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

Objective: Care temperature is reduced spontaneously after asphyxial cardia c arrest in rats. To determine whether spontaneous hypothermia influences n eurologic damage after asphyxial arrest, we compared neurologic outcome in mts permitted to develop spontaneous hypothermia vs. rats managed with cont rolled normothermia. Interventions Male Sprague-Dawley rats were asphyxiated far 8 mins and resu scitated. After extubation, a cohort of rats was managed with controlled no rmothermia (CN) by placement in a servo-controlled incubator set to maintai n rectal temperature at 37.4 degrees C for 48 hrs. GN rats were compared wi th permissive hypothermia (PH) mts that were returned to an ambient tempera ture environment after extubation. Rats were killed at either 72 hrs (PH72h r, n = 14; CN72hr, n = 9) or 6 wks (PH6wk, n = 6, CN6wk, n = 6) after resus citation. PH72 rats were historic controls for the CN72 rats, whereas PH6 a nd CN6 rats were randomized and studied contemporaneously. Measurements: A clinical neurodeficit score (NDS) was determined daily. A p athologist blinded to group scored 40 hematoxylin and eosin -stained brain regions for damage by using a 5-point scale (0 = none, 5 = severe). Quantit ative analysis of CA1 hippocampus injury was performed by counting normal-a ppearing neurons in a defined subsection of CA1. Main Results: Mean rectal temperatures measured in the PH6wk rats (n = 6) w ere 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 progre ssion of NDS (p = .04) and less weight loss (P < .005) compared with CN. Me dian histopathology scores were lower (less damage) in PH72hr vs. CN72hr fo r 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 naive contro ls). In contrast, PH72hr rats demonstrated marked protection (97 +/- 23 nor mal-appearing neurons) that was still evident, although attenuated, at 6 wk s (42 +/- 24 normal-appearing neurons, PH6wk). Conclusion: Rats resuscitated from asphyxial cardiac arrest develop delayed , mild to moderate, prolonged hypothermia that is neuroprotective.