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Biomedical subjects

L Dumont

Publications and source records attributed to L Dumont.

At least 19 recordsLinked to original sources
PubMed1992

Mechanism of halothane attenuation of isometric tension induced by serotonin in isolated canine coronary artery rings.

We explored the mechanism of halothane's interaction with the serotoninergic contractile response of isolated canine coronary artery rings. The serotoninergic contractile response of both intact and denuded rings was measured with and without halothane. In some experiments, rings were pretreated with methiothepin, a 5-HT1 and 5-HT2 antagonist, or ketanserin, a 5-HT2 antagonist. The contractile responses to 5-carboxamidotryptamine (5-CT) and alpha-methylserotonin, a 5-HT1 and a 5-HT2 receptor agonist, respectively, were measured with and without halothane. Finally, the response to prostaglandin F2-alpha, another spasm mediator, was also measured with and without halothane. Halothane attenuated the coronary artery response to serotonin (5-hydroxytryptamine, 5-HT), and specific 5-HT1 and 5-HT2 agonists, and prostaglandin F2 alpha (PGF2 alpha). Its inhibitory effect on the serotoninergic response was abolished in vessels pretreated with either 5-HT1 or 5-HT2 blockers. These data suggest that halothane is not a direct smooth muscle depressant, that it is not a specific 5-HT1- or 5-HT2-subtype antagonist in canine coronary arteries, and that it might interfere with intracellular pathways activated by agonist-receptor interactions.

Animals↗
PubMed1992

The effect of a new calcium channel blocker (TA-3090) on lipoprotein profile and intestinal lipid handling in rodents.

Recent interest has focused on findings that drugs used to lower blood pressure may adversely modify plasma lipids and lipoprotein metabolism. This observation may explain why pharmacologic control of hypertension has failed to reduce the incidence of morbidity and mortality from coronary artery disease. The present study aims to evaluate the effect of TA-3090, a new calcium channel blocker, on fasting plasma lipids and lipoproteins, as well as on processes of intestinal fat absorption. Rats were treated by gavage with TA-3090 (10 mg/kg twice daily) for 4 days and compared with controls (n = 6 per group). Plasma cholesterol was increased in the treated group to (mean +/- SE) 74 +/- 2 vs 60 +/- 4 mg/dl (P less than 0.01), due mainly to an increased high density lipoprotein-cholesterol level (50 +/- 2 vs 37 +/- 3 mg/dl, P less than 0.005). Notably plasma triglycerides (TG) and low density lipoprotein-cholesterol were not significantly affected. Another group of TA-3090-treated animals was given an intraduodenal fat meal, and the rise in plasma TG and chylomicrons followed over 4 hr. Postprandial hypertriglyceridemia and chylomicronemia were significantly lower at 2 hr (P less than 0.05) and 3 hr (P less than 0.01) compared with controls. In a separate group of animals, the addition of TA-3090 to a 2% intralipid infusion intraduodenally was associated with significantly reduced TG and chylomicron-TG transport into lymph (P less than 0.05). Furthermore, experiments in rats pretreated with TA-3090 intraperitoneally and then given 2% intralipid intraduodenally were shown to have a significant decrease in mean flow rate (27%), TG transport (31%) and chylomicron-TG output (37%), when compared with controls. In vitro studies using jejunal organ culture to examine the effect of TA-3090 on intracellular lipid synthesis and secretion revealed that the addition of the drug to the medium resulted in significantly decreased TG synthesis and secretion. These data suggest that TA-3090 could be effective in increasing HDL-cholesterol and reducing postprandial chylomicronemia. Our findings support a role for TA-3090 directly on enterocyte absorption and/or intracellular lipid transport, and thus indicate the importance of intracellular calcium on these processes.

Animals↗
PubMed1991

Beneficial effects of volatile anesthetics on decrease in coronary flow and myocardial contractility induced by oxygen-derived free radicals in isolated rabbit hearts.

