Antiinflammatory agent BW 755 C in ischemic reperfused porcine hearts.
The effect of the antiinflammatory compound BW 755 C on myocardial infarctions was evaluated in regionally ischemic reperfused hearts of 35 pigs. The left anterior descending coronary artery was occluded distally in 23 anesthetized pigs for 45 min and was reperfused for 24 h. The BW 755 C (10 mg/kg) was intravenously injected prior to ischemia in seven pigs (group A). A second dose of BW 755 C (5 mg/kg) was given after 4 h of reperfusion. Group B consisted of eight animals. They were treated with BW 755 C immediately before (10 mg/kg i.v.) and after 4 h of reperfusion (5 mg/kg). Another eight pigs served as controls. At the end of the experiments, infarct size was determined as the ratio of the infarcted myocardium (tetrazolium stain) over the risk region (fluorescent dye). Leukocyte infiltration of the risk region was histologically quantitated in one slice of each experiment. In a second set of experiments recovery of regional myocardial function of the risk region was determined by sonomicrometry during 2 weeks of reperfusion. The BW 755 C (10 mg/kg) was injected intravenously in six pigs before ischemia and at a dose of 5 mg/kg after 4 h of reperfusion. Six pigs served as controls. Hemodynamic parameters and total leukocyte blood count did not differ between the groups. Treatment protocol of group A reduced the infarct size from 72 +/- 13% (control group) to 50.9 +/- 12% (p less than 0.005). Infarct size of group B (65 +/- 16%) did not differ from control experiments. Leukocyte infiltration of the risk region was only attenuated in group A (p = 0.01) compared with the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
Klein
H H
HH
Department of Cardiology, University of Göttingen, F.R.G.
Pich
S
S
Bohle
R M
RM
Lindert
S
S
Nebendahl
K
K
Buchwald
A
A
Schuff-Werner
P
P
Kreuzer
H
H
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000758:Anesthesia; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D066298:In Vitro Techniques; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D011720:Pyrazoles / Q000494:pharmacology*; D013552:Swine; D014693:Ventricular Fibrillation / Q000503:physiopathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006454:Hemoglobins; D011720:Pyrazoles; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine