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Biomedical subjects

H Harasaki

Publications and source records attributed to H Harasaki.

At least 19 recordsLinked to original sources

Effects of design geometry of intravascular endoprostheses on stenosis rate in normal rabbits.

To investigate the effects of gaps between the individual wire coils of a shape memory Nitinol alloy intravascular endoprosthesis, 20 stents with and without gaps were implanted transluminally into the infrarenal abdominal aortas of 10 normal rabbits after balloon angioplasty. Digital subtraction angiography (DSA) was done at 4, 12, 16, 20, and 24 weeks after stent implantation to examine the stenosis rate and major side branch patency. Stenosis rate within stents with gaps were significantly lower than those without gaps: 8.1 +/- 5.0% versus 15.0 +/- 6.8% at 12 weeks, 13.6 +/- 6.0% versus 26.0 +/- 9.4% at 24 weeks by DSA, p greater than 0.005 and p less than 0.01 respectively. The maximum and mean neointimal thickness measured histologically at the time of animal death correlated significantly to the narrowest diameter obtained from the DSA studies, (r = 0.84 and r = 0.79, respectively, p less than 0.01). Greater hyperplasia of the neointima was evident in the stented arterial segments with stents without gaps compared with those with gaps (83 +/- 22 versus 187 +/- 46 microns mean thickness, p less than 0.001). The patency rate of the side branches in the stented arterial segment was significantly (p less than 0.05) higher in stents having gaps. These results suggest that the placement of gaps between wire pitches reduced the neointimal thickness within stents and prevented the obstruction of arterial side branches.

Angioplasty, Balloon

Biodegradable pericardial implants for bladder augmentation: a 2.5-year study in dogs.

Bladder augmentation using biodegradable pericardial tissue was evaluated in canine bladders. Acetic acid and acetic anhydride treated pericardial tissue grafts were stored in 75% ethanol for 18 to 27 months before implant. Ten dogs weighing 20 to 25 kg. were subjected to a 50% partial cystectomy. After careful separation of the mucosa, bladder muscle and adventitial layers a pericardial graft volumetrically equivalent to the portion of the bladder removed was sutured to the bladder remnant in 2 layers. In 1 control dog the bladder was opened, 50% of the bladder was removed and the bladder was closed primarily. In another control dog the excised bladder was replaced with fresh chemically treated patch material that was never subjected to ethanol storage. Excretory urography and cystography were performed on all dogs. Urodynamics with filling pressures and bladder volumes measured before and after the operation at intervals of up to 36 months confirmed that adequate bladder capacity was achieved. There were no operative complications. Postmortem histological evaluations revealed a smooth epithelialized inner surface with no traces of any surface irregularities or suture lines. The bladder apex showed an intact epithelium and the absence of a smooth muscle layer. The biodegradable acetylated tissue provides an intact structural reservoir for urine and serves as a template for epithelial regeneration. This permits volumetric bladder enlargement while the graft is progressively reabsorbed with time.

Animals

Damage to erythrocytes from long-term heat stress.

1. Erythrocytes are known to haemolyse in vitro at 48-50 degrees C. We hypothesized that erythrocytes might be damaged at much lower temperatures if they are incubated for prolonged periods. Erythrocytes from healthy human donors (n = 7) were incubated at 37, 40, 42, 44, 46 or 48 degrees C for 4-48 h. The haemolytic percentage and osmotic fragility were then measured by a modification of the method of Parpart et al. 2. Significant haemolysis and increased fragility were not observed at any temperatures after incubation for 4 h. However, the haemolytic percentage increased after incubation for 24 h at 44 degrees C (9.1 +/- 4.9%, P less than 0.01), 46 degrees C (52.4 +/- 14.1%, P less than 0.01) and 48 degrees C (98.0 +/- 2.6%, P less than 0.01) and after incubation for 48 h at 42 degrees C (9.8 +/- 4.5%, P less than 0.01) when compared with the values before heating (1.1 +/- 0.9%). The osmotic fragility also increased after incubation for 24 h at and above 42 degrees C. 3. Although heat-induced haemolysis and an increase in fragility have not been known to occur below 48 degrees C, these were quite apparent after incubation for 24-48 h at only 42 degrees C. This suggests that with regard to thermal effects, it is important to consider not only the temperature but also the duration of heating.

