Effects of Tongxinluo-facilitated cellular cardiomyoplasty with autologous bone marrow-mesenchymal stem cells on postinfarct swine hearts.

BACKGROUND: Treatment of ischemic heart disease remains an important challenge, though there have been enormous progresses in cardiovascular therapeutics. This study was conducted to evaluate whether Tongxinluo (TXL) treatment around the transplantation of mesenchymal stem cells (MSCs) can improve survival and subsequent activities of implanted cells in swine hearts with acute myocardial infarction (AMI) and reperfusion. METHODS: Twenty-eight Chinese mini-pigs were divided into four groups including a control group (n = 7); group 2, administration of low-dose TXL alone from the 3rd day prior to AMI to the 4th day post transplantation (n = 7); group 3, MSCs alone (n = 7) and group 4, TXL + MSCs (n = 7). AMI models were made by occlusion of the left anterior descending coronary artery for 90 minutes. Autologous bone marrow-MSCs (3 x 10(7) cells/animal) were then injected into the post-infarct myocardium immediately after AMI and reperfusion. The survival and differentiation of implanted cells in vivo were detected by immunofluorescent analysis. The data of cardiac function were obtained at baseline (1 week after transplantation) and endpoint (6 weeks after transplantation) by single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). Apoptosis was detected by TUNEL assay and the oxidative stress level was investigated in the post-infarct myocardium at endpoint. RESULTS: At endpoint, there was less fibrosis and inflammatory cell infiltration with more surviving myocardium in group 4 than in the control group. In group 4 the survival and differentiation of implanted MSCs were significantly improved more than that seen in group 3 alone (P < 0.0001); the capillary density was also significantly greater than in the control group, group 2 or 3 both in the infarcted zone (P < 0.0001) and the peri-infarct zone (P < 0.0001). MRI showed that parameters at baseline were not significantly different between the 4 groups. At endpoint, regional wall thickening and the left ventricular ejection fraction were increased while the left ventricular mass index, dyskinetic segments and infarcted size were decreased only in group 4 compared with control group (P < 0.0001). SPECT showed that the area of perfusion defect was significantly decreased at endpoint only in group 4 compared with control group (P < 0.0001). TUNEL assay indicated that TXL administration significantly decreased cell apoptosis in peri-infarct myocardium in groups 2 and 4. Furthermore, superoxide dismutase (SOD) significantly increased and malondialdehyde (MDA) decreased in groups 2 and 4 by the administration of TXL. CONCLUSIONS: Our study demonstrates the following: (1) immediate intramyocardial injection of MSCs after AMI and reperfusion resulted in limited survival and differentiation potential of implanted cells in vivo, thus being incapable of beneficially affecting post-hearts; (2) TXL-facilitation resulted in a significant survival and differentiation potential of implanted cells in vivo via inhibition of apoptosis and oxidative stress, accompanied by significant benefits in cardiac function.

[Morpho-functional study of electrostimulated latissimus dorsi muscle flap for diaphragm substitution]. / Estudio morfofuncional de una plastia electroestimulada del músculo latissimus dorsi para sustitución diafragmática.

Based on practical applications of the muscle latissimus dorsi (MLD) as much in reconstruction thoracic-abdominal defects as functionally in cardiomyoplasty, and in our experience in the electrostimulation with diaphragm pacing, we elaborated the primary objective of this work consisting of the creation of functional muscle plasty of MLD for substitution of the diaphragm. In two groups of cats formed by 6 animals each one, with section of the corresponding phrenic nerve, MLD plasty has been done to replace hemidiaphragm, conserving the thoracodorsal pedicle, by thoracic route in a group (intrathoracic plasty), and in the other by abdominal route (intraabdominal plasty). In a second intervention the stimulador electrode is implanted on thoracodorsal pedicle and the rest of components of the diaphragmatic pacing in a subcutaneous pocket. During a month progressive electroestimulation of MLD plasty is made, carrying out radiological and spirometric evaluation, that compares with evaluation control made before making plasty. After the sacrifice of the animals planimetric and histologic evaluation of the extirpated diaphragm were performed. Morphologic and functional results obtained allow us to affirm that functional plasty of MLD is an effective diaphragmatic substitute, although with a smaller degree of function than the original diaphragm, and functionally intraabdominal plasty has been superior to intratorácica plasty.

