Biomedical subjects

H V Forster

Publications and source records attributed to H V Forster.

At least 55 records · Page 3Linked to original sources

PubMed1996

Effects of cooling the ventrolateral medulla on diaphragm activity during NREM sleep.

Dysfunction through cooling of neurons near the ventrolateral medullary (VLM) surface results in apnea in the anesthetized state, whereas similar neuronal dysfunction in the awake state only modestly decreases breathing. The purpose of this study was to investigate effects on breathing, as measured by diaphragm electromyogram (EMGdi), of VLM neuronal dysfunction during NREM sleep, a naturally occurring change in state. In six goats, thermodes for cooling were chronically implanted between the first hypoglossal rootlet and the pontomedullary junction (area M and area S). During wakefulness and NREM sleep, bilateral VLM cooling (thermode temp = 20 degrees C) for 30 sec decreased EMGdi mean activity and minute EMGdi (p < 0.05) and lengthened the time between diaphragm contractions. During NREM sleep, reductions in mean and minute EMGdi during cooling tended to be greater than during waking, but not significantly. However, following carotid body denervation. VLM cooling caused prolonged apnea during NREM sleep but only a brief apnea in the awake state. The data suggest that either intact VLM neuronal mechanisms or intact carotid afferents are necessary for sustained EMGdi activity during NREM sleep.

Animals↗

PubMed1996

Imaging of VMS activity during blood pressure challenges in awake and anesthetized goats.

We examined scattered-light changes in a rostral ventral medullary surface (VMS) area from five goats after blood pressure challenges during waking and halothane anesthesia. Reflected 660-nm images were digitized at 1/s after baseline; intravenous saline; 5, 10, or 15 micrograms/kg phenylephrine administration; or sodium nitroprusside infusion sufficient to lower blood pressure by 50%. Phenylephrine elicited a dose-dependent, blood pressure elevation during both states and a substantial transient reflectance increase (interpreted as activity decline) during anesthesia, but only a minimal, long-latency, slow-reflectance decrease activity increase) during waking. Sodium nitroprusside elicited lowering of blood pressure and decreased reflectance in the rostral site during anesthesia. The magnitude of the reflectance change to depressor challenge increased 30%, and the onset latency shortened during waking. Isolated regions of enhanced reflectance changes appeared during both challenges. Activity in this rostral VMS site differentially responds to blood pressure elevation or lowering, and state markedly alters the responses. We speculate that VMS responses to depressor challenge represent reflex activation of respiratory regions.

Anesthesia, General↗

PubMed1996

Effect of dichloroacetate on PaCO2 responses to hypoxia in awake goats.

To gain insight into the role of cerebral lactic acidosis in the hypoxic ventilatory response, we administered dichloroacetate (DCA) intravenously to inhibit lactic acid production in 7 awake goats (40-70 kg) during 0.5 h of normoxia (inspired O2 fraction = 0.209) and 5 h of poikilocapnic hypoxia (inspired O2 fraction = 0.125). On separate days, these goats were also studied with a continuous saline infusion (18 ml/h iv) during 5 h of normoxia and hypoxia. Arterial PCO2 (PaCO2) did not change during the 5-h normoxic period. During hypoxia, arterial PO2 fell significantly (P < 0.05) with both saline (from 111.3 to 39.0 Torr) and DCA (from 111.8 to 42.0 Torr) infusions. PaCO2 decreased (P < 0.05) during the first 0.5 h of both the saline and DCA hypoxia protocols. The decrease was greater (P < 0.05) during DCA (from 36.5 to 33.5 Torr) than during saline infusion (from 37.7 to 36.3 Torr). With saline infusion, PaCO2 decreased (P < 0.05) by 4.9 Torr between 0.5 and 5.0 h of hypoxia. However, over this period of DCA hypoxia, PaCO2 did not significantly decrease (P > 0.05). We conclude that the enhanced hyperventilation with DCA during acute hypoxia is consistent with brain lactic acidosis depressing breathing. Absence of additional significant hyperventilation after 0.5 h of DCA hypoxia suggests that a time-dependent alleviation of brain lactic acidosis might normally contribute to ventilatory acclimatization to hypoxia.

Acid-Base Equilibrium↗

PubMed1996

Effect on breathing of ventral medullary surface cooling in neonatal goats.

