Randy R. Miller

Alterations in cerebral blood flow and oxygen consumption during prolonged hypocarbia.

ABSTRACT. The effect of prolonged (2 h) hypocarbia on cerebral blood flow, oxygen delivery, extraction, and consumption was studied in eight, 1- to 4-day-old piglets. Hyperventilation to PaCO2 < 20 mm Hg acutely (30 min) decreased cerebral blood flow and oxygen oconsumption. Cerebral oxygen consumption was subsequently restored via increases in cerebral blood flow and thus, cerebral oxygen delivery. Cerebral oxygen extraction rose from a normocarbic baseline of 50 to 75% with acute hypocarbia and was maintained at this level. The percent decrease in blood flow to the cerebrum was greater than that to other brain regions during hypocarbia.

Gastrointestinal Blood Flow and O2 Uptake in Piglets: Recovery from Hypoxemia

ABSTRACT: Gastrointestinal (GI) blood flow, O2 transport, and O2 uptake were measured during recovery from severe hypoxemia in newborn piglets. Hypoxemia was induced by lowering the inspired O2 concentration to 0.05 for 15 min. This resulted in an 82% decrease in GI O2 uptake. Recovery measurements were obtained 5 and 65 min after restoration of normoxia. During early recovery (5 min), GI O2 uptake increased above prehypoxemia baseline, presumably to “repay” the O2 deficit incurred during hypoxemia. This was mediated by an increase in the arteriovenous O2 content difference, as GI blood flow did not increase above prehypoxemia baseline. During late recovery (65 min), GI blood flow, O2 delivery, and arteriovenous O2 content difference decreased below prehypoxemia baseline. This resulted in a 52% decrease in GI O2 uptake below prehypoxemia baseline. Therefore, early recovery was characterized by an appropriate increase in GI O2 uptake; however, late recovery was characterized by a significant reduction in GI O2 transport and uptake. Circulatory homeostasis was not reestablished during the late recovery period.

The Effect of Naloxone on the Hemodynamics of the Newborn Piglet with Septic Shock

ABSTRACT. Naloxone has been shown to reverse the hemodynamic sequelae of experimental septic shock in adult animal models. Its effectiveness in the newborn has not been studied. To further investigate the efficacy of naloxone, we instrumented 18 piglets for continuous measurement of mean arterial pressure, mean pulmonary arterial pressure, central venous pressure, heart rate, left ventricular pressure, contractility, cardiac output, and O2. Oxygen consumption, systemic vascular resistance, and pulmonary vascular resistance were calculated. Following a stabilization period, group B β-hemolytic Streptococci were infused over 30 min. Following the infusion, naloxone (1 mg/kg) was given followed by a continuous infusion of 1 mg/kg/h in nine treatment animals. Nine control animals were given an equal volume of saline. Both groups developed significant increases in mean pulmonary arterial pressure followed by a return to baseline. Oxygen consumption, cardiac output, contractility and mean arterial pressure decreased in both groups. Treatment with naloxone was associated with a cessation in the fall in the mean arterial pressure and the contractility. The difference in mean arterial pressure and contractility between groups was significant. The naloxone group had significantly improved 5–h survival. We speculate that naloxone may reverse some of the hemodynamic sequelae and improve survival in newborns with septic shock.

Prognostic Significance of Cystic Intracranial Lesions in Neonates

Thirty-five infants with cystic parenchymal lesions detected by ultrasonography during the neonatal period were evaluated via periodic neurologic and developmental assessments. Long-term neurologic status (abnormal, normal, and isolated motor deficit) was assigned at 2 years of age. Abnormal neurologic status was strongly associated with bilateral cystic lesions as well as hydrocephalus during the neonatal period. Microcephaly at 6–8 months of age also correlated with abnormal status at 2 years of age. The neurologic exam at discharge and at 6–8 months of age added further negative predictive value for the infants with isolated motor delays. A literature review was conducted to determine the incidence of motor and mental delays in a large series of infants with cystic intracranial lesions.

