Static Cardiomyoplasty With Synthetic Elastic Net Suppresses Ventricular Dilatation and Dysfunction After Myocardial Infarction in the Rat: A Chronic Study

Although static cardiomyoplasty prevents the left ventricle (LV) from dilatation, it may interfere with diastolic relaxation, or cause restriction. We developed a synthetic net with dual elasticity and tested its effect late after myocardial infarction in the rat. LV pressure–volume relationships (PVR) were successively analyzed before, after intravenous volume load, and 10 minutes after occlusion of the left anterior descending artery. Rats were then randomized into groups receiving synthetic net wrapping around the heart (NET+, n = 8) and only partially behind LV (NET–, n = 9), and they underwent the same PVR studies 6 weeks later. End‐diastolic and end‐systolic PVR were defined, and LV size and function were compared under standardized loading conditions. Although there was no difference in Day 0, increase in LV end‐diastolic and end‐systolic volumes were significantly attenuated in NET+ rats 6 weeks later when there was a significant correlation between LV volumes by PVR estimation and actual measurements, with significant differences in both measures between the groups: NET+ < NET–. The presence or absence of net did not show restrictive hemodynamics under acute volume load. Static cardiomyoplasty using a synthetic elastic net significantly attenuated LV dilatation and dysfunction without restriction late after myocardial infarction in the rat.     

Myocardial Oxygen Consumption Is Affected by Dynamic Cardiomyoplasty in Dogs with Adriamycin-Induced Cardiomyopathy

The purpose of the study was to investigate a possible myocardial sparing effect by dynamic cardiomyoplasty. We directly measured cardiac work and myocardial oxygen consumption after dynamic cardiomyopathy in dogs with adriamycin-induced cardiomyopathy. Ten dogs with cardiomyopathy induced by 4 weekly intracoronary infusions of adriamycin were studied. Five dogs underwent right latissimus dorsi cardiomyoplasty with progressive myostimulation, and five served as controls. Right heart and coronary sinus catheterizations were performed at 0, 10, and 15 weeks. Four and two dogs, respectively, the cardiomyoplasty and the control group, survived until 15 weeks. Cardiac work was not different between the control and the cardiomyoplasty groups (p = 0.42). Myocardial oxygen consumption was less in the cardiomyoplasty group (185.70 +/- 37.22; 165.75 +/- 25.86; 161.40 +/- 54.14 J/min at 0, 10, and 15 weeks, respectively) compared to the control group (147.80 +/- 70.99; 275.00 +/- 103.24; 263.50 +/- 52.75 J/min at 0, 10, and 15 weeks, respectively, p = 0.019). Mechanical cardiac efficiency was not meaningfully different between the cardiomyoplasty group (16.08% +/- 5.39%; 20.51% +/- 5.89%; 20.67% +/- 11.98% at 0, 10, and 15 weeks, respectively) compared to the control group (15.29% +/- 8.06%; 9.40% +/- 1.22%; 13.40% +/- 2.29% at 0, 10, and 15 weeks, respectively, p = 0.093). Acute changes of the cardiosynchronization ratio (2:1, 1:1, OFF) did not affect myocardial oxygen consumption or cardiac work within the cardiomyoplasty group. Dynamic cardiomyoplasty reduced myocardial oxygen consumption in dogs with adriamycin-induced cardiomyopathy.     

Cardiomyoplasty

The article analyses the current state of the problem of cardiomyoplasty as a new method for the treatment of patients with myocardial cardiac insufficiency. The authors show the experimental and clinical material on the possibility and efficacy of using skeletal muscles for improving myocardial contractility and raising the cardiac index. Experience gained in our country (6 operations) in cardiomyoplasty in patients with severe form of ischemic heart disease is discussed. The authors used an original Soviet produced cardiosynchronized electroneurostimulator "Stiminak" for stimulation of the muscles. Analysis of personal experimental material allows new ways for the development of the problem to be planned.     

