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Biomedical subjects

S Murabayashi

Publications and source records attributed to S Murabayashi.

At least 55 records · Page 3Linked to original sources

Hormonal response to insulin-induced hypoglycemia in patients with Shy-Drager syndrome.

We examined the response of plasma glucose concentration and glucose counterregulatory factors (eg, glucagon, epinephrine, growth hormone, cortisol, and norepinephrine) to insulin-induced hypoglycemia in four patients with Shy-Drager syndrome and in five control subjects to determine if glucose counterregulation occurred in the patients with sympathetic and parasympathetic nervous system defects. The recovery of plasma glucose from hypoglycemia in a slower phase in the patients appeared to be almost similar to that in the control subjects, along with the absence of an initial rapid recovery phase; that is, there was no significant difference in the plasma glucose levels observed at any point between the patients and the control subjects. Although the insulin-induced hypoglycemia in the control subjects provoked a rapid release of epinephrine, followed by an increase in the plasma glucagon, growth hormone, and cortisol levels, it did not cause a significant increase in any of the glucose counterregulatory factors in the patients. Our findings that the restoration of normoglycemia after insulin-induced hypoglycemia occurred despite no significant increase in the counterregulatory hormonal factors suggest that other glucose counterregulatory mechanisms (eg, increased glucose release from the liver by the intrinsic effect of hypoglycemia on the liver) than the hormonal glucose counterregulatory factors might play an important role in the recovery of plasma glucose from insulin-induced hypoglycemia in a state of chronic deficiency of hormonal factors.

Autonomic Nervous System Diseases↗

Pituitary-adrenocortical system in patients with Shy-Drager syndrome.

We examined ACTH responses to the three main mechanisms of ACTH secretion, i.e., stress, negative feedback and circadian rhythm, in six patients with Shy-Drager syndrome and in six control subjects to determine whether or not injury to the central autonomic nervous system provokes some disturbances in ACTH secretion. The patients showed a poor cortisol response to the stress of insulin induced hypoglycemia along with a normal ACTH and urinary 17-OHCS response to metyrapone and a normal cortisol circadian rhythm. The discrepancy between the above-mentioned functional tests of ACTH secretion is rare to our knowledge. These findings suggested the existence of a glucoreceptor defect in such patients, or the possibility that the stress of insulin induced hypoglycemia stimulates ACTH secretion by way of the autonomic nervous system.

Adrenocorticotropic Hormone↗

The mechanism of aldosterone response to furosemide test in patients with Shy-Drager syndrome.

We examined the renin-angiotensin-aldosterone system in seven patients with Shy-Drager syndrome by studying their response to the stimulation of 1 mg/kg furosemide injection followed by sitting for 1 hour. Six of the seven patients showed a low response of plasma renin activity to the stimulation. However, in five of the low responders, the plasma aldosterone levels after stimulation were observed to be similar to those of the control subjects; in addition, an increment in the plasma cortisol level appeared although no such increment was observed in normal subjects. Next, we studied the aldosterone response to angiotensin II. The five patients who showed a low plasma renin activity response and a normal aldosterone response to furosemide administration also showed low plasma aldosterone response to angiotensin II. Furthermore, in the patients who demonstrated a low plasma renin activity response and a normal aldosterone response to furosemide administration, the pretreatment with 2 mg dexamethasone for 2 days caused a marked inhibition of aldosterone response to the stimulation. These findings suggested that in most patients with Shy-Drager syndrome, the plasma aldosterone response to the stimulation of furosemide injection followed by sitting for 1 hour might be controlled by ACTH but not by plasma renin activity.

Adult↗

Experimental results for chronic left ventricular assist and total artificial heart development.

After more than 20 years of research on the artificial heart, it is now accepted that the pneumatically actuated total artificial heart can maintain near-normal physiology in experimental animals for several months. Such systems are clinically acceptable for short-term application (a few months) in patients waiting for a suitable heart transplant. However, realistically, a cardiac prosthesis that has the capability of being totally implantable for over 2 years must be available. Based on this premise, our group initiated the development of a mechanically actuated total artificial heart, capable of coupling with either a thermal or electrical actuation system. Since 1977, under the National Institutes of Health chronic left ventricular assist program, we have used two different pusher-plate pumps and electrical systems. Taking advantage of technology generated in these programs, we began developing a prosthesis to replace the total cardiac function. This paper is a summary of both the chronic left ventricular assist and total artificial heart development progress in this laboratory.

Animals↗

Renin-angiotensin system and plasma aldosterone in Cushing's syndrome.

