[Are all HMG-CoA reductase inhibitors protective against ischemic heart disease?].
Effects of pravastatin, simvastatin, atorvastatin, fluvastatin and cerivastatin on myocardial contractile dysfunction during reperfusion after brief ischemia were examined in dogs. Pretreatment of the dog with lipophilic HMG-CoA reductase inhibitors for 3 weeks, simvastatin (2 mg/kg/day), atorvastatin (2 mg/kg/day), fluvastatin (4 mg/kg/day), and cerivastatin (40 micrograms/kg/day) worsened recovery of myocardial contraction during reperfusion after brief ischemia in association with reduced myocardial ATP level. A hydrophilic HMG-CoA reductase inhibitor, pravastatin (2 and 4 mg/kg/day), did not affect the recovery of myocardial contractile function and ATP level during reperfusion following ischemia. The lipophilic inhibitors may enter the myocardial cell, inhibit ubiquinone biosynthesis, and depress ATP generation in mitochondria, leading to worsening of the myocardial stunning after reperfusion subsequent to ischemia.
Ichihara
K
K
Department of Pharmacology, Hokkaido College of Pharmacy, Otaru, Japan.
Satoh
K
K
Yamamoto
A
A
Hoshi
K
K
D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D000069059:Atorvastatin; D004285:Dogs; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use; D000077340:Fluvastatin; D006538:Heptanoic Acids / Q000627:therapeutic use; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007211:Indoles / Q000627:therapeutic use; D009200:Myocardial Contraction / Q000502:physiology; D017202:Myocardial Ischemia / Q000517:prevention & control*; D017682:Myocardial Stunning; D009206:Myocardium / Q000737:chemistry; D017035:Pravastatin / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D019821:Simvastatin / Q000627:therapeutic use
D005229:Fatty Acids, Monounsaturated; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D011725:Pyridines; D011758:Pyrroles; D000077340:Fluvastatin; D000255:Adenosine Triphosphate; D000069059:Atorvastatin; D019821:Simvastatin; C086276:cerivastatin; D017035:Pravastatin