Articles       99        Changes in Ca²⁺-regulatory muscle membrane proteins during the chroni clow-frequency
                                stimulation induced fast-to-slow transition process
                                K Ohlendieck     [Full text pdf 673Kb]  

                 107        Metabolic and muscle adaptation to aerobic training in patients affected by Chronic 
                               Progressive  External Ophthalmoplegia
                               G Siciliano, ML Manca, M Mancuso, LE Pollina, P Iacconi, and L Murri    [Full text pdf 148Kb]  

              
                 113        Dynamic cardiomyoplasty: clinical experience after seven years
                               C Werling, C Jungheim and W Saggau     [Full text pdf 190Kb] 

                
                 119        Chronic aortic counterpulsation with latissimus dorsi: clinical follow-up cardiomyoplasty comparison
                               J Trainini, J Barisani, J Mouras, EI Cabrera Fischer, and AI Christen     [Full text pdf 142Kb]

                 
                 127        Validation of Doppler flow guidewire for peak aortic flow measurement in order to establishits sensitivity
                               for recognition of cardiac assistance in Demand Dynamic Cardiomyoplasty
                               G Rigatelli, M Barbiero, G Docali, M Zanchetta, L Pedon, A Baratto, P Maiolino, G Rigatelli, U Carraro, and S Dalla Volta    
                               [Full text pdf 57.2Kb]

                  
                 131        Pathological findings of latissimus dorsi muscle grafts after short and long-term dynamic cardiomyoplasty.
                               Review of published autopsies and a recent post-mortem study of and  unconditioned graft
                               R Scelsi, L Scelsi, AH El Messlemani and U Carraro    [Full text pdf 29.6Kb]
 

                 137         Is injury to the thoracodorsal nerve present after long term dynamic cardiomyoplasty in goats?
                                E Monnet, EC Orton, G Child, D Getzy, G Jacobs, and L Metelman   [Full text pdf 306Kb]
 
 
 
 
 

Changes in Ca²⁺-Regulatory Muscle Membrane Proteins During the Chronic Low-Frequency Stimulation Induced Fast-To-Slow Transition Process

Kay Ohlendieck

Department of Pharmacology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland

Electro-stimulation has a profound effect on the abundance and isoform expression pattern of many contractile and regulatory elements of skeletal muscle fibres. This review summarizes the effects of chronic low-frequency stimulation on Ca²⁺-regulatory membrane proteins involved in excitation-contraction coupling and muscle relaxation. Isoform switching and/or changes in the abundance of marker proteins due to muscle conditioning encompasses elements of the transverse-tubular voltage sensor, the sarcoplasmic reticulum Ca²⁺-release units, the luminal Ca²⁺-reservoir complex and the Ca²⁺-uptake apparatus of the longitudinal tubules. During the early phase of the fast-to-slow transition process an exchange between the RyR1 and RyR2 isoforms of the Ca²⁺-release channel, the a_1S-subunit and the a_1C-subunit isoforms of the dihydropyridine receptor, the fCSQ and sCSQ isoforms of the Ca²⁺-binding protein calsequestrin and the SERCA1 and SERCA2 isoforms of the sarcoplasmic reticulum Ca²⁺-ATPase occur.These changes appear to reflect molecular adaptations to changed physiological demands and are at least partially due to degeneration-regeneration processes. In addition, the shift from fast isoforms to slow and/or cardiac isoforms indicates that electro-stimulated muscle fibres possibly exhibit a cardiac/neonatal-like mode of the excitation-contraction-relaxation cycle.

Key words: Ca²⁺-ATPase, calsequestrin, chronic low-frequency stimulation, dihydropyridine receptor, excitation-contraction coupling, ryanodine receptor.

Basic Appl Myol 10 (3): 99-106, 2000

Address correspondence to:

Dr. Kay Ohlendieck, Department of Pharmacology, University College Dublin, Belfield, Dublin 4, Ireland, tel. 353 1 7061557, fax 353 1 2692749, Email kay.ohlendieck@ucd.ie.

