COMPARISON OF PROTECTION BY PROPRANOLOL, BEPRIDIL, VERAPAMIL, AND CAPTOPRIL ON DEPLETING ATP, ADP, AND AMP IN HEART, BRAIN, AND LIVER BY ANOXIA PLUS ISOPRENALINE

Mice were injected with 5 mg/kg isoprenaline 45 min prior to being sub ject to 12 min global anoxia and ATP, ADP, and AMP were assayed in the heart, brain, and liver by reverse phase HPLC with UV detection at 25 4 nm. In myocardium the depletion of ATP by global anoxia was 72.5% of the total and only 7.5% due to the addition of isoprenaline. In the b rain and liver, globally anoxic depletion of ATP was much less; a larg e fraction of ATP depletion was caused by isoprenaline. The depletion of ATP, ADP, and AMP in the heart by anoxia plus isoprenaline was part ially protected by propranolol, and the protection by bepridil, verapa mil, and captopril was weak. In the cerebrum bepridil, propranolol, an d verapamil were potent protectors of ATP and total high energy bonds. Bepridil was the most effective, and its protection against cerebral ischemia was reproduced by limiting the infarcted zone and relieving t he abnormal behavior after occlusion of the middle cerebral artery in rats. In liver all four drugs exerted a mild protection. In summary, i soprenaline is more toxic to the brain and liver in depleting ATP in t he presence of global ischemia and the protection by bepridil against cerebral ischemia is attributed to its dual blocking effect on sodium and calcium channels. (C) 1997 Wiley-Liss, Inc.