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Biomedical subjects

R L Coon

Publications and source records attributed to R L Coon.

At least 37 records · Page 2Linked to original sources
PubMed1989

Influence of lung inflation reflex on vascular capacitance in the systemic circulation.

The effects of sustained lung inflation on systemic vascular capacitance (SVC), systemic vascular resistance (SVR), and cardiac sympathetic efferent nerve activity (SENA) were investigated in anesthetized dogs. By use of a total cardiopulmonary bypass, the lungs were inflated to tracheal pressures of 10, 15, and 20 mmHg. Tracheal pressures of 10, 15, and 20 mmHg increased system vascular capacitance by 1.4, 3.1, and 4.3 ml/kg and decreased systemic vascular resistance by 0.11, 0.15, and 0.16 mmHg.kg.min-ml-1, respectively, at low carotid sinus pressure (CSP) of 41 mmHg. SENA showed a concomitant decrease. Bilateral vagotomy attenuated the change in SVR by 69%, SVC by 62%, and SENA by 97% when lungs were inflated to a tracheal pressure of 20 mmHg at a low CSP. These results indicate that lung inflation causes a reflex induced increase in SVC as well as a decrease in both SVR and SENA. The lung inflation reflex is mediated primarily through vagal afferent nerve fibers with a small contribution from other afferent nerve pathways.

Animals↗
PubMed1989

Chronic vascular catheters in growing piglets.

Chronic vascular catheterization of growing piglets is problematic because the animals grow rapidly and disrupt each others catheters when housed together. We successfully maintained chronic arterial and venous catheters in growing piglets for the first two months of life using the Vascular-Access-Port, a totally implantable catheter system. Two Vascular-Access-Ports (one venous and one arterial) were surgically placed in each of ten, 3-7 days-old piglets. Nine piglets survived the perioperative period, and for eight piglets the ports were successfully used for experimental purposes to infuse drugs, monitor arterial blood pressure and obtain blood samples for approximately two months. During this period the piglets averaged an eight-fold increase in body weight. This technique of chronic vascular catheterization is useful for experiments employing conscious, growing animals.

Animals↗
PubMed1988

Left ventricular reflex control of venous return and systemic vascular capacitance in dogs.

The reflex effects of left ventricular distension on venous return, vascular capacitance, vascular resistance, and sympathetic efferent nerve activity were examined in dogs anesthetized with sodium pentobarbital. In addition, the interaction of left ventricular distension and the carotid sinus baroreflex was examined. Vascular capacitance was assessed by measuring changes in systemic blood volume, using extracorporeal circulation with constant cardiac output and constant central venous pressure. Left ventricular distension produced by balloon inflation caused a transient biphasic change in venous return; an initial small increase was followed by a late relatively large decrease. Left ventricular distension increased systemic blood volume by 3.8 +/- 0.6 mL/kg and decreased systemic blood pressure by 27 +/- 2 mmHg (1 mmHg = 133.3 Pa) at an isolated carotid sinus pressure of 50 mmHg. These changes were accompanied by a simultaneous decrease in sympathetic efferent nerve activity. When the carotid sinus pressure was increased to 125 and 200 mmHg, these responses were attenuated. It is suggested that left ventricular mechanoreceptors and carotid baroreceptors contribute importantly to the control of venous return and vascular capacitance.

Animals↗
PubMed1987

Pulmonary depressor reflex elicited by capsaicin in conscious intact and lung-denervated dogs.

A pulmonary depressor reflex has been shown to be elicited in anesthetized cats, dogs, and rats by intravenous injection of capsaicin. The effects observed include apnea, hypotension, and bradycardia with some investigators reporting tachypnea following the apneic period. We investigated the response to a bolus injection of capsaicin (20 micrograms/kg) into the cephalic vein in 11 conscious beagle dogs. Five control dogs underwent sham thoracotomies, and six dogs underwent selective denervation of the lungs. A low dead-space latex rubber mask was used to monitor ventilation, and arterial blood pressure was obtained by catheterizing an exteriorized carotid artery. In four of the five control dogs the observed response was apnea concomitant with hypotension and bradycardia, followed by tachypnea. In five of the six lung-denervated dogs there was a slight tachypnea along with hypertension. It is concluded that the pulmonary depressor reflex can be elicited in conscious dogs by intravenous injection of capsaicin but is absent in lung-denervated dogs.

Animals↗
PubMed1987

Reinnervation of pulmonary stretch receptors.

The Breuer-Hering reflex (BHR) reappears 12-14 wk after surgical lung denervation in beagle dogs (J. Appl. Physiol. 54: 1451-1456, 1983). To demonstrate that this is due to reinnervation of pulmonary stretch receptors, we recorded nerve activity from regenerated branches of the left vagus nerve in five beagle dogs. Ten days postdenervation the BHR was absent, whereas by 19 mo it was clearly present. Multifiber pulmonary afferent activity was observed in all five dogs with single-fiber activity observed in three. Sectioning the right vagus nerve did not alter the BHR, but sectioning all the regenerated branches of the left vagus abolished the reflex. In two additional dogs studied 17 mo postsurgery, recordings were made from few fiber nerve bundles of the left cervical vagus. Nerve activity was increased during gentle stroking of the surface of the left upper and lower lobes, indicating receptive fields in both lobes. These data demonstrate that reinnervation of pulmonary stretch receptors does occur and provides evidence that reinnervation of these receptors is responsible for return of the BHR after pulmonary denervation.

