Search PubMed⌕ Search

Biomedical subjects

L W Stephenson

Publications and source records attributed to L W Stephenson.

At least 73 records · Page 4Linked to original sources

In vivo 31P-NMR spectroscopy of chronically stimulated canine skeletal muscle.

Chronic stimulation converts skeletal muscle of mixed fiber type to a uniform muscle made up of type I, fatigue-resistant fibers. Here, the bioenergetic correlates of fatigue resistance in conditioned canine latissimus dorsi are assessed with in vivo phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopy. After chronic electrical stimulation, five dogs underwent 31P-NMR spectroscopic and isometric tension measurements on conditioned and contralateral control muscle during stimulation for 200, 300, 500, and 800 ms of an 1,100-ms duty cycle. With stimulation, phosphocreatine (PCr) fell proportional to the degree of stimulation in both conditioned and control muscle but fell significantly less in conditioned muscle at all but the least intense stimulation period (200 ms). Isometric tension, expressed as a tension time index per gram muscle, was significantly greater in the conditioned muscle at the two longest stimulation periods. The overall small change in PCr and the lack of a plateau in tension observed in the conditioned muscle are similar to that seen in cardiac muscle during increased energy demand. This study indicates that the conditioned muscle's markedly enhanced resistance to fatigue is in part the result of its increased capacity for oxidative phosphorylation.

Animals↗

Skeletal muscle grafts applied to the heart. A word of caution.

Latissimus dorsi pedicle grafts (LDPGs) were wrapped around the heart in eight dogs. In four dogs, the LDPGs were stimulated chronically; the remaining four dogs served as unstimulated controls. Right-sided cardiac filling pressures were normal in all dogs when measured 4 months after graft application. Mean tension generated by the viable LDPGs was 153 +/- 49.9 g. LDPGs contracting in synchrony with the heart did not increase cardiac output. In one dog, the aortic pressure changed from 140/100 to 155/85 mm Hg during synchronous contraction of the LDPG. Three dogs were placed on cardiopulmonary bypass, and their hearts were placed in fibrillation. The LDPGs were then stimulated at a burst frequency of 85 Hz and contracted vigorously. Under these conditions, the left ventricular pressure increased by an average of 15 mm Hg with each LDPG contraction; however, the mean aortic pressure was virtually unchanged. Left ventricular and aortic pressures of 125/20 and 125/65 mm Hg, respectively, could be obtained with manual compression of the fibrillating heart. This study indicates that although LDPGs can be made to contract chronically and in synchrony with the heart, they do not necessarily augment left ventricular performance.

Animals↗

Skeletal muscle as the potential power source for a cardiovascular pump: assessment in vivo.

Skeletal muscle ventricles (SMVs) were constructed from canine latissimus dorsi and connected to a totally implantable mock circulation device. The SMVs, stimulated by an implantable pulse generator, pumped continuously for up to 8 weeks in free-running beagle dogs. Systolic pressures produced by the SMVs, initially of 139 +/- 7.2 mmHg and after 1 month of continuous pumping of 107 +/- 7 mmHg, were comparable to normal physiologic pressures in the adult beagles (114 +/- 21 mmHg). After 2 weeks of continuous pumping, the mean stroke work of the SMVs was 0.4 X 10(6) ergs, a performance that compares favorably with the animal's cardiac ventricles. This study shows that canine skeletal muscle which has not received prior training or electrical conditioning can perform sustained work at the high levels needed for an auxiliary cardiovascular pump. It might be possible eventually to use such muscle pumps in humans to assist the failing circulation and to provide support in children with certain types of congenital heart defects.

Adenosine Triphosphatases↗

Canine diaphragm muscle after 1 yr of continuous electrical stimulation: its potential as a myocardial substitute.

