Biomedical subjects

M A Douse

Publications and source records attributed to M A Douse.

10 recordsLinked to original sources

PubMed1992

Role of upper cervical inspiratory neurons studied by cross-correlation in the cat.

Axonal projections and synaptic connectivity of upper cervical inspiratory neurons (UCINs) were investigated in anaesthetised cats to clarify their role as propriospinal respiratory interneurons. Antidromic mapping showed axonal collaterals near phrenic and intercostal motonuclei. Of the UCINs tested, 37% had collaterals at T3-4; 55% had ipsilateral projections and 45% had contralateral projections. Ipsilateral or contralateral cross-correlations of the activity of pairs of UCINs (one on each side of the spinal cord) with the discharge of internal intercostal, external intercostal (T3-4) or phrenic nerves revealed similar features. Those with the internal intercostal and phrenic nerves were interpreted as evidence for shared or oligosynaptic excitation, those with the external intercostal nerve as shared excitation and inhibition. No evidence for monosynaptic connections was found. Monosynaptic connections could also not be demonstrated between inspiratory intercostal neurons located near (less than 0.5 mm) the UCINs collateral arborizations in T3-4, examined by cross-correlation. Afferent feedback from internal intercostal nerves (T3-4) was investigated by cross-correlating nerve stimulation with UCINs activity. Ipsilateral and contralateral cross-correlograms had similar features, providing evidence for excitation in some cases and inhibition in others. Finally, cross-correlations between ipsilateral UCINs and cervical sympathetic nerves were featureless. The results suggest that the role of UCINs as part of a respiratory propriospinal control system analogous to forelimb motor control is untenable, although they may be part of an intercostal afferent feedback loop.

Action Potentials↗

PubMed1992

Effects of vagotomy on ventilatory responses to CO2 in alligators.

Reptiles increase ventilation during hypercapnia at a constant temperature. In this study, the contributions of vagal vs non-vagal receptors to CO2 ventilatory responses were investigated in 16 sedated Alligator mississippiensis (25 mg/kg pentobarbital; 3 days prior to data collection). Four animals served as controls to assess the effects of time and/or anesthetic drift on ventilation and blood gases; significant ventilatory drift was not detected during the observation period. The effects of bilateral vagotomy on CO2 ventilatory responses were determined during spontaneous breathing (n = 6) and unidirectional ventilation (UDV; n = 6) at two body temperatures (Tb = 30 and 20 degrees C). Resting PaCO2, minute ventilation (VI), tidal volume (VT) and breathing frequency (f) were elevated at 30 degrees C relative to 20 degrees C in spontaneously breathing alligators. Increasing inspired CO2 to 5% increased PaCO2, f, VT and VI at both levels of Tb. Ventilatory sensitivity to CO2 (S = delta VI/delta PaCO2) was higher at 30 degrees C with a temperature coefficient (Q10) of 2.3. Vagotomy increased PaCO2 and VT, decreased f and had no effect on VI at either Tb. After vagotomy, hypercapnia had no effects on ventilation. When CO2 feedback loops were opened by UDV at a high flow rate (greater than 2 L/min), Tb had no effects on ventilatory efforts at constant PCO2, but hypercapnia significantly increased f, VT and VI. S was variable with a Q10 of 2.1. After vagotomy, a significant CO2-ventilatory response remained during UDV, but S was unaffected by Tb (Q10 = 0.8). The results indicate that non-vagal chemoreceptors contribute to CO2 ventilatory responses in alligators, although their contribution following vagotomy is evident only during unidirectional ventilation. Although tentative, the data also suggest that CO2-sensitive vagal receptors may be necessary for the temperature dependency of S.

Alligators and Crocodiles↗

PubMed1992

Episodic breathing in alligators: role of sensory feedback.