Estudio morfofuncional de una plastia electroestimulada del músculo latissimus dorsi para sustitución diafragmática / Morpho-functional study of electrostimulated latissimus dorsi muscle flap for diaphragm sustitution

Basándonos en las aplicaciones prácticas del músculo latissimus dorsi (MLD) o dorsal ancho tanto en reconstrucción de defectos toracoabdominales como funcionalmente en la cardiomioplastia, y en nuestra experiencia en la electroestimulación con marcapasos diafragmático, elaboramos el objetivo principal de este trabajo consistente en la creación de una plastia funcional muscular de MLD para sustitución del diafragma. En dos grupos de gatos de 6 animales cada uno, con sección del nervio frénico correspondiente, se ha practicado una plastia de MLD para sustituir a un hemidiafragma, conservando el pedículo tóracico dorsal, en un grupo por vía torácica (plastia intratorácica) y en el otro por vía abdominal (plastia intraabdominal). Posteriormente en una segunda intervención implantamos el electrodo estimulador sobre el pedículo toracodorsal y el resto de componentes del marcapasos diafragmático en un bolsillo subcutáneo. Durante un mes se realiza, de forma progresiva, electroestimulación de la plastia de MLD, llevando a cabo evaluación radiológica y espirométrica, que se compara con evaluaciones control practicadas antes de realizar la plastia. Después del sacrificio de los animales se practica valoración planimétrica e histológica del diafragma extirpado. Los resultados morfológicos y funcionales obtenidos nos permiten afirmar que la plastia funcional de MLD es un sustituto diafragmático efectivo, aunque con un menor grado de función que el diafragma original, y funcionalmente la plastia intraabdominal ha resultado superior a la plastia intratorácica (AU)

Based on practical applications of the muscle latissimus dorsi (MLD) as much in reconstruction thoracic-abdominal defects as functionally in cardiomyoplasty, and in our experience in the electrostimulation with diaphragm pacing, we elaborated the primary objective of this work consisting of the creation of functional muscle plasty of MLD for substitution of the diaphragm. In two groups of cats formed by 6 animals each one, with section of the corresponding phrenic nerve, MLD plasty has been done to replace hemidiaphragm, conserving the thoracodorsal pedicle, by thoracic route in a group (intrathoracic plasty), and in the other by abdominal route (intraabdominal plasty). In a second intervention the stimulador electrode is implanted on thoracodorsal pedicle and the rest of components of the diaphragmatic pacing in a subcutaneous pocket. During a month progressive electroestimulation of MLD plasty is made, carrying out radiological and spirometric evaluation, that compares with evaluation control made before making plasty. After the sacrifice of the animals planimetric and histologic evaluation of the extirpated diaphragm were performed. Morphologic and functional results obtained allow us to affirm that functional plasty of MLD is an effective diaphragmatic substitute, although with a smaller degree of function than the original diaphragm, and functionally intraabdominal plasty has been superior to intratorácica plasty (AU)

Cellular cardiomyoplasty for myocardial regeneration.

The evolving challenge of managing patients with congestive heart failure is the need to develop new therapeutic strategies. The cellular, molecular, and genetic approaches investigated aim to reinforce the weak, failing heart muscle while restoring its functional potential. This approach is principally cellular therapy (i.e. cellular cardiomyoplasty), the preferred therapeutic choice because of its clinical applicability and regenerative capacity. Different stem cells: bone marrow cells, skeletal and smooth muscle cells, vascular endothelial cells, mesothelial cells, adipose tissue stroma cells, dental stem cells, and embryonic and fetal cells, have been proposed for regenerative medicine and biology. Stem cell mobilization with G-CSF cytokine was also proposed as a single therapy for myocardial infarction. We investigated the association of cell therapy with electrostimulation (dynamic cellular cardiomyoplasty), the use of autologous human serum for cell cultures, and a new catheter for simultaneous infarct detection and cell delivery. Our team conducted cell-based myogenic and angiogenic clinical trials for chronic ischemic heart disease. Cellular cardiomyoplasty constitutes a new approach for myocardial regeneration; the ultimate goal is to avoid the progression of ventricular remodeling and heart failure for patients presenting with ischemic and non-ischemic cardiomyopathies.

