Delayed, spontaneous hypothermia reduces neuronal damage after asphyxial cardiac arrest in rats.

OBJECTIVE: Core temperature is reduced spontaneously after asphyxial cardiac arrest in rats. To determine whether spontaneous hypothermia influences neurologic damage after asphyxial arrest, we compared neurologic outcome in rats permitted to develop spontaneous hypothermia vs. rats managed with controlled normothermia. INTERVENTIONS: Male Sprague-Dawley rats were asphyxiated for 8 mins and resuscitated. After extubation, a cohort of rats was managed with controlled normothermia (CN) by placement in a servo-controlled incubator set to maintain rectal temperature at 37.4 degrees C for 48 hrs. CN rats were compared with permissive hypothermia (PH) rats that were returned to an ambient temperature environment after extubation. Rats were killed at either 72 hrs (PH72hr, n = 14; CN72hr, n = 9) or 6 wks (PH6wk, n = 6, CN6wk, n = 6) after resuscitation. PH72 rats were historic controls for the CN72 rats, whereas PH6 and CN6 rats were randomized and studied contemporaneously. MEASUREMENTS: A clinical neurodeficit score (NDS) was determined daily. A pathologist blinded to group scored 40 hematoxylin and eosin -stained brain regions for damage by using a 5-point scale (0 = none, 5 = severe). Quantitative analysis of CA1 hippocampus injury was performed by counting normal-appearing neurons in a defined subsection of CA1. MAIN RESULTS: Mean rectal temperatures measured in the PH6wk rats (n = 6) were 36.9, 34.8, 35.5, 36.7, and 37.4 degrees C at 2, 8, 12, 24, and 36 hrs, respectively. Mortality rate (before termination) was lower in PH compared with CN (0/20 vs. 7/15; p < .005). PH demonstrated a more favorable progression of NDS (p = .04) and less weight loss (p < .005) compared with CN. Median histopathology scores were lower (less damage) in PH72hr vs. CN72hr for temporal cortex (0 vs. 2.5), parietal cortex (0 vs. 2), thalamus (0 vs. 3), CA1 hippocampus (1.5 vs. 4.5), CA2 hippocampus (0 vs. 3.5), subiculum (0 vs. 4), and cerebellar Purkinje cell layer (2 vs. 4) (all p < .05). There was almost complete loss of normal-appearing CA1 neurons in CN72hr rats (6 +/- 2 [mean +/- SD] normal neurons compared with 109 +/- 12 in naïve controls). In contrast, PH72hr rats demonstrated marked protection (97 +/- 23 normal-appearing neurons) that was still evident, although attenuated, at 6 wks (42 +/- 24 normal-appearing neurons, PH6wk). CONCLUSION: Rats resuscitated from asphyxial cardiac arrest develop delayed, mild to moderate, prolonged hypothermia that is neuroprotective.

Hypothermia and hyperthermia in children after resuscitation from cardiac arrest.

OBJECTIVE: In experimental models of ischemic-anoxic brain injury, changes in body temperature after the insult have a profound influence on neurologic outcome. Specifically, hypothermia ameliorates whereas hyperthermia exacerbates neurologic injury. Accordingly, we sought to determine the temperature changes occurring in children after resuscitation from cardiac arrest. STUDY DESIGN: The clinical records of 13 children resuscitated from cardiac arrest were analyzed. Patients were identified through the emergency department and pediatric intensive care unit arrest logs. Only patients surviving for > or =12 hours after resuscitation were considered for analysis. Charts were reviewed for body temperatures, warming or cooling interventions, antipyretic and antimicrobial administration, and evidence of infection. RESULTS: Seven patients had a minimum temperature (T min) of < or =35 degrees C and 11 had a maximum temperature (T max) of > or =38.1 degrees C. Hypothermia often preceded hyperthermia. All 7 patients with T min < or =35 degrees C were actively warmed with heating lamps and 5 of 7 responded to warming with a rebound of body temperatures > or =38.1 degrees C. None of the 6 patients with T min >35 degrees C were actively warmed but all developed T max > or =38.1 degrees C. Six patients received antipyretics and 11 received antibiotics. Fever was not associated with a positive culture in any case. Conclusion. Spontaneous hypothermia followed by hyperthermia is common after resuscitation from cardiac arrest. Temperature should be closely monitored after cardiac arrest and fever should be managed expectantly.

Methyl isobutyl amiloride delays normalization of brain intracellular pH after cardiac arrest in rats.

OBJECTIVE: The sodium/hydrogen ion (Na+/H+) antiporter system of brain cells is responsible for reducing intracellular acid loads and regulating cellular volume. Activation of this system during reperfusion following cardiac arrest may contribute to cerebral edema and subsequent brain damage. Therefore, we wished to determine whether administration of methyl isobutyl amiloride, a known inhibitor of the Na+/H+ antiporter system, would cross the blood brain barrier and delay the return of brain intracellular pH to normal values during reperfusion after cardiac arrest in rats. DESIGN: a) Prospective sequential evaluation of the regional brain blood flow and 3H-methyl isobutyl amiloride extraction fraction in rats; b) prospective sequential evaluation of brain intracellular pH in rats treated with methyl isobutyl amiloride compared with untreated control rats. SETTING: A research laboratory. SUBJECTS: Thirteen male Wistar rats: a) three rats to study regional brain blood flow and 3H-methyl isobutyl amiloride cerebral extraction; and b) ten rats to study the effect of methyl isobutyl amiloride on brain intracellular pH after cardiac arrest and reperfusion. INTERVENTIONS: a) Rats were injected with 14C iodoantipyrine and 3H-methyl isobutyl amiloride, and their brains were subsequently analyzed to determine regional cerebral blood flow and percent of cerebral extraction of methyl isobutyl amiloride. b) Cardiac arrest was induced with potassium chloride followed by resuscitation 7 mins later in untreated control rats and rats treated with methyl isobutyl amiloride. MEASUREMENTS AND MAIN RESULTS: a) Regional cerebral blood flow (mL/100 g/min) determined with 14C iodoantipyrine and percent of cerebral extraction of 3H-methyl isobutyl amiloride were evaluated in various regions of the brain. Mean +/- SD values were 167 +/- 15 and 7 +/- 1 for the frontal cerebral cortex; 159 +/- 10 and 7 +/- 2 for the parietal cerebral cortex, 130 +/- 17 and 8 +/- 1 for the hippocampus, 154 +/- 33 and 13 +/- 4 for the cerebellum and 166 +/- 27 and 6 +/- 1 for the striatum (mL/100 g/min). These values were determined by a dual label indicator fractionation method. b) Brain intracellular pH was measured by neutral red histophotometry after 15 mins of reperfusion following cardiac arrest. As compared with untreated control rats, methyl isobutyl amiloride-treated animals had significantly lower brain intracellular pH values after 15 mins of reperfusion. Mean +/- SD pH values were 6.78 +/- 0.18 for the rats treated with methyl isobutyl amiloride vs. normal intracellular pH of 7.11 +/- 0.07 for the untreated control rats. CONCLUSIONS: a) Methyl isobutyl amiloride crosses the blood brain barrier of rats. b) The Na+/H+ antiporter system is operative during reperfusion after cardiac arrest in rats.