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

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 α₁ and α₂), prazosin (selective α₁), propranolol (nonselective β₁ and β₂), and atenolol (selective β₁). 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 ~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 β-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 α₁ and α₂), prazosin (selective α₁), propranolol (nonselective β₁ and β₂), and atenolol (selective β₁) 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.