Thorac cardiovasc Surg 1999; 47(3): 137-143
DOI: 10.1055/s-2007-1013128
Original Cardiovascular

© Georg Thieme Verlag Stuttgart · New York

Aminoguanidine Inhibits Inducible NOS and Reverses Cardiac Dysfunction Late After Ischemia and Reperfusion - Implications for iNOS-Mediated Myocardial Stunning

S. M. Wildhirt1 , C. Schulze1 , N. Conrad1 , A. Kornberg1 , D. Horstman2 , B. Reichart1
  • 1Department of Cardiac Surgery, Ludwig-Maximilians University, Munich, Germany
  • 2Department of Anesthesiology, University of Charlottesville, Virginia, USA
Further Information

Publication History

1998

Publication Date:
19 March 2008 (online)

Abstract

Background: The functional significance of inducible nitric oxide synthase (iNOS) activation in response to myocardial ischemia and reperfusion (I/R) was investigated. Methods: New Zealand rabbits were randomly treated with either placebo, aminoguanidine (AMG; selective iNOS inhibitor), or L-arginine. Left-ventricular hemodynamics and myocardial blood flow were measured before coronary occlusion and 30 minutes and 48 h after initiation of reperfusion. Results: I/R resulted in left-ventricular dysfunction and increased myocardial iNOS activity. Placebo treatment had no effects on myocardial function. However, AMG significantly inhibited iNOS activity, significantly improved left-ventricular maximum + dP/dt and decreased LVEDP, whereas administration of L-arginine reduced + dP/dt and slightly increased LVEDP, compared to AMG-treated animals. Myocardial blood flow in the affected myocardium significantly increased after both AMG and L-arginine. Conclusions: The present data indicate that induction of myocardial iNOS after 48 h I/R contributes to the development of reversible left-ventricular dysfunction, suggesting the involvement of iNOS in myocardial stunning. Whereas L-arginine is associated with further reduction of left-ventricular contractility, continuous inhibition of iNOS activation by AMG improves left-ventricular performance; this may be a novel and clinically important therapeutic modality in certain disease states associated with I/R, including cardiac operations using extracorporeal circulation and coronary angioplastic procedures.