Resuscitation from experimental heatstroke by transplantation of human umbilical cord blood cells.
OBJECTIVE
Human umbilical cord blood cells (HUCBCs) are effective in the treatment of conventional stroke in experimental models. In the study described herein, we administered HUCBCs into the femoral vein or directly into the cerebral ventricular system and assessed their effects on circulatory shock, cerebral ischemia, and damage during heatstroke.


METHODS
Controlled, prospective study.


METHODS
Hospital medical research laboratory.


METHODS
Sprague-Dawley rats (287 +/- 16 g body weight, males).


METHODS
Anesthetized rats, immediately after the onset of heatstroke, were divided into four major groups and given the following: a) normal saline or AIM-V medium intravenously (0.3 mL) or intracerebroventricularly (10 microL); b) peripheral blood mononuclear cells (5 x 10 in 0.3 mL AIM-V medium, intravenously, or 5 x 10 in 10 microL AIM-V medium, intracerebroventricularly); or c) HUCBCs (5 x 10 in 0.3 mL AIM-V medium, intravenously, or 5 x 10 in 10 microL AIM-V medium, intracerebroventricularly). Another group of rats, under urethane anesthesia, were exposed to room temperature (26 degrees C) and used as normothermic controls. Urethane-anesthetized animals were exposed to an ambient temperature of 43 degrees C to induce heatstroke. Their physiologic and biochemical parameters were continuously monitored.


RESULTS
When the vehicle-treated rats underwent heat exposure, their survival time values were found to be 21-23 mins. Resuscitation with intravenous or intracerebroventricular doses of HUCBCs, but not peripheral blood mononuclear cells, immediately at the onset of heatstroke significantly improved survival during heatstroke (61-148 mins). As compared with values for normothermic controls, the vehicle-treated heatstroke rats had lower mean arterial pressure, cerebral blood flow, and brain PO2 values but higher intracranial pressure and cerebral ischemia values and more injury markers. The circulatory shock, intracranial hypertension, cerebral hypoperfusion and hypoxia, increment of cerebral ischemia, and damage markers during heatstroke were all significantly attenuated by intravenous or intracerebroventricular delivery of HUCBCs but not peripheral blood mononuclear cells.


CONCLUSIONS
We successfully demonstrate that HUCBC therapy may resuscitate heatstroke victims by reducing circulatory shock and cerebral ischemic injury; central delivery of HUCBCs seems superior to systemic delivery of HUCBCs in resuscitating patients with heatstroke.
Chen
Sheng-Hsien
SH
Institute of Clinical Medicine, School of Medicine, National Cheng Kung University, Chi-Mei Medical Center, Tainan, Taiwan.
Chang
Fong-Ming
FM
Tsai
Yung-Chieh
YC
Huang
Kuo-Feng
KF
Lin
Mao-Tsun
MT
D000704:Analysis of Variance; D000818:Animals; D002545:Brain Ischemia / Q000473:pathology / Q000517:prevention & control*; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D018883:Heat Stroke / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D011446:Prospective Studies; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation / Q000379:methods*; D012769:Shock / Q000473:pathology / Q000517:prevention & control*; D018709:Statistics, Nonparametric; D016019:Survival Analysis
D009569:Nitric Oxide