Afferent Pathways↗
PubMed1986

Respiratory arrhythmias and airway CO2, lung receptors, and central inspiratory activity.

The purpose of this study was to determine whether hypocapnia affects heart rate secondary to an effect on pulmonary receptors. Dogs were anesthetized and placed on cardiopulmonary bypass. Interrelationships among airway CO2, central inspiratory activity, and lung receptor effects on respiratory-related heart rate changes (respiratory arrhythmias) were studied after vagal efferent activity was increased secondary to baroreceptor stimulation. Hypocapnia, isolated to the lungs, produced an increase in the magnitude of the respiratory arrhythmias observed. Two mechanisms may produce these results. Hypocapnia affects pulmonary receptors, which 1) reflexly alter heart rate and 2) modulate breathing frequency, thus altering the dynamics of the respiratory arrhythmias that were produced. The results also suggested that the reflex increase in heart rate in response to lung inflation and the Hering-Breuer expiratory-facilitatory reflex are either produced by different pulmonary receptors or by the same pulmonary receptors but may be mediated by different central mechanisms.

Adaptation, Physiological↗
PubMed1986

Arterial hypocapnia during exercise in beagle dogs.

Previous investigators have assumed that during exercise there is a tight coupling of ventilation with CO2 delivery to the lungs such that arterial blood remains isocapnic. We measured arterial blood gases in a group of 10 beagle dogs in which arterial blood sampling could be accomplished via exteriorized carotid artery loops and in six of the same dogs following chronic pulmonary denervation. Samples were taken at rest, at 15-s intervals during the first minute of unrestrained treadmill exercise at 5.0 km/h, 0% grade, and then at 2 and 3 min at the same work load. Mean resting arterial PCO2 for the control dogs was 37.1 Torr. At the onset of exercise arterial PCO2 fell progressively to a nadir of 34.6 Torr during the 30- to 45-s sampling period. Samples at 2 and 3 min remained significantly hypocapnic (PCO2 = 34.8 Torr). The arterial PCO2 and pH responses to exercise in the lung-denervated dogs were not significantly different from those of the control dogs, although arterial PO2 was lower at rest and during exercise following denervation of the lungs. The arterial hypocapnia exhibited in intact beagle dogs at the onset of exercise persists into the steady state and suggests that there is not a tight coupling of ventilation with pulmonary CO2 delivery. The similarity of the response in lung-denervated dogs suggests that intrapulmonary receptors with afferents in the vagi are not the primary mediators of the ventilatory response to exercise.

Animals↗
PubMed1986

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.

Animals↗
PubMed1985

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.

Animals↗
PubMed1984

Systemic arterial pH servocontrolled ventilator simulation of the respiratory control system.

The terminology 'isocapnic hyperpnea' has been used to describe the ability of the respiratory control system to increase ventilation in response to inhalation of low levels of CO2 without an apparent change in the error signal (arterial pH or PCO2). Recently a control system for the systemic arterial pH (pHa) servocontrol of mechanical ventilation has been developed. The combination of proportional and integral control used produced a system by which the desired set point was maintained with virtually a zero steady-state error. The purpose of these experiments was to use this system to produce isocapnic hyperpnea in response to low levels of inspired CO2 and thus to demonstrate how, through integral control, a biological system could produce a particular response without an apparent change in the controlled variable. Adding 1.0 to 3.5% CO2 to the inspired gas of dogs connected to the pHa servocontrolled ventilator produced increases in minute ventilation with little or no change in pHa or PaCO2. Whether such a control system has any relevance to the physiological control system is questionable. It does however allow a unique way of investigating the possibilities by which the physiological system may work.

Animals↗
PubMed1983

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.

Animals↗
PubMed1982

Interrelationships among airway CO2, airway pressure, and breathing frequency.

The breathing frequency response to changes in airway CO2 of a vascularly isolated lobe of the canine lung has previously been shown to be primarily dependent on CO2-mediated changes in airway pressure. This study was carried out to determine what contribution changes in airway pressure make in the whole lung airway CO2-mediated breathing frequency response. Mongrel dogs were anesthetized and placed on cardiopulmonary bypass. Diaphragm electromyogram (EMG) was used to monitor respiratory center output and to trigger ventilation of the lungs. Isoproterenol administered to the lungs prevented hypocapnic airway constriction but only partially blocked the decrease in breathing frequency, suggesting that in the whole lung preparation, airway CO2 in part alters breathing frequency through a direct effect on pulmonary receptors. At constant positive end-expired pressures (1-6 Torr), 0% airway CO2 produced greater increases in expiratory time than 10% CO2. Thus airway CO2 can affect breathing frequency in the absence of CO2-related changes in airway pressure at pressures that would produce lung volumes similar to those observed at end expiration in the intact animal. An argument is presented that the receptors directly affected by CO2 are probably not located in the airways constricted by hypocapnia.

