Sodium Nitroprusside Exacerbates Myocardial Ischemia–Reperfusion Injury

doi:10.1016/S0003-4975(97)01089-8

The Annals of Thoracic Surgery

Volume 64, Issue 6, December 1997, Pages 1656-1660

Presented at the Thirty-third Annual Meeting of The Society of Thoracic Surgeons, San Diego, CA, Feb 3–5, 1997.

https://doi.org/10.1016/S0003-4975(97)01089-8 Get rights and content

Abstract

Background. The role of nitric oxide in myocardial ischemia–reperfusion is controversial. Although many studies claim that nitric oxide ameliorates reperfusion injury, others suggest that it exacerbates such injury, possibly through peroxynitrite production. These discordant results may be attributable to a dose-dependent phenomenon.

Methods. Isolated rabbit hearts sustained sequential periods of blood perfusion (20 minutes), warm ischemia (30 minutes), and reperfusion (20 minutes). During reperfusion, four groups underwent intracoronary infusion of saline solution (n = 6), or the nitric oxide donor sodium nitroprusside (100 nm/min [SNP100, n = 6], 1 nmol · L⁻¹/min⁻¹ [SNP1, n = 6], or 0.01 nmol · L⁻¹ · min⁻¹ [SNP0.01]). Left ventricular-developed pressure and oxygen consumption were measured after preischemic perfusion and reperfusion. Levels of myocardial nitrotyrosine, a marker for peroxynitrite, were measured after reperfusion with an immunoradiochemical assay.

Results. Postischemic-developed pressure and myocardial oxygen consumption were significantly higher in the saline group than all nitroprusside-reperfused groups (p < 0.01 for both parameters). However, there were no differences in either parameter between SNP100, SNP1, or SNP0.01. Nitrotyrosine levels were similar among the four groups (p = 0.43).

Conclusions. Nitroprusside exacerbates myocardial ischemia–reperfusion injury over a wide range of doses, although the mechanism does not appear to be mediated by peroxynitrite.

Section snippets

Material and Methods

Adult New Zealand white rabbits were used for all protocols described herein. The Animal Review Committee of the University of Virginia reviewed and approved the protocols for this study. All animals received humane care in compliance with the “Principles of Laboratory Animal Care” formulated by the National Society for Medical Research and the “Guide for the Care and Use of Laboratory Animals” prepared by the Institute of Laboratory Animal Resources and published by the National Institutes of

Functional and Metabolic Data

Table 1 presents mean LVP data of isolated hearts after 20 minutes of baseline preischemic perfusion (preischemic LVP) and after 20 minutes of reperfusion with saline or one of the three doses of SNP (postischemic LVP). Also presented is the percent recovery of ventricular function (%LVP recovery) for each group, which was calculated as follows: %LVPrecovery = postischemicLVP/preischemicLVP × 100%. Although the mean baseline LVP before the initiation of ischemia was similar between the four

Comment

The results of the current investigation demonstrate that intracoronary administration of the NO donor SNP during reperfusion exacerbates myocardial IR injury. This conclusion is based on the observed significant reductions in postischemic cardiac functional (LVP) and metabolic (MVO₂) indices of the three groups undergoing reperfusion with SNP, compared with hearts reperfused in the presence of saline vehicle only. Contrary to our hypothesis, a wide range of SNP doses impaired postischemic

Acknowledgements

We express our appreciation to Anthony J. Herring for his invaluable technical assistance. In addition, we owe a debt of gratitude to Dr Harry Ischiropoulos for his generous efforts in performing the nitrotyrosine assays.

This work was supported by a National Research Service Award (Fellowship No. 1 F32 HL09065-01A2) granted by the National Heart, Lung, and Blood Institute of the National Institutes of Health.

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Original ArticlesSodium Nitroprusside Exacerbates Myocardial Ischemia–Reperfusion Injury

Abstract

Section snippets

Material and Methods

Functional and Metabolic Data

Comment

Acknowledgements

Biochem Biophys Res Commun

Ann Thorac Surg

The role of l-arginine in ameliorating reperfusion injury after myocardial ischemia in the cat

Circulation

Intracoronary l-arginine during reperfusion improves endothelial function and reduces infarct size

Am J Physiol

Cardioprotection and attenuation of endothelial dysfunction by organic nitric oxide donors in myocardial ischemia-reperfusion

J Pharmacol Exp Ther

Endothelial and myocardial cell protection by a cysteine-containing nitric oxide donor after myocardial ischemia and reperfusion

J Cardiovasc Pharmacol

Antineutrophil and myocardial protecting actions of a novel nitric oxide donor after acute myocardial ischemia and reperfusion in dogs

Circulation

Endothelium-derived relaxing factor inhibits in vitro platelet aggregation

Br J Pharmacol

Role of l-arginine-nitric oxide pathway in myocardial reoxygenation injury

Am J Physiol

Original Articles
Sodium Nitroprusside Exacerbates Myocardial Ischemia–Reperfusion Injury