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G V Letsou

Publications and source records attributed to G V Letsou.

50 records · Page 3Linked to original sources
PubMed1995

Skeletal muscle for cardiac assist.

Although current efforts at cardiomyoplasty have not produced the anticipated clear-cut benefits in cardiac function, replicable improvements in subjective function have resulted. Efforts at optimizing conditioning protocols, skeletal muscle strength, and timing of skeletal muscle assist devices should provide further improvements in cardiomyoplasty. Further work with alternative ways of configuring skeletal muscle for cardiac assist is extremely promising. SMVs, in particular, offer potential to augment cardiac function directly or indirectly powering pumps. Work in all these areas is in early stages, but the future is bright.

Animals↗
PubMed1994

Latency of skeletal muscle contraction after pulse train stimulation: an important factor in correct timing of skeletal muscle cardiac assist devices.

Various configurations of conditioned skeletal muscle are under investigation for cardiac assistance in patients with end-stage cardiac failure. Optimal timing of conditioned skeletal muscle contraction is essential for effective cardiac augmentation. However, unlike mechanical methods of assistance, skeletal muscle requires time to develop peak tension. We measured "time to 50% peak tension" and "time to 90% peak tension" using an electrical strain gauge in 12 canine latissimus dorsi muscles (6 untrained controls and 6 trained with 3 months of electrical stimulation at 25 Hz with a 15% duty cycle). The "time to 50% relaxation" and the "time to 90% relaxation" after discontinuation of the stimulus were also measured. Conditioned skeletal muscle required significantly more time to develop peak tension than unconditioned skeletal muscle. Relaxation was also significantly prolonged in conditioned muscle. Notably, conditioned lattisimus needed, on average, 0.35 sec to develop peak tension and 0.20 sec for 90% relaxation. Thus, 0.55 sec of each muscle contraction/relaxation cycle was devoted to development of peak tension and subsequent relaxation. At normal canine heart rates of approximately 120 beats per minute (0.50 sec per cardiac cycle), conditioned skeletal muscle may take up to 70% of each cardiac cycle (0.35 sec) to develop 90% of peak tension. The recognition of this phenomenon in conditioned skeletal muscle is important for effective contraction timing of both human and animal skeletal muscle assist devices. Development of proper conditioning regimens for such devices may benefit from identification of those training parameters which produce a minimal "time to peak tension."

Animals↗
PubMed1993

Pulmonary artery balloon counterpulsation: safe after peripheral placement.

Pulmonary artery balloon counterpulsation is a promising experimental technique for treatment of right ventricular failure. However, clinical application has been limited in that the only device presently available (the large-volume intraaortic balloon) must be placed within a synthetic graft. Because a balloon with a smaller volume (which could be placed through a peripheral vein and be contained entirely within the pulmonary artery) would make the technique feasible on a wider scale, we tested an 8-mL pulmonary artery balloon placed through the femoral vein in 12 dogs. Two groups of animals were compared. One group had the pulmonary artery balloon in place but not counterpulsating; the other had the pulmonary artery balloon in place and counterpulsating. Each group was studied for 12 hours. A variety of hemodynamic parameters were measured. Effective diastolic augmentation and systolic unloading were noted in all 6 dogs that underwent counterpulsation (5.0 +/- 1.1 mm Hg of diastolic augmentation and 9.5 +/- 1.6 mm Hg of systolic unloading). Pulmonary function, as measured by arterial blood gas sampling and pulmonary vascular resistance, was not impaired. Examination of the heart and lungs showed no detrimental pathologic effects of pulmonary artery balloon counterpulsation. Placement of the balloon through a peripheral vein with a guidewire was easy and uncomplicated. We conclude that pulmonary artery balloon counterpulsation is safe over an extended period of 12 hours in the canine model and that diastolic augmentation and systolic unloading can be produced.

Animals↗
PubMed1993

Improved ultrastructural lung preservation with prostaglandin E1 as donor pretreatment in a primate model of heart-lung transplantation.

