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Biomedical subjects

L W Stephenson

Publications and source records attributed to L W Stephenson.

At least 37 records · Page 2Linked to original sources

Chronic changes of end-systolic pressure-volume relationship after regional myocardial infarction.

The chronic changes of the end-systolic pressure-volume relationship (ESPVR) after regional myocardial infarction were evaluated in a sheep model. Pressure-volume area (PVA) obtained from the pressure-volume diagram and left ventricular oxygen consumption (LVO2) were studied. The regional myocardial infarction was created by ligating distal branches of the left coronary artery. ESPVR was obtained using a conductance catheter during transient inferior vena cava occlusion. Measurements were performed at baseline (n = 13), 1 hour (n = 8), 3 months (n = 9), and 6 months (n = 4) after infarction. Ees, the slope of the ESPVR did not change at 1 hour after infarction and remained the same at 3-month and 6-month measurements (baseline 2.26 +/- 1.24 mmHg/mL, 1 hour 2.71 +/- 1.06, 3 months 3.46 +/- 1.51, 6 months 2.45 +/- 0.64, NS). Because of the ventricular dilatation, which was demonstrated as an increase in changes of end-systolic volume (Ves) correlating with the time course after infarction (y = -3.21 + 0.12x, r = 0.454, p < 0.05), V0, the volume intercept of the ESPVR increased at 1 hour after the infarction, and showed a tendency to increase at 3 months and 6 months after the infarction (baseline -18.0 +/- 22.5 mL; 1 hour -0.9 +/- 11.6; 3 months 5.4 +/- 10.9, 6 months 9.2 +/- 23.1, baseline vs 3 months p < 0.05, baseline vs 6 months p < 0.05). PVA and LVO2 were unchanged over time after infarction (PVA: baseline 2097 +/- 1526 mmHg/mL per 100 g-1; 1 hour 1771 +/- 699; 3 months 2483 +/- 1086; 6 months 1,608 +/- 1,010, NS), (LVO2: baseline 40.6 +/- 13.1 x 10(-3) mL/100 g-1 per beat-1; 1 hour 42.9 +/- 9.7; 3 months 35.0 +/- 8.6; 6 months 31.2 +/- 18.1, NS). Chronic regional infarction in the sheep model did not affect Ees over 6 months, but significantly increased V0 after the increase in the acute phase. PVA and LVO2 were not affected by this regional infarction either acutely or over 6 months.

Animals↗

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 x 10(6) ergs) and 37% of that of the left ventricle (LV) at rest (0.298 +/- 0.61 x 10(6) 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.

Animals↗

Percutaneous balloon valvuloplasty compared with open surgical commissurotomy for mitral stenosis.

BACKGROUND: Percutaneous balloon mitral valvuloplasty has been proposed as an alternative to open surgical commissurotomy for the treatment of rheumatic mitral-valve stenosis. METHODS: We enrolled 60 patients with severe mitral stenosis and favorable valvular anatomy in a prospective, randomized trial comparing the two procedures. All patients underwent cardiac catheterization before the procedure and one week, six months, and three years thereafter. Hemodynamic data were analyzed by investigators who were blinded to the patients' treatment assignments. RESULTS: Mitral-valve areas improved initially in both groups, from a mean (+/- SD) of 0.9 +/- 0.3 cm2 to 2.1 +/- 0.6 cm2 in the balloon-valvuloplasty group (30 patients; P < 0.01) and from 0.9 +/- 0.3 cm2 to 2.0 +/- 0.6 cm2 in the surgical group (30 patients; P < 0.001). Although improvement was maintained in both groups, mitral-valve areas were greater in the patients in the balloon-valvuloplasty group at three years (2.4 +/- 0.6 cm2, vs. 1.8 +/- 0.4 cm2 in the surgery group, P < 0.001). Restenosis occurred in three patients in the balloon-valvuloplasty group and four in the surgery group. One patient in the balloon-valvuloplasty group died of an apparent stroke after 2.5 years; four patients in the balloon-valvuloplasty group had residual atrial septal defects, and three patients (two in the balloon-valvuloplasty group and one in the surgery group) were judged to have severe mitral regurgitation. Seventy-two percent of the patients who underwent balloon valvuloplasty and 57 percent of the surgically treated patients were in New York Heart Association functional class I (i.e., they had no cardiovascular symptoms) at three years. No patient was lost to follow-up. CONCLUSIONS: In the treatment of mitral stenosis, balloon valvuloplasty and open surgical commissurotomy have comparable initial results and low rates of restenosis, and both produce good functional capacity for at least three years. The potential complications associated with balloon valvuloplasty should be noted. The better hemodynamic results at three years, lower cost, and elimination of the need for thoracotomy suggest that balloon valvuloplasty should be considered for all patients with favorable mitral-valve anatomy.

