Mechanism of the attenuated cardiac response to beta-adrenergic stimulation in chronic hypoxia

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Abstract
A blunting of chronotropic and inotropic responses of the heart to .beta.-adrenergic stimulation occurs following chronic exposure to hypobaric hypoxia. To pursue the mechanism(s) involved, observations were made in 6 intact, conscious goats at sea level and in another 6 goats maintained in a decompression chamber at 445 Torr (.apprx. 4300 m) for 10 days (.hivin.PaO2 [O2 arterial partial pressure] = 43 Torr). No significant group differences in cardiac frequency and various indices of myocardial performance were demonstrable before or after cholinergic blockade with i.v. atropine methyl bromide, 1 mg/kg. Following hemodynamic studies, thoracotomies were performed, and full-thickness biopsies were obtained from the free wall of each cardiac chamber. Neither monoamine oxidase activity nor norepinephrine level of any region of the heart was altered by chronic hypoxia. However, a 2-fold increase (P < 0.001) in catechol O-methyltransferase activity above sea-level values was found in the atria and ventricles of hypoxic animals. Attenuation in cardiac responsiveness to .beta.-adrenoceptor stimulation in chronic hypoxia appears unrelated to vagal activity level, but may be attributable to enhanced enzymatic inactivation of catecholamines.