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Biomedical subjects

Vladimir A Kulchitsky

Publications and source records attributed to Vladimir A Kulchitsky.

5 recordsLinked to original sources
PubMed2003

Bilateral splanchnicotomy does not affect lipopolysaccharide-induced fever in rats.

Intraperitoneal capsaicin desensitizes sensory fibers traveling within both the vagus and splanchnic nerves. Because capsaicin desensitization blocks the first phase of lipopolysaccharide (LPS) fever, whereas surgical vagotomy does not, splanchnic mediation of the first phase was proposed. However, all phases of the febrile response of splanchnicotomized rats to intravenous LPS (10 microg/kg) were similar to those of sham-operated controls. Hence, the splanchnic nerve is likely uninvolved in LPS fever.

Animals↗
PubMed2003

Platelet-activating factor: a previously unrecognized mediator of fever.

Lipopolysaccharide (LPS)-induced systemic inflammation is accompanied by either hypothermia (prevails when the ambient temperature (Ta) is subneutral) or fever (prevails when Ta is neutral or higher). Because platelet-activating factor (PAF) is a proximal mediator of LPS inflammation, it should mediate both thermoregulatory responses to LPS. That PAF possesses hypothermic activity and mediates LPS-induced hypothermia is known. We asked whether PAF possesses pyrogenic activity (Expt 1) and mediates LPS fever (Expt 2). The study was conducted in Long-Evans rats implanted with jugular catheters. A complex with bovine serum albumin (BSA) was infused as a physiologically relevant form of PAF; free (aggregated) PAF was used as a control. In Expt 1, either form of PAF caused hypothermia when infused (83 pmol kg-1 min-1, 60 min, i.v.) at a subneutral Ta of 20 degrees C, but the response to the PAF-BSA complex (-4.5 +/- 0.5 degrees C, nadir) was ~4 times larger than that to free PAF. At a neutral Ta of 30 degrees C, both forms caused fever preceded by tail skin vasoconstriction, but the febrile response to PAF-BSA (1.0 +/- 0.1 degrees C, peak) was > 2 times higher than that to free PAF. Both the hypothermic (at 20 degrees C) and febrile (at 30 degrees C) responses to PAF-BSA started when the total amount of PAF infused was extremely small, < 830 pmol kg-1. In Expt 2 (conducted at 30 degrees C), the PAF receptor antagonist BN 52021 (29 micromol kg-1, i.v.) had no thermal effect of itself. However, it strongly (~2 times) attenuated the febrile response to PAF (5 nmol kg-1, i.v.), implying that this response involves the PAF receptor and is not due to a detergent-like effect of PAF on cell membranes. BN 52021 (but not its vehicle) was similarly effective in attenuating LPS (10 microg kg-1, i.v.) fever. It is concluded that PAF is a highly potent endogenous pyrogenic substance and a mediator of LPS fever.

Animals↗
PubMed2003

Role for the cholecystokinin-A receptor in fever: a study of a mutant rat strain and a pharmacological analysis.

The involvement of the cholecystokinin (CCK)-A receptor in fever was studied. The polyphasic febrile responses to lipopolysaccharide (LPS; 10 microg kg-1, I.V.) were compared between wild-type Long-Evans (LE) rats and the CCK-A-receptor-deficient Otsuka LE Tokushima Fatty (OLETF) rats. The response of the wild-type rats was biphasic, which is typical for LE rats. Phases 1 and 2 of the response of the OLETF rats were similar to those of the LE rats, but the OLETF rats also developed a robust phase 3. This late enhancement of the febrile response could reflect either the absence of the A receptor per se or a secondary trait of the mutant strain. To distinguish between these possibilities, we conducted a pharmacological analysis. We studied whether the normally low phase 3 of LE rats can be enhanced by a CCK-A-receptor antagonist, sodium lorglumide (4.3 microg kg-1 min-1, 120 min, I.V.), and whether the normally high phase 3 of Wistar rats can be attenuated by a CCK-A receptor agonist, sulphated CCK-8 (up to 0.17 microg kg-1 min-1, 120 min, I.V.). The dose of sodium lorglumide used was sufficient to increase food intake (to block satiety), but it did not affect the fever response. In both febrile and afebrile rats, CCK-8 induced dose-dependent skin vasodilatation and decreased body temperature, but it failed to produce any effects specific for phase 3. We conclude that the exaggeration of phase 3 in OLETF rats reflects a secondary trait of this strain and not the lack of the CCK-A receptor per se. None of the three known phases of the febrile response of rats to LPS requires the CCK-A receptor.

Animals↗
PubMed2002

NO-ergic mechanisms are implicated in a disturbed cardiac rhythm after systemic application of lipopolysaccharide E. coli to rats.

In acute experiments on nembutal-urethan-anaesthetized rats, a slow infusion of subseptic dose of lipopolysaccharide (LPS) Escherichia coli (1 mg/ml) via the right jugular vein immediately led to bradycardia and extrasystoles. Preliminary administration of 20 mg/kg N(G)-nitro-L-arginine methyl ester (L-NAME) or 30 mg/kg aminoguanidine hydrochloride prevented the LPS-induced extrasystoles but did not affect the pattern of bradycardia. We conclude that nitric oxide (NO)-ergic mechanisms are involved in provoking electrical instability of the heart in conditions of endotoxemia.

Animals↗