Hemodynamic Effects of Cardiomyoplasty in an Experimental Model of Acute Heart Failure and Atrial Fibrillation

Abstract: The aim of our work was to study the hemodynamic effects of dynamic cardiomyoplasty on an acute animal model of atrial fibrillated heart failure. Eight anesthetized open chest dogs suffering from atrial fibrillation and heart failure, obtained by topic acetylcholine and propranolol, were treated by a cardiomyoplasty procedure performed with an electrostimulated latissimus dorsi muscle flap (LDMF). Values considered for analysis during LDMF stimulation were selected from cardiac cycles with R-R intervals similar to those when the LDMF was not stimulated (±20 ms). Atrial fibrillated heart failure showed a significant increase of systemic vascular resistance, end diastolic left ventricular pressure (EDLVP) and right atrial pressure (p < 0.05), and a significant decrease in cardiac output, systolic left ventricular pressure (SLVP), and mean aortic pressure (p < 0.05) compared with control values. LDMF stimulation in atrial fibrillated heart failure resulted in a significant increase of SLVP, cardiac output, and mean aortic pressure (p < 0.05) and a significant decrease of systemic vascular resistance, EDLVP, and right atrial pressure (p < 0.05) compared with nonstimulated values. The highest LVP values were obtained with R-R intervals long enough to allow an adequate LV filling. We conclude that dynamic cardiomyoplasty provides an appropriate recovery in this animal model of atrial fibrillated heart failure. Cardiomyoplasty is an appropriate procedure for cardiac assist when R-R intervals allow an adequate LV filling.     

Clinical Results of Dynamic Cardiomyoplasty

Thirty-five cardiomyoplasty procedures were performed in five patients with dilated and 30 patients with ischemic cardiomyopathies. Russian-made cardiomyostimulators (CMS) were implanted in these patients. Twenty-one patients underwent a one-step procedure using a left thoracotomy for cardiomyoplasty, while in 14 patients, a two-step procedure that included a mid-line sternotomy was carried out. During the average follow-up period of 9 ± 2.1 months, studies were carried out that showed in survivors improved clinical functional status and decreased heart failure symptoms. Evidence of revascularization of the ischemic myocardium from the latissimus dorsi muscle (LDM) wrap was obtained by angiography and radioactive scintigraphy. In five patients, the CMS had to be removed due to complications, and in all these patients, their clinical functional status deteriorated following the cessation of cardiomyostimulation.     

Binocular Blindness Following Dynamic Cardiomyoplasty

A bstract A 40-year-old man with viral cardiomyopathy underwent uncomplicated dynamic cardiomyoplasty. On the third postoperative day, he was rescued from an 8-hour period of severe cardiogenic shock. Eleven days postoperatively, he was withdrawn and uncooperative, preferring to be left alone. He then complained of total blindness, which persisted to his sudden death on postoperative day 26. Clinical examination revealed no neurological abnormality except for signs consistent with a diagnosis of ischemic optic neuropathy. The optic nerve in the scleral canal is especially vulnerable to hypoperfusion. Blindness has been reported following severe hemorrhage, bilateral neck dissection, and has an incidence of 1 per 1100 cases following cardiopulmonary bypass. Anemia and hypotension may be consistent risk factors predisposing patients to this catastrophic complication.     

Clinical Experience with Dynamic Cardiomyoplasty

Dynamic cardiomyoplasty using the latissimus dorsi muscle graft (LDMG) was applied to 11 patients with dilated cardiomyopathy of different etiologies. Our first case was operated on July 1987. All patients were in Functional Class (FC) IV New York Heart Association (NYHA) and had multiple previous admissions in intensive care units for intractable cardiac insufficiency. Two patients died during the procedure, the perioperative mortality was 18%. One patient died of recurrent acute myocarditis at the fourth postoperative month and a second patient died in the sixteenth postoperative month. Both patients were asymptomatic, in FC I-II, and the cause of death was sudden arrhythmia (ventricular fibrillation). The remaining seven patients (63.6%) were in FC I-II and the longest follow-up was 30 months. In all patients, the ejection fraction (EF) by radioisotopic ventriculography improved an average of 50% as well as their ergometric test. Dynamic cardiomyoplasty appears to be a satisfactory alternative for the treatment of patients with severe cardiac insufficiency secondary to dilated cardiomyopathy. Its main advantage seems to be a significant improvement in the quality of life for these patients.     