Oxygen-derived free radicals have been implicated in reperfusion injury whereas volatile anesthetics have been shown to enhance myocardial recovery during reperfusion. To explore the mechanism by which these agents improve myocardial recovery, we measured the effect of volatile anesthetics on the free radical-induced reduction in left ventricular pressure (LVP), coronary flow, and endothelium-dependent dilation induced by acetylcholine (Ach). Isolated rabbit hearts were perfused in a Langendorff apparatus. Isovolumetric LVP and coronary flow were measured throughout the study. Oxygen-derived free radicals were produced by the electrolysis (direct current of 0.6 mA) of the perfusate. The following volatile anesthetics were used: halothane 0.5 or 1.0%, isoflurane 0.7 or 1.4%, and enflurane 1.0 or 2.0%. Oxygen free radicals induced a significant decrease in systolic LVP and coronary flow. Pretreatment of the heart with enflurane 1.0 or 2.0%, halothane 1.0%, or isoflurane 0.7% attenuated the effect of the free radicals on both systolic LVP and coronary flow. Free radicals reduced the dilating response induced by 0.1 microM Ach with or without addition of volatile anesthetics. These data suggest that the volatile agents have beneficial effects on the free radical cell damage pathway and that this protection is not related to the preservation of endothelium-dependent dilation.

Anesthetics↗
PubMed1991

Peripheral vasodilator and cardiac properties of the 1,5-benzothiazepine calcium antagonist analog, TA-3090, in dogs.

Diltiazem, a 1,5-benzothiazepine, has demonstrated efficacy in the treatment of numerous cardiovascular diseases. TA-3090, a newly synthetized 1,5-benzothiazepine compound was studied in open-chest anesthetized dogs to characterize its hemodynamic properties, to compare it with diltiazem, and finally to correlate hemodynamic properties and plasma level concentrations. Anesthetized open-chest dogs were instrumented with electronic devices and fluid-filled catheters to monitor cardiac, coronary, and peripheral hemodynamic changes. A cumulative intravenous bolus administration of TA-3090 (n = 16) or diltiazem (n = 15) (15, 50, 200, and 400 micrograms/kg) was carried out, and blood samples were taken before and 5 min following each dose administration. Hemodynamic changes were followed for 30 min after each administration, at which time most hemodynamic parameters were back to baseline levels. The results indicate that both TA-3090 and diltiazem elicit slight peripheral and coronary vasodilator properties at low doses (15 and 50 micrograms/kg). With higher dosage, hemodynamic effects were maximal: coronary blood flow increased by 75%, arterial pressure decreased by 25%, and reflex positive inotropic effects were also observed. Heart rate was significantly reduced (10%). Comparison between TA-3090 and diltiazem indicates that both drugs elicit coronary vasodilator selectivity and TA-3090 has a prolonged duration of action compared with that of diltiazem. A straightforward relationship is demonstrated between vasodilator properties and plasma levels of either TA-3090 or diltiazem. Our data suggest that with plasma levels between 40 and 80 ng/mL, significant hemodynamic changes were observed with TA-3090. Changes of heart rate were not correlated with plasma levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Acute hypercalcemia and increased work load in canine transplanted heart. Coronary blood flow adjustments.

Coronary vasodilator adjustments following cardiac transplantation might be adversely affected during severe rejection. We studied the coronary blood flow response following intravenous bolus administration of calcium (0.04-0.05 mEq/kg) in canine cardiac transplants. Fifteen dogs were submitted to orthotopic heart transplantation and equipped with electronic implants for monitoring of hemodynamic parameters. Of these animals, 9 were not immunosuppressed, while 6 were treated with ciclosporin, azathioprine, and prednisone. The effects of calcium administration upon cardiac function were evaluated during the postoperative period, at recovery (2-3 days after transplantation) and during severe rejection (7-10 days after transplantation), and also in immunosuppressed animals. Rapid calcium administration elicits brief increases in arterial pressure, cardiac index, stroke work, and coronary blood flow. There were significant differences in these effects, depending on the hemodynamic status of these animals. Coronary blood flow was significantly increased in all experiments, except when severe rejection was evidenced. These results indicate that changes in myocardial metabolic demand (work load) are not adequately matched with coronary blood flow adjustments in the presence of severe rejection.

Acute Disease↗
PubMed1989

Positive hemodynamic interaction between amrinone and diltiazem in anesthetized dogs.