Myocardial tissue engineering and regeneration as a therapeutic alternative to transplantation.

Ischemic cardiomyopathy leading to congestive heart failure remains the leading source of morbidity and mortality in Western society and medical management of this condition offers only palliative treatment. While allogeneic heart transplantation can both extend and improve the quality of life for patients with end-stage heart failure, this therapeutic option is limited by donor organ shortage. Even after successful transplantation, chronic cardiac rejection in the form of cardiac allograft vasculopathy can severely limit the lifespan of the transplanted organ. Current experimental efforts focus on cellular cardiomyoplasty, myocardial tissue engineering, and myocardial regeneration as alternative approaches to whole organ transplantation. Such strategies may offer novel forms of therapy to patients with end-stage heart failure within the near future.

A review of the concept of circulatory bioassist focused on the "new" demand dynamic cardiomyoplasty: the renewal of dynamic cardiomyoplasty?

After the initial enthusiasm, the dynamic cardiomyoplasty lost its reputation owing to the poor long-term results, caused by the muscular degeneration subsequent to chronic continuous electrical stimulation of the latissimus dorsi. An activity-rest stimulation protocol that avoids full transformation of the skeletal muscle, maintaining muscular properties over time, has been successfully tried. This "demand" stimulation protocol showed in humans good results improving NYHA class, ejection fraction value, and survival. The discussion about the capability of this and a unique kind of cardiocirculatory bioassist is due to be reopened. In fact, heart transplant, percutaneous circulatory-supporting device, multisites stimulation therapy, and total artificial heart have some drawbacks, one of which is the economic cost. In developing countries the more economic demand dynamic cardiomyoplasty may still play a role.

Maintained benefits and improved survival of dynamic cardiomyoplasty by activity-rest stimulation: 5-year results of the Italian trial on "demand" dynamic cardiomyoplasty.

OBJECTIVE: Latissimus dorsi (LD) muscular degeneration caused by continuous electrical stimulation has been the main cause of the poor results of dynamic cardiomyoplasty (DCMP) and its exclusion from the recent international guidelines on heart failure. To avoid full transformation of the LD and to improve results, a new stimulation protocol was developed; fewer impulses per day are delivered, providing the LD wrap with daily periods of rest ("demand" stimulation), based on a heart rate cut-off. The aim of this work is to report the results at 5 years of follow-up of the Italian Trial of Demand Dynamic Cardiomyoplasty and to discuss their impact on the destiny of this type of cardiac assistance. METHODS: Twelve patients with dilated myocardiopathy (M/F=11/1, mean age 58.2+/-5.8 years, sinus rhythm/atrial fibrillation=11/1) were submitted during the period 1993-1996 to DCMP and at different intervals to demand protocol. Clinical, echocardiographic, mechanographic and cardiac invasive assessments were scheduled before initiating the demand protocol and during the follow-up at 0, 6 and every 12 months. RESULTS: The mean duration of follow-up was 40.2+/-13.8 months (range 18-64). There were no perioperative deaths. The demand stimulation protocol showed a decrease in 5 years in New York Health Association (NYHA) class (3.17+/-0.38-1.67+/-0.77, P=0.0001), an improvement of left ventricular ejection fraction (22.6+/-4.38-32.0+/-7.0, P<0.001), a 5-year actuarial survival of 83.3% (one patient was switched to heart transplantation programme due to clinical worsening and another one died of massive pulmonary embolism). CONCLUSIONS: Demand DCMP maintains over time LD muscular properties, enhances clinical benefits and improves survival of DCMP, thus reopening the debate whether this type of treatment should be considered in patients with end-stage heart failure.

Cardiomyoplasty: long-term results in ischemic cardiomyopathy.

