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Biomedical subjects

R Shirakura

Publications and source records attributed to R Shirakura.

At least 145 records · Page 8Linked to original sources

Single lung transplantation in rats with chemically induced pulmonary hypertension.

Physiologic effects of single lung transplantation on pulmonary hypertension were studied in rats with monocrotaline-induced pulmonary hypertension. Inbred rats treated with monocrotaline (40 mg/kg) received a left lung isograft from a normal donor 2 weeks later, when pulmonary hypertension became significant (transplant group; n = 6). These rats and control rats treated with monocrotaline (mediated control group; n = 11) or vehicle alone (normal control group; n = 9) were followed up weekly by metabolic treadmill testing for exercise tolerance and oxygen consumption up to 6 weeks after monocrotaline (4 weeks after transplantation), when all rats underwent hemodynamic and histologic examinations. Whereas maximal oxygen consumption and exercise tolerance consistently deteriorated in the medicated control group of rats, indices in the transplant group stopped deteriorating 2 weeks after lung transplantation and remained at levels similar to those of normal control rats. Severe pulmonary hypertension (68 +/- 19 mm Hg) and right ventricular hypertrophy (right ventricular/left ventricular weight ratio, 0.95 +/- 0.19) were confirmed in medicated control rats in contrast to transplant animals, in which these two indices remained at normal control levels. Whereas left-to-right lung perfusion ratio was constant among rats not receiving transplants (0.69 +/- 0.16), it was significantly elevated (2.27 +/- 0.65; p less than 0.001) in those receiving transplants, suggesting preferential flow through the lung isograft. The results suggest that, in the early phase of pulmonary hypertension, single lung transplantation shifts pulmonary perfusion to the grafted lung, avoiding right ventricular pressure overload and thereby preserving exercise tolerance at a nearly normal level in rats with monocrotaline-induced pulmonary hypertension.

Animals↗

Determination of optimal perfusion flow rate for deep hypothermic cardiopulmonary bypass in the adult based on distributions of blood flow and oxygen consumption.

To determine the optimal perfusion flow in deep hypothermic cardiopulmonary bypass at 20 degrees C in human beings, we studied the relationship of perfusion flow to the whole body and to regional oxygen consumption. In adult patients (n = 11, average age 54 years) with valvular or coronary heart disease, the distributions of perfusion flow rate and oxygen consumption were analyzed by dividing into the superior and inferior vena caval areas. Measurements (n = 39) were made at various perfusion flow rates (perfusion flow rate in the superior vena caval area plus that in the inferior vena caval area equals whole-body perfusion flow rate: 0.4 to 2.2 L/min/m2) in a setting of average hemoglobin levels of 8.1 gm/dl. Between whole-body perfusion flow rate and oxygen consumption (total oxygen consumption equals superior plus inferior vena caval oxygen consumption), there was a hyperbolic correlation (r = 0.73; p less than 0.001; asymptote = 29.0 ml/min/m2). A positive linear correlation was found between whole-body perfusion flow rate and inferior vena caval oxygen consumption (r = 0.75; p less than 0.001), whereas no significant relation was seen between whole-body perfusion flow rate and superior vena caval oxygen consumption. For distributional changes in inferior vena caval perfusion flow rate/whole body perfusion flow rate and inferior vena caval oxygen consumption/whole body oxygen consumption, the broken-line regression analysis showed respective critical points where both parameters started to drop when whole-body perfusion flow rate was gradually reduced: 1.2 L/min/m2 for inferior vena caval perfusion flow rate/whole-body perfusion flow rate and 0.8 L/min/m2 for inferior vena caval oxygen consumption/whole-body oxygen consumption. The results indicate that (1) the oxygen consumption to the superior vena caval area was maintained independent of the perfusion in a relatively wide range in contrast to that for the inferior vena caval area and (2) when the redistribution of oxygen consumption is considered as undesirable under low-flow perfusion, the optimal perfusion flow for 20 degrees C deep hypothermic cardiopulmonary bypass appeared to be 0.8 L/min/m2.

Adult↗

Long-term survival and complications after composite graft replacement for ascending aortic aneurysm associated with aortic regurgitation.

The Bentall operation was performed in 44 patients between March 1972 and December 1988. Twenty patients had stigmata of Marfan's syndrome, and 15 had aortic dissection. All showed annuloaortic ectasia. Follow-up ranged from 1 to 16 years (mean, 5.8 years). There were six early deaths (14%) and seven late deaths (16%), with actuarial survival at 10 years of 65 +/- 8%. The late deaths were mostly related to aneurysms occurring in the remainder of the aorta. No patient has undergone reoperation related to the composite graft, but six patients required seven subsequent operations on the remaining aorta. The actuarial probability of freedom from late death and subsequent operation at 8 years was 64 +/- 9% for the operative survivors, but it was 44 +/- 17% for the patients with aortic dissection and 37 +/- 19% for those with Marfan's syndrome. Postoperative angiography performed 3-168 months (mean, 42 months) postoperatively in 23 nonselective patients demonstrated recurrent true aneurysms at both or one of the coronary ostia (seven), persistent dissection distal to the distal aortic anastomosis (five), pseudoaneurysm at the left coronary ostium (one), pseudoaneurysm due to a small leak at the proximal aortic anastomosis (one), and partial dehiscence of the distal aortic suture line (one). Composite graft replacement carries a potential risk of various late complications. Our data support the concept that earlier detection and aggressive treatment of the late complications occurring in the remainder of the diseased aorta is necessary to improve long-term survival after the Bentall operation.

