Verapamil enhances brain function tolerance against severe hypoxia without enhancing cerebral blood flow in the rat.
In spontaneously breathing, lightly anesthetized rats with chronically implanted epicortical electrodes, tolerance times were measured from onset of progressive hypoxia, anoxia or decapitation, until ultimate apnea and subsequent cessation of brain electrical activities. Arterial and cerebrovenous blood was collected initially and during progressive hypoxia, starting 5 min after intravenous verapamil or NaCl (controls). Verapamil induced significant hyperpnea, arterial alkalosis, slight bradycardia and brain venous acidosis. During progressive hypoxia, hyperpnea persisted and heart rate remained stable for a longer period than in controls. Tolerance times were significantly prolonged. Time courses of arterial PO2 and PCO2 and of cerebrovenous PO2 were hardly influenced. However, arterial alkalosis and brain venous acidosis became highly significant versus control courses. This raised the O2 saturation in arterial and O2 extraction in cerebral venous blood. Sinus sagittalis puncture needle outflow (as a measure of CBF) tended to be below the control rat courses throughout. This led to a higher O2 supply to the brain in verapamil rats only during severe hypoxia. Verapamil did not prolong tolerance times in anoxia or ischemia. It is concluded that the verapamil-induced increase of tolerance to hypoxia is primarily due to the acid-base (Bohr) effects observed in response to hyperpnea and prolonged cerebral metabolic activity.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D002245:Carbon Dioxide / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004562:Electrocardiography; D004567:Electrodes, Implanted; D004569:Electroencephalography; D006339:Heart Rate / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000188:drug therapy*; D008297:Male; D010100:Oxygen / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000627:therapeutic use*
D002245:Carbon Dioxide; D014700:Verapamil; D010100:Oxygen