Multiorgan dysfunction ensuing from severe
heatstroke includes
hypotension, hepatic and
renal failure, hypercoagulable state, activated
inflammation, and
cerebral ischemia and injury. We attempted to assess whether human umbilical cord blood-derived CD34+
cell therapy improves survival during experimental
heatstroke by attenuating multiorgan dysfunction. Anesthetized rats, immediately after the onset of
heatstroke, were divided into 2 major groups and given CD34- or CD34+ cells (1 x 10(5)-5 x 10(5)/mL/kg
body weight) i.v. They were exposed to ambient temperature of 43 degrees C to induce
heatstroke. Another group of rats were exposed to room temperature (26 degrees C) and used as normothermic controls.
Hypotension, hepatic and
renal failure (evidenced by increased serum
urea nitrogen,
creatinine,
aspartate aminotransferase,
alanine aminotransferase, and
alkaline phosphatase levels in plasma), hypercoagulable state (evidenced by increased prothrombin time, activated partial thromboplastin time, and
D-dimer, and decreased platelet count and
protein C in plasma), activated
inflammation (evidence by increased
TNF-alpha levels in serum), and cerebral dysfunction (evidenced by
intracranial hypertension, cerebral hypoperfusion and
hypoxia, and
cerebral ischemia and injury) were monitored. When the CD34- cell-treated or untreated rats underwent heat stress, their survival time values were found to be 19 to 23 min.
Resuscitation with CD34+ cells significantly improved survival time (duration, 63-291 min). As compared with normothermic controls, all CD34- cell-treated
heatstroke animals displayed
hypotension, hepatic and
renal failure, hypercoagulable state, activated
inflammation, and
cerebral ischemia and injury. However, CD34+
cell therapy significantly caused attenuation of all the above-mentioned
heatstroke reactions. In addition, the levels of
IL-10 in plasma and
glial cell line-derived neurotrophic factors in brain were all significantly increased after CD34+
cell therapy during
heatstroke. Our data indicate that CD34+
cell therapy may resuscitate persons who had a
heatstroke by reducing multiorgan dysfunction or failure.