Cerebral acidosis in focal ischemia: II. Nimodipine and verapamil normalize cerebral pH following middle cerebral artery occlusion in the rat.
The effects of prostacyclin, nimodipine, and verapamil on local cerebral pH (LCpH) and CBF (LCBF) in middle cerebral artery (MCA)-occluded rats were compared with those in controls and others receiving nimodipine carrier. LCpH and LCBF were determined simultaneously by a double-label autoradiographic technique. The infusions were intravenous, started 15 min following the occlusion, and ended at decapitation 4 h postocclusion. The dosages were 0.5 micrograms/kg/min for nimodipine, 40 micrograms/kg/min for verapamil, and 5 ng/kg/min for prostacyclin. Cortical LCpH in the MCA territory of control and carrier-infused rats varied between 6.72 +/- 0.05 and 6.76 +/- 0.05 (means +/- SEM). These values were significantly lower than the LCpH in the same structures in the contralateral hemisphere (7.09 +/- 0.06; p less than 0.05). LCBF on the side of occlusion varied between 54 +/- 5 ml/100 g/min for the parietal and 57 +/- 7 ml/100 g/min for the sensorimotor cortex, while on the contralateral side, LCBF in these same structures was 190 +/- 18 and 191 +/- 4 ml/100 g/min, respectively. LCpH was not modified by prostacyclin treatment following MCA occlusion, but the pH in the structures that were acidotic in the controls became indistinguishable from contralateral values in nimodipine- and verapamil-treated animals. In contrast, LCBF was statistically higher than controls in many structures only in rats treated with prostacyclin. This suggested that the correction of LCpH produced by calcium blockers was not related to an effect they had on blood flow. Animals receiving calcium blockers tended to have smaller areas of infarction. These results may have therapeutic implications in cerebral ischemia.
D000138:Acidosis / Q000209:etiology*; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D001921:Brain / Q000378:metabolism; D001927:Brain Diseases / Q000209:etiology*; D002545:Brain Ischemia / Q000150:complications*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002560:Cerebrovascular Circulation; D002561:Cerebrovascular Disorders / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D006863:Hydrogen-Ion Concentration; D008297:Male; D009553:Nimodipine / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000627:therapeutic use
D002121:Calcium Channel Blockers; D009553:Nimodipine; D014700:Verapamil