Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Right and left guinea-pig atria responded to decreasing temperatures (42-27 degrees C) with elevation for force of contraction and concomitant increases in cAMP. When atria were rapidly cooled from 42 to 27 degrees C the increase in cAMP occurred prior to the onset of the inotropic responses. Papaverine (3 X 10(-5) M) potentiated the effects of temperature on cAMP and force of contraction on left atria driven at 0.5 Hz. On right atria beating spontaneously at frequencies above 2 Hz papaverine only potentiated the effect of decreasing temperatures on the response of cAMP but not on that of force of contraction. Time course studies of the effects of isoprenaline (3 X 10(-8) M) on right atria at 27 degrees C showed large inotropic responses to isoprenaline which were accompanied by increases in cAMP. At 42 degrees C the responses of force of contraction and cAMP to isoprenaline occurred faster and were only short-lasting. As with the time courses for isoprenaline, dose-response curves for the effect of isoprenaline and papaverine on cAMP content and force of contraction also appeared to be shifted towards higher levels at hypothemia. However, pD2 values reflected increases in affinity for inotropic, but not for the cAMP responses to isoprenaline and papaverine at hypothermia. These results show that cyclic AMP is involved in the inotropic responses to hypothermia, but not in the supersensitivity of heart to isoprenaline and papaverine as observed at low temperatures.
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PMID:The role of cyclic AMP in temperature-dependent changes of contractile force and sensitivity ot isoprenaline and papaverine in guinea-pig atria. 20 21

The effects of two vasodilators, papaverine and pentoxifylline (a methylxanthine derivative), on liver function after 19 hr hypothermic preservation were investigated. Hypothermic preservation was performed according to the standard technique, and liver hemodynamics and function were studied during 70 min immediately after reperfusion in an isolated perfused rat liver system. No significant changes occurred after hypothermic storage for 5 hr. However, when the storage was prolonged to 19 hr, bile flow and taurocholate intrinsic clearance were significantly reduced; transaminase release was markedly increased and histological studies demonstrated centrilobular necrosis. Concomitantly, liver blood flow was significantly reduced and intrahepatic vascular resistance was increased. Papaverine and pentoxifylline administered during preservation and at the time of reperfusion significantly improved all parameters. The improvement was more pronounced after pentoxifylline, and this group showed no significant difference in any of the studied parameters from the control livers. The results show that two vasodilators significantly protect the liver during long hypothermic preservation. The data suggest that abnormalities of liver microcirculation are of major importance in the pathogenesis of liver injury after hypothermic storage.
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PMID:Protective effect of vasodilators on liver function after long hypothermic preservation: a study in the isolated perfused rat liver. 265 94

The O2 supply of the blood-free perfused brain cortex of the guinea pig was investigated by measuring polarographically the local distribution of tissue PO2 at 18 degrees C, 24 degrees C, and 37 degrees C. The perfusion was performed in situ, using a medium equilibrated by a gas mixture of 95% O2 and 5% CO2. Papaverine was added to prevent vasoconstriction during hypothermia. To avoid measuring artefacts thin micro electrodes with a small sharpened tip of ca. 4 microns in diameter were used and a special puncturing technique was applied. The experimental results indicate the presence of a large variation of local tissue PO2. Local mean PO2 increased up to a depth of 1000 microns, reached a plateau, and then decreased towards 3000 microns. This demonstrates that the O2 supply changes in dependence of the distance of the brain surface. This may partly be caused by the special vascularization pattern of the brain cortex. As it follows from the PO2 histograms, at 24 degrees C the tissue layer between 0-2000 microns (layer I) was well supplied with oxygen, whereas at the same time the layer between 2001-3000 microns (layer II) was hypoxic. At 37 degrees C, both layers were hypoxic, but layer III showed the more pronounced tissue hypoxia. To obtain a sufficient oxygen supply the temperature had to be reduced below 24 degrees C to sufficiently decrease tissue O2 consumption: at 18 degrees C, there was no sign of hypoxia any more. In comparison with the PO2 histogram of the tissue the PO2 histogram of the pial surface was shifted to higher PO2 values.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxygen supply of the blood-free perfused guinea-pig brain in normo- and hypothermia measured by the local distribution of oxygen pressure. 275 77

