Biomedical subjects

Yusuke Iwata

Publications and source records attributed to Yusuke Iwata.

3 recordsLinked to original sources

PubMed2006

Cerebral endothelial nitric oxide synthase expression is reduced after very-low-flow bypass.

BACKGROUND: In previous studies we have shown that delayed capillary reperfusion after low flow bypass predicts neurologic injury. In this acute study, we hypothesized that low flow reduces endothelial nitric oxide synthase (eNOS) expression, which may lead to more profound inflammatory response and delayed capillary perfusion. METHODS: Twelve piglets (13.2 +/- 0.7 kg) had a cranial window placed over the parietal cerebral cortex for direct examination of the microcirculation using intravital fluorescence microscopy. Animals were cooled to 15 degrees C or 34 degrees C on cardiopulmonary bypass (pH stat, hematocrit 30%, pump flow 100 mL/kg/minute) followed by 2 hours of low flow (50 mL/kg/minute) or very low flow (10 mL/kg/minute). Rhodamine staining was used to observe adherent and rolling leukocytes in postcapillary venules. The eNOS protein expression was determined by Western immunoblotting. RESULTS: High temperature and low flow rate correlated with significantly reduced eNOS expression (p < 0.01). Univariate comparisons based on Student t tests indicated that eNOS protein levels were lower at 34 degrees C than at 15 degrees C (0.7 +/- 0.6 vs 1.7 +/- 0.5, p < 0.01) and at 10 mL/kg per minute compared with 50 mL/kg per minute (0.8 +/- 0.7 vs 1.6 +/- 0.5, p = 0.03). Moreover, two-way analysis of variance revealed that temperature (F = 21.6, p < 0.001) and flow rate (F = 13.8, p = 0.005) were independent multivariate predictors of eNOS expression. During low flow bypass, eNOS was inversely correlated with numbers of adherent (p = 0.002) and rolling (p = 0.006) leukocytes, following an exponential decay curve closely. CONCLUSIONS: eNOS expression is reduced after very low flow bypass, particularly at a higher bypass temperature. This is associated with delayed capillary reperfusion. Reduced eNOS is also associated with increased white cell activation which may lead to greater neurologic injury.

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PubMed2006

Aprotinin improves cerebral protection: evidence from a survival porcine model.

OBJECTIVE: Aprotinin is a serine protease inhibitor used during cardiac surgery to reduce blood loss and preserve platelet function. It has also been shown to reduce leukocyte activation during and after cardiopulmonary bypass. The goal of the study was to test the hypothesis that aprotinin could reduce cerebral injury after low-flow cardiopulmonary bypass and deep hypothermic circulatory arrest. METHODS: Sixteen piglets (mean weight, 13.6 +/- 1.3 kg) were randomly assigned to receive aprotinin or placebo (8 animals per group) before a 120-minute period of deep hypothermic circulatory arrest (15 degrees C) or 25 mL x kg(-1) x min(-1) low-flow cardiopulmonary bypass (25 degrees C or 34 degrees C). Piglets had a cranial window placed over the parietal cerebral cortex for direct examination of the microcirculation by means of intravital microscopy. Rhodamine-stained leukocytes were observed in postcapillary venules, with analysis for adhesion and rolling. Plasma was labeled with fluorescein isothiocyanate-dextran for assessment of functional capillary density. Neurologic and histologic scores were used as the primary outcome measures. RESULTS: During rewarming, the mean number of both rolling and adherent leukocytes was significantly lower after aprotinin administration (P < .05). At 5 and 15 minutes of rewarming, functional capillary density recovered faster with aprotinin treatment (P < .05). Functional outcome (neurologic deficit score) on postoperative day 1 was significantly improved in aprotinin-treated piglets (P < .05). CONCLUSIONS: Aprotinin reduces inflammation and improves neurologic outcome after a prolonged period of deep hypothermic circulatory arrest or low-flow cardiopulmonary bypass.

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PubMed2005

Specific bypass conditions determine safe minimum flow rate.

BACKGROUND: The purpose of this study is to define a safe minimum flow rate for specific bypass conditions using continuous monitoring with near-infrared spectroscopy and direct observation of the cerebral microcirculation. METHODS: Two series of experiments (n = 72 in each) were conducted in which piglets were cooled to a temperature of 15 degrees, 25 degrees, or 34 degrees C on cardiopulmonary bypass with hematocrit 20% or 30%, pH-stat management in all, followed by 1 or 2 hours of reduced flow (10, 25, or 50 mL.kg(-1).min(-1)). Animals in series one had a cranial window placed over the parietal cortex to evaluate the microcirculation with intravital microscopy. Plasma was labeled with fluorescein-isothiocyanate-dextran for assessment of functional capillary density (FCD) and microvascular diameter. In series two, near-infrared spectroscopy was utilized to detect tissue oxygenation index (TOI). Outcome measures included histologic and neurologic injury scores. RESULTS: The TOI during low flow and FCD during rewarming and after weaning from cardiopulmonary bypass were associated with neurologic injury. Failure of FCD to return to baseline during rewarming predicted worse functional and histologic outcome (p < 0.001). Regression analysis indicated that temperature and low-flow rate were multivariable predictors of TOI and FCD during rewarming (p < 0.001). CONCLUSIONS: Tissue oxygen index derived from near-infrared spectroscopy is a useful real-time monitor for detecting inadequate cerebral perfusion during cardiopulmonary bypass. Minimal safe pump flow rate varies according to the conditions of bypass: using pH stat management and with an hematocrit of either 20% or 30%, a flow rate as low as 10 mL.kg(-1).min(-1) is safe for as long as 2 hours at a temperature of 15 degrees C. However, under the same conditions at 34 degrees C, a flow rate of 10 mL.kg(-1).min(-1) is very likely to be associated with neurologic injury.

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