Reviews       145        Cardiomyoplasty: cellular and tissue engineering approache
                                   M Papadaki and R Langer     [Full text pdf 448Kb]

                    155        Vascular delay, angiogenesis and cardiomyoplas
                                   RW Stremel, WP Santamore, GR Tobin and JH Barker    [Full text pdf 30.3Kb]

Articles       161        Optimizing muscle wrap orientation for aortomyoplasty
                                  BL Cmolik, DR Thompson, JT Sherwood, AL Rovner, AS Geha and DT George
                                  [Full text pdf 130Kb]

                    169        Linear muscle power for cardiac support: a progress report
                                  DR Trumble and JA Magovern     [Full text pdf 155Kb]

                    181        Cardioverter-defibrillator implantation to safeguard against fatal arrhythmias in cardiomyoplasty patients
                                  VS Chekanov and S Deshpande     [Full text pdf 41.1Kb]

Cardiomyoplasty: Cellular and Tissue Engineering Approaches

Maria Papadaki and Robert Langer

Division of Health Sciences & Technology and Department of Chemical Engineering, MIT, Cambridge

Myocardial infarction is a major cause of morbidity and mortality in the western world. After injury, myocardial repair is limited since cardiomyocytes cannot significantly regenerate in vivo. Current therapeutic options such as medical therapy and whole heart transplantation have either limited clinical benefit or restricted applicability. Over the past years, the shortcomings associated with the available therapies have led to consider cellular-based strategies for the treatment of heart disease. Cellular therapies include the endogenous augmentation of the number of cardiomyocytes, and the transplantation of dissociated cells or cardiac muscle-like tissues in the diseased heart. Herein we review current knowledge on the status, the potential advantages, disadvantages and the clinical applications of the cellular based therapies with an emphasis on cellular and tissue transplantation.

Key words: myocardial infarction, cellular cardiomyoplasty, tissue cardiomyoplasty, tissue engineering.

Basic Appl. Myol. 9 (4): 145-153, 1999

Address correspondence to:

Maria Papadaki Ph.D., Division of Health Sciences & Technology and Department of Chemical Engineering, MIT, Building E25-342, 45 Carleton St., Cambridge, MA 02139, phone (617) 253 3123, fax (617) 258 8827, Email papadaki@mit.edu.

Vascular Delay, Angiogenesis and Cardiomyoplasty

Richard W. Stremel, William P. Santamore, Gordon R. Tobin and John H. Barker

Department of Physiology & Biophysics, Division of Plastic & Reconstructive Surgery, Department of Surgery, Health Sciences Center, University of Louisville, Louisville KY and Cardiology Section, School of Medicine, Temple University, Philadelphia PA

Vascular delay is a surgical technique that renders a skin flap sub-lethally ischemic and produces significant alterations in the characteristics of the tissue perfusion. The enhanced perfusion is associated with decreased distal flap necrosis and increased viability. Applying this technique to skeletal muscle flaps produces similar vascular changes and results in enhanced perfusion and contractile function. The changes in vascular architecture and total blood flow for both skin and muscle flaps represent alterations in basic arteriogenic and angiogenic activity. The recruitment of previously collapsed collateral vessels and growth and development of new vessels occurs over a period of days. The optimal period of vascular delay for rat latissimus dorsi muscle (LDM) is 3-14 days and 14 days has been used for human LDM. The mechanism(s) underlying the changes in angiogenic activity are likely to involve vascular growth factors such as basic fibroblast growth factor (b-FGF) and vascular endothelial growth factor (VEGF). The use of such adjuncts have significant potential benefits to the use of the LDM in cardiomyoplasty.

Key words: perfusion, vascularization, vascular architecture, muscle contraction, surgical delay.

Basic Appl. Myol. 9 (4): 155-159, 1999

Address correspondence to:

Richard W. Stremel, Ph.D., Department of Physiology & Biophysics, 1115A HSC, School of Medicine, University of Louisville, Louisville, KY 40292, phone (502) 852 5381, fax (502) 852 6239, Email r.stremel@louisville.edu.