INTRODUCTION: Cardiomyoplasty was introduced into clinical practice in 1985 by Alain Carpentier. Since then, the procedure has been performed on more than 400 patients worldwide. The latissimus dorsi muscle is prepared maintaining the vascular supply, then the muscle flap is wrapped around the heart and connected to a cardiomyostimulator. The muscle is later stimulated synchronously with ventricular systole to augment the cardiac contractility. METHODS: To evaluate the long-term outcome of cardiomyoplasty, we investigated 3 patients electively undergoing this procedure in our hospital. All of these patients (2 male, 1 female) had severe chronic heart failure which did not respond to optimal medical treatment. The mean follow-up time was 42 months (range 24 - 60). All patients showed symptoms corresponding to NYHA class III, and one patient intermittently showed class IV despite conventional medical therapy. Patients were evaluated at 6-month intervals for 2 years with right heart catheterization, radionuclide scans, echocardiography, as well as questionnaires for assessing quality of life. RESULTS: There was no operative mortality. One patient experienced sudden death 2 years after operation. There were no significant changes in hemodynamic variables at 6, 12 or 24 months after surgery, respectively. Left ventricular ejection fraction increased from 20.0 ( 9.2 to 40.0 +/- 7.1 % (p = 0.05) 1 year after operation. Considerable improvement of symptoms was seen in all, and 1 patient returned to work. NYHA-class decreased from 3.1 to 2.0 (p = 0.02). CONCLUSIONS: Following cardiomyoplasty, patients may exhibit impressive clinical improvement with less striking changes of objective hemodynamic parameters. Thus, in our patients, dynamic cardiomyoplasty improves quality of life. We do not consider this treatment to be an alternative to heart transplantation. It does, however, provide a therapeutic option for patients for whom transplantation is contraindicated.

Dynamic cardiomyoplasty: expectations and results.

BACKGROUND: Cardiac transplantation is an option for only a small minority of patients with severe, chronic congestive heart failure. Transformed skeletal muscle has the potential to provide a durable form of fatigue-resistant muscle power to assist the cardiovascular system. METHODS: Since the first dynamic cardiomyoplasty performed by Carpentier and colleagues in 1985, the techniques to make this operative procedure an effective assist to the failed myocardium have been refined. Much has been learned about optimum patient selection so that perioperative morbidity and mortality is minimized. The cardiomyostimulator developed by Medtronic has undergone several revisions, primarily so that the stimulation of the muscle wrap is adaptive to variations in cardiac performance, such as those that occur with arrhythmia or during exercise. RESULTS: A review of the data to date suggest a substantial number of patients who undergo the procedure experience an enhanced quality of life, and an alleviation of their heart failure symptoms. Details of patient selection underscore that cardiomyoplasty is not an alternative to transplant. Seriously compromised patients with low peak oxygen uptake and very low ejection fractions have the highest short term mortality. CONCLUSIONS: Dynamic cardiomyoplasty remains a promising surgical option for patients with moderately-severe congestive heart failure (i.e. NYHA Class III patients). The ongoing randomized trial comparing cardiomyoplasty to standard medical therapy is expected to provide more detailed information about the benefits of this procedure.

Multistep approach to electrical stimulation after cardiomyoplasty.