The present study was designed to determine whether neurons near the ventral medullary surface (VMS) that are important to control of breathing in adult mammals are also important to control of breathing in neonates. In 7-day-old goats (n = 22), the VMS was surgically exposed under halothane anesthesia. Stainless steel thermodes (2 x 2 mm) were used to cool (20 degrees C) and thereby create neuronal dysfunction of discrete VMS sites. Bilateral cooling under anesthesia 0-2 or 2-4 mm lateral to the midline between the exit of cranial nerves VI and XII resulted in a reduction (P < 0.05) of breathing and most often in apnea. Cooling caudal or rostral to this area did not have a consistent effect on breathing. In 7-day-old goats (n = 8), 3 x 3-mm thermodes were chronically implanted bilaterally on the VMS surface between the exit of cranial nerves VI and XII. The goats recovered and were studied over several days thereafter. VMS cooling while the goats were awake caused breathing to decrease (P < 0.05), but apnea was never observed. The decrease was less (P < 0.05) than while the goats were anesthetized. After 10 s of cooling, the hypopnea while the goats were awake was uniform during eupnea, hypercapnia, hyperoxia, and hypoxia, but after 10 s of cooling, the decrease was relatively greater (P < 0.05) during hyperoxia and hypercapnia. These effects of VMS cooling are qualitatively the same as in adult goats; thus the data are consistent with mature VMS contribution to the control of breathing in neonatal goats.

Animals↗

PubMed1995

Rostral ventral medullary surface activity during hypercapnic challenges in awake and anesthetized goats.

Regions within the rostral ventral medullary surface (RVMS) play an important role in cardiorespiratory responses to CO2 during anesthesia. Activity within a RVMS area, in which local cooling elicited marked ventilatory and blood pressure reductions, was measured as 660 nm scattered light changes in 5 goats following 5% CO2 challenges during waking and anesthetic states. During wakefulness, hypercapnia elicited a substantial, short latency transient (1-1.5 min) activity increase, followed by a sustained decrease. Stimulus cessation elicited a large and rapid off-transient activity increase which persisted for approximately 20 min. In contrast, during halothane anesthesia, the initial activation was absent, and the later activity decline and off-response were much reduced. We conclude that biphasic RVMS activity responses emerge to CO2 stimulation, and are state-dependent.

Administration, Inhalation↗

PubMed1995

Contribution of acid-base changes to control of breathing during exercise.

The mechanisms mediating the exercise hyperpnea remain controversial; there is no unequivocal evidence that any of numerous proposed mechanisms mediates the hyperpnea. However, a great deal has been learned including the potential role of changes in PCO2, [H+], strong ion differences (SID), weak acids, or any other acid-base component. The contribution of acid-base changes to the hyperpnea during exercise is likely through known or postulated chemoreceptors. Two of these, pulmonary and intracranial chemoreceptors, do not appear critical for the ventilatory adjustments to meet the metabolic demands of exercise. A third, the carotid chemoreceptors, appear to fine-tune alveolar ventilation during exercise to minimize disruptions in arterial blood gases. The role of the fourth chemoreceptors, those within skeletal muscles, is least clear. However, there is evidence that they do contribute to the hyperpnea, and it is quite clear that a muscle chemoreflex contributes to the exercise muscle pressor reflex; thus the contribution of these chemoreceptors to the exercise hyperpnea requires additional study.

Acid-Base Equilibrium↗

PubMed1995

Ventilatory responses to cooling the ventrolateral medullary surface of awake and anesthetized goats.

