Published Online
on March 24, 2003

A more recent version of this article appeared on April 8, 2003

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Submitted on October 22, 2002
Revised on December 13, 2002
Accepted on December 17, 2002

Sodium-Hydrogen Exchange Inhibition During Ventricular Fibrillation. Beneficial Effects on Ischemic Contracture, Action Potential Duration, Reperfusion Arrhythmias, Myocardial Function, and Resuscitability

Iyad M. Ayoub MS, Julieta Kolarova MD, Zhong Yi MD, Atul Trevedi MD, Hanumant Deshmukh MD, David L. Lubell MD, Michael R. Franz MD, PhD, Frank A. Maldonado MD, and Raúl J. Gazmuri MD, PhD^*

From the Medical Service, North Chicago VA Medical Center and Departments of Medicine and of Physiology and Biophysics, Finch University of Health Sciences, The Chicago Medical School, North Chicago, Ill (I.M.A., J.K., Z.Y., A.T., H.D., D.L.L., F.A.M., R.J.G.), and Arrhythmia Service, Washington VA Medical Center and Georgetown University, Washington, DC (M.R.F.).

^* To whom correspondence should be addressed. E-mail: raul.gazmuri{at}med.va.gov.

Background--Inhibition of the sarcolemmal sodium-hydrogen exchanger isoform-1 (NHE-1) is emerging as a promising novel strategy for ameliorating myocardial injury associated with ischemia and reperfusion. We investigated whether NHE-1 inhibition (with cariporide) could minimize mechanical and electrical myocardial abnormalities that develop during ventricular fibrillation (VF) and improve outcome using a porcine model of closed-chest resuscitation.

Methods and Results--Two groups of 8 pigs each were subjected to 8 minutes of untreated VF and randomized to receive either a 3-mg/kg bolus of cariporide or 0.9% NaCl immediately before an 8-minute interval of conventional closed-chest resuscitation. Cariporide prevented progressive increases in left ventricular free-wall thickness (from 1.0±0.2 to 1.5±0.3 cm with NaCl, P<0.001 versus 0.9±0.1 to 1.1±0.3 cm with cariporide, P=NS), maintained the coronary perfusion pressure above resuscitability thresholds (10±8 versus 19±3 mm Hg before attempting defibrillation, P<0.05), and increased resuscitability (2 of 8 versus 8 of 8, P<0.005). In 2 additional groups of 4 pigs each subjected to a briefer interval of untreated VF, cariporide ameliorated postresuscitation shortening of the action potential duration (APD) at 30%, 60%, and 90% repolarization (ie, APD₆₀ at 2 minutes after resuscitation; 75±29 versus 226±16 ms, P<0.05), minimized postresuscitation ventricular ectopic activity preventing recurrent VF, and lessened postresuscitation myocardial dysfunction.

Conclusions--NHE-1 inhibition may represent a highly potent novel strategy for resuscitation from VF that can ameliorate myocardial manifestations of ischemic injury and improve the effectiveness and outcome of closed-chest resuscitation.

Key words: action potentials • cardiopulmonary resuscitation • defibrillation • ischemia • myocardium

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