UNLABELLED: Still a controversial procedure, cardiomyoplasty (CMP) improves the failing heart's ability to contract by using a latissimus dorsi muscle (LDM), but to date, hemodynamic results correlate poorly with clinical improvement. The following two causes for apprehension bar attempting to change the conventional electrical stimulation (ES) protocol to improve CMP results: (1) fear of beginning ES for LDM-assisted contraction immediately postmobilization and CMP and (2) fear of stopping or slowing ES during sleep periods. METHODS: In ten different experimental series, I used animal models of CMP to determine how to apply ES to newly mobilized LDM, how to begin partial cardiac assist immediately post-CMP, and how to suspend ES for 12 hours daily. RESULTS: From my experimental series I noted the following three results. (1) Different ES regimens applied 1 hour postmobilization changed the contractile force (CF). After a 30-minute fatigue test, CF decreased by 34% +/- 3% with continuous ES at 30 contractions per minute (cpm), by 23% +/- 2% with continuous ES at 15 cpm, by 25% +/- 5% with ES in a work-rest regimen at 30 cpm, and by 8% +/- 3% with ES in a work-rest regimen at 15 cpm. (2) Imitation of partial cardiac assist immediately postmobilization slightly decreased CF. Sixteen days postmobilization, during a 30-minute fatigue test in animals in which ES had been started immediately after mobilization, CF decreased by only 6% +/- 3% and did not change when ES was combined with imitation of cardiac assist for 30 minutes twice daily (work-rest regimen). (3) ES cessation for 24 hours daily or 12 hours daily in CMP model created no difference in ejection fraction (EF) with ES (54% +/- 4% vs 53% +/- 5%, respectively (or in left ventricular end-diastolic volume (LVEDV, 234.3 ml +/- 1.0 ml vs 24.8 mL +/- 0.6 mL, respectively) or in LV end-systolic volume (LVESV; 12.1 mL +/- 0.7 mL vs 12.8 mL +/- 0.7 mL, respectively). CONCLUSION: For improving angiographic potential in the LDM, ES can be started safely immediately post-CMP at 15 cpm (a 1:4 or 1:5 regimen) and single impulses per burst. For partial cardiac assist and for improving LDM performance, cardiac assist can be used for 30 minutes twice daily immediately post-CMP. To rest the muscle and save it from overuse, muscle contraction can be either stopped or slowed down during hours of sleep.

Activity-rest stimulation of latissimus dorsi for cardiomyoplasty: 1-year results in sheep.

BACKGROUND: In dynamic cardiomyoplasty electro-stimulation achieves full transformation of the latissimus dorsi (LD); therefore, its slowness limits the systolic support. Daily activity-rest could maintain partial transformation of the LD. METHODS: Sheep LD were burst-stimulated either 10 or 24 hours/day. Before and 2, 4, 6, and 12 months after stimulation, LD power output, fatigue resistance, and tetanic fusion frequency were assessed. Latissimus dorsi were biopsied at 6 months, and sheep sacrificed at 12 months. RESULTS: After 1 year of 10 hours/day stimulation LD was substantially conserved and contained large amounts of fast type myosin. From 2 months to 1 year of stimulation the power per muscle of the daily rested LD was greater than that of the left ventricle, being three to four times higher than in the 24-hour/day stimulation. CONCLUSIONS: If extended to humans, these results could be the rationale for the need of a cardiomyostimulator, whose discontinuous activity could offer to patients the long-standing advantage of a faster and powerful muscle contraction.

Progressive latissimus dorsi muscle denervation for free-flap dynamic cardiomyoplasty.

BACKGROUND: The creation of free muscle grafts for surgical myoplasty is limited by the dependence of muscle on its original nerve supply. The aim of this study was to develop a model of gradual denervation of a large skeletal muscle (latissimus dorsi) and evaluate the possibility that atrophic degeneration and loss of function would be reduced using progressive nerve compression instead of surgical division of the nerve. The effects of chronic stimulation prior to, and after, denervation were also evaluated. METHODS: Electrodes connected to a myostimulator were implanted on 24 latissimus dorsi muscles of 12 goats. Denervation of these muscles was achieved either by sectioning of the nerve by progressive compression using ameroid rings placed around the nerve. Electrostimulation of the muscle started either 5 weeks before (prestimulation), or immediately after the denervation. RESULTS: The model of gradual nerve compression was successfully created and did have less atrophy and loss of function at mid-term when compared with nerve division. Chronic electrostimulation of the muscle after nerve division had a beneficial effect on function and on the atrophic process. Chronic electrostimulation in our model of gradual nerve compression did not mirror these beneficial results. Detrimental results were observed in groups in which chronic electrostimulation was applied prior to nerve division or constriction.

Dynamic myoplasty: surgical transfer and stimulation of skeletal muscle for functional substitution or enhancement.