Metabolic and Muscle Adaptation to Aerobic Training in Patients Affected by Chronic Progressive External Ophthalmoplegia

Gabriele Siciliano, Maria L Manca, Michelangelo Mancuso, Luca E Pollina⁽¹⁾, Pietro Iacconi⁽¹⁾, and Luigi Murri

Department of Neurosciences, Neurological Clinics, and (1) Department of Oncology, University of Pisa, Pisa, Italy

Mitochondrial myopathies with respiratory chain defects are multisystem diseases characterised by mitochondrial DNA (mtDNA) mutations responsible for impairment of aerobic cell metabolism. At the skeletal muscle level involvement of respiratory chain function is the cause of insufficient ATP production and deranged metabolism, a main effect of which is represented by abnormal production of lactate. Recently, it has been reported beneficial effects of aerobic training on muscle performance in mitochondrial myopathy subjects. Aim of this study was to evaluate in 9 patients affected by chronic progressive external ophthalmoplegia (CPEO) and large-scale mtDNA rearrangements functional adaptation of skeletal muscle to aerobic training, and to relate it to muscle biopsies parameters assessed before the training. To this purpose, CPEO patients underwent an exercise test performed at the anaerobic lactate threshold before and after a supervised 10-week course of aerobic training. A correlation was found between the training-related decrement in exercise peak lactate and cytochrome c oxidase (COX) enzyme activity (inverse correlation, r=-0.81, p<0.05), and with the number of COX- (r=0.72, p<0.05) and ragged red fibers (r=0.64, p=0.05). On the contrary, no relation was found with the amount of deleted mtDNA in muscle biopsy. These results indicate that aerobic training can be beneficial also in those CPEO patients more severely affected by mitochondrial dysfunction. The level of COX activity in muscle biopsy rather than the amount of mutated mtDNA seems to be a useful predictor for the effectiveness of aerobic training program, suggesting some gene expression mechanisms in mediating muscle adaptation to training itself in these patients.

Key words: aerobic training, lactate, mitochondrial diseases, muscle biopsy.

Basic Appl Myol 10 (3): 107-111, 2000

Address correspondence to:

Dr. Gabriele Siciliano, MD, PhD, Department of Neurosciences, Neurological Clinics, Via Roma 67 - 56126 Pisa (I), tel. 39 050 993046/993334, fax 39 050 554808, Email gsicilia@neuro.med.unipi.it.

Dynamic Cardiomyoplasty: Clinical Experience after Seven Years

Christiane Werling, Christoph Jungheim and Werner Saggau

Klinikum Ludwigshafen, Heartcenter, Cardiac Surgery, Ludwigshafen, Germany

Since 1993 Dynamic Cardiomyoplasty (CMP) was performed in 23 patients (P) aged between 33 and 68 years. Two P suffered from ischemic and 21 P from dilated cardiomyopathy. Mean preoperative NYHA class was III, LVEF 22%, CI 2,0, LVEDP 22mmHg, PAPsys 44 mmHg, VO₂max 15,4 ml/kg/min and LVEDD 69mm. 15 P were in sinus rhythm, 8 had atrial fibrillation. Two P had documented sustained VT, 2 VF with successful reanimation. Chronic stimulation was performed with 6 pulses every second beat. There was only a moderate change of conventionally measured hemodynamics, whereas clinical status improved significantly. Perioperatively one P with ischemic cardiomyopathy died caused by acute myocardial infarction, a second one after 5 days because of VF and one P after 12 days because of a sepsis. 8 late deaths occurred. Three P had a sudden death after 3, 6 and 25 months, 2 P died of heart failure after 1,5 and 14 months and 3 P had a non cardiac cause of death. In 1996 four of ten of our P lived in psychosocial unstable conditions, for instance were alcohol or drug addicts. All cardiac deceased belonged to this risk group. Since then only 2 of 13 P from this risk group were operated and one of them also had a cardiac death. Until now we provided 5 P with ICD and cardiomyostimulator. All of them had episodes of VT or VF in the follow up period. On the other hand we lost 4 P because of sudden death. Our total survival rate amounts to 52% after 7 years. If you only take in account the cardiac deceased the survival rate is 70% and if you exclude the patients, who had a sudden death and were not provided with an ICD, the survival rate would be 87% and probably could be highly improved by combining an ICD with an cardiomyostimulator in every patient.