体外循环缺血-再灌注心肌肌钙蛋白I丢失与心功能障碍的关系

目的　探讨体外循环缺血 -再灌注心肌肌钙蛋白 I(Tn I)丢失与心功能障碍的关系。　方法　 12条雄性杂种狼犬 ,按体外循环升主动脉阻断时间不同分为两组 :组 (n=6 ) :主动脉阻断 2 5分钟 ;组 (n=6 ) :主动脉阻断 15 0分钟。分别于转流前、主动脉开放后 10分钟、30分钟、6 0分钟时测定动脉和冠状静脉窦血清 Tn I浓度 ,同时监测围术期冠状静脉窦血流量和血流动力学。　结果　再灌注后冠状静脉窦血清 Tn I浓度持续高于动脉血清 Tn I浓度 (P<0 .0 1) ,提示心肌丢失 Tn I。组 与组 比较 ,组 心肌 Tn I丢失水平更显著 ,且终止体外循环后心脏指数、每搏指数、左心室每搏作功指数均显著降低 (P<0 .0 5 )。　结论　体外循环缺血 -再灌注心肌 Tn I丢失程度与心功能障碍的发生密切有关 ,提示心肌细胞 Tn I丢失很可能是导致缺血后心肌功能障碍的分子基础之一。     

Mannitol But Not Dantrolene Prevents Myocardial Dysfunction Following Intra-cranial Hypertension in Rats

Cardiac complications stemming from intra-cranial hypertension may result from impaired intra-cellular Ca(2+) homeostasis. The aim of this study was to examine the effects of dantrolene, a blocker of sarcoplasmic reticulum (SR) Ca(2+) release, on myocardial dysfunction associated with intra-cranial hypertension in rats. Dantrolene (10 mg) with and without 15% mannitol was administered to halothane-anesthetized rats prior to induction of intra-cranial hypertension by subdural balloon inflation. Its effects were compared to 3% and 15% mannitol and 5% Pentaspan. Dantrolene with mannitol or 15% mannitol alone prevented the transient intra-cranial hypertension-induced hyperdynamic response and ensuing circulatory collapse that was found in animals pre-treated with 3% mannitol solution or pentaspan. Moreover, hemodynamic function was preserved irrespective of TnI cleavage. However, only animals treated with high dose 15% mannitol exhibited lower lipid peroxidation content in the heart. In contrast, pre-treatment with dantrolene alone did not prevent the cardiac complications associated with intra-cranial hypertension. In conclusion, 15% mannitol attenuated the cardiopulmonary complications associated with intra-cranial hypertension. Dantrolene without mannitol was without effect. Since mannitol exhibits free radical scavenging properties, protection could be the result of a decrease in oxidative stress after intra-cranial hypertension.     

Present Trends in Clinical Experience with Dynamic Cardiomyoplasty

Abstract: Dynamic cardiomyoplasty has been performed to reinforce the myocardium in the treatment of patients with severe cardiomyopathies. At the Heart Institute of S˜o Paulo University Medical School, 36 patients were submitted to cardiomyoplasty between May 1988 and December 1993. The indications were idiopathic dilated car-diomyopathy in 31, ischemic cardiomyopathy in 3, and Chagas' disease cardiomyopathy in 2 patients. Twenty-eight patients were categorized in New York Heart Association (NYHA) Class III and 8 in Class IV despite the use of maximal medical therapy. There were no hospital deaths, and patients were followed up from 2 to 70 months (mean, 24 months). Besides the improvement of NYHA functional class from 3.2 ± 0.6 to 1.6 ± 0.9 at 6 months of follow-up, patients also presented significant changes in the left ventricular systolic and diastolic functions. Nevertheless, 16 patients died, and 2 patients were submitted to heart transplantation during late follow-up. Actuarial survival rates were 82.3% at 1 year, 61.5% at 2 years, and 38.8% at 5 years of follow-up. Otherwise, the analysis of factors influencing the outcome showed that long-term survival was significantly affected by preoper-ative functional class and by pulmonary vascular resistance. The 26 patients operated in NYHA functional Class III and with pulmonary vascular resistance below 4 Wood units presented survival rates of 72.7% at 2 years and of 63% at 5 years of follow-up. In conclusion dynamic cardiomyoplasty improves functional class and left ventricular function in patients with severe cardiomyopathies. However, the long-term survival after this surgical procedure may be limited by the patients' condition before the operation.     