Skeletal muscle has been rendered fatigue resistant by chronic stimulation and therefore has potential as an active substitute for damaged myocardium. It is therefore important to know whether stimulation produces any deleterious effects in the long term. Hemidiaphragm muscles of four dogs were examined after chronic stimulation for 1 yr at either 2 or 4 Hz. The stimulated hemidiaphragms appeared normal on gross inspection and were still contracting vigorously. By histochemical and immunohistochemical criteria, they had acquired a uniformly type I character, in contrast to the mixed fiber type composition of the unstimulated hemidiaphragms. This transformation was also reflected in their complement of myosin isozymes. There was some enzymatic evidence of an associated shift towards aerobic pathways of energy generation. Histological examination revealed no evidence of degenerative changes. Trends, observed in the shorter term (6-8 wk), toward a decrease in fiber area and an increase in connective tissue showed no further progression at 1 yr. Thus hemidiaphragm muscle stimulated at frequencies at or above the normal heart rate does not appear to undergo adverse long-term changes that would constrain its use in a myocardial assist role.

Animals↗

Power output of skeletal muscle ventricles in circulation: short-term studies.

Skeletal muscle ventricles (SMVs) were constructed from preconditioned latissimus dorsi muscles in eight dogs and then connected to each animal's systemic arterial circulation in short-term experiments. The lengths of time that SMVs could produce hemodynamic work as left ventricular assist devices were recorded. After 4 hr of continuous pumping at approximately 55 beats/min, six of eight SMVs were able to generate systolic pressures of 128 +/- 23 mm Hg and flows of 340 +/- 31 ml/min, representing 20 +/- 4% of the animals' cardiac output. After 8 hr of continuous pumping, five of the eight SMVs generated pressures of 110 +/- 15 mm Hg and flows of 308 +/- 88 ml/min, or 15 +/- 7% of the animals' cardiac output. The stroke work produced by the SMVs was intermediate between that of the animals' left and right ventricles. Although the SMVs were stimulated to contract at only about one-third the heart rate, the power output of the SMVs approximated that of the right ventricles because of the greater stroke work of the SMVs. Two SMVs functioned as LVADs for 14 hr. Deterioration in SMV function eventually occurred. In each case, however, complications such as anemia, hypoxia, and hypotension, which are inherent to prolonged short-term experiments of this type, contributed to the deterioration of SMV function. The results presented here suggest that skeletal muscle has the potential to directly support the circulation; however, the length of time such muscle pumps are capable of functioning has yet to be determined.

Animals↗

Skeletal muscle ventricles in circulation. One to eleven weeks' experience.

Skeletal muscle ventricles were constructed from canine latissimus dorsi and connected to the thoracic aorta in six dogs. These ventricles were stimulated to contract synchronously during diastole. The skeletal muscle ventricles were capable of continuous stroke work when placed within the arterial circulation for several weeks. Effective synchronous diastolic counterpulsation was produced. These results demonstrate that diastolic counterpulsators can be constructed from skeletal muscle and in the future may provide a feasible therapeutic alternative for the treatment of end-stage cardiac failure.

Animals↗

Simultaneous implantation of St. Jude Medical aortic and mitral prostheses.

Since January 1980, 92 consecutive patients received St. Jude Medical aortic and mitral prostheses simultaneously. Mean age was 57.6 years (standard deviation 12.4); 14 were 70 years or older. Twenty-three had a previous cardiac operation and 22 had additional procedures performed at the time of double valve replacement. Before the operation 62% of the patients were in New York Heart Association functional class III and 29% were in class IV or required emergency operation. There were six (6.5%) deaths within 30 days. None of the hospital deaths were valve related; all occurred in patients who had additional risk concerns. Follow-up is 100% complete and ranges from 2 to 80 months, totaling 242 patient-years (mean 33.8 months). All except four hospital survivors reached class I or II and 40 patients (47%) remain asymptomatic. The actuarial survival rates are 82% at 1 year, 70% at 3 years, and 60% at 5 years. Causes of late death include heart failure (10), sudden, unexplained death (five), reoperation for coronary artery disease (one), noncardiac (four), and valve related (five). The linearized rate of fatal valve-related events is 2.1% pt-yr. A total of 22 valve-related complications (including five fatal) occurred is 18 patients, for a linearized rate or incidence of 9.1%/pt-yr. Eleven thromboembolic episodes (rate 4.6%/pt-yr) occurred in nine patients; three of these (1.2%/pt-yr) were fatal. Thromboembolic and bleeding complications represented 64% of all valve-related complications. Four patients had six episodes of prosthetic valve endocarditis (incidence 2.5%/pt-yr), of which one (incidence 0.4%/pt-yr) was fatal. Paravalvular leak contributed to the fifth valve-related death. At 5 years, 83% of patients were free of thromboembolic complications; 94% were free of anticoagulant-related hemorrhage; and 71% were free of all valve-related complications. There are few comparable data for patients who have had simultaneous replacement of aortic and mitral valves with other mechanical prostheses. The total incidence of valve-related complications for patients with bioprostheses ranges between 3.9%/pt-yr and 10.4%/pt-yr and is similar to the 9.1%/pt-yr observed in the present series. The type of valve-related complication (thromboemboli and bleeding versus valve deterioration) is the principal difference between St. Jude Medical and bioprosthetic valves in patients who require simultaneous replacement of aortic and mitral valves.

Actuarial Analysis↗

Value of CT in the preoperative assessment of lung cancer: a survey of thoracic surgeons.

Practicing thoracic surgeons were randomly surveyed to evaluate how computed tomography (CT) has influenced the preoperative evaluation of bronchogenic carcinoma. Thirty-six percent of the 529 respondents routinely requested CT and 62% did so selectively. Approximately 40% indicated that CT provided useful information in most cases. Nearly all surgeons (98.7%) do not rely on the identification of enlarged lymph nodes with CT to spare the patient surgical staging; however, 77.5% are influenced by CT results in their staging procedures. Fifty-seven percent reported that a negative CT study eliminates surgical staging entirely unless the patient has a "coin lesion," in which case 75% are willing to proceed directly to thoracotomy. For surgeons who use CT selectively, an abnormal mediastinal contour on the radiograph was the most frequent radiologic abnormality to prompt CT (85%). Thirty-seven percent are influenced by tumor histology in their decision to request CT. There was little difference in the pattern of CT use between university and community hospital surgeons.

Health Surveys↗

Histochemical and fatigue characteristics of conditioned canine latissimus dorsi muscle.

To induce fatigue resistance in the latissimus dorsi muscle of the dog in preparation for possible myocardial assistance, eight adult male beagles underwent unilateral electrical stimulation of the thoracodorsal nerve at a frequency of 2 Hz (120 stimuli/min) and 10 Hz (600 stimuli/min) for a 6-week period. The conditioned muscles were compared with their unconditioned contralateral controls by fiber typing, pyrophosphate gel electrophoresis, isometric characteristics, and fatigue rates. At the end of the period of stimulation, the conditioned muscles had a greater percentage of slow-twitch, fatigue-resistant fibers on acid and alkaline stains (100 +/- 0.7% and 83 +/- 15.3%), respectively, than did their contralateral controls (45 +/- 7.6% and 43 +/- 7.0). Pyrophosphate gel electrophoresis revealed an increase in the slow myosin and a decrease in the fast myosin content in the conditioned muscles; the stimulated muscles also demonstrated a slower contraction time (87 +/- 20 msec vs. 57 +/- 17.9 msec), a lower initial tension (4.4 +/- 1.45 kg vs. 7.2 +/- 2.11 kg), and a slower fatigue rate during a 30-minute fatigue test than did their contralateral controls. The muscles stimulated at 2 Hz had fatigue rates similar to those stimulated at 10 Hz, but generally had less diminution in muscle fiber diameters and less interfiber connective tissue. Thus, it is possible to make canine latissimus dorsi muscles more fatigue resistant, and, theoretically, more capable of myocardial assistance by electrical stimulation of the thoracodorsal nerve at a frequency as low as 2 Hz--the natural canine heart rate.

