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Skeletal muscle ventricles (SMVs) were constructed from the latissimus dorsi muscle in 15 beagles. The animals were divided into two groups based on modifications in the SMV construction: group I consisted of 5 animals and group II of 10 animals. After a 3-week vascular delay and 6 to 8 weeks of 2-Hz electrical conditioning, the SMVs were connected to the thoracic aorta. In group I, counterpulsation at 33 Hz resulted in an initial 24.4% augmentation of the mean diastolic pressure, a 27.1% decrease in the presystolic pressure, and a 15.9% increase in the endocardial viability ratio. In group II, the mean diastolic pressure rose by 24.7%, the presystolic pressure decreased by 14.3%, and the endocardial viability ratio increased by 24.5%. During propranolol-induced heart failure, the percentage increase in the mean diastolic pressure was improved (12.9% before propranolol infusion versus 27.6% during propranolol infusion), as was the percentage increase in the endocardial viability ratio (11.2% versus 28.7%). Under low cardiac output conditions, SMV contraction resulted in small but statistically significant increases in the total cardiac output (4.3% at 33 Hz, 7.6% at 85 Hz). One animal in group I survived for 589 days with a functioning SMV before progressive dilation of the SMV (impending rupture) developed. Delayed rupture of the SMV sewing ring anastomosis occurred in 2 dogs. Five animals in group II are all alive, with functioning SMVs in the circulation for 377 to 464 days. No animals in group II had rupture of their SMV or showed evidence of thrombus formation.

Skeletal muscle ventricles (SMVs) were constructed from the latissimus dorsi muscle in 12 dogs. In group I (n = 6), SMVs were placed intrathoracic, in the apex of the left hemithorax. In group II (n = 6), SMVs were positioned extrathoracic between the chest wall and subcutaneous tissue. After a 3-week vascular delay period, SMVs were electrically pre-conditioned with 2-Hz continuous stimulation for 6 weeks. At a second procedure, a valved conduit was placed between the left ventricular (LV) apex and the SMV, and a second valved conduit between the SMV and the thoracic aorta. The SMVs were stimulated to contract during diastole at a 1:2 ratio with the heart. In group I, SMVs generated peak pressures of 91 +/- 10 mmHg, pumped 47% of the systemic blood flow (0.73 +/- 0.25 vs 1.54 +/- 0.42 L/min; p < 0.05), and produced a 25% decrease in the LV systolic tension-time index (TTI) (16.9 +/- 2.7 vs 12.5 +/- 3.3 mmHg.sec; p < 0.05). In group II, SMV peak pressure was 93 +/- 10 mmHg, SMVs pumped 51% of the systemic blood flow (0.78 +/- 0.10 vs 1.53 +/- 0.42 L/min; p < 0.05), and the LV systolic TTI decreased 29% (14.0 +/- 0.8 vs 9.9 +/- 2.0 mmHg.sec; p < 0.05). There was no significant difference between group I and II. These data indicate that the SMV:LV apex-to-aorta configuration is the most effective method reported to date for skeletal muscle cardiac assist. Extrathoracic and intrathoracic SMVs functioned equally well after connection to the circulation.

Skeletal muscle ventricles (SMVs) were constructed from the latissimus dorsi muscle in 6 dogs. After 3 weeks of vascular delay followed by 6 weeks of 2-Hz continuous electrical conditioning, a valved conduit was placed between the left ventricular apex and the SMV and a second valved conduit, between the SMV and the aorta. The SMV was stimulated to contract during diastole at a 1:2 ratio with the heart. The SMV pumped 47% of the systemic blood flow initially (0.73 +/- 0.23 versus 1.54 +/- 0.42 L/min) and 40% after 3 hours. Skeletal muscle ventricle stimulation resulted in a 58% increase in mean diastolic pressure initially (52 +/- 9 to 82 +/- 11 mm Hg; p < 0.05) and a 73% increase (45 +/- 7 to 78 +/- 8 mm Hg) after 3 hours of continuous pumping. This was associated with a 68% increase in the endocardial viability ratio initially and a 63% increase at 3 hours. The systolic tension-time index decreased by 26% initially and 25% at 3 hours. This study indicates that the SMV configuration of left ventricular apex to aorta may be particularly suitable for left ventricular assist.

