PubMed Health⌕ Search

Biomedical subjects

B K Lum

Publications and source records attributed to B K Lum.

At least 19 recordsLinked to original sources
PubMed1992

Effects of nicardipine in rats subjected to endotoxic shock.

1. The calcium channel blocker, nicardipine, produced a dose-dependent reduction in the mortality caused by endotoxin in rats. 2. The drug also reduced most of the hematological and gross pathological manifestations of disseminated intravascular coagulation (DIC) caused by endotoxin. 3. The endotoxin-induced monocytopenia but not the granulocytopenia, lymphocytopenia or thrombocytopenia was inhibited by the drug. 4. The results suggest that the protective action of nicardipine is causally related to prevention of the endotoxin-induced DIC and that an effect of the drug on monocytes may be of importance.

Analysis of Variance↗
PubMed1989

The effects of the calcium entry blockers, nilvadipine and nitrendipine, on endotoxin-induced disseminated intravascular coagulation.

We previously reported that calcium entry blockers (CEBs) protected against endotoxin-induced mortality in rats. In this investigation, the i.v. injection of endotoxin (ETX) in control awake male Wistar rats was found to produce pathophysiological changes indicative of disseminated intravascular coagulation (DIC). The latter included increased serum fibrin (ogen) degradation products (FDP), decreased plasma fibrinogen, reduced blood platelet count as well as microscopic findings of fibrin microthrombi in small blood vessels of visceral organs. Gross pathological examination revealed pronounced hemorrhagic congestion of the gastrointestinal tract and petechial and ecchymotic hemorrhages in other visceral organs. Pretreatment with the CEBs, nilvadipine (FR 34235) and nitrendipine, inhibited the elevation in serum FDP and decrease in plasma fibrinogen but did not prevent the thrombocytopenia produced by ETX. The gross pathological manifestations of DIC were also inhibited by pretreatment with the CEBs. The results suggest that the protective effect of CEBs against endotoxin-induced mortality in rats may be related to inhibition of DIC caused by the lipopolysaccharide.

Agglutination Tests↗
PubMed1986

Protective action of calcium entry blockers in endotoxin shock.

Calcium entry blockers (CEBs) have been reported to protect against cellular necrosis caused by experimental ischemia and the beneficial effect has been related to prevention of ischemia-induced calcium overload by the CEBs. Since circulatory shock can be expected to produce generalized tissue hypoxia, the possibility that CEBs might be beneficial in shock produced by endotoxin was investigated. In control male Wistar rats, a 10-mg/kg dose of E. coli endotoxin (Difco 0127:B8) produced a fall in blood pressure and a transient increase followed by a progressive slowing of the heart rate. Mortality 48 hours after endotoxin (10 mg/kg) was 84%. The calcium entry blockers (CEBs) verapamil, nitrendipine, and nilvadipine [corrected], administered i.v. 15 min before endotoxin, produced a dose-dependent reduction in mortality. The CEBs were less effective when given as post-treatment (15 to 30 min after endotoxin). Measurements of total tissue and mitochondrial calcium levels in control rats revealed that endotoxin did not produce an increase in the calcium content of heart, lung, pancreas, small intestine, kidney, and aorta. Since increased cellular calcium levels did not occur in response to endotoxin, the protection induced by CEBs in endotoxin shock does not appear to be related to prevention of calcium overload; however, the possibility that the CEBs may beneficially prevent an excessive accumulation of calcium in discrete cells or intracellular compartments (which may not be detected by our methods) cannot be excluded.

Animals↗
PubMed1983

Role of cyclic AMP in adrenergically-induced tracheal muscle relaxation.

Studies were performed on the isolated bovine tracheal muscle preparation to assess the possible role of adenosine 3',5'-cyclic monophosphate (cyclic AMP) in adrenergically-induced smooth muscle relaxation. Isoproterenol, epinephrine, terbutaline and soterenol were found to relax the tracheal muscle and to increase its cyclic AMP content. The two events generally paralleled one another when analyzed in terms of dose-response and time-response relationships. Propranolol antagonized the relaxation and the increase in cyclic AMP produced by isoproterenol. However, other findings suggested that there may not be a cause and effect relationship between the biochemical and mechanical responses. Thus, salbutamol and carbuterol failed to increase muscle cyclic AMP even in concentrations which produced maximum relaxation. Additionally, butoxamine and H35/25 antagonized the biochemical response but had additive effects (instead of antagonistic effects) on the mechanical response to isoproterenol. Furthermore, it was observed that low concentrations of H35/25 produced tracheal muscle relaxation associated with an increase in tissue cyclic AMP; however, use of a high concentration of H35/25 paradoxically resulted in autoblockade of the increase in cyclic AMP but not the smooth muscle relaxation.

