Biomedical subjects

H Harasaki

Publications and source records attributed to H Harasaki.

At least 127 records · Page 7Linked to original sources

PubMedDate not supplied

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↗

PubMedDate not supplied

Effects of mechanical ventilation and spontaneous respiration on hemodynamics in calves with total artificial hearts.

The effects of respiration on hemodynamics were evaluated in four Holstein calves with total artificial hearts (TAH). The electrohydraulic actuated E4T-TAH has a continuously reciprocating actuator packaged between two alternately ejecting blood pumps that passively fill. The hemodynamic parameters (right atrial pressure [RAP], left atrial pressure [LAP], pulmonary artery pressure [PAP], aortic pressure [AoP]), and right and left pump filling (Rt% fill and Lt% fill) were measured when the animal was intubated and mechanically ventilated. These measurements were repeated with spontaneous respiration after the animal was extubated. With mechanical ventilation, LAP, PAP, and AoP were significantly higher during inspiration than during expiration. However, RAP during inspiration was slightly lower than that during expiration. The Rt% fill during inspiration was significantly lower than during expiration, but Lt% fill during inspiration was significantly higher than during expiration. During spontaneous respiration, these changes were opposite to those observed during mechanical ventilation. That mechanical ventilation generates positive intrathoracic pressure during inspiration, but spontaneous respiration generates negative pressure may explain these results. The change in venous return to the right atrium caused the change in RAP to be opposite in direction to that of the other pressures.

Animals↗

PubMedDate not supplied

Initial in vivo tests of an electrohydraulic actuated total artificial heart.

The authors are involved in developing a total artificial heart (TAH) for permanent human use. This device was designed to fit human anatomy, and it has housings made of carbon fiber-epoxy composite and titanium. Tissue valves and protein coating of blood contacting surfaces minimize the need for anticoagulants. A continuously reciprocating electrohydraulic actuator is packaged between two alternately ejecting and passively filling ventricles. The control system varies the pump rate to maintain average left ventricular filling at 90%. This TAH in vivo successively progressed through 1, 5, 9, and 45 day implants in calves of 84, 94, 82, and 82 kg preoperative body weights. The operating modes include automatic and fixed rate. The chronic and acute effects of varying the right pump displaced stroke volume indicated the need for it to be limited to 85% of that of the left for stable hemodynamics at maximum flow. The pump exhibited afterload insensitive and preload sensitive performance. Pump output ranged from 4.0-9.5 L/min at left atrial pressures of 7-16 mmHg at pump rates of 80-160 beats/min in these four experiments. These data suggest that this device will meet clinical hemodynamic requirements; it has the potential for total implantable cardiac replacement.

Animals↗

PubMedDate not supplied

The effects of radiation therapy on the tissue capsule of soft tissue implants.

A prosthesis has been developed for cosmesis after lumpectomy surgery for breast carcinoma. The device is saline filled and percutaneously adjustable in volume to permit an optimal cosmetic result after surgical wound healing. A series of 24 studies of 18 weeks' duration using the adult rabbit animal model were first used to study tissue capsule formation around textured versus smooth surface control implants and to evaluate the effects of volume adjustments on the tissue capsule. Single or multiple adjustments of implant volume had no effect on tissue capsule thickness or morphology. Because lumpectomy surgery is invariably followed by radiation therapy, a series of six studies was then conducted to determine the effects of a typical course of radiation therapy on tissue capsule formation. One week after device implantation, a 4 x 4 cm field including the implant was irradiated with 5,000 rad (200 rad/day x 5 days/week x 5 weeks). The animals were maintained for a 6 week period after radiation treatment. After sacrifice, the implants were removed, and the tissue capsules studied using conventional histologic techniques, including scanning and transmission electron microscopy. There was no statistically significant difference in tissue capsule thickness compared to nonirradiated controls. Tissue capsule morphology, however, differed markedly. Radiation therapy decreased angiogenesis, cellularity, and the inflammatory cell response to the implants. Qualitatively, radiation treatment seemingly improved rather than compromised the connective tissue response to the implants.

Animals↗

PubMedDate not supplied

Adaptation of tissue to a chronic heat load.

