Influence of carotid denervation on the arousal and cardiopulmonary responses to upper airway obstruction in lambs

Experiments were done on five lambs to determine if carotid denervation influences the arousal and cardiopulmonary responses to upper airway obstruction during sleep. Each lamb was anesthetized and instrumented for recordings of electrocorticogram, electro-oculogram, nuchal and diaphragm electromyograms, and measurements of arterial blood pressure and arterial Hb oxygen saturation. A tracheotomy was done and a fenestrated tracheotomy tube placed in the trachea. During the study, a 5 F balloon-tipped catheter was inserted into the tracheotomy tube so that air flow could be obstructed by inflating the balloon. No sooner than 3 d after surgery, measurements were made in quiet sleep and active sleep during control periods when the animal was breathing room air and during experimental periods of upper airway obstruction. Carotid denervation significantly affected the arousal response to upper airway obstruction. Arousal occurred during 14 of 14 epochs in quiet sleep and during 12 of 13 epochs in active sleep before the arterial Hb oxygen saturation decreased to 30%. However, the time to arousal was increased and the arterial Hb oxygen saturation at arousal was decreased in carotid-denervated lambs compared with what we have previously observed in carotid-intact lambs. These data provide evidence that the carotid chemoreceptors and/or carotid baroreceptors play a major role in causing arousal from sleep during upper airway obstruction in lambs. Our results may have implications for sudden infant death syndrome, because it is possible that alterations in the arousal response to respiratory stimuli play a role in sudden infant death.     

Effect of beta-adrenergic receptor blockade on responses to acute hypoxemia in lambs

We studied the effects of beta-adrenergic receptor blockade on general circulatory and metabolic responses to moderate (FIO2 = 0.09) acute hypoxemia in newborn (protocol 1) and 3-wk-old (protocol 2) lambs, and on regional blood flow distribution in newborn lambs (protocol 1). Via a left thoracotomy we placed an electromagnetic flow transducer around the ascending aorta and inserted various vascular catheters. After 2 days of recovery, the lambs were studied. In protocol 1, we measured cardiovascular variables and regional blood flow distribution during control conditions, after 45 min of acute hypoxemia, and after 0.5 mg/kg of propranolol during acute hypoxemia. In protocol 2, we measured cardiovascular variables during control conditions and after 45 min of acute hypoxemia with and without propranolol pretreatment. In both groups, propranolol limited the increase in cardiac output and heart rate caused by hypoxemia, and thus decreased oxygen delivery. However, propranolol also decreased oxygen consumption so that pulmonary arterial pO2 was either higher (protocol 1) or the same (protocol 2) as during acute hypoxemia alone. Neither metabolic acidosis nor hypothermia ensued. In protocol 1, propranolol decreased renal, carcass, and most importantly, myocardial blood flows. However, myocardial O2 consumption also fell, coronary sinus pO2 increased, and blood was redistributed toward the subendocardium, suggesting that myocardial perfusion improved. Thus, beta-adrenergic receptor blockade during acute moderate hypoxemia may have a beneficial effect by reducing total body and myocardial oxygen demand in excess of the reduction in oxygen delivery.     

Desensitization of beta-receptor mediated responses to epinephrine in fetal lambs by prolonged ritodrine administration

During prolonged administration of beta-agonists such as ritodrine directly to chronically cannulated fetal lambs, the cardiovascular, metabolic, and endocrine changes observed during the 1st day of administration, lessen and return to normal within 3-4 d despite continuing drug administration. In our investigation, heart rate, plasma FFA, lactate, glucose, and insulin concentrations all increased significantly during the 1st day of ritodrine infusion (10 micrograms/min), whereas blood PO2 and base excess were significantly decreased. After 3 d, despite continued drug infusion, all these changes had ameliorated. To examine the hypothesis that this tachyphylaxis to ritodrine also results in decreased sensitivity to endogenous catecholamines, epinephrine (1 microgram/min i.v. for 60 min, then 2 micrograms/min i.v. for a further 60 min) was infused into fetal lambs (124-130 d gestation) 1 d before, then 5 +/- 1 d after, and again 10 +/- 1 d after beginning ritodrine infusion. Before ritodrine administration, epinephrine significantly increased plasma FFA, lactate, glucose, and glucagon concentrations and decreased insulin. However, after ritodrine treatment for either 5 +/- 1 or 10 +/- 1 d, epinephrine resulted in no significant increases in FFA or glucagon, and those in lactate and glucose were significantly reduced. Decreases in insulin during epinephrine administration were unchanged by ritodrine. Initial responses of mean arterial pressure and heart rate to epinephrine were significantly greater during prolonged ritodrine treatment. Fetal responses to epinephrine mediated through beta-adrenergic receptor mechanisms were clearly decreased when administration of beta-agonists was prolonged beyond 24 h.     