Animals↗
PubMed1981

Location of lung receptors mediating the breathing frequency response to pulmonary CO2.

Pulmonary stretch receptors are thought to mediate the breathing frequency (bf) response to changes in pulmonary CO2. However, the location and distribution of these receptors is disputed. The purpose of this study was to determine what contribution the extrapulmonary receptors make in the pulmonary CO2 bf response. Mongrel dogs were anesthetized and placed on cardiopulmonary bypass. The diaphragm electromyogram was used to monitor respiratory center output and to trigger a ventilator. Exposure of an upper airway segment to CO2 or positive end-expired pressure failed to produce changes in the bf. Denervation of the upper airway down to but not including the hilum caused similar insignificant changes in the CO2 bf response. Lungs collapsed by suction showed minimal Hering-Breuer inhibition when compared with inflated lungs. Bronchial arterial perfusion with hypocapnic followed by hypercapnic blood failed to produce changes in the bf while similar perfusion of the pulmonary arterial system resulted in significant increases in bf. It appears that the receptors mainly responsible for the pulmonary CO2 response are located in the more peripheral regions of the lung.

Animals↗
PubMed1981

Segmental ventricular adjustments to brief periods of ischemia in the dog.

The changes in left ventricular segmented contractile force induced by brief periods of ischemia (15-90 s) and subsequent reperfusions were analyzed in anesthetized dogs. Segmental coronary artery occlusion (left anterior descending or left circumflex) produced a decrease in segmental ventricular function in the occluded area and an increase in contractile force in the myocardial segment away from the occluded area. With reperfusion, a transient overshoot in contractile force above preischemic control levels was observed in the occluded segment. This overshoot was shown not to be dependent on adrenergic mechanisms but appears to indicate changes in calcium permeability.

Animals↗
PubMed1981

Measurement of dead space ventilation using a pHa servo-controlled ventilator.

A control system for the systemic arterial pH (pHa) servo control of mechanical ventilation has recently been developed. If pHa is maintained constant by the change, separation of minute volume into alveolar ventilation and physiological dead space ventilation (VE = fVA VDp) can be manipulated to show that VDp = (VE1 - VE 2)/(f1 - fe) where f1 and f2 are different ventilator frequencies and VE1 and VE2 are expired minute volumes at these frequencies. Also, added dead space can be measured. VDadded = (VE2 - VE1)/f where VE1 and VE2 are the minute volumes before and after the dead space was added. The validity of these equations was tested in the anesthetized dog. The measured added dead space was in close agreement with the volume of dead space which was added and with that measured by another independent method. The measurement of VDp, probably as a result of tidal volume-related changes in VDp, did not agree as well with VDp measured by an independent method.

Animals↗
PubMed1981

Effect of verapamil on pulmonary reflexes in the vascularly isolated canine lung: physiology.

Breathing frequency (BF) may be affected by changes in the percent inspired CO2 administered to vascularly isolated lungs. Pulmonary CO2 probably affects BF, in part, through a secondary effect of CO2 on airway smooth muscle. To further determine the role of pulmonary mechanics in the pulmonary CO2-mediated BF response, Verapamil, a Ca++ blocking agent which blocks hypocapnic airway constriction, was administered to the vascularly isolated lungs of the dog. Verapamil blocked the hypocapnic airway constriction which occurred when pulmonary CO2 was reduced; however, the decrease in BF was not only blocked but in some animals there was an increase in BF. Also, the decrease in BF produced by hyperinflation of the lungs (Hering-Breuer reflex) was either blocked or an increase in BF occurred after administration of Verapamil.

Airway Resistance↗
PubMed1980

Effect of anodal blockade of myelinated fibers on vagal C-fiber afferents.

The effects of monopolar cathodal, monopolar anodal, and bipolar anodal polarizing currents on vagal A- and C-fiber activity were studied in anesthetized dogs. Monopolar cathodal polarization consistently produced excitation of spontaneous and evoked A- and C-fibers. Monopolar anodal and bipolar anodal polarizations differentially blocked A-fibers as a function of fiber diameter. The specific purpose of this study was to compare the effects of monopolar anodal and bipolar anodal currents on C-fiber excitability. Small fiber preparations were dissected from the vagal trunk, cut centrally, and placed on recording electrodes. A constant-current stimulus pulse was applied to the nerve at various distances from the blocking electrodes. The stimulus current strength was increased until an isolated C-fiber spike was observed. This value was defined as 100% of threshold. The stimulus current was then reduced to zero, the blocking current was increased slowly to 100 microA, and the procedure repeated. Threshold data obtained in this manner for each set of stimulation electrodes was plotted as a function of distance from the blocking electrode(s) for both modes of anodal blockade. No significant change in C-fiber excitability was observed with bipolar anodal blockade, whereas excitability was significantly (P less than or equal to 0.05) decreased using the monopolar technique. Thus, monopolar anodal block may reduce the possibility of asynchronous C-fiber discharge, which has been associated with a bipolar block of A-fibers.

Afferent Pathways↗