CHARACTERIZATION OF ACUTE RESPONSE TO SURVANTA® (BERACTANT) IN THE TREATMENT OF NEONATAL RDS † 1589

Previously the acute pulmonary responses to Survanta were studied by monitoring intermittent changes in ventilatory and blood gas measurements. This study is designed to continuously characterize the acute response to Survanta during the 60 minutes following the initial dose administered to premature infants weighing 650-1500g diagnosed with significant RDS (a/A PO2≤ 0.3) prior to 2 hours of life. For the study duration (10 min prior to and 60 min following treatment) oxygen saturation, ventilator rate, and tidal volume are maintained within target ranges 93-98%, 45-60/min, and 5-7mL/kg, respectively. Survanta 4 mL/kg is administered intratracheally using a 5 Fr TrachCare MAC™ without interrupting ventilation. Software for the Drager Babylog 8000 ventilator allows continuous monitoring and recording of ventilator parameters, including FiO2, minute ventilation, MAP, and others. SaO2 is continuously monitored and recorded at 5 min intervals. Acute effects on FiO2 for the initial 9 patients indicate a marked linear decrease in FiO2(± SEM) during the 30 minutes following dosing, with a continued decline thereafter. The a/A PO2 ratio increased by two fold, and SaO2 was kept stable throughout. Other parameters are being evaluated. No administration side effects were observed. Enrollment is expected to total 40 infants.

Real-Time Spectral Analysis of Brachial Doppler Signals in Neonates with Patent Ductus Arteriosus

Twenty-three Doppler examinations of the brachial artery were performed on 10 infants with patent ductus arteriosus (PDA). The continuous-wave (CW) zerocrossing recordings were compared with the waveforms obtained from spectral analysis (SA) of the audio signal from the CW flowmeter by means of the pulsatility index (PI). The CWPI correlated well with the SAPI (r = 0.89, P < 0.001). The patients were easily grouped into those infants who were normal or had clinically insignificant PDAs from those with a significant PDA using the PI. Although spectral analysis can detect and prevent sampling artifacts, the CW zero-crossing detector provided clinically-useful information.

1728 SEROTONIN (5HT) PULMONARY VASCULAR RESPONSES IN THE NEWBORN PIG: VASOCONSTRICTION AND REFLEX VASODILATION ARE INDEPENDENT PROCESSES

We have previously reported two-receptor mediation of 5HT pulmonary vasoconstriction and differences in the dose–response curves of acutely instrumented animals versus awoke chronic preparations.To further characterize 5HT pulmonary vascular responses, we investigated 5HT action in 0–5 day old pigs (n=12). In each experiment, animals underwent instrumentation for measurement of aortic pressure (peripheral cannula), pulmonary artery (PA) pressure and PA flow (via thoracotomy). For dose–response curves, 5HT was infused as a series of rapid bolus doses, ranging from 1–100 mcg/kg. Pharmacologic mediation of the response was investigated by repeating 5HT infusions after treatment with ketanserin (a 5HT–2 blocker) or lidocaine (an endothelial uptake blocker).The PA pressure response to 5HT was qualitatively consistent, but its magnitude exhibited a wide range of variation. The PA tracing was always biphasic, consisting of a rapid increase (2–10 torr) in PA pressure over 30–40 seconds, followed by reflex vasodilation (1–4 torr below baseline), which was slower in onset (1–2 min) and in time to recovery (4–6 min). The active dose range and peak vasoconstriction response were inversely related to baseline pressure (partly a function of age). Ketanserin blocked vasoconstriction completely at doses of 0.03–0.30 mg/kg, but the “reflex” vasodilation was unaffected. Lidocaine produced no blockade of vasoconstriction, but ablated the vasodilation phase.We speculate that 5HT pulmonary vasoconstriction is a direct effect on vascular smooth muscle, while the accompanying reflex vasodilation represents release of a second mediator in response to endothelial 5HT uptake.

1409 BRAIN BLOOD FLOW ALTERATIONS DURING PROLONGED RESPIRATORY ALKALOSIS (RA)

Hypocarbic RA acutely reduces brain blood flow (BBF) by 40-50%, however, most evidence in adult subjects suggests BBF normalizes during prolonged hypocarbia. We investigated the time course of this change in hyperventilated (HV) newborn piglets. Cardiac output (C.O.) and BBF (n=8) were determined by the microsphere method and brain oxygen consumption (VO2) and extraction (EO2) measured from the sagittal vein. Following baseline (B) (PaCO2 35-40) determinations, RA (PaCO2 15-20) was induced by hyperventilation. Measurements were repeated at 30, 60 and 120 minutes. Similar timed measurements in control piglets (PaCO2 35-40) showed no significant variation over time. Acutely (30″), RA decreased BBF (40%), but this degree of vasoconstriction was not maintained. EO2 was maintained at a consistantly elevated level during RA. Thus, VO2 initially decreased but then returned to B. We speculate that RA induced a maximal increase in EO2, with the late increase in BBF representing a vascular escape phenomenon which serves to preserve VO2.