Actuarial Analysis↗

Experimental evaluation of myocardial protective effect of prostacyclin analog (OP-41483) as an adjunct to cardioplegic solution.

A stable prostacyclin analog (OP-41483) was evaluated for myocardial protective effect against global ischemia with the use of cardioplegia. Isolated canine hearts (n = 25) were exposed to 60 minutes of warm (37 degrees C) global ischemia after the arrest by crystalloid cardioplegia. Prostaglandin analog was given in three different ways: preadministration (700 ng/kg body weight per minute) before ischemia for 30 minutes (group I, n = 5), given as a component of cardioplegic solution (600 ng/ml, group II, n, = 6), and post-administration (25 ng/kg body weight per minute) during reperfusion for 30 minutes (group III, n = 7). During reperfusion, coronary sinus blood flow, 6-keto-prostaglandin F1 alpha in coronary sinus blood, and myocardial oxygen consumption were measured during reperfusion. As a result, groups II and III showed significantly better global left ventricular function (developed pressure, maximum dP/dt, and diastolic compliance) than the control group (without prostaglandin analog, n = 7) and group I. Myocardial oxygen consumption at reperfusion (1 minute) was significantly larger in group II than in the control group. 6-keto-prostaglandin F1 alpha flux was significantly larger in group II than in the other three groups during reperfusion. The results indicated that prostaglandin analog has a beneficial effect on myocardial protection under global ischemia with cardioplegia, particularly when used as a component of cardioplegic solution and also during reperfusion. The mechanism may relate to the cytoprotective effect (including protection of endothelium with enhanced endogenous prostacyclin production at reperfusion and also to the modulation of reperfusion per se.

6-Ketoprostaglandin F1 alpha↗

Canine heart-lung transplantation after 24-hour hypothermic preservation.

We compared the efficacy of Belzer UW solution (UWS) with modified Collins solution (MCS) in a 24 h canine heterotopic heart-lung transplantation model. Nine pairs of mongrel dogs were divided into 2 groups: MCS group (n = 5) and UWS group (n = 4). The donor heart was arrested with cardioplegia. The heart and lung were flushed with MCS or UWS, excised en bloc and immersed in 4 degrees C MCS or UWS for 24 h. Graft function was adequate in 1 of 5 grafts in the MCS group and in all 4 grafts in the UWS group (P less than 0.05). In the UWS group, the prepreservation and posttransplantation cardiac output was 71.2 +/- 21.6 and 96.4 +/- 44.4 ml/min per kg, the PaO2 was 80.8 +/- 12.9 and 74.1 +/- 2.7 mmHg, and the PaCO2 was 25.6 +/- 5.5 and 35.9 +/- 13.3 mmHg, respectively. No difference was significant. In the UWS group, the pulmonary vascular resistance increased significantly to 13.8 +/- 3.7 from 8.8 +/- 5.2 Wood units (P less than 0.05). Post-transplantation myocardial water content in the UWS group (78.6 +/- 2.0) was less than in the MCS group (81.1 +/- 1.4, P less than 0.05). The wet/dry ratio of the lung increased significantly to 8.3 +/- 1.6 from 4.4 +/- 0.6 in the UWS group (P less than 0.01) and to 10.3 +/- 0.8 from 4.1 +/- 0.1 in the MCS group (P less than 0.01), but was less in the UWS group (P less than 0.05). These results suggest that UWS is more effective than MCS in 24 h heart-lung preservation, but does not prevent pulmonary oedema adequately.

Animals↗

Prolonged preservation of cadaver heart with Belzer UW solution: 24-hour storage system for asphyxiated canine hearts.

The efficacy of Belzer UW solution was compared to Collins' solution in the preservation of asphyxiated cadaver hearts in a canine model. Donor hearts were stored for 24 h: 2 h of in situ hypothermic (15 degrees C) coronary perfusion plus 22 h of simple immersion in ice-cold solution. Verapamil, propranolol and prostacyclin were used for myocytoprotection in both groups. After orthotopic transplantation, all animals were weaned off bypass without inotropic support. After 1 h, however, the cardiac output was significantly higher in the Belzer UW solution group (128 +/- 28 vs. 67 +/- 13 ml/kg/min, p less than 0.01).

Adenosine↗