Adrenoceptor blockade modifies regional cerebral blood flow responses to hyperbaric hyperoxia: protection against CNS oxygen toxicity

Exposure to extreme hyperbaric oxygen (HBO2) > 5-6 atmospheres absolute (ATA) produces baroreflex impairment, sympathetic hyperactivation, hypertension, tachycardia, and cerebral hyperemia, known as phase II, culminating in seizures. We hypothesized that attenuation of the effects of high sympathetic outflow would preserve regional cerebral blood flow (rCBF) and protect against HBO2-induced seizures. To explore this possibility, we tested four adrenoceptor antagonists in conscious and anesthetized rats exposed to HBO2 at 5 and 6 ATA, respectively: phentolamine (nonselective alpha(1) and alpha(2)), prazosin (selective alpha(1)), propranolol (nonselective beta(1) and beta(2)), and atenolol (selective alpha(1)). In conscious rats, four drug doses were administered to rats before HBO2 exposures, and seizure latencies were recorded. Drug doses that provided similar protection against seizures were administered before HBO2 exposures in anesthetized rats to determine the effects of adrenoceptor blockade on mean arterial pressure, heart rate, rCBF, and EEG spikes. All four drugs modified cardiovascular and rCBF responses in HBO2 that aligned with epileptiform discharges, but only phentolamine and propranolol effectively increased EEG spike latencies by similar to 20 and 36 min, respectively. When phentolamine and propranolol were delivered during HBO2 at the onset of phase II, only propranolol led to sustained reductions in heart rate and rCBF, preventing the appearance of epileptiform discharges. The enhanced effectiveness of propranolol may extend beyond beta-adrenoceptor blockade, i. e., membrane stability and reduced metabolic activity. These results indicate that adrenoceptor drug pretreatment will minimize the effects of excessive sympathetic outflow on rCBF and extend HBO2 exposure time. NEW & NOTEWORTHY Blocking adrenergic receptors with phentolamine (nonselective alpha(1) and alpha(2)), prazosin (selective alpha(1)), propranolol (nonselective beta(1) and beta(2)), and atenolol (selective beta(1)) modified cardiovascular and regional cerebral blood flow (rCBF) responses in hyperbaric oxygen (HBO2) at 6 atmospheres absolute (ATA); however, only phentolamine and propranolol extended EEG spike latencies. When these two agents were delivered at the onset of sympathetic hyperactivation, only propranolol reduced heart rate and rCBF throughout the exposure and prevented epileptiform discharges. These data validate the strong role of adrenergic control of cardiovascular function and rCBF in extreme HBO2 and the potential use of antiadrenergic drugs to prevent seizures.