Optimizing Muscle Wrap Orientation for Aortomyoplasty

Brian L. Cmolik, Dirk R. Thompson, J. Timothy Sherwood, Aleksandr L. Rovner, Alexander S. Geha and David T. George

Division of Cardiothoracic Surgery, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA

Background: Aortomyoplasty is a treatment for heart failure in which the latissimus dorsi muscle is wrapped around the aorta and stimulated to contract during diastole to provide chronic diastolic counterpulsation. We hypothesized that the manner in which the latissimus dorsi muscle is wrapped around the aorta determines the effectiveness of counterpulsation.

Methods: Nine mongrel dogs were studied. The left latissimus dorsi muscle (LDM) was isolated and wrapped around the descending thoracic aorta using three different muscle wrap techniques- a helical coil (HC) wrap, a circumferential (CM) wrap, and a "wringer" (WR) wrap. The three wraps were done in each dog. Left-ventricular and aortic pressures and coronary and aortic blood flows proximal and distal to the muscle-wrapped region were measured. Mean diastolic aortic pressure, endocardial-viability ratio, coronary blood flow, and blood volume ejected from the wrapped segment (wrap stroke volume) were calculated.

Results: Wrap stroke volume was greater for the WR (5.24± 1.00 mL, p<0.05 compared with HC), compared with the CM (3.70± 0.64 mL) or the HC (1.96± 0.83 mL). The increases in mean diastolic aortic pressure were similar for the WR (10.6± 4.7%) and CM (9.7± 4.4%) wraps and these were greater than the HC wrap (4.9± 4.7%). Endocardial-viability ratio was increased similarly by the WR (19.3± 10.8%) and CM (19.8± 14.6%) wraps and these increases were greater than observed during the HC wrap (10.5± 6.3%). The WR wrap provided the greatest increase in coronary blood flow (24.3± 23.0%) compared with the CM (17.8± 12.9%) and HC (5.7± 4.6%).

Conclusion: These data suggest that: 1) all muscle wrap techniques effect diastolic counterpulsation; 2) muscle wrap orientation influences ameliorative potential; and 3) wringer and adjacent are better than helical coil. Chronic studies should be done to test whether the differences are maintained.

Key words: aortomyoplasty, diastolic counterpulsation, skeletal muscle cardiac assist.

Basic Appl. Myol. 9 (4): 161-167, 1999

Address correspondence to:

Brian L. Cmolik, MD, Division of Cardiothoracic Surgery, Case Western Reserve University School of Medicine, 11100 Euclid Avenue, Cleveland, Ohio, USA, 44106-5011, phone 216 844 3055, fax 216 844 7597, Email blc3@po.cwru.edu.

Linear Muscle Power for Cardiac Support: a Progress Report

Dennis R. Trumble and James A. Magovern

Cardiothoracic Surgery Research, Allegheny-Singer Research Institute, Department of Surgery, Allegheny General Hospital, Pittsburgh, Pennsylvania

The use of electrically-stimulated skeletal muscle as an endogenous power source is an attractive approach to long-term cardiac assistance. The principle advantage of this technique over current methods is that it obviates the need for extracorporeal power sources and provides a reliable, low-cost, self-sustaining source of energy without immune compromise or loss of patient autonomy. This article briefly examines the various approaches to harnessing muscle power, details the rationale for the use of muscle in a linear configuration, and reviews our progress to date regarding development of a ventricular assist device powered by in situ skeletal muscle.

Key words: skeletal muscle, cardiac assist, electrical stimulation, conditioning, linear contraction, prosthesis, latissimus dorsi.

Basic Appl. Myol. 9 (4): 169-180, 1999

Address correspondence to:

Dennis R. Trumble, Cardiothoracic Surgery Research, Allegheny-Singer Research Institute, 9th floor - South Tower, 320 East North Avenue, Pittsburgh, PA 15212, phone (412) 359 3660, fax (412) 359 3878, Email trumble@pgh.auhs.edu.