Adrenergic alpha-Agonists↗
PubMed1982

Experimental studies on the effects of physostigmine and of isoproterenol on toxicity produced by tricyclic antidepressant agents.

The IV infusion of nortriptyline and amitriptyline (0.5 mg/kg/min) in anesthetized cats produced death within 60 min of continuous infusion. The tricyclic antidepressant agents produced a quinidine-like depression of the myocardium characterized by bradycardia, depression of contractile force, conduction defects, bradyarrhythmias, and hypotension. The simultaneous IV infusion of isoproterenol (0.1 microgram/ kg/min) produced significant protection against death produced by the TCA drugs. The results suggested that the positive chronotropic, inotropic, and dromotropic actions of isoproterenol may all be contributory factors in the protection. Pretreatment with a large dose of physostigmine (0.2 mg/kg) produced a rightward shift of the nortriptyline time-mortality curve. The small degree of protection produced by the anticholinesterase drug may be due to a respiratory stimulant action rather than a cardiac action.

Amitriptyline↗
PubMed1982

Protective action of diazepam and of sympathomimetic amines against amitryptyline-induced toxicity.

Factors that contribute to the lethality of amitriptyline overdosage were studied in cats. Amitriptyline (50 mg/kg) given i.p. to unanesthetized cats produced convulsions in all of the animals and death in five of six animals; pretreatment with diazepam (5 mg/kg) protected against the convulsions and death. Respiratory depression contributed to the mortality when amitriptyline was given i.v. in cats anesthetized with pentobarbital as indicated by the finding that artificial respiration delayed the time of death induced by a continuous i.v. infusion of the drug. The i.v. infusion of amitriptyline in pentobarbitalized cats under artificial respiration produced death due to cardiovascular collapse. The latter was characterized by hypotension, bradycardia, depression of myocardial contractile force, atrioventricular block, intraventricular conduction delay and cardiac arrhythmias. These effects appear to be due to a direct membrane (quindine-like) cardiotoxic action of amitriptyline. Dopamine and dobutamine were effective in protecting the animals against the acute cardiovascular collapse induced by amitriptyline. The protection was associated with a diminution of the hypotension, the negative inotropic and chronotropic actions and the incidence of atrioventricular block produced by the tricyclic antidepressant drug. The results suggest that the positive chronotropic, inotropic and dromotropic actions of the amines may all be contributory factors in their protection action. Isoproterenol and norepinephrine were less effective than the other two amines.

Amitriptyline↗
PubMed1977

Effects of adrenalectomy and adrenergic antagonists on potassium metabolism.

We had previously reported that drugs which stimulate beta-2 adrenergic receptors decreased the hyperkalemia produced by infused KCI and thus protected animals against KCI intoxication; these effects were mediated by an action of beta-2 agonists which enhanced tissue uptake of K+. In this study, cats were given an i.v. infusion of KCI which was not lethal in control animals. Acute adrenalectomy markedly increased the hyperkalemic and mortality responses to infused KCI. This impairment in K+ metabolism was corrected by the administration of epinephrine but not by hydrocortisone. Pretreatment with propranolol (which blocks beta-1 and beta-2 receptors) and H35/25 (which blocks beta-2 receptors) produced a similar impairment in K+ metabolism; on the other hand, practolol (which blocks beta-1 receptors) had little or no effect on the mortality and hyperkalemic responses to infused KCI. Evidence that KCI stimulates an adrenal release of catecholamines is presented. This stimulation of adrenal release may be important in conferring resistance to intoxication produced by infused KCI since the released amines can attenuate the KCI-induced hyperkalemia via a beta-2 action which enhances tissue uptake of K+.

Adrenalectomy↗