Does verapamil limit myocardial infarct size in a heart deficient in xanthine oxidase?
1. The delay of ischaemic myocardial necrosis by verapamil has been reported in the dog heart, which contains a high level of xanthine oxidase, a potential source of cytotoxic free radicals. To test whether the retardation of ischaemic myocyte death by verapamil is not an isolated phenomenon in the xanthine oxidase rich heart, we assessed the effect of verapamil in the rabbit heart, which lacks xanthine oxidase. 2. Verapamil (200 micrograms/kg, i.v. bolus plus 40 micrograms/kg per min) was administered in a group of rabbits (n = 5) to test the haemodynamic response to this agent. The heart rate, blood pressure and left ventricular dp/dt max were reduced by 11, 25 and 57%, respectively, and the plasma concentration of verapamil was maintained at 300-400 ng/mL during the infusion. 3. In other groups of rabbits, the effect of the same dosage of verapamil on the size of myocardial infarct after 20 or 30 min ischaemia and 72 h reperfusion was examined. The verapamil was administered for 45 min, starting 15 min prior to ischaemia. The percentage of area at risk infarcted (%I/AAR) was 15.2 +/- 3.9% in the 20 min ischaemia control group and 15.4 +/- 4.5% in the 20 min ischaemia verapamil group, 49.1 +/- 3.4% in the 30 min ischaemia control group and 41.2 +/- 3.3% in the 30 min ischaemia verapamil group. The %I/AAR was significantly smaller in the 20 min ischaemia control groups and 15.4 +/- 4.5% in the 20 min ischaemia there was no difference in %I/AAR between the control and verapamil treated animals in either the 20 or the 30 min ischaemia groups. 4. These results suggest that verapamil does not delay the transition from reversible to irreversible myocardial injury during coronary occlusion in the rabbit, which like the human, lacks myocardial xanthine oxidase.
Adachi
T
T
Second Department of Internal Medicine, Sapporo Medical College, Japan.
Miura
T
T
Noto
T
T
Ooiwa
H
H
Ogawa
T
T
Tsuchida
A
A
Iwamoto
T
T
Goto
M
M
Iimura
O
O
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology*; D009206:Myocardium / Q000201:enzymology*; D011817:Rabbits; D013997:Time Factors; D014700:Verapamil / Q000097:blood / Q000494:pharmacology*; D014969:Xanthine Oxidase / Q000172:deficiency*
D014700:Verapamil; D014969:Xanthine Oxidase