Animals↗

The automatic implantable cardioverter-defibrillator: efficacy, complications, and device failures.

Twenty-six patients with refractory ventricular arrhythmias received the automatic implantable cardioverter-defibrillator. A patch lead only was placed during arrhythmia surgery in 7 other patients. During 13 +/- 6 (SD) months, the device discharged in 10 patients because of a sustained ventricular arrhythmia. No sudden deaths occurred. There were 31 complications in 17 patients, including postoperative refractory heart failure, coronary artery erosion, subclavian vein thrombosis, postoperative stroke after conversion of atrial fibrillation, atelectasis with pneumonia, symptomatic pleural effusions, and infection at the generator site. The cardioverter-defibrillator discharged in 9 asymptomatic patients, failed to terminate ventricular fibrillation during postoperative testing in 3 patients, and had premature battery failure in 4 patients. Tachycardia slowing during chronic amiodarone therapy and unipolar ventricular pacing during ventricular fibrillation precluded or delayed arrhythmia sensing. Thus, the cardioverter-defibrillator can be life saving, but its potential complications and interactions with antiarrhythmic drugs and pacemakers must be considered at patient selection.

Adolescent↗

An autologous biologic pump motor.

Latissimus dorsi skeletal muscle ventricles were constructed in six beagles. They first underwent a period of vascular delay and of electrical preconditioning over several weeks. The skeletal muscle ventricles were then connected to a totally implantable mock circulation that allowed for the chronic measurement of pressures and flows produced by the muscle. The skeletal muscle ventricles were actuated by stimulation of the motor nerve with an implanted generator that delivered brief pulse trains. The skeletal muscle ventricles pumped continuously against an afterload of 80 mm Hg with a preload of 40 to 50 mm Hg at a rate of 54 times per minute. At initiation of pumping, systolic pressure was 135 +/- 24 mm Hg and flow was 464 +/- 116 ml/min. After 2 weeks of continuous pumping, the systolic pressure was 104 +/- 1 mm Hg and continuous flow was 206 +/- 16 ml/min. Two of the skeletal muscle ventricles pumped continuously for 5 and 9 weeks, respectively. At the end of that time one was still capable of generating pressure up to 205 mm Hg and the other, 160 mm Hg. These results suggest that a chronic auxiliary skeletal muscle ventricle is a feasible approach to the treatment of end-stage cardiac failure.

Animals↗

Hydraulic pouches of canine latissimus dorsi. Potential for left ventricular assistance.

We have studied the fatigue rates of hydraulic pouches constructed in the form of a multilayered conical spiral using the latissimus dorsi muscle of 17 beagles. The roles that electrical muscle conditioning and early interruption of collateral blood supply have in the prevention of pouch fatigue were evaluated. The length of time that a pouch could generate flow in a hydraulic test system was measured; afterload was set at 80 mm Hg and preload 24 mm Hg. Pouches (N = 3) fashioned from muscles subject to neither electrical conditioning nor a vascular delay generated an initial flow of 990 +/- 346 ml/min, but could sustain flow for only 2.3, 3.8 and 3.6 minutes. Pouches (N = 5) constructed with electrically unconditioned muscles after a vascular delay (median 3 weeks) demonstrated a variable improvement in fatigue rates (initial flow 826 +/- 265 ml/min; time to no forward flow, 2.5, 7.5, 7.5, 10, and 200 minutes). Four of six pouches that received the benefit of long-term electrical muscle conditioning and a vascular delay (N = 6) were able to generate flow for a 4 hour period, at which time the experiment was terminated (initial flow 478 +/- 204 ml/min; final flow 195 +/- 157 ml/min). After the 4 hour fatigue test was completed, one electrically conditioned pouch was placed in series with the heart and served as a counterpulsator. The initial volume of blood pumped by the muscle pouch was 262 ml/min or 13.8% of cardiac output. After the pouch had contracted at a rate of approximately 45 beats/min for 1 hour, the volume of blood pumped was 178 ml/min, or 11% of cardiac output. In three other animals a pouch was fashioned and then left in situ for a 1 to 3 week period before hydraulic testing. These pouches generated significant initial flows (390 +/- 60 ml/min), which demonstrates the feasibility of further study of permanent pouches. These results suggest that permanent electrical muscle conditioning and perhaps a vascular collateral delay might permit an auxiliary skeletal muscle-powered ventricle to assume a portion of left ventricular function.

