The fraction of inspired oxygen in infants receiving oxygen via nasal cannula often exceeds safe levels.

OBJECTIVE: Measure the fraction of inspired oxygen (F(IO(2))) in infants receiving supplemental oxygen via nasal cannula and identify clinical variables that affect F(IO(2)). METHODS: Hypopharyngeal gas samples were obtained from 20 infants receiving oxygen via nasal cannula at flows between 0 and 4 L/min. F(IO(2)) was calculated using the alveolar gas equation and measurements of partial pressure of oxygen in the samples and the barometric pressure. RESULTS: F(IO(2)) increased as oxygen flow was increased. F(IO(2)) exceeded safe levels (> 60%) in two thirds of samples when the oxygen flow was 2 L/min or higher. Tachypnea (respiratory rate > 40 breaths/min) was associated with lower F(IO(2)). CONCLUSION: Infants receiving oxygen via nasal cannula at > or = 2 L/min may be at risk for hyperoxic lung injury. Therefore, we recommend using the lowest possible oxygen flow needed to maintain normoxia in infants requiring prolonged oxygen therapy via nasal cannula.

Role of nitric oxide in the cerebrovascular and thermoregulatory response to interleukin-1 beta.

Central administration of interleukin-1 beta (IL-1 beta) increases cerebral blood flow (CBF) and body temperature, in part, through the production of prostaglandins. In previous studies, the temporal relationship between these effects of IL-1 beta have not been measured. In this study, we hypothesized that the increase in CBF occurs before any change in brain or body temperature and that the cerebrovascular and thermoregulatory effects of IL-1 beta would be attenuated by inhibiting the production of nitric oxide (NO). Adult male rats received 100 ng intracerebroventricular (icv) injection of IL-1 beta, and cortical CBF (cCBF) was measured by laser-Doppler in the contralateral cerebral cortex. A central injection of IL-1 beta caused a rapid increase in cCBF to 133 +/- 12% of baseline within 15 min and to an average of 137 +/- 12% for the remainder of the 3-h experiment. Brain and rectal temperature increased by 0.4 +/- 0.2 and 0.5 +/- 0.2 degrees C, but not until 45 min after IL-1 beta administration. Pretreatment with N(omega)-nitro-L-arginine methyl ester (L-NAME; 5 mg/kg iv) completely prevented the changes in cCBF and brain and rectal temperature induced by IL-1 beta. L-Arginine (150 mg/kg iv) partially reversed the effects of L-NAME and resulted in increases in both cCBF and temperature. These findings suggest that the vasodilatory effects of IL-1 beta in the cerebral vasculature are independent of temperature and that NO plays a major role in both the cerebrovascular and thermoregulatory effects of centrally administered IL-1 beta.

Cerebral blood flow during partial liquid ventilation in surfactant-deficient lungs under varying ventilation strategies.

OBJECTIVE: To test the hypothesis that cerebral and other regional organ blood flow would be maintained during partial liquid ventilation (PLV) in an animal model of acute lung injury during different ventilation strategies. DESIGN: A prospective, randomized study. SETTING: Animal research facility. SUBJECTS: Sixteen piglets, 2 to 4 wks of age. INTERVENTIONS: Severe lung injury was induced in infant piglets by repeated saline lavage and high tidal volume ventilation. Animals were then randomized to either conventional volume-controlled ventilation or PLV. MEASUREMENTS AND MAIN RESULTS: Organ blood flow was determined in both groups using radiolabeled microspheres under four conditions: high mean airway pressure, Paw; high Paco(2), high Paw; normal Paco(2); low Paw, high Paco(2); low Paw, normal Paco(2). There were no differences in cerebral blood flow during conventional ventilation and PLV, regardless of ventilation strategy. CONCLUSIONS: These results suggest in an acute lung injury model, PLV does not affect cerebral blood flow or other regional organ blood flow over a range of airway pressures.

Portosystemic shunting in children during the era of endoscopic therapy: improved postoperative growth parameters.