Key words: arrhythmia, cardiomyoplasty, follow up, ICD, outcome, risk factors.

Basic Appl Myol 10 (3): 113-117, 2000

Address correspondence to:

Christiane Werling, M.D., Herzzentrum Ludwigshafen, Klinik für Herzchirurgie, Bremserstrasse 73, Postfach 21 73 52, D-67063 Ludwigshafen, Germany, tel. +49 621 503 4050, fax +49 621 503 4060, Email werlingc@klilu.de.

Chronic Aortic Counterpulsation with Latissimus Dorsi: Clinical Follow-Up. Cardiomyoplasty Comparison

Jorge Trainini, José Barisani, Jorge Mouras, Edmundo I. Cabrera Fischer, and Alejandra I. Christen

Presidente Perón Hospital, Avellaneda, Buenos Aires, Argentina

Dynamic aortomyoplasty is an alternative technique to heart transplantation. The goal of our study was to evaluate the benefits of aortic counterpulsation obtained by dynamic aortomyoplasty in patients with heart failure refractory to pharmacological treatment and contraindications to heart transplant or cardiomyoplasty.In this study we compared preoperative and postoperative data of selected patients submitted who were treated with dynamic thoracic aortomyoplasty. This surgical technique wrap the right latissimus dorsi muscle flap around the ascending aorta. This muscle flap was electrically stimulated during diastole, following a muscle-conditioning protocol, to obtain diastolic augmentation. At twelve months follow-up period we evaluated, invasively and noninvasively, the hemodynamic and clinical effects of aortomyoplasty. We observed a significant decrease in the number of hospitalizations (p<0.001), NYHA functional class (p<0.001), left atrial diameter (p<0.05), wedge pressure (p<0.05), left ventricular diameter (p<0.05) and pulmonary artery systolic pressure (p<0.05); and a significant increase in the 6-minute walking test (p<0.001), cardiac index (p<0.01), noninvasive evaluation of diastolic augmentation (p=0.01), left ventricular shortening fraction (p<0.05), and radioisotopic left ventricular ejection fraction (p<0.05). We also found a non significant decrease in peak oxygen consumption (p=0.05). This nine patients operated with aortomyoplasty was compared with sixteen patients treated with cardiomyoplasty at twelve months of follow-up. Dynamic biologic assistance with latissimus dorsi in heart failure, either aortomyoplasty or cardiomyoplasty in selected patients with severe heart failure, resulted in an important improvement of hemodynamic parameters, heart functional data and clinical functional, without significant differences between the results of both techniques.

Key words: aortomyoplasty, cardiomyopathy, cardiomyoplasty, latissimus dorsi muscle, skeletal muscle.

Basic Appl Myol 10 (3): 119-125, 200

Address correspondence to:

Dr. Jorge Trainini, M.D., Brandsen 1690 - 3 A, (1287) Buenos Aires, Argentina. Phone and fax (54 11) 4302 3810, EMail alumni@ffinme.edu.ar.