Ouabain effects on oxygen physiology in anemic lambs

We studied the effects of anemia and ouabain administration on cardiac function, oxygen physiology, and blood catecholamine levels in nine newborn lambs. We measured oxygen consumption continuously, along with traditional hemodynamic variables. Oxygen transport was calculated. Following baseline measurements, lambs were made anemic (mean hematocrit = 12%) by isovolemic exchange transfusion with Plasmanate, and measurements were repeated. Thereafter ouabain was administered as a 75 micrograms/kg bolus, followed by 30 min of infusion at a rate of 0.05 microgram/kg/min. Measurements were repeated at the conclusion of infusion. Anemia was associated with a heart rate related rise in left ventricular rate of pressure rise, a rise in oxygen consumption, an increase in cardiac output, a decrease in systemic vascular resistance, and a rise in fractional oxygen extraction (oxygen consumption/transport). Following ouabain administration, cardiac output, oxygen consumption, and stroke work fell, but left ventricular rate of pressure rise and the extraction ratio did not change. Serum levels of epinephrine and norepinephrine rose with sustained anemia and ouabain infusion. In this setting, ouabain effects are manifested primarily by alterations in oxygen transport and metabolism rather than by changes in traditional assessments of left ventricular contractile function.     

Pulmonary and systemic vascular response to promethazine in conscious lambs

Summary Promethazine is an antihistamine commonly used for sedation in clinical pediatric medicine. We studied the cardiovascular effects of promethazine in normoxic, conscious, chronically instrumented neonatal lambs. Eight lambs received 1.3 mg/kg of promethazine intravenously (i.v.) while at rest. In all lambs, promethazine led to elevations of pulmonary vascular resistance, mean pulmonary arterial pressure, mean transpulmonary pressure, mean left atrial pressure, and the ratio of pulmonary-to-systemic vascular resistance. In addition, five (63%) of the lambs demonstrated an increase in mean systemic arterial pressure and systemic vascular resistance to promethazine. A subgroup of three lambs, which tended to be younger, failed to demonstrate the systemic vascular response to promethazine. Promethazine given i.v. has important cardiovascular effects. We hypothesize that promethazine used for sedation before cardiac catheterization in children may alter subsequent hemodynamic observations.Dr. Gimotty is now located at Michigan Cancer Foundation, 110 East Warren Avenue, Detroit, Michigan, USA.This research was performed at the University of Florida.A portion of this research was presented at the Southern Society for Pediatric Research in New Orleans, Louisiana, USA, January 1981.     

Naloxone does not alter the arousal response decrement after repeated exposure to hypoxemia during sleep in lambs.

Experiments were done to determine if endogenous opiates cause the arousal response decrement that follows repeated exposure to hypoxemia during sleep in lambs. Five lambs were anesthetized and instrumented for sleep staging and measurement of arterial Hb oxygen saturation. No sooner than 3 d after surgery, measurements were made in quiet sleep and active sleep during control periods when the lambs were breathing 21% oxygen and during experimental periods when the lambs were breathing 5% oxygen. The experimental period was terminated during each epoch by changing the inspired gas mixture back to 21% oxygen, once the lamb aroused from sleep. After each lamb had been exposed to 5% oxygen during 100 consecutive epochs of sleep, naloxone--an opiate antagonist--was given i.v. in a dose of 3 mg/kg as a bolus. The animals continued to be exposed to 5% oxygen during six more epochs of sleep after the administration of naloxone. Arousal occurred from both sleep states during rapidly developing hypoxemia but was delayed in active sleep compared to quiet sleep. The arterial Hb oxygen saturation at arousal was significantly lower, and the time to arousal was significantly longer with repeated exposure to hypoxemia during both quiet sleep and active sleep. Naloxone did not alter this arousal response decrement to hypoxemia. Thus, our data provide evidence that endogenous opiates do not play a major role in causing the arousal response decrement that follows repeated exposure to hypoxemia during sleep in lambs.     

