Afferent and efferent components of the cardiovascular reflex responses to acute hypoxia in term fetal sheep.

Abstract

SUMMARY1. We studied the effects of acute isocapnic hypoxia on arterial and central venous pressures, carotid and femoral blood flows and heart rate in intact and carotid denervated fetal sheep between 118 and 125 days gestation, after pre-treatment with either saline, atropine or phentolamine. Electrocortical activity (ECoG) and the incidence of fetal breathing movements (FBM) were also compared between intact and carotid denervated fetuses.2. There were no significant differences between intact and denervated fetuses in any variable measured during normoxia. Soon after the onset of hypoxia a marked bradyeardia occurred in intact, but not in denervated fetuses. Femoral blood flow and femoral vascular resistance (perfusion pressure/femoral blood flow) increased in intact, but not in denervated fetuses. Carotid blood flow increased in both groups of fetuses during hypoxia, but carotid vascular resistance did not change. During hypoxia, the incidence of FBM and low-voltage ECoG was similarly reduced in both groups of fetuses.3. Atropine produced a rise in fetal heart rate during the control period in intact but not in denervated fetuses. At the onset of hypoxia atropine prevented the initial bradycardia seen in intact fetuses. In denervated fetuses a further increase in heart rate occurred throughout the hypoxia.4. All denervated fetuses treated with phentolamine died during the hypoxic challenge, but nine out of fourteen intact fetuses treated with phentolamine survived.5. In intact fetuses which survived hypoxia after treatment with phentolamine, the increase in arterial blood pressure was smaller and the increase in femoral resistance did not occur. In these fetuses a rise in heart rate occurred in hypoxia. Carotid vascular resistance decreased during hypoxia after administration of phentolamine.6. Our results indicate that the initial cardiovascular responses of the late gestation sheep fetus to hypoxia are reflex, and that the carotid chemoreceptors provide the afferent limb of this reflex. The bradyeardia is mediated through a muscarinic pathway, as it is blocked by atropine. The femoral vasoconstriction is MS 9935 D. A. GIUSSANI AND OTHERS mediated through an ac-adrenergic mechanism, mediated both neurally by a carotid chemoreflex and via catecholamines released directly from the adrenal medulla. Both these components are blocked by phentolamine.7. The differences in survival between intact and denervated fetuses during hypoxia after phentolamine suggest that the carotid chemoreflex response to hypoxia involves mechanisms in addition to vagal efferents to the heart and a-adrenergic actions at peripheral blood vessels. These additional mechanisms are as yet undefined, but clearly play an important role in fetal survival during acute episodes of hypoxia.

Effects of chest compressions on cardiovascular and cerebral hemodynamics in asphyxiated near-term lambs

“…If low cardiac output persists despite effective positive pressure ventilation, the newborn is likely to suffer increasingly severe hypoxia and acidemia, leading to hypoxic/ischemic injury. Continued asphyxia further depresses myocardial function, leading to low systolic and diastolic blood pressures despite a chemoreceptor-mediated peripheral vasoconstriction (5,6). Current international neonatal resuscitation guidelines recommend that if heart rate is less than 60 BPM despite effective positive pressure ventilation, CCs should be applied (7,8).…”

Enhanced Umbilical Blood Flow During Acute Hypoxemia After Chronic Umbilical Cord Compression

“…In the remaining 7 fetuses, the occluder cuff was not inflated throughout the duration of the protocol (sham compressed). Between 2 and 7 days after the end of umbilical cord compression or sham compression, 6 UCC and 5 control fetuses were exposed to an episode of acute hypoxemia (induced for 1 hour by alteration of inhaled maternal gases) 3,6,7 either during fetal intravenous infusion with saline (0.9% NaCl at 0.25 mL/min) or during fetal combined intravenous treatment with N G -nitro-Larginine methyl ester (L-NAME) and sodium nitroprusside (the NO clamp: L-NAME, Sigma; 100 mg/kg bolus dissolved in 1 mL saline, injected intravenously, and a 5.1Ϯ2.0 g/kg per minute, meanϮ1 SD, infusion of nitroprusside dissolved in saline; Sigma). The NO clamp is a well-established technique that combines fetal treatment with the NO synthase inhibitor L-NAME with the NO donor sodium nitroprusside to block de novo synthesis of NO while compensating for the tonic production of the gas and thereby maintaining basal cardiovascular function.…”

“…4 In the healthy fetus, survival during acute hypoxemia is promoted through a redistribution of the combined ventricular output away from ancillary and toward essential vascular beds such as the cerebral, myocardial, adrenal, and umbilical circulations. 5 The redistribution of blood flow is partly mediated by peripheral vasoconstriction 5,6 and partly by maintained or increased perfusion of the essential vascular beds through either passive, pressure-dependent changes in blood flow 7 or active vasodilation. 8 -11 In the compromised fetus that has been exposed to a period of cord compression, there is an increase in nitric oxide (NO) activity that overcomes vasoconstrictor influences on the fetal femoral circulation during acute hypoxemia.…”

Variations on fetal heart rate variability

“…During labour, the fetus may be exposed to acute hypoxia during uterine contractions or intrapartum insults, and has well‐established cardiovascular compensatory defence mechanisms, which ideally prevent hypoxic–ischaemic encephalopathy by maintaining perfusion pressure and substrate delivery to essential organs (Giussani et al . 1993). Failure of these compensatory mechanisms results in a progressively worsening metabolic acidosis.…”

“…Using this experimental model, previous studies have shown that acute hypoxia activates both arms of the autonomic nervous system controlling FHR but in favour of vagal dominance and that activation of the sympathetic nervous system (SNS) is key to providing rapid support to increase fetal peripheral vascular resistance and maintain blood pressure despite slowing of the fetal heart rate (Giussani et al . 1993). Further, advancing gestational age (Fletcher et al .…”