Crespo Maria J, Cruz Nildris, Quidgley Jose, Torres Hector, Hernandez Cesar, Casiano Hector, Rivera Karines
Department of Physiology, University of Puerto Rico School of Medicine, San Juan, P.R., USA.
Pharmacology. 2014;93(1-2):84-91. doi: 10.1159/000358256. Epub 2014 Feb 18.
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.
围手术期短期服用他汀类药物已被认为可改善接受心脏和血管手术患者的心血管（CV）结局。然而，这种治疗方法的有效性、最佳给药时间以及最适合在高血糖条件下改善心脏功能的他汀类药物尚不清楚。在本研究中，我们比较了10mg/kg/天的辛伐他汀（SV）、普伐他汀（PV）和阿托伐他汀（AV）对链脲佐菌素诱导的糖尿病大鼠在诱导糖尿病4周后、处于完全麻醉状态下的CV状态的影响。在此阶段，心脏功能受损。将大鼠麻醉以模拟术前状态。通过超声心动图对心脏状态进行两次评估，第一次在给予他汀类药物后24小时，然后在每天给予他汀类药物1周后。给予他汀类药物24小时后，CV参数未得到改善。相比之下，在1周内持续每日给予SV和AV，显著提高了射血分数，从治疗前的52.20±2.33%提高到使用AV时的64.89±1.12%以及使用SV时的69.71±2.30%（n = 9，p < 0.05）。心输出量指数也从治疗前的51.13±6.86 ml/min×100 g体重（BW）显著提高到使用AV时的98.74±13.78 ml/min×100 g BW以及使用SV时的84.94±8.64 ml/min×100 g BW。只有AV使每搏输出量从0.50±0.08增加到0.83±0.13 ml（n = 9，p < 0.05）。与其他测试的他汀类药物不同，无论给药方案如何，PV均未产生有益效果。我们的结果表明，在完全麻醉的糖尿病大鼠中，每日给予AV和SV 1周可增强心脏功能。这项关于短期他汀类药物给药的研究可能对改善糖尿病患者的围手术期结局具有重要的临床意义。