Influence of intravenous sildenafil on cerebral oxygenation measured by near-infrared spectroscopy in infants after cardiac surgery

Sildenafil (Viagra) has been shown to be an effective pulmonary vasodilator and is increasingly used in patients with pulmonary hypertension. Its effects on the cerebral circulation are unclear and have not yet been described. We investigated the effect of i.v. sildenafil treatment on cerebral oxygenation in 13 children with elevated pulmonary vascular resistance due to congenital heart defects after cardiac surgery using near-infrared spectroscopy (NIRS). Median age was 4.5 mo, and median weight was 5.5 +/- 1.8 kg. Sildenafil was administered in three steps of 15 min each with cumulative doses of 0.025, 0.1, and 0.25 mg/kg. We examined the changes of oxygenated hemoglobin (HbO2), deoxygenated hemoglobin (HHb), total hemoglobin (tHb) concentration, cytochrome oxidase (CytOx) oxygenation, and cerebral tissue oxygenation index (TOI) in 13 children. A significant increase in cerebral HbO2 and tHb at the beginning of i.v. sildenafil administration with a decrease in HHb was observed. These changes led to a significant elevation in cerebral TOI from 63.4 +/- 2.5% to 65.7 +/- 2.8%, whereas mean systemic arterial pressure and arterial oxygen partial pressure tended to decrease. In conclusion, we observed a reversible increase of HbO2, tHb, and hemoglobin oxygen saturation in the scanned tissue section after i.v. sildenafil administration. These findings may be clinically relevant because they indicate that after cardiac surgery, sildenafil may increase cerebral blood flow (CBF), probably due to general endothelial dysfunction after cardiopulmonary bypass (CPB).     

The circulatory effects of nifedipine in the conscious newborn lamb

The cardiac, pulmonary vascular, and systemic vascular effects of bolus injections (2.5, 25, 50 micrograms/kg) and 5-min infusions of 50 micrograms/kg/min of Nifedipine were tested in conscious, chronically instrumented newborn lambs. While breathing room air, bolus injections of 50 micrograms/kg into the pulmonary artery caused the cardiac index and left ventricular dp/dt to fall as did systemic arterial pressure and calculated resistance (all changes significant p less than 0.05). Pulmonary artery, pulmonary vein, and left atrial pressure all tended to increase and there was a shift in flow away from the injected lung (14 +/- 0.05%). Pulmonary arteriolar resistance in the injected lung increased significantly (p less than 0.05). Nifedipine failed to prevent hypoxia-induced pulmonary vasoconstriction, and when given during hypoxia, caused a further rise in pulmonary artery pressure with a marked fall in left ventricular dp/dt and systemic vascular resistance. These acute effects peaked 30 s to 2 min after injection and all hemodynamic variables returned to baseline by 10 min. Five-min infusions caused similar effects which completely reversed 20 min after the infusion was stopped. Nifedipine causes significant cardiac depression combined with systemic vasodilatation and pulmonary arteriolar constriction in conscious newborn lambs. Assuming similar actions in humans, it seems quite unsuitable for the therapy of pulmonary hypertensive problems of newborn infants.     

