Effects of statins on myocardial and coronary artery response to ischemia-reperfusion

Abstract

This study tested the hypotheses that (i) lipophilic statins (atorvastatin and simvastatin) impair ventricular recovery from myocardial ischemia–reperfusion, owing to their greater myocyte permeability, compared with a hydrophilic statin (pravastatin), and (ii) statins enhance endothelium-dependent vasodilation of isolated coronary arteries from the ischemic region. Farm pigs consumed chow supplemented with atorvastatin (2.5 mg·kg–1·d–1; n = 6), pravastatin (10 (n = 3) or 20 (n = 2) mg·kg–1·d–1), simvastatin (5 mg·kg–1·d–1; n = 6), or no statin (control; n = 6) for 3 weeks. Animals were anesthetized and instrumented to measure regional (% segment shortening) and global (dP/dt max) left ventricular (LV) function during coronary artery occlusion (10 min) and reperfusion (30 min). Coronary resistance (i.d. = 119 ± 3 µm) and conductance (i.d. = 487 ± 11 µm) arteries were isolated from the ischemic region to measure receptor-dependent (acetylcholine (ACh)) and -independent (KCl) vasoconstriction, and endothelium-dependent (bradykinin (BK)) and -independent (sodium nitroprusside (SNP)) vasodilation. At 30 min reperfusion, neither percent recovery of regional ventricular function (atorvastatin, 24% ± 15%; pravastatin, 36% ± 13%; simvastatin, 29% ± 13%; control, 36% ± 13%) nor percent recovery of global LV cardiac function differed among groups. However, BK-induced vasorelaxation of coronary conductance vessels was greater (P < 0.05) in statins versus controls, and ACh-induced vasoconstriction was less in simvastatin-treated animals, suggesting the potential for enhanced coronary arterial blood flow to the jeopardized region. In conclusion, our data suggest that ischemia-induced myocardial stunning is similar among pigs treated for 3 weeks with atorvastatin, pravastatin, or simvastatin, even though statin treatment appears to augment endothelium-dependent vasodilation of conductance, but not resistance, vessels subjected to ischemia–reperfusion.Key words: ischemia, reperfusion, statins, vascocontriction–dilation, ventricular function.