Effects of statins on myocardial and coronary artery response to ischemia-reperfusion.
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 microm) and conductance (i.d. = 487 +/- 11 microm) 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.
Rendig
Stephen V
SV
Department of Internal Medicine, University of California, Davis 95616, USA.
Symons
J David
JD
Amsterdam
Ezra A
EA
D000818:Animals; D008078:Cholesterol, LDL / Q000097:blood; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D013552:Swine; D013553:Swine Diseases / Q000188:drug therapy* / Q000503:physiopathology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors