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Sodium-hydrogen exchange inhibitors improve postischaemic recovery of function in the perfused rabbit heart

Sodium-hydrogen exchange inhibitors improve postischaemic recovery of function in the perfused... Abstract Objective: The aim was to examine the effects of the Na+/H+ exchange inhibitors amiloride and methylisobutyl amiloride (MIA) in buffer perfused rabbit hearts subjected to one hour of normothermic ischaemia (37 °C) followed by reperfusion. Methods: Experiments were carried out in five groups of Langendorff perfused rabbit hearts: (1) control, (2) amiloride, and (3) MIA (agents in both the preischaemic and reperfusion perfusate), (4) amiloride-R and (5) MIA-R (agents added at reperfusion only). Functional evaluation included serial measurement of resting tension, force, rates of ventricular force development and relaxation, and coronary perfusion pressure. Samples of coronary effluent were obtained for creatine kinase assay and hearts were freeze clamped for metabolite assays. Results: Reperfusion resulted in a marked increase in resting tension in group (1) which was statistically significant compared to groups (2) and (3). Groups (2) and (3) also showed significantly improved recovery of ventricular force, rate of force development, and rate of ventricular relaxation. Addition of either agent only during reperfusion failed to produce a significant beneficial effect. There were no significant differences among the groups with respect to postreperfusion creatine kinase release or end reperfusion metabolite levels. Conclusion: This study shows for the first time that both of the Na+/H+ exchange inhibitors amiloride and MIA produce improved recovery of ventricular function in rabbit hearts subjected to ischaemia and reperfusion, although the beneficial effect was not obtained with drug administration at the time of reperfusion only. sodium-hydrogen exchange, reperfusion injury, amiloride, methylisobutylamiloride This content is only available as a PDF. Author notes 1 MK is a Career Investigator of the Heart and Stroke Foundation of Ontario. ☆ This work was funded by the Heart and Stroke Foundation of Ontario (grant No A2400) and the Medical Research Council of Canada (grant No MT-10284). Copyright © 1995, European Society of Cardiology http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Cardiovascular Research Oxford University Press

Sodium-hydrogen exchange inhibitors improve postischaemic recovery of function in the perfused rabbit heart

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Publisher
Oxford University Press
Copyright
Copyright © 1995, European Society of Cardiology
ISSN
0008-6363
eISSN
1755-3245
DOI
10.1016/S0008-6363(96)88572-5
Publisher site
See Article on Publisher Site

Abstract

Abstract Objective: The aim was to examine the effects of the Na+/H+ exchange inhibitors amiloride and methylisobutyl amiloride (MIA) in buffer perfused rabbit hearts subjected to one hour of normothermic ischaemia (37 °C) followed by reperfusion. Methods: Experiments were carried out in five groups of Langendorff perfused rabbit hearts: (1) control, (2) amiloride, and (3) MIA (agents in both the preischaemic and reperfusion perfusate), (4) amiloride-R and (5) MIA-R (agents added at reperfusion only). Functional evaluation included serial measurement of resting tension, force, rates of ventricular force development and relaxation, and coronary perfusion pressure. Samples of coronary effluent were obtained for creatine kinase assay and hearts were freeze clamped for metabolite assays. Results: Reperfusion resulted in a marked increase in resting tension in group (1) which was statistically significant compared to groups (2) and (3). Groups (2) and (3) also showed significantly improved recovery of ventricular force, rate of force development, and rate of ventricular relaxation. Addition of either agent only during reperfusion failed to produce a significant beneficial effect. There were no significant differences among the groups with respect to postreperfusion creatine kinase release or end reperfusion metabolite levels. Conclusion: This study shows for the first time that both of the Na+/H+ exchange inhibitors amiloride and MIA produce improved recovery of ventricular function in rabbit hearts subjected to ischaemia and reperfusion, although the beneficial effect was not obtained with drug administration at the time of reperfusion only. sodium-hydrogen exchange, reperfusion injury, amiloride, methylisobutylamiloride This content is only available as a PDF. Author notes 1 MK is a Career Investigator of the Heart and Stroke Foundation of Ontario. ☆ This work was funded by the Heart and Stroke Foundation of Ontario (grant No A2400) and the Medical Research Council of Canada (grant No MT-10284). Copyright © 1995, European Society of Cardiology

Journal

Cardiovascular Research – Oxford University Press

Published: Feb 1, 1995

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