Identification of a time window for therapy to reduce experimental canine myocardial injury: suppression of neutrophil activation during 72 hours of reperfusion.
The cardio-protective effects of neutrophil depletion or inhibition of neutrophil activation early in the course of myocardial reperfusion has been established. Whether these treatments would be effective during extended periods of reperfusion has not been ascertained. Open-chest anesthetized dogs were subjected to left circumflex artery (LCX) occlusion for 90 minutes followed by 72 hours of reperfusion. Dogs were randomized into one of four groups: 1) control; 2) Ilo-2 (iloprost 100 ng/kg/min administered via the left atrium beginning 10 minutes after LCX occlusion and continuing 2 hours into reperfusion); 3) Ilo-48 (iloprost 100 ng/kg/min administered as above until 1 hour after reperfusion then 25 ng/kg/min for 48 hours of reperfusion; or 4) antibody (neutrophil antibody administered before occlusion and 1/2 hourly for 2 hours of reperfusion and then every 24 hours). Myocardial infarct size, as a percentage of the area at risk assessed after 72 hours of reperfusion, was significantly smaller in the antibody-treated group (32.1 +/- 5.0% mean +/- SEM) or Ilo-48 (22.6 +/- 4.0%) treatment group compared with control (48.7 +/- 5.6%) or Ilo-2 (57.6 +/- 5.2%) groups. Regional myocardial blood flow studies demonstrated that all groups developed similar degrees of ischemia. The iloprost-treated groups had lower mean arterial blood pressures during occlusion and reperfusion than groups 1 and 4 (p less than 0.05). Circulating neutrophil counts were increased in groups 1 and 2 at 24 and 48 hours after reperfusion compared to groups 3 and 4 (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Simpson
P J
PJ
Department of Pharmacology, University of Michigan Medical School, Ann Arbor.
Fantone
J C
JC
Mickelson
J K
JK
Gallagher
K P
KP
Lucchesi
B R
BR
D000818:Animals; D002317:Cardiovascular Agents / Q000627:therapeutic use; D002452:Cell Count; D003326:Coronary Circulation; D003327:Coronary Disease / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D004285:Dogs; D011464:Epoprostenol / Q000627:therapeutic use*; D006439:Hemodynamics; D016285:Iloprost; D007249:Inflammation / Q000473:pathology; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology*; D009504:Neutrophils / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D013997:Time Factors
D002317:Cardiovascular Agents; D011464:Epoprostenol; D009195:Peroxidase; D016285:Iloprost