Effect of histamine h 2 receptor antagonist cimetidine on the concentrations of zinc and calcium in plasma and heart muscle of rats with hemorrhagic shock

Naveh, Y.; Paz, S.; Bitterman, H.

Trace Elements in Medicine 9(1): 38-42

1992


ISSN/ISBN: 0174-7371
Accession: 007249611

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Abstract
Following the routine use of histamine H2 receptor antagonists in patients with upper gastrointestinal bleeding, side effects such as hypotension and bradycardia have been reported. In a recent study with male rats treated with high oral doses of cimetidine, we found high contents of zinc and calcium in heart muscle. In the present study we investigated the effect of intravenous bolus of cimetidine on male rats with hemorrhagic shock. The study included 5 groups: 1) sham shock group treated with cimetidine 40 mg/kg (n = 9); 2) sham shock group treated with 0.9% NaCl (n = 9); 3) shock group treated with cimetidine 10 mg/kg (n = 8); 4) shock group treated with cimetidine 40 mg/kg (n = 9); and 5) shock group treated with 0.9% NaCl (n = 9). Mean arterial blood pressure (MABP), heart rate, plasma zinc and calcium concentrations, and zinc and calcium contents of heart muscle were measured. Starting MABP was similar in all groups and ranged between 140-149 mmHg. Temporary significant decrease of MABP (40 mmHg) was noted in the sham group treated with cimetidine. The 3 groups with the hemorrhagic shock exhibited a gradual decrease of MABP to 44-48 mmHg at the end of bleeding. After 100-120 min, MABP increased to 68-72 mmHg. Intravenous administration of 40 mg/kg cimetidine to the shock group resulted in insignificant further decrease of MABP from 73 .+-. 4 to 58 .+-. 6 mmHg. MABP decrease following cimetidine administration may be the result of reduction of the total peripheral resistance. Zinc and calcium contents in heart muscle of all groups did not differ significantly. At the end of the experiments, plasma zinc levels in the sham shock group treated with cimetidine and in the shock group treated with saline were significantly lower than those of the other 3 groups. Plasma calcium level in the shock group, treated with cimetidine 40 mg/kg was significantly higher at the end of the experiment than at the beginning, and was even significantly higher than the corresponding control sham shock group treated with the same dosage of cimetidine. Plasma calcium level was significantly higher at the end of the experiment in the shock group treated with saline than in the corresponding control sham shock group treated with saline. On the other hand, there were no significant differences in plasma calcium levels among the 3 shock groups. We conclude that, meanwhile, there is no unequivocal explantation for hitherto undescribed fluctuations of plasma zinc and calcium levels of the 5 groups studied. Changes in plasma calcium concentrations may be the result of metabolic acidosis in addition to changes in calcium regulating gland function.