CEREBROVASCULAR DYSFUNCTION IS AN ATTRACTIVE TARGET FOR THERAPY IN HEAT STROKE^¶

Abstract

2. All heat-stressed rodents, even under general anaesthesia, have hyperthermia, systemic inflammation, hypercoagulable state, arterial hypotension and tissue ischaemia and injury in multiple organs. These findings demonstrate that rodent heat stroke models can nearly mirror the full spectrum of human heat stroke. Experimental heat stroke fulfills the empirical triad used for the dignosis of classical human heat stroke, namely hyperthermia, central nervous system alterations and a history of heat stress.3. These physiological dysfunctions and survival during heat stroke can be improved by whole-body or brain cooling therapy adopted immediately after the onset of heat stroke.4. However, in the absence of body or brain cooling, these heat stroke reactions can still be reduced by the following measures: (i) fluid replacement with 3% NaCl solution, 10% human albumin or hydroxyethyl starch; (ii) intravenous delivery of antiinflammatory drugs, free radical scavengers or interleukin-1 receptor antagonists; (iii) hyperbaric oxygen therapy; or (iv) transplantation of human umbilical cord blood cells.5. In addition, before initiation of heat stress, prior manipulations with one of the following measures was found to be able to protect against heat stroke reactions: (i) systemic delivery of α α α α-tocopherol, mannitol, inducible nitric oxide synthase inhibitors, mu-opioid receptor antagonists, endothelin ET A receptor antagonists, serotoninergic nerve depletors or receptor antagonists, or glutamate receptor antagonists; or (ii) heat shock portein 72 preconditioning.6. There is compelling evidence that cerebrovascular dysfunction is an attractive target for therapy in heat stroke.

Human Umbilical Cord Blood-Derived Cd34+ Cells Cause Attenuation of Multiorgan Dysfunction During Experimental Heatstroke

“…The full spectrum of the signs and symptoms occurring during heatstroke in humans can be mimicked by the rodent heatstroke model (2, 6Y10). Evidence has accumulated to indicate that cerebrovascular dysfunction is an attractive target for therapy in heatstroke (2).…”

“…Heatstroke is a life-threatening illness defined as hyperthermia and multiorgan dysfunction or failure (1,2). Multiorgan dysfunction ensuing from severe heatstroke includes arterial hypotension, hepatic and renal failure, disseminated intravascular coagulation or hypercoagulable state, systemic inflammation, and cerebral ischemia and disorders in humans (1Y5).…”

Improved Detection of Heat Stroke-Induced Brain Injury by High B-Value Diffusion-Weighted Imaging

“…Among several mechanisms proposed to give rise to heat stroke-induced brain injury, ischemia is thought to induce restricted diffusion. Ischemia of brain tissue results from attempts of the body's autoregulatory mechanisms to divert blood flow towards periphery to dissipate excessive heat (21,22). Increased intracranial pressure secondary to venous congestion and brain edema as the result of increased permeability of blood-brain or blood-cerebrospinal fluid barrier may also…”

Commentary: Heat stress-induced neuroinflammation and aberration in monoamine levels in hypothalamus are associated with temperature dysregulation

“…30% of heat stroke survivors experience disability and neurological dysfunction even after cooling of the entire body [9][10][11] . It is inevitable that brain ischemia, inflammation and neuronal damage are the main causes of heat stroke, rather than body hyperthermia [12][13][14][15] . Generally, exertional heat stroke occurs in active healthy individuals during strenuous activity under HS conditions while nonexertional heat stroke occurs in elderly, COPD, chronic diabetics or immunocompromised individuals having systemic inflammation 7 .…”