Determination of the chronic effect of heat on tissue is one of the important issues facing mechanically actuated total artificial heart (TAH) development. In an effort to characterize this effect, implantations of heating devices producing constant heat fluxes of 0.04 watts/cm2, 0.06 W/cm2, and 0.08 W/cm2 were performed in 11 calves (H-series). Heated disks were implanted adjacent to lung and muscle tissue for a period of 7 weeks. Temperature sensors were placed at the surface as part of the heater assemblies. The results showed that initially, temperature elevations above body temperature (delta T) were 6.4 +/- 0.6 degrees C, 4.5 +/- 0.2 degrees C, and 1.8 +/- 0.5 degrees C at the muscle heater surface for 0.08, 0.06, and 0.04 W/cm2, respectively. At 2 weeks after implant delta T values changed to 5.5 +/- 0.6 degrees C, 3.4 +/- 0.2 degrees C, and 1.8 +/- 0.2 degrees C, respectively. Seven weeks after implant, delta T values decreased to 3.7 +/- 1.2 degrees C, 2.8 +/- 0.1 degrees C, and 0.8 degrees C for 0.08, 0.06, and 0.04 W/cm2, respectively. The authors think this change is attributable to an adaptive response of the tissue to increase heat dissipation through angiogenesis. Results from three TAH cases indicated that at two measured tissue interfaces, delta T decreased by 1 degrees C during a 15 day period. At the same time, the waste heat (volts x current in-flow x afterload to the blood) remained constant at 11.1 +/- 0.5 W during this period. This decrease in delta T corresponded to that observed for the H-series experiments at the higher heat fluxes. Thus, it appears that adaptation observed in the H-series experiments also is seen for tissues surrounding heat sources such as the TAH.

Adaptation, Physiological↗

PubMedDate not supplied

Assessment of circulating blood volume in calves with a total artificial heart.

Measurement of the circulating blood volume (CBV) is essential to a proper understanding of the hemodynamic performance of total artificial hearts (TAHs). Recently, the authors employed CBV measurements using indocyanine green dye in calves with a TAH. The advantages of this method over previous methods using radionuclides include simplicity, low cost, and the capability of repeated and frequent measurements. Reproducibility of the measurements was demonstrated in three normal calves with a relative standard deviation of 3.9 +/- 2.4%. CBV was measured in eight calves with the Cleveland Clinic-Nimbus TAH and compared with that of seven calves that underwent mitral valve replacement. Small standard deviations in pre operative values in both TAH and mitral valve replacement groups demonstrated the precision of CBV measurements. Although there was no change in CBV in the mitral valve replacement group, CBV in the TAH group increased to more than twice the pre operative value after 2 weeks. Although the right atrial pressure increased similarly after TAH implantation, there was no correlation (r = 0.08) between the right atrial pressure and CBV, which suggested a possible inaccuracy in estimating CBV from the right atrial pressure. A negative correlation between the hematocrit value and CBV suggested that hemodilution might be one of the causes of anemia observed in our TAH animals.

Animals↗

PubMedDate not supplied

A comprehensive hematologic study in calves with total artificial hearts.

Thromboembolism and infection remain potential threats for long-term circulatory assist and replacement devices. The alteration of the hemostatic system and of blood cell functions caused by device implantation may predispose the recipient to these complications. Many sensitive coagulation assays and the technology of flow cytometry would be powerful tools for this investigation. The availability of such immunologic technologies for animal species other than humans has yet to be established. In a series of in vitro tests we found that the following assays, among others, are usable in calves: TAT, TxB2, platelet surface glycoprotein IIbIIIa, and membrane aminophospholipid. F1.2, D-dimer, beta TG, PF-4, and platelet surface expression of GMP-140 and receptors for fibronectin, thrombospondin, and vWF were not measurable. A sustained mild decrease in hematocrit levels in six calves with the Cleveland Clinic-Nimbus total artificial heart for 11-120 days was attributed to an increase in circulating blood volume, but not to red blood cell damage. Whole blood platelet aggregation was suppressed only for the first 3 post operative days, with decreased GPIIbIIIa expression. Polymorphonuclear phagocytosis, chemotaxis, and superoxide anion production were not altered. Device infection and thromboembolism occurred in one of 13 cases overall.

Animals↗

PubMedDate not supplied

Anatomic fitting studies of a total artificial heart in heart transplant recipients. Critical dimensions and prediction of fit.