The ventrolateral medulla (VLM) has been reported to be important as a source of tonic facilitation of dorsal respiratory neurons and as a site critical for respiratory rhythmogenesis. We investigated these theories in awake and anesthetized goats (n = 13) by using chronically implanted thermodes to create reversible neuronal dysfunction at superficial VLM sites between the first hypoglossal rootlet and the pontomedullary junction (area M (rostral) and area S). During halothane anesthesia (arterial PCO2 = 57.4 +/- 4.5 Torr), bilateral cooling (thermode temperature = 20 degrees C) of 60-100% of areas M and S for 30 s produced a sustained apnea (46 +/- 4 s) that lasted beyond the period of cooling. While the animals were awake (arterial PCO2 = 36.0 +/- 1.9 Torr), cooling the identical region in the same goats resulted in a decrease (approximately 50%) in pulmonary ventilation, with a brief apnea seen only in one goat. Reductions in both tidal volume and frequency were observed. Qualitatively similar responses were obtained when cooling caudal area M-rostral area S and rostral area M, but the responses were less pronounced. Minimal effects were seen in response to cooling caudal area S. During anesthesia, breathing is critically dependent on superficial VLM neurons, whereas in the awake state these neurons are not essential for the maintenance of respiratory rhythm. Our data are consistent with these superficial VLM neuronal regions providing tonic facilitation to more dorsal respiratory neurons in both the anesthetized and awake states.

Anesthesia↗

PubMed1995

Effects on breathing of ventrolateral medullary cooling in awake goats.

Our objective was to investigate the role of the ventrolateral medulla (VLM) in the control of breathing during the awake state. In 17 awake adult goats, chronically implanted thermodes were used to cool the VLM and thereby cause reversible neuronal dysfunction in all or portions of the area between the first hypoglossal rootlet and the ponto-medullary junction (so-called area M (rostral) and area S). Within 5 s after the initiation of cooling, 60-100% of areas M and S, pulmonary ventilation (VE) decreased uniformly over conditions of eucapnia, hypercapnia, hypoxia, and exercise (P < 0.05). Between 10 and 20 s of cooling, the reduction in VE was approximately 10% greater during eucapnia and hypercapnia than during hypoxia and exercise (P < 0.05). For the remaining 10 s of cooling and for about 1 min after cooling, VE increased to and above control level. Cooling only rostral area M or only caudal area M-rostral area S affected breathing qualitatively in the same manner as when 60-100% of areas M and S were cooled. However, cooling caudal area S had effects that differed significantly (P < 0.05) from more rostral cooling in that the initial decrease in VE was attenuated and the subsequent increase was accentuated. The initial uniform decreased VE during cooling suggests that superficial VLM nonchemoreceptor neurons facilitate breathing. The subsequent relatively greater effect of cooling during eucapnia and hypercapnia probably reflects dysfunction of chemoreceptor-related neurons that normally stimulate breathing. The stimulation of breathing during the later stages and after cooling may suggest that some VLM neurons inhibit breathing.

Animals↗

PubMed1995

Differential effect of ventrolateral medullary cooling on respiratory muscles of goats.

The objective was to determine whether there is an inhomogeneous response of respiratory muscles during cooling-induced ventrolateral medullary (VLM) neuronal dysfunction in anesthetized and awake goats. Thermodes for cooling were chronically implanted on all or portions of rostral, intermediate, and caudal areas of the VLM of 16 adult goats. Electromyograms (EMGs) were obtained from chronically implanted wires in the diaphragm (di), transversus abdominis (TA), and triangularis sterni (TS) muscles. During some periods of cooling in 9 of 16 anesthetized airway-intubated goats, complete cessation of EMGdi coincided with a reduced yet sustained inspiratory flow. In six awake tracheotomized goats, VLM cooling decreased (P < 0.05) EMGdi duration and minute activity more than inspiratory duration and minute ventilation. Cooling thus decreased activation of the diaphragm more than activation of other respiratory muscles. On the other hand, during VLM cooling in 3 of 10 airway-intact awake goats, cessation of inspiratory flow coincided with sustained EMGdi, suggesting that cooling decreased stimulation of the upper airway muscles more than stimulation of the diaphragm. Finally, VLM cooling in a majority of goats decreased EMGTA and EMGTS more than EMGdi. We conclude that VLM neuronal dysfunction has a differential effect on respiratory muscles of adult anesthetized and awake goats.

Anesthesia↗

PubMed1995

Effect of multiple denervations on the exercise hyperpnea in awake ponies.

