Inhibition of neutrophil adhesion reduces myocardial infarct size.
Neutrophil accumulation and activation within the myocardium during ischemia and reperfusion has been shown to play a prominent role in the development of myocardial stunning and infarction. To determine if a simple inhibitor of neutrophil adhesion could reduce myocardial infarct size, we administered NPC 15669 (a new antiinflammatory agent that inhibits neutrophil adhesion) to 12 pigs (6 controls, 6 NPC-treated) in a porcine model of ischemia and reperfusion injury. Each animal received a continuous infusion of either NPC (10 mg/kg intravenous bolus followed by 6 mg.kg-1 x h-1 intravenous infusion) or an equal volume of normal saline solution during 1 hour of left anterior descending artery occlusion and 2 hours of reperfusion. There were no significant differences in the pre-ischemia, mid-ischemia, or postischemia rate-pressure product between control and experimental groups. The regions at risk were similar in both groups. However, the mean myocardial infarct size was reduced by 51% with administration of NPC 15669 (30.7% +/- 6.8%) compared with controls (62.3% +/- 5.4%; p < 0.01). These data indicate that NPC 15669, an inhibitor of neutrophil adhesion, substantially reduces myocardial infarct size after transient left anterior descending artery occlusion and that adhesion of the white cell to vascular endothelium may be an important element of the pathogenesis of myocardial infarction.
Curtis
W E
WE
Department of Cardiac Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Gillinov
A M
AM
Wilson
I C
IC
Bator
J M
JM
Burch
R M
RM
Cameron
D E
DE
Gardner
T J
TJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D001013:Aorta, Thoracic; D001157:Arterial Occlusive Diseases / Q000473:pathology / Q000517:prevention & control*; D015815:Cell Adhesion Molecules / Q000187:drug effects; D007262:Infusions, Intravenous; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008954:Models, Biological; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D009504:Neutrophils / Q000187:drug effects; D012307:Risk Factors; D013552:Swine; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015815:Cell Adhesion Molecules; C071244:N-(9H-(2,7-dimethylfluoren-9-ylmethoxy)carbonyl)leucine; D007930:Leucine