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Biomedical subjects

G S Mitchell

Publications and source records attributed to G S Mitchell.

13 recordsLinked to original sources
PubMed1992

5-Hydroxytryptophan (5-HTP) augments spontaneous and evoked phrenic motoneuron discharge in spinalized rats.

Experiments on anesthetized, spinalized rats were conducted to determine the effects of systemic 5-hydroxytryptophan (5-HTP) administration on: (1) spontaneous phrenic nerve activity and (2) evoked phrenic responses to short latency, non-serotonergic synaptic inputs elicited by electrical stimulation of lateral funiculus. 5-HTP augmented spontaneous phrenic activity and allowed expression of a second, longer latency evoked response. Both effects were antagonized by methysergide. Our results suggest that spinal serotonin increases the efficacy of synaptic inputs to phrenic motoneurons.

5-Hydroxytryptophan↗
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

Intracarotid norepinephrine infusions inhibit ventilation in goats.

Plasma norepinephrine (NE) increases from rest to exercise during normoxic exercise, and significantly more during hypoxic exercise in goats. To determine carotid body (CB) mediated effects of increased NE on ventilatory control, we investigated ventilatory responses to intracarotid NE infusions in awake, resting goats. NE was infused (0.5-5.0 micrograms.kg-1 x min-1, 2-3 min) into either a CB intact or contralateral CB-denervated carotid artery in both normoxia and hypoxia (FIO2. = 0.11). PRE-infusion measurements of arterial blood gases, blood pressure and pulmonary ventilation (VI) were compared with values 30-45 sec after beginning NE infusions at 1.0 micrograms.kg-1 x min-1. On the CB-intact side, NE infusions decreased VI by an average of 43% (P < 0.05) and increased PaCO2 4.0 +/- 0.3 mmHg (P < 0.05); ventilatory inhibition preceded an increase in arterial blood pressure. NE infusions on the CB-denervated side had no significant effects on VI or PaCO2, but still increased blood pressure to the same level as infusions on the CB-intact side. In hypoxia, NE infusions on the intact side no longer inhibited VI. NE induced VI inhibition in normoxia was similar in magnitude and time course to dopamine induced VI inhibition. Experiments were repeated following administration the alpha-adrenergic receptor antagonist, phenoxybenzamine (1 mg.kg-1, i.v.) the beta-adrenergic receptor antagonist, propranolol (1 mg.kg-1, i.v.) and the D2-dopamine receptor antagonist, domperidone (1 mg.kg-1, i.v.). Phenoxybenzamine partially blocked NE induced ventilatory depression and domperidone blocked it, but propranolol had no effect. These data indicate that NE inhibits ventilation in goats via effects on carotid chemoreceptors. NE induced inhibition is independent of changes in blood pressure or baroreceptor feedback, and appears to involve both alpha-adrenergic and D2-dopaminergic receptors.

Animals↗
PubMed1991

Role of catecholamines and beta-receptors in ventilatory response during hypoxic exercise.

The ventilatory response to moderate exercise in hypoxia is potentiated in goats, decreasing PaCO2 more than in normoxic exercise. We investigated the hypothesis that this potentiation results from a ventilatory stimulus provided by increased levels of circulating catecholamines (norepinephrine and/or epinephrine), acting via beta-receptors. Plasma norepinephrine [NE] and epinephrine [E] concentrations, arterial blood gases and ventilation were measured in normoxia and hypoxia (PaO2 = 34-38 Torr) at rest and during moderate exercise (5.6 kph; 5% grade) in seven female goats. PaCO2 decreased from rest to exercise in normoxia (2.9 +/- 0.7 Torr; P less than 0.01), and decreased significantly more from rest during hypoxic exercise (6.4 +/- 0.6 Torr; P less than 0.01). [NE] increased in both normoxic (1.1 +/- 0.4 ng/ml; P less than 0.05) and hypoxic exercise (2.5 +/- 0.5 ng/ml; P less than 0.01); the [NE] increase in hypoxia was significantly greater (P less than 0.01). [E] increased in normoxic (0.3 +/- 0.1 ng/ml; P less than 0.05) but not hypoxic exercise (0.6 +/- 0.5 ng/ml; P greater than 0.2). Experiments were repeated following administration of the beta-adrenergic receptor blocker, propranolol (2 mg/kg, i.v.). After beta-blockade, PaCO2 decreases from rest to exercise in normoxia (3.2 +/- 0.7 Torr; P less than 0.01) and hypoxia (8.1 +/- 0.7 Torr; P less than 0.001) were not significantly different from control. The data indicate that beta-adrenergic receptor stimulation is not necessary for a greater decrease in PaCO2 during hypoxic versus normoxic exercise. The greater rise in [NE] suggests a possible role in ventilatory control during hypoxic exercise, perhaps via alpha-adrenergic receptors. However, recent evidence suggests that NE is inhibitory in goats, and that NE is unlikely to mediate extra ventilatory stimulation during hypoxic exercise.

Animals↗
PubMed1979

Ventilatory responses to carbon dioxide inhalation after vagotomy in chickens.

Both vagus nerves in 7 anesthetized chickens were cut midcervically. Inspired PCO2 was increased from 0 to 28 torr by successive 3.5 or 7 torr increments and then increased directly to 70 torr. At each level of PICO2, steady-state measures of PaCO2, [H+]a, VT, f and VE were made. When PICO2 was raised to 7 torr, PaCO2 AND [H+]a were above their control levels (i.e. PICO2 = 0); at each successive level of PICO2, both PaCO2 and [H+]a increased. Minute volume increased at 28 torr PICO2 but changes in VT and f individually were not significant. At 70 torr PICO2, VE and VT increased but f was not changed from its control value. We have previously suggested that CO2-sensitive intrapulmonary chemoreceptors mediate the arterial isocapnic hyperpnea at low PICO2 in chickens. The observation that vagotomy abolishes regulation of PaCO2 at low PICO2 is consistent with this hypothesis, since the afferent pathway of avian intrapulmonary chemoreceptors is predominantly vagal.