Cells, Cultured

Cardiovascular implant calcification: a survey and update.

Calcification of cardiovascular prosthetic implants is a common and important problem. This review provides an update based upon the Conference on Cardiovascular Implant Calcification held as part of the 13th World Congress of the International Society for Heart Research, 1989. A variety of cardiovascular prostheses are affected clinically by calcification, including bioprosthetic heart valves, aortic homografts and trileaflet polymeric valve prostheses. In addition, experimental studies have demonstrated calcification of artificial heart devices in ventricular assist systems in long-term calf studies. The pathophysiology of this disease process is incompletely understood. A common element between the various types of cardiovascular implant calcification is the localization of calcific deposits to devitalized cells and membranous debris. Prevention of cardiovascular implant calcification by either biomaterial modifications or regional drug therapy (controlled release) is being investigated.

Animals

Effects of single-dose infusion of pyridoxalated-hemoglobin-polyoxyethylene conjugate solution on canine renal function.

Pyridoxalated-hemoglobin-polyoxyethylene conjugate (PHP) is an acellular oxygen-carrying red blood cell substitute made from outdated human red blood cells. This study assessed the effect of PHP on renal function when PHP was infused with a clinically relevant dosage. A single dose of PHP that contains 8% wt/vol each of hemoglobin and maltose or an 8% maltose control solution was infused into the intact circulation of eight dogs (five dogs for PHP and three for the control; 20 ml/kg each, at the rate of 2.5 ml/h/kg for 8 h) in the awake state. Serial measurements of glomerular filtration rate (GFR) and renal plasma flow (RPF) were carried out before and after infusion for up to 2 weeks, along with determinations of urine volume flow rate, fractional excretion of sodium (FES), and free water clearance (CH2O). The results showed an elevation of plasma colloid osmotic pressure by an average of 4.4 mm Hg immediately postinfusion with PHP solution. An average 23% decrease in GFR, without notable changes in RPF immediately postinfusion, was observed in the PHP group; the value returned to the preinfusion level by 1 week postinfusion. Increases in parameters such as urine output, FES, and CH2O, which were more pronounced in the PHP group, were observed for 24 h after the infusion in both groups. Light microscopic examination of kidney specimens taken at 2 weeks postinfusion revealed a slight degree of vacuole formation in approximately 80% of the proximal tubules in the PHP group. The tubules were devoid of typical pathologic features of acute renal failure, and the vacuoles did not cause any observable changes in the assessed tubular functions.

Animals

Vascular stenting in normal and atherosclerotic rabbits. Studies of the intravascular endoprosthesis of titanium-nickel-alloy.

Percutaneous transluminal balloon angioplasty would be more effective if the rate of recurrent stenosis were reduced. To evaluate the prevention of restenosis after percutaneous transluminal angioplasty, intravascular endoprosthetic stents of titanium-nickel-alloy were implanted transluminally in seven normal and 21 atherosclerotic rabbits. In normal rabbits, a 3.5-mm diameter stent was implanted in the aorta and a 2.5-mm diameter stent in the right iliac artery, which were followed with serial angiograms from 6 weeks (n = 7) to 8 months (n = 4). There was a mean stenosis of 13.1% in the 2.5-mm and 13.6% in the 3.5-mm stent. There was no significant narrowing compared with the adjacent control segments of artery; histopathology showed a thin, fibrous neointima with smooth muscle cells. Each atherosclerotic rabbit was balloon dilated at two separate stenotic sites; each site was 2.0 cm in length. The aortic site (with 28.8 +/- 13.8% mean stenosis [+/- SD]) was dilated with a 3.5-mm balloon, and the iliac site (with 36.5 +/- 14.2% stenosis) was dilated with a 2.5-mm balloon. In each site, an intravascular stent of corresponding diameter and 7-mm length was implanted in one half of the dilated segment, assigned randomly, and the other half served as the angioplasty control. Angiographically observed restenosis rates and the corresponding histopathology were similar in the atherosclerotic segments that had angioplasty alone versus the atherosclerotic segments that had angioplasty plus stenting. The mean neointimal thickness in the aortas and iliac arteries, respectively, measured 247 +/- 181 microns (+/- SD) and 218 +/- 77 microns after 6 weeks (n = 8) versus 321 +/- 168 and 308 +/- 189 microns after 20 weeks (n = 5, p = NS). At 20 weeks follow-up, there was 29.1 +/- 29.8% (median, 16.4%) stenosis in the aortic stent versus 38.9 +/- 24.1% (median, 34.0%) stenosis in the percutaneous transluminal angioplasty control segment of aorta (n = 5, p = NS) and 81.4 +/- 25.5% stenosis in the iliac artery stent versus 89.3 +/- 15.3% stenosis in the PTA control segment of the right iliac artery (n = 5, p = NS). Comparing stenotic arterial segments treated with angioplasty alone with angioplasty plus intravascular stenting in the atherosclerotic rabbits showed that there was no significant difference in either the histopathologic changes or the restenosis rates.