Physiologic and neuropathologic aspects of hypothermic circulatory arrest in newborn dogs

A model of hypothermic circulatory arrest has been developed in the newborn dog. Ten puppies were anesthetized with halothane, paralyzed, and artificially ventilated with 70% nitrous oxide 30% oxygen to arterial oxygen pressure greater than 8.0 kPa (60 mm Hg), arterial carbon dioxide pressure of 4.4-5.6 kPa (33-42 mm Hg), and arterial pH of 7.35-7.42. Animals were surface cooled to 20 degrees C, after which cardiac arrest was produced with i.v. KCl. Dogs remained asystolic without ventilation for 1.0 (n = 4), 1.5 (n = 3), or 2.0 (n = 3) h. Resuscitation was accomplished with closed-chest compression, mechanical ventilation, i.v. epinephrine and NaHCO3, and rewarming to 37 degrees C. Postarrest recovery was maintained for 3-4 h; thereafter, the puppies underwent perfusion-fixation of their brains for pathologic analysis. Plasma glucose (control = 8.3 mmol/L) increased slightly during hypothermic cardiac arrest (+36%) but was markedly elevated at 15 min postarrest (20 mmol/L). Blood lactate (control = 1.1 mmol/L) increased almost 200% during hypothermic circulatory arrest, with a further rise to 9.0 mmol/L at 15 min postarrest. Thereafter, lactate decreased in the 1-h arrested dogs but increased progressively in the other groups. Mean arterial blood pressure returned to baseline (73 mm Hg) by 15 min postarrest, remained stable in the 1-h dogs, but fell at 3 h to 62 and 34 mm Hg in the 1.5- and 2.0-h groups, respectively. No neuropathologic alterations were seen in puppies arrested for 1 h, whereas all puppies arrested for 1.5 or 2 h had varying degrees of cerebral cortical and hippocampal damage.(ABSTRACT TRUNCATED AT 250 WORDS)     

An initial sustained inflation improves the respiratory and cardiovascular transition at birth in preterm lambs

A sustained inflation (SI) facilitates lung aeration after birth but may impair the neonatal cardiovascular transition. We aimed to determine the effect of an initial SI on pulmonary arterial and carotid blood flow (PBF and CBF) after preterm birth. Fetal sheep were instrumented at ～ 122 d of gestation (d). Lambs were delivered at ～ 127 d and received either an initial SI (40 cm H2O for 1 min or until a volume of 20 mL/kg was administered) followed by ventilation for 30 min (SI; n = 7) or ventilation for 30 min (non-SI; n = 6). At 10 min after ventilation onset, inspired O2 content increased from 21 to 100% for 10 min. PBF, CBF, pulmonary arterial and carotid pressures, tidal volume, and inspiratory pressures were recorded. PBF was greater during the SI (p < 0.05) but thereafter was similar between groups. Non-SI lambs were hypoxemic and had higher CBF than SI lambs (p < 0.05). Cerebral oxygen delivery was constant in SI lambs but increased ～ 4-fold in non-SI lambs during ventilation with 100% O2 (p < 0.05). Lung compliance and respiratory status were better in SI than non-SI lambs (p < 0.05). A SI improved lung function without adverse circulatory effects, seemed to stabilize neonatal cerebral O2 delivery, and may protect against cerebral hyperoxia.     

Chloralose alters both basal hemodynamics and cardiovascular responses to alveolar hypoxia in chronically instrumented, spontaneously breathing lambs

We studied the effects of chloralose anesthesia on the basal hemodynamic state and on the cardiovascular response to alveolar hypoxia in chronically instrumented, spontaneously breathing lambs, compared with responses to the saline vehicle. Chloralose significantly increased heart rate (23%), mean systemic arterial pressure (11%), systemic vascular resistance (21%), mean pulmonary arterial pressure (23%), and pulmonary vascular resistance (46%) (n = 30, p less than 0.05, ANOVA). These changes were unrelated to baseline tone of the circulation, cardiac output, mean left atrial pressure, or physiologically important changes in arterial blood gas tensions. In addition, chloralose-treated lambs had increased heart rate, systemic vascular resistance, and pulmonary vascular resistance compared to controls during alveolar hypoxia (13-15% FiO2). Importantly, chloralose-treated lambs did not increase their cardiac output during alveolar hypoxia as did control lambs. During hypoxia, systemic vascular resistance remained elevated in chloralose-treated lambs, but declined in control lambs. Chloralose has been recommended as an ideal anesthetic agent for cardiovascular experimentation. Our data suggest that chloralose-induced alterations in basal hemodynamics and in cardiovascular responses to alveolar hypoxia represent an uncontrolled variable in acute experimental studies. Complex cardiovascular alterations caused by anesthesia should be considered in experimental design.     

