Effects of dantrolene on cooling times and cardiovascular parameters in an immature porcine model of heatstroke

OBJECTIVE To evaluate the effects of dantrolene on cooling times and cardiovascular parameters in an immature porcine model of heatstroke. DESIGN Prospective, randomized, controlled, multigroup study. SETTING Research animal laboratory. SUBJECTS Yorkshire piglets (n = 16), 4 to 5 wks of age, 3.5 to 4.5 kg of body weight. INTERVENTIONS Animals were slowly heated with a radiant heat source to 43 degrees C and then maintained at this temperature for 30 mins. The animals were then removed from the heat source and randomized into one of four groups to receive either conventional cooling methods consisting of fluid resuscitation with 0.9% sodium chloride solution, sponging with room temperature water, mechanical fanning, and gastric lavage with iced 0.9% sodium chloride solution (group 1), conventional cooling methods and dantrolene (group 2), conventional cooling methods and dantrolene's vehicle mannitol (group 3), or no treatment (group 4). Cooling times, defined as the time required to reach a core body temperature of 38.5 degrees C, and cardiovascular parameters for each group were then compared. MEASUREMENTS AND MAIN RESULTS Animals in groups 1, 2, and 3 had significantly (p < .05) lower core body temperatures than animals that received no treatment at the conclusion of the experiment. Piglets in groups 2 and 3 had faster cooling times than piglets in group 1 (p < .05). However, there was no statistically significant difference in cooling times between the animals in groups 2 and 3. There were no statistically significant differences in heart rate, mean arterial pressure, central venous pressure, pulmonary artery occlusion pressure, or systemic vascular resistance index between animals in groups 1, 2, or 3. Group 3 piglets had higher cardiac indices and stroke indices than the piglets in the other groups (p < .05). CONCLUSIONS Therapeutic interventions with conventional cooling or conventional cooling and dantrolene provided significant improvement in cardiovascular function in an immature porcine heatstroke model. Dantrolene, given with conventional cooling methods, offered no significant improvement in cardiovascular parameters compared with conventional cooling methods alone. Dantrolene significantly shortened the cooling time compared with conventional cooling but did not significantly shorten the cooling time compared with its vehicle, mannitol. Although dantrolene significantly shortened the cooling time, it did not appear to be superior compared with