The episodic breathing pattern in many reptiles consists of two or more clustered breaths separated by variable non-ventilatory periods. This pattern is commonly postulated to result from oscillations in lung and/or blood PO2 or PCO2 via chemoreceptor feedback. We tested this hypothesis by monitoring breathing pattern in: (1) awake, undisturbed alligators and (2) sedated alligators (approx. 25 mg/kg pentobarbital, i.p.; 3 days prior to data collection). In sedated alligators, measurements were made: (1) before and after bilateral cervical vagotomy, a procedure that removes peripheral arterial chemoreceptors, CO2-sensitive intrapulmonary chemoreceptors and pulmonary stretch receptors (n = 6); and (2) during unidirectional ventilation (UDV) at high flow rates (greater than 2 L/min), thereby minimizing oscillations in lung and blood PO2 and PCO2 (n = 6). Measurements on sedated alligators were made at 30 and 20 degrees C in each of these conditions. In awake, undisturbed alligators, breathing was typically episodic with 2-7 breaths/cluster, although the pattern was easily altered (increased breaths/cluster) by even seemingly minor disturbances. In sedated alligators, episodic breathing was still evident after vagotomy, but only at increased inspired CO2; at 5% CO2 four of six alligators exhibited episodic breathing consisting of 2-3 breaths/cluster interspersed with occasional single breaths. An episodic breathing pattern was also evident during UDV; at low levels of CO2, 2-4 breaths/cluster interspersed with occasional single breaths were evident in four alligators, while two had 6-8 breaths/cluster. Increasing CO2 in the UDV gas stream generally increased the number of breaths/cluster. After vagotomy, all six alligators could manifest an episodic breathing pattern during UDV in at least one CO2 condition (greater than 2 breaths/cluster interspersed with occasional single breaths). The episodic breathing pattern was very labile, sometimes changing to single breaths without apparent cause. The results suggest: (1) episodic breathing requires neither feedback from vagal sensory receptors nor oscillations in respiratory gases; and (2) changes in arterial PCO2 modulate, but do not initiate episodic breathing. Episodic breathing in alligators may be due to complex interactions of higher brain structures with the central rhythm generator.

Alligators and Crocodiles↗

PubMed1992

Projections to Bötzinger expiratory neurons by dorsal and ventral respiratory group neurons.

Bötzinger complex (BOT) augmenting expiratory neuron efferent connection are well established, but little is known concerning the afferent neural projections to BOT. The dorsal (DRG) and ventral (VRG) respiratory groups were extensively searched in 17 pentobarbital anaesthetized cats for inspiratory neurons that were anti-dromically activated from BOT. Only 1 of the 60 VRG inspiratory neurons with confirmed spinal projection was antidromically activated from BOT. Another 3 VRG inspiratory neurons and 4 of the 30 DRG inspiratory neurons were activated from BOT, but none of these neurons had confirmed spinal cord projections. All 15 early burst neurons were antidromically activated from BOT. Neural projections to BOT from DRG and VRG inspiratory neurons are rare, but neural projections from early burst neurons are common.

Afferent Pathways↗

PubMed1991

Time course of temperature effects on arterial acid-base status in Alligator mississippiensis.

Temperature effects on extracellular acid-base status in terrestrial poikilotherms are well known. Comparatively less is known concerning the time course of acid-base responses to prolonged changes in temperature. In this study, two questions were addressed: (1) what is the time course of acid-base responses to a temperature change of 5 days duration in Alligator mississippiensis?; and (2) what are the relative contributions of respiratory vs metabolic (strong ion) processes to the acid-base response? The effects of acute (4-6 h) vs chronic (24-120 h) decreases in ambient temperature from 30 to 20 degrees C were determined on arterial blood gases, acid-base status and plasma electrolyte concentrations ([Na+], [K+] and [Cl-]) in 7 awake alligators. In addition, in vivo and in vitro non-bicarbonate buffer values were determined in 6 anesthetized alligators. Acute decreases in temperature decreased PaCO2 (31 to 18 mmHg) and PaO2 (91 to 50 mmHg), increased pH (7.48 to 7.66), but had no significant effect on plasma bicarbonate concentration ([HCO3-]). Chronic exposure to 20 degrees C had no further effect on any variable. dpH/dT ranged between -0.018 and -0.011 U/degrees C, over the duration of the experiment. Temperature did not alter [Na+] or [Cl-] at any time, and had only minor effects on [K+]. In vivo (11.5 +/- 0.7 mEq/L/pH unit) and in vitro (16.1 +/- 0.9 mEq/L/pH unit) buffer values were significantly different, but neither was affected by temperature. Temperature had no effect on the base excess (estimated with either in vitro or in vivo buffer values), nor on estimates of the strong ion difference. We conclude that pH changes during prolonged exposure to decreased temperature occur rapidly and can be explained by changes in PaCO2, CO2 solubility and pK', without major contributions from metabolic or strong ion adjustments.

Acid-Base Equilibrium↗

PubMed1990

Episodic respiratory related discharge in turtle cranial motoneurons: in vivo and in vitro studies.

An in vitro brainstem-spinal cord preparation from adult turtles was used to study mechanisms underlying the episodic breathing pattern in poikilothermic vertebrates. The preparation (1) generates a stable, episodic burst pattern in cranial motoneuron discharge lasting several days; and (2) is similar to discharge patterns in vivo that are synchronous with respiratory airflow. Episodic breathing in reptiles appears to be intrinsic to the CNS in turtles, and does not require oscillations in afferent feedback.

Action Potentials↗

PubMed1990

Halothane effects on ventilatory responses to changes in intrapulmonary CO2 in geese.

Experiments were conducted to test the hypothesis that halothane anesthesia functionally disrupts CO2-sensitive intrapulmonary chemoreceptors (IPC) in birds. Halothane effects on ventilatory reflexes elicited by changes in lung CO2 without extrapulmonary halothane or CO2 effects were studied in 6 anesthetized (pentobarbital, 30 mg/kg) and unidirectionally ventilated geese. Each lung was independently ventilated. Halothane was added only to gases ventilating the left lung. The left pulmonary artery was occluded to prevent changes in PCO2 or halothane concentration within the left lung from affecting arterial blood. The right lung allowed control of arterial blood gases and was vagally denervated. Left lung CO2 reflexes were observed at different levels of halothane concentration between 0 and 2% while arterial PCO2 and PO2 were held constant. Higher levels of chemical drive were necessary to initiate ventilatory movements in geese (PACO2 = 40-60 mmHg) relative to previous reports on chickens using similar experimental procedures (PaCO2 less than or equal to 30 mmHg). The amplitude of sternal movements or respiratory amplitude (RA) increased as left lung PCO2 increased from 6 to 55 mmHg, and then reached a plateau. Adding halothane (1 or 2%) to the left lung increased RA through a limited range of PCO2, but had no effect on its maximum value. Neither CO2 nor halothane in the left lung had any effect on respiratory frequency. We conclude that halothane impairs lung CO2 reflexes largely due to its effects on IPC since intrapulmonary halothane augments ventilatory activity at low, but not high intrapulmonary PCO2. Effects of halothane on IPC may play a role in the unique ventilatory effects of halothane anesthesia in intact, spontaneously breathing birds relative to mammals at equipotent anesthetic levels.

Anesthesia↗

PubMed1990

Receptor interactions in modulating ventilatory activity.

The ventilatory control system utilizes a variety of sensory receptor groups, including chemoreceptors and mechanoreceptors, to provide feedback concerning the status of controlled variables. Most ventilatory responses to altered receptor inputs generally involve a complex interaction between several receptor groups, central integrative mechanisms, and other modulatory inputs (e.g., "state," hormonal, or neurotransmitter status). Because the control system is complex, nonlinear, and dynamic, the ultimate ventilatory response elicited by a given stimulus is not easy to predict based on the reflex effects of individual receptor groups studied in isolation. A full understanding of the role that sensory receptors play in ventilatory control requires information concerning interactions among receptor groups and with other elements of the control system. The complexity of the problem and the lack of a uniform definition of the term "interaction" has hindered research in this area. An interaction is defined as a nonadditive relationship between independent inputs to the system. Within this definition, five domains of interaction are described. 1) Algebraic interactions occur in ventilation and/or its components because of their multiplicative and nonlinear relationship. 2) Closed-loop interactions occur because of the prevalence of feedback loops within the respiratory control system. 3) Neural interactions reflect central nervous system integration of simultaneous receptor inputs and are demonstrated when feedback loops are opened. Three subdomains of neural interactions are defined: modulatory, dynamic, and range-specific neural interactions. 4) Mechanical interactions result from nonlinear transformations of motoneuron output into mechanical actions. 5) Adaptive interactions occur when paired receptor or modulatory inputs alter future responses. To understand the role of any sensory receptor group in ventilatory control, it is necessary to define its interactions with other control system elements in each of these domains. Understanding the mechanisms of these interactions requires detailed information about the physical system subserving ventilatory control (mechanics and gas exchange) and the relevant properties of the neural network coordinating their actions.

Adaptation, Physiological↗

PubMed1989

Temperature effects on pulmonary receptor responses to airway pressure and CO2 in Alligator mississippiensis.

The effects of body temperature (Tb) on pulmonary stretch receptor (PSR) and CO2-sensitive intrapulmonary chemoreceptor (IPC) response characteristics may have important effects on ventilatory control in reptiles. In this study, three questions were addressed: (1) what are the effects of Tb on PSR and IPC responses to airway pressure (Paw) and lung CO2 (PCO2); (2) what are the effects of acute (less than 12 h) vs chronic (greater than 1 week) changes in Tb on both receptor groups; and (3) can predicted changes in the fractional dissociation of imidazole (alpha im), calculated via independent changes in Tb and PCO2, explain the CO2-sensitivity of either IPC or PSR? Single fiber PSR and IPC responses to Paw, PCO2 and Tb were determined in 11 anesthetized Alligator mississippiensis (pentobarbital; 30 mg/kg), acclimated at 20 degrees C (N = 5) or at 30 degrees C (N = 6). PSR activity increased as Paw increased at both Tb, but PSR activity and sensitivity to Paw were lower at 20 degrees C. The average Q10 was 2.1. Increasing inhaled CO2 from 1 to 7% decreased PSR activity by 27 +/- 6% at 20 degrees C and 18 +/- 5% at 30 degrees C. IPC activity decreased as PCO2 increased at both Tb, but IPC activity and sensitivity were reduced at 20 degrees C. The average Q10 was 3.2. Increasing Paw from 2 to 10 cm H2O had inconsistent effects on IPC activity. There were no differences between the effects of acute or chronic changes in Tb on either PSR or IPC responses. Predicted changes in alpha im could not explain the CO2-sensitivity of either IPC or PSR. We conclude that PSR and IPC adapt rapidly to Tb changes. The larger Q10 of IPC suggests that the relative role of IPC vs PSR in ventilatory control may be greater at elevated body temperatures.

Alligators and Crocodiles↗

PubMed1988

Temperature effects on CO2-sensitive intrapulmonary chemoreceptors in the lizard, Tupinambis nigropunctatus.

Body temperature (Tb) effects on CO2 responses of 17 intrapulmonary chemoreceptors (IPC) were investigated in 9 anesthetized (pentobarbital; 30 mg/kg) and unidirectionally ventilated tegu lizards (Tupinambis nigropunctatus). At 30 degrees C, all IPC (n = 15) had a stable discharge pattern. At 20 degrees C, IPC discharge (n = 14) was stable at high PCO2 but irregular at low PCO2 and often (10/14) consisted of bursts of activity separated by one or more seconds of quiescence. Responses of IPC to static and dynamic changes in PCO2 were quantified at both Tb and the discharge rate vs PCO2 response curves were compared. Static discharge frequency (fSTAT) decreased as PCO2 increased at both Tb. At 20 degrees C: (1) fSTAT was diminished at all PCO2 levels relative to 30 degrees C; and (2) the slope of the fSTAT vs PCO2 relationship was markedly attenuated. The Q10 was 3.7 +/- 0.5 and was independent of PCO2. The peak discharge associated with a step decrease in PCO2 (dynamic response; fDYN) also decreased as PCO2 increased. At 20 degrees C: (1) fDYN was diminished at all PCO2 levels relative to 30 degrees C; but (2) the slope of the fDYN vs PCO2 relationship was similar at both Tb. The Q10 was 2.6 +/- 0.3 and was significantly less than the Q10 of fSTAT (P less than 0.05). Acute changes in Tb exert large effects on the CO2 response and discharge pattern of IPC; these effects on IPC may be important in ventilatory control at different Tb in lizards.

Animals↗