Browsing by Author "Moskvin, Alexander N"

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    Adrenoceptor blockade modifies regional cerebral blood flow responses to hyperbaric hyperoxia: Protection against CNS oxygen toxicity.
    (Journal of applied physiology (Bethesda, Md. : 1985), 2018-07-19) Gasier, Heath G; Demchenko, Ivan T; Zhilyaev, Sergei Yu; Moskvin, Alexander N; Krivchenko, Alexander I; Piantadosi, Claude A
    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 2), prazosin (selective α1), propranolol (nonselective β1 and 2) and atenolol (selective β1). In conscious rats, 4 drug-doses were administered to rats prior to 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 pre-treatment will minimize the effects of excessive sympathetic outflow on rCBF and extend HBO2 exposure time.
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    Baroreceptor afferents modulate brain excitation and influence susceptibility to toxic effects of hyperbaric oxygen.
    (Journal of applied physiology (Bethesda, Md. : 1985), 2014-09) Demchenko, Ivan T; Gasier, Heath G; Zhilyaev, Sergei Yu; Moskvin, Alexander N; Krivchenko, Alexander I; Piantadosi, Claude A; Allen, Barry W
    Unexplained adjustments in baroreflex sensitivity occur in conjunction with exposures to potentially toxic levels of hyperbaric oxygen. To investigate this, we monitored central nervous system, autonomic and cardiovascular responses in conscious and anesthetized rats exposed to hyperbaric oxygen at 5 and 6 atmospheres absolute, respectively. We observed two contrasting phases associated with time-dependent alterations in the functional state of the arterial baroreflex. The first phase, which conferred protection against potentially neurotoxic doses of oxygen, was concurrent with an increase in baroreflex sensitivity and included decreases in cerebral blood flow, heart rate, cardiac output, and sympathetic drive. The second phase was characterized by baroreflex impairment, cerebral hyperemia, spiking on the electroencephalogram, increased sympathetic drive, parasympatholysis, and pulmonary injury. Complete arterial baroreceptor deafferentation abolished the initial protective response, whereas electrical stimulation of intact arterial baroreceptor afferents prolonged it. We concluded that increased afferent traffic attributable to arterial baroreflex activation delays the development of excessive central excitation and seizures. Baroreflex inactivation or impairment removes this protection, and seizures may follow. Finally, electrical stimulation of intact baroreceptor afferents extends the normal delay in seizure development. These findings reveal that the autonomic nervous system is a powerful determinant of susceptibility to sympathetic hyperactivation and seizures in hyperbaric oxygen and the ensuing neurogenic pulmonary injury.