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DOI: 10.1055/s-0030-1269014
Rosuvastatin reloading augments myocardial and coronary function after cardiac surgery with cardiopulmonary bypass
Objective: Long-term statin pretreatment attenuates myocardial ischemia-reperfusion (I/R) injury in cardiac surgery patients. We tested in a porcine CPB model whether statin-related cardioprotection is further enhanced by an acute preoperative rosuvastatin reloading therapy.
Methods: Placebo- (n=6), rosuvastatin-pretreated (n=6; 20mg/d for 7d, oral treatment) and rosuvastatin-reloaded (n=6; oral treatment plus 0.1mg/KG/h iv during surgery) pigs were subjected to CPB for 2 hours (h) with 1h cardioplegic cardiac arrest. Systemic hemodynamics, cardiac index (CI), coronary blood flow (CBF) and left ventricular (LV) function (PVA, PRSW) were determined before and 4h post CPB. Myocardial expression (PCR) and protein content (western blot) of endothelial NO-synthase (eNOS) and phosphatase-and-tensin-homolog-deleted-on chromosome-ten (PTEN) were measured, and right coronary relaxation was assessed post-mortem. All data are given as mean and standard deviation.
Results: Preoperative plasma LDL, HDL and cholesterol did not differ between treatment groups. Compared to control, oral treatment improved post-CPB CI, CBF, maximal LV-dpdt and PVA (P<0.05). Significant enhancement was achieved with perioperative reloading therapy (CI: 5.2±1.0 vs. 3.9±1.5 L/min/m2; CBF: 76.3±32.3 vs. 43.6±8.0 mL/min; dpdt: 2316±876 vs. 1249±461mmHg/s; PVA: 6955±941 vs. 3252±1822mmHg*mL; P<0.05) with improved in-vitro NO-dependent coronary relaxation (101.7±9.9% vs. 79.2±14.4%; p=0.003). Short-term perioperative statin treatment (po and iv) augmented myocardial eNOS and PTEN content (p<0.05), but failed to increase cardiac eNOS or PTEN expression after CPB.
Conclusions: Periprocedural statin reloading therapy enhances myocardial and coronary function after cardiac surgery with CPB and may therefore provide a novel therapeutic approach for the reduction of myocardial I/R injury.