Sodium-hydrogen exchange inhibition during ventricular fibrillation: Beneficial effects on ischemic contracture, action potential duration, reperfusion arrhythmias, myocardial function, and resuscitability

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 myocard...

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Published in:	Circulation (New York, N.Y.) Vol. 107; no. 13; pp. 1804 - 1809
Main Authors:	AYOUB, Iyad M, KOLAROVA, Julieta, ZHONG YI, TREVEDI, Atul, DESHMUKH, Hanumant, LUBELL, David L, FRANZ, Michael R, MALDONADO, Frank A, GAZMURI, Raul J
Format:	Journal Article
Language:	English
Published:	Hagerstown, MD Lippincott Williams & Wilkins 08-04-2003 American Heart Association, Inc
Subjects:	Action Potentials - drug effects Animals Anti-Arrhythmia Agents - therapeutic use Arrhythmias, Cardiac - etiology Arrhythmias, Cardiac - pathology Arrhythmias, Cardiac - physiopathology Arrhythmias, Cardiac - prevention & control Biological and medical sciences Cardiac dysrhythmias Cardiology. Vascular system Combined Modality Therapy Echocardiography, Transesophageal Guanidines - therapeutic use Heart Heart - physiopathology Male Medical sciences Myocardial Reperfusion Injury - pathology Myocardial Reperfusion Injury - physiopathology Myocardial Reperfusion Injury - prevention & control Resuscitation Secondary Prevention Sodium-Hydrogen Exchangers - antagonists & inhibitors Sulfones - therapeutic use Swine Ventricular Fibrillation - diagnostic imaging Ventricular Fibrillation - drug therapy Ventricular Fibrillation - physiopathology Ventricular Fibrillation - therapy Ventricular Function, Left Cardiac performance Arrhythmia Pathogenesis Electrophysiology Cardiovascular disease Action potential Myocardial disease Ventricular fibrillation Vascular disease cardiopulmonary resuscitation Ischemia defibrillation Heart disease Sodium ion Ion exchange Hydrogen ion Ungulata action potentials Coronary heart disease Excitability disorder Pig Vertebrata Mammalia Animal Myocardium Artiodactyla
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Summary:	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. 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. 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0009-7322 1524-4539
DOI:	10.1161/01.CIR.0000058704.45646.0D