Alloys

Conjugated human hemoglobin as a physiological oxygen carrier--pyridoxalated hemoglobin polyoxyethylene conjugate (PHP).

Problems associated with specific physiological properties of Hb-based blood substitutes, such as low P50, short plasma half-life and nephrotoxicity are still major issues to be addressed. Extensive investigations aimed at overcoming these problems have resulted in the preparation of pyridoxalated-hemoglobin-polyoxyethylene conjugate (PHP). PHP was developed from human hemoglobin by two major chemical modifications; pyridoxylation for the purpose of lowering the oxygen affinity (P50 of 19.5 +/- 1.2 mmHg), and coupling with polyoxyethylene (POE) to increase its molecular weight (to approximately 90 kdaltons). The circulating half-life of PHP is about 40 hours in dogs. Toxicological and physiological studies including renal function assessments have demonstrated that PHP does not have untoward effects on major organ functions. Its efficacy in transporting oxygen has been shown in ET and intracoronary perfusion, and in in vitro studies with sickle cells. Studies to date suggest that PHP is a promising candidate as a physiological oxygen carrier. In this paper the properties of PHP, its safety and efficacy aspects, and its potential as a clinical oxygen carrier are reviewed based on studies conducted in the Author's laboratory.

Animals

Radionuclide assessment of the natural heart ejection fraction before and after LVAD implantation.

Complete pressure unloading of the ventricles can preserve ischemically damaged myocardium. Most clinical left heart assist device (LVAD) systems used after ischemic injury of the heart apply atrial cannulation which does not ensure pressure unloading. In order to assess the effect of the implantation of an intracorporeal LVAD on the function of the natural heart, we determined the ejection fraction (EF) in four male Holstein calves (90-105 kg) before and after insertion of a Cleveland Clinic pneumatic LVAD. A gated blood pool scan was obtained with a gamma camera after injection of 40 mCi Tc-labelled albumin. The animals were restrained in a sling to avoid movement artifacts. All animals showed a drop of 65 +/- 12% to 42 +/- 14% EF in the first postoperative (p.o.) week. Left ventricular output did not maintain sufficient blood pressure as assessed by pump-off tests. Systolic blood pressure dropped from 122 +/- 6.5 mm Hg to 81 +/- 6 mm Hg without pump support on the morning of the first p.o. day. Apical coring and possible restrained heart movement by the implanted LVAD may lead to impaired myocardial function that renders the individual LVAD dependent until adaptative corrections take place.

Animals

Titanium-nickel intravascular endoprosthesis: a 2-year study in dogs.