Paced Skeletal Muscle for Dynamic Cardiomyoplasty

Four patients, each with a history of myocardial infarction and diffuse coronary artery disease, underwent application of left latissimus dorsi (LD) muscle with intact neurovascular bundle to the anterolateral wall of the left ventricle. The muscle was conditioned over a six-week period subsequent to operation in 3 patients and was conditioned preoperatively with a burst stimulus in the fourth. Biopsy specimens confirm the experimental data that human skeletal muscle can be electrically conditioned over a six- to ten-week period to contain mainly fatigue-resistant type I fibers. All patients survived the procedure, and 3 showed improvement secondary to aneurysmectomy. In Patient 1, a modified resection was performed, and at 28 months after operation, at the 75-W level of exercise, the ejection fraction was 54% paced versus 45% nonpaced. In Patient 2, at 12 months, the ejection fraction at rest was 44% paced versus 30% nonpaced. Doppler echo studies confirmed the presence of the flap and its function in the paced and nonpaced mode. The third patient died of a sudden ventricular arrhythmia 2 months following operation. An infected, nonfunctioning, degenerated flap was found at autopsy. Patient 4 did not have an aneurysm. She received a bypass graft to the right coronary artery and underwent cardiomyopexy in an attempt to relieve medically refractory incapacitating chronic congestive heart failure. Ten months postoperatively, ejection fraction at rest was 33% paced versus 25% nonpaced. Constrictive myopathy has not been encountered in any of these patients.     

Nonsurgical Infarctectomy in Acute Experimental Myocardial Infarction

This study examines whether a catheter mounted left intraventricular balloon may prevent left ventricular (LV) dysfunction following acute experimental myocardial infarction. In 10 anesthetized pigs, multiple coronary arterial ligations were applied around the apex of the heart. LV end-diastolic pressure (LVEDP), aortic flow (AF), and LV long and short axis fractional shortening (FS) were measured before and at 15 min intervals after ligations. At the 60th min after ligation, the LV long axis FS and AF decreased by 7.2 ± 2.6% (p < 0.05) and 13.25 ± 2.68% (p < 0.01), respectively, and the LVEDP increased by 4.3 ± 1.1 mm Hg (p < 0.01) while no change was noted in the LV short axis FS. An intraventricular catheter mounted nonpulsating balloon was positioned over the endocardium of the infarcted area at the LV apex. Inflation of the nonpulsating balloon to an optimal volume, which was found to be equal to 8–10% of the LV end-diastolic volume, resulted in a reduction (by 3.8 ± 1.2 mm Hg, p < 0.01) of the already increased LVEDP and in an increase (by 6.6 ± 2.1%, p < 0.05) in the LV short axis FS while no statistically significant change was noted in the AF and LV long axis FS. It is concluded that an intraventricular catheter mounted balloon patch positioned over the endocardium of the infarcted area may ameliorate early LV dysfunction, possibly by interfering with the functional geometry of the LV contraction.     

Potential Role of Neutrophil Anti-Adhesion Therapy in Myocardial Stunning,Myocardial Infarction,and Organ Dysfunction After Cardiopulmonary Bypass

Abstract When activated neutrophils are recruited and bind to endothelial tissues, they release leukotrienes, proteolytic enzymes, and free radicals. The latter has been implicated in myocardial stunning following periods of ischemia and reperfusion, as may occur following cardiopulmonary bypass (CPB). The neutrophil surface complex CD11/CD18 promotes the neutrophil-endothelial adhesion process. Monoclonal antibodies have been developed that can block neutrophil adhesion to the endothelium by preventing CD11/CD18 binding to adhesion molecules (ICAM-1 or ELAM-1) located on endothelial cells. We used monoclonal IgG antibody 60.3 to block neutrophil adherence and thereby potentially reduce myocardial stunning. Pretreatment of rabbits subjected to myocardial ischemia/reperfusion with either monoclonal 60.3 or saline resulted in only a small increase in the rate of recovery of preload recruitable stroke work index during reperfusion. More severe occlusion may have been needed to see significant results. We also evaluated the effects of anti-neutrophil therapy in animal models of CPB. Rhesus monkeys were subjected to deep hypothermia and CPB, followed by 24 hours of fluid resuscitation. Animals receiving monoclonal 60.3 (N = 3) showed less weight gain, less infused resuscitative fluid, and higher terminal hematocrit and PaO₂ than controls (N = 3). Anti-neutrophil therapy may prevent multiorgan system failure in certain high risk patients.