Hiroshi Niinami

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.

Use of skeletal muscle grafts for cardiac assist

Skeletal muscle is a potential power source for cardiac assist. Two approaches have been used to harvest this power: dynamic cardiomyoplasty, which involves the application of a muscle directly to the heart to support cardiac contractile function; and the construction of skeletal muscle pouches or ventricles, which are used as separate pumps working either in parallel or in series with the heart. These techniques may represent an alternate therapeutic approach in patients with end-stage heart disease or in infants with certain congenital heart anomalies.

Konno procedure for congenital aortic stenosis with a single coronary artery from the left coronary sinus.

A right coronary artery originating from the left coronary sinus and traversing anteriorly is thought to be one of the contraindications for a Konno aortoventriculoplasty in congenital aortic stenosis because this procedure necessitates incision of the right ventricular outflow tract. The case of a 5‐year‐old girl with congenital aortic stenosis associated with a single coronary artery, successfully treated surgically by the Konno procedure and right coronary artery reimplantation, is reported. Preoperatively there was a pressure gradient between the left ventricle and the ascending aorta of 109 mmHg, which disappeared postoperatively. A postoperative angiography showed a patent right coronary artery.

Skeletal muscle. New techniques for treating heart failure.

Presently, only cardiomyoplasty has been used clinically. This is not surprising because it is a relatively safe operation to perform, avoids problems of thrombosis, and is unlikely to do harm. Evidence is beginning to emerge that clinical improvement may be due to enhanced cardiac output and not simply to limiting ventricular distension or to a placebo effect. We consider skeletal muscle ventricles to be experimental; however, our experiment in which one dog continues to do well after one year demonstrates that long-term function is achievable. Many problems remain. Further refinement may enable SMVs to work at even lower filling pressures. Although the great majority of cardiac failure occurs in adults, a significant number of children are born with congenital cardiac deficiencies for whom skeletal muscle assist also may offer potential therapy.