S. Dai

Effects of ranitidine and cimetidine on experimentally induced ventricular arrhythmias in anaesthetized rats.

The effects of two histamine H2-receptor antagonists, ramitidine and cimetidine, on ventricular arrhythmias induced by acute coronary artery ligation and by aconitine infusion were studied in pentobarbitone-anaesthetized rats. The changes in arterial blood pressure and heart rate were also observed. It was found that both drugs significantly reduced the incidence, and prolonged the time of onset, of ventricular tachycardia and ventricular fibrillation following acute coronary artery ligation; however, they did not significantly alter the incidence or time of onset of ventricular dysrhythmias caused by aconitine infusion. These findings further support the hypothesis that histamine release may contribute to the genesis of early ventricular arrhythmias resulting from acute myocardial ischaemia. Since the decreased blood pressure induced by coronary artery ligation was not significantly prevented by pretreatment with either histamine H2-receptor blocker, this suggests that histamine may not be responsible for the blood pressure changes during acute myocardial ischaemia.

Rapid induction of dependence to morphine in rats

The rate of development of dependence to morphine was studied in female rats which were given increasing concentrations of morphine sulphate in their drinking fluid (5% sucrose solution). The occurrence of physical dependence was determined by the naloxone-precipitated withdrawal syndrome at various times during the 3-week experimental period. It was found that a significant degree of the withdrawal syndrome precipitated by naloxone was evident at 24 hr after starting administration of morphine; the syndrome reached its greatest intensity after the rats had received the opiate for 7 days. This study shows that dependence on morphine can be induced in rats by administration of the opiate in drinking fluid for a period shorter than 7 days.

A study on the aetiology of reserpine ulceration and the antiulcer action of solcoseryl in rat stomach.

The aetiology of reserpine‐induced gastric ulcer formation and the antiulcer effects of solcoseryl were studied in rats. Intraperitoneal injection of reserpine produced severe ulceration, as well as mast cell and histamine depletion, in the gastric glandular mucosa. Mepyramine and Cimetidine markedly antagonized the gastric lesions, but did not influence the reduced mast cell count; atropine pretreatment significantly inhibited both parameters. Intramuscular injection of solcoseryl lessened ulcer severity and prevented the decreased mast cell counts and histamine levels in reserpine‐treated rats. However, the same dose of solcoseryl injected intraperitoneally was ineffective. Solcoseryl, irrespective of the route of administration, did not influence the gastric secretory activities of reserpine. It is concluded that resperine ulceration is both cholinergic‐ and histamine‐mediated, and that the antiulcer effects of solcoseryl appear to be due to prevention of histamine depletion in the gastric mucosa.

Ventricular histamine concentrations in naive and morphine-treated rats during acute myocardial ischaemia

The ventricular histamine concentrations of naive and morphine-treated rats subjected to acute left coronary artery ligation were examined. In naive animals, there was a significant increase in the right ventricular histamine level at 5 min following ligation, but not at 3 or 10 min. Left ventricular histamine concentrations tended to decrease, but the changes were not statistically significant. In shamoperated rats, neither acute nor chronic morphine treatment significantly altered either right or left ventricular histamine levels. Acute morphine treatment also did not significantly affect the ventricular histamine content at 5 min following coronary artery ligation. However, both right and left ventricular histamine concentrations were found to be significantly lower in chronic morphine-treated rats than in the naive animals when they were subjected to acute myocardial ischaemia. If the hypothesis that histamine release may contribute to the genesis of early ventricular arrhythmias resulting from acute myocardial ischaemia is accepted, the present findings suggest that the previously reported decreased incidence and delayed onset of early ventricular arrhythmias induced by acute left coronary artery ligation in chronic morphine-treated rats may be attributed to the reduced ventricular histamine concentrations.

Ventricular histamine concentrations and arrhythmias during acute myocardial ischaemia in rats

The relation between ventricular histamine concentrations and the occurrence of early ventricular arrhythmias during acute myocardial ischaemia was investigated in pentobarbitone-anaesthetized rats. There was significant decrease in the left, but not the right, ventricular histamine level at 5 min following acute left coronary artery ligation. Pretreatment with rhodanine caused remarkable reduction in ventricular histamine concentrations as well as significantly lower incidence and slower onset of ventricular tachycardia and fibrillation resulting from acute myocardial ischaemia. On the contrary, aminoguanidine pretreatment did not significantly alter ventricular histamine levels nor did it influence the occurrence of early ventricular arrhythmias induced by coronary artery ligation. The responses of blood pressure and heart rate to acute coronary artery ligation were not noticeably affected by rhodanine or aminoguanidine pretreatment. These findings support the hypothesis that histamine release from cardiac tissues may contribute to the genesis of early ventricular arrhythmias, but not to the changes in blood pressure and heart rate, during acute myocardial ischaemia.

THE EFFECT OF ZINC ON ANAPHYLAXIS in vivo IN THE GUINEA-PIG

The protective effects of pretreatment with zinc sulphate aerosols against bronchoconstriction induced by egg albumen or histamine aerosols were assessed in sensitized or non‐sensitized guinea‐pigs respectively. Pretreatment with an adequate concentration of zinc sulphate aerosol significantly prolonged the time of onset of bronchoconstriction in sensitized guinea‐pigs challenged with egg albumen, but did not appreciably alter the onset time of histamine‐induced bronchoconstriction in non‐sensitized animals. These findings suggest that zinc aerosols may be of prophylactic value against bronchoconstriction of allergic origin.

Effects of morphine on cardiovascular responses to acute myocardial ischaemia in rats

1 The effects of acute coronary artery ligation on cardiac rhythm and haemodynamics were studied in rats receiving either acute or chronic morphine‐treatment. 2 In chronic opiate‐treated animals, increasing concentrations of morphine sulphate were administered in drinking water over a 3 week period, and the development of morphine tolerance and dependence was verified by decreased analgesic responses to morphine in the tail‐immersion test and the occurrence of naloxone‐precipitated withdrawal syndromes, respectively. 3 Acute coronary artery ligation induced a decrease in blood pressure, a slight increase in heart rate, and ventricular tachycardia or fibrillation in anaesthetized rats. 4 The changes in blood pressure and heart rate following acute coronary artery ligation were not significantly altered by acute or chronic morphine administration. 5 The incidence and the time of onset of ventricular tachycardia or fibrillation were found to be significantly reduced and prolonged, respectively, in chronically morphine‐treated rats, but were not significantly affected by acute morphine administration in naïve animals. 6 These findings suggest that chronic morphine treatment lessens the occurrence of early ventricular arrhythmias caused by acute myocardial ischaemia in rats. The mechanism of this effect is unclear.

Effects of Zinc Sulphate Pretreatment on Gastric Acid Secretion and Lesion Formation in Rats Infused Intravenously with Graded Doses of Methacholine

The effects of intraperitoneal pretreatment with zinc sulphate (22, 44 or 88 mg/kg) were studied on gastric acid secretion and lesion formation induced by methacholine (125, 250 or 500 microgram/kg/h) infused intravenously in rats with stomachs perfused in situ. Graded infusions of methacholine produced dose-dependent increases in gastric acid secretion and lesion incidence in saline-pretreated control rats. These effects were progressively reduced by increasing pretreatment doses of zinc sulphate. The relationship between these findings and the action of zinc on gastric mast cells is discussed.

Ventricular histamine concentrations and mast cell counts in the rat heart during acute ischaemia

The ventricular histamine concentrations and mast cell counts of naive and disodium cromoglycatetreated rats subjected to acute left coronary artery ligation under pentobarbitone anaesthesia were examined. In naive animals, there was a significant increase in the right ventricular histamine level at 2 min following left coronary artery ligation. Left ventricular histamine concentrations tended to decrease, and were significantly lower than those of the right ventricle at 5 min. However, there were no significant changes in mast cell counts of the right or left ventricles after left coronary artery ligation. Treatment with disodium cromoglycate did not significantly alter the ventricular mast cell counts, interfere with the changes in ventricular histamine concentrations, or the occurrence of early ventricular arrhythmias and haemodynamic changes in response to acute left coronary artery ligation. It is suggested that the increase in the right and decrease in the left ventricular histamine concentrations during acute myocardial ischaemia involves mainly the non-mast cell stores, instead of mast cell sources, of cardiac histamine.

Production of physical dependence in rats by drinking a morphine solution

The plasma concentrations of morphine and glucose, the body weight, and the severity of the naloxone-precipitated withdrawal syndrome were studied in female rats in which morphine dependence was induced by administration of the opiate, with or without sucrose, in their drinking water. It was found that sucrose encouraged the animals to consume more morphine and that the initial plasma concentrations of the opiate, as well as the rate of development of physical dependence, were higher than the group not given sucrose. Plasma glucose concentrations, maximum plasma morphine levels and the maximum severity of the naloxone-precipitated withdrawal syndrome were, however, not significantly different between the two groups. The findings suggest that both regimens of administering the opiate in drinking fluid are effective in inducing morphine dependence in rats; the addition of sucrose tends to speed up the development of physical dependence, probably by increasing intake of the opiate through consuming more sucrose solution.