Effects of chronic right-to-left cardiac shunt on hypoxic sensitivity of mongrel dogs.

Resting ventilation (VI), blood gases, hypoxic sensitivity, and the ventilatory responses to intravenous sodium cyanide (NaCN, 100 micrograms/kg), doxapram (DOX, 500 micrograms/kg), and dopamine (DOPA, 20 micrograms/kg) were analyzed in four normal mongrel dogs (group I-N) and seven mongrel dogs with chronic (5-11 yr) right-to-left cardiac shunt (group II). The group I-N animals were also studied during steady-state isocapnic hypoxia (group I-H). The shunt procedure used for these studies produced a model for ventilatory studies during chronic shunt hypoxemia. The increases in VI per percent decrease in O2 saturation, which occurred during a four-breath N2 test, were 30, 43, and 13 ml X kg-1 X min-1 in groups I-N, I-H, and II, respectively. The decrease in hypoxic sensitivity of the group II animals, compared with groups I-N and I-H, occurred in the presence of an increase in PaCO2 from 21.9 to 26.0 Torr during the four-breath N2 test. A decrease in PaCO2 from 34.7 to 30.0 and from 33.6 to 30.4 Torr was observed in groups I-N and I-H. The response to DOX, a general analeptic agent, was greatest in group II and least in group I-N. However, the ventilatory responses to NaCN and DOPA were not sufficiently different among the three groups to suggest a difference in carotid body function as assessed by these drugs.

Baroreceptor reflex control of heart rate during isoflurane anesthesia in humans.

The effect of isoflurane alone (Group 1) and isoflurane following thiopental (Groups 2 and 3) on baroreflex control of heart rate in humans was investigated in this study. Phenylephrine (the pressor test) and sodium nitroprusside (the depressor test) were used to induce moderate changes in arterial blood pressure and to alter the stimulation of baroreceptor sites. In addition, graded neck suction was employed to examine carotid baroreflex control of heart rate. In Group 3 subjects, phenylephrine was infused continuously during anesthesia to maintain mean arterial blood pressure near control levels. The pressor- and neck-suction-derived baroreflex slopes were decreased progressively from awake to 1.0 and 1.5 MAC isoflurane. The slopes of the depressor responses were decreased at 1.0 MAC but showed little further depression at 1.5 MAC. For each method, the depression of baroreceptor slopes from control to 1.0 MAC and 1.5 MAC was similar among the three groups. Maintenance of arterial blood pressure (Group 3) and the utilization of thiopental (Group 2) did not significantly alter the depression of baroreflex responses during increasing levels of isoflurane anesthesia. Neck suction derived slopes compared favorably with the pressor test slopes (r = 0.75, P less than 0.001). This study indicates that the depression of arterial baroreflex heart rate responses under isoflurane anesthesia are less pronounced than the depression of baroreflex responses noted by other investigators for halothane or enflurane. The neck suction technique appears to be a sensitive method useful in assessing the carotid sinus reflex in awake and anesthetized humans.

Chronic localized hypotension and resetting of carotid sinus baroreceptors. Electrophysiological and histological studies in the dog.

Resetting of carotid sinus (CS) baroreceptors to chronically elevated systemic pressure in hypertension has been demonstrated. The effects of chronic system hypotension on CS baroreceptor afferents has not been elucidated, however. The purpose of the present study was to determine the electrophysiological and histological characteristics of CS baroreceptors exposed to chronic hypotension. Chronic unilateral hypotension was produced by anastomosis of the common carotid artery to the external jugular vein. CS nerve activity and histology of the normotensive sinus (mean CS pressure +/- SD = 96 +/- 10.9 torr) were compared to those of the hypotensive sinus (mean CF pressure 50 +/- 14.2 torr) 44-49 days after anastomosis in nine mongrel dogs. An isolated CS pouch preparation was used to produce standard pressure changes. Threshold pressure for hypotensive sinuses (15.5 +/- 5.19 torr) was significantly less (P less than 0.05) than for normotensive sinuses (40.6 +/- 9.73 torr). Saturation pressure was also significantly less in the hypotensive sinus (P less than 0.05). There were no significant differences between slopes of the stimulus-response curve or in architecture of intima or media of the two sides. Thus, the stimulus-response curve was shifted to the left in chronic CS hypotension, and this effect could not be related to a change in CS light microscopic histology.

Coarctation of the aorta and baroreceptor resetting. A study of carotid baroreceptor stimulus-response characteristics before and after surgical repair in the dog.

