The effects of prostaglandin inhibition on whole-body ischemia-reperfusion in swine.
BACKGROUND
Prostaglandins (PGs), particularly PGE2 and PGI2, have a salutary effect on myocardial ischemia-reperfusion-induced myocardial damage.


OBJECTIVE
We investigated acute PG synthesis inhibition on outcomes from whole-body ischemia-reperfusion injury using a well-characterized model of ventricular fibrillation (VF)-induced cardiac arrest in pigs. In addition, we assessed early postresuscitation myocardial function in survivors using echocardiography as well as a biochemical measure of myocardial tissue damage.


METHODS
Twenty-six animals (weight range, 25-35 kg) received indomethacin (INDO; 2 mg/kg, nonselective cyclooxygenase (COX) 1 and 2 inhibitor), celecoxib (2 mg/kg; selective COX-2 inhibitor [COX-2-I]), or saline placebo 30 minutes before induction of VF. After 3 minutes of VF with no intervention, the animals received standard chest compression using an automated chest compression device (Thumper; Michigan Instruments, Grand Rapids, Mich) for 15 minutes. After 18 minutes of VF, a single dose of vasopressin and bicarbonate were administered and defibrillation attempted. Hemodynamics, regional blood flow, echocardiography, and serum troponin I measurements were performed before and after drug infusion or placebo, during cardiopulmonary resuscitation (CPR), and after return of spontaneous circulation (ROSC).


RESULTS
Return of spontaneous circulation to 180 minutes occurred in 9 of 10 animals receiving placebo, 7 of 8 animals given COX-2-I, and 3 of 8 animals given INDO (P = .01, placebo or COX-2-I vs INDO). Hemodynamics did not differ among groups over time. Indomethacin and COX-2-I attenuated the increase in regional blood flow in the heart and brain, observed in the placebo group, 30 minutes after ROSC. All 3 study groups had significant decrease in percentage of ejection fraction and fractional shortening after ROSC and significant increase in wall motion score index after ROSC. In the COX-2-I group, troponin I increased 9-fold compared with placebo, 180 minutes after ROSC. Whole-body ischemia-reperfusion and CPR significantly increased PGE2 and PGI2 levels. The latter were blunted by pretreatment with COX inhibition.


CONCLUSIONS
These findings suggest that PGs have a critical role in myocardial function and viability during low-blood-flow states produced by CPR and possibly other low-blood-flow clinical conditions.
Lozano
Hector
H
Division of Cardiology, Mount Sinai Medical Center of Greater Miami, Miami Beach, FL 33140, USA.
Wu
Dongmei
D
Bassuk
Jorge
J
Aria
Jaqueline
J
Kurlansky
Paul
P
Lamas
Gervasio A
GA
Adams
Jose A
JA
D000818:Animals; D016887:Cardiopulmonary Resuscitation; D000068579:Celecoxib; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000502:physiology; D004195:Disease Models, Animal; D011464:Epoprostenol / Q000502:physiology; D006321:Heart / Q000502:physiology*; D006324:Heart Arrest, Induced; D006336:Heart Massage; D007213:Indomethacin / Q000494:pharmacology; D009206:Myocardium / Q000473:pathology; D011453:Prostaglandins / Q000502:physiology*; D011720:Pyrazoles / Q000494:pharmacology; D012039:Regional Blood Flow; D015427:Reperfusion Injury / Q000503:physiopathology*; D013449:Sulfonamides / Q000494:pharmacology; D013552:Swine; D019210:Troponin I / Q000097:blood
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D011720:Pyrazoles; D013449:Sulfonamides; D019210:Troponin I; D011464:Epoprostenol; D000068579:Celecoxib; D015232:Dinoprostone; D007213:Indomethacin