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Biomedical subjects

L W Stephenson

Publications and source records attributed to L W Stephenson.

At least 55 records · Page 3Linked to original sources
PubMed1991

Skeletal muscle ventricles: update after 18 months in circulation.

Skeletal muscle ventricles (SMVs) have been constructed from canine latissimus dorsi muscle and connected to the aorta as aortic diastolic counterpulsators. Presently one dog remains alive and well with an SMV that has been functioning continuously in circulation for 18 months, without evidence of thromboembolic complications. SMVs are able to perform cardiac-type work with an output equal to that of the left ventricle at physiologic preloads, when tested with a mock circulation device in our laboratory. SMVs have been used for right-sided cardiac assist. In acute experiments these ventricles have functioned effectively, bypassing the right side of the heart for up to 8 h. Most recently we have tested SMVs using them chronically to pump blood in the right-sided circulation, and at the time of writing they have been shown to function effectively in this configuration for up to 18 days. SMVs may be used in the future as a method of treating patients with left- or right-sided heart failure.

Animals↗
PubMed1991

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.

Cardiac Surgical Procedures↗
PubMed1991

Intrathoracic skeletal muscle ventricles: a feasibility study.

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.

Animals↗
PubMed1991

Canine latissimus dorsi cardio-double myoplasty: acute feasibility study.

Cardio-double myoplasty was performed in eight mongrel dogs. Both latissimus dorsi muscles were dissected from the chest wall and wrapped around the heart. They were then stimulated using an R wave synchronous stimulator. Hemodynamic measurements were obtained, first with the stimulator off and then with stimulator activated. After measuring hemodynamic effects in a normal heart, acute heart failure was induced by the infusion of propranolol (5 mg/kg). Hemodynamic data were then obtained in the same fashion. In a normal heart state, cardio-double myoplasty increased the cardiac output 9.9% +/- 2.24 (p less than 0.005), the left ventricular pressure 18.7% +/- 3.53 (p less than 0.001), the pulmonary artery pressure 72.2% +/- 25.4 (p less than 0.01), and the stroke volume 13.4% +/- 5.73 (p less than 0.05). In a failing heart, the cardiac output increased 21.6% +/- 3.34 (p less than 0.005), the left ventricular pressure increased 20.8% +/- 3.34 (p less than 0.005), the pulmonary artery pressure increased 87.2% +/- 39.9 (p less than 0.05), and the stroke volume increased 46.9% +/- 22.9 (p less than 0.05). The left ventricular end-diastolic pressure decreased slightly and the central venous pressure did not change in either the normal state or during cardiac failure. Cardio-double myoplasty resulted in a significant circulatory augmentation particularly in the setting of cardiac failure.

Animals↗
PubMed1991

Skeletal muscle bioenergetics during frequency-dependent fatigue.

The bioenergetic correlates of skeletal muscle fatigue were assessed in vivo with phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopy. After surgical construction of latissimus dorsi muscle ventricles, seven beagles underwent 31P-NMR spectroscopy during 12-min exercise protocols at 25- and 85-Hz stimulation frequencies and during both isovolumetric and dynamic contractions. Exercise at 85 Hz was associated with significantly greater fatigue than exercise at 25 Hz. At both frequencies, the onset of exercise was associated with a marked increase in inorganic phosphate (Pi) and a decrease in phosphocreatine (PCr). As the muscle fatigued at 85 Hz but not at 25 Hz, the phosphorus spectra returned to near baseline with a decrease in Pi and increase in PCr. For a given amount of force generated, the Pi-to-PCr ratio was higher for dynamic contractions than for isovolumetric contractions. This study indicates that high-frequency fatigue is unlikely to result from the direct effects of high-energy phosphate metabolism and that contractions producing external work consume more metabolic energy than equally forceful isometric contractions.

Animals↗
PubMed1991

Correlates of fatigue resistance in canine skeletal muscle stimulated electrically for up to one year.

