Rosuvastatin reloading before cardiac surgery with cardiopulmonary bypass.

BACKGROUND/PURPOSE: Recent evidence suggests that statin-mediated cardioprotection after chronic statin therapy decreases over time and can be reactivated by preprocedural high-dose statin reloading therapy. We tested in a porcine cardiopulmonary bypass (CPB) model whether statin-related cardioprotection is further enhanced by a preoperative rosuvastatin reloading therapy. METHODS: Control (n = 6), rosuvastatin-pretreated (n = 6; 20 mg/day for 7 days p.o.) and rosuvastatin-reloaded (n = 6; p.o. treatment plus 0.10 mg/kg/h i.v. during surgery) pigs (Deutsche Landrasse) were subjected to CPB for 2 h with 1 h of cardioplegic cardiac arrest. Systemic hemodynamics, cardiac index (CI), coronary blood flow (CBF) and left ventricular (LV) function [pressure-volume area (PVA), preload recruitable stroke work (PRSW)] were determined before and 4 h after 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 postmortem. All data are given as mean ± SD. RESULTS: Preoperative plasma LDL, HDL and cholesterol did not differ between treatment groups. Compared to control, oral treatment improved post-CPB CI, CBF, first derivative of maximal LV-pressure (LVdp/dt) 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/m(2); CBF: 76 ± 32 vs. 43 ± 8 ml/min; LVdp/dt: 1,980 ± 333 vs. 1,249 ± 461 mm Hg/s; PVA: 6,954 ± 941 vs. 3,252 ± 1,822 mm Hg·ml; p < 0.05) with improved in vitro NO-dependent coronary relaxation (102 ± 10 vs. 79 ± 14%; p = 0.003). Irrespective of recapture therapy statin pretreatment augmented myocardial eNOS and PTEN (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 valuable therapeutic approach for the reduction of myocardial ischemia-reperfusion injury.

Current evidence for perioperative statins in cardiac surgery.

Cardiac surgery improves life expectancy and quality of life for the constantly ageing population in developed countries. Mediated by their lipid-dependent and lipid-independent mechanisms, statins are sought to provide benefit with regard to better outcomes after cardiac surgery. Current guidelines recommend statin use in patients undergoing coronary artery bypass grafting, while less evidence is available for patients referred to heart valve surgery. Optimal selection of statin drug and dosage including perioperative timing of statin therapy remains largely unknown, but results of ongoing meta-analyses and future randomized trials will add important evidence to guide perioperative statin treatment of cardiac surgery patients.

Pericardial suction blood separation attenuates inflammatory response and hemolysis after cardiopulmonary bypass.

OBJECTIVES: Retransfusion of pericardial suction blood (PSB) is critically considered under the aspect of the biocompatibility of the cardiopulmonary bypass (CPB). We investigated various indicators of inflammation and blood cell activation associated with CPB and re-transfusion of PSB during cardiac surgery. DESIGN: Thirty-five patients undergoing elective coronary artery bypass grafting were prospectively randomized into two groups. In group A (n = 15, retransfusion group) the pericardial suction blood was continuously retransfused during CPB, in group B (n = 20, no-retransfusion group) the suction blood was separated. Parameters indicating the status of the inflammation and blood cell activation were analyzed before and at the end of CPB, latest after 90 minutes on CPB. RESULTS: Patients' perioperative data did not differ between groups. The inflammatory markers C-reactive protein, PMN-Elastase and Interleukin-6 increased in both groups after CPB (p < 0.04) with significantly lower values in the no-retransfusion group (p < 0.02). Leukocytes and platelet activation markers beta-Thromboglobulin and soluble P-Selectin also experienced a significant elevation during observation time (p < 0.02) without any difference between the groups. Free hemoglobin and LDH tremendously increased during CPB with lower values in the no-retransfusion group. CONCLUSIONS: Cardiotomy suction is a major cause of hemolysis and contributes significantly to the systemic inflammatory response.

Circulating endothelial cells demonstrate an attenuation of endothelial damage by minimizing the extracorporeal circulation.

OBJECTIVE: Detachment of endothelial cells may represent serious injury of the endothelium after cardiopulmonary bypass. We investigated whether the extent of endothelial injury is related to the type of cardiopulmonary bypass system used (conventional or minimized) and determined circulating endothelial cells as well as von Willebrand factor and soluble thrombomodulin. METHODS: Twenty patients scheduled for elective coronary bypass grafting were randomly assigned to either the minimal extracorporeal circulation system or the standard cardiopulmonary bypass. Ten healthy volunteers served as controls. Circulating endothelial cells per milliliter of full blood were perioperatively determined by immunomagnetic cell separation technique. Endothelial plasma markers were measured by enzyme-linked immunosorbent assay. RESULTS: Preoperative circulating endothelial cell numbers did not differ between the experimental groups, but were significantly higher than in the healthy controls (18.6 +/- 5.6 vs 7.2 +/- 3.8, P < .001). At 6 hours, circulating endothelial cell numbers increased significantly compared with baseline in both experimental groups and peaked at 12 hours after cardiopulmonary bypass initiation, each time with significantly lower values in the minimal extracorporeal circulation group (6 hours: 44.0 +/- 9.9 vs 29.6 +/- 9.8, P = .007; 12 hours: 48.1 +/- 6.8 vs 31.8 +/- 7.1, P < .001). Likewise, von Willebrand factor and soluble thrombomodulin postoperatively increased in both groups with a tendency toward lower levels in the minimal extracorporeal circulation group. Although circulating endothelial cells gradually declined, continually with lower numbers in the minimal extracorporeal circulation group, the endothelial plasma markers remained elevated during observation time. CONCLUSIONS: Circulating endothelial cells represent a novel marker of the intrinsic endothelial damage caused by cardiopulmonary bypass. Its analysis facilitates the evaluation of cardiopulmonary bypass modifications as the minimal extracorporeal circulation system could be proven to be less injurious to endothelium and myocardium.