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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A pharmacological profile of the effects of nimodipine, nifedipine and nitrendipine (2.5-20 mg/kg p.o.) in several models which are indicative of possible antidepressant activity, was tested in mice and rats. These compounds, as well as verapamil (short-lasting effect), but not diltiazem, reduced the hypothermia induced by a large dose of apomorphine in mice. Nimodipine and nifedipine slightly increased the behavioural action of L-DOPA in mice, and nimodipine facilitated the action of imipramine in the L-DOPA test. Nimodipine, nifedipine, verapamil and diltiazem slightly reduced the clonidine-induced hypoactivity in rats. The hypothermia induced by reserpine or clonidine in mice was not changed by these drugs. Various antidepressants (imipramine, amitriptyline, citalopram, mianserin) used in the behavioural despair test in mice, in doses which were not effective by themselves, increased the immobility-reducing effect when given jointly with 1,4-dihydropyridine calcium channel antagonists (5 mg/kg). The above results indicate that the psychopharmacological profile of nimodipine, nifedipine and nitrendipine resembles that of antidepressants in some tests only; moreover, these results support the assumption that concomitant administration of antidepressants and 1,4-dihydropyridine calcium channel antagonists may result in a greater antidepressant efficacy.
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PMID:Dihydropyridine calcium channel antagonists as antidepressant drugs in mice and rats. 272 49

Lowering temperature from 37 degrees C to 22, 18, and 14 degrees C triggered automaticity of smooth longitudinal muscle of guinea pig isolated ileum. The amplitude of the hypothermia-induced automaticity was dependent on the degree of temperature drop: the greater the temperature drop, the greater the amplitude. However, when the preparation was initially prepared and maintained at 14 degrees C and then the temperature was raised at a similar rate to 18, 22, and 37 degrees C, the automaticity was not observed. This series of observations suggests that cooling rate may be the trigger and/or part of the triggering mechanism for the observed automaticity. Mepenzolate (1.0 x 10(-6) M), a specific muscarinic receptor antagonist, blocked the automaticity suggesting the involvement of muscarinic receptors in the pathogenesis and/or the manifestation of the automaticity. Verapamil (1.0 x 10(-7) M), a calcium channel blocker which inhibits the transmembrane Ca2+ influx into smooth muscle cells during excitation, blocked the automaticity suggesting that transmembrane Ca2+ influx plays a significant role in the pathogenesis and/or manifestation of the automaticity. A specific cytoplasmic calcium channel blocker, 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate hydrochloride (1.0 x 10(-6) M) blocked the automaticity, suggesting that cytoplasmic calcium also plays a significant role in the pathogenesis and/or manifestation of the automaticity. In order to characterize the temperature-induced changes in the muscarinic receptors, an attempt was made to use the classic method of Furchgott and Burstyn to determine the dissociation constants of acetylcholine at muscarinic receptors at different temperatures. However, the alkylation of muscarinic receptors with phenoxybenzamine at lower temperatures was erratic and the recovery from the occlusion was too rapid to apply the method of Furchgott and Burstyn. We concluded that the lack of reversibility of the effects of phenoxybenzamine at 37 degrees C is due to the predominance of covalent bonding of phenoxybenzamine with the receptors, whereas at lower temperatures like 24 degrees C, the blockade of the muscarinic receptors by phenoxybenzamine is mainly due to simple occlusion.
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PMID:Low temperature and muscarinic receptor activities. 279 13

