Effect of chronic pulmonary denervation on ventilatory responses to exercise.

To assess the role of intrapulmonary receptors on the ventilatory responses to exercise we studied six beagle dogs before and after chronic pulmonary denervation and five dogs before and after sham thoracotomies. Each exercise challenge consisted of 6 min of treadmill exercise with measurements taken during the third minute at 3.2 km/h, 0% grade, and during the third minute at 5.0 km/h, 0% grade. Inspiratory and expiratory airflows were monitored with a low-dead-space latex mask and pneumotachographs coupled to differential pressure transducers. Both pre- and postsurgery, all dogs exhibited a significant arterial hypocapnia and alkalosis during exercise. Denervation of the lungs had no significant effect on minute ventilation at rest or during exercise, although there was a lower frequency and higher tidal volume in the lung-denervated dogs at all measurement periods. Breathing frequency increased significantly during exercise in lung-denervated dogs but to a lesser magnitude than in the control dogs. The changes that occurred in breathing frequency in all animals were due predominantly to the shortening of expiratory time. Inspiratory time did not shorten significantly during exercise following lung denervation. We conclude from these data that intrapulmonary receptors which are deafferented by sectioning the vagi at the hilum are not responsible for setting the level of ventilation during rest or exercise but are involved in determining the pattern of breathing.

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.

Effects of isoflurane on the baroreceptor reflex.

The baroreceptor reflex has been found to be attenuated during anesthesia, but the effects of the relatively new anesthetic, isoflurane, on baroreflex function have not been examined thoroughly. This study was performed to determine the effects of isoflurane on each component of the baroreceptor reflex arc, including the receptors, afferent and efferent nerve pathways, central integratory centers, peripheral ganglia, and the heart. Baroreflex effects on heart rate initiated by systemic pressure changes were examined in conscious and anesthetized dogs (1.3% and 2.6% isoflurane). The effects on individual components of the reflex arc were determined by examining carotid sinus baroreceptor afferent activity, sympathetic efferent nerve activity, and heart rate response to direct sympathetic and parasympathetic efferent nerve stimulation in anesthetized dogs. Preganglionic and postganglionic nerve activities were recorded simultaneously during baroreflex activation to determine ganglionic effects of isoflurane. Baroreflex-induced changes in heart rate were not depressed significantly until 2.6% isoflurane if blood pressure changes due to anesthetic administration were prevented. Significant decreases in baseline sympathetic efferent nerve activity were found at 1.3% and 2.6% isoflurane, with depression of postganglionic activity significantly greater than preganglionic activity at 2.6% isoflurane, indicating a ganglionic effect of isoflurane. Cardiac chronotropic responses to direct stimulation of sympathetic and vagal fibers were attenuated significantly by isoflurane, with sympathetic stimulation showing the greater sensitivity to the anesthetic. Carotid baroreceptor afferent activity was increased by isoflurane, and this sensitization of the baroreceptors appeared to contribute to the decreased levels of sympathetic tone. Therefore, although isoflurane was found to alter the baroreceptor reflex through its effects at multiple sites of the baroreflex arc, significant depression of the cardiac chronotropic component of the reflex was seen only at 2.6% isoflurane.

Lidocaine and bupivacaine differential blockade of isolated canine nerves.

In vitro studies of pharmacologic actions of local anesthetics are usually performed at room temperature using amphibian nerves exposed to local anesthetics for substantial periods of time. We performed in vitro studies of pharmacologic responses of motor A fibers and sensory C fibers to lidocaine and bupivacaine in clinically effective concentrations using a canine nerve preparation at body temperature with short exposure times to evaluate responses under clinically relevant conditions. Differential blockade of isolated, desheathed phrenic and vagus nerves was achieved with bupivacaine (0.58 mM), C fibers being blocked before A fibers (P less than 0.05). Lidocaine (2.8 mM) did not block A and C fibers differentially.

Pulmonary denervation in the dog.

To produce a chronically lung-denervated animal model, a single-stage surgical procedure was performed on five beagle dogs. A left thoracotomy allowed hilar stripping of the pulmonary contributions to the left vagus nerve and transection of the right vagal trunk. The criterion for denervation was defined as the absence of the Hering-Breuer reflex (HBR). The five denervated dogs (DD) as well as five control dogs (CD) were evaluated for presence of the HBR under pentobarbital sodium (Nembutal, 30 mg/kg) anesthesia. Between the 3rd and 8th wk postsurgery, the HBR was clearly abolished in the DD but present in the CD. By the 12th-14th wk postsurgery, the HBR was again present in the DD. This relatively uncomplicated surgical procedure effectively produced a lung-denervated animal model. However, reinnervation occurred relatively soon, thus demonstrating the importance of regular frequent evaluation of the HBR when using this and any other surgically produced pulmonary denervation model.

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.