Cerebral metabolism in the newborn lamb with polycythemia

Infants with polycythemia and hyperviscosity are known to have a reduced cerebral blood flow. Eight newborn lambs were studied to determine what effect the reduction in cerebral blood flow might have on the cerebral delivery and uptake of oxygen, glucose, lactate, pyruvate, beta-hydroxybutyrate, and acetoacetate. Measurements of cerebral blood flow, hematocrit, blood viscosity as well as delivery and uptake of the forementioned substrates were made during a control period and at 60, 180, and 300 min after an exchange transfusion with packed newborn red blood cells was performed to increase the hematocrit. Sixty min after the exchange transfusion, cerebral blood flow fell while cerebral oxygen delivery and uptake were stable. Although arterial glucose concentration remained unchanged, there was a significant fall in cerebral glucose delivery. At 180 min after the exchange transfusion, the arterial glucose concentration fell from 90 to 70 mg/100 ml causing the cerebral glucose delivery to further decrease. This resulted in a significant fall in the cerebral glucose uptake and glucose:oxygen quotient. At 300 min arterial glucose concentration remained low but a rise in cerebral blood flow resulted in a small increase in the cerebral glucose delivery and consequently the cerebral glucose uptake and glucose:oxygen quotient returned to normal. We conclude that polycythemia results in a decrease in cerebral glucose delivery and uptake during normoglycemia.     

PAH clearance, sodium excretion, and PAH extraction ratio in acidotic near-term lambs treated with hypertonic sodium bicarbonate.

The electrolyte changes and renal hemodynamic adjustment to hypertonic sodium bicarbonate (NaHCO3) correction of a metabolic acidosis were studied in 4 neonatal lambs and in 2 controls. PAH clearance increased from 0.92 to 1.65 ml/min/kg (p less than 0.05), urine flow from 0.37 to 0.61 ml/min/kg (p less than 0.05), and Na excretion from 8.4 to 23.7 muEq/min/kg (p less than 0.05) during the NaHCO3 infusion. These increases were transient and returned to pre-infusion levels following NaHCO3 infusion. Calculation of Na intake and output revealed a net retention of 5.1 mEq/kg in the study lambs which was reflected in a rise of serum Na and osmolarity (Osm) during the post-NaHCO3 -infusion period. The extraction ratio of sodium p-aminohippurate (EPAH) and its relationship to arterial pH were studied in 4 additional lambs. The EPAH did not change with metabolic acidosis but for unknown reasons, the infusion of NaHCO3 resulted in a temporary depression of EPAH (p less than 0.001).     

Effects of deferoxamine, a chelator of free iron, on NA(+), K(+)-ATPase activity of cortical brain cell membrane during early reperfusion after hypoxia-ischemia in newborn lambs

Free iron chelation after hypoxia-ischemia can reduce free radical-induced damage to brain cell membranes and preserve electrical brain activity. We investigated whether chelation of free iron with deferoxamine (DFO) preserved cortical cell membrane activity of Na(+),K(+)-ATPase and electrocortical brain activity (ECBA) of newborn lambs during early reperfusion after severe hypoxia-ischemia. Hypoxia was induced in 16 lambs by decreasing the fraction of inspired oxygen to 0.07 for 30 min, followed by a 5-min period of hypotension (mean arterial blood pressure <35 mm Hg). ECBA (in microvolts) was measured using a cerebral function monitor. Immediately after hypoxia and additional ischemia, eight lambs received DFO (2.5 mg/kg, i.v.), and seven lambs received a placebo (PLAC). Two lambs underwent sham operation. One hundred eighty minutes after completion of hypoxia and ischemia, the brains were obtained and frozen. Na(+),K(+)-ATPase activity was measured in the P(2) fraction of cortical tissue. Na(+),K(+)-ATPase activity was 35.1 +/- 7.4, 42.0 +/- 7.6, and 40.7 +/- 1.4 micromol inorganic phosphate/mg protein per hour in PLAC-treated, DFO-treated, and sham-operated lambs, respectively (p < 0.05: DFO versus PLAC). ECBA was 11.2 +/- 6.1, 14.8 +/- 4.8, and 17.5+/-.0.5 microV in PLAC-treated, DFO-treated, and sham-operated lambs, respectively (p = 0.06: DFO versus PLAC). Na(+),K(+)-ATPase activity correlated with ECBA at 180 min of reperfusion (r = 0.85, p < 0.001). We conclude that Na(+),K(+)-ATPase activity of cortical brain tissue was higher in DFO-treated lambs compared with PLAC-treated animals during the early reperfusion phase after severe hypoxia-ischemia, suggesting a reduction of free radical formation by DFO. Furthermore, a positive relationship was found between Na(+),K(+)-ATPase activity and ECBA.     