Previous results (J. Pharm. Dyn., 7, 342, 1984) from this laboratory indicated that papaverine, a classical phosphodiesterase inhibitor, inhibited the transport of organic anions such as p-aminohippurate (PAH) and urate in rat kidney cortical slices. The transport of papaverine itself, an organic cationic drug, in the kidney is not yet understood. The purpose of this study was to examine the interaction of papaverine with incubated slices and basolateral membrane vesicles prepared from rat kidney cortex, in terms of the possibility of the intracellular action of papaverine in kidney cells. Papaverine was taken up against a concentration gradient by kidney cortical slices and by liver slices. The uptake of papaverine by the former slices was depressed by hypothermia and anoxia with metabolic inhibitors, but that of the drug by the latter slices was not affected by hypothermic condition. Tetraethylammonium (TEA) as a prototype for organic cationic drugs did not depress papaverine transport. TEA also had no effect on the inhibitory effect of papaverine on PAH accumulation in kidney cortical slices. Papaverine, however, inhibited TEA accumulation prominently. Kinetic studies using the slices indicated that papaverine increased the Km for TEA accumulation and decreased Vmax. Then, papaverine inhibition was a "mixed type". TEA uptake by basolateral membrane vesicles was markedly inhibited by papaverine, but PAH uptake by the vesicles was not affected by the drug. The present results indicate that papaverine may be at least partly transported by the same system which handles TEA, but some aspect of the transport system for papaverine may be qualitatively different from that for TEA. Additional studies are required, however, to unequivocally establish the relationships between papaverine and TEA renal transport mechanisms.
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PMID:Transport of papaverine in rat kidney cortical slices. 653 Jun 47

Administered intracisternally, adenosine (ADO), 2-chloroadenosine (CADO), adenosine-5'-cyclopropylcarboxamide (ACC) and adenosine-5'-ethylcarboxamide (AEC) caused dose-related increases in hot plate reaction times in mice. The rank order of potency was AEC=ACC greater than CADO greater than ADO and ACC exerted demonstrable effects with doses as low as 10 ng/mouse. ADO itself was more potent than AMP, ADP, ATP and several other related compounds of interest. Theophylline, caffeine and 8-phenyltheophylline antagonized the antinocisponsive effect of CADO or ACC. Papaverine (an adenosine uptake blocker) and erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA: an adenosine deaminase inhibitor) potentiated the effect of ADO. EHNA did not potentiate the action of CADO in this procedure. The antinocisponsive effect of CADO was not antagonized by a host of neurally active agents including naloxone, clonidine and RO 20-1724. Time course studies indicated that the antinocisponsive effect of ADO was transient with the peak effect occurring 5 min after injection and disappearing by 60 min, whereas the effect of CADO persisted for at least 90 min. Intracisternally administered CADO also caused a pronounced hypothermia, loss of muscle tone and was active in the mouse writhing test. Taken together, these data demonstrate that purine exert potent in vivo behavioral effects and are consonant with the existence of a central purinergic P1-receptor which is amenable to selective pharmacological manipulation.
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PMID:In vivo behavioral assessment of central nervous system purinergic receptors. 689 75

Mild hypothermia (32-34 degrees C of brain temperature) was used for brain protection in patients with progressive ischemic neurological deficits associated with severe cerebral vasospasm and who did not respond to medical treatment or intravascular angioplasty. Results showed that 2 of 3 patients in Hunt & Kosnik grade I to III and 2 patients who underwent delayed operation on day 5 and 9 each and had ischemic neurological deficits made good recovery with this treatment. Favourable outcome was obtained in 4 of 9 patients in grade IV and V. Mild hypothermia is thought to provide brain protection in critical ischemia due to severe cerebral vasospasm and can lengthen therapeutic time to employ angioplasty and intraarterial Papaverin infusion.
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PMID:Protective effect of mild hypothermia on symptomatic vasospasm: a preliminary report. 1145 87

Phosphodiesterases (PDEs) form a family of enzymes involved in the hydrolysis of cyclic adenosine and guanosine monophosphate (cAMP and cGMP). PDE10A is a member of this family that is almost exclusively expressed in the striatum. Increasing cAMP/cGMP levels via inhibition of PDE10A is under consideration as a novel therapeutic avenue in the discovery of antipsychotics. Papaverine has been used as a pharmacological tool to establish the possible clinical use of PDE10A inhibitors as antipsychotics. Papaverine is known to increase cAMP levels in striatum and to decrease blood pressure, body temperature and locomotor activity after systemic administration. In this study, the effects of papaverine are compared to those of a more specific PDE10A inhibitor MP10. Papaverine raised striatal cAMP levels with hypothermia, hypoactivity and decreased cardiovascular responses. The more selective MP10 had significantly less effects on body temperature and cardiovascular functions, but reduced locomotor activity to a similar extend as papaverine.
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PMID:Effects of phosphodiesterase 10 inhibition on striatal cyclic AMP and peripheral physiology in rats. 2040 82