BACKGROUND: Surgical portosystemic shunting has been performed less frequently in recent years. In this retrospective study, recent outcomes of portosystemic shunting in children are described, to evaluate its role in the era of endoscopic therapy. METHODS: Retrospective chart review of children who underwent surgical portosystemic shunt procedures between October 1994 and October 1997. RESULTS: Twelve children (age range, 1-16 years) underwent shunting procedures. The causes of portal hypertension were extrahepatic portal vein thrombosis (n = 6), congenital hepatic fibrosis (n = 2), hepatic cirrhosis (n = 2), and other (n = 2). None of the patients were immediate candidates for liver transplantation. Types of shunt included: distal splenorenal (n = 10), portocaval (n = 1), and other (n = 1). Median follow-up was 35 months (range, 24-48 months). All patients are currently alive and well with patent shunts. The mean hospital stay was 8 days. Three patients required readmission for further interventions because of shunt stenosis in two and small bowel obstruction in the other. Mild portosystemic encephalopathy was seen in one child with pre-existing neurobehavioral disturbance. Excluding a patient who underwent placement of a portosystemic shunt for a complication of liver transplantation, mean weight-for-age z score in nine prepubertal patients improved from -1.16 SD to +0.15 SD (P = 0.023), and mean height-for-age z score from -1.23 SD to 0.00 SD (P = 0.048) by 2 years after surgery. CONCLUSIONS: Surgical portosystemic shunting is a safe and effective method for the management of portal hypertension in childhood. Patients show significant improvements in growth parameters after the procedure. Surgical portosystemic shunting should be actively considered in selected children with portal hypertension.

Ten days of orotracheal intubation with successful extubation in an infant with junctional epidermolysis bullosa.

OBJECTIVE: The most severe form of generalized junctional epidermolysis bullosa, the Herlitz variant, is associated with a number of extracutaneous manifestations. We report on a 45-day-old infant with laryngotracheobronchial mucosa involvement who underwent successful tracheal extubation after 10 days of orotracheal intubation and mechanical ventilatory support. Issues regarding airway management and mechanical ventilatory support in the pediatric intensive care unit are discussed.

Hemodynamic effects of nitric oxide synthase inhibition before and after cardiac arrest in infant piglets.

Using infant piglets, we studied the effects of nonspecific inhibition of nitric oxide (NO) synthase by NG-nitro-L-arginine methyl ester (L-NAME; 3 mg/kg) on vascular pressures, regional blood flow, and cerebral metabolism before 8 min of cardiac arrest, during 6 min of cardiopulmonary resuscitation (CPR), and at 10 and 60 min of reperfusion. We tested the hypotheses that nonspecific NO synthase inhibition 1) will attenuate early postreperfusion hyperemia while still allowing for successful resuscitation after cardiac arrest, 2) will allow for normalization of blood flow to the kidneys and intestines after cardiac arrest, and 3) will maintain cerebral metabolism in the face of altered cerebral blood flow after reperfusion. Before cardiac arrest, L-NAME increased vascular pressures and cardiac output and decreased blood flow to brain (by 18%), heart (by 36%), kidney (by 46%), and intestine (by 52%) compared with placebo. During CPR, myocardial flow was maintained in all groups to successfully resuscitate 24 of 28 animals [P value not significant (NS)]. Significantly, L-NAME attenuated postresuscitation hyperemia in cerebellum, diencephalon, anterior cerebral, and anterior-middle watershed cortical brain regions and to the heart. Likewise, cerebral metabolic rates of glucose (CMRGluc) and of lactate production (CMRLac) were not elevated at 10 min of reperfusion. These cerebral blood flow and metabolic effects were reversed by L-arginine. Flows returned to baseline levels by 60 min of reperfusion. Kidney and intestinal flow, however, remained depressed throughout reperfusion in all three groups. Thus nonspecific inhibition of NO synthase did not adversely affect the rate of resuscitation from cardiac arrest while attenuating cerebral and myocardial hyperemia. Even though CMRGluc and CMRLac early after resuscitation were decreased, they were maintained at baseline levels. This may be clinically advantageous in protecting the brain and heart from the damaging effects of hyperemia, such as blood-brain barrier disruption.

Selective brain cooling in infant piglets after cardiac arrest and resuscitation.

OBJECTIVES: To test the hypothesis that selective brain cooling could be performed in an infant model of cardiac arrest and resuscitation without changing core temperature and to study its acute effects on regional organ blood flow, cerebral metabolism, and systemic hemodynamics. DESIGN: Prospective, randomized, controlled study. SETTING: Research laboratory at a university medical center. SUBJECTS: Fourteen healthy infant piglets, weighing 3.5 to 6.0 kg. INTERVENTIONS: piglets were anesthetized and mechanically ventilated, and had vascular catheters placed. Parietal cortex (superficial brain), caudate nucleus (deep brain), esophageal, and rectal temperatures were monitored. All animals underwent 6 mins of cardiac arrest induced by ventricular fibrillation, 6 mins of external cardiopulmonary resuscitation (CPR), defibrillation, and 2 hrs of reperfusion. Normal core temperature (rectal) was regulated in all animals. In seven control animals (group 1), brain temperature was not manipulated. In seven experimental animals (group 2), selective brain cooling was begin during CPR, using a cooling cap filled with -30 degrees C solution. Selective brain cooling was continued for 45 mins of reperfusion after which passive rewarming was allowed. Regional blood flow (microspheres) and arterial and sagittal sinus blood gases were measured prearrest, during CPR, and at 10 mins, 45 mins, and 2 hrs of reperfusion. MEASUREMENTS AND MAIN RESULTS: Rectal temperature did not change over time in either group. In group 1, brain temperature remained constant except for a decrease of 0.6 degrees C at 10 mins of reperfusion. In group 2, superficial and deep brain temperatures were lowered to 32.8 +/- 0.7 (SEM) degrees C and 34.9 +/- 0.4 degrees C, respectively, by 15 mins of reperfusion. Superficial and deep brain temperatures were further lowered to 27.8 +/- 0.8 degrees C and 31.1 +/- 0.3 degrees C, respectively, at 45 mins of reperfusion. Both temperatures returned to baseline by 120 mins. Cerebral blood flow was not different between groups at any time point, although there was a trend for higher flow in group 2 at 10 mins of reperfusion (314% of baseline) compared with group 1 (230% of baseline). Cerebral oxygen uptake was lower in group 2 than in group 1 (69% vs. 44% of baseline, p=.02) at 45 mins of reperfusion. During CPR, aortic diastolic pressure was lower in group 2 than in group 1 (27 +/- 1 vs. 23 +/- 1 mm Hg, p = .007). Myocardial blood flow during CPR was also lower in group 2 (80 +/- 7 vs. 43 +/- 7 mL/min/100 g, p=.002). Kidney and intestinal blood flows were reduced during CPR in both groups; however, group 2 animals also had lower intestinal flow vs. group 1 at 45 and 120 mins of reperfusion. CONCLUSIONS: Selective brain cooling by surface cooling can be achieved rapidly in an infant animal model of cardiac arrest and resuscitation without changing core temperature. Brain temperatures known to improve neurologic outcome can be achieved by this technique with minimal adverse effects. Because of its ease of application, selective brain cooling may prove to be an effective, inexpensive method of cerebral resuscitation during pediatric CPR.

Effect of corticosteroids on survival of children with acquired immunodeficiency syndrome and Pneumocystis carinii-related respiratory failure.

The medical records of patients with acquired immunodeficiency syndrome were reviewed to evaluate the effect of our adoption to the pediatric population of the National Institutes of Health recommendation for adjunctive corticosteroid therapy in adults with Pneumocystis carinii pneumonia. In 21 episodes of P. carinii-related respiratory failure, only adjunctive corticosteroids were associated with a significant improvement in survival to successful removal of the tracheal tube, from a historical rate of 11% to 91%.

Early endothelial damage and leukocyte accumulation in piglet brains following cardiac arrest.

This study examined the early microvascular and neuronal consequences of cardiac arrest and resuscitation in piglets. We hypothesized that early morphological changes occur after cardiac arrest and reperfusion, and that these findings are partly caused by post-resuscitation hypertension. Three groups of normothermic piglets (37.5 degrees - 38.5 degrees C) were investigated: group 1, non-ischemic time controls; group 2, piglets undergoing 8 min of cardiac arrest by ventricular fibrillation, 6 min of cardiopulmonary resuscitation (CPR) and 4 h of reperfusion; and group 3, non-ischemic hypertensive controls, receiving 6 min of CPR after only 10 s of cardiac arrest followed by 4-h survival. Immediately following resuscitation, acute hypertension occurred with peak systolic pressure equal to 197 +/- 15 mm Hg usually lasting less than 10 min. In reacted vibratome sections, isolated foci of extravasated horseradish peroxidase were noted throughout the brain within surface cortical layers and around penetrating vessels in group 2. Stained plastic sections of leaky sites demonstrated variable degrees of tissue injury. While many sections were unremarkable except for luminal red blood cells and leukocytes, other specimens contained abnormal neurons, some appearing irreversibly injured. The number of vessels containing leukocytes was higher in group 2 than in controls (3.8 +/- 0.6% vs 1.4 +/- 0.4% of vessels, P < 0.05). Evidence for irreversible neuronal injury was only seen in group 2. Endothelial vacuolization was higher in groups 2 and 3 than in group 1 (P < 0.05). Ultrastructural examination of leaky sites identified mononuclear and polymorphonuclear leukocytes adhering to the endothelium of venules and capillaries only in group 2. The early appearance of luminal leukocytes in ischemic animals indicates that these cells may contribute to the genesis of ischemia reperfusion injury in this model. In both groups 2 and 3 endothelial cells demonstrated vacuolation and luminal discontinuities with evidence of perivascular astrocytic swelling. Widespread microvascular and neuronal damage is present as early as 4 h after cardiac arrest in infant piglets. Hypertension appears to play a role in the production of some of the endothelial changes.

Effect of vest cardiopulmonary resuscitation on cerebral and coronary perfusion in an infant porcine model.

OBJECTIVES: To determine cerebral and myocardial blood flow rates during vest cardiopulmonary resuscitation (CPR) without direct cardiac compression in an infant porcine model. Also, to determine if circumferential chest compression without the chest deformity ordinarily associated with precordial compression maintains cerebral and myocardial blood flow rates during prolonged CPR. Finally, to establish the effect of compression rate and duty cycle on cerebral and myocardial blood flow rates during vest CPR in this model. DESIGN: Prospective, randomized comparison of two compression rates and two duty cycles in four groups during prolonged CPR. SETTING: University cerebral resuscitation laboratory. SUBJECTS: Thirty-two infant domestic swine. INTERVENTIONS: Microsphere-determined cerebral and myocardial blood flow rates, perfusion pressures, and chest dimensions, were measured before and during prolonged vest CPR. Immediately after ventricular fibrillation, epinephrine administration was started and thoracic vest CPR was performed using a single combination of compression rates of 100 or 150/min and duty cycles of 30% or 60%. Measurements were made before and at 5, 10, 20, 35, and 50 mins of CPR. MEASUREMENTS AND MAIN RESULTS: Five minutes into CPR, between-group comparisons showed that cerebral blood flow was 16 to 20 mL/min/100 g and myocardial blood flow was 34 to 45 mL/min/100 g (48% to 62% and 25% to 33% of prearrest values). When CPR was prolonged, cerebral blood flow deteriorated similarly in all groups. Myocardial blood flow decreased over time but was better maintained in the groups with a 30% duty cycle (24 vs. 4 mL/min/100 g; p < .006). There were no differences between the two compression rates. Chest deformity after cessation of 50 mins of compression was < 3%. CONCLUSIONS: Cerebral and myocardial blood flow rates produced by vest CPR are comparable with rates reported using other types of CPR in this model. Deterioration in blood flow during prolonged CPR occurs despite a lack of chest deformation. The deterioration in myocardial blood flow during prolonged CPR is greater when a long duty cycle is used in this model.

Reduced blood-brain barrier permeability after cardiac arrest by conjugated superoxide dismutase and catalase in piglets.

BACKGROUND AND PURPOSE: Cardiac arrest and resuscitation in immature piglets result in a delayed increase in blood-brain barrier permeability. We tested the hypothesis that pretreatment with oxygen radical scavengers reduces postischemic permeability. METHODS: Permeability was assessed by measuring the plasma-to-brain transfer coefficient of the small amino acid, alpha-aminoisobutyric acid, in 2- to 3-week-old anesthetized piglets. Three groups were studied: (1) a nonischemic time control group (n = 5), (2) an ischemia group (n = 8) pretreated with 5 mL of polyethylene glycol vehicle, and (3) an ischemia group (n = 8) pretreated with polyethylene glycol conjugated to superoxide dismutase (10,000 U/kg) and to catalase (20,000 U/kg). The ischemia protocol consisted of 8 minutes of ventricular fibrillation, 6 minutes of cardiopulmonary resuscitation, defibrillation, and 4 hours of spontaneous circulation. RESULTS: The mean +/- SEM of the transfer coefficient of alpha-aminoisobutyric acid in cerebrum was (in microL/g per minute): 1.54 +/- 0.37 in the nonischemic group, 2.04 +/- 0.26 in the ischemia group treated with vehicle, and 1.29 +/- 0.25 in the ischemia group treated with oxygen radical scavengers. Postischemic values with scavenger treatment were significantly lower than those with vehicle treatment in cerebrum, cerebellum, medulla and cervical spinal cord. CONCLUSIONS: Pretreatment with oxygen radical scavengers reduces postischemic blood-brain barrier permeability by a small amino acid. These data are consistent with oxygen radical-mediated dysfunction of cerebral endothelium in a pediatric model of cardiopulmonary resuscitation.

The effect of nitric oxide synthase inhibition on infarct volume after reversible focal cerebral ischemia in conscious rats.

BACKGROUND AND PURPOSE: Previous in vitro and in vivo studies of the effects of nitric oxide synthase inhibition in the central nervous system have yielded conflicting results concerning the role of nitric oxide in the events that lead to ischemic injury. In this study, we tested the hypothesis that preischemic inhibition of nitric oxide synthase increases infarct volume after reversible focal cerebral ischemia in rats. METHODS: NG-nitro-L-arginine methyl ester hydrochloride 15 mg/kg IV or an equivalent volume of saline was administered to adult Wistar rats 15 minutes before middle cerebral artery occlusion by the intraluminal suture method. After 2 hours of ischemia, the suture was withdrawn, and rats were allowed to survive for 3 days. Areas of infarction in 10 hematoxylin-eosin-stained sections were measured and used to determine infarct volume. RESULTS: Administration of NG-nitro-L-arginine methyl ester hydrochloride increased hemispheric infarct volume by 137% over control (60.9 +/- 30.5 to 144.3 +/- 19.6 mm3, P < .05; mean +/- SEM). Cortical and subcortical infarct volumes were increased by 176% (33.8 +/- 21.9 to 93.3 +/- 15.2 mm3, P < .05) and 103% (25.1 +/- 9.4 to 51.0 +/- 5.5 mm3, P < .03), respectively. CONCLUSIONS: Nitric oxide synthase inhibition increases infarct volume and decreases the variability of the response to middle cerebral artery occlusion in Wistar rats, a strain that is normally resistant to focal cerebral ischemic injury owing to extensive collateralization. The mechanism of the deleterious effect of nitric oxide synthase inhibition likely involves a more severe degree of blood flow reduction during and after middle cerebral artery occlusion, primarily by preventing the vasodilatory response of collateral vessels to proximal middle cerebral artery occlusion. Maintenance of nitric oxide synthase activity during and after focal cerebral ischemia appears to minimize ischemic injury.

Fructose-1,6-bisphosphate reduces infarct volume after reversible middle cerebral artery occlusion in rats.

BACKGROUND AND PURPOSE: We tested the hypothesis that fructose-1,6-bisphosphate, when administered 10 minutes before the end of 2 hours of reversible middle cerebral artery occlusion, reduces ischemia-reperfusion injury and infarct volume measured after a 3-day survival period in rats. METHODS: After 1 hour and 50 minutes of middle cerebral artery occlusion by the intraluminal suture method, fructose-1,6-bisphosphate, 500 mg/kg in group 1 and 350 mg/kg in group 2 (or an equivalent volume of 1.8% saline as placebo in each group), was given intravenously for a period of 15 minutes to fasted adult Sprague-Dawley rats. After 2 hours of ischemia, the suture was withdrawn and the rats allowed to survive for 3 days. The areas of infarction in 10 hematoxylin-eosin-stained coronal sections of the brain were measured and used to calculate infarct volume. RESULTS: In group 1, fructose-1,6-bisphosphate decreased total cerebral hemispheric infarct volume by 43% (from 199.6 +/- 11.2 to 114.2 +/- 35.8 mm3, P < .04; mean +/- SEM). Cerebral cortical and subcortical infarct volumes were decreased by 46% (from 137.3 +/- 7.5 to 74.1 +/- 28.6 mm3, P < .04) and 36% (from 62.3 +/- 5.1 to 40.0 +/- 8.3 mm3, P < .04), respectively. In group 2, fructose-1,6-bisphosphate had no effect on infarct volume in rats that developed mild intraischemic hyperthermia, but in rats kept normothermic during ischemia, fructose-1,6-bisphosphate reduced subcortical infarct volume from 53.7 +/- 8.1 to 18.4 +/- 8.0 mm3 (P < .03). CONCLUSIONS: Fructose-1,6-bisphosphate improves functional neurological outcome and reduces infarct volume after reversible middle cerebral artery occlusion in rats.

Selective brain cooling increases cortical cerebral blood flow in rats.

To evaluate the effect of selective brain cooling on cortical cerebral blood flow, we reduced brain temperature in nitrous oxide anesthetized adult rats using a high speed fan while keeping rectal temperature at 37-38 degrees C. During selective brain cooling, cortical cerebral blood flow, as measured by laser-Doppler flowmetry, increased to 215 +/- 26% (mean +/- SE) of baseline at a cortical brain temperature of 30.9 +/- 0.5 degrees C and a rectal temperature of 37.5 +/- 0.1 degrees C. During rewarming, as brain temperature increased, cortical cerebral blood flow decreased. The cerebral vasodilatory response to hypothermia may explain its protective effects during and after cerebral ischemia.

Cardiopulmonary bypass and the blood-brain barrier. An experimental study.

The diffuse inflammation produced by cardiopulmonary bypass might disrupt the blood-brain barrier and lead to the transient neurologic dysfunction occasionally seen after cardiac operations. To evaluate this possibility, blood-brain barrier integrity was measured by carbon 14-aminoisobutyric acid tracer technique after 2 hours of cardiopulmonary bypass in piglets. Six animals were cooled to 28 degrees C on cardiopulmonary bypass and then rewarmed to 38 degrees C before carbon 14-aminosisobutyric acid was injected intraarterially. A control group of six animals underwent median sternotomy and heparinization but were not placed on cardiopulmonary bypass. Blood-to-brain transfer coefficients for carbon 14-aminosisobutyric acid were calculated for multiple brain regions; higher coefficients reflect greater flux of carbon 14-aminosisobutyric acid and suggest loss of blood-brain barrier integrity. The brain regions examined and their transfer coefficients (cardiopulmonary bypass versus control mean +/- standard error of the mean ml/gm/min) were middle cerebral artery territory cortex (0.0032 +/- 0.0002 versus 0.0030 +/- 0.0002; p = 0.42), diencephalon (0.0031 +/- 0.0003 versus 0.0029 +/- 0.0002; p = 0.50), midbrain (0.0028 +/- 0.0002 versus 0.0027 +/- 0.0002; p = 0.86), cerebellum (0.0036 +/- 0.0003 versus 0.0029 +/- 0.0002; p = 0.22), and spinal cord (0.0035 +/- 0.0003 versus 0.0041 +/- 0.0008; p = 0.48). There were no significant differences in transfer coefficients between animals placed on cardiopulmonary bypass and control animals in any brain region examined. The pituitary gland lacks a blood-brain barrier and had a correspondingly high coefficient in control animals and those undergoing cardiopulmonary bypass (0.077 +/- 0.012 versus 0.048 +/- 0.008; p = 0.07). Two hours of moderately hypothermic cardiopulmonary bypass does not disrupt the blood-brain barrier.

Brain bioenergetics during cardiopulmonary resuscitation in dogs.

Cardiac arrest causes a rapid loss of cerebral adenosine triphosphate [corrected] (ATP) and a decrease in cerebral intracellular pH (pHi). Depending on the efficacy of cardiopulmonary resuscitation (CPR), cerebral blood flow levels (CBF) ranging from near zero to near normal have been reported experimentally. Using 31P magnetic resonance spectroscopy, the authors tested whether experimental CPR with normal levels of cerebral blood flow can rapidly restore cerebral ATP and pHi despite the progressive systemic acidemia associated with CPR. After 6 min of ventricular fibrillation in six dogs anesthetized with fentanyl and pentobarbital, ATP was reduced to undetectable concentrations and pHi decreased from 7.11 +/- 0.02 to 6.28 +/- 0.09 (+/- SE) as measured by 31P magnetic resonance spectroscopy. Application of cyclic chest compression by an inflatable vest placed around the thorax and infusion of epinephrine (40 micrograms/kg bolus plus 8 micrograms/kg/min, intravenously) maintained cerebral perfusion pressure greater than 70 mmHg for 50 min with the dog remaining in the magnet. Prearrest cerebral blood flows were generated. Cerebral pHi recovered to 7.03 +/- 0.03 by 35 min of CPR, whereas arterial pH decreased from 7.41 +/- 0.4 to 7.08 +/- 0.04 and cerebral venous pH decreased from 7.29 +/- 0.03 to 7.01 +/- 0.04. Cerebral ATP levels recovered to 86 +/- 7% (+/- SE) of prearrest concentration by 6 min of CPR. There was no further recovery of ATP, which remained significantly less than control. Therefore, in contrast to hyperemic reperfusion with spontaneous circulation and full ATP recovery, experimental CPR may not be able to restore ATP completely after 6 min of global ischemia despite restoration of CBF and brain pHi to prearrest levels.

Effect of adrenergic drugs on cerebral blood flow, metabolism, and evoked potentials after delayed cardiopulmonary resuscitation in dogs.

BACKGROUND AND PURPOSE: Epinephrine administration during cardiopulmonary resuscitation increases cerebral blood flow by increasing arterial pressure. We tested whether potential beta-adrenergic effects of epinephrine directly influence cerebral blood flow and oxygen consumption independently of raising perfusion pressure. METHODS: Four groups of seven anesthetized dogs were subjected to 8 minutes of fibrillatory arrest followed by 6 minutes of chest compression, ventricular defibrillation, and 4 hours of spontaneous circulation. Cerebral perfusion pressure was increased to approximately equivalent ranges during resuscitation by either 1) epinephrine infusion, 2) epinephrine infusion after pretreatment with the lipophilic beta-adrenergic antagonist pindolol, 3) infusion of the alpha-adrenergic agonist phenylephrine, or 4) descending aortic balloon inflation without pressor agents. RESULTS: We found no difference in cerebral blood flow, oxygen extraction, or oxygen consumption during chest compression among groups. After ventricular defibrillation, depressed levels of cerebral blood flow, cerebral oxygen consumption, and somatosensory evoked potential amplitude were not different among groups. CONCLUSIONS: We detected no evidence that after 8 minutes of complete ischemia, epinephrine administration during resuscitation substantially influences cerebral blood flow or cerebral oxygen consumption independent of its action of raising arterial pressure or or that epinephrine has a negative impact on immediate metabolic or electrophysiological recovery attributable to its beta-adrenergic activity.