Anatomic fitting studies of the Cleveland Clinic-Nimbus total artificial heart were performed in 33 patients undergoing heart transplantation. The pump fit in the pericardial space in 20 men (80%) and 4 women (50%). There was no significant difference between the Fit and Non-Fit groups in external chest dimensions. Among 42 intrathoracic dimensions, the distance from the center of the mitral valve to the diaphragm (Fit: 5.6 +/- 2.2 cm, Non-Fit: 3.6 +/- 0.4 cm, p < 0.00001) and the distance from the caudal end of the pulmonary valve to the diaphragm (Fit: 9.4 +/- 1.6 cm, Non-Fit: 6.3 +/- 0.8 cm, p < 0.0001) were the most critical. To predict anatomic fit, an index (A x B x C) was obtained from chest X-ray measurements (A, the craniocaudal distance from the dorsal region of the 8th left rib to the left diaphragm; B, the maximum left chest width; and C, the maximum anteroposterior sternum-vertebrae dimension). The pump fit in 88.5% of the patients with an index above 1200 cm3, whereas it fit in only 14.3% of the patients with an index below 1200 cm3 (p < 0.001). This index was an easily obtainable, good predictor of anatomic fit.

Diaphragm↗

PubMedDate not supplied

In vitro evaluation of automatic control performance of a total artificial heart with changes in pump orientation.

Unlike in animal experiments, the pump orientation of a total artificial heart (TAH) can change remarkably in humans with the recipient's posture (upright, supine, or prone), thus affecting its filling characteristics. The left master alternate control mode of the Cleveland Clinic-Nimbus (CC-N) TAH adjusts beat rate by maintaining the left pump at 90% filling, producing a Frank-Starling like preload sensitivity. In order to verify that the CC-N TAH functions properly regardless of the gravity effects on pump filling, the preload sensitivity curves of the CC-N TAH were evaluated on a mock circulatory loop with the simulated supine (right pump up) and prone (left pump up) positions in humans. The right preload sensitivity was slightly higher when the right pump was up versus down, and likewise the left preload sensitivity was higher when the left pump was up versus down. Despite these gravity effects on pump filling, right and left preload sensitivity remained within physiologic range and the automatic control of the CC-N TAH functioned properly without significant postural effects.

Animals↗

PubMedDate not supplied

Microencapsulated vaccines to provide prolonged immunity with a single administration.

Vaccines that provide lasting immunity with a single administration of the antigen can reduce the cost of routine immunization programs while increasing their efficacy by lessening the need for patient compliance. The authors have been developing methods for using biodegradable polymer microspheres to encapsulate vaccines. These microcapsules are designed to provide timed release of the antigen on a schedule that mimics conventional booster shots. The microspheres are made from poly-DL-lactide-co-glycolide. The rate of biodegradation of this polymer is controllable by varying the molar ratio of the monomers. High performance liquid chromatography was used to measure release kinetics in vitro, and a process was developed for the encapsulation of water soluble protein antigens. This process then was used to prepare a microencapsulated vaccine for type A botulism made using a recombinant C fragment antigen. A series of 27 adult C57BL/6J mice were used to study the efficacy of this vaccine. Six mice injected with saline filled microspheres served as a control group. Plasma samples were taken weekly to measure antibody levels using enzyme linked immunosorbent assay. At 14 weeks, 21 immunized mice and six control subjects were used for an aerosol challenge test with botulinum toxin. All control subjects died within 72 hrs. Fifteen (71%) of the immunized mice survived.

Animals↗

PubMedDate not supplied

Platelets are deposited early post-operatively on the leaflet of a mechanical heart valve in sheep without post-operative anticoagulants or antiplatelet agents. A scanning electron microscopic observation of the pyrolytic carbon surface in a mechanical heart valve.

Pyrolytic carbon has been used for mechanical heart valves as a thromboresistant, wear resistant, and fatigue resistant material. Thrombosis and thromboembolism, however, remain major mechanical heart valve associated complications and may frequently occur during the early post-operative period. In depth morphologic studies on blood-pyrolytic carbon surface interactions are limited. The purpose of this study was to evaluate the blood compatibility of the pyrolytic carbon surface of St. Jude Medical mechanical heart valves that were implanted in the mitral position of sheep without the administration of post-operative anticoagulants or antiplatelet agents for 2, 4, and 6 weeks. Almost the entire leaflet and orifice ring surfaces were observed by scanning electron microscopy. Although the surfaces appeared clean macroscopically, when observed by electron microscopy, the surface were mottled, mainly by solitary platelets and aggregations. There were only a few leukocytes or red blood cells observed. No fibrin clots were observed on the leaflets. The density of platelet deposition was higher in the vicinity of the pivots and near the edges of the leaflets. The sizes of the platelet aggregations decreased with longer duration. The outer surfaces of the pivot guards were covered by various amounts of deposition composed of platelet aggregations and thrombi. Thus, the administration of antiplatelet agents is recommended during the early post-operative period after mechanical heart valve implantation.