Adolescent↗

Pericardium-lined skeletal muscle ventricles in circulation up to 589 days.

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.

Animals↗

Intrathoracic and extrathoracic skeletal muscle ventricles in circulation: left ventricular apex-to-aorta configuration.

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.

Anastomosis, Surgical↗

Detection of canine allograft lung rejection by pulmonary lymphoscintigraphy.

We previously demonstrated that lymphoscintigraphy could be used to study pulmonary lymphatic flow. Radiocolloids, high-molecular-weight proteins tagged with radioactive markers, are injected percutaneously in the periphery of the lung. These molecules enter the lymph, are transported via lymphatic channels, and concentrate in the tributary hilar and mediastinal lymph nodes, where they can be visualized by nuclear scan. The goal of this study was to determine whether pulmonary lymphoscintigraphy could be used to detect allograft rejection after lung transplantation. Thirteen mongrel dogs underwent left lung allotransplantation. Cyclosporine 15 mg/kg per day and azathioprine 1 mg/kg per day were given orally for postoperative immunosuppression. Lymphoscintigraphic studies were obtained 1 week after the operation and then at weekly intervals. In five dogs (group A), immunosuppression was continued until the animal died or was put to death 6 weeks later. Lymphoscintigraphy demonstrated reestablishment of lymphatic drainage between the lung graft and the mediastinum in all the animals 2 to 4 weeks after transplantation. In eight dogs (group B), immunosuppression was discontinued after reestablishment of graft lymphatic drainage was documented by two consecutive lymphoscintigraphic studies. The dogs continued to be studied with weekly scans. In group B, lymphatic drainage from the lung graft to the mediastinum disappeared 1 to 4 weeks after immunosuppression was stopped. Rejection was diagnosed clinically and confirmed histologically with open lung biopsies and/or autopsies in all animals. This study shows that canine allograft lung rejection is associated with disappearance of lymphatic drainage from lung graft to mediastinum, which can be documented by pulmonary lymphoscintigraphy, a minimally invasive technique that can be easily repeated. Pulmonary lymphoscintigraphy may be useful for early detection of lung allograft rejection.

Acute Disease↗

Functional evaluation of intrathoracic versus extrathoracic skeletal muscle ventricles.

Skeletal muscle ventricles (SMVs) were constructed from the latissimus dorsi muscle in 10 dogs. In Group I (n = 5), SMVs were left in an extrathoracic position on the chest wall. In Group II (n = 5), SMVs were placed within the chest cavity. After a 3- to 4-week vascular 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 function was evaluated under differing conditions of preload and afterload. SMVs in Group II were significantly more compliant, as demonstrated by the end diastolic pressure volume relationship, than those in Group I (P < 0.01). SMVs in Group II were also capable of generating greater stroke work than those in Group I (P < 0.05). SMVs in Group II were also capable of greater stroke work than those in Group I at physiologic preloads (P < 0.05). These findings suggest that SMVs placed in an intrathoracic position exhibit better diastolic and systolic function.

Animals↗

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.

Animals↗

Reestablishment of lymphatic drainage after canine lung transplantation.

The technique of pulmonary lymphoscintigraphy was used to evaluate pulmonary lymphatic flow and to assess reestablishment of lymphatic drainage after lung transplantation. A first group of six control dogs underwent percutaneous transthoracic injection of a radiocolloid into the periphery of the left upper and lower lobes. Radiocolloids are large molecules tagged with radioisotopes that are absorbed only through lymph and are concentrated in tributary lymph nodes. Twenty-four hours after injection the dogs underwent scintigraphic studies of the chest and upper part of the abdomen. Mediastinal lymph nodes were visualized in all animals. A second group of four dogs underwent partial reimplantation of the native left lung, with interruption of all lymphatic connections between the lung and mediastinum. Lymphoscintigraphic studies of the left lung were obtained on the third postoperative day and then weekly for 4 weeks. Three of the four dogs in this group did not have visible mediastinal nodes 3 days after the operation. Nodes were visualized in all animals at 1 week and at all following studies. A third group of five dogs were subjected to left lung allotransplantation by means of standard surgical techniques, as well as immunosuppression. The animals were studied with radiocolloid injections and lung lymphoscintigraphy at weekly intervals for 6 weeks. Mediastinal nodes were visualized for the first time 2 to 4 weeks after the operation and at every subsequent study. We conclude that lung lymphoscintigraphy is a reliable technique for the study of pulmonary lymphatic flow. This experiment demonstrates that lymphatic drainage after lung transplantation is reestablished as early as the second postoperative week.