Calcium channel blockers have an important role in the pharmacotherapy of cardiovascular disorders. These agents act by inhibiting the slow inward current into excitable cells, exert direct negative inotropic, chronotropic, and dromotropic activity, and are potent vasodilators. These direct effects are modified by reflex autonomic stimulation and by pathologic states. Serious adverse effects of the calcium channel blockers are most frequently observed in patients with ventricular dysfunction, conduction system disease, or concomitant beta blockade. Calcium channel blockers are indicated in the treatment of angina pectoris, supraventricular arrhythmias, and hypertension. The use of these agents in patients with hypertrophic cardiomyopathy, congestive heart failure, and pulmonary hypertension is investigational. The calcium channel blockers are gaining increased importance in the management of patients undergoing cardiac surgery. Verapamil is indicated for the treatment of post-cardiac-surgical atrial flutter and fibrillation; however, the calcium antagonists are not effective as prophylaxis against postoperative supraventricular arrhythmias. Laboratory studies have shown that drug interactions exist between calcium channel blockers and inhalational anesthetics and nondepolarizing neuromuscular blocking agents; clinical studies have demonstrated that these interactions are rarely significant. Perioperative coronary spasm can be effectively treated with the calcium channel blockers. The timing of calcium antagonist withdrawal prior to surgery is controversial, but continuation of therapy until surgery is usually safe. The clinical significance of platelet function inhibition by the calcium antagonists is unknown. Protection of ischemic myocardium by calcium channel blockers has been demonstrated. Important interactions between the calcium antagonists, hypothermia, and the ionic constituents of cardioplegia require further study before the role of these agents as adjuncts to clinical cardioplegia is defined. Expanded indications and the introduction of new calcium channel blockers will result in increased use of these agents in the future.
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PMID:Calcium channel blockers and cardiac surgery. 297 80

Nifedipine exhibits a greater incidence of side effects than the other currently marketed calcium channel antagonists. In addition to those effects attributable to calcium channel blockade, nifedipine produces side effects similar to the effects of adenosine. It is probable that nifedipine exerts part of its physiological actions through potentiation of adenosine. Adenosine, an endogenous calcium channel blocker, modifies synaptic events throughout the nervous system and causes sedation, smooth and skeletal muscle relaxation, anticonvulsion, hypotension and hypothermia, all reversible by caffeine or theophylline administration. Nifedipine inhibits adenosine uptake from, and release into, the extracellular space and binds at an adenosine receptor. Both nifedipine and adenosine interact with benzodiazepine binding sites. Interaction between nifedipine and adenosine should be kept in mind when treating patients with nifedipine.
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PMID:Nifedipine: more than a calcium channel blocker. 301 14

Administration of the opiate U-50,488H (3-20 mg/kg s.c.), a selective kappa receptor agonist, produced a dose-dependent decrease of rectal temperature in rats. This hypothermic effect of U-50,488H was accompanied by an enhanced activity of Ca2+/Mg2+ ATPase in crude synaptosomal (P2) fractions obtained from hypothalamus but not from cortex or cerebellum. Mg2+ ATPase activity in these regions was not altered by U-50,488H (15 mg/kg s.c.). Naloxone (5 mg/kg) partially and MR2266 (5 mg/kg) completely reversed the temperature and enzyme changes. Pretreatment with the calcium channel blockers nimodipine (1 mg/kg s.c.), diltiazem (10 mg/kg s.c.) and verapamil (2.5 mg/kg s.c.) potentiated the hypothermic effect of U-50,488H as well as the stimulation of Ca2+/Mg2+ ATPase in hypothalamus. These observations suggest that kappa agonists may produce opiate receptor mediated hypothermia through changes in intracellular Ca2+ levels in the hypothalamus.
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PMID:Interaction of kappa receptor agonists with Ca2+ channel antagonists in the modulation of hypothermia. 302 38

Presently myocardial protection can be obtained in three main ways: 1) energy conservation through chemical induction of rapid and complete diastolic arrest, 2) slowing of the metabolic rate and degradative process through the use of hypothermia, and 3) prevention or reversal of unfavourable ischemic-induced changes with various protective agents. These methods of myocardial protection and their effectiveness, the calcium metabolism during myocardial ischemia, and the effects of calcium channel blockers are briefly reviewed and discussed. It is stressed that myocardial protection during ischemic arrest is a complex entity, and that new modes of myocardial protection are needed in the future.
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PMID:Cardioplegia and myocardial ischemia during cardiopulmonary bypass. 352 Nov 95

