to CMP and AMP, achieving similar anatomy and physiology to the open technique, thus offering a future direction to improve surgical outcome of these procedures.
 
 

DYNAMIC CARDIOMYOPLASTY:
7 YEARS EXPERIENCE AT LA PITIÉ HOSPITAL

V. Bors, R. Dorent, G. Jondeau, A. Decourt
and I. Gandjbakhch

La Pitié Hospital, Paris, France

Between January 1992 and June 1997, 29 patients (24 males, 5 females, mean age: 49 years (ranged from 35 to 62 years) underwent dynamic cardiomyoplasty (DC). Etiology of advanced heart failure was: idiopathic (n = 22), ischemic (n = 7). DC was performed with the left latissimus dorsi muscle according to Carpentier-Chachques’s technique and stimulation protocol. No concomitant surgical procedure was associated.

In the early experience, 4 patients died post-operatively. Causes of deaths were: multiorgan failure in 3 cases and electromechanical dissociation in 1 case. During the follow-up, 3 patients developed congestive heart failure and died at 20, 33 and 65 months respectively. Sudden death occurred in 2 out-hospital patients at 15 and 32 months.

Hemodynamic follow-up was completed at 6, 12 and 24 months in 16 patients. Results showed a significant improvement of left ventricular ejection faction in comparison to pre-operative data (pre: 21±7% vs 24 months: 27.3±9.4 To. p = 0.0013). At 24 months, functional class was significantly improved (pre: NYHA 2,9 vs 24 months NYHA 1.8).

Five other patients required orthotopic heart transplantation 15 to 72 months after hospital discharge. In these five patients, the distal part of the LD muscle flap was harvested for morphological and histochemical study. Despite focal fibrosis and fatty infiltration, up to 80% of the muscle samples showed normal aspect, and satisfactory transformation of muscle fiber from type II to type I.

Out 7 years follow-up data show that, in selected patients, DC is compatible with long term survival with an improvement in functional status. After 5 years, muscle damage remains limited.
 
 

DYNAMIC CARDIOMYOPLASTY:
LONG TERM RESULTS AFTER SEVEN YEARS

C. Werling, C. Jungheim and W. Saggau

Department of Cardiac Surgery, Herzzentrum Ludwigshafen, Germany

Since April 1993 until October 1999 Dynamic Cardiomyoplasty (CMP) was performed in 23 patients (P), aged between 33 and 68 years. Two P suffered from ischemic cardiomyopathy (IC), 21 P from dilated cardiomyopathy (DC). Mean preoperative NYHA class was 3, LVEF 22%, cardiac index (CI) 2,0, LVEDP 22 mmHg, systolic pulmonary artery pressure (SPAP) 44 mmHg, V02max 15,4 ml/kg/min and LVEDD 69 mm. 15 P were in sinus rhythm, 8 P had atrial fibrillation, 4 of them intermittent. 2 P had documented sustained ventricular tachycardia (VT) and 2 P ventricular fibrillation (VF) with successful reanimation. Therefore all of these 4 P had an indication for ICD implantation.

CMP was performed without cardiopulmonary bypass and without concomitant surgery by using the left latissimus dorsi muscle. Muscle stimulation started 2 weeks after the operation, following the standard protocol. In the last 3 P the progressive pulse number protocol was used. After 10 weeks the muscle was stimulated with 6 bursts every second beat. The follow-up time ranges from 11 to 58 months. Follow up examinations including left and right heart catheterisation were performed after 6 month, 1 year and every following year, Hemodynamic parameters were measured with stimulation and without stimulation for 1 5 min.

Our data show a slide improvement of LVEF and CI, a decrease of PWCP and no change of SPAP. Without myostimulation LVEF and CI reach preoperative values. Although the changes of hemodynamics only are moderate there is a significant improvement of clinical status. Perioperativety one P died immediately because of acute myocardial infarction, one P after 5 days because of VF and one after 12 days because, of sepsis. In the follow up period of 78 month 8 late death occurred 3 P had a sudden death (after 3, 6 and 25 months), 2 P died of heart failure (one with DC after 6 weeks and one with IC after 14 months), 3 P had a non cardiac cause of death. 70% of the cardiac deceased were alcohol abusers. Both P with IC died. All survivors are in NYHA class I or II (mean 1,3).

Until now we provided 5.P with ICD and cardiomyostimulator, 3 of them before CNP and 2 after CMP. All of them had episodes of VT or VF in the follow up period.

CMP reduces the symptoms of heart failure and is a sufficient therapy for P with dilated cardiomyopathy, which are on an optimized drug treatment in NYHA III. In our opinion, beside the known hemodynamic risk factors, malignant ventricular arrhythmias, alcohol and drug abuse, adverse psychosocial factors and ischemic cardiomyopathy are predictors for unfavourable outcome. For these reasons, in the presence of VF or sustained VT we implant an ICD, we insist on a successful alcohol and drug withdrawal before CMP and prefer P with dilated cardiomyopathy.
 
 

In conclusion, local administration at the heart/muscle interface of growth factors increases muscle vascularization and avoids muscle atrophy in an experimental model of cardiomyoplasty. The catheter system allows for simple and reliable delivery of growth factors. These results are promising for muscle and myocutaneous flap use in the clinical setting of cardiomyoplasty or plastic and reconstructive surgery. These growth factors, improving the development of the collateral circulation between the heart, the LDM and the mediastin structures by stimulation of angiogenesis, are of great interest for the treatment of ischemic myocardial diseases.
 