Donor pretreatment with prostaglandin E1 as a pulmonary vasodilator has developed as a simple, effective means to provide excellent preservation in heart-lung transplantation. This study was undertaken to investigate the degree of ultrastructural preservation of the lung with prostaglandin E1 and other pulmonary vasodilators in a primate heart-lung transplantation model. Heart-lung transplantation was performed in 14 African green monkeys. Donor cardiac preservation was achieved with cold crystalloid cardioplegic solution (10 ml/kg). Lung preservation was achieved with cold, modified Euro-Collins solution delivered into the main pulmonary artery (60 ml/kg total). Vasodilator agents were administered intravenously 15 minutes before aortic crossclamping. The heart-lung grafts were stored at 4 degrees C for 6 hours. Three groups of animals were studied: five donors with prostaglandin E1 (0.1 to 4.0 micrograms/kg per minute), five donors with prostacyclin (0.1 to 0.35 micrograms/kg per minute), and four donors with nitroprusside (0.8 to 5.0 micrograms/kg per minute). After transplantation, arterial blood gas measurements and lung biopsies were performed at 1- and 3-hour intervals. Five formalin blocks per specimen were sectioned for hematoxylin and eosin staining. Cellular preservation and endothelial cell swelling were evaluated with electron microscopy. The specimens were graded for alveolar hemorrhage, endothelial cell swelling, and cellular preservation (grade 0, minimal, to grade 3, severe) and a mean score was obtained for each preservative agent. Prostaglandin E1-treated specimens demonstrated the least amount of endothelial swelling (mean score of 1.0) compared with prostacyclin- and nitroprusside-treated specimens (mean scores of 1.4 and 2.7, respectively). All nitroprusside-treated specimens demonstrated moderate to severe endothelial cell swelling. Interstitial and alveolar hemorrhage was noted in poorly preserved specimens, but there were no significant differences between groups. We conclude that prostaglandin E1 provides improved cellular preservation by decreasing the extent of endothelial cell swelling as observed on electron microscopy.

Alprostadil↗
PubMed1992

Is cardiopulmonary bypass effective for treatment of hypothermic arrest due to drowning or exposure?

Various techniques have been advocated for resuscitation from hypothermic arrest caused by ice-cold freshwater drowning or exposure. We have resuscitated five such patients after emergency hospital admission using cardiopulmonary bypass initiated via median sternotomy. All patients presented to our facility with core temperatures less than 26 degrees C. Three patients had been in full cardiopulmonary arrest for more than 30 minutes prior to arrival. The fourth patient presented in ventricular fibrillation; the fifth was admitted to the hospital in sinus bradycardia that quickly deteriorated to asystole. All had cardiopulmonary bypass emergently initiated via median sternotomy. All were rewarmed on bypass to 37 degrees C and all survived at least 24 hours. Three of the five patients are currently alive and well with normal neurologic function. Cardiopulmonary bypass is an effective technique for resuscitation after hypothermic arrest due to near drowning and/or exposure.

Adult↗
PubMed1992

Comparison of 180-degree and 360-degree skeletal muscle nerve cuff electrodes.

Use of skeletal muscle for cardiac augmentation is a promising technique for treatment of end-stage cardiac failure. An electrode woven through the latissimus dorsi that recruits nearby nerve fibers is commonly used to pace skeletal muscles both in clinical practice and in the laboratory. A proximally placed nerve cuff electrode offers potential advantages in improved recruitment of muscle fibers and low threshold for stimulation. We tested the effectiveness of a nerve cuff electrode passed directly about the proximal thoracodorsal nerve. Our report looks at the efficacy of nerve cuff electrode stimulation and compares electrical and histologic characteristics of a 180-degree wrap of the thoracodorsal nerve to a 360-degree wrap in dogs over 3 months. Threshold voltage at the commonly used pulse width of 200 microseconds was typically in the range of 400 to 600 mV for each electrode after 3 months. Statistical analysis revealed no significant difference (p < 0.05) in threshold voltage or current between the 180-degree and 360-degree nerve cuff electrode either at acute evaluation or after 3 months. Even contraction of latissimus dorsi was achieved with all implants. Adenosine triphosphatase staining revealed 100% conversion of type II to type I fibers in all stimulated muscles. Histologic examination of the thoracodorsal nerve and latissimus dorsi muscle revealed no abnormalities grossly or by light microscopy. Thus, a carefully applied nerve cuff electrode is an atraumatic, effective method for skeletal muscle stimulation. The 180-degree and 360-degree nerve cuff configurations are equally effective.

