Ionic movement and tolerance to ischemia in congenital heart disease : Sodium movement via the Na^+/H^+ exchange during reoxygenation is a determinant of post-ischemic functional recovery in the rat myocardium

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 16591383
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Akita University
• Principal Investigator: YAMAMOTO Hiroshi Akita University, School of Medicine, Associate Professor, 医学部, 助教授 (10270795)
• Co-Investigator(Kenkyū-buntansha): ISHIBASH Kazuyuki Akita University, school of Medicine, Lectuer, 医学部, 講師 (00291617) ; NARITA Takuya Akita University, school of Medicine, Assistant Professor, 医学部, 助手 (60396554) ; YAMAMOTO Fumio Akita Uniyersity, School of Medicine, Professor, 医学部, 教授 (00127474) ; YAMAURA Gembu Akita University, School of Medicine, Assistant Professor, 医学部, 助手 (40375241)
• Project Period (FY): 2004 – 2006
• Keywords: myocardium / ischemia / reperfusion injury / sodium ion / proton / Na^+ / H^+ exchange / dimethyl amiloride / Na^+ / HCO_3^- cotransporter

Research Abstract

Objectives : To determine whether or not sodium ion movement during reoxygenation is a determinant of post-ischemic recovery of cardiac function, we examined i) the effect of Na^+/H^+ exchange inhibition during reperfusion or reoxygenation on post-ischemic recovery of cardiac function and ii) the involvement of Na+/HCO_3^-cotransporter in the sodium ion movement.
Methods : Isolated rat hearts were Langendorff-perfused with Krebs-Henseleit bicarbonate buffer and subjected to 20 minutes of normothermic (37C) global ischemia followed by normothermic (37℃) reperfusion. i) 100 μM dimethyl amiloride (DMA) was given during the first 10 min of reperfusion (protocol I) or for 10 minutes after 5-minute hypoxic reperfusion (protocol II). ii) a bicarbonate-free HEPES buffer was used during the first 10 minutes of reperfusion (protocol III). All the protocols were then followed by 25 minutes of noromoxic reperfusion.
Results : i) In protocols I and II, the post-ischemic recovery of left ventricular developed pressure (%LVDP) was significantly greater in the DMA group than in the control group (68.6±5.9 vs. 52.0±6.1%, respectively in protocol Land 66.6±2.8 vs. 52.0±5.5%, respectively in protocol II). In protocol III, there was no difference between the bicarbonate-free group and the control group (35.9±4.9 vs. 24.7±6.7%, respectively).
Conclusions : Sodium ion movement via the Na^+/H^+ exchange during reoxygenation is a determinant of post-ischemic recovery of cardiac function. The Na^+/HCO_3^- cotransporter may not be involved in the sodium ion movement during reperfusion.