Animals↗

PubMedDate not supplied

Effects of heat on fragility and morphology of human and calf erythrocytes.

It is important to know the species differences when data from animal experiments are interpreted for human application. This in vitro study focused on the effects of heat, a major concern in mechanically actuated artificial heart development, on the physiology of human and calf erythrocytes (RBC). RBC from calves and healthy human donors were incubated at 25, 37, 46, 48, 50, or 52 degrees C for 1 h. Osmotic fragility was tested and morphological changes were then observed by scanning electron microscopy. The osmotic fragility of human and calf RBC increased at and above 50 degrees C. After incubation at 50 degrees C, 6% of human and 1% of calf RBC hemolyzed. Changes in surface morphology, which included spherocytic or echinocytic forms, were observed in 97% of human and 19% of calf RBC after incubation at 50 degrees C. In conclusion, human RBC showed greater changes in osmotic fragility and morphology at and above 50 degrees C. These changes, however, were not observed in either species after 1 h incubation at 46 degrees C.

Analysis of Variance↗

PubMedDate not supplied

Effect of oral and intravenous diltiazem on whole blood platelet aggregability.

Diltiazem, a calcium channel blocker, is known to suppress platelet function in vitro. However, its in vivo effects on platelets have been controversial. The effect of diltiazem on both human and calf platelets was studied using impedance whole-blood aggregometry. In vitro, platelet aggregation induced by ADP (5 microM) or collagen (1 micrograms/ml) was significantly suppressed by 0.1 to 1.0 mM (45 to 450 micrograms/ml) of diltiazem in both species. In calves weighting 70 to 90 kg, platelet aggregability did not change after the oral administration of 180 mg diltiazem. In this condition, diltiazem was not detected in plasma samples. Intravenous injection of 0.5 mg/kg diltiazem also did not significantly alter the aggregability, although the PR interval on the ECG elongated (40 msec, p < .05), mean arterial pressure dropped (14 mmHg, p < .05), and diltiazem was readily detected in plasma (199 ng/ml, 0.4 microM). In conclusion, platelet aggregability is not altered by a clinical dosage of diltiazem that is sufficient to induce hemodynamic changes with therapeutic plasma concentrations.

Administration, Oral↗

PubMedDate not supplied

Anatomic study for in vivo evaluation of a total artificial heart in calves.

A poor fit will negate any physiologic evaluation of an implantable total artificial heart (TAH). Fifteen Holstein calves (weight, 65-111 kg) were used to measure intrathoracic dimensions for TAH design, to find correlations between intrathoracic and external parameters for preoperative animal selection, and to suggest minor modifications for fitting a TAH in calf chests. The following dimensions were found to be critical to avoid compromising venous return: 1) mitral annulus center (MVC)-sternum, 10.4 +/- 1.0 cm; 2) tricuspid annulus center (TVC)-sternum, 9.8 +/- 1.6 cm; 3) MVC-TVC, 5.5 +/- 0.4 cm; 4) MVC-diaphragm, 3.4 +/- 0.8 cm; 5) MVC-left chest wall, 4.5 +/- 0.9 cm; and 6) TVC-right chest wall, 4.5 +/- 1.0 cm. These dimensions had no statistically significant correlation with body weight, but three of them did with the following external parameters: 1) bronchial carina-sternum on chest radiograph, p less than 0.05; 2) dorsoventral dimension at xiphoid, p less than 0.05; and 3) circumference at the caudal end of the scapula, p less than 0.05. Based on these results, the port orientation of the left housing of this electrohydraulic TAH designed for humans was modified for in vivo evaluation in calves. No other pump features required change. These data should prove useful to others involved in TAH development.

Animals↗

PubMedDate not supplied

Development of the E4T electrohydraulic total artificial heart.