Animals↗

Potential uses of skeletal muscle for myocardial assistance.

The potential for skeletal muscle to assist in cardiac function is reviewed. Skeletal muscle can be transformed into a fatigue-resistant state through chronic electrical stimulation. Thus it might be an ideal muscle for replacing or augmenting failing heart muscle.

Adaptation, Physiological↗

Pneumothorax during positive-pressure mechanical ventilation.

The hemodynamic and respiratory effects of unilateral pneumothorax were studied during positive-pressure mechanical ventilation in five sheep. The sheep were anesthetized, intubated, and placed on mechanical ventilation with positive end-expiratory pressure (5 cm H2O). After baseline studies, including chest roentgenograms, were taken, increments of air were injected into the right pleural cavity. Measurements were repeated at pneumothoraces of 500, 1,000, and 1,500 ml. There was a steady fall in cardiac output (p less than 0.02) at pneumothoraces of 1,000 and 1,500 ml. The decrease in cardiac stroke volume paralleled that of cardiac output. Heart rate rose (p less than 0.05) at a pneumothorax of 1,500 ml. There appeared to be a linear relationship between the percent increase in pneumothorax as estimated by roentgenogram and the percent fall in cardiac output (r = 0.991). There was a steady rise in mean pulmonary arterial, pulmonary arterial capillary wedge, superior vena caval, and inferior vena caval pressures, although the changes in inferior vena caval pressure were not statistically different from baseline. Peak airway pressure increased from baseline at pneumothoraces of 1,000 and 1,500 ml. Both right and left end-expiratory intrapleural pressures increased and were statistically different (p less than 0.01) from baseline. However, there was a substantially greater rise in right intrapleural pressure than left. Arterial oxygen tension remained physiological throughout the study. This study indicates that cardiac output decreases as the amount of pneumothorax increases in sheep during mechanical ventilation. This study also demonstrates that, during positive-pressure mechanical ventilation, a relatively benign-appearing pneumothorax by chest roentgenogram may be associated with a significantly depressed cardiac output. In addition, arterial oxygen tension may not be useful in predicting the onset of pneumothorax during mechanical ventilation.

Animals↗

Clinical comparison of St. Jude and porcine aortic valve prostheses.

One hundred eighty-seven consecutive patients who had aortic valve replacement with either a St. Jude or porcine heterograft prosthesis were studied prospectively. The two groups were similar with respect to 67 clinical and operative factors, which allowed comparison of valve performance as an independent variable. Total follow-up was 6162 patient-months (mean 32 months, range 23 to 62, 99% complete). There were no statistical differences in symptomatic improvement or mortality by life-table analysis. Valve-related complications expressed as percent per patient-year included: reoperation, 0.6 St. Jude and 1.2 porcine; endocarditis, 1.1 and 0.9; regurgitant murmur, 3.4 and 2.7; hemolysis, 2.8 and 0.0; thromboembolism, 2.8 and 1.5 (all not significant); and hemorrhage, 7.9 and 2.4 (p less than .005). Anticoagulant-related bleeding was the only significant difference between the two valves in morbidity and mortality 32 to 34 months after operation.

Adolescent↗