Time course of cardiovascular neural regulation during programmed 20-sec apnea in rats

Objectives: Long-term hypoxia results in hemodynamic breakdown in patients in the intensive care unit; however, intermittent hypoxia causes hypertension in individuals with sleep apnea. The objective of this study was to explore the sequential cardiovascular neural alterations in response to acute hypoxic apnea. Design: The authors conducted a prospective, randomized animal study. Setting: The study was conducted in a university animal laboratory. Methods: A programmable apnea model was developed in anesthetized rats, in which a 20-sec period of apnea was produced and subsequently divided into the early (2.0 to 7.9 secs), middle (8.0 to 13.9 secs), and late apneic phases (14.0 to 19.9 secs) and immediate reventilatory phase (20.0 to 25.9 secs). Results: Evident hypoxia developed during 20-sec apnea. Arterial pressure increased in the early apneic phase and returned to control level in the middle phase. Significant hypotension developed in the late apneic phase and deteriorated in the reventilatory phase. Interbeat interval increased mildly along the apneic event. The increase of pressure in the early and middle phases was inhibited by propranolol (1.0 mg/kg intravenously [iv]) but was provoked by phentolamine (2.5 mg/kg iv). The decrease of pressure in the late and reventilatory phases was reversed, at least in part, by phentolamine. Atropine (0.5 mg/kg iv) did not produce discernible effects in the arterial pressure. The increase of interbeat interval was suppressed by propranolol. Power spectral analysis of arterial pressure variability demonstrated significant increases of the low-frequency (sympathetic vasomotor activity) and normalized high-frequency (cardiac sympathetic modulation) power after reventilation. Conclusion: Although the sympathetic activity is excited during and after a hypoxic apnea, the immediate pressor effect is related to an inotropic response of cardiac sympathetic regulation, whereas the negative chronotropic and subsequent depressor effect is associated with a failure in the cardiovascular response to sympathetic excitation.