Animals↗

Update on skeletal muscle ventricles as aortic diastolic counterpulsators.

Skeletal muscle ventricles are constructed from canine latissimus dorsi muscle. These skeletal muscle ventricles can be placed subcutaneously on the chest wall or inside the chest cavity. Skeletal muscle ventricles are connected to the descending thoracic aorta and activated to pump blood as aortic diastolic counterpulsators. The skeletal muscle ventricle in 1 animal pumped blood in the circulation for 27 months. Skeletal muscle ventricles can also function effectively under the condition of low cardiac output. Although thrombus has been detected in some skeletal muscle ventricles, thromboembolism to distal organs has been detected only rarely during the past few years. This research appears promising; however, skeletal muscle ventricle rupture remains a problem and currently accounts for about 30% of the mortality in the long-term experiments. It occurs at the site between the skeletal muscle ventricle outlet and the Dacron sewing ring that is necessary to connect conduits from the skeletal muscle ventricle to the animal's circulation. We believe that skeletal muscle ventricle rupture is likely to be a solvable problem. Once a solution has been found, skeletal muscle ventricles may be ready for clinical use in patients with chronic congestive heart failure.

Animals↗

[Functional evaluation of skeletal muscle ventricles for circulatory assist].

Skeletal muscle has a potential power for cardiac assist. Two approaches have been used to harvest this power: dynamic cardiomyoplasty, which involves the application of 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. In this study, we evaluated the function of the skeletal muscle ventricles (SMVs) for circulatory assist. In six dogs (18.5 +/- 2.3 kg, mean +/- S.E.M.), SMVs were constructed from the right latissimus dorsi muscle, and placed in the right hemithorax. After a 3-week vascular delay period, the SMVs were preconditioned electrically by 2 Hz continuous stimulation for six weeks. Nine weeks later, SMVs were connected to a mock circulation device for functional evaluation. As right-sided pumps, at a preload of 10 mmHg, SMVs generated stroke work of 0.63 +/- 0.04 x 10(6) ergs with 25 Hz and 0.80 +/- 0.06 x 10(6) ergs with 85 Hz, which exceeded that of the native right ventricle. As left sided pumps, also at a preload of 10 mmHg, SMV stroke work was 0.49 +/- 0.13 x 10(6) with 25 Hz 0.90 +/- 0.09 x 10(6) ergs, which was roughly half that of the left ventricle. These results demonstrate that SMVs have the potential to function as left or right heart assist devices.

Animals↗

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.

Animals↗

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.

Animals↗

Skeletal muscle ventricles in the pulmonary circulation: up to 16 weeks' experience.

Skeletal muscle ventricles (SMVs) were constructed from the right latissimus dorsi muscle of 8 mongrel dogs. After a 3-week vascular delay period, each SMV was electrically preconditioned with 2-Hz continuous stimulation of the thoracodorsal nerve for 6 weeks. A porcine-valved conduit was then anastomosed between the right ventricle and the SMV, with a second valved conduit connecting the SMV to the main pulmonary artery. The pulmonary artery was then ligated proximal to the conduit. The SMVs were stimulated to contract in 1:2 diastolic mode with a 33-Hz burst frequency. Effective right ventricular assist was achieved in all dogs. Cardiac output increased by 22.6% (1,799 +/- 97 versus 1,467 +/- 84 mL/min; p less than 0.001), systemic systolic arterial pressure by 9.3% (90.1 +/- 3.5 versus 82.4 +/- 3.9 mm Hg; p less than 0.005), and peak pulmonary artery pressure by 31.8% (27.8 +/- 2.0 versus 21.1 +/- 1.7 mm Hg; p less than 0.001) at the initiation of this study. In 6 dogs, effective right heart assist was sustained for periods of between 1 week and 12 weeks. Two dogs survived for longer than 3 months, though with evidence of deteriorating SMV function. These results demonstrate the feasibility of providing sustained right ventricular assist using this modified "Rastelli-SMV" configuration, which obviates the limitations imposed by low right atrial preload.

Adaptation, Physiological↗

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.

Animals↗

Skeletal muscle for cardiac assistance.

The last few years have witnessed considerable interest in the use of skeletal muscle to assist the heart. This review outlines developments of particular relevance and importance to this field during the past 12 months. The use of conditioned, fatigue resistant latissimus dorsi muscle has been proposed for cardiomyoplasty, for constructing separate pumping chambers, and for powering alternative assist systems. Although the cardiomyoplasty procedure has been applied clinically, the other techniques remain experimental, but promising, modes of support.

Animals↗