Renato Ruggiero

Skeletal muscle ventricles: Left ventricular apex to aorta configuration

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.

Skeletal muscle ventricles as left atrial-aortic pumps: short-term studies.

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 with improved thromboresistance : 28 weeks in circulation

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.

A new configuration for right ventricular assist with skeletal muscle ventricle. Short-term studies.

BackgroundPrevious attempts to provide right heart assistance with skeletal muscle ventricles (SMYs) have been frustrated by the low preload supplied by the systemic venous blood pressure. In the present study, right ventricular pressure was exploited to provide more optimal preload, the SMV being connected by valved conduits between right ventricular free wall and the main pulmonary artery. Methods and ResultsSMVs were constructed from the right latissimus dorsi muscle in seven mongrel dogs. Following a delay period of 4 weeks, SMVs were preconditioned with 2-Hz continuous stimulation for 5–6 weeks. The SMV was then connected to the right ventricle using porcine valved Dacron conduit. A similar valved conduit connected the SMV to the main pulmonary artery that had been ligated proximally. SMVs were stimulated with 33-Hz burst frequency to contract synchronously with ventricular diastole in a 1:2 mode. The stimulator was intermittently turned off to permit comparison of assisted and nonassisted circulation. Cardiac output increased by 27% at 1 hour (1,437 ± 54 versus 1,140 % 64 ml/min, p < 0.005) and 30N at 4 hours (1,403 ± 161 versus 1,074 % 99 ml/min, p < 0.005), systemic arterial systolic pressure increased at 1 hour by 12% (87.1 ± 4.9 versus 78.0 ± 4.9 mm Hg, p < 0.05) and by 13% 4 hours (81.4 % 2.8 versus 72.3 ± 3.4 mm Hg, p < 0.005), and peak pulmonary arterial pressure increased at 1 hour by 35% (28.0 ± 2.1 versus 20.9 ± 1.8 mm Hg, p < 0.01) and by 37% at 4 hours 31.5 ± 2.6 versus 23.0 ± 0.4 mm Hg, p < 0.05). Peak SMY pressure was 52.8 ± 2.0 mm Hg at 1 hour and 49.9 ± 3.3 mm Hg at 4 hours (p = NS). ConclusionsThe improved preload supplied by this configuration of right ventricular assist enabled an SMV to provide stable and effective circulatory support throughout the 4-hour duration of the experiment.

Double cardiomyoplasty: Acute versus chronic results☆☆☆

We previously found that double cardiomyoplasty using both acutely raised, unconditioned latissimus dorsi muscles increased cardiac output by 9.6% (1,547 +/- 154 versus 1,695 +/- 166 mL/min), stroke volume by 18.2% (12.1 +/- 0.6 versus 14.3 +/- 0.7 mL), peak left ventricular pressure by 18.4% (98 +/- 3 versus 116 +/- 5 mm Hg), and peak right ventricular pressure by 62.5% (24 +/- 2 versus 39 +/- 4 mm Hg) (p < 0.05 for all differences). In this study 10 dogs underwent double cardiomyoplasty: 3 died perioperatively, and 7 underwent 8 weeks of muscle conditioning. After the conditioning period, the muscle flaps did not contract in 2 of the 7 dogs. Hemodynamics were measured in the remaining 5 dogs. Using fatigue-resistant muscle, cardiac output decreased by 3.7% (1,279 +/- 262 versus 1,233 +/- 274 mL/min), stroke volume decreased by 9.0% (9.5 +/- 1.2 versus 8.8 +/- 1.2 mL), and peak left ventricular pressure increased by 10.6% (82.1 +/- 6.5 versus 90.8 +/- 3.2 mm Hg), but not significantly. Peak right ventricular pressure increased significantly by 31.3% (24.3 +/- 2.1 versus 31.9 +/- 3.6 mm Hg; p < 0.05). Hemodynamic effects of individual left or right muscle contractions versus bilateral muscle stimulation were not significantly different except for a greater percentage increase in peak right ventricular pressure (right, 24.9 +/- 2.1 mm Hg unstimulated versus 28.0 +/- 2.1 stimulated; left, 26.3 +/- 0.9 mm Hg unstimulated versus 30.7 +/- 2.4 mm Hg stimulated; bilateral, 24.3 +/- 2.1 mm Hg unstimulated versus 31.9 +/- 3.4 mm Hg stimulated; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Skeletal muscle ventricles: a promising treatment option for heart failure.