Twelve 5-mm-internal-diameter intravascular endoprostheses of noncorrosive, shape-memory titanium-nickel (TiNi) alloy were delivered transluminally by catheter and implanted in the iliac (n = 10) and femoral (n = 2) arteries of six normal dogs for either 1 or 2 years in order to evaluate the implantation technique and long-term effects. The patency rates were as follows: at 1 month, 92% (11/12); at 1 year, 100% 11/12 widely patent; 1/12 recanalized); and at 2 years, 100% (3/4 without stenosis; 1/4 with 20% stenosis). No migration, erosion, inflammation, surface thrombus, or stenosis of the side branches was seen; an absence of untoward angiographic and histopathologic effects was detected at 1 and 2 years. The neointima was completely endothelialized, without changes in thickness over time, 229.3 +/- 127.6 microns after 1 year and 223.3 +/- 216.7 microns after 2 years (p = not significant). The neointimal layer became thicker toward its distal aspect (p less than or equal to .05). Satisfactory delivery, long-term patency, and biocompatibility (manifested as a thin, stable neointima) were observed for the TiNi intravascular endoprosthesis at 1 and 2 years.

Animals

In vivo evaluation of a pyridoxylated-hemoglobin-polyoxyethylene conjugate.

A pyridoxylated-hemoglobin-polyoxyethylene conjugate (PHP) was developed from outdated human red cell hemoglobin through chemical modifications. The PHP has a mean molecular weight of approximately 90,000 daltons, with an acceptable P50 of 22 +/- 0.7 mmHg. This report describes exchange transfusion studies (ET) to a final hematocrit of 5 +/- 2% (n = 5) with PHP in mongrel dogs. Hespan (a plasma expander) was used as a control (n = 6). All the animals with PHP tolerated the procedure well and have survived more than 8 months to date. Five out of the six dogs receiving Hespan died within a week (p = 0.004). Reduction of hematological and coagulation parameters occurred following the ET and returned to the normal range by 4 weeks post ET. Serum electrolytes and renal function parameters (urea, creatinine) remained in the normal range. A transient slight increase in the hepatic enzyme SGOT was observed. At 2 weeks post ET open biopsies of major organs showed vacuolized cells in the liver and kidneys. Normal histology was noted at 3 months. The oxygen transporting properties examined showed effective oxygen delivery to the tissues for 6 hours post ET. PHP continued to transport oxygen for up to 48 hours studied post ET. Half-life of PHP in the circulation was 36.3 +/- 3.5 hours. Urinary loss of hemoglobin measured up to 48 hours after ET was 9.4 +/- 1.6% of the injected net hemoglobin. The PHP effectively supported life at lethal levels of anemia and is a physiologically acceptable solution. It has a relatively long intravascular residence time and transports oxygen to the tissue effectively for at least 6 hours.

Animals

Heat dissipation through the blood contacting surface of a thermally driven LVAS.

A heat exchanger for a totally implantable heat driven LVAD is an essential element in overall system thermal management. The heat exchange is accomplished by supplying cooling water from a pusher-plate driven water pump to the engine and then to the heat exchanger on the pump housing. The temperature of the interface between the blood and pump surface is of critical importance for clinically acceptable operation of the system. Temperatures were measured by instrumenting a pump housing with thermocouples and an electric heater on a mock circulatory loop. Flows were varied from 1 to 8 l/min and heat input was 20 watts. At 1.0 l/min pump flow the maximum inner surface temperature rise is 4.5 degrees C. In vitro tests were conducted to examine the effect of elevated temperature on platelete function. Both platelet aggregation and adhesion were reduced at elevated temperatures of 42 and 47 degrees C indicating a potential benefit of reduced thrombogenesis on the heated housing surface.

Assisted Circulation

Biological performance of TiNi shape memory alloy vascular ring prostheses: a two year study.

A method was developed for the noninvasive insertion of a vascular ring prostheses aimed at preserving arterial patency and preventing restenosis following angioplasty. Using a specially designed 7F catheter 22 nitinol (TiNi) wire prostheses (I.D. 5 mm; 0.25 mm thickness) were torsion reduced in diameter and inserted under fluoroscopy into both carotid (n = 2) and iliac-femoral arteries (n = 20) of dogs. Aspirin (650 mg BID) and Persantin (200 mg BID) were given for only 30 days postoperatively. Angiography of all rings at 1, 6, 12 months exhibited excellent biocompatibility and long term patency 91% (20/22) as reported in Trans ASAIO 32:30, 1986. Four rings inserted in the right and left common iliac arteries and femoral artery were followed for up to 2 years and exhibited 100% patency. Angiography demonstrated that the anchorage of the prostheses was stable and the lumen was uniformly covered by a thin neointimal layer of endothelial like cells. The prostheses were patent with no evidence of thrombosis or inflammation. In view of the problem of recurrent stenosis occurring during the healing period after balloon angioplasty (PTA or PTCA), this approach may lead to a new means of clinical intervention in atherosclerosis.

