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)

To determine whether the calcium antagonist verapamil can produce satisfactory myocardial preservation during global ischemia, we studied three groups of eight dogs. Serial left ventricular biopsy specimens were taken for adenosine triphosphate and creatine phosphate content. Arterial and coronary sinus blood samples were obtained for lactate and oxygen content determination prior to ischemia, immediately after the ischemic interval, and after a 30 minute reperfusion period. Starling and isovolumetric ventricular function curves were determined prior to ischemic arrest and after 45 minutes of reperfusion. All animals were systemically cooled to 25 degrees C, and the aorta was clamped for 120 minutes. Group I had a potassium cardioplegic solution (30 mEq/L) chilled to 4 degrees C and injected into the aortic root. The initial dose was 200 ml and an additional 100 ml was infused at 20 minute intervals. Group II had a solution containing verapamil (0.15 mg/kg/L), diluted in Ringer's solution (4 degrees C), injected into the aortic root. The initial and subsequent doses were as in Group I. Group III received the same solution as Group II, but at room temperature. Alterations in lactate metabolism were not significantly different in any of the three treatment groups. A reduction in oxygen consumption was seen in Group III, but was not found to be statistically significant. However, the reduction in coronary flow at the end of reperfusion was statistically significant in Group III (p less than 0.05). Verapamil given at room temperature resulted in poor preservation of left ventricular function and high-energy stores. Verapamil combined with extreme hypothermia (Group II) provided excellent preservation of left ventricular compliance and contractility. Cold verapamil cardioplegia was superior to potassium cardioplegia for the preservation of adenosine triphosphate.
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PMID:Verapamil cardioplegia: improved myocardial preservation during global ischemia. 673 3

The influence of verapamil, nifedipine and cinnarizine on clonidine-induced hypothermia, spontaneous and explorative motility was investigated in mice. Verapamil 5 and 15 mg/kg, nifedipine 17.5 and 50 mg/kg and cinnarizine 75 and 200 mg/kg (that is 1/30 and 1/10 of LD50 respectively) were injected intraperitoneally. The drugs were given in single doses (1/10 LD50) and in repeated doses (1/30 LD50) during a 10 days course. In acute experiments the drugs were given 60 min before clonidine administration, while in chronic experiments clonidine was given on the 11th day of the experiment. Nifedipine prevents clonidine-induced hypothermia in both the applied doses, verapamil only in a single dose, and cinnarizine in repeated doses. Only repeated administration of nifedipine and cinnarizine weakens the clonidine-induced sedation in the studies of spontaneous motility, and as for nifedipine also in explorative motility.
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PMID:The influence of calcium channel blockers on the central action of clonidine. 800 Apr 43

The effects of nifedipine (17.5 and 50 mg/kg), verapamil (5 and 15 mg/kg) and cinnarizine (75 and 200 mg/kg) on acute toxicity and central actions of ethanol (i.e. ethanol-induced sleep and hypothermia, disturbances of rota-rod performance and spontaneous activity) were investigated in mice. Additionally, effects of these drugs on the development of tolerance to hypothermic and sleep-inducing action of ethanol were studied in rats. Calcium antagonists were given acutely 30 min before ethanol administration, or chronically once daily (lower dose) for 10 days, and on the 11th day the animals received an ethanol injection. Single doses of nifedipine increased the acute toxicity of ethanol and potentiated its central effects. After long-term administration of nifedipine no significant alterations in the central actions of ethanol were observed. Verapamil and cinnarizine antagonized the ethanol-induced sleep and impairment of locomotor activity. Nifedipine did not affect the development of tolerance to hypnotic and hypothermic action of ethanol. Verapamil prevents the development of tolerance to hypnotic action of ethanol, whereas cinnarizine prevents the development of tolerance to the hypnotic and hypothermic action of ethanol.
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PMID:Effects of calcium antagonists on central actions of ethanol: comparative studies with nifedipine, verapamil and cinnarizine. 814 73

The effects of cold and restraint and of some of the antiulcer drugs on adenosine nucleotide content in the gastric glandular mucosa were examined. A bioluminescence technique was used to measure the amount of ATP and its metabolites in gastric mucosal tissue. Cold-restraint produced gastric lesions and increased the gastric mucosal ATP. Verapamil pretreatment attenuated these lesions and further intensified the ATP increase in a dose-related manner. The ATP/ADP ratio and the Atkinson index were also elevated. Calcium gluconate produced similar effects. Atropine or EGTA pretreatment protected or worsened the gastric lesion, respectively, but did not have any influence on the changes in mucosal energy metabolism. Ranitidine pretreatment lessened the lesion formation but had no influence on the nucleotide content. These findings indicate that the metabolic rate of the gastric mucosa is suppressed during cold-restraint conditions; this depression is probably due to hypothermia and reduction of mucosal metabolism. The lesion-protecting mechanisms of the drugs do not seem to be mediated through their effects on mucosal energy metabolism. The oxygen- and ATP-sparing effects of verapamil may contribute partly to its gastro-protective effect.
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PMID:Role of gastric glandular mucosal energy metabolism in cold-restraint gastric lesion formation. 818 16

Ca2+ accumulates in the nucleus and DNA undergoes enzymatic cleavage into internucleosome-length fragments before acetaminophen and dimethylnitrosamine produce hepatic necrosis in vivo and toxic cell death in vitro. However, Ca(2+)-endonuclease fragmentation of DNA is characteristic of apoptosis, a type of cell death considered biochemically and functionally distinct from toxic cell death. The present studies investigate DNA fragmentation as a critical event in toxic cell death by testing whether the Ca(2+)-calmodulin antagonist chlorpromazine and the Ca2+ channel blocker verapamil prevent acetaminophen-induced hepatic necrosis by inhibiting Ca2+ deregulation and DNA damage. Acetaminophen overdose in mice produced accumulation of Ca2+ in the nucleus (358% of control) and fragmentation of DNA (250% of control) by 6 h, with peak release of ALT occurring at 12-24 h (38,000 U/l). Pretreatment with chlorpromazine prevented increases in nuclear Ca2+ and DNA fragmentation and nearly abolished biochemical evidence of toxic cell death. Verapamil pretreatment also decreased Ca2+ accumulation and DNA damage while attenuating liver injury. The Ca2+ antagonists did not protect against toxic cell death through hypothermia because neither produced the delay in toxicity that is customarily associated with hypothermia. Nor did chlorpromazine or verapamil protect through inhibiting acetaminophen bioactivation. Chlorpromazine failed to diminish glutathione depletion in whole liver and isolated nuclei. Verapamil (250 microM) also failed to alter glutathione depletion in whole liver and had no effect on acetaminophen-glutathione adduct formation by mouse liver microsomes and by cultured mouse hepatocytes. Collectively, these results support the hypothesis that Ca(2+)-induced DNA fragmentation plays a significant role in cell necrosis produced by acetaminophen and may contribute to toxic cell death caused by other alkylating hepatotoxins.
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PMID:Ca2+ antagonists inhibit DNA fragmentation and toxic cell death induced by acetaminophen. 846 87

Levine-prepared, female, Sprague-Dawley rats were used to investigate the possible protective effects of the NMDA receptor-blocker anesthetic ketamine and the Ca2+ channel-blocker verapamil (0.4 mg kg-1 'low dose', and 1.0 mg kg-1 'high dose') in rats during acute 2400 ppm carbon monoxide (CO) poisoning. Blood glucose and lactate concentrations, heart rate, mean arterial blood pressure (BP), body temperature (BT), neurological function and cerebral cortical water content were measured. In most cases glucose increased after 45 min and then fell to initial values after 90 min. Lactate concentration increased sharply during CO exposure in the saline and in the low- and high-dose verapamil groups, while the lactate increase in rats given ketamine at 40 mg kg-1 was significantly lower than with saline. Lactate was also significantly lower in these rats after 90 min than in the high-dose verapamil group. Lactate was normal in all four groups after 2 and 4 h of air recovery. Ketamine significantly lowered the heart rate prior to CO exposure, and the heart rate remained significantly below values for the saline and for the low- and high-dose verapamil groups throughout CO exposure. The BP decreased in all groups during CO exposure, and the BP recovery which took place in all four groups was significantly more rapid in the ketamine group. Recovery from CO-induced hypothermia was similar in the ketamine and saline groups, whereas rewarming tended to occur more slowly and less completely in the two verapamil-treated groups. There were no significant differences in neurological function among the four groups, as assessed after 4 h of recovery. However, cerebral edema was significantly reduced by treatment with 40 mg kg-1 ketamine as compared with saline. Verapamil at neither the low nor the high doses was of significant benefit in this regard. No rat in the 40 mg kg-1 ketamine group died during CO exposure, whereas all deaths in the other groups took place during CO exposure. The use of higher and lower doses of ketamine suggest 40-80 mg kg-1 as most effective in suppressing lactate production; 40 mg kg-1 ketamine may be optimal with regard to survival. The results suggest that ketamine is beneficial, when administered before and during acute severe CO poisoning, in reducing blood lactate and cerebral edema and in improving BP recovery and survival. Verapamil, in contrast, appears to provide no benefits in these respects.
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PMID:NMDA receptor-blocker ketamine protects during acute carbon monoxide poisoning, while calcium channel-blocker verapamil does not. 885 15


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