Circulation Research, Vol 71, 1429-1440, Copyright © 1992 by American Heart Association

ARTICLES

Reperfusion-induced arrhythmias. A role for washout of extracellular protons?

M Avkiran and C Ibuki
Cardiovascular Research, Rayne Institute, St. Thomas' Hospital, London, UK.

Rapid washout of extracellular H+ accumulated during preceding ischemia (i.e., the abrupt restoration of extracellular pH) has been implicated as an arrhythmogenic factor during reperfusion. Therefore, we hypothesized that by limiting the rate at which extracellular pH was restored during early reperfusion it should be possible to protect against reperfusion-induced arrhythmias. To test this, we used isolated rat hearts (n = 12 per group) and a novel dual coronary perfusion cannula that permitted the induction of regional ischemia (10 minutes) and the selective reperfusion (8 minutes) of the ischemic zone with modified solutions. We examined the antiarrhythmic efficacy of 1) acidic (pH 6.6) reperfusion with stepwise restoration of extracellular pH to 7.4 (stepped pH) and 2) transient (2-minute) acidic (pH 7.1, 6.8, 6.6, or 6.4) reperfusion with subsequent abrupt restoration of extracellular pH to 7.4. Hearts in two contemporary control groups were reperfused with solution at pH 7.4 throughout. In all groups, 100% of hearts exhibited ventricular tachycardia (VT) on reperfusion. VT degenerated into ventricular fibrillation (VF) in 100% of hearts in the control group but in only 42% of hearts in the stepped-pH group (p < 0.05). In the groups subjected to transient acidic reperfusion, there was a pH-dependent prolongation of VT cycle length (measured at 15 seconds of reperfusion), which was 47.1 +/- 3.9, 51.1 +/- 5.5, 56.0 +/- 1.9, 60.4 +/- 2.8 (p < 0.05), and 68.8 +/- 5.0 (p < 0.05) msec in the pH 7.4 (control), 7.1, 6.8, 6.6, and 6.4 groups, respectively. In these groups, VT degenerated into VF in 92%, 92%, 83%, 42% (p < 0.05), and 33% (p < 0.05) of hearts, respectively. In conclusion, limiting the rate at which extracellular pH is restored during early reperfusion does not affect the rapid induction of VT but inhibits the degeneration of VT into VF and promotes spontaneous reversion to normal sinus rhythm. This is consistent with a major arrhythmogenic role, during uncontrolled reperfusion, for the rapid washout of extracellular H+.

This article has been cited by other articles:

				C. Bazzani, S. Guarini, A. R. Botticelli, D. Zaffe, A. Tomasi, A. Bini, M. M. Cainazzo, G. Ferrazza, C. Mioni, and A. Bertolini Protective Effect of Melanocortin Peptides in Rat Myocardial Ischemia J. Pharmacol. Exp. Ther., June 1, 2001; 297(3): 1082 - 1087. [Abstract] [Full Text]

				D.J. Hearse Ischaemia, reperfusion and cardioprotection: successes and failures in the journey from molecule to man Eur. Heart J. Suppl., June 1, 2001; 3(suppl_C): C11 - C21. [Abstract] [PDF]

				E. Carmeliet Cardiac Ionic Currents and Acute Ischemia: From Channels to Arrhythmias Physiol Rev, July 1, 1999; 79(3): 917 - 1017. [Abstract] [Full Text] [PDF]

				T. Yamauchi, H. Ichikawa, Y. Sawa, N. Fukushima, K. Kagisaki, K. Maeda, H. Matsuda, and R. Shirakura The Contribution of Na+/H+ Exchange to Ischemia-Reperfusion Injury After Hypothermic Cardioplegic Arrest Ann. Thorac. Surg., April 1, 1997; 63(4): 1107 - 1112. [Abstract] [Full Text]

				M. Yasutake, R. S. Haworth, A. King, and M. Avkiran Thrombin Activates the Sarcolemmal Na+-H+ Exchanger: Evidence for a Receptor-Mediated Mechanism Involving Protein Kinase C Circ. Res., October 1, 1996; 79(4): 705 - 715. [Abstract] [Full Text]

				T. Ohashi, F. Yamamoto, H. Yamamoto, H. Ichikawa, T. Shibata, and Y. Kawashima TRANSIENT REPERFUSION WITH ACIDIC SOLUTION AFFECTS POSTISCHEMIC FUNCTIONAL RECOVERY: STUDIES IN THE ISOLATED WORKING RAT HEART J. Thorac. Cardiovasc. Surg., March 1, 1996; 111(3): 613 - 620. [Abstract] [Full Text]

				F. C. Faes, Y. Sawa, H. Ichikawa, Y. Shimazaki, T. Ohashi, H. Fukuda, R. Shirakura, and H. Matsuda Inhibition of Na+/H+ Exchanger Attenuates Neutrophil-Mediated Reperfusion Injury Ann. Thorac. Surg., August 1, 1995; 60(2): 377 - 381. [Abstract] [Full Text]