Daily administration of atorvastatin and simvastatin for one week improves cardiac function in type 1 diabetic rats

Pharmacology. 2014;93(1-2):84-91. doi: 10.1159/000358256. Epub 2014 Feb 18.

Abstract

Short-term administration of statins during the perioperative period has been suggested to improve cardiovascular (CV) outcomes in patients undergoing cardiac and vascular surgery. The effectiveness of this therapy, the optimal administration time and the statin best suited to improve cardiac performance under hyperglycemic conditions, however, are unknown. In this study, we compared the effects of 10 mg/kg/day simvastatin (SV), pravastatin (PV) and atorvastatin (AV), on the CV status of fully anesthetized streptozotocin-induced diabetic rats 4 weeks following diabetes induction. At this stage, cardiac function is compromised. The rats were anesthetized to mimic presurgical conditions. Cardiac status was evaluated twice by echocardiography, first 24 h after statin administration, and then after daily statin administration for 1 week. After 24 h of statin administration, CV parameters were not improved. Continued daily administration of SV and AV over a 1-week period, by contrast, significantly improved ejection fraction from 52.20 ± 2.33% before treatment to 64.89 ± 1.12% with AV and to 69.71 ± 2.30% with SV (n = 9, p < 0.05). The cardiac output index was also significantly improved from 51.13 ± 6.86 ml/min × 100 g body weight (BW) before treatment to 98.74 ± 13.78 ml/min × 100 g BW with AV and to 84.94 ± 8.64 ml/min × 100 g BW with SV. Only AV increased stroke volume from 0.50 ± 0.08 to 0.83 ± 0.13 ml (n = 9, p < 0.05). Unlike the other statins tested, PV provided no beneficial effects, regardless of the regimen of administration. Our results indicate that daily administration of AV and SV for 1 week enhances cardiac performance in fully anesthetized diabetic rats. This study of short-term statin administration may have strong clinical implications for improving perioperative outcomes in diabetic patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atorvastatin
  • Blood Glucose / analysis
  • Cardiac Output / drug effects
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / physiopathology
  • Drug Administration Schedule
  • Heart / drug effects*
  • Heart / physiopathology
  • Heart Rate / drug effects
  • Heptanoic Acids / administration & dosage*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
  • Pravastatin / administration & dosage
  • Pyrroles / administration & dosage*
  • Rats
  • Rats, Sprague-Dawley
  • Simvastatin / administration & dosage*
  • Ventricular Function, Left / drug effects

Substances

  • Blood Glucose
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Atorvastatin
  • Simvastatin
  • Pravastatin