Since the gradient between aortic pressure and left ventricular diastolic pressure is a major determinant of coronary blood flow, a change in left ventricular relaxation by its effect on early diastole could diminish early diastolic coronary flow. Two interventions that resulted in impaired left ventricular relaxation, hypothermia, and reperfusion following a left anterior descending coronary artery occlusion were studied to evaluate whether there were associated changes in coronary blood flow. With both interventions, there was a significant prolongation of left ventricular relaxation (p less than 0.01) accompanied by a significant decrease in early diastolic coronary blood flow (p less than 0.01). Verapamil did not have a significant effect on these hemodynamic changes during hypothermia. However, verapamil significantly blunted the effects of reperfusion following ischemia on ventricular relaxation (p less than 0.002) and early diastolic coronary blood flow (p less than 0.01). Thus, impaired left ventricular relaxation has an adverse impact on early diastolic coronary blood flow, which, under the condition of reperfusion following regional myocardial ischemia, can be alleviated with calcium channel blockade.
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PMID:Effect of changes in ventricular relaxation on early diastolic coronary blood flow in canine hearts. 366 79

Adjuvant slow calcium channel blockade theoretically minimizes the calcium influx attendant to potassium-induced cardioplegic arrest, particularly if clinically acceptable levels of cardiac hypothermia are not maintained. The present study assessed the efficacy of diltiazem therapy in ameliorating perturbations of myocardial oxygen consumption that could be attributable to postischemic intracellular calcium accumulation. In 30 canine hearts, myocardial oxygen consumption was determined during incremental isovolumic pressure-volume loading before and 30 minutes after 2 hours of either 20 or 28 degrees C potassium cardioplegic arrest. The intracoronary perfusate in randomized hearts was modified by the addition of diltiazem, 150 micrograms/kg. Although systolic performance (as defined by peak developed pressure as compared with balloon volume curves) was unchanged after 20 degrees C ischemia, adjuvant diltiazem therapy prevented the 44 +/- 2% (p less than .01) decrease in peak developed pressure after 28 degrees C arrest. Moreover, the 39% augmentation of postischemic myocardial oxygen consumption at specific peak developed pressure following both 20 and 28 degrees C ischemia was attenuated with diltiazem only after the warmer ischemic interval. This difference was characterized by a larger (35 +/- 2 vs. 26 +/- 2%; p less than .025) decrease in postischemic oxygen extraction despite a comparable hyperemia. These data suggest that adjuvant diltiazem therapy during potassium-induced cardioplegic arrest preserves energy-efficient pump function only after warmer ischemia, thereby limiting the clinical application of this myoprotective regimen.
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PMID:Temperature-specific effects of adjuvant diltiazem therapy on myocardial energetics following potassium cardioplegic arrest. 378 58

Adult mice (Binghamton Heterogeneous stock) received different doses of ethanol (0.5, 1.0, or 2.0 g/kg) administered alone or in combination with the voltage-sensitive calcium channel antagonist, nimodipine (Bay e 9736). Both 20 and 60 minutes later, sensitivity to ethanol was assessed in terms of rotorod activity and changes in rectal temperatures. Nimodipine (5 mg/kg) alone did not alter rectal temperature or motor coordination, but at both observation periods nimodipine potentiated the hypothermia induced by the highest dose of alcohol (2.0 g/kg) and exaggerated alcohol-induced motor incoordination at all doses. The present set of results indicates that the inhibition of voltage-dependent calcium channels can exaggerate ethanol-induced effects.
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PMID:Nimodipine's interactions with other drugs: I. Ethanol. 399 24

Adult Binghamton Heterogeneous (HET) stock mice were administered one of three doses of diazepam (0.1, 2.5, or 5.0 mg/kg) immediately followed by a second injection of either the slow calcium channel blocker, nimodipine (Bay e 9736), or its vehicle. Hypothermic responses and muscular incoordination were measured twenty and sixty minutes later as assessed by changes in rectal temperature and motoric activity on a rotating rod. Nimodipine (5 mg/kg) alone did not significantly affect body temperature or motor coordination. However, when administered in combination with the two highest doses of diazepam, nimodipine significantly potentiated the hypothermic response produced by these doses both twenty minutes and sixty minutes post-injection. Administration of high doses of diazepam (2.5 and 5.0 mg/kg) resulted in significant motor incoordination at both observation periods, but this effect was not potentiated by nimodipine.
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PMID:Nimodipine's interactions with other drugs: II. Diazepam. 406 97


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