SP/W-5186, A cysteine-containing nitric oxide donor, attenuates postischemic myocardial injury.

Authors

• G L Liu
• T A Christopher
• B L Lopez
• F Gao
• Y Guo
• E Gao
• K Knuettel
• M Feelisch
• X L Ma

Publication/Presentation Date

11-1-1998

Abstract

The effects of SP/W-5186, a cysteine-containing nitric oxide (.NO) donor, on myocardial reperfusion injury were studied in a rabbit ischemia (45 min) and reperfusion (180 min) model. Five min before reperfusion, either low-dose (0.3 micromol/kg) or high-dose (1 micromol/kg) SP/W-5186 was given intravenously as a bolus. Administration of 0.3 micromol/kg SP/W-5186 did not change mean arterial blood pressure, heart rate or pressure-rate index. However, administration of low-dose SP/W-5186 exerted marked cardioprotective effects as evidenced by improved cardiac functional recovery (P < .05 vs. vehicle), decreased plasma creatine kinase concentration (P < . 01) and reduced infarct size (P < .01). Moreover, administration of SP/W-5186 significantly decreased platelet aggregation (P < .01 vs. vehicle), attenuated polymorphonuclear leukocyte (PMN) accumulation in myocardial tissue, inhibited PMN adhesion to endothelial cells and preserved endothelial function. Administration of high-dose SP/W-5186 resulted in a transient but significant decrease in mean arterial blood pressure and exerted more cardiac protection compared with low-dose treatment. However, the effects on platelet aggregation, PMN accumulation and PMN adhesion did not differ significantly between the two SP/W-5186 groups. Furthermore, administration of SP/W-6373, an analogue of SP/W-5186 that lacks the NO moiety, failed to exert any protective effects. These results demonstrate that NO released from SP/W-5186 significantly protected myocardial tissue from reperfusion injury. The primary mechanisms of the observed cardioprotection by SP/W-5186 involve inhibition of platelet aggregation, attenuation of PMN-endothelium interaction and preservation of endothelial function.

Volume

287

Issue

2

First Page

527

Last Page

537

ISSN

0022-3565

Published In/Presented At

Liu, G. L., Christopher, T. A., Lopez, B. L., Gao, F., Guo, Y., Gao, E., Knuettel, K., Feelisch, M., & Ma, X. L. (1998). SP/W-5186, A cysteine-containing nitric oxide donor, attenuates postischemic myocardial injury. The Journal of pharmacology and experimental therapeutics, 287(2), 527–537.

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

9808677

Department(s)

Administration and Leadership

Document Type

Article