The effect of intraventricular blood on cerebral blood flow in newborn dogs.

We investigated the effect of intraventricular blood on cerebral blood flow in the newborn puppy by infusing autologous blood into the lateral ventricle to produce and maintain an intraventricular pressure of approximately 15 mm Hg (mild insult), 30 mm Hg (moderate insult), or 50 mm Hg (severe insult) for 20 min. As the intraventricular pressure increased, flow decreased progressively to all areas of the brain directly proportional to the cerebral perfusion pressure. On return of the intraventricular pressure to baseline level, cerebral blood flow normalized despite the continued presence of a large amount of blood within the lateral ventricles. We suggest that blood within the ventricular system can result in a significant acute reduction of cerebral blood flow which appears to be mediated through the effect on cerebral perfusion pressure.

The accuracy and precision of an open-circuit system to measure oxygen consumption and carbon dioxide production in neonates.

We measured the oxygen consumption, carbon dioxide production, and respiratory quotient during the combustion of a known mass of anhydrous ethanol and methanol to assess the accuracy of an open-circuit flow-through system. Continuous measurements were made of the mass of alcohol burned, the velocity of gas flow through the apparatus, and simultaneous measurements of the fractional concentration of oxygen, carbon dioxide and nitrogen of the inlet and outlet gas using paramagnetic oxygen analyzer, infrared carbon dioxide meter, and mass spectrometer. Standard respiratory and stoichiometric equations were used to calculate the oxygen consumption, carbon dioxide production and RQ for the mass of absolute alcohol combustion per unit time. In a series of 12 consecutive laboratory experiments (on 7 days), the measured values of gas exchange (similar to the rate of respiratory gas exchange by an infant of 1-4 kg) were in agreement within 5% of the true values for ethanol and methanol combustion, confirming the validity of the open-circuit method. The paramagnetic oxygen analyzer and the mass spectrometer gave similar oxygen consumption results and differed very little when the rate of absolute alcohol combustion was used to quantify the accuracy of the complete measurement system. A positive measurement error was observed for the carbon dioxide production results from both the IR meter and mass spectrometer, with the result that the respiratory quotient measurements were 3.4-4.7% higher than the true value. The mass spectrometer gave more precise oxygen consumption results, whereas smaller variance of carbon dioxide production measurements was observed using the infrared CO2 meter.(ABSTRACT TRUNCATED AT 250 WORDS)

Day-to-day energy expenditure variability in low birth weight neonates.

We estimated the metabolic rate of 13 low birth weight infants over a 9-day period, using indirect calorimetry in conjunction with serial measurements of oxygen consumption, carbon dioxide production, and total urinary nitrogen excretion. The mean percent error for oxygen consumption and carbon dioxide production measurements (determined by alcohol combustion experiments) assignable to the open-circuit system was 0.4 and 3.8%, respectively. Error in the total urinary nitrogen excretion measurement was less than 1% by the Kjeldahl technique. In the clinical setting, however, the range of deviation of measured oxygen consumption, carbon dioxide production and total urinary nitrogen excretion was +/- 12, 12, and 15% of the mean value respectively for an individual patient under standardized controlled conditions. The variability of metabolic rate between infants may be as much as 76%. Factors that had a small effect on metabolic rate were difficult to detect because of the variability inherent in the short-term measurement of metabolic rate. It was virtually impossible to control the sources of variation in the resting metabolism of low birth weight neonates over extended experimental periods. Day-to-day variations in resting energy expenditure may explain, in part, the widely different growth rates of premature infants receiving similar caloric intakes.

Incidence and severity of intraventricular hemorrhage: 1981-1984.