Adenosine Triphosphatases↗
PubMed1992

Isolation and characterization of rabbit cardiac endothelial cells: response to cyclic strain and growth factors in vitro.

Studies of the cardiac endothelium have been complicated by difficulties in isolating and maintaining cardiac endothelial cells (EC) in culture. We present in this paper a method of obtaining pure EC from rabbit hearts by collagenase digestion and membrane filtration. Pure cultures of EC displaying characteristic EC morphology, uptake of di-I-acetylated LDL, and contact-inhibition of growth were successfully maintained in culture for several weeks in media supplemented with fetal bovine serum, bovine retina-derived growth factor (RDGF), and antibiotics. Since EC in vivo are exposed to a complex pattern of physical forces we also sought to determine the proliferative response of cardiac EC subjected to pulsatile strain in vitro and compared it with the response to the addition of an exogenous growth factor, RDGF. The results demonstrate that a regimen of 60 cycles per minute, 24% cyclic strain induced a significant increase in cardiac EC proliferation and suggests that physical forces may have a trophic effect on EC proliferation.

Animals↗
PubMed1990

Heart-lung transplantation: initial experience in New England.

Between May 1988 and June 1989, five combined heart-lung transplants were performed. There were two males, age 16 and 19 years, and three females age 33, 34, and 19 years. Three patients had primary pulmonary hypertension, one had cystic fibrosis, and the fifth had doxorubicin-induced cardiomyopathy with associated pulmonary hypertension. All patients were severely restricted in functional capacity and were oxygen-dependent. Four grafts were distantly procured (ischemic times 1:15, 2:35, 2:45, 3:45); one was procured on-site (ischemic time 0:58). Four of five grafts functioned well (PO2 on FIO2 30% postoperatively: 102, 120, 180, and 129 torr). One graft (distantly procured with an ischemic time of 1:15) showed total failure of oxygenation secondary to fluid overload during donor surgery; the recipient could not be weaned from cardiopulmonary bypass. All patients were extubated 24 to 30 hours postoperatively. Rejection episodes have been infrequent and all have been successfully treated with pulse steroids. Four of the five patients are alive and well with normal cardiopulmonary function and normal functional capacity 15, 12, 8, and 6 months after surgery. Heart-lung transplantation is an effective therapy for properly selected patients with end-stage cardiopulmonary disease resulting from a variety of primary disorders.

Adolescent↗
PubMed1990

Isolated bilateral renal artery thrombosis: an unusual consequence of blunt abdominal trauma--case report.

Bilateral renal artery thrombosis with anuria following blunt abdominal trauma is distinctly unusual. We report a 16-year-old female in whom emergency revascularization with a primary reimplantation on the right and a hypogastric artery interposition graft on the left was performed following angiographic documentation of bilateral renal artery occlusion. Excellent renal function was demonstrated bilaterally at 7 weeks. Bilateral renal revascularization is feasible in the acute setting and can yield excellent results.

Abdominal Injuries↗
PubMedDate not supplied

Skeletal muscle ventricles in continuity with the bloodstream.