Validation of Doppler Flow Guidewire for Peak Aortic Flow Measurement in Order to Establish Its Sensitivity for Recognition of Cardiac Assistance in Demand Dynamic Cardiomyoplasty

Gianluca Rigatelli, Mario Barbiero⁽¹⁾, Giorgio Docali⁽¹⁾, Mario Zanchetta⁽²⁾, Luigi Pedon⁽²⁾, Adriano Baratto⁽²⁾, Pietro Maiolino⁽²⁾, Giorgio Rigatelli⁽¹⁾, Ugo Carraro⁽³⁾, and Sergio Dalla Volta

Department of Cardiology, Padua School of Medicine, Padua, (1) Division of Cardiology, Cardiomyoplasty Project, Legnago General Hospital, Verona, (2) Division of Cardiology, Cittadella General Hospital, Padua, and (3) Department of Biomedical Sciences, University of Padua, Padua, Italy

INTRODUCTION: there are no certain data regarding the real cardiac assistance of cardiomyoplasty. We tested the use of doppler flow wire for measurement of aortic flow velocity (directly related with cardiac output) in order to demonstrate that this method is able to measure systolic assistance during stimulated beats in cardiomyoplasty.

METHOD: the technique has been tested in five coronaropathic patients (M/F = 4/1; age = 61±7.1; atrial fibrillation / sinus rhythm = 1/4; VTD = 76.6±8.26 ml/mq; EF = 67.4±8.56). The measures were performed during a normal cardiac left catheterization for coronarography using a Flex^TM Doppler flow wire of .018 inch through a 4F introducer femoral arterial access. Stimulated beats were obtained with a right ventricle stimulator catheter through a femoral venous access.

RESULTS: fourth series of measures, composed by 10 normal beats and 1 stimulated beat, were recorded: we measured the maximal peak velocity of beat n°9 (normal) and beat n°1 (post-stimulated beat) of the subsequent series. The values respectively for normal beats and for post-stimulated beats were: - first series: 50.4±13.5 and 63.4±17.5 cm/s (P = 0.0091); - second series: 65.4±15.4 and 75.2±14.4 cm/s (P = 0.0044); - third series: 49.8±8.43 and 62.4±17.7 cm/s (P = 0.0249); - fourth series: 56.8±15.4 and 63.4±13.3 cm/s (P = 0.0024). No complications were observed after the procedure.

DISCUSSION: Statistical analysis showed a significant increasing in peak flow velocity after the stimulated beats. Therefore the technique is safe and effective and may be sensitive enough to detect a similar phenomenon related to a real systolic improvement owe to latissimus dorsi graft contraction. In the first two demand dynamic cardiomyoplasty operated patients tested with this method, it has been showed an increase of 10% in aortic flow velocity between stimulated and no-stimulated beats.

Key words: intravascular ultrasound, heart failure.

Basic Appl Myol 10 (3): 127-130, 2000

Address correspondence to:

Dr. G. Rigatelli, Department of Cardiology, Padua School of Medicine, Via T. Speri, 18, 37040 Legnago, Italy, Email jackyheart@katamail.com.

Pathological Findings of Latissimus Dorsi Muscle Grafts After Short and Long-Term Dynamic Cardiomyoplasty. Review of Published Autopsies and a Recent Post-Mortem Study of an Unconditioned Graft

Roberto Scelsi, Laura Scelsi⁽¹⁾, Abdul Hassib El Messlemani⁽²⁾ and Ugo Carraro⁽²⁾

Department of Human Pathology, (1) Department of Cardiology, University of Pavia and IRCCS Policlinico S. Matteo, Pavia, and (2) Department of Biomedical Sciences, University of Padova, Padova, Italy