The renin-angiotensin system was studied in eight patients with Cushing's syndrome (four with adrenal adenoma and four with adrenal hyperplasia) and in five normal controls. Basal plasma renin activity (PRA) and aldosterone concentration (PAC) were similar in supine position among Cushing's syndrome due to adrenal adenoma (PRA; 1.0 +/- 0.3 ng/ml/h, PAC; 7.4 +/- 1.0 ng/dl, mean +/- SE), those due to adrenal hyperplasia (1.0 +/- 0.2, 6.9 +/- 0.8) and the controls (0.8 +/- 0.1, 6.4 +/- 0.4). The PRA after furosemide (1 mg/kg i.v.) and 120 min. upright posture stimulation was similar among Cushing's syndrome due to adrenal adenoma (2.2 +/- 0.7 ng/ml/h), those due to adrenal hyperplasia (2.6 +/- 1.7) and the controls (2.5 +/- 1.2). However, the PAC response after the stimulation in Cushing's syndrome due to adrenal hyperplasia (7.1 +/- 1.2 ng/dl) was significantly lower than that in the controls (17.5 +/- 2.1) (p less than 0.01), although there was no significant difference between the PAC response in Cushing's syndrome due to adrenal adenoma (12.6 +/- 1.0) and the controls. These results indicate that PAC response to furosemide and upright pasture stimulation might be suppressed in Cushing's syndrome due to adrenal hyperplasia.

Adenoma↗

Hexsyn trileaflet valve: application to temporary blood pumps.

A trileaflet valve, compression molded of Hexsyn rubber, was evaluated as a component in temporary blood pumps. A pair of valves was integrated into an LVAD which was tested in vitro and in vivo. The valve's hemodynamic performance was satisfactory and the blood compatibility was excellent in a three-week, in vivo experiment conducted to demonstrate performance in a short-term application. Hexsyn, which has excellent properties and produces high quality, complex components with ease of fabrication, offers a potential for low-cost blood pump valves.

Alkenes↗

Pusher-plate type TAH system operated in the left and right free-running variable rate mode.

A TAH system utilizing two pusher-plate type pumps was developed and tested in two calves for 45 and 108 days with excellent results. A Hall effect sensor was utilized to operate each pump with a full stroke at variable rates (VR); each pump was then allowed to run independently at different rates depending on its own preload and afterload. With this system, the animals' atrial pressures were kept to near-normal levels (less than 10 mmHg). However, significant differences in the left and right pump flows were observed (left higher than right) and they ranged from 5 to 30% of the left flow with a mean of 15%. These flow differences may be due to the bronchial circulation and related shunts. Right pump flows averaged 70 to 95 ml/min-kg and circulating blood volume ranged from 67 to 95 ml/kg. When various control modes including fixed rate and master-slave type simultaneously or alternatively ejecting VR modes were applied in the same animals and both pump flows were forced to be equal, unphysiological atrial pressures resulted. This result indicates that perhaps left and right flow differences are necessary physiological conditions to regulate the atrial pressures within normal ranges. Metabolic data also indicated that under simultaneously and alternately ejecting modes, A-V O2 content differences were increased due to decreased right pump flow as compared with those of the free-running VR mode. The left and right free-running VR mode of operation imposed minimal constraints on the animals' cardiovascular system and therefore yielded excellent hemodynamic and metabolic results.

Animals↗

Compliance effect on patency of small diameter vascular grafts.

The compliance mismatch hypothesis as a cause of failure of small diameter grafts was investigated using 4 mm internal diameter, 5 cm long Biolized polyurethane grafts. The luminal surface of 0.5 mm thick Biomer sponge grafts was covered with 100 microns of crosslinked gelatin. Compliance matched, and noncompliant grafts had in vivo compliance values of 13.5 +/- 2.89 and 1.0 +/- 0.7 X 10(-2%) per mmHg, respectively. In vivo compliance defined as 2 X dD/dP X 1/Do was measured in situ using the ultrasonic Hokanson probe. Compliance values of compliant grafts equaled that of the canine carotid artery at 100 mmHg mean arterial pressure. Grafts were implanted using an end-to-end anastomosis in 14 dogs for 6 wk. Patency rates for compliant vs. noncompliant grafts were 64% (9/14) and 50% (7/14). Compliance values for compliant grafts decreased to a mean of 7.14 X 10(-2%) per mmHg. Anastomotic intimal hyperplasia at the proximal and distal ends of compliant and noncompliant grafts measured 239.9 +/- 128, 197 +/- 129 microns, 338.9 +/- 273.6, and 304.3 +/- 179.3 microns, respectively. There were no significant differences in localized anastomotic intimal hyperplasia at either graft end for either graft type. This study did not show any positive effects of graft compliance.

Anastomosis, Surgical↗

Development of an antithrombogenic and antitraumatic blood pump: the Gyro C1E3.