BACKGROUND AND AIM OF STUDY: The prevalence of end-stage congestive heart failure and limitation of clinical alternative treatments present the need for creative new solutions. Formation of a ventricle from skeletal muscle (SMV) has shown promise in the animal laboratory. Two modes of the SMV for cardiac assistance, the counterpulsation (CP-SMV) and the ventricular assist (VA-SMV), using the latissimus dorsi muscle were applied in a canine model. Ability to augment arterial pressure was assessed. The effect of stimulation delay on the degree of augmentation was also evaluated. METHODS AND RESULTS: Thirty-five SMVs were connected in continuity with the bloodstream in the two modes: (1) CP-SMV (aorta-to-aorta) (n = 12); and (2) VA-SMV (left ventricular [LV] apex-to-aorta) (n = 23). In the CP-SMV mode, designed to simulate the intra-aortic balloon pump, the SMV was simply interposed into the path of the descending aorta (DAo) without prosthetic valves in either the inflow or the outflow conduit. In order to obligate blood flow through the SMV, the DAo was ligated between the two grafts. In the VA-SMV mode, the connection was made with valved conduits from the LV apex (inflow) to the ascending aorta (outflow) (n = 11) or to the DAo (n = 12). The ascending aorta (AAo) was also ligated proximal to the outflow conduit for the same reason of obligating blood flow through the SMV. The SMV was timed to contract in diastole in both the CP-SMV mode and the VA-SMV mode. In the VA-SMV mode, the average systolic pressure without stimulation was 101.6 +/- 2.2 mmHg and with stimulation 118.21 +/- 4.78 mmHg (mean augmentation, 14.5 +/- 2.6 mmHg) (p < 0.01). In the CP-SMV mode, the average systolic pressure without stimulation was 97 +/- 32 mmHg and with stimulation, 122 +/- 26 mmHg (mean augmentation, 25 +/- 8.6 mmHg) (p < 0.001). We also extended earlier work on timing of stimulation of isolated SMV by evaluating the effect of stimulation delay on the degree of augmentation in continuity with the bloodstream with the SMV in the VA-SMV configuration. Delays of 50 msec to 225 msec were evaluated. SMV stimulation was via the thoracodorsal nerve at an amplitude of 1.5 V and a frequency of 25 Hz. The greatest augmentation occurred at a stimulation delay of 150 msec (p < 0.001). CONCLUSION: Both counterpulsation and assist configurations produced effective diastolic augmentation. Although diastolic augmentation occurred with all timing delays, the optimal delay was 150 msec. Complications in the survival animals include AAo problems, SMV rupture, respiratory insufficiency, intraoperative instability, and thrombosis (which occurred in 51% [18/35] of the animals). This high frequency of thrombosis in the canine model suggests the use of a less thrombogenic SMV lining, more aggressive or prolonged anticoagulation, or an alternative animal model.

Animals↗
PubMedDate not supplied

Stimulation of adenylate cyclase activity in cultured endothelial cells subjected to cyclic stretch.

While vascular endothelial cells are repeatedly stretched by the pulsatile nature of cardiac output, in vitro models traditionally used to study vascular biology involve static culture techniques. We have recently shown that pulsatile stretching of endothelial cells in culture will increase their rates of proliferation and regulate their secretion of macromolecules. The aim of this study was to determine whether membrane adenylate cyclase is involved in intracellular signalling during pulsatile stress. Bovine aortic endothelial cells were seeded on flexible-bottomed culture wells (3 x 10(5) cells/25 mm well) and allowed to attach for 48 hours. The culture wells were placed in a vacuum-operated stress providing instrument and subjected to 0.5 s of 24% strain, 0.5 s relaxation (60 cycles/min) for 0, 1, 3, 5, 7, 10 and 15 minutes (N = 24 wells/time point). Cells were homogenized and a crude membrane preparation (27,000 x g) was assayed for adenylate cyclase under basal and forskolin (100 microM) stimulated conditions. The results indicate that there is a time-dependent increase in both basal and stimulated adenylate cyclase with cyclic deformation and suggest that there may be a "stretch receptor" coupled to adenylate cyclase which can modulate endothelial cell function with hemodynamic changes.

Adenylyl Cyclases↗