Daily Administration of Atorvastatin and Simvastatin for One Week Improves Cardiac Function in Type 1 Diabetic Rats

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.

Atorvastatin, but not pravastatin, inhibits cardiac Akt/mTOR signaling and disturbs mitochondrial ultrastructure in cardiac myocytes

“…Statins were shown to decrease Ca 2+ ATPase activity thereby increasing sarcoplasmic Ca 2+ (61,62). In rats with type 1 diabetes, a 7 d administration of atorvastatin or simvastatin, but not of pravastatin, improved cardiac systolic function (63), and the researchers speculated that short-term lipophilic statin treatment increased the contractile capacity in these diabetic hearts. Because it has been shown that calcium flux from the ER to the mitochondria is an important regulator for mitochondrial function (64,65), we speculate that weakened ERmitochondrial contact sites disturbed cellular calcium flux in cVclKO mice.…”

“…Statins were shown to decrease Ca 2+ ATPase activity thereby increasing sarcoplasmic Ca 2+ (61,62). In rats with type 1 diabetes, a 7 d administration of atorvastatin or simvastatin, but not of pravastatin, improved cardiac systolic function (63), and the researchers speculated that short-term lipophilic statin treatment increased the contractile capacity in these diabetic hearts.…”