High brain tissue oxygen tension during ventilation with 100% oxygen after fetal asphyxia in newborn sheep

The optimal inhaled oxygen fraction for newborn resuscitation is still not settled. We hypothesized that short-lasting oxygen ventilation after intrauterine asphyxia would not cause arterial or cerebral hyperoxia, and therefore be innocuous. The umbilical cord of fetal sheep was clamped and 10 min later, after delivery, ventilation with air (n = 7) or with 100% oxygen for 3 (n = 6) or 30 min (n = 5), followed by air, was started. Among the 11 lambs given 100% oxygen, oxygen tension (PO2) was 10.7 (1.8-56) kPa [median (range)] in arterial samples taken after 2.5 min of ventilation. In those ventilated with 100% oxygen for 30 min, brain tissue PO2 (PbtO2) increased from less than 0.1 kPa in each lamb to individual maxima of 56 (30-61) kPa, whereas in those given oxygen for just 3 min, PbtO2 peaked at 4.2 (2.9-46) kPa. The maximal PbtO2 in air-ventilated lambs was 2.9 (0.8-5.4) kPa. Heart rate and blood pressure increased equally fast in the three groups. Thus, prolonged ventilation with 100% oxygen caused an increase in PbtO2 of a magnitude previously only reported under hyperbaric conditions. Reducing the time of 100% oxygen ventilation to 3 min did not consistently avert systemic hyperoxia.     

Antenatal glucocorticoids alter postnatal preterm lamb renal and cardiovascular responses to intravascular volume expansion

We assessed renal and cardiovascular function in preterm newborn lambs after antenatal glucocorticoid exposure. Pregnant ewes were randomly assigned to receive betamethasone or saline via either direct fetal or maternal injection at 122 d gestation. Lambs were delivered 15 h later, and cardiovascular and renal function was assessed. Two hours after delivery, baseline urine flow, urinary sodium excretion, and urinary osmolar clearance were similar in all groups. Volume expansion (saline, 2.5% of body weight, for 10 min) increased values for urine flow (0.23 +/- 0.04 to 0.58 +/- 0.09 mL x min(-1) x kg(-1)), urinary sodium excretion (29.7 +/- 5.8 to 76.2 +/- 12.3 microEq x min(-1) x kg(-1)), and osmolar clearance (12.2 +/- 1.2 to 24.3 +/- 1.6 mL/100 mL GFR) in the fetal group. Increases in urine values were also observed in the maternal group, but control values did not change significantly. Mean arterial pressure was increased in both betamethasone-treated groups relative to controls. Short-term antenatal betamethasone exposure 1) augments preterm newborn kidney adaptive responses to acute volume expansion, and 2) increases postnatal blood pressure in preterm newborn lambs.     

Effects of dopamine and nifedipine infusions on the pulmonary circulation of the lamb

