Cardioprotective and endothelial protective effects of [Ala‐IL8]77 in a rabbit model of myocardial ischaemia and reperfusion

• Published in: British journal of pharmacology 1991-05, Vol.103 (1), p.1153-1159
• Main Authors: Lefer, Allan M., III, Gerald Johnson, Ma, Xin‐liang, Tsao, Phillip S., Thomas, G. Roger
• Format: Article
• Language: English
• Subjects: Acetylcholine - pharmacology; Animals; Biological and medical sciences; Blood Pressure - drug effects; Calcimycin - pharmacology; Cardiovascular system; Coronary Disease - prevention & control; Endothelial cell interleukin‐8; Endothelium, Vascular - drug effects; endothelium‐derived relaxing factor; granulocytes; Heart Diseases - chemically induced; Heart Diseases - prevention & control; Heart Rate - drug effects; In Vitro Techniques; Interleukin-8 - analogs & derivatives; Interleukin-8 - pharmacology; Male; Medical sciences; Miscellaneous; myeloperoxidase activity; Myocardial Reperfusion Injury - prevention & control; Myocardium - cytology; Myocardium - enzymology; neutrophil adherence; Neutrophils - drug effects; Nitric Oxide - pharmacology; Peroxidase - metabolism; Pharmacology. Drug treatments; Rabbits; reperfusion injury; Superoxides - metabolism
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1991.tb12316.x

1 We studied the effects of a form of interleukin‐8 (i.e., [Ala‐IL8]77) on endothelial dysfunction and myocardial injury in rabbits. Pentobarbitone‐anaesthetized rabbits were subjected to 1.5 h occlusion of the marginal coronary artery and 3.5 h reperfusion. [Ala‐IL8]77 (50 μg or its vehicle) was given i.v. as a bolus 10 min prior to reperfusion. [Ala‐IL8]77 was also studied in isolated perfused hearts of rabbits. 2 Myocardial ischaemia plus reperfusion in untreated rabbits produced severe endothelial dysfunction and myocardial injury, including marked myocardial necrosis, elevated cardiac myeloperoxidase (MPO) activity in ischaemic cardiac tissue, and loss of response of marginal coronary rings to the endothelium‐dependent vasodilators, acetylchloline (ACh) and A23187. 3 Administration of [Ala‐IL8]77 10 min prior to reperfusion resulted in significant protective effects in post‐ischaemic reperfusion. Compared with untreated rabbits, [Ala‐IL8]77 caused a reduced necrotic zone (P < 0.01), lower MPO activity in the necrotic zone (P < 0.05), and significantly preserved vasorelaxant responses of marginal coronary artery rings to endothelium‐dependent vasodilators, ACh (P < 0.001) and A23187(P < 0.001). 4 These results indicate that myocardial ischaemia and reperfusion result in a severe endothelial dysfunction and myocardial injury which involved the interaction of neutrophils and endothelial cells. However, [Ala‐IL8]77 did not appear to exert a direct endothelial protective effect in the absence of neutrophils in rabbit isolated perfused hearts. 5 Inhibition of neutrophil accumulation in the myocardium, perhaps by prevention of endothelial dysfunction resulting from [Ala‐IL8]77, leads to significant protective effects in ischaemia and reperfusion in rabbits.