In response to patterns of chronic electrical stimulation that increase its overall level of use, mammalian skeletal muscle becomes highly resistant to fatigue. The metabolic basis for this adaptation is well documented in the rabbit, but up to now it has not been possible to identify analogous changes in the dog. In this study, canine latissimus dorsi muscles were stimulated in situ for 2, 6 and 12 mo. Marked increases in fatigue resistance were consistently demonstrated. Citrate synthase and succinic dehydrogenase, conventionally used as markers of oxidative metabolism, did not increase in activity, but enzymes involved in major pathways supplying substrates to the tricarboxylic acid cycle increased up to threefold. Stimulation elevated the volume fraction of mitochondria 1.5-fold and that of lipid droplets 4.5-fold. After 6 mo of stimulation, mean fiber diameter had decreased by 30% and the area occupied by nonmuscle tissue had increased by 11%; these changes showed no further progression at 12 mo. Thus stimulated muscle becomes stably adapted to an increase in use, but the metabolic strategies for achieving increased fatigue resistance vary between species.

Adaptation, Physiological↗
PubMed1991

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

BACKGROUND: Previous attempts to provide right heart assistance with skeletal muscle ventricles (SMVs) 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 RESULTS: SMVs 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 a 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 less than 0.005) and by 30% at 4 hours (1,403 +/- 161 versus 1,074 +/- 99 ml/min, p less than 0.005), systemic arterial systolic pressure increased at 1 hour by 12% (87.1 +/- 4.9 versus 78.0 +/- 4.9 mm Hg, p less than 0.05) and by 13% at 4 hours (81.4 +/- 2.8 versus 72.3 +/- 3.4 mm Hg, p less than 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 less than 0.01) and by 37% at 4 hours (31.5 +/- 2.6 versus 23.0 +/- 0.4 mm Hg, p less than 0.05). Peak SMV pressure was 52.8 +/- 2.0 mm Hg at 1 hour and 49.9 +/- 3.3 mm Hg at 4 hours (p = NS). CONCLUSIONS: The 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.

Animals↗
PubMed1991

Skeletal muscle as a myocardial substitute.

Although skeletal muscle currently offers a realistic means for providing functional support of the failing myocardium, more research is required to define the optimal mode of assist. The mechanism by which cardiomyoplasty augments cardiac function is unclear, although symptomatic improvement following the procedure is being increasingly reported. Skeletal muscle ventricles, on the other hand, have the potential to replace left ventricular function and have pumped effectively in the circulation for more than 1 year. With continued improvements in SMV design, the future for this mode of support is optimistic. The efficacy of some other forms of circulatory support using skeletal muscle remains to be elucidated.

Animals↗
PubMed1991

Autogenously lined skeletal muscle ventricles in circulation. Up to nine months' experience.

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.

Animals↗
PubMed1990

Skeletal muscle ventricles for total heart replacement.

Skeletal muscle ventricles (SMV) were constructed from canine left latissimus dorsi muscle. The animals were divided into three groups: group A (n = 5), SMVs rested 4 weeks without electrical conditioning; group B (n = 6), SMVs rested 4 weeks and then electrically conditioned for 6 weeks; group C (n = 5), SMVs rested 18 weeks without electrical conditioning. At the end of each protocol, the SMVs were acutely tested by connecting them to a mock-circulation device. The SMVs in group C developed stroke work at physiologic preloads superior to any previously reported, as high as 194% of left ventricular stroke work at afterloads of 80 mmHg. The SMVs in group B developed work outputs equivalent to 53% of the left ventricle, which is still more than four times that of the right ventricle. The results show that it is possible to harvest sufficient work from skeletal muscle ventricles to fully replace cardiac function at physiologic preloads.

Adaptation, Physiological↗
PubMed1989

Effects of collateral blood vessel ligation and electrical conditioning on blood flow in dog latissimus dorsi muscle.

Utilization of skeletal muscle as a myocardial substitute requires it to undergo two major modifications: mobilization to the site of action and adaptation to continuous activity. We have examined the effects of collateral blood vessel ligation, which would accompany mobilization, on blood flow in control and electrically conditioned canine latissimus dorsi (LD) muscle. Blood flows were measured at rest and during a vigorous isometric fatigue test. In 22 control muscles, electrical stimulation during the fatigue test resulted in a sevenfold increase in muscle blood flow (0.26 +/- 0.18 ml/g/min at rest, 1.69 +/- 0.84 ml/g/min during stimulation). No difference was detected in flow to distal and proximal portions of the muscle. In three muscles where collateral vessels were ligated immediately before measurement of blood flow, flow in the proximal portion of the muscle was not significantly different from control, but in the distal portion, stimulation failed to elicit an increase in flow (0.12 +/- 0.13 ml/g/min at rest, 0.16 +/- 0.07 ml/g/min during stimulation). In animals allowed a 3-week recovery period following collateral vessel ligation, stimulation-induced increases in blood flow were detected but remained lower than control. Muscles which had been conditioned by continuous electrical stimulation for 6-7 weeks at 2 or 10 Hz generated less peak isometric tension than controls (peak tension = 4.5 +/- 1.7 kg control, 2.4 +/- 0.7 kg following 2 Hz conditioning, 1.6 +/- 0.4 kg following 10 Hz conditioning). However, these muscles demonstrated an increased resistance to fatigue.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗
PubMed1989

Skeletal muscle ventricles: improved performance at physiologic preloads.

We attempted to construct skeletal muscle ventricles (SMVs) so that they would develop optimal stroke work at physiologic preloads of 5 to 15 mm Hg. Thirty-one SMVs were constructed in mongrel dogs. The effects of electrical preconditioning with 2 Hz continuous and 25 Hz burst patterns were evaluated, as well as the application of passive stretch to the muscle fibers during preconditioning. We evaluated the stroke work developed by these SMVs at afterloads of 30 mm Hg and 80 mm Hg in vivo, using a mock circulation device. During mock circulation studies, the SMVs were stimulated via the thoracodorsal nerve with either a 25 Hz or 85 Hz burst pattern. SMVs with 2 Hz preconditioning developed significantly higher stroke work than SMVs with 25 Hz preconditioning under all conditions of afterload, preload, and stimulation frequency (p less than or equal to 0.001). Under these conditions, for the 2 Hz preconditioned SMVs, passive stretch during preconditioning resulted in a further significant increase in developed stroke work (p less than 0.05). For these SMVs, with an 85 Hz stimulation frequency, stroke work averaged 410% of canine RV stroke work, and 59% of canine LV stroke work at physiologic preloads and afterloads.

Animals↗
PubMed1989

Surgery for left ventricular aneurysm. Early survival with and without endocardial resection.

In the past 3 years, 86 patients had left ventricular aneurysms resected or plicated. Sixty-eight had recurrent sustained ventricular tachycardia as the indication for surgery and had preoperative and intraoperative electrophysiologic mapping. There were 14 hospital deaths (16%). Eight preoperative potential risk factors for early hospital mortality were analyzed by multivariate analysis. Only acute myocardial infarction within 30 days before surgery correlated with hospital death at the p less than 0.05 level. History of previous heart surgery and advanced New York Heart Association functional class were important risk factors at the p less than 0.1 level. Hospital mortality was 17.6% for patients who had intraoperative mapping and endocardial resection and 11.1% for the others. Patients who had aneurysm repair for ventricular tachycardia had a significantly higher incidence of low cardiac output early after surgery (p less than 0.025).

Adult↗
PubMed1989

Functional right-heart replacement with skeletal muscle ventricles.

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.

Animals↗
PubMed1988

Open-heart surgery in octogenarians.

One hundred consecutive patients 80 years of age or older consented to and subsequently underwent open-heart operations at our institution between July 1976 and May 1987. Fifty of the patients had aortic valvular disease (28 with coexisting coronary artery disease), and 41 had isolated coronary artery disease. Eight patients had mitral valvular disease, and one had a dissecting aortic aneurysm. Ninety had Class IV disease that was functional, ischemic, or both. The most compelling indications for operation in 85 patients were unstable or postinfarction angina, syncope, acute pulmonary edema, or cardiogenic shock. Twenty-nine patients died soon after operation (within 90 days). New York Heart Association Class IV disease, previous myocardial infarction, cachexia, and emergency operation were preoperative variables associated with early death. Forty-three patients had no complications except for atrial arrhythmias and were discharged from the hospital a mean (+/- SD) of 11.5 +/- 3.7 days after operation. Low cardiac output, acute myocardial infarction, reoperation for bleeding, renal insufficiency, pneumonia, and prolonged endotracheal intubation were the most common serious postoperative complications. Twenty-eight patients who survived postoperative complications were discharged 24.9 +/- 19.6 days after operation. Seventeen patients died 2 to 104 months after discharge from the hospital. Actuarial calculation predicts the survival of 59 percent of patients at three years and 54 percent at five years. Of the 54 patients still alive at this writing, 53 have disease within New York Heart Association and Canadian Cardiovascular Society Classes I or II. For selected octogenarians with unmanageable cardiac symptoms, operation may be an effective therapeutic option.

Aged↗