The aim of this study was to investigate the
therapeutic effect of
platonin, a cyanine photosensitizing
dye as well as an inhibitor of proinflammatory
cytokines, in an animal model of
heat stroke. Anesthetized rats, immediately after the onset of
heat stroke, were divided into two major groups and given the following:
normal saline (1 mL per kg
body weight) intravenously, or
platonin (12.5-50 microg/mL per kg
body weight) intravenously. They were exposed to ambient temperature of 43 degrees C to induce
heat stroke. Another group of rats was exposed to room temperature (26 degrees C) and used as normothermic controls. Their physiologic and biochemical parameters were continuously monitored. When the vehicle-treated rats underwent heat exposure, their survival time values were found to be 18 to 22 min.
Resuscitation with intravenous doses of
platonin, but not
normal saline, immediately at the onset of
heat stroke, significantly improved survival during
heat stroke (41-147 min). All heat-stressed animals displayed systemic
inflammation and activated coagulation, evidenced by increased
tumor necrosis factor-alpha, prothrombin time, activated partial thromboplastin time,
fibrinogen degradation products, and
D-dimer, and decreased platelet count and
protein C.
Biochemical markers evidenced cellular
ischemia and injury/dysfunction: plasma levels of blood
urea nitrogen,
creatinine,
glutamic oxaloacetic transaminase,
glutamic pyruvic transaminase, and
alkaline phosphatase, and striatal levels of partial pressure of
oxygen, local cerebral blood flow,
glycerol,
glutamate, and
lactate/
pyruvate were all elevated during
heat stroke. The systemic
inflammation, hypercoagulable state, and
cerebral ischemia and injury during
heat stroke were all significantly suppressed by
platonin. The data demonstrate that
platonin therapy may resuscitate
heat stroke victims by reducing circulatory
shock, systemic
inflammation, hypercoagulable state, and tissue
ischemia and injury.