In three previously reported studies, we had documented that the normal exercise hyperventilation in ponies is accentuated by carotid body denervation (CBD), not affected by hilar nerve pulmonary vagal denervation (HND), and mildly attenuated by spinal cord ablation of the dorsal lateral columns at L2 (SA). In the present study, we hypothesized that if redundancy of control existed in exercising ponies, then multiple denervations of theoretically important pathways in the same animal might attenuate the ventilatory response to exercise in a way not predictable by the individual lesion experiments alone. There were three major findings in the various combinations of CBD, HND, and SA in ponies during treadmill exercise. First, the combination of CBD with HND or SA resulted generally in an accentuation of the hypocapnia during exercise that was predictable on the basis of CBD alone. However, in one pony that showed a hypercapnic exercise response after SA alone, CBD subsequently caused a greater exercise hypercapnia. Second, HND in a CBD or SA pony did not affect the exercise arterial PCO2 response, which is consistent with previous data showing the lack of an HND effect in otherwise intact ponies. Third, in ponies with all three denervations together, the predominant response was an increase, not a decrease, in the exercise hyperventilation; this increase was greater than that predicted from the individual lesions. We conclude that these data do not provide evidence of redundancy in mechanism for the exercise hyperpnea other than instances of carotid chemoreceptor error sensing when hypercapnia occurs during exercise.

Afferent Pathways↗

PubMed1995

Effect of carotid chemoreceptor denervation on breathing during ventrolateral medullary cooling in goats.

It has been postulated that the so-called area S of the ventrolateral medulla (VLM) integrates peripheral chemoreceptor activity; thus cooling-induced dysfunction of neurons in this VLM area should functionally eliminate carotid chemoreceptor stimulation of breathing. Accordingly, carotid chemoreceptor denervation (CBD) should not alter the breathing effects of VLM neuronal dysfunction. To test this hypothesis in awake goats, chronically implanted thermodes were used to cool the VLM and thereby cause reversible neuronal dysfunction in all or portions of VLM areas M and S. Within 5 s after initiation of cooling approximately 60-100% of areas M and S in (P < 0.05) uniformly over conditions of eupnea, hypercapnia, and hypoxia. Between 10 and 20 s of cooling, the reduction in VI was approximately 10% greater (P < 0.05) during hypercapnia than during eupnea and hypoxia. For the remaining 10 s of cooling and for approximately 1 min after cooling, VI increased to and above control for all conditions. For all conditions, CBD accentuated the depression of VI during cooling, causing VI to decrease (P < 0.05) 10-40% more than before CBD. After CBD, the greatest effect on VI of cooling was again during hypercapnia. Thus the carotid bodies in intact goats appear to sense blood gas errors caused during VLM cooling to minimize the decreases in VI. We conclude that the data from this study do not support the concept that the VLM integrates carotid chemoreceptor activity.

Animals↗

PubMed1995

Effect on breathing of neuronal dysfunction in the caudal ventral medulla of goats.

It has been reported that the caudal ventrolateral medulla (VLM) is important in central chemoreception and the control of breathing. The objective of this study was to determine in adult goats the effects on breathing of neuronal dysfunction of this caudal VLM region (area L; caudal to rostral hypoglossal nerve rootlet). Thermodes were chronically implanted on the VLM to cool neurons and thereby cause neuronal dysfunction. During awake and (halothane) anesthetized states, cooling the caudal VLM for 20 s to 20 degrees C did not alter breathing (P > 0.10). However, between 20 and 30 s of cooling and during recovery from cooling 0-4 mm caudal to the rostral hypoglossal rootlet, there was a 12 (awake) to 25% (anesthetized) increase (P < 0.05) in breathing. This tachypneic hyperpnea was uniform over conditions of eucapnia, hypercapnia, and hypoxia and resulted from reduced inspiratory time that increased frequency. We conclude that in goats inhibitory neurons are located in area L and the lateral caudal ventral medulla.

Anesthesia↗

PubMed1994

Ventral medullary surface activity during sleep, waking, and anesthetic states in the goat.

We examined activity, measured as changes in reflected light, from the surface of a rostral ventral medullary area that is involved in cardiorespiratory control. We collected images during sleep and waking states and during halothane anesthesia in five adult unrestrained goats. During quiet sleep, overall activity increased and overall variability decreased compared with waking levels, whereas rapid eye movement sleep increased variability, and average activity decreased to near-waking levels. Distinct regions of activation and suppression appeared during sleep states. Deep anesthesia decreased activity and minimized variation. We speculate that alterations in rostral ventral medullary surface activity may play a role in state-dependent changes in cardiorespiratory control mechanisms.

