Effects of BIBR-277, an angiotensin II type 1 receptor antagonist, on stunned myocardium in dogs.
BACKGROUND
Angiotensin converting enzyme inhibitors can protect the myocardium from ischaemic damage. We examined the effect of BIBR-277, an angiotensin II receptor type 1 antagonist, on myocardial stunning in dogs.


METHODS
Pentobarbital-anaesthetized open-chest dogs were subjected to 20 min ligation of the left anterior descending coronary artery, followed by reperfusion for 60 min. Saline or 0.3, 1 or 3 mg/kg body weight BIBR-277 was injected intravenously 10 min before coronary ligation. The myocardial contractile function was measured by ultrasonometry. The tissue levels of energy metabolites in the 60 min reperfused heart were determined.


RESULTS
Myocardial contractile function assessed in terms of percentage segment-shortening in the saline-treated group decreased during ischaemia and returned towards the pre-ischaemic level during reperfusion but incompletely (myocardial stunning). A significant and dose-dependent improvement in the percentage segment-shortening during reperfusion was observed in the BIBR-277-treated groups. The levels of ATP, ADP and AMP in the reperfused heart were not modified by BIBR-277 treatment compared with those in the saline-treated group.


CONCLUSIONS
BIBR-277 ameliorates the myocardial contractile dysfunction during reperfusion after ischaemia, although it did not bring about any improvement in the high-energy phosphate levels in the reperfused heart.
Izumi
H
H
Department of Pharmacology, Hokkaido College of Pharmacy, Otaru, Japan.
Nakai
T
T
Kano
S
S
Hoshi
K
K
Ichihara
K
K
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001562:Benzimidazoles / Q000627:therapeutic use*; D001565:Benzoates / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D017682:Myocardial Stunning / Q000188:drug therapy* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D000077333:Telmisartan
D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001565:Benzoates; D000077333:Telmisartan