Our most recent work on cardiac assist with canine latissimus dorsi muscle in a skeletal muscle ventricle (SMV) configuration is reported here. One animals SMV has been pumping blood effectively in the circulation for more than 16 months. To date there is no evidence of thromboembolism, and the dog has suffered no untoward effects. It has recently been shown, in a mock circulation study, that canine SMVs are capable of developing stroke work, at physiological preloads, much greater than that of the right ventricle and equivalent to that of the left ventricle. The improved ability of conditioned SMVs to perform work, independent of the circulation, during severe hypotension is also demonstrated. In the face of a 75% drop in left ventricular stroke work, the SMV stroke work dropped by only 50%. The continuing work on this subject suggests that a skeletal muscle ventricle may have the potential of becoming a viable alternative in the treatment of heart failure.

Intrathoracic Skeletal Muscle Ventricles: A Feasibility Study

Abstract 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 106). 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 106). SMVs may conveniently be positioned inside the chest, where they have the potential to function as left or right heart assist devices.

Autologous Skeletal Muscle, an Alternative for Cardiac Assistance

Original attempts to use skeletal muscle for cardiac assistance were soon abandoned when the problem of muscle fatigue could not be solved. In the last 2 decades, better understanding of muscle physiology and the development of successful protocols of electrical muscle conditioning have given new impetus to researchers around the world to proceed in the effort to identify useful applications of skeletal muscle to support the heart. More than 100 patients around the world have undergone cardiomyoplasty, mostly for cardiac failure. While subjective improvement in symptoms was noticed in the majority of the patients, only recently favorable hemodynamic changes have been documented. The other alternative that has been pursued in the laboratory is the construction of skeletal muscle ventricles that, after conditioning and vascular delay, have been shown to provide significant cardiac support when used for diastolic counterpulsation or for right heart bypass in animal models.

Canine skeletal muscle ventricles: functional assessment using the pressure-volume plane.

In five dogs, skeletal muscle ventricles (SMVs) were constructed from the latissimus dorsi muscle, and placed within the thoracic cavity. After a 3‐week delay period, SMVs were electrically preconditioned with 2‐Hz continuous stimulation for 6 weeks. At a second procedure, SMVs were connected to a mock‐circulation system, and performance was evaluated according to pressure‐volume relationships at three different SMV contraction rates (33, 54, and 97 per min) and three stimulation protocols (25, 43, and 85 Hz) under varying loading conditions. Under appropriate conditions of afterload, the end‐diastolic pressure‐volume relation of SMVs was comparable with that of the cardiac ventricles, although SMVs were less compliant. At higher burst stimulation frequencies, SMV compliance was increased. Compliance was not affected by varying the rate of SMV contraction. End‐systolic elastance, a reflection of contractility, appeared to be constant for each SMV, in contrast to cardiac ventricles, and was not influenced by changes in burst stimulation frequency or contraction rate. In this study, SMVs were capable of a level of stroke work 180% of that of the native right ventricle (RV) at rest (0.397 ± 0.047 × 106 ergs) and 37% of that of the left ventricle (LV) at rest (0.298 ± 0.61 × 106 ergs), at 33 contractions per minute (CPM), 25‐Hz burst frequency, and physiological preload, but this level could not be sustained at higher contraction rates. Nevertheless, power output (SMV stroke work x contraction rate) was maximal at 97 CPM. These findings demonstrate important function differences between pumping chambers constructed from conditioned skeletal muscle, and those composed of cardiac muscle, which must be considered when using skeletal muscle ventricles for cardiac support or replacement.

Functional Evaluation of Dynamic Cardiomyoplasty in Chronic Heart Failure Model

The mechanism of action of cardiomyoplasty was evaluated in a setting of left heart failure in sheep, using the pressure-volume relationship. A heart failure model was made by ligation of the coronary artery. Three months after infarction, five sheep underwent cardiomyoplasty, using a left latissimus dorsi muscle. After their muscle grafts had been electrically conditioned for 2 months, a terminal experiment was performed. The systemic pressure and cardiac output were not significantly different when measured 3 months after infarction and 2 months after cardiomyoplasty. However, the post-cardiomyoplasty pressure volume-loops generated at the time of terminal measurements were altered in all animals. End-systolic elastance (Ees) increased significantly after cardiomyoplasty, from 2.66 ± 0.41 to 4.59 ± 0.77 mmHg/ml. Pressure-volume area decreased significantly after cardiomyoplasty, compared with post-infarct (1932 ± 275 vs 3776 ± 537mmHg • ml). These findings suggest that the probable mechanism of action of cardiomyoplasty is that it actively supports the geometry of damaged cardiac muscle. The reduced oxygen consumption of the myocardium after cardiomyoplasty may be related to increased ventricular wall thickness and prevention of further ventricular dilatation.