Therapeutic of hypothermiaThe Pharmacologic Inhibition of Thermoregulation

Mohanad AlBayatiMohanad AbdulSattar Ali Al-Bayati, BVM&S, MSc. Physiol., PhD.

Assistant Professor of Pharmacology and ToxicologyDepartment of Physiology and Pharmacology

College of Veterinary MedicineUniversity of Baghdad

Al Ameria, Baghdad Phone: 0964 7802120391

E. Mail: aumnmumu@covm.uobaghdad.edu.iq

aumnmumu@yahoo.com

Hypothermia <35.0 °C (95.0 °F)

Normal 36.5–37.5 °C (97.7–99.5 °F)

Fever >37.5–38.3 °C (99.5–100.9 °F)

Hyperthermia >37.5–38.3 °C (99.5–100.9 °F)

Hyperpyrexia >40.0–41.5 °C (104–106.7 °F)

The external heat transfer mechanisms are Radiation Conduction Convection Evaporation of perspirationThe process is far more than the passive operation ofthese heat transfer mechanisms, however. The bodytakes a very active role in temperature regulation

Possible Mechanisms Underlying The BeneficialEffects of Hypothermia

Possible Mechanisms Underlying The Risk

Factors of Hypothermia

The most obvious thermoregulatory responses are behavioral. Whenthe temperature of the preoptic area of the hypothalamus rises, thisproduces the sense of being warm; cooling of the skin and possiblyother receptors produces the awareness of being cold. Effectivebehavioral control of temperature depends on both an intactsensory-motor system and an ability to communicate perceptions.Regulation of body temperature is inadequate below the level atwhich the sympathetic nerves leave the cord in spinal cordtransection. This occurs because the hypothalamus can no longercontrol skin blood flow or the degree to which sweating is possible.Critically ill infants and children have a limited ability to alter theirenvironment in response to their perception of temperaturevariations. Moreover, their ability to communicate their perceptionsis often limited by their developmental stage and the severity of theirillness.

Control of Body Temperature

Excitotoxicitya phenomenon that which was first described by Olney in the seventies,

implies the activation in the CNS of the so-called glutamate receptors.nineteen-seventies1, involves the activation of glutamate receptors in the central nervoussystem (CNS). Glutamate, an excitatory amino acid, activates different types of ionchannel forming receptors (named ionotropic) channel-forming receptors(ionotropic) and G-protein-coupled receptors (named metabotropic) to developtheir essential role in the functional activity of the brain. However, highconcentrations of glutamate, or neurotoxins acting at the same receptors, causecell death through the excessive activation of these receptors. In physiologicalconditions, the presence of glutamate in the synapse is highly regulated by veryactive, ATP-dependent transporters in neurones and glia. For instance, in CNSischaemia a decrease in the levels of glucose exerts causes a decrease in ATPproduction, leading to an impairment of glutamate uptake. Moreover, themembrane potential of presynaptic neurones is lost and efflux of excitatory aminoacids occurs, contributing to the excessive activation of post-synaptic glutamatepostsynaptic receptors

Excitotoxicity

Glutamate receptors

As pointed out earlier, above, glutamate and other amino acids canactivate both ionotropic and metabotropic receptors (for review, 3). The latter aresubdivided into three main families, and can be coupled to phospholipase C (PLC)or to adenylyl cyclase (AC). The ion channel forming channel-forming receptorsare subdivided into three different receptor classes that are named by theirselective agonists: AMPA (a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)receptors, kainate receptors and NMDA (N-methyl-D-aspartic acid) receptors.AMPA and kainate receptors trigger rapid excitatory neurotransmission in theCNS,CNS by promoting entry of Na+ into neurones. However, a subset ofneurones in the hippocampus, cortex and the retina express AMPA receptors thatare also permeable to Ca2+. NMDA receptors are associated to a highconductance with a high-conductance Ca2+ channel that in resting, non-depolarising conditions is blocked by Mg2+ in a voltage-dependent manner. Theiractivation is secondary to AMPA or AMPA- or kainate-kainate receptor activationthat receptor activation, which depolarises the neurone, allowing for the reliefthe release of the Mg2+ blockade.