dinoprost and Hypothermia

NSAIDs are promising agents for preventing cold injury (frigoprotectors). The influence of prophylactic administration of the non-selective COX inhibitor diclofenac sodium (7 mg/kg) and the highly selective COX-2 inhibitor etoricoxib (5 mg/kg) on cyclooxygenase pathway biomarkers was studied on the model of acute general cooling (air hypothermia at -18 °С for 2 hours). Diclofenac completely prevented a decrease in body temperature, surpassing etoricoxib. In the liver of the rats immediately after cold exposure, the content of COX-1 was increased moderately and the content of COX-2 highly significantly. Very significantly, the level of PGE2 decreased, and the levels of PGF2α, especially PGI2 and TXB2, were elevated. In the blood serum, the level of COX-1 was decreased, and the changes in COX-2 and prostaglandins levels were similar to those in the liver. Diclofenac exerted a moderate effect towards the normalization of both COX isoforms in the liver, moderately increased the content of PGE2, and decreased - PGF2α and TXB2 without changing the level of PGI2. In serum, diclofenac reduced COX-1 level to subnormal values, and its effect on other biomarkers was similar to that in the liver, except for a moderate decrease in PGI2. Thus, diclofenac was inferior to etoricoxib, which normalized COX-1, COX-2, PGE2, and PGI2 in the liver and reduced the content of PGF2α and TXB2 in the liver to subnormal values. At the same time, in the blood serum, it decreased COX-1, COX-2, and PGE2 to subnormal values, normalized PGF2α, and PGI2, and significantly reduced TXB2. The opposite degree of intensity of the influence of diclofenac and etoricoxib on the cyclooxygenase pathway and body temperature indicates a dissociation of anti-inflammatory and frigoprotective activity. Inhibition of oxidative stress is not determinative for the frigoprotective activity of NSAIDs since diclofenac, despite the weaker influence on the content of 8-isoprostane in the liver, still exerts the maximum frigoprotective activity.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acid; Body Temperature; Cyclooxygenase 2; Diclofenac; Dinoprost; Dinoprostone; Etoricoxib; Hypothermia; Rats

The effect of mild and moderate hypothermia on ischemia-induced glutamate release and eicosanoid production was evaluated in WKY rats subjected to incomplete forebrain ischemia. Under isoflurane anesthesia, microdialysis probes were inserted into the hippocampus and caudate nucleus. In four groups of rats, the intraischemic temperature was maintained at either 38 degrees C (normothermia), 36 degrees C, 34 degrees C (mild hypothermia) and 30 degrees C (moderate hypothermia). In these groups, normothermia was restored immediately upon reperfusion. In two additional groups, both intra- and post-ischemic temperatures were maintained at either 34 degrees C or 30 degrees C. The levels of glutamate were measured in the dialysate collected during ischemia and the levels of TxB2, 6-keto-PGF1 alpha and PGF2 alpha were measured in dialysate collected prior to and after ischemia. As expected, hypothermia reduced ischemia-induced glutamate release in both structures. However, the application of mild hypothermia did not attenuate post-ischemic levels of all eicosanoids measured. Moderate hypothermia (30 degrees C) attenuated the post-ischemic increase in the levels of PGF2 alpha. The data suggest that the processes that lead to eicosanoid formation are less sensitive to temperature reduction than those that lead to glutamate release.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Body Temperature; Brain Chemistry; Brain Ischemia; Caudate Nucleus; Dinoprost; Eicosanoids; Glutamic Acid; Hippocampus; Hypothermia; Microdialysis; Rats; Rats, Inbred WKY; Reperfusion; Thromboxane B2

The effects of hypothermia and hyperthermia on the cerebral microcirculation were studied using isolated perfused intracerebral (parenchymal) arterioles obtained from rats. In a temperature-dependent manner, hypothermia (20.0 degrees to 35.0 degrees C) dilated the spontaneous tone developed by the arterioles and also diminished their contractile response to potassium and prostaglandin F2 alpha. In contrast, hyperthermia (40.0 degrees to 45.0 degrees C) induced a biphasic response consisting of initial vasoconstriction and secondary vasodilation. Exposure of the vessels to 45.0 degrees C for 30 minutes irreversibly abolished the spontaneous tone and responsiveness of the arterioles when the temperature of the preparation was returned to 37.5 degrees C. In calcium-free solutions, however, the arteriolar diameter was not affected within a temperature range of 20.0 degrees to 45 degrees C. Furthermore, arterioles that had been in a calcium-free solution during exposure to 45 degrees C temperature recovered their viability at 37.5 degrees C. These results suggest that changes in ambient temperature alter calcium-induced contraction in arteriolar smooth muscle, and that the irreversible effects of hyperthermia on the arterioles are dependent upon extracellular calcium. These studies indicate that alterations in brain temperature may affect the pathogenesis of cerebral ischemia by mechanisms that are in part independent of parenchymal metabolism.

Topics: Analysis of Variance; Animals; Arterioles; Calcium; Cerebrovascular Circulation; Dinoprost; Fever; Hydrogen-Ion Concentration; Hypothermia; In Vitro Techniques; Potassium; Rats; Vasoconstriction; Vasodilation