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)

The Flinders Sensitive Line of rats (FSL) has been selectively bred to have increased sensitivity to cholinergic drugs. Typically, these rats react with twice as great a hypothermic effect to muscarinic agonists such as oxotremorine, as do similarly bred Flinders Resistant Line rats (FRL). We compared the effects of three chemically different calcium channel inhibitors (diltiazem, nicardipine and verapamil) on the hypothermia induced in FRL and FSL rats by oxotremorine (0.2 mg kg-1 s.c.). Each drug was injected i.p. in a dose of 20 mumol kg-1 30 min before oxotremorine. Methylatropine (2 mg kg-1 s.c.) was administered 15 min before oxotremorine to block the peripheral effects of the agonist. The hypothermic effect of oxotremorine in FSL rats was antagonized by nicardipine and diltiazem. In contrast, verapamil failed to influence the hypothermic response in FSL rats. Verapamil significantly (P less than 0.05) augmented oxotremorine hypothermia in FRL rats. Diltiazem and nicardipine were without effect on oxotremorine-induced hypothermia in FRL rats. There were no significant changes in temperature in separate groups of FRL and FSL rats treated with calcium channel inhibitors alone.
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PMID:Effects of calcium channel inhibitors on the hypothermic response to oxotremorine in normo and hypercholinergic rats. 168 Oct 59

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

Using an isolated rat heart preparation (Langendorff perfusion, perfusion pressure 100 cm H2O) the response of the hypertrophied heart (spontaneous hypertensive rats lv/bw ratio 3.6 +/- 0.5) to global normothermic (30 min) and hypothermic (25 degrees C, 120 min) ischemic and cardioplegic arrest and reperfusion (30 min) was examined and compared with normal hearts (Wistar rats lv/bw ratio 2.0 +/- 0.3). St. Thomas solution and verapamil (2 mg/l Ringer solution) were used as cardioplegic agents. Before ischemia hypertrophied hearts had a significantly higher pressure-rate product, a lower myocardial perfusion/g myocardium and a lower myocardial ATP and adenine nucleotide content. Unmodified ischemia reduced myocardial function in the hypertrophied hearts to a greater degree than in normal hearts in both normo- and hypothermia. St. Thomas solution and verapamil protected significantly the myocardial function in the normal and hypertrophied heart after normothermic ischemia in a similar manner (60-70% of the initial value). In the hypertrophied ventricle ATP decay and adenine nucleotide loss was greater in verapamil than in St. Thomas solution treated hearts. In hypothermic ischemia only St. Thomas solution protected left ventricular function and adenine nucleotide loss in both normal and hypertrophied hearts. Verapamil was ineffective in the normal ventricle and protected left ventricular function but not the ATP and adenine nucleotide decay in the hypertrophied heart.
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PMID:Function and energy-rich phosphate content of the hypertrophied ventricle after global ischemia and reperfusion. 294 60

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

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

Guide cannulae for microinjection and push-pull perfusion in the unrestrained cat were implanted bilaterally in the anterior hypothalamic, preoptic area (AH/POA) and posterior hypothalamus (PH). Postoperatively, the region was first identified in AH/POA which was reactive to norepinephrine or in PH to excess Ca++ ions; in both cases a hypothermic response was produced. Then either an artificial CSF control vehicle or the Ca++ ion channel blocking agent, verapamil, was perfused for 30 min by means of push-pull cannulae at a rate of 25.0 microliters/min. Verapamil 0.4, 2.0 and 4.0 micrograms/microliter) induced a concentration-dependent hypothermia when perfused within AH/POA sites but hyperthermia when perfused in the caudal hypothalamus. An anatomical analysis of the sites of perfusion revealed that verapamil's thermolytic effect was localized within the classical thermosensitive region of the cat's diencephalon, a region ventral to the anterior commissure and dorsal to the optic chiasm. On the other hand, the loci in which verapamil evoked thermogenesis were localized to a region dorsal to the mammillary bodies and caudal to the descending columns of the fornix. It is suggested that verapamil interferes with Ca++ ion channels in the PH to shift the cat's "set-point" temperature. Conversely, however, verapamil apparently could act on catecholaminergic terminals in AH/POA to enhance the presynaptic release of norepinephrine which, in turn, stimulates the heat loss pathway to yield hypothermia.
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PMID:Neuroanatomical mapping of hypothalamic regions mediating verapamil hyper- and hypothermia in the cat. 376 34

Postoperative supraventricular tachyarrhythmia may occur more often in patients with persistent atrial activity during hyperkalemic hypothermic cardioplegic arrest. Cannulation of both venae cavae with simultaneous right atrial intra-cavitary cooling reduces atrial activity but is cumbersome. To evaluate pharmacologically-induced atrial arrest using verapamil, bipolar ventricular and right atrial electrograms were recorded in 12 dogs during one hour of hyperkalemic hypothermic cardioplegic arrest and cardiopulmonary bypass using single caval cannula. Group I (n = 6) received hyperkalemic hypothermic cardioplegic solution (4 degrees C) (20 mEq/1 K+) with verapamil (1 mg/L) by intermittent intra-aortic infusion during systemic hypothermia (28 degrees C). Group II (n = 6) received hyperkalemic hypothermic cardioplegia without verapamil. The percentage of time atrial activity was present (greater than 10 beats/min) in Group I, was significantly less than in Group II. Similarly the total number of atrial beats in Group I was less than in Group II. Recovery of normal sinus rhythm during reperfusion was prolonged in Group I in comparison to Group II. Verapamil induces significant and persistent atrial suppression during hyperkalemic hypothermic cardioplegic arrest but prolongs recovery of normal sinus rhythm during reperfusion. It remains to be established clinically whether verapamil-induced atrial suppression is associated with less postoperative supraventricular tachyarrhythmia. The potential disadvantage of prolonged sinus node recovery time must also be assessed.
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PMID:Persistent atrial activity during cardioplegic arrest: suppression by verapamil. 376 89

Male, adult mice of the Binghamton heterogeneous stock received one of two doses of ethanol (1.0 g/kg or 2.0 g/kg in saline) alone or in combination with the calcium (Ca2+) slow channel blocker, verapamil (5.45 mg/kg in 25% v/v ethanol in saline). Hypothermic responses and motor incoordination were assessed in terms of rectal temperatures and rotorod activity both 20 and 60 min after drug administration. Verapamil alone did not affect body temperature, but it potentiated ethanol-induced hypothermia at both post-administration test times. Both verapamil and ethanol impaired muscular coordination and these effects were additive at the two observation periods. Verapamil did not affect ethanol blood levels from 10 to 80 min after administration of the drugs. Since motor impairment was observed when verapamil was administered with only its ethanol vehicle, this suggests a powerful interactive effect between the two drugs.
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PMID:The effects of verapamil and ethanol on body temperature and motor coordination. 378 70

The ability of nifedipine, verapamil, and diltiazem to enhance cardioplegic protection has been assessed using an isolated rat heart preparation as a model of cardiopulmonary bypass and ischemic arrest. With normothermic ischemia (30 or 35 min at 37 degrees C), the addition of these compounds enhanced the protective properties of the St. Thomas' cardioplegic solution. All these compounds showed bell-shaped dose-response characteristics, with the optimal concentrations in terms of functional recovery and enzyme leakage of verapamil being 1.0 mumole/liter; nifedipine, 0.075 mumole/liter; and diltiazem, 0.5 mumole/liter. However, under conditions of hypothermia (150 or 180 min at 20 degrees C), none of these compounds improved postischemic functional recovery, although there was some reduction in enzyme leakage. From these results, further experiments were undertaken to investigate the relationship between calcium antagonists and temperature. Verapamil improved functional recovery at 34, 31 and 29 degrees C, but not at 27, 25, and 20 degrees C. These results suggest a common site of action between hypothermia and calcium antagonists in promoting functional recovery after ischemia.
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PMID:Calcium antagonists and myocardial protection during cardioplegic arrest. 399 50

Diltiazem, a calcium slow channel blocker, greatly potentiated and prolonged the antinociceptive effect of morphine in rats. Hypothermia, the primary thermoregulatory effect of morphine, was also potentiated. Verapamil, another calcium blocker elicited corresponding changes in the analgetic and thermoregulatory effects of morphine. These findings seem to be in concert with the suggestions that opiate effects on thermoregulation and nociception are exerted via modulation of calcium fluxes across neural membranes.
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PMID:Potentiation of thermoregulatory and analgesic effects of morphine by calcium antagonists. 650 60


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