Cardioverter-Defibrillator Implantation to Safeguard Against Fatal Arrhythmias in Cardiomyoplasty Patients

Valeri S. Chekanov and Sanjay Deshpande⁽¹⁾

Milwaukee Heart Institute of Sinai Samaritan Medical Center, Milwaukee, Wisconsin and (1) University of Wisconsin Medical School, Milwaukee Clinical Campus

A potentially low-risk surgery to improve hemodynamics and functional class in heart failure patients and others with advanced ventricular dysfunction, dynamic cardiomyoplasty (CMP) has been performed over 1,000 times worldwide. During long-term follow-up, arrhythmic sudden cardiac death remains a major cause of death with any advanced medical management (i.e., a 15%- 50% risk of recurrent cardiac arrest despite drug suppression of inducible arrhythmia, including amiodarone).

Combining our research expertise and clinical capabilities in electrophysiology with the technological expertise of Medtronic, Inc., a newly devised protocol for combined cardioverter-defibrillator implantation (ICD) and CMP was created from Medtronic protocols for cardiomyoplasty, ICD implantation, and prevention of "cross-talk" (i.e., adverse interaction due to over-sensing signals emitted by another implanted device).

In this largest published series of patients who have undergone CMP with concomitant ICD implantation (5 patients at the Milwaukee Heart Institute), we describe measures to prevent cross-talk and categorize cases according to timing of ICD implantation: 1) soon after CMP, 2) several months after CMP (in patients who develop ventricular tachycardia), or 3) considerably before CMP. We have not yet experienced a fourth scenario, i.e., simultaneous ICD implantation and CMP; however, we believe that we have established the groundwork for this eventuality.

Key words: aged skeletal muscle, cardiomyoplasty, contractile force, electrical stimulation.

Basic Appl. Myol. 9 (4): 181-188, 1999

Address correspondence to:

Valeri Chekanov, MD, PhD, 945 North Twelfth Street, Box 342, Milwaukee, WI 53402-0342, phone 001 414 219 7899, fax 001 414 219 6266.

Demand Dynamic Cardiomyoplasty: Two-year results
 

Mario Barbiero1, Ugo Carraro2, Roberto Riccardi3, Angelo Cotogni1, Giorgio Rigatelli1, Dino Casarotto4, Claudio Muneretto5
 
 

In Dynamic Cardiomyoplasty the standard clinical Protocol for Latissimus Dorsi (LD) stimulation produces a highly fatigue-resistant muscle which shows undesirable dynamic characteristics. The fully transformed LD could show more than fivefold reduction in shortening velocity and peak power. To obtain fatigue-resistance while preserving muscle force and velocity, we introduced the concept of daily activity-rest stimulation. LD wrap is allowed to rest during periods of hours (e.g., during the night while the patient is asleep). To determine LD contractile characteristics we developed a new noninvasive diagnostic tool (LD wrap "mechanogram") by echocardiography and a standard polygraph. Based on experimental results obtained with burst-intermittent stimulation in animals, and on clinical results of the heart/wrap synchronization obtained with LD wrap mechanogram, we implemented in a small series of patients a light regime of LD activity-rest stimulation (cardiac rate-based demand stimulation). By mechanogram and echo Doppler imaging we determine: 1) optimal synchronization delay between the contraction of the cardiac events and LD wrap; 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 wrap is related to the stimulation protocols used. After Demand Dynamic Cardiomyoplasty in the eight patients who achieved at least 6 month follow-up (mean 14+/_3 months), there are no deaths. Quality of life is substantially improved with significant reduction of heart failure symptoms. In the subset of patients in which light stimulation started with the muscle conditioning and Demand Dynamic Cardiomyoplasty was introduced earlier than one-year after surgery, exercise capacity increases or, at least, not significantly decreases at two-year follow-up (VO2 max: pre-op 12.3+/-0.7 v.s. 16.6+/-1.7 post-Demand Dynamic Cardiomyoplasty, p = 0.05).

In conclusion, Demand Dynamic Cardiomyoplasty is safe, well tolerated, and by maintaining an intermediate fast-to-slow LD wrap conversion provides up to two-year post-operation excellent clinical results. The activity-rest stimulation promises to offer long-term the benefits of Dynamic Cardiomyoplasty to patients with advanced heart failure.

Key words: Demand Dynamic Cardiomyoplasty, non-invasive monitoring, human LD, dynamic contractile characteristics; fiber type transformation; activity-rest stimulation; LD wrap mechanogram; echocardiography
 

Basic Appl Myol, 9 (4) xxx-xxx, 1999