Animals↗
PubMed1978

Intrapulmonary and systemic CO2-chemoreceptor interaction in the control of avian respiration.

Experiments on anesthetized chickens were conducted to study interactions between afferent activity from the intrapulmonary and systemic CO2-sensitive chemoreceptors in the generation of respiratory amplitude (RA) and respiratory frequency (f). The thoracoabdominal cavity was opened, air sacs ruptured and each lung independently and unidirectionally ventilated. Intrapulmonary chemoreceptor activity was altered by changing the PCO2 of the ventilatory gas (PICO2) to the vascularly isolated right lung (VIL); systemic chemoreceptor activity was altered by changing the PICO2 to the denervated left gas exchange lung (GEL). Respiratory amplitude and frequency responses to changes in intrapulmonary PCO2 were determined at four levels of systemic arterial PCO2 (PaCO2). The results indicate that elevating PaCO2 shifts the pulmonary CO2-response curves for both RA and f to the left and increases the sensitivity of the RA-CO2 response curve but decreases the sensitivity of the f-CO2 response curve. We conclude that (1) interaction occurs between intrapulmonary and systemic afferent activity in the generation of RA and f, (2) the nature of the interaction is synergism with respect to RA and interference with respect to f, and (3) the interaction is greater during hypocapnia than hypercapnia.

Animals↗
PubMed1978

Avian intrapulmonary chemoreceptors: respiratory response to a step decrease in PCO2.

The contribution of intrapulmonary chemoreceptors (IPC) to the respiratory response, following a step decrease in PICO2 was assessed in anesthetized and unidirectionally ventilated chickens. Step changes in the PCO2 of the ventilatory gas (PICO2) to a single lung were introduced with PICO2 to the contralateral lung held constant. Respiratory amplitude and frequency were monitored. Experimental series were conducted under conditions such that (I) both systemic chemoreceptors and IPC, (II) systemic chemoreceptors alone and (III) IPC alone contribute to the ventilatory response. The results indicate (1) that a rapid component of the transient response (complete in 25 sec) is eliminated by sectioning the pulmonary nerves (Series II), and (2) within the rapid component, a localized minimum in respiratory amplitude was observed which was not seen in either Series II or Series III experiments. We conclude that the rapid component of the transient response is due to the CO2-sensitive IPC and that intrapulmonary and systemic chemoreceptors are not simply additive in the generation of respiratory amplitude and frequency, but a more complex interaction must be involved.

Animals↗
PubMed1977

Ventilatory responses to CO2 in the chicken: intrapulmonary and systemic chemoreceptors.

The independent effects of pulmonary and arterial Pco2 on respiratory amplitude (RA) and respiratory frequency (f) were studied in unidirectionally ventilated chickens anesthetized with phenobarbital (160 mg-kg-1). Pulmonary Pco2 was set by the level of PIco2 ventilating the vascularly isolated right lung (VIL), whereas the systemic arterial Pco2 was set by the level of PIco2 ventilating the denervated left or gas exchange lung (GEL). The following results were obtained: 1) Increasing the PIco2 to the VIL from 0 to 35 torr and maintaining Paco2 constant at 2. torr increased RA from apnea to 76% of the animals' maximal hypercapnic response and decreased f: further increases in PIco2 to VIL had only minimal effects on RA and f. 2) increasing Paco2 from 19 to 61 torr and maintaining pulmonary Pco2 constant increased RA and decreased further increases in Paco2 had only slight effects on RA ulmonary chemoreflex and can dominate the control of RA during hypocapnic conditions, and (2) systemic CO2-sensitive chemoreceptors dominate the control of RA during hypercapnic conditions. It is suggested that the intrapulmonary chemoreceptors may act as a sensory system which plays a pertinent role in the regulation of parabronchial ventilation.

Animals↗
PubMed1977

Regulation of arterial PCO2 during inhalation of CO2 in chickens.

Since CO2-sensitive intrapulmonary chemoreceptors have been shown to exist in the avian lung, we conducted a series of experiments to determine if birds could regulate PaCO2 when confronted with an inspired CO2 load. Chickens were anesthetized with either pentobarbital (30 mg.kg-1) or phenobarbital (160 mg.kg-1). The PICO2 was either increased or decreased in successive 7 torr steps between 0 and 35 torr. At each level of PICO2, steady-state measurements of PaCO2, PaO2 and [H+]a were made. In three of ten experiments, tidal volume and respiratory frequency were determined and minute ventilation calculated. Our results indicate that as PICO2 is varied between 0 and 21 torr, minute ventilation increases and arterial homeostasis of PCO2 and [H+] is maintained; as the PICO2 is increased above 21 torr, PaCO2 increases. We conclude that the isocapnic hyperpnea associated with inhalation of CO2 in chickens is a CO2-coupled phenomenon and that it is mediated by CO2-sensitive intrapulmonary chemoreceptors.

Animals↗
PubMed1977

The Age/Sex Register: estimation of the practice population.

Determination of the number of patients served by a family practice is important for health services delivery and research. A sound estimate of the practice population should enhance the patient management responsibilities of the family physician. This methodology uses the Age/Sex Register to provide a series of estimations of a "teaching" unit population. Results of a sample survey indicate that 21.3% of "inactive patients" (those who have not received services from the practice in two years) still consider themselves under the care of the practice. Replication of this approach is suggested for other practices to improve planning and resource allocation.

Age Factors↗