The response to hypoxia of arterial chemoreceptors in fetal sheep and new‐born lambs.

Blanco, Carlos E.; Dawes, G. S.; Hanson, Mark A.; McCooke, H. B.

doi:10.1113/jphysiol.1984.sp015229

Cited by 261 publications

(143 citation statements)

References 18 publications

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“…In newborn lambs, an increase in ventilation stimulates pulmonary stretch receptors and thus can counteract the chemoreceptor-induced decrease in heart rate (1 5). However, resetting of the aortic and carotid chemoreceptor bodies after birth, as measured by their nerve activities, has been reported in newborn lambs (9,13). The functional changes underlying the difference in response to hypoxemia between the fetus and the newborn remain to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

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Carotid, Not Aortic, Chemoreceptors Mediate the Fetal Cardiovascular Response to Acute Hypoxemia in Lambs

Bartelds

et al. 1993

Pediatr Res

102

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ABSTRACI'. The fetal cardiovascular response to acute hypoxemia consists of a decrease in heart rate, a variable change in mean arterial pressure, and an increase in peripheral vascular resistance. This response is mediated by the arterial chemoreceptors. To determine whether chemoreceptors in the carotid artery or in the aorta mediate the fetal cardiovascular response to acute hypoxemia, we studied the response to acute hypoxemia in fetal lambs at 125 to 130 d of gestation after selective carotid (six fetuses) or aortic (five fetuses) denervation. One to 3 d after insertion of catheters, hypoxemia was induced by inflating a balloon occluder around the ewe's hypogastric artery or by giving the ewe 95% Nz and 5% 0 2 to breathe. The chemoreflex response was measured as decrease in heart rate per decrease in H b O2 saturation. To validate our results, we also studied the response to chemical stimulation of the chemoreceptors by injection of sodium cyanide into the inferior vena cava. We found that carotid denervation abolished the heart rate and peripheral vascular resistance responses to hypoxemia but that aortic denervation did not. Responses after injection of sodium cyanide were similar.to those seen during acute hypoxemia. We conclude that the carotid chemoreceptors, and not the aortic chemoreceptors, mediate the fetal cardiovascular response to acute hypoxemia. (Pediatr Res 34: [51][52][53][54][55] 1993) Abbreviations AHRIASa02, decrease in heart rate to decrease in oxygen saturation AHRIABP, decrease in heart rate to increase in mean arterial pressure NaCN, sodium cyanideThe fetal cardiovascular response to acute hypoxemia consists of a decrease in heart rate, a variable change in mean arterial pressure, an increase in peripheral vascular resistance, and a redistribution of blood flow (1-3). The changes in heart rate are mediated by arterial chemoreceptors located in the common carotid artery and aortic arch (4-6). Changes in arterial pressure, peripheral vascular resistance, and blood flow redistribution are mediated in part by chemoreceptors, but also by local mechanisms (3). However, whether the carotid or the aortic chemore- Based on studies in fetal lambs, Dawes et al. (7) suggested that the aortic chemoreceptors mediate the response to acute hypoxemia. They also suggested that the carotid chemoreceptors are inactive in the fetal physiologic range (8), although carotid-nerve activity has been recorded in fetal lambs (9). However, all of these experiments were performed in acutely exteriorized fetal lambs, whereas the ewe was given chloralose anesthesia. The effects of exteriorization and anesthesia may have influenced the results.The aim of this study was to determine whether chemoreceptors located in the carotid artery or in the aorta mediate the fetal cardiovascular response to acute hypoxemia. To avoid any effects of exteriorization and anesthesia, we studied the response to hypoxemia in six carotid-and five aortic-chemoreceptor-denervated fetal lambs chronically instrumented in urero at 125 to 13...

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Section: Discussionmentioning

confidence: 99%

“…They also suggested that the carotid chemoreceptors are inactive in the fetal physiologic range (8), although carotid-nerve activity has been recorded in fetal lambs (9). However, all of these experiments were performed in acutely exteriorized fetal lambs, whereas the ewe was given chloralose anesthesia.…”

mentioning

confidence: 99%

Carotid, Not Aortic, Chemoreceptors Mediate the Fetal Cardiovascular Response to Acute Hypoxemia in Lambs

Bartelds

et al. 1993

Pediatr Res

102

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“…The mechanism of this late fall is less clear. Among the possible mechanisms are recruitment of other peripheral chemoreceptor input (Bartelds et al, 1993), a synergistic effect of severe hypercarbia on carotid chemoreceptors (Blanco et al, 1984), a direct effect of ischemia on cardiac pacemaker cells (Gryshchenko et al, 2002), and an activation of the cardioinhibitory Bezold-Jarisch reflex (Aviado and Guevara, 2001;Dawes and Comroe, Jr., 1954). This latter reflex originates from the stimulation of both mechanically and chemically sensitive receptors in the ventricle which can be elicited by coronary ischemia and asphyxia (Thoren, 1972).…”