Dynamic myoplasty combines muscle transfer with electrical stimulation to provide contractile function that augments or replaces impaired organ function. Dynamic cardiomyoplasty was the first clinical application in which a skeletal muscle, latissimus dorsi, was transferred and stimulated to provide cardiac assistance, a function different from its original one. The problem of early muscle fatigue that was encountered in the initial implementation of the method was solved by training the muscle with electrical stimulation and thus changing its fiber composition. With intramuscular electrodes, the conditioned latissimus dorsi is stimulated in synchrony with the heart muscle. Safeguards are built into the two-channel implanted stimulator to avoid excessively high pulse rates. Clinicians report that 80% of patients with moderate to severe heart failure prior to operation showed a clinical improvement of 1.6 New York Heart Association classes. Alternative methods of providing cardiac assistance that are also being investigated include wrapping the muscle around the aorta, creating a skeletal muscle ventricle, and using the muscle to power an implantable pump. These latter techniques are still under preclinical investigation. Compared with heart transplant, cardiomyoplasty has the great advantage of not being subject to tissue rejection. The second principal application of dynamic myoplasty is treatment of fecal incontinence through creation of an electrically stimulated skeletal muscle neosphincter (ESMNS). The gracilis muscle of the leg is mobilized, wrapped around the anal canal, and conditioned with electrical stimulation to become more fatigue resistant. To achieve continence, the muscle is continuously stimulated except when the patient wishes to defecate. Overall success rates in achieving continence are 60-65%. Both cardiomyoplasty and the ESMNS technique, and their associated devices, are being refined through ongoing clinical trials.

[Circulatory support by an electrically stimulated muscle flap. Experimental experiences]. / Kreislaufunterstützung durch elektrisch stimulierte Muskellappen. Experimentelle Erfahrungen.

Functional electrical stimulation of the latissimus dorsi muscle flap for circulatory assistance extends the traditional concept of using this flap for reconstructive procedures into the field of cardiac surgery. It requires a transformed muscle which is able to contract for long periods of time without fatigue. Two main groups of experiments have been carried out in sheep. In six sheep the latissimus dorsi muscle (MLD) was transformed into a fatigue-resistant muscle by the means of multichannel stimulation of the supplying motor nerve. After that, stimulation of MLD at a frequency of 70 contractions per minute could be performed continuously without significant muscle fatigue. The loss of maximal force caused by the conditioning procedure was about one third of the initial force. In a second series of acute experiments the MLD was used for cardiomyoplasty. The muscle was divided into two parts which were wrapped around the heart in two different forms. The resting tension of the muscle was preserved. EKG-synchronous stimulation resulted in an increase in left ventricular pressure between 12 and 53%. The increase in arterial pressure was between 10,6 and 58%.

Association of latissimus dorsi muscle expansion with electrostimulation before cardiomyoplasty.

BACKGROUND: The principle of cardiomyoplasty is chronic electrostimulation of the latissimus dorsi muscle (LDM) flap wrapped around the heart to obtain a phasic activity that can be integrated to ventricular kinetics. In clinical cardiomyoplasty procedures, a complete wrap of both ventricles by the LDM cannot always be obtained in cases of extremely dilated hearts. This is due to the limited LDM length available for wrapping. In most of these cases, benefits of cardiomyoplasty are very limited. We have investigated the feasibility of progressive LDM expansion associated with electrostimulation. The aim was to increase the muscle area before cardiomyoplasty, while preserving the electrophysiologic characteristics of muscle fibers. METHODS: In 5 goats, a silicone LDM expander with two incorporated muscular pacing electrodes was inserted deep into the LDM through a paravertebral incision along the posterior edge of the muscle. The pacing leads were connected to a myostimulator implanted in a subcutaneous pocket. The expander was progressively inflated over 8 weeks, up to 500 mL. Simultaneously the LDM was electrostimulated. RESULTS: At 2 months planimetric studies demonstrated an increase of the LDM surface from 175 +/- 12 to 229 +/- 17 cm2 (+31% +/- 4%; p < 0.05). The expanded LDM showed preserved electrophysiologic characteristics. The analysis of biopsy samples revealed histologic integrity of muscle fibers and preservation of their mean diameter. CONCLUSIONS: Potential benefits of this procedure are (1) increase of muscle surface, (2) training of muscular fibers and preservation of muscular tone, and (3) division of the distal vascular supply at implantation, which may potentiate vascularization from the LDM main pedicle. An LDM expansion could be considered before cardiomyoplasty in cases of significant heart dilatation. This device was successfully implanted in 2 patients, 2 months before cardiomyoplasty. Cardiomyoplasties were performed without difficulty, and a complete biventricular wrap was obtained in both patients in spite of massive cardiomegaly.

