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Biomedical subjects

Y Nishinaka

Publications and source records attributed to Y Nishinaka.

24 records · Page 2Linked to original sources
PubMed1993

Protective effect of FK506 on ischemia/reperfusion-induced myocardial damage in canine heart.

We investigated the cardioprotective effect of FK506, a newly developed immunosuppressive agent, on ischemia-reperfusion-induced myocardial damage and the inhibitory effect of FK506 on superoxide radical formation by neutrophils. Open-chest anesthetized dogs were divided into two groups: group 1, 2-h occlusion of the coronary artery followed by 1-h reperfusion; and group 2, 2-h occlusion followed by 1-h reperfusion with preadministration of FK506 (0.5 mg/kg). After reperfusion, heart mitochondria were prepared from the normal and reperfused areas and mitochondrial function and mitochondrial GSH (the reduced form of glutathione) and GSSG (the oxidized form of glutathione) concentrations were measured. In addition, neutrophils were collected from normal healthy dogs, and the inhibitory effect of FK506 on superoxide radical formation by neutrophils was also investigated. One-hour reperfusion after 2-h coronary occlusion induced significant mitochondrial dysfunction associated with a marked depletion of mitochondrial GSH concentration. FK506 reduced mitochondrial dysfunction, depletion of mitochondrial GSH concentration, and development of reperfusion arrhythmias. FK506 also reduced stimulant-induced superoxide radical formation by normal neutrophils dose dependently. Radical scavenging activity decreased in association with reperfusion, and FK506 reduced superoxide radical formation by neutrophils, which might contribute to lessening ischemia-reperfusion damage.

Animals↗
PubMed1993

Abnormal postexercise systolic blood pressure response is a good indicator of impaired left ventricular filling during supine cycle ergometer exercise in patients with coronary artery disease.

To determine whether the postexercise systolic blood pressure (SBP) response is a useful marker of left ventricular filling abnormalities, supine leg exercise testing was conducted in 14 control subjects and 70 patients with coronary artery disease (CAD). An abnormal postexercise SBP response (the ratio of SBP after 3 min of recovery to the peak exercise SBP) was defined as 0.85 or more, which represented the cutoff point with the highest sensitivity and specificity for prediction of pulmonary artery wedge pressure (PAWP) of at least 20 mmHg at peak exercise in CAD patients. There was a significant difference between the SBP ratios of the two groups (Control, 0.72 +/- 0.05; CAD, 0.86 +/- 0.13; p < 0.01). There was no significant difference between the PAWP of the two groups at rest, but the PAWP at peak exercise was significantly higher in the CAD group (20.2 +/- 8.9 mmHg) than in the control group (11.5 +/- 4.0 mmHg)(p < 0.01). PAWP at peak exercise was > or = 20 mmHg in 35 (50%) of the 70 CAD subjects. The SBP ratio was significantly correlated with PAWP at peak exercise (r = 0.67, p < 0.01) in the CAD group, but not in the control group. An SBP ratio of > or = 0.85 showed a sensitivity of 80% and a specificity of 80% for predicting a peak exercise PAWP of > or = 20 mmHg in CAD patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

[Myocardial metabolism during dynamic exercise].

The development of Webster catheterization has enabled us to make clinical measurement of coronary sinus blood flow and to estimate the kinetics in myocardial substrate uptake. In this study, exercise tolerance test using supine multistage bicycle ergometer test was performed and exercise-induced hemodynamic alteration was evaluated in 18 patients with ischemic heart disease (16 males and 2 females, average age 56.3 years). The change in substrate kinetics in myocardial metabolism was also examined in terms of two indexes; myocardial uptake rate and myocardial uptake. The following results were obtained. 1) The myocardial uptake rates of glutamate and free fatty acid were significantly decreased by exercise, while those of glucose and lactate showed no significant change. 2) The myocardial uptakes of glutamate, glucose and lactate were significantly increased by exercise, but that of free fatty acid did not change significantly. 3) A significant negative correlation (r = -0.52, p < 0.05) was observed between the change in myocardial glutamate uptake and the change in pulmonary artery wedge pressure induced by exercise, suggesting that patients with ischemic heart disease might fail in glutamate uptake induced by exercise. The difference in the kinetics of myocardial uptake rate and myocardial uptake for glutamate, alanine, glucose, free fatty acid and lactate is observed. This difference occurs from the decrease in uptake rate due to the increase in coronary sinus blood flow. Myocardial uptake, which directly reflects myocardial energy metabolism is regarded as a more useful index of myocardial metabolism than myocardial uptake rate.