We have examined the trend in the incidence and mortality of intraventricular hemorrhage (IVH) in low birthweight infants from 1981 through 1984. During this time we admitted 407 infants in the first week of life with a birthweight less than or equal to 1500 gm in whom a cranial ultrasonogram or autopsy had been performed. Though the mean birthweight and gestational age, proportion of infants who were inborn, and percentage of infants requiring mechanical ventilation did not change over the 4 years, cesarean deliveries were performed more frequently (P less than .001). The overall incidence of IVH was 62% in 1981, 56% in 1982, 49% in 1983, and 58% in 1984, thus no significant trend was evident. Although the incidence of minor hemorrhages (grades I and II) remained relatively constant, there was a decrease in the incidence of grade III IVH (1981, 11%; 1984, 2%, P = .01). The incidence of grade IV hemorrhage did not change during the 4 years and ranged from 7 to 9%. Mortality rate for all infants weighing less than or equal to 1500 gm and for infants with a minor hemorrhage remained unchanged; however, the mortality rate for infants with a major hemorrhage (grade III or IV) tended to decrease (P = .07). We conclude that although some minor changes in the incidence and mortality have occurred, IVH continues to be a major problem in very-low-birthweight infants at our institution.

Energy metabolism and substrate utilization in low birth weight neonates under radiant warmers.

We evaluated the metabolic response to the thermal demands of an open radiant warmer device, as distinct from convection incubator, in 13 healthy premature infants (1.395 +/- 169 g, 28 +/- 12 days of age, mean +/- SD). Metabolic rate was 10% higher for infants under the radiant warmer than in the incubator (2.60 +/- 0.4 v 2.36 +/- 0.3 kcal/kg/h; P less than .05). The radiant warmer also induced a small (4%), but significant, increase in nonprotein respiratory quotient (0.94 +/- 0.1 v 0.90 +/- 0.1; P less than .05) and a 13% increase in carbon dioxide production (8.26 +/- 1.1 v 7.31 +/- 1.1 mL/kg/min; P less than .05). Subcutaneous fat accumulation (estimated from 60-second skin-fold thickness measurements) was greater under the radiant warmer than in the incubator (0.08 +/- 0.05 v 0.04 +/- 0.04 mm/d; P less than .05). Under the warmer, the infant's mean skin temperatures and core temperatures were normal and similar to those found in the incubator, but the foot temperature was on average 0.6 degrees C cooler. The average rate of weight gain (18 g/kg/d) was the same in the radiant environment. The pattern of the elevated metabolic rate, shift of respiratory quotient coupled with the accumulation of subcutaneous fat, and cool extremities of infants under the radiant warmer may represent a physiologic adaptive response to thermal stress. However, the reasons for the elevated metabolic rate are unclear, because activation of the sympathetic nervous system with the release of catecholamines is not apparently involved.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of pneumothorax-induced systemic blood pressure alterations on the cerebral circulation in newborn dogs.

Pneumothorax has been associated with intraventricular hemorrhage in premature infants, although the mechanism for this relationship is not clear. Because alterations in cerebral blood flow are believed to be important in the pathogenesis of intraventricular hemorrhage, the effect of induced pneumothorax and subsequent evacuation on the cerebral circulation in 16 newborn dogs was evaluated. Continuous Doppler ultrasound was used to monitor changes in cerebral blood velocity. Pneumothorax was induced by slow infusion (5 cc/kg/min) or rapid infusion (5 to 10 seconds) of air to reduce mean arterial blood pressure to half of base-line levels. Both methods of pneumothorax induction resulted in significant elevations of central venous pressure and intrapleural pressure, whereas mean arterial blood pressure and cerebral blood velocity decreased significantly. In each group, the pneumothorax was evacuated either by slow withdrawal of air (10 cc/kg/min) or as rapidly as possible. Rapid evacuation of air resulted in an immediate increase in mean arterial blood pressure and cerebral blood velocity to supranormal levels. Slow evacuation led to a more gradual normalization of mean arterial blood pressure and cerebral blood velocity. It is suggested that the precipitous increases in mean arterial blood pressure and cerebral blood velocity following rapid evacuation of a tension pneumothorax may account for the observed association between pneumothorax and intraventricular hemorrhage in premature infants.

Blood-brain barrier permeability to lactic acid in the newborn dog: lactate as a cerebral metabolic fuel.