The direct negative inotropic actions of calcium channel blockers limit the use of these otherwise effective systemic and coronary vasodilators in patients with heart failure. We studied the effects of amrinone pretreatment on the dose--hemodynamic response curve of diltiazem in order to test the hypothesis that amrinone might potentiate diltiazem's positive effects in anesthetized dogs. The control group (no pretreatment, n = 6) had a typical dose-related response to diltiazem (50, 100, and 150 micrograms/kg): coronary and systemic vasodilation, increased stroke volume, and no change in myocardial work and power. Amrinone pretreatment of the study group (n = 7) altered the hemodynamic response, thus maximal systemic vasodilation and stroke volume increase at a lower diltiazem dose, a 15 to 35% increase in myocardial work and power, and more profound coronary vasodilation. We propose that amrinone, by inhibiting phosphodiesterase, potentiates diltiazem vasodilation and reflexly secreted catecholamines' actions on the heart. This positive interaction may permit effective use of lower doses of diltiazem, thus circumventing its dose-limiting direct negative effects while still profitting from beneficial peripheral, reflex, and coronary actions.

Amrinone↗
PubMed1988

Cardiac rejection following transplantation in dogs: transmural myocardial blood flow changes.

In cardiac allografts acute rejection produces deleterious effects on blood flow adjustments. In order to differentiate the role of rejection over that of denervation cardiac denervated and cardiac transplanted dogs were compared. A canine model of orthotopic cardiac transplantation was utilized. Electronic devices were implanted for chronic hemodynamic studies. Regional myocardial blood flow distribution was assessed by radioactive microspheres (15 micron in diameter). Studies were carried out when animals had fully recovered (two to three days postoperatively), then in the 'early rejection' stage (five to six days post transplant) and in the 'severe rejection' stage (24 h before death). No significant difference in hemodynamic data or blood flow values were observed between groups in the recovery stage. In the denervated group, adequate cardiac function and myocardial blood perfusion was maintained throughout the study. In the transplanted group, significant loss of function was observed at the severe rejection stage. This was combined with significant decrement in blood flow to all areas of the myocardium. No selective area of underperfusion nor an early reduction in total blood flow could be observed. This study indicates that within cardiac rejection there is a parallel impairment in function and transmural myocardial blood flow which is unrelated to denervation or interruption of lymphatics.

Animals↗
PubMed1986

Acute hypercalcemia and cardiac autotransplantation in dogs: long-term hemodynamic adaptability.

Cardiac autotransplantation (excision and reimplantation) is a unique model that isolates totally the cardiac afferent and efferent neural pathways and results in hemodynamic misadaptability to many provocative tests. Since the cardiovascular response to acute hypercalcemia is modulated by numerous factors among which the autonomic innervation plays a major role, the hemodynamic response to bolus administration of calcium gluconate was compared in normal and cardiac autotransplanted dogs. Twenty-two animals underwent an autotransplantation while a sham procedure was performed in 18 animals. Each dog was equipped with an electromagnetic flow probe positioned around the ascending aorta and with central venous and aortic catheters. Hemodynamic data were collected daily during 1 month, before and during rapid intravenous administration of calcium gluconate (0.90 mEq). Baseline hemodynamic studies indicate that for both groups myocardial failure is evident in the immediate postoperative period; despite progressive recovery, the autotransplants always show lower cardiovascular performance. Calcium administration elicits transient positive inotropism, which is more important in presence of myocardial failure; this is true for both control and autotransplanted dogs. In the early postoperative period, hemodynamic adaptability to this stress is impaired in the autotransplants. However, long-term results indicate that minimal differences subsist over time in response to calcium administration, and when they are observed, they result from interferences in baroreceptor regulation and reflexes.

Animals↗
PubMed1985

Profile of the oppositely acting enantiomers of the dihydropyridine 202-791 in cardiac preparations: receptor binding, electrophysiological, and pharmacological studies.

Receptor binding, electrophysiological, and inotropic effects of the pure dihydropyridine enantiomers (+)S202-791 and (-)R202-791 were studied in cardiac preparations. The KI for (+)S202-791 binding correlated with the ED50's for an increase in contractile force and an increase in calcium current, the latter effect occurring at depolarized as well as resting holding potentials. The KI for (-)R202-791 binding was much lower than the IC50's for inhibition of calcium current measured at holding potentials of -80 or -90 mV and a negative inotropic effect, but correlated closely with the IC50 for inhibition of calcium current measured at -30 mV. Thus, (+)S202-791, is a voltage independent calcium channel activator and (-)R202-791 is a voltage dependent calcium channel inhibitor.

Animals↗