Beneficial effects of SPM-5185, a cysteine-containing NO donor in myocardial ischemia-reperfusion.

Abstract

Intravenous administration of SPM-5185 [N-nitratopivaloyl-S-(N'-acetylalanyl)-cysteine ethyl ester], a cysteine-containing nitric oxide (NO) donor, or SPM-5267 [pivaloyl-S-(N'-acetylalanyl)-cysteine ethyl ester], an analogue of SPM-5185 that lacks the NO moiety, was studied in a feline myocardial ischemia-reperfusion model. Administration of SPM-5185 (1 mg/kg), followed by a 2-mg.kg-1.h-1 infusion starting 10 min before reperfusion, resulted in significant protection 4.5 h postreperfusion. In the myocardial ischemia (MI)+SPM-5267 group, 38 +/- 4% of the area at risk was necrotic, whereas the necrotic area/area at risk was only 7 +/- 2% in the MI+SPM-5185 group (P less than 0.01). Moreover, SPM-5185 treatment markedly attenuated the endothelial dysfunction observed in the left anterior descending coronary artery after reperfusion by 50%. These beneficial effects occurred despite the absence of a significant change in myocardial oxygen demand, as measured by the pressure-rate index. In vitro experiments demonstrated that SMP-5185, but not SPM-5267, decreased adherence of neutrophils to the coronary vascular endothelium and decreased production of superoxide radicals. Therefore, a likely mechanism of the observed cardioprotection by SPM-5185 involves attenuation of polymorphonuclear leukocyte-induced endothelial dysfunction.

• Authors: M R Siegfried, C Carey, X L Ma, A M Lefer
• Journal: The American journal of physiology (Am J Physiol) Vol. 263 Issue 3 Pt 2 Pg. H771-7 (Sep 1992) ISSN: 0002-9513 [Print] United States
• PMID: 1415601 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Dipeptides
• N-nitratopivaloyl-S-(N'-acetylalanyl)-cysteine ethyl ester
• pivaloyl-S-(N'-acetylalanyl)-cysteine ethyl ester
• Nitric Oxide
• Cysteine

Topics

• Animals
• Cats
• Coronary Disease (physiopathology)
• Cysteine (analogs & derivatives, analysis, chemistry, pharmacology)
• Dipeptides
• Electrocardiography
• Hemodynamics (drug effects)
• Male
• Myocardial Reperfusion
• Myocardial Reperfusion Injury (prevention & control)
• Necrosis
• Neutrophils (physiology)
• Nitric Oxide (analysis)
• Risk Factors