Effects of vagotomy on cardiovascular response to periodic apneas in sedated pigs

Abstract

Slamowitz, D., L. Chen, and S. M. Scharf. Effects of vagotomy on cardiovascular response to periodic apneas in sedated pigs. J. Appl. Physiol. 86(6): 1890-1896, 1999There are few studies investigating the influence of vagally mediated reflexes on the cardiovascular response to apneas. In 12 sedated preinstrumented pigs, we studied the effects of vagotomy during apneas, controlling for apnea periodicity and thoracic mechanical effects. Nonobstructive apneas were produced by paralyzing and mechanically ventilating the animals, then turning the ventilator off and on every 30 s. Before vagotomy, relative to baseline, apnea caused increased mean arterial pressure (MAP; ϩ19 Ϯ 25%, P Ͻ 0.05), systemic vascular resistance (SVR; ϩ33 Ϯ 16%, P Ͻ 0.0005), and heart rate (HR; ϩ5 Ϯ 6%, P Ͻ 0.05) and decreased cardiac output (CO) and stroke volume (SV; Ϫ16 Ϯ 10% P Ͻ 0.001). After vagotomy, no significant change occurred in MAP, SVR, and SV during apneas, but CO and HR increased relative to baseline. HR was always greater (ϳ14%, P Ͻ 0.01) during the interapneic interval compared with during apnea. We conclude that vagally mediated reflexes are important mediators of the apneic pressor response. HR increases after apnea termination are related, at least in part, to nonvagally mediated reflexes. apnea; vagus; hemodynamics OBSTRUCTIVE SLEEP APNEA is a relatively common clinical condition in which upper airway collapse and cessation of airflow produce an acute cardiovascular response, including elevations in blood pressure as well as changes in heart rate and ventricular function (3,24,26). In general, cardiovascular variables fluctuate during the apnea-interapnea periods because of mechanical alterations and reflex changes in autonomic tone. Reflex effects leading to changes in autonomic tone may be activated through 1) changes in thoracic mechanics from obstructed respiratory efforts (4), 2) changes in blood-gas tensions (hypoxia and/or hypercapnia) (12, 18), and 3) postapneic arousals. These factors ultimately culminate in an increase in sympathoadrenal tone (9, 13), which is associated with a pressor response during the apnea and postapnea periods. Studies to date have focused mainly on the relative effect of these physiological alterations with regard to the overall cardiovascular response to apneas. However, few studies have examined specific autonomic pathways mediating this response. In particular, little is known about the relative contribution of vagal traffic in the modulation of the sympathetic response. The vagus nerve could play a prominent role in the cardiovascular response to apneas because of afferent and/or efferent autonomic signals carried within the nerve. Sensory afferent signals from aortic receptors (baroreceptors and/or chemoreceptors) or mechanoreceptors carried via the vagus could be responsible for the augmentation in sympathetic tone during apneas (1, 25). In addition, mechanoreceptor afferents carried via the vagus could increase sympathetically mediated responses through an arousal mechanism (11,14)....

Effects of aortic nerve on hemodynamic response to obstructive apnea in sedated pigs

“…5). We have previously presented evidence that the depression in cardiac output and stroke volume results from increased left ventricular afterload (increased MAP) that is associated with vasoconstriction during apnea (3)(4)(5)(6)23), an explanation consistent with our present findings.…”

“…Nine female Yorkshire farm pigs (weight 18-22 kg) were preinstrumented with an electromagnetic flow probe that was used for later measurement of cardiac output and stroke volume during the data-collection phase (see Data-Collection Phase). The preparation has been reported in detail in previous studies from our laboratory (3)(4)(5)(6)23). In brief, the animals were anesthetized by using ketamine (20 mg/kg im) and xylazine (2 mg/kg im).…”

“…The advantages and limitations of our sedated porcine model have been extensively reviewed previously (3)(4)(5)(6)23). In brief, acute major surgery and anesthesia at the time of data collection are avoided by using sedated and chronically instrumented animals, thus minimizing cardiorespiratory depression.…”

“…A recent study from this laboratory demonstrated that bilateral cervical vagotomy blunted the pressor response to periodic apnea in a sedated porcine model of periodic nonobstructive apneas (23). In that study, it was noted that blunting of the pressor response to apneas could have been due to sympathetic stimulation by vagal afferents.…”

“…Bilateral cervical vagotomy was also performed to evaluate the effects of vagal traffic apart from the aortic nerve. We tested the hypothesis that aortic nerve traffic is responsible for the previously reported depressor effect of vagotomy during apnea (23); that is, that the previously reported effects of cervical vagotomy were primarily due to concomitant section of the aortic nerve.…”