The purpose of this study was to test the hypothesis that nifedipine when given with dopamine will lower pulmonary vascular resistance in hypoxic lambs without altering systemic vascular resistance. We studied six unanesthetized lambs (ranging in age from 13 to 35 days) as they breathed air or on a separate day as they breathed 10% O2 and 3% CO2 in nitrogen. First, we infused dopamine at progressively higher rates (10, 20, 40, 80, and 160 micrograms/kg/min) while measuring mean aortic, pulmonary arterial, and left atrial pressures and heart rate continuously and cardiac output and arterial blood gas tensions at frequent intervals. Then, while maintaining the dopamine infusion at 160 micrograms/kg/min, we infused boluses of nifedipine intravenously (10 micrograms/kg) every 5 min until a cumulative dose of 50 micrograms/kg had been administered. In both groups of lambs, cardiac output increased with increasing rates of dopamine infusion (baseline to maximum dopamine: 260 +/- 20 ml/kg/min to 420 +/- 60 ml/kg/min for normoxic lambs and 400 +/- 50 ml/kg/min to 560 +/- 80 ml/kg/min for hypoxic lambs). While systemic vascular resistance and pulmonary vascular resistance did not change significantly in either group during dopamine infusion, the ratio of pulmonary vascular resistance to systemic vascular resistance increased at low rates of infusion and decreased at high rates. The peak in this ratio occurred at a rate of infusion of 20-40 micrograms/kg/min in normoxic lambs and 40-80 micrograms/kg/min in hypoxic lambs. Infusion of nifedipine did not affect cardiac output in normoxic lambs but decreased it significantly in hypoxic lambs. Nifedipine infusion did not affect pulmonary vascular resistance in the normoxic lambs and increased pulmonary vascular resistance in the hypoxic lambs. We conclude that nifedipine, even when given with high doses of dopamine, is not a specific pulmonary vasodilator.     

Liquid ventilation: effects on pulmonary function in distressed meconium-stained lambs

Seven lambs (0.93 term gestation) were delivered by cesarean section with evidence of meconium in the amniotic fluid, meconium staining, and respiratory distress. The initial arterial blood gas and acid-base status indicated severe hypoxemia and acidosis. Three of these lambs developed pneumothoraces and died on control gas ventilation with positive end expiratory pressure. During the control period (90 min) with ventilatory support, there were no significant alterations in mean arterial oxygen tension (PaO2) and alveolar-arterial oxygen gradient (A-aDO2). The initial hypercarbia and acidosis were effectively controlled and corrected using mechanical ventilation and bicarbonate infusion. Fifteen min after the onset of fluorocarbon ventilation mean PaO2 significantly increased and A-aDo2 decreased. After 90 min of fluorocarbon ventilation, lambs were returned to gas ventilation. During this recovery period, PaO2 and A-aDo2 remained significantly improved compared with control gas values. Dynamic lung compliance increased, alveolar and peak tracheal pressure decreased and inspiratory elastic work of breathing decreased during liquid ventilation.     

Chronic anemia in the newborn lamb: cardiovascular adaptations and comparison to chronic hypoxemia

The cardiovascular adaptations to chronic anemia were studied in the newborn lamb and then compared with the adaptations to chronic hypoxemia. Eight chronically instrumented newborn lambs underwent repeat isovolemic exchange transfusions to maintain their Hb concentrations at 60% of normal for age. Hemodynamic studies were performed twice weekly for 2 wk after which time regional blood flows were measured using radionuclide-labeled microspheres. The major compensatory responses after 2 wk of anemia were moderate increases in heart rate (229 +/- 20 versus 187 +/- 15 beats/min) and cardiac output (226 +/- 36 versus 165 +/- 38 ml/kg/min), an increase in fractional extraction of oxygen (65 versus 40%), and a redistribution of regional blood flow. Blood flows to the heart and brain increased whereas blood flows to the viscera and carcass did not change. These compensatory responses were different from those that occur during chronic hypoxemia: specifically, cardiac output did increase, growth was not suppressed, and the pattern of redistribution of regional blood flows was different. The dissimilar effects of anemia (decreasing systemic oxygen content) versus hypoxemia (decreasing systemic oxygen tension) on local tissue receptors and peripheral chemoreceptors may account for these differences.     

Changes in plasma arginine vasopressin during transition from fetus to newborn following minimal trauma delivery of lambs and goats

Vasopressin in umbilical arterial and venous blood is high at delivery and may be important in the maintenance of arterial pressure and absorption of lung liquid. We used chronically instrumented near-term fetal lambs and goats to investigate the changes in plasma vasopressin that occur during perinatal cardiovascular transition following cesarean section without labor. Plasma arginine vasopressin was more than 5 times greater 15 min following birth than immediately prior to clamping the umbilicus, and it fell progressively over the ensuing 2-5 h to levels not significantly different from before birth. Fifteen min after delivery, neither arterial pressure, blood gases, nor pH appeared to account for the increase.