Energy Metabolism↗
PubMed1992

The effects of a high dose of ascorbate on ischemia-reperfusion-induced mitochondrial dysfunction in canine hearts.

The cardioprotective effects of a high dose of ascorbate on ischemia-reperfusion-induced myocardial damage were investigated using open chest anesthetized dogs. Two-hour occlusion of the left anterior descending coronary artery (LAD) induced mitochondrial dysfunction with a depletion of mitochondrial glutathione (GSH) concentration. Two-hour LAD occlusion followed by 1-h reperfusion worsened the ischemia-induced mitochondrial dysfunction together with a marked depletion of mitochondrial GSH concentration. Ascorbate reduced the mitochondrial dysfunction and prevented the depletion of mitochondrial GSH concentration after 2-h LAD occlusion and 1-h reperfusion. Activities of mitochondrial glutathione peroxidase and glutathione reductase did not change significantly in each group. Administration of ascorbate also prevented reperfusion arrhythmias without affecting blood pressure or heart rate. These results suggest that coronary reperfusion induces mitochondrial dysfunction and a depletion of mitochondrial GSH concentration, and that a high dose of ascorbate prevents reperfusion damage.

Animals↗
PubMed1991

The cardioprotective effect of gamma-glutamylcysteine ethyl ester during coronary reperfusion in canine hearts.

1. The cardioprotective effect of gamma-glutamylcysteine ethyl ester was investigated on ischaemia-reperfusion-induced myocardial damage in anaesthetized dogs. 2. Open chest anaesthetized dogs were divided into four groups: 2 h occlusion of the left anterior descending coronary artery (LAD); 2 h LAD occlusion followed by 1 h reperfusion; 2 h LAD occlusion followed by 1 h reperfusion with administration of gamma-glutamylcysteine ethyl ester (10 mg kg-1 just before reperfusion); 2 h LAD occlusion followed by 1 h reperfusion with administration of GSH (the reduced form of glutathione, 10 mg kg-1 just before reperfusion). 3. After occlusion or reperfusion, heart mitochondria were prepared from the normal area and the occluded or the reperfused area, and mitochondrial function (rate of oxygen consumption in State III, and respiratory control index) was measured polarographically. 4. Mitochondrial GSH and GSSG (the oxidized form of glutathione) concentrations, and activities of glutathione peroxidase and glutathione reductase were measured. 5. Two h of LAD occlusion induced mitochondrial dysfunction with depletion of mitochondrial GSH concentration. One h of reperfusion after 2 h LAD occlusion induced significant mitochondrial dysfunction associated with a marked depletion of mitochondrial GSH concentration. 6. gamma-Glutamylcysteine ethyl ester reduced mitochondrial dysfunction and depletion of mitochondrial GSH concentration after 2 h LAD occlusion and 1 h reperfusion. In contrast, GSH did not prevent depletion of mitochondrial GSH concentration and mitochondrial dysfunction after 2 h LAD occlusion followed by 1 h reperfusion. 7. The activities of glutathione peroxidase and glutathione reductase did not change significantly in each group. 8. One h of reperfusion after 2 h occlusion of LAD induced ventricular arrhythmias. gamma-Glutamylcysteine ethyl ester markedly reduced the development of reperfusion arrhythmias, whilst GSH showed no protective effect.9. Gamma-Glutamylcysteine ethyl ester maintained mitochondrial GSH concentration, prevented reperfusion myocardial damage, and reduced reperfusion arrhythmias.

Animals↗