Alloys

Biomaterial-associated calcification: pathology, mechanisms, and strategies for prevention.

Deposition of calcium-containing apatite mineral occurs widely in association with cardiovascular and noncardiovascular medical devices and biomaterials, is the leading cause of failure of contemporary bioprosthetic heart valves, and limits the functional lifetime of experimental (and potentially clinical) mechanical blood pumps and polymeric heart valves. Calcification of bioprosthetic tissue is primarily intrinsic, related to cuspal connective tissue cells and fragments, and collagen. In contrast, the predominant site of calcific crystals on flexing polymeric surfaces in blood pumps or valve prostheses is extrinsic, associated with adherent cells, thrombus, or pseudointima. Pathologic calcification shares key features with physiologic skeletal mineralization, including crystal initiation through the mediation of cell membranes, usually in the form of extracellular vesicles. This suggests a unified hypothesis for normal and abnormal mineralization. Several approaches are being studied experimentally for the inhibition of bioprosthetic heart valve calcification. Controlled-release diphosphonate therapy, perhaps in conjunction with an anticalcification cuspal pretreatment, appears most effective. Research objectives in biomaterial-associated calcification include (1) development of animal models, (2) determination of initial crystal nucleation events and sites, (3) elucidation of the relative roles of host, implant, and mechanical determinants, and (4) development of approaches for the inhibition of mineralization.

Assisted Circulation

Anatomicomechanical study for the hydraulic line of a thermal left ventricular assist system.

A thermal left ventricular assist system currently under development consists of two separate major components, i.e., a pump/actuator module and an engine/thermal battery module. The possible implantation site of the engine/battery module is tentatively determined to be the iliac fossa, which requires a flexible interconnecting line to the pump/actuator module. A quantitative and biomechanical study was done on the effect of the implanted hydraulic line on the bendability of the torso. It revealed that the semirigid interconnecting line would not severely restrict the movement of the patient provided it has the proper prebend configuration. The cadaver fitting study proved the anatomical feasibility of the retroperitoneal iliac fossa as the implant site of the Thermal Ventricular Assist System 8 (TVAS 8) engine/battery module. The location and configuration of the interconnecting line of the TVAS 8 were determined using biomechanical analysis so that the restriction of the body movement due to the line could be minimized. The main route of the line was the left side of the trunk, and the line is W shaped in configuration. The line elongation is the most critical resistive factor and accordingly there may still be rigidity during lateral flexion.

Assisted Circulation

Experimental evaluation of complete electrically powered ventricular assist system.

The LVAS utilizing an intrathoracic blood pump and a parathoracic, electrohydraulic energy converter has a number of promising features. These include: transcutaneous energy transmission and an implanted variable volume device which eliminate the need for percutaneous access; utilization of an intrathoracic blood pump and variable volume device which allow the diaphragm and abdominal cavity to remain intact; parathoracic or subcutaneous location of the transformer secondary, energy converter, internal battery and interconnecting elements allowing replacement with a minor surgical procedure; employment of the "biolized" continuous blood contacting surface which has the potential of long-term use without anticoagulants and utilization of an electrohydraulic energy converter which provides synchronization without requiring transducers and associated electronics and which provides lubrication of mechanical components. The development effort, which began separately in 1977 and has been conducted jointly by Nimbus and the Cleveland Clinic since 1980, has demonstrated that the above features can be incorporated in a reliable LVAS. In particular, the system in vivo test series have demonstrated the soundness of the basic concepts and led to refinements which were demonstrated in the 6-1/2 mo test. All elements of the system have been utilized during the in vivo test program. Component tests of significance include: LVAS and total heart blood pump in vivo experiments of up to 7 mos duration which demonstrate the blood compatibility of the biolized surface without the use of long-term anticoagulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals