Intraneuronal calcium release after traumatic brain injury and hemorrhagic hypotension: a comparison between small-volume hypertonic saline and large-volume lactated Ringer's infusions

Introduction

Calcium is one of the triggers involved in ischemic neuronal death. The injury can be truly delayed, even after cells repolarize and resume physiological and metabolic functions. Therefore, it would be reasonable to prevent calcium influx in early stages of traumatic brain injury (TBI). In the same way, hypertonic saline (7.5%NaCl) infused to hemorrhaged animals rapidly restores cardiac output and arterial pressure. Because hypotension is a strong predictor of outcome in TBI, we tested the hypothesis that hypertonic saline blunts calcium influx in hemorrhagic shock associated with head injury, compared with lactated Ringer's.

Method

Fifteen ketamine-halotane anesthetized mongrel dogs (18.7 ± 1.4 kg) received a localized criogenic brain injury simultaneously with blood withdrawal to a mean arterial pressure (MAP) of 40 mmHg in 5 min, which was maintained at this level for 20 min (shed blood volume 25.5 ± 6.5 ml/kg) and then randomized into three groups: HS, 7.5%NaCl, 4 ml/kg, in 3 min; LR, lactated Ringer's, 33 ml/kg, in 15 min; and CT, controls, which received no treatment. After 20 min, cerebral biopsies were obtained next to the lesion (`clinical penumbra') and from the corresponding contralateral side (`lesion's mirror'), to determine intracellular calcium by fluorescence signals of FURA-2 loaded cells.

Results

Controls remained in hypotension and in a low-flow state, while fluid resuscitation improved hemodynamic profile. There was a significant increase in intracellular calcium in the injured hemisphere in CT (1035 ± 782 nM), compared to both HS (457 ± 149 nM; P = 0.028) and LR (392 ± 178 nM; P = 0.017), with no differences between HS and LR (P = 0.38). Intracellular calcium at the contralateral, uninjured hemisphere, was 438 ± 192 nM in CT, 510 ± 196 nM in HS, and 311 ± 51 nM in LR, with no significant differences between them.

Conclusion

Both small volume hypertonic saline and large volume lactated Ringer's blunts calcium influx in early stages of TBI associated with hemorrhagic shock, suggesting a potential, early benefit, specially during immediate care and transport.

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