We studied baroreceptor function in dogs before and after surgical repair of coarctation of the aorta by direct recording of multifiber carotid sinus (CS) nerve activity (NA) during alteration of pulsatile arterial pressure with systemic phenylephrine and nitroprusside, and during static pressure changes using a CS pouch preparation. Coarctation was induced by banding the proximal thoracic aorta in ten 3- to 5-day old puppies. One and one-half years later, five of these coarctated animals were studied before, and five were studied 3-7 months after, surgical repair. Five adult animals also were studied 4-6 months after the proximal thoracic aorta had been banded. Controls were eight normal adult dogs. Threshold pressure at which NA began, saturation pressure at which NA reached a maximum, and slope (% Max NA/mm Hg) of the linear portion of the stimulus-response curve were determined. Pulsatile manipulations of pressure elicited normal sensitivity (slope) in dogs with coarctation but static nonpulsatile pressure changes showed depressed sensitivity compared to controls. After surgical repair, threshold and saturation returned toward normal; sensitivity determined with static pressure manipulations returned to control value. Coarctation reset CS baroreceptors to operate at higher pressures in both puppies and adult dogs and repair of coarctation returned function toward normal. We conclude that resolution of hypertension after repair of coarctation may depend upon baroreceptor readaptation.

Cardiac, aortic, pericardial, and pulmonary receptors in the dog.

Afferent nerve activity from left and right atrial, left and right ventricular, interventricular septal, papillary muscle, pericardial, aortic and pulmonary vascular receptors was recorded from the left T3 white ramus communicans and the innominate, dorsal, recurrent, ventromedial, craniovagal and caudovagal cardiac nerves in alpha-chloralose-anesthetized dogs. The receptors were localized and the nature of the stimuli required to excite these receptors was also determined. Some ventricular receptors were excited during maximal contraction of the myocardium. Other ventricular and aortic receptors were stimulated by elevation of intracardiac or aortic pressure. The pericardial, atrial, and papillary muscle receptors were excited by stretching the surrounding tissue. The discharge patterns of these receptors were not always synchronous with the events of the cardiac cycle. The stimuli required to excite each type of receptor (ventricular, atrial, etc.) and their resultant discharge patterns were not identical for all of the receptors. Excitation of cardiac receptors with sympathetic afferents resulted in 1--2 spikes per cardiac cycle, whereas receptors with vagal afferents resulted in bursts of spikes per cardiac cycle.

Breathing frequency responses to pulmonary CO2 in an isolated lobe of the canine lung.

Recent studies have indicated that the breathing frequency responses to inspired CO2 in part result from changes in pulmonary stretch receptor activity. Pulmonary CO2 may alter frequency by direct inhibition of stretch receptor discharge, or secondarily, by changes in airway mechanics. The vascularly isolated left lower lobe (LLL) of the canine lung was used to determine the effect of hypocapnic airway constriction on the pulmonary CO2 reflex. The upper and middle lobes of the left lung were removed and the right vagus nerve sectioned. Blood was recirculated through the LLL. Diaphragm electromyogram was used as an index of respiratory center activity and to trigger ventilation of the left lower lobe. Lobar hypocapnia increased peak airway pressure and reduced respiratory rate. However, infusion of isoproterenol or the use of a mechanical overflow system to block the airway pressure response prevented the frequency changes associated with CO2. Although both the direct and mechanical effects of CO2 on stretch receptors may contribute to the reflex, in the LLL preparation the mechanical effects predominate.

Respiratory inhibition with sympathetic afferent stimulation in the canine and primate.

Inhibition of phrenic efferent nerve activity, diaphragm electromyogram (EMG), and external intercostal EMG was observed in halothane- and pentobarbital-anesthetized mongrel dogs and pentobarbital-anesthetized monkeys with stimulation of sympathetic afferents. The central end of the transected ventral limb of the left ansa subclavia, the sympathetic chain, or individual white rami were stimulated while simultaneously recording phrenic efferent nerve activity, diaphragm EMG, or the external intercostal EMG. Averaged phrenic efferent bursts or MEG were used to trigger an electronic respirator. In all of the dogs and monkeys, electrical stimulation of sympathetic afferent pathways resulted in inhibition of phrenic efferent nerve activity, diaphragm EMG, or external intercostal EMG. Although the exact origin of these fibers was not determined, the conduction velocities of these afferents were 4-7 m/s, which places them in the Adelta fiber-type range. The importance of these afferents in the regulation of respiration in the awake animal remains unknown.

Reflex effects of thoracic sympathetic afferent nerve stimulation on the kidney.

Thoracic sympathetic afferents may play a role in the reflex control of renal vascular resistance during hypotension. Mongrel dogs were anesthetized with ketamine hydrochloride and maintained on a 50-50, O2-N2O mixture supplemented with 0.5%-1.0% halothane. Systemic arterial blood pressure was lowered to 50 mmHg with use of a constant pressure hemorrhage technique. The renal circulation was perfused with a constant-flow perfusion system. Low-frequency (3 Hz) stimulation of thoracic sympathetic afferents produced renal vasodilation. A reduction of renal vascular resistance was measured as a decrease in constant-flow perfusion pressure. Vagotomy accentuated the dilator response to stimulation. High-frequency (30 Hz) afferent stimulation produced renal vasoconstriction. Renal efferent nerve activity and renal blood flow responded to afferent stimulation (3 Hz) by transient inhibition of efferent activity and increases in renal blood flow. Afferent stimulation (30 Hz) caused increases in renal efferent nerve activity and decreases in renal blood flow. The thoracic sympathetic afferents carry information from cardiopulmonary structures that alter renal efferent nerve activity and renal hemodynamics during hypotension.