The Gyro C1E3 is a centrifugal blood pump. Its antithrombogenic and antitraumatic blood features were demonstrated by prior studies. Based upon these studies, a mass production model of the C1E3 is becoming commercially available. Therefore, this feasibility study was conducted using the mass production models of the Gyro C1E3 for long-term cardiac assist in ex vivo animal experiments. Five healthy calves were used and 15 pump heads were applied for different time periods (Group 1, 30 days; Group 2, 14 days; Group 3, 10 and 7 days; Group 4, 4 days; and Group 5, 2 days). Activated clotting time (ACT) was kept at 200-250 sec. All five calves demonstrated neither abnormal signs nor abnormal blood examination data throughout the experiment. During necropsy, no thromboembolism was found in any downstream organs. Groups 1-4 showed thrombi inside the pump heads while two pumps in Group 5 had no thrombi formations. Bearing deformation or possible wear did not increase after 2 days of pumping. The C1E3 is capable of long-term assist circulation. However, after 2 days of pumping, careful observation is necessary since thrombi may occur inside the pump when ACT is controlled under 250 sec. During the weaning stage or low flow (under 2 L/min), over 250 sec of ACT is recommended to assure the safety of the patient.

Animals↗

Development of an implantable small right ventricular assist device.

Currently, at least two permanent implantable left ventricular assist devices (LVADs) are used clinically. Unfortunately, there is no small implantable right ventricular assist device (RVAD) available, even though at least 25-30% of this patient population has right ventricular failure. If a small implantable RVAD were available, biventricular assist could support patients with right ventricular failure. A small atraumatic and antithrombogenic RVAD is being developed to meet this clinical need. This small centrifugal blood pump, the Gyro PI pump, is 6.5 cm in diameter and 4.6 cm in height and has three unique characteristics to prevent thrombus formation: (1) the double pivot bearing and magnetic coupling system enable this pump to be completely sealless; (2) the secondary vanes at the bottom of the impeller accelerate the blood flow and prevent blood stagnation; and (3) the eccentric inlet port enables the top female bearing to be embedded into the top housing and decrease blood cell trauma. The inflow conduit consists of a wire reinforced tube and a hat-shaped tip that is biolized with gelatin to create a thrombus resistant material. This conduit is directly implanted into the right ventricle, and the outflow conduit is anastomosed to the PA. The pump can be implanted inside the abdominal wall or in the thoracic cavity. Biocompatibility of this pump was proved in two calves by thrombus free implantation as an LVAD for 284 days and 200 days. Two RVAD implantations were conducted, aiming for 1-month system feasibility studies. During the month, the RVADs operated satisfactorily without any thromboembolic incident. No blood clots or abnormal findings were seen inside the pump, nor were there abnormal findings in the explanted lungs except for small areas of atelectasis. The pump flow was 3.02 +/- 0.38 L/min in calf 1 and 3.75 +/- 1.18 L/min in calf 2. The power requirement was 7.28 +/- 0.43W for calf 1 and 14.52 +/- 3.93W for calf 2. The PaO2 was 72.0 +/- 3.60 mm Hg (calf 1) and 72.0 +/- 7.63 mm Hg (calf 2); PaCO2 was 38.3 +/- 2.17 mm Hg (calf 1) and 34.1 +/- 1.95 mm Hg (calf 2); and SaO2 was 94.1 +/- 1.37% (calf1) and 95.0 +/- 1.95% (calf 2). Gas exchange via the lungs was maintained. These studies indicate that the Gyro PI pump is suitable as a single implantable RVAD, and is a feasible RVAD as a part of a BiVAD system in terms of pump performance and thrombus resistance.

Animals↗

Preclinical evaluation of a hollow fiber silicone membrane oxygenator for extracorporeal membrane oxygenator application.

A silicone membrane hollow fiber oxygenator applicable for use as an extracorporeal membrane oxygenator (ECMO) has been developed in our laboratory. This silicone hollow fiber displays astonishing mechanical stability, is barely compressible or stretchable, and assembles easily while maintaining good gas permeability. The priming volume is 140 cc with a surface area of 0.8 m2. This study evaluated the gas transfer performances and biocompatibility of the oxygenator under ECMO and CPB conditions. In vitro studies that were performed at a blood flow rate of 2 L/min, and revealed O2 and CO2 gas transfer rates of 82.35 +/- 0.56 ml/m2/L/min and 38.72 +/- 2.88 ml/m2/L/min, respectively. The commercially available Kolobow (Avecor 1500) oxygenator was used as the control, and had O2 and CO2 gas transfer rates of 53.8 +/- 0.5 ml/m2/L/min and 24.7 +/- 2.0 ml/m2/L/min. To evaluate blood trauma, Normalized Index of Hemolysis (NIH) was measured according to American Society of Testing and Materials (ASTM) standards. The NIH findings were 0.0112 g/100L at a blood flow of 1 L/min, and 0.0152 g/100L at 5 L/min. Three ex vivo experiments, using a blood flow rate of 1 L/min, were performed with venoarterial bypass, and O2 transfer rate and CO2 transfer rate of the oxygenators were well maintained. This indicates that this preclinical silicone membrane hollow fiber oxygenator has superior efficiency, less blood trauma, and is smaller when compared with the only clinically available Kolobow oxygenator.

Animals↗