Section: Discussionmentioning

confidence: 99%

Mild chronic hypoxia modifies the fetal sheep neural and cardiovascular responses to repeated umbilical cord occlusion

et al. 2007

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We have shown that five days of mild hypoxia has significant effects on fetal ECoG activity, heart rate and blood pressure. We now studied if mild prolonged hypoxemia had an adverse effect on the fetal cardiovascular and neural responses to repeated cord occlusion and on the magnitude of neuronal damage. Fetal and maternal catheters were placed at 120 days' gestation and animals allocated at random to receive intratracheal maternal administration of nitrogen (n=8) or compressed air in controls (n=7). Five days after surgery, nitrogen infusion was adjusted to reduce fetal brachial artery pO 2 by 25%. After 5 days of chronic hypoxemia the umbilical cord was completely occluded for 5 minutes every 30 minutes for a total of four occlusions. Data are presented as mean ± SEM and were analyzed by Two Way ANOVA or two sample t test. Nitrogen infusion decreased fetal pO 2 by 26% (20.5±1.7 vs. 14.3±0.8 mmHg) without changing fetal pCO 2 or pH. Pre-existing hypoxia fetuses had a greater terminal fall in heart rate in occlusions II, III and IV, and also had a more severe terminal hypotension in the final occlusion. Pre-existing hypoxia was associated with a greater fall in spectral edge frequency during occlussions from 14.4±0.9 Hz to 6.9±0.4 Hz vs. 13.6±1.64 Hz to 10.6±0.77 Hz in controls, p<0.05. In addition, during the three-day post-occlusion period the contribution of theta and alpha band frequencies to total ECoG activity was significantly lower in the pre-existing hypoxia fetuses (p<0.05). These effects were associated with increased neuronal loss in the striatum (p<0.05). In summary, the cardiovascular and neural response indicate a detrimental effect of preexisting mild hypoxia on fetal outcome following repeated umbilical cord occlusions.

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“…In the 10-day-old lamb, the magnitude of the rapid response to inspired hypercapnic gas, which is mediated by the peripheral chemoreceptors, is small (9,14,50). Calculations based on the data of Carroll et al (14), and our own unpublished data, suggest that within the brief three-to four-breath time span of the ventilatory period of PB in the lamb, only an 8% increase in ventilation is predicted when a CO 2 stimulus similar to that expected during PB is applied (ϳ7 Torr; Ref.…”

Section: Theoretical Modelmentioning

confidence: 99%

Impact of changes in inspired oxygen and carbon dioxide on respiratory instability in the lamb

Wilkinson¹,

Sia²,

Skuza³

et al. 2005

Journal of Applied Physiology

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. Impact of changes in inspired oxygen and carbon dioxide on respiratory instability in the lamb. J Appl Physiol 98: 437-446, 2005. First published October 8, 2004 doi:10.1152/japplphysiol.00532.2004We examined the effect of hypoxia and hypercapnia administered during deliberately induced periodic breathing (PB) in seven lambs following posthyperventilation apnea. Based on our theoretical analysis, the sensitivity or loop gain (LG) of the respiratory control system of the lamb is directly proportional to the difference between alveolar PO2 and inspired PO2. This analysis indicates that during PB, when by necessity LG is Ͼ1, replacement of the inspired gas with one of reduced PO2 lowers LG; if we made inspired PO2 approximate alveolar PO2, we predict that LG would be approximately zero and breathing would promptly stabilize. In six lambs, we switched the inspired gas from an inspiratory oxygen fraction of 0.4 to one of 0.12 during an epoch of PB; PB was immediately suppressed, supporting the view that the peripheral chemoreceptors play a pivotal role in the genesis and control of unstable breathing in the lamb. In the six lambs in which we administered hypercapnic gas during PB, breathing instability was also suppressed, but only after a considerable time lag, indicating the CO2 effect is likely to have been mediated through the central chemoreceptors. When we simulated both interventions in a published model of the adult respiratory controller, PB was immediately suppressed by CO2 inhalation and exacerbated by inhalation of hypoxic gas. These fundamentally different responses in lambs and adult humans demonstrate that PB has differing underlying mechanisms in the two species.Cheyne-Stokes respiration; hypoxia; hypercapnia; sleep apnea syndromes; control of breathing; periodic breathing PERIODIC BREATHING (PB), or Cheyne-Stokes respiration, appears under a wide range of physiological and clinical conditions. It is particularly prevalent during sleep, occurring at sea level in apparently normal-term and preterm infants (22,43), at high altitude in normal adults (27), and after hypoxic exposure in experimental animals (11,21). It also occurs in patients with congestive heart failure (36), with idiopathic central sleep apnea (52), with bilateral brain stem lesions (40), and in periodic obstructive sleep apnea (41). A form of PB can also be found in hibernating animals (7,34).Although it is often assumed that the underlying mechanisms causing PB in infants and adults are similar, in each case involving instability of the chemical control system that regulates breathing, there are some marked differences in the pattern of PB and its responses to changes in inspired gas that remain largely unexplained. For example, in preterm infants, the waxing and waning pattern of PB that is characteristic of the adult is replaced by a more or less abrupt on-off pattern that shows little change in tidal volume during the breathing phase (42); this pattern resembles that seen in hibernating animals (34). Furthermore, although the re...

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The response to hypoxia of arterial chemoreceptors in fetal sheep and new‐born lambs.

Cited by 261 publications

References 18 publications

Carotid, Not Aortic, Chemoreceptors Mediate the Fetal Cardiovascular Response to Acute Hypoxemia in Lambs

Carotid, Not Aortic, Chemoreceptors Mediate the Fetal Cardiovascular Response to Acute Hypoxemia in Lambs

Mild chronic hypoxia modifies the fetal sheep neural and cardiovascular responses to repeated umbilical cord occlusion

Impact of changes in inspired oxygen and carbon dioxide on respiratory instability in the lamb

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