| Project/Area Number |
03670435
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Akita University |
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Principal Investigator |
MIURA Mamoru Akita University, School of Medicine, Professor, 医学部, 教授 (10006710)
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| Co-Investigator(Kenkyū-buntansha) |
TAJIKA Takehiko Akita University, School of Medicine, Assoceate Professor, 医学部, 助教授 (80171718)
MATSUOKA Hotoshi Akita University, School of Medicine, Lecturer, 医学部, 講師 (60181707)
ABE Toyohiko Akita University, School of Medicine, Research Assistant, 医学部, 助手 (30231963)
KOBAYASHI Masao Akita University, School of Medicine, Research Assistant, 医学部, 助手 (70178333)
SAITO Takashi Akita University, School of Medicine, Lecturer, 医学部, 講師 (90178484)
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| Project Period (FY) |
1991 – 1993
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| Keywords | Stunned Myocardium / Ischemia-Sensitized Myocardium / Preconditioning / Reperfusion / Cardiac Metabolism / Glycolysis / Dichloroacetate |
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| Research Abstract |
(1) To elucidate the characteristics in cardiac metabolism of reperfused myocardium, the left anterior descending coronary artery was occluded three times in the following order in canine hearts in situ : 2 minutes occlusion (Trial 1) followed by 15 minutes reperfusion ; then 5 minutes occlusion followed by 90 minutes reperfusion and 2 minutes occlusion (Trial 2). In control dogs, the 2 minutes occlusion underwent twice at a 110 minutes reperfusion interval (also reffered to as Trial 1 and Trial 2) to make the same temporal sequence as the intervention group (5 minutes occlusion group). The dogs were monitored by epicardial surface ECG, while regional wall motion was estimated by sonomicrometry. Continuous measurements of myocardial tissue PCO2, pH and extracellular potassium concentration (K) were made concurrently. Results : Both trials produced a biphasic change in R wave amplitude characterised by a transient initial decrease succeeded by an increase with ST elevation. This biphasi
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c change in R wave was indistinguishable between Trial 1 and Trial 2 in the control group. By contrast, in the 5 minutes occlusion group, the R wave initially decreased to a grester degree in Trial 2 than in Trial 1. More rapid contractile failure was also noticed in Trial 2, suggesting the possible involvement of mechanically induced electrical changes in the genesis of decreased R wave amplitude. However, the increase in R wave and ST elevation were significantly reduced in Trial 2. This reduction in ST change was concomitant with decreased changes in PCO2, pH and K in Trial 2. These altered electrical response and attenuated metabolic changes during ischemia reflects the latent sequelae in reperfused myocardium (ischemia-sensitized myocardium).
(2) The underlying mechanisms for altered metabolic response to ischemia in ischemia-sensitized myocardium is not clear from the study above. To test our hypothesis that the limited glucose utilization is involved in this phenomenon, glycogen store in reperfused myocardium was examined by histochemical techmique. As the results ; a marked loss of glycogen staining in reperfused area was noticed even after a single brief ischemia. Treatment with a modulator of glucose uptake and oxidation, dichloroacetate, significantly inhibited the attenuation of metabolic response to the subsequent ischemia in ischemia-sensitized myocardium. These data suggest that involvement of the preferential use of glucose (substrate switch), but its limitation because of the loss of glycogen store in altered response to ischemia in reperfused myocardium. Less
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