We tested to find out whether pravastatin restores the infarct size (IS)-limiting effect of ischemic preconditioning (IP) and if it has any effect on the IP-induced activation of adenosine producing enzyme ecto-5′-nucleotidase which plays a key role in the IP-induced cardioprotection.
BACKGROUND
The IS-limiting effect of IP is blunted by hypercholesterolemia. Recently, HMG-CoA reductase inhibitors are shown to have direct cytoprotective effects.
METHODS
Rabbits were fed with a normal or cholesterol (1%) added diet with or without pravastatin (5 mg/kg/day) treatment. Infarct size was measured after 30 min occlusion and 3 h reperfusion of circumflex coronary artery with or without the IP procedure (5 min occlusion and 10 min reperfusion). Additionally, ecto-5′-nucleotidase activities of ischemic and nonischemic myocardium were measured immediately after IP procedure.
RESULTS
This dose of pravastatin did not normalize the increased level of serum cholesterol. The IS-limiting effect of preceding IP (IS reduced from 36.7% to 9.6%, p < 0.001) was abolished by hypercholesterolemia (from 46.1% to 31.3%, p = NS) and restored by pravastatin treatment (from 35.2% to 9.4%, p < 0.001). Pravastatin treatment did not affect IS or the effect of IP under normocholesterolemia. The activation of ecto-5′-nucleotidase presented as the activity ratio of ischemic to nonischemic myocardium (3.1-fold in normocholesterolemia) was blunted by hypercholesterolemia (1.8-fold, p < 0.05) and restored by pravastatin treatment (2.9-fold).
CONCLUSIONS
Pravastatin, at the dose serum cholesterol was not normalized, restored the IS-limiting effect of IP and IP-induced ecto-5′-nucleotidase activation, which were both blunted by hypercholesterolemia. The activation of ecto-5′-nucleotidase may be worth further investigation as a possible mechanism for the hypercholesterolemia-induced retardation and pravastatin-mediated restoration of the cardioprotective effect of IP. 相似文献
To explore the renoprotective and anti-inflammatory effects of pravastatin, we analyzed the changes in renal function and urinary monocyte chemoattractant protein-1 (MCP-1) level as a renal tubulointerstitial inflammatory biomarker and serum MCP-1 level as a systemic inflammatory biomarker following the introduction of treatment with 10 mg/day of pravastatin in 10 hyperlipidemic type 2 diabetic patients with normoalbuminuria. Twelve months of the pravastatin treatment did not affect urinary levels of albumin, transferrin, N-acetylglucosaminidase, or MCP-1 in the hyperlipidemic diabetic patients, whereas the treatment significantly reduced serum levels of MCP-1 in the patients. The pravastatin treatment effectively lowered low-density lipoprotein cholesterol (LDL-C) levels in the hyperlipidemic diabetic patients to levels nearly to those in 11 non-hyperlipidemic type 2 diabetic patients with normoalbuminuria. Interestingly, serum MCP-1 levels were significantly lower in the hyperlipidemic patients treated with pravastatin than in the non-hyperlipidemic patients. No significant correlation was observed between serum LDL-C and MCP-1 levels in all the data in the hyperlipidemic patients before and after the pravastatin treatment and in the non-hyperlipidemic patients. These results collectively indicate that pravastatin may ameliorate systemic vascular inflammation rather than local renal inflammation in hyperlipidemic type 2 diabetic patients with normoalbuminuria, independent of its cholesterol-lowering effects. 相似文献
Objective Coronary artery disease (CAD) is presently the major cause of mortality and morbidity. Anti-hyperlipidemic treatment is one
of the main treatment steps in the management of CAD. Statins are the cornerstones in this treatment. Ezetimibe can be reliably
used, when statins prove ineffective in treatment, or to reduce their side effects. In the present study we examined the effects
of high-dose pravastatin (40 mg) and low-dose pravastatin (10 mg) + ezetimibe (10 mg) combination therapy on lipid and glucose
mechanism, as well as inflammation.
Methods This study registered 100 cases. Of the cases, 50 [57.1 ± 11.1 years (24 (48%) females and 26 (52%) males)] were administered
40 mg/day pravastatin (group 1) and 50 [53.2 ± 12.2 years (27 (54%) females and 23 (46%) males)] were administered 10 mg pravastatin
+ 10 mg ezetimibe (group 2).
Results In group 1, total cholesterol fell from 231.1 ± 83.5 mg/dl to 211.3 ± 37.2 mg/dl (p = 0.03), triglyceride from 243.5 ± 96.8 mg/dl to 190.9 ± 55.2 mg/dl (p = 0.003), and LDL cholesterol from 165.7 ± 29.7 mg/dl to 133.4 ± 26.6 mg/dl (p = 0.02). In group 2, total cholesterol dropped from 250.9 ± 51.8 mg/dl to 187.9 ± 34.9 mg/dl (p = 0.001), triglyceride from 270.3 ± 158.9 mg/dl to 154.6 ± 60.7 mg/dl (p = 0.001), and LDL cholesterol from 158.1 ± 47.5 mg/dl to 116.9 ± 26.4 mg/dl (p = 0.001). Insulin resistance decreased from 4.05 ± 2.31 to 3.16 ± 1.90 (p = 0.07) in group 1 and from 2.96 ± 1.50 to 2.05 ± 0.55 (p = 0.009) in group 2. High sensitive C-reactive protein fell from 6.69 ± 6.11 mg/l to 3.02 ± 1.70 mg/l (p = 0.01) in group 1 and from 6.36 ± 2.06 mg/l to 2.68 ± 1.69 mg/l (p = 0.001) in group 2.
Conclusion Both therapy regimes are effective. However, we found that low-dose pravastatin and ezetimibe combination therapy is more
effective than high-dose pravastatin therapy on lipid metabolism, glucose metabolism and inflammation. 相似文献
AIMS: To assess the additional benefit gained from high compliancein the West of Scotland Coronary Prevention Study and to examinecases where withdrawal from trial medication was due to an adverseevent. METHODS: The incidence of definite coronary heart disease or non-fatalmyocardial infarction, cardiovascular mortality, definite orsuspect coronary heart disease death or non-fatal myocardialinfarction, the need for coronary revascularization procedures,all-cause mortality and incident cancers were measured in theentire cohort and compared with the high compliance group. Theadverse events associated with withdrawal were coded by bodysystem. RESULTS: In subjects with compliance 75%, treatment with pravastatinresulted in a 38% risk reduction for definite coronary heartdisease death or non-fatal myocardial infarction and for cardiovascularmortality, a 46% reduction in risk or coronary revascularizationand a 32% risk reduction (P=0·015) for all-cause mortality. CONCLUSION: The analysis of the effect of pravastatin in the subgroup ofhigh compliers to randomized medication demonstrated a substantialincrease in the estimated risk reductions in comparison withthat achieved in the intention-to-treat analysis. This resulthas significant implications for the motivation of high complianceamong patients and for the assessment of the cost-effectivenessof treatment. 相似文献
Statins are effective in the prevention of coronary heart disease (CHD), a leading cause of heart failure (HF). Secondary analyses from 11 randomized clinical trials of patients with high-risk acute or stable coronary heart disease, but without HF, suggest that statins may prevent new-onset HF or HF-related hospitalization. In persons with established HF, several cohort studies found an approximate 35% relative risk reduction in all-cause mortality. While ongoing randomized clinical trials will help to determine the efficacy of statins in persons with established HF, it is reasonable to consider this class of medications in patients with a history of cardiovascular disease, dyslipidemia or diabetes mellitus, and who have either developed, or who remain at risk of, HF. 相似文献