The arteriovenous difference (A-V) method was utilized to assess the permeability of the blood-brain barrier to lactic acid in paralyzed and artificially ventilated newborn dogs. A femoral artery and the sagittal sinus were cannulated to sample arterial and cerebral venous blood simultaneously for measurements of glucose and lactate during normoglycemia, normoglycemia and hyperlactatemia insulin-induced hypoglycemia, or hypoglycemia and hyperlactatemia. During normoglycemia, arterial lactate concentrations remained less than 2 mmoles/liter for up to 2 h; mean A-V lactate was essentially zero. Arterial lactate increased up to 8 mmoles/liter during intravenous infusion of neutralized 10 mM L-lactic acid. During hyperlactatemia, the A-V lactate was directly proportional to the arterial concentration of the metabolite, a finding which is consistent with transport into brain either by simple diffusion or via a carrier with saturability greater than 8 simple diffusion or via a carrier with saturability greater than 8 mmoles/liter. During hypoglycemia (mean arterial glucose=27 mg/dl), A-V glucose was reduced by 71% with a significant increase in A-V lactate at an arterial lactate level of 1.3 mmoles/liter. Hyperlactatemia combined with hypoglycemia resulted in A-V lactate which was 2-3 fold greater than during normoglycemia at similar arterial lactate concentrations. Brain/blood lactate ratios declined by 83% during hypoglycemia compared with normoglycemic ratios, indicating that, once in brain, lactic acid was actively consumed for oxidative processes. These experimental observations may have clinical relevance in newborn human infants when concentrations of lactate in blood often approach or even exceed those of glucose.

Cerebral carbohydrate and energy metabolism during hypoglycemia in newborn dogs.

The metabolic responses of the perinatal brain to hypoglycemia were studied in newborn dogs. Hypoglycemia, induced by the intravenous injection of regular insulin (0.2-0.3 U/g body wt), resulted in final blood glucose concentrations ranging from 0.1 to 1.5 mmol/l; blood lactate levels were little changed from normoglycemic values. Righting, sucking, and nociceptive withdrawal reflexes were progressively lost during the course of hypoglycemia. Slowing of the electroencephalogram was apparent at or below 1.5 mmol/l blood glucose and advanced to paroxysmal discharges and convulsive activity as glucose approached 0.5 mmol/l. In lightly anesthetized, paralyzed, and artificially ventilated puppies, blood glucose concentrations approximating 1.0 mmol/l were associated with a 91% reduction in cerebral glucose; the concentrations of other glycolytic intermediates (glucose 6-phosphate, fructose 6-phosphate, fructose 1,6-diphosphate, pyruvate, lactate) were unchanged from control. Further declines in blood glucose resulted in cerebral glucose levels below 0.1 mmol/kg as well as in partial depletions of all measured glycolytic intermediates including lactate. These changes reflect reduced cerebral glucose consumption and glycolytic flux. Despite the alterations in carbohydrate metabolism, both lactate/pyruvate ratios and high-energy phosphate reserves (phosphocreatine, ATP, ADP) in brain were well preserved even at the extreme of hypoglycemia. The present data, coupled with previous findings of enhanced lactic acid entry into and consumption by newborn dog brain, suggest that this metabolite serves as an important, if not the predominant, substitute fuel for cerebral oxidative metabolism during perinatal hypoglycemia.

Cerebral metabolism during hypoglycemia dn asphyxia in newborn dogs.

The cerebral metabolic responses to perinatal hypoglycemia (blood glucose less than or equal to 1 mmol/l) combined with asphyxia were studied in paralyzed, lightly anesthetized newborn dogs. No major differences in heart rate, blood pressure or arterial acid-base balance between control and hypoglycemic animals occurred either prior to or during asphyxia. The electroencephalogram, unaltered by hypoglycermia alone, became isoelectric at the same intervals in both groups following respiratory arrest. Intravenous carbon black infusion at 5 min of asphyxia demonstrated no relationship between blood glucose level and cerebral perfusion (p > 0.05), whereas a positive correlation did exist between systemic blood pressure and cerebral perfusion (p < 0.01). During asphyxia, anaerobic glycolysis in brain was less enhanced in hypoglycemic dogs, resulting in a more rapid exhaustion of high-energy phosphate reserves (phosphocreatine, ATP and ADP). Thus, the cerebral metabolic responses to asphyxia superimposed upon hypoglycemia were the direct consequence of insufficient cerebral glucose stores coupled with deficient circulating glucose to brain. These metabolic disturbances were no more the result of cerebral ischemia than that which occurs during asphyxia alone. The findings also suggest that systemic physiological monitoring may be an inadequate means of appraising cerebral homeostasis during combined hypoglycemia ad hypoxia.