In 5 dogs, skeletal muscle ventricles (SMVs) were constructed from the latissimus dorsi muscle and placed in the left hemithorax. After a 3-week vascular delay period, SMVs were electrically preconditioned with 2-Hz stimulation for 6 weeks. At a second operation, SMVs were connected between the left atrium and thoracic aorta by afferent and efferent aortic root homografts, and stimulated to contract in a 1:2 diastolic mode. At a mean left atrial pressure of 12.4 +/- 1.3 mm Hg and a burst stimulation frequency of 33 Hz, SMV stroke volume was initially 43% of that of the native left ventricle, achieving a flow equivalent to 21% of cardiac output (194 +/- 38 versus 902 +/- 85 mL/min). At 50-Hz stimulation, this figure rose to 27% (246 +/- 41 mL/min; p less than 0.05). Skeletal muscle ventricle power output (the product of stroke work and contraction rate) at 33 Hz was 0.016 +/- 0.003 W, increasing to 0.024 +/- 0.004 W at 50 Hz (p less than 0.05), corresponding to 14% and 22%, respectively, of left ventricular power output (0.11 +/- 0.012 W). After 4 hours of continuous pumping, four of the SMVs were still generating flows of more than 70% of starting values and more than 60% of initial power output. This study demonstrates that SMVs can function in the systemic circulation at physiologic left atrial preloads.

Skeletal muscle ventricles (SMVs) were constructed from the left latissimus dorsi in 22 mongrel dogs. The configuration of these SMVs was different from those previously reported. The animals were divided into two groups: group A (n = 11) SMVs rested for 10 weeks after construction; group B (n = 11) SMVs rested for 18 weeks. At the end of the delay period, SMVs were tested in vivo with a mock circulation device. The SMVs in group B developed stroke work greater than those in group A. After acute testing, SMVs (n = 12) were connected to the descending thoracic aorta and stimulated to contract during diastole. Aortic diastolic counterpulsation was achieved in all dogs, with 9 animals surviving from 1 to beyond 28 weeks. In all of the dogs surviving 1 week or more, the SMVs remained free of thrombus. Aspirin was used as the only antithrombotic agent. Skeletal muscle ventricles in this study were able to develop stroke work similar to that previously reported, intermediate between that of the right and left ventricular stroke work, with a significantly decreased incidence of thromboembolism.

For skeletal muscle ventricles (SMVs) to be applied clinically, it is likely that they will have to be placed within the chest. Ease of subsequent connection to the circulation, and avoidance of significant lung compression, are factors that could influence SMV size and shape in a way that may prejudice their ability to pump effectively at physiological preloads. In five dogs, specially designed SMVs were constructed from the latissimus dorsi muscle, and placed in the apex of the left hemithorax. After a 3-week delay, the muscle was preconditioned electrically by 2-Hz continuous stimulation for 6 weeks. At a later thoracotomy, this positioning of SMVs permitted easy surgical access to the heart and great vessels. SMVs were then connected to a mock circulation device for functional evaluation. As right-sided pumps, at a preload of 10 mmHg, SMVs generated a stroke volume (SV) and stroke work (SW) exceeding that of the native right ventricle (SV = 8.9 +/- 0.8 vs 7.9 +/- 0.6 mL; SW = 0.44 +/- 0.03 vs 0.20 ergs x 10(6)). As left-sided pumps, also at a preload of 10 mmHg, SMV SV, and SW was roughly half that of the left ventricle (SV = 3.7 +/- 0.2 vs 7.9 +/- 0.6 mL; SW = 0.29 +/- 0.03 vs 0.57 +/- 0.05 ergs x 10(6)). SMVs may conveniently be positioned inside the chest, where they have the potential to function as left or right heart assist devices.

Skeletal muscle ventricles were constructed in fifteen dogs. After a delay period of 4 weeks the skeletal muscle ventricles were connected to the descending thoracic aorta with a polytetrafluoroethylene bifurcation graft (Gore-Tex bifurcation graft, W.L. Gore & Associates, Inc., Elkton, Md.). The aorta was ligated between the two limbs of the graft so that there was obligatory blood flow through the skeletal muscle ventricle. Nine skeletal muscle ventricles were lined with autogenously derived tissue, either pleura or pericardium, whereas six had no specific lining other than an induced fibrous reaction. The skeletal muscle ventricles were activated to contract during cardiac diastole. Aortic diastolic counterpulsation was achieved in all dogs, with ten surviving from 1 week to beyond 9 months. Thrombus eventually developed in all but three of the skeletal muscle ventricles, but no dog had clinical evidence of thromboemboli. The three thrombus-free skeletal muscle ventricles were lined with pleura, including the animal surviving beyond 9 months. These results indicate that canine skeletal muscle can provide aortic diastolic counterpulsation for 9 months without clinically apparent thromboembolic complications.