A completely implantable total artificial heart (TAH) is being developed based on many years of research performed at the Cleveland Clinic Foundation and Nimbus, Inc. The pumping unit consists of biolized surface-treated pusher plate blood pumps powered by an interventricular electrohydraulic energy converter. A variable volume device references the back side of the pusher plates to lung pressure. Electrical power is supplied by a transcutaneous energy transmission system, integrated with a wearable external battery pack. An implanted internal battery provides back-up power. System design and optimization efforts have resulted in a compact pumping unit package and an overall TAH that meets anatomic, physiologic, and engineering requirements. Overall pumping unit basic dimensions are 98 mm diameter and 80 mm thick. The blood pumps have a truncated conical shape and are separated by a thin interventricular septum 21 mm thick. Theoretical stroke volume is 64 ml, and maximum stroke length is 13.2 mm. Normal pump operation is at 90% of full stroke, which yields a net output of 53 ml, with valve regurgitation taken into account.

Cardiac Output↗

PubMedDate not supplied

An intrathoracic left ventricular assist system: utilization of results from a development program.

An intrathoracic, electrohydraulically actuated, left ventricular assist system (LVAS) was subjected to formal device readiness testing. Endurance testing was initiated on eight systems before testing was halted due to failure of four of the systems. Three failed due to environmental leakage. Solutions were straightforward, involving gasket changes and o-ring resizing. The fourth failure involved a magnetic coupling piston swelling and seizing. The failure was attributed, after long investigation, to hydrogen adsorption by the samarium-cobalt magnets. An unknown number of coupling magnets were affected in this fashion, necessitating complete replacement of magnets to resolve the problem. However, this was beyond the scope of the program, and no further endurance testing was accomplished. The test experience of the Nimbus/CCF LVAS has demonstrated all functional aspects of the complete LVAS, both in vitro and in vivo, and the endurance and reliability potential is indicated as well. Although the LVAS program is currently inactive, its legacy of technical innovations continue to drive the development of other medical devices.

Animals↗

PubMedDate not supplied

Effect of a pulsing electromagnetic field on metabolically derived osteoporosis in rats: a pilot study.

The literature suggests that a pulsating electromagnetic field (PEMF) is effective against bone loss in disuse osteoporosis. This study was conducted to evaluate the effects of PEMF on metabolically derived osteoporosis in rats. Sixteen 5 month old female Sprague-Dawley rats were divided into three groups (G-1,2,3). G-1 was given a normal diet and no exposure to PEMF; G-2,3 were oophrectomized and fed a low calcium diet for 8 months; and G-3 was also exposed for 24 hr/day to PEMF generated by applying a 15 Hz, 5.6 A peak to peak square wave to Helmholtz coils (64 cm I.D., 200 turns/coil). The rats were sacrificed at 4, 6, and 8 months. Skeletal changes were analyzed by measurements of acid extracted bone calcium and bone mineral content (BMC) using single photon absorptiometry (SPA). Although all animals started at approximately the same weight (mean of 290.0 g), G-2 showed a more progressive increase. While the mean weight after 8 months in G-1 was 350.0 g, and 352.5 g for G-3, that in G-2 was 400.0 g. The calcium content of the femur in G-2 and G-3 at 8 months was lower than that of G-1, but there were no significant differences among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Effects of prostaglandin I2, superoxide dismutase, and catalase on ischemia-reperfusion injury in liver transplantation.

This study evaluated the effects of a prostaglandin I2 analogue (aPGI2), superoxide dismutase (SOD), and catalase (CAT) on hepatic injury after warm ischemia and reperfusion in terms of survival, mitochondrial function, serum enzymes, and histology. Hepatic ischemia was created in rats by clamping the hepatoduodenal ligament for 90 min with splenofemoral bypass. Reperfusion was induced by unclamping the vessels and disconnecting the splenofemoral bypass. Then aPGI2 (350 ng/kg/min) was infused for 60 min just before hepatic ischemia, and SOD and CAT (5,000 units/kg each) were administered immediately before the start of reperfusion. Serum enzyme and mitochondrial function assessments of livers were made just after ischemia, and after 2 hr of reperfusion. Survival rate was also assessed in a separate group of rats. Liver enzymes such as SGOT, SGPT, and LDH showed no correlation to liver viability. The administration of aPGI2 alone showed no effect on ischemically injured mitochondria; however, the free radical scavengers (SOD, CAT), in combination with aPGI2, showed significant improvement of mitochondrial function together with extension of survival. The ultrastructure of hepatocytes was better preserved in the treated groups. These agents improved the viability of ischemic-reperfused injured livers.

Alanine Transaminase↗