Activity Cycles↗

PubMed1994

Diaphragm and lung afferents contribute to inspiratory load compensation in awake ponies.

We determined the effect of pulmonary vagal (hilar nerve) denervation (HND) and diaphragm deafferentation (DD) on inspiratory load compensation. We studied awake intact (I; n = 10), DD (n = 5), HND (n = 4), and DD+HND (n = 7) ponies at rest and during mild (1.8 mph, 5% grade) and moderate (1.8 mph, 15% grade) treadmill exercise before, during, and after resistance of the inspiratory circuit was increased from approximately 1.5 to approximately 20 cmH2O.l-1.s. During the first loaded breath in I ponies at rest, inspiratory time (TI) increased, expiratory time decreased, and inspiratory drive increased. There were minimal changes after the first breath, and inspiratory minute ventilation (VI) and arterial PCO2 did not change (P > 0.10) from control values. On the first loaded breath during exercise, TI increased but inspiratory drive either did not change or decreased from control values. TI and drive increased after the first breath, but the increases were insufficient to maintain VI and arterial PCO2 at control levels. First-breath load compensation remained after DD, HND, and DD+HND, but after DD+HND tidal volume and VI were compensated 5-10% less (P < 0.05) than in I ponies. In all groups inspiratory drive, tidal volume, and VI were markedly augmented on the first breath after loading was terminated with a gradual return toward control. We conclude that diaphragm and pulmonary afferents contribute to but are not essential for inspiratory load compensation in awake ponies.

Animals↗

PubMed1994

Changes in respiratory muscle activity in ponies when end-expiratory lung volume is increased.

The objective of the present study was to determine whether lung and diaphragm afferents contribute to the changes in respiratory muscle activity when end-expiratory lung volume (EELV) is changed in ponies. We studied the responses of the diaphragm and the transversus abdominis (TA) muscles to passive increases in EELV in awake intact (I), diaphragm-deafferented (DD), pulmonary vagal- (hilar nerve) denervated (HND), and DD + HND ponies. Negative pressure of -10 or -20 cmH2O applied around the ponies' torsos [positive transrespiratory (TR) pressure] increased (P < 0.05) EELV in all ponies; the increases were more (P < 0.05) in HND and less (P < 0.05) in DD than in I ponies. In I ponies, positive TR pressure increased (P < 0.05) the rate of rise of the integrated diaphragmatic electromyogram (EMG), reflecting increased drive to the muscle. This increase was less (P < 0.05) in DD and HND than in I ponies. In DD + HND ponies, there was no significant (P > 0.10) change in drive to the diaphragm during positive TR pressure. In I ponies, positive TR pressure increased (P < 0.05) the duration and mean activity of the TA EMG. In HND and DD + HND ponies, the TA EMG was not altered by positive TR pressure. I and DD ponies decreased (P < 0.05) breathing frequency but maintained tidal volume (VT) during positive TR pressure. HND and DD+HND ponies increased breathing frequency (P < 0.05) and decreased (P < 0.05) VT during positive TR pressure. We conclude that, during positive TR pressure when the diaphragm is presumably at a mechanical disadvantage, diaphragm and vagal afferents mediate increased drive to the diaphragm to prevent VT from decreasing. In addition, during positive TR pressure, vagal afferents mediate an increase in duration of TA activity, which minimizes the increase in EELV.

Animals↗

PubMed1994

Comparison of ventilatory responses to sustained reduction in arterial oxygen tension vs. content in awake ponies.