 
 
 

CELLULAR CARDIOMYOPLASTY
ON A CANINE MODEL
OF IDIOPATHIC DILATED CARDIOMYOPATHY

N, Borenstein¹, C. Rajnoch, J.C. Chachques, V. Chetboul¹, JL. Pouchelon¹, JF. Toussaint, C. Desbois1, P. Fayolle¹, P. Bruneval and A. Carpentier

Laboratory of Cardiac Grafts and Prostheses, Broussais Hospital, Paris, and (1) National Veterinary School of Maisons-Alfort, France

The concept of cellular cardiomyoplasty is based on the contribution of exogenous myogenic cells in the myocardium to replace lost or altered cardiomyocytes. The ultimate aim is to repair, replace or enhance the biological function of the altered cells, to restore a functional myocardial mass and to improve the contractile performances of the heart.

Recent publications have shown encouraging results of the functional impact after myoblast transplantation into the myocardium. In the experimental protocols, myocardial lesions were always induced in order to create a heart failure model and very often on small rodents.

Several canine breeds suffer from idiopathic dilated cardiomyopathies which resembles the human cardiomyopathy from the clinical, anatomo-pathological and histological point view. The nature of this disease and the canine breeds affected by it (> 30 kg) give rise to a pre-clinical model.

The study presented involves the implantation of autologous myoblasts in dogs suffering from idiopathic dilated cardiomyopathy. The objectives were the following: (1) to create a viable and reproducible technique of primary dog myoblast cultures, (2) to evaluate the clinical and hemodynamic effects of intramyocardial cell implantation.

The experimental protocol was laid out as follows: a sartorius muscles biopsy, two weeks of cell culture, intramyocardial implantation, hemodynamic and viability evaluations of the myocardium by colour Doppler echocardiography, by tissue Doppler echocardiography and by SPECT.

Four dogs suffering from dilated cardiomyopathy were included in the protocol. Three primary culture techniques were compared. Cellular implantation was carried out by thoracotomy and epicardial injections; 20 sites were grafted with 2.5 x 10⁶ myoblast each, hence a total of 5 x 10⁷ cells.

The skeletal muscles were healthy in four out of four animals. Cell culture by monoenzymatic collagenase digestion allowed for a yield of more than 93% myoblasts. Two animals died during the post-operative phase. The grafted cells could not be found within the two autopsied hearts. The follow-up of the two other dogs was at 2 and 4 months. A distinguished improvement in the clinical state, in hemodynamics, in the left ventricular free wall thickness and contraction, as well as in the myocardial viability of these animals was observed: improvement of their NYHA class, shortening fractions rising from 20% to 24% in one dog and from 25% to 36% in the second one, systolic volumes indexed to body surface decreased from 67.8 to 50.8 ml/m2 and from 56.3 to 39.4 ml/m² respectively. At three weeks post-implantation, a 50% recovery of the myocardial viability in the apical zone was noted.

The remarkable improvement of the functional parameters is to be confirmed by a randomized study with a larger number of dogs. This way, the pre-clinical results could validate satellite cell implantation into the myocardium as a simple and cheap alternative for heart failure treatment.

* Grant by the Academie Nationale de Medecine, Paris, France
 
 

PRIMARY CELL TRANSPLANTATION
TO TREAT HEART FAILURE

Ch. Rajnoch, N. Borenstein, J.C. Chachques, A. Berrebi and A. Carpentier

Laboratory of cardiac grafts and prostheses, Broussais Hospital, Paris, France

The drawbacks of cardiac transplantation in the treatment of heart failure are: a shortage of donor hearts, complications of immunosuppression and the failure of grafted organs. Therefore, the transplantation of single cells instead of entire organs could be a potential therapy in the repair of injured myocardium.

The aim of cell transplantation into heart muscle is to compensate for damaged cells to restore myocardial functions. Two types of cells most currently used for this purpose in research are cardiomyocytes and skeletal myoblasts. Cell lines of these cell types were initially used to determine the fate of the cell grafts in the heart. However, cell lines pose a potential problem concerning the risk of tumour formation and genetic drift of the cell line. For this reason, primary cell cultures seem more suitable to be grafted into the myocardium.

Primary cardiomyocytes used in cell transplantation originating from embryonic or foetal tissues bring about an ethical issue. Another disadvantage of cardiomyocyte grafts is the need for immunosuppression to avoid graft rejection. Skeletal myoblasts, in turn, can be transplanted in an autologous fashion. For this reason we choose skeletal myoblast transplantation into the myocardium, also called cellular cardiomyoplasty, as the most interesting option.

Experimental work on cellular cardiomyoplasty has been carried out on rats, dogs and sheep in our laboratory. The research is directed to obtain answers on topics such as cell graft survival, transplanted cell differentiation, host-cell interactions, and mechanical and electrical coupling of transplanted cells. In addition to histological studies, functional assessment of the myocardium before and after cell transplantation are being accomplished. Finally, the most difficult question to be answered is whether primary skeletal myoblasts transdifferentiate into cells with a cardiac phenotype induced by the cardiac environment.