Adrenoceptor blockade modifies regional cerebral blood flow responses to hyperbaric hyperoxia: protection against CNS oxygen toxicity
Abstract
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 HBO2at 5 and 6 ATA, respectively: phentolamine (nonselective α1and α2), prazosin (selective α1), propranolol (nonselective β1and β2), and atenolol (selective β1). In conscious rats, four drug doses were administered to rats before HBO2exposures, and seizure latencies were recorded. Drug doses that provided similar protection against seizures were administered before HBO2exposures 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 HBO2that 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 HBO2at 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 HBO2exposure time.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 01, 2018
- Source ID
- 10.1152/japplphysiol.00540.2018
Entities
People
- Alexander I. Krivchenko
- Alexander N. Moskvin
- Claude A. Piantadosi
- Heath G Gasier
- Ivan T. Demchenko
- Sergei Yu Zhilyaev
Organizations
- Duke University
- Office of Naval Research
- Russian Academy of Sciences
- Uniformed Services University of the Health Sciences