To gain insight into central and peripheral contributions to changes in breathing during hypoxia, we compared effects on breathing of reducing inspired PO2 (hypoxic hypoxia) with reducing arterial O2 content (CaO2) through elevation of carboxy-hemoglobin (COHb) (CO hypoxia). Twelve awake ponies were studied during 1 h of breathing room air followed by 6 h when COHb was increased to 25% and CaO2 was decreased by 17%. When COHb was increased, arterial PCO2 (PaCO2) increased gradually to 1.3 Torr above (P < 0.05) control level between 30 and 45 min of CO exposure. Pulmonary ventilation (VE) decreased (P = 0.09) approximately 1 liter the first 30 min of CO exposure. After approximately 45 min, PaCO2 began to decrease, steadily reaching 1.5 Torr below (P < 0.05) control level by 4.5 h of CO hypoxia. VE did not change significantly after 30 min of elevated COHb. Eight ponies were also studied during 5 h of hypoxic hypoxia (arterial PO2 approximately 40 Torr). PaCO2 decreased 5 Torr (P < 0.05) within 5 min of hypoxia and decreased another 4 Torr (P < 0.05) between 30 min and 5 h of hypoxia consistent with hypoxic ventilatory acclimatization. VE increased (P < 0.05) within 3 min of hypoxic hypoxia but then decreased (P < 0.05; VE roll off) toward control and did not increase significantly with acclimatization. Because CO and hypoxic hypoxia both decrease brain oxygenation but only hypoxic hypoxia increases carotid chemoreceptor activity, we conclude that initial hypoventilation with CO hypoxia and VE roll off with hypoxic hypoxia are consistent with hypoxic ventilatory depression within the brain. In addition, hyperventilation with prolonged CO hypoxia is consistent with a central nervous system mechanism contributing to this phase of hypoxic ventilatory acclimatization in ponies.

Animals↗

PubMed1994

Effect of metabolic rate on ventilatory roll-off during hypoxia.

This study was done to determine 1) whether goats demonstrate the roll-off phenomenon, i.e., a secondary decrease in minute ventilation (VE), after an initial hyperventilation during various levels of hypoxia and, if so, 2) whether roll-off could be due to changes in metabolic rate. We hypothesized that roll-off occurs in the goat during hypoxia but is not due to hypometabolism. To answer question 1, eight unanesthetized adult goats were exposed to 15-20 min of hypoxia at 0.15, 0.12, and 0.09 inspired O2 fraction (FIO2), resulting in 60, 40, and 30 Torr arterial PO2, respectively. Goats were fitted with a face mask connected to a spirometer to measure VE, and arterial blood gas samples were obtained via carotid arterial catheters. Roll-off was seen with 0.15 and 0.12 FIO2, whereas VE steadily increased with 0.09 FIO2. During hypoxia, arterial PCO2 fell 2, 3, and 7 Torr at 0.15, 0.12, and 0.09 FIO2, respectively. In the second series of experiments, nine different goats were exposed to 30 min of 0.12 FIO2. O2 consumption and CO2 production were measured five times during baseline and hypoxia. VE increased to 32% above baseline values after 2 min of hypoxia and then gradually decreased by 18%. Changes in breathing frequency and tidal volume contributed to the roll-off. O2 consumption decreased (P = 0.0029, analysis of variance) and CO2 production increased (P = 0.0027) during hypoxia, although both changes were small (< 7%) compared with the eventual 18% decrease in VE. We conclude that the adult goat demonstrates the roll-off phenomenon during moderate levels of hypoxia. (ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Effect of hypoxia on metabolic rate in awake ponies.

To determine the effect of hypoxia on metabolic rate (VO2) of ponies, on 2 days we studied ponies that were breathing room air for 1 h followed by 5 h of either hypoxic hypoxia (fractional concn of inspired O2 = 0.126) or 5 h of CO hypoxia. Control arterial PO2 was 103 +/- 1.2 Torr, and at 5 min and 5 h of hypoxic hypoxia, arterial PO2 was 53.1 +/- 1.8 and 41.0 +/- 1.8 Torr, respectively. There was a time-dependent hypocapnia and alkalosis during hypoxic hypoxia. During CO hypoxia, carboxyhemoglobin increased to 25% after 30 min and remained constant thereafter. With increased carboxyhemoglobin, arterial PCO2 was 1.3 Torr above (P < 0.05) and 1.5 Torr (P < 0.05) below control levels after 30 min and 3 h, respectively. There were no significant (P > 0.10) changes in VO2 during either hypoxic or CO hypoxia. However, in 50% of the ponies, VO2, pulmonary ventilation, and rectal temperature increased and shivering was evident after 30 min of hypoxia. Peak values of pulmonary ventilation, VO2, and shivering occurred at approximately 2 h with a subsequent return toward control levels. We conclude that, in contrast to smaller mammals, acute hypoxia does not depress VO2 of ponies. The hypermetabolism and hyperthermia during chronic hypoxia in some ponies may reflect a transient failure in thermoregulation.

Animals↗