title: Rosuvastatin reloading before cardiac surgery with cardiopulmonary bypass.
abstract: OBJECTIVE
  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.
authors: Department of Cardiothoracic Surgery, Heart Center, University of Cologne, Cologne, Germany. elmar.kuhn@uk-koeln.de
authors: Elmar W
authors: EW
authors: Kuhn
authors: Oliver J
authors: OJ
authors: Liakopoulos
authors: Antje C
authors: AC
authors: Deppe
authors: Ingo
authors: I
authors: Slottosch
authors: Klaus
authors: K
authors: Neef
authors: Anja
authors: A
authors: Sterner-Kock
authors: Navid
authors: N
authors: Madershahian
authors: Yeong H
authors: YH
authors: Choi
authors: Thorsten
authors: T
authors: Wahlers
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002315:Cardiopulmonary Bypass; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005464:Fluorobenzenes / Q000008:administration & dosage*; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008055:Lipids / Q000097:blood; D009206:Myocardium / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011300:Preoperative Care / Q000379:methods*; D011743:Pyrimidines / Q000008:administration & dosage*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000008:administration & dosage*; D013552:Swine
chemical_list: D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D010710:Phosphates; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium