Paradoxical bradycardic response to murine hemorrhagic shock onset predicts cardiovascular function and survival after resuscitation

Cardiac dysfunction after hemorrhagic shock (HS) compromises vital organ perfusion and survival. Our mouse HS model demonstrates that cardiac dysfunction and inflammation is attenuated by mild hypothermia, an effect associated with relative bradycardia during shock and improved survival. Since initial vagal tone during shock could similarly decrease heart rate and inflammation, we further studied heart rate response to initial HS onset. Anesthetized male C57BL6 mice (n = 45) were bled and maintained at a mean arterial pressure of 35 mmHg for 90 min (S90), then resuscitated with remaining shed blood and crystalloid and monitored for 180 min or until death. Overall 180 min survival was 44%. Although similar at baseline, survivors displayed lower initial heart rates than non‐survivors (270 ± 78 bpm vs 312 ± 48 bpm, p < 0.05) within 20 min of HS onset. While these heart rate differences resolved by S90, remaining shed blood volume was higher in survivors compared to non‐survivors (26.2 ± 8.2 mL/kg vs 17.4 ± 6.7 mL/kg, p = 0.0005), suggesting improved cardiovascular function. After resuscitation, echocardiography demonstrated an over 50% reduction in ejection fraction in the non‐survivor group. We conclude that initial bradycardia following hemorrhage is associated with improved cardiac function. Individual differences in the autonomic reflex to shock may help predict survival in this model. Support: NIH T32 HL‐09482.