Dynamic Cardiomyoplasty (DC) is a surgical procedure consisting of mobilization of the Latissimus Dorsi muscle (LDM) with its intact thoracodorsal neurovascular pedicle, followed by transposition into the thorax. The muscle is wrapped around the ventricles and electrically stimulated synchronously with cardiac contraction in order to assist a failing heart. The morphological findings of the LDM specimens were analyzed in 13 published post-mortem cases in which the LDM graft was used for Dynamic Cardiomyoplasty (DC). The patients survived for 1 month to 8 years. Moreover muscle fibre and vascular changes are described after surgical deafferentation and transposition in an unconditioned LDM of a patient survived one month after DC. At this time post-operative ‘degeneration of muscle fibres with interstitial oedema and extensive fibrous and fatty infiltration were observed. The epicardial-muscle interface showed signs of the recent surgery with inflammation and fibrinous adhesions. Numerical reduction and necrosis of capillaries were detected mainly in the distal part of LDM graft. At 1, 5 and 7 months after DC, the patients submitted to electric myostimulation showed mild muscular alterations and incomplete fibre type transformation. In long-term conditioned cases the electric stimulation induced an almost complete transformation of fibres into slow fatigue-resistant type 1 fibres. Four cases were studied after 2 years DC. The LDM graft structure was preserved and variable fibrous and fatty infiltration of muscle mainly in the distal muscle was observed. In a case, LDM fibre atrophy with internal nuclei was seen at the periphery of muscle; fibre degeneration and moderate fibrosis was confined in the region between the electrodes. In a second case, the study of LDM vasculature showed a number of arteries 4 times higher than unstimulated contralateral LDM. In the long-term cardiomyoplasty, even after more than 8 years of electric stimulation, the LDM appeared to be thinner compared with that observed at the time of the surgery and showed some changes as a fibre atrophy and internal nuclei. In all cases variable fatty infiltration and connective tissue ingrowth were observed. These changes were not related to the distance from the electrodes. In the histochemically checked case, the fibre type transformation of LDM was consistent, with marked increase of type 1 fibres. The authors conclude that surgical deafferentation of LDM mainly supporting the distal part of muscle caused ischemic changes in muscle fibres and that long-term electric stimulation induce a remodeling of the vascular bed and a progressive increase of intramuscular capillaries with discrete preservation of muscle fibres.

Key words: conditioned LDM, dynamic cardiomyoplasty, LD muscle grafts.

Basic Appl Myol 10 (3): 131-136, 2000

Address correspondence to:

Prof. Roberto Scelsi, Istituto di Anatomia e Istologia Patologica, via Forlanini 14, 27100 Pavia, Italy.

Is Injury to the Thoracodorsal Nerve Present after Long Term Dynamic Cardiomyoplasty in Goats?

Eric Monnet, E. Christopher Orton, Georgina Child, David Getzy⁽¹⁾, Gordon Jacobs⁽²⁾, and Lisa Metelman

Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, (1) IDEXX Veterinary Services, Broomfield, and (2) Telectronics Pacing Systems, Inc, Englewood, USA

Long term dynamic cardiomyoplasty is associated with atrophy, fibrosis, and fatty infiltration of the latissimus dorsi muscle (LDM). Ischemia, decreased muscle preload and chronic electrical stimulation have been recognized as factors for muscle deterioration after cardiomyoplasty. Transposition of the LDM around the heart might be associated with damages to the thoracodorsal nerve that can contribute to LDM deterioration. The purpose of the study was to evaluate the neuromuscular function of the thoracodorsal nerve and LDM after dynamic cardiomyoplasty. We performed neuromuscular functional analysis and histology on the LDM and thoracodorsal nerve of 6 normal goats and 6 goats after 6 months of dynamic cardiomyoplasty. Electromyographic analysis showed positive sharp waves and fibrillation potentials in the LDM of 3 goats from the dynamic cardiomyoplasty group. Conduction velocity of the thoracodorsal nerve of goats from the dynamic cardiomyoplasty group (58.32±9.80m/s) was reduced compared to the goats from the control group (71.48±5.71m/s, p=0.02). Loss of myelin sheaths, collapse of endoneurial connective tissue, and solitary foci of axonophagia and myelinophagia further documented severe injury to the thoracodorsal nerve in goats from the dynamic cardiomyoplasty group. The LDM wrap was denervated after long term dynamic cardiomyoplasty.

Key words: cardiac assist, degeneration, electromyography, goat, skeletal muscle.

Basic Appl Myol 10 (3): 137-143, 2000

Address correspondence to:

Dr. Eric Monnet, Department of Clinical Sciences, Colorado State University, Fort Collins, Co 80523, phone (970) 491 4450, fax (970) 491 1275, Email emonnet@vth.colostate.edu.