Volume 77, Issue 2, Pages (May 2008)

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Volume 77, Issue 2, Pages 250-257 (May 2008) Non-selective cyclooxygenase inhibition before periodic acceleration (pGz) cardiopulmonary resuscitation (CPR) in a porcine model of ventricular fibrillation Jorge A. Bassuk, Dongmei Wu, Hector Lozano, Jaqueline Arias, Paul Kurlansky, Gervasio A. Lamas, Jose A. Adams Resuscitation Volume 77, Issue 2, Pages 250-257 (May 2008) DOI: 10.1016/j.resuscitation.2007.11.018 Copyright © 2007 Elsevier Ireland Ltd Terms and Conditions

Figure 1 Schematic of the experimental protocol. Resuscitation 2008 77, 250-257DOI: (10.1016/j.resuscitation.2007.11.018) Copyright © 2007 Elsevier Ireland Ltd Terms and Conditions

Figure 2 Survival in each group is plotted as a function of time. INDO=indomethacin pretreatment (n=8), CONTROL=saline placebo control (n=9) and INDO+L-NAME=combined indomethacin and L-NAME pretreatment (n=5) (additional animal experiments performed to ascertain the effects of combined prostaglandin and nitric oxide inhibition). Resuscitation 2008 77, 250-257DOI: (10.1016/j.resuscitation.2007.11.018) Copyright © 2007 Elsevier Ireland Ltd Terms and Conditions

Figure 3 Top panel is mean arterial blood pressure as a function of time. Bottom panel is coronary perfusion pressure (CPP) also as a function of time. BL=baseline. After infusion, denotes the time after either saline or indomethacin infusion. CPR=cardiopulmonary resuscitation, ROSC 30, 60, 120, 180 denotes 30–180min after return of circulation. Both mean arterial pressure and CPP were significantly different from baseline during CPR. Resuscitation 2008 77, 250-257DOI: (10.1016/j.resuscitation.2007.11.018) Copyright © 2007 Elsevier Ireland Ltd Terms and Conditions

Figure 4 Regional blood flows as a percent change from baseline values over time. (Top panel cerebral cortex) Indomethacin (INDO) significantly decreased cerebral blood flow compared to placebo (CONTROL) after infusion, during CPR, and at 30 and 120min after ROSC (†p<0.05 INDO vs. CONT) ‡p<0.05. After infusion CONT values vs. CONT values at CPR, 30 and 120min after ROSC. (Middle panel brain stem) Indomethacin (INDO) significantly decreased brain stem blood flow compared to placebo (CONTROL) after infusion, during CPR, and at 30 and 120min after ROSC (†p<0.05. INDO vs. CONT) ‡p<0.05. After infusion, CONT values vs. CONT values at CPR, 30 and 120min after ROSC. (Bottom panel cerebellum) Indomethacin (INDO) significantly decreased cerebellar blood flow compared to placebo (CONTROL) after infusion, during CPR, and at 30min after ROSC †p<0.05. INDO vs. CONT ‡p<0.05. After infusion, CONT values vs. CONT values at CPR and 30 and 120min after ROSC. Resuscitation 2008 77, 250-257DOI: (10.1016/j.resuscitation.2007.11.018) Copyright © 2007 Elsevier Ireland Ltd Terms and Conditions

Figure 5 Regional blood flow (RBF) of the left (top panel) and right ventricles (lower panel). Indomethacin treated animals had significantly less increase in right and left ventricular RBF at 30min after ROSC (†p<0.05 INDO vs. CONT). Both CONT and INDO groups had a significant decrease in RBF to both right and left ventricles and a significant increase in RBF 30min after ROSC (‡p<0.05, after infusion values vs. CONT and INDO values). Resuscitation 2008 77, 250-257DOI: (10.1016/j.resuscitation.2007.11.018) Copyright © 2007 Elsevier Ireland Ltd Terms and Conditions

Figure 6 Ratio of regional blood flows of the epicardial and endocardium of the left ventricle. A ratio of 1 denotes equivalent blood flow to each area ‡p<0.05. Baseline values vs. CPR values for both groups. Resuscitation 2008 77, 250-257DOI: (10.1016/j.resuscitation.2007.11.018) Copyright © 2007 Elsevier Ireland Ltd Terms and Conditions

Figure 7 Echocardiography data at baseline (BL), after infusion of placebo or indomethacin, and return of circulation at 30 and 180min (ROSC 30, 180). (Top panel percent ejection fraction (%EF)) Both groups had significantly decreased %EF, compared to baseline values at 30 and 180min after ROSC (‡p<0.05, baseline values vs. values at 30 and 180min after ROSC for both groups). (Middle panel percent fractional shortening (%FS)) Both groups had significantly decreased %FS, compared to baseline values at 30 and 180min after ROSC (‡p<0.05, baseline values vs. values at 30 and 180min after ROSC for both groups). (Lower panel wall motion score index (WMSI)) Significant wall motion abnormalities were present after ROSC at 30 and 180min in both groups compared to baseline values. (‡p<0.05, baseline values vs. values at 30 and 180min after ROSC for both groups). INDO treated animals had significantly worse WMSI compared to CONT (†p<0.05 INDO vs. CONT). Resuscitation 2008 77, 250-257DOI: (10.1016/j.resuscitation.2007.11.018) Copyright © 2007 Elsevier Ireland Ltd Terms and Conditions

Figure 8 Biochemical indices of tissue injury. (Top Panel) Creatine phosphokinase (CPK) and (Bottom Panel) Troponin I. Indomethacin treated animals had significant increase in CPK and Troponin I 180min after ROSC, compared to CONT (†p<0.05 INDO vs. CONT). Resuscitation 2008 77, 250-257DOI: (10.1016/j.resuscitation.2007.11.018) Copyright © 2007 Elsevier Ireland Ltd Terms and Conditions