Dynamic cardiomyoplasty: indication, surgical technique, and results.

The efficacy of dynamic cardiomyoplasty is still controversial. To date more than 400 patients have been operated worldwide. In recent years the indication and the surgical technique have become more uniform, which makes results from different centers eligible for comparison. We performed cardiomyoplasty exclusively in patients with contraindications for heart transplantation, such as chronic and recurrent infections or severe, irreversible sequelae of diabetes. Between August 1990 and October 1994, 8 isolated cardiomyoplasty procedures were performed in patients with cardiomyopathy (EF 14-32%, all in NYHA III). One patient died 2 months after surgery. Reported are the results of 7 patients after a mean follow-up of 41.1 +/- 14.1 months. Considerable symptomatic improvement was found in 6 or 7 patients, 3 of whom went back to work. One patient with severe pulmonary hypertension exhibited no improvement. In the others NYHA class improved by at least one. Echocardiography showed an increase in fractional shortening in all patients. LVEF increased from 21.2 +/- 5.2% to 38.1 +/- 15.9% (n = 7, p < 0.015) at 1 year, to 36.6 +/- 17.6% (n = 6, p < 0.05) at two years, and to 36.4 +/- 18.9% (n = 5, NS) at three years. Pulmonary artery pressure tended to decrease at rest over time. Resting lung function showed no change of vital capacity and FEV1. No significant change in exercise level and maximal O2-consumption during treadmill testing was observed. One patient died 34 months after the operation from sudden death. Our preliminary results show that patients after cardiomyoplasty may exhibit an impressive clinical improvement with less striking changes of objective hemodynamic parameters. This data is in agreement with the results of all other investigators. Some possible mechanisms of action are discussed and a risk profile suggested. According to the current state of experience with cardiomyoplasty, we do not consider this method an alternative to heart transplantation, but reserve it for patients with contraindications for heart transplantation.

Is it possible to perform immediate cardiac assist using untrained latissimus dorsi muscle in a work-rest regimen?

The authors investigated what contractile force (CF) could be obtained from unconditioned latissimus dorsi muscle immediately after mobilization and for the 2 week vascular period of recovery. Latissimus dorsi muscle mobilization was performed on seven adult (4 experimental and 3 control) sheep leaving only the pedicle and the peripheral muscle intact. Telectronics stimulators (Myostim 7220; Teletronics Pacing Systems, Inc, Englewood, CO) were implanted. Immediately after mobilization 11-35% of the initial CF was lost. A 30 min fatigue test was performed 1 hr after mobilization (20 g/kg preload, 10 V, 10 Hz, 15 BPM, 6 impulses per burst) using a 1 min work-1 min rest regimen. Two sheep lost 2-12% of initial CF; two increased CF by 14-24%. At the end of the fatigue test, CF consisted of 74-89% of immobilized CF. Electrical stimulation training of the muscle was then initiated with the following regimen in the experimental animals only: 15 BPM, single impulses, 5 V, 10 Hz. Every day the muscle was exercised using a work-rest regimen to mimic cardiac assist, starting with 20 min on day 2, and increasing by 2 min per day until a total of 50 min was reached on day 16. All animals were retested for CF using a 42 min fatigue test on days 6, 11, and 16. On day 6, there was no fatigue evident in the experimental group during the 42 min test. CF after testing was 59-81% (mean 67%) of initial data. In the control group (animals with no electrical stimulation training protocol), CF decreased by 11% (from 64 to 53%). On day 11, there was no fatigue evident in the experimental group; CF in all animals increased by 2-8%. On day 16, there was also no fatigue evident in the experimental group; CF increased by 0-9%. An additional 20 min of continuous contraction (15 BPM) fatigue testing was performed on the muscle without rest between the tests. No fatigue was evident at the end of testing. Light microscopic analysis of latissimus dorsi muscle biopsy specimens taken on the days of testing showed no evidence of necrotic damage. Our investigations suggest that it may be possible to start muscle transformation immediately after mobilization and use the untrained latissimus dorsi muscle for cardiac assist immediately after surgery for short periods.