Skeletal muscle ventricles were constructed in 12 dogs. In one group of dogs (n = 7) the skeletal muscle ventricles were constructed around a 17 ml Teflon mandrel, and in the other group (n = 5) a 45 ml mandrel was used. Use of the larger mandrel resulted in an increase in compliance and greater stroke work over the physiologic range of preloads and afterloads. With the larger mandrel, stroke work consistently exceeded normal canine stroke work at physiologic filling pressures.

The effect of chronic electrical stimulation on muscle mass of pedicled diaphragmatic muscle grafts (DMGs) implanted into the right ventricle was studied in 21 dogs. Nineteen dogs, followed up to 70 days (mean, 34 days), were divided into three groups. In six dogs (control) the DMG was not stimulated. In six other dogs the DMG was stimulated at 50 stimuli/min with a fixed-rate unipolar pacemaker. In seven animals the graft was paced 1:1 with the dog's own rhythm with an R-wave synchronous pacemaker. Surface area of the DMG decreased 34% to 43% (P less than 0.05) in all dogs. DMG thickness increased in all dogs (P less than 0.05). The increase was 29% for control animals and 132% and 134% for the two paced groups. The volume of the DMG decreased 24% in the nonpaced animals but increased 29% and 51% in the two paced groups. Histologic studies showed some degree of muscle degeneration and atrophy in all grafts. However, morphometric studies showed relatively normal fiber diversity in paced grafts. Fiber size decreased in nonpaced grafts, indicating muscle atrophy. Perfusion studies with labeled microspheres and silicone injections demonstrated collateral circulation with the host ventricle as early as 28 days. However, total blood flow to DMGs implanted for 4 to 6 weeks averaged only 32% of the blood flow to normal ventricular myocardium. Chronic electrical stimulation of DMGs reduces muscle degeneration and atrophy and is associated with an increase in graft thickness and volume.

Skeletal muscle ventricles were constructed from the latissimus dorsi in seven dogs. All skeletal muscle ventricles underwent a vascular delay period followed by 4-7 weeks of electrical preconditioning. In group 1 (n = 5), the skeletal muscle ventricle was used to replace native right-heart function. Venous return from the superior and inferior venae cavae was directed to the skeletal muscle ventricle with outflow directed to the pulmonary artery. In group 2 (n = 2), the skeletal muscle ventricle was used for partial bypass of the right heart. In both groups, right-heart bypass was continued for as long as 8 hours. In group 1 after 4 hours of continuous complete right-heart bypass, stroke work was 163 +/- 63% of canine right ventricular stroke work. Skeletal muscle ventricle output was 1.14 +/- 0.02 l/min, central venous pressure was 13 +/- 1.5 mm Hg, and systemic systolic blood pressure was 95 +/- 9 mm Hg. Skeletal muscle ventricles are capable of performing the work of the right heart with near-physiological filling pressures.

A pedicled diaphragmatic skeletal muscle graft was used to replace a portion of resected right ventricle in 35 dogs. The graft contracted when electrically stimulated directly or via the phrenic nerve before and after insertion. The electrical pacing threshold was lower for phrenic nerve stimulation (0.9 +/- 0.20 mamp) than for direct graft stimulation (2.3 +/- 1.19 mamp). The heart could be captured and paced by stimulating the muscle graft with higher current (16.2 +/- 4.49 mamp). The delay from pacing stimulus to muscle graft contraction when the graft was paced directly was 10 msec. The epicardial activation time delay when the heart was paced through the muscle graft was 27.0 +/- 9.08 msec. When the muscle graft pedicle was transected, the graft lost its ability to contract. The heart, however, could still be captured electrically through the graft for up to 4 hours. Strain gauge studies of the nonstimulated muscle graft showed tension development during pre-ejection ventricular contraction identical to that of the right ventricle. In the ejection phase, muscle graft tension slowly declined. The stimulated muscle graft developed active tension and echographically demonstrated muscle thickening during contraction. This study demonstrates that a vascularized, neurally innervated diaphragmatic muscle graft can be placed into the right ventricle. The graft retains its ability to contract in response to direct or phrenic nerve stimulation. It can be made to contract during any phase of the cardiac cycle. Thus diaphragmatic muscle grafts may provide a method to augment ventricular cavity size with synchronously contracting muscle.