The role of platelet-activating factor in regional myocardial ischemia-reperfusion injury.
BACKGROUND
This swine model was designed to elucidate the role of platelet-activating factor in regional myocardial ischemia-reperfusion injury.


METHODS
In groups 1 and 2 (n = 12 each), the left anterior descending coronary artery was ligated for 60 minutes to induce regional myocardial ischemia followed by 6 hours of reperfusion. Group 1 received the platelet-activating factor antagonist TCV-309 before ischemia, whereas group 2 did not. Group 3 (n = 3) had a sham operation.


RESULTS
Animals in group 2 exhibited significant (p < 0.05) hemodynamic instability and myocardial depression during the reperfusion period. Despite preventive measures, 7 of the 12 animals experienced severe dysrhythmias in the form of atrial and ventricular fibrillation leading to cardiac arrest. In contrast, animals in group 1 in whom the effects of platelet-activating factor were blocked by the specific platelet-activating factor receptor antagonist TCV-309 were hemodynamically stable and had significantly (p < 0.05) better myocardial function. This significant difference in global myocardial function between the groups was observed in the presence of similar morphologic findings and regional myocardial function.


CONCLUSIONS
These results suggest that platelet-activating factor has a definite influence on global myocardial dysfunction associated with regional myocardial ischemia-reperfusion injury.
Qayumi
A K
AK
Department of Surgery, The University of British Columbia, Vancouver Hospital and Health Sciences Centre, Canada. qayumi@unixg.ubc.ca
English
J C
JC
Godin
D V
DV
Ansley
D M
DM
Loucks
E B
EB
Lee
J U
JU
Kim
C W
CW
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology; D001281:Atrial Fibrillation / Q000209:etiology; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002306:Cardiac Volume / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006323:Heart Arrest / Q000209:etiology; D006439:Hemodynamics / Q000187:drug effects; D007546:Isoquinolines / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology; D017202:Myocardial Ischemia / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000494:pharmacology; D011897:Random Allocation; D013318:Stroke Volume / Q000187:drug effects; D013552:Swine; D044005:Tetrahydroisoquinolines; D014693:Ventricular Fibrillation / Q000209:etiology; D016276:Ventricular Function / Q000187:drug effects
D007546:Isoquinolines; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D011726:Pyridinium Compounds; D044005:Tetrahydroisoquinolines; C067430:TCV 309