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Biomedical subjects

L Dumont

Publications and source records attributed to L Dumont.

At least 109 records · Page 6Linked to original sources
PubMed1983

Intravenous infusion of nitroprusside: effects upon cardiovascular dynamics and regional blood flow distribution in conscious dogs.

Intravenous infusion of nitroprusside (5 micrograms/kg/min) was carried out in conscious dogs over a 15-min period in order to describe changes in both central and peripheral vascular areas. Dogs were prepared with an electromagnetic flow probe positioned at the root of the aorta, and microspheres (9 microns) were used to measure regional blood flow distribution before and after 15 min of infusion. Controlled hypotension (-15 to -20 mmHg) was maintained throughout the infusion period and this hypotensive state was associated with a significant decrease in stroke volume (-16%), left ventricular power (-25%) and work (-40%) while cardiac index was not significantly affected. Those values were almost back to control levels 5 min following the end of infusion. Regional blood flow studies showed that at the fifteenth min of infusion, nitroprusside induced a significant decrease in blood perfusion to all areas of the myocardium (range -10% to -25%) while their local vascular resistances were not affected significantly. Blood perfusion to liver (hepatic artery), spleen and intestine was also modified significantly (-17%, -12% and -16%, respectively) while their vascular resistances remained close to control values. By the time measurements were made, blood flow to cerebral and renal tissues remained normal while their vascular resistances fell significantly (15% for brain and 20% for kidneys). For each organ studies, blood perfusion was uniform. These results indicate that nitroprusside elicits both central and peripheral hemodynamic changes and that reflex adjustments modify the vasodilator effect of the drug in most vascular beds that we have studied.

Animals↗
PubMed1982

Intravenous infusion of nitroglycerin: effects upon cardiovascular dynamics and regional blood flow distribution in conscious dogs.

We have studied both central and peripheral hemodynamic changes induced by infusion of nitroglycerin (55 micrograms/kg per minute) over a 15-min period in conscious dogs to clarify its mechanism of action. Dogs were prepared with an electromagnetic flow probe positioned at the root of the aorta, and microspheres (9 microns) were used to measure regional blood flow distribution before and after 15 min of infusion. Controlled hypotension (-15 to -20 mmHg (1 mmHg = 133.322 Pa)) was maintained throughout the infusion period and this hypotensive state was associated with a significant decrease in stroke volume (-30%), cardiac index (-20%), and left ventricular work (-43%). Regional blood flow studies showed that at the 15th min of infusion, nitroglycerin induced significant decrease in blood flow to all components of the myocardium (range -12 to -20%) while their vascular resistances were not affected significantly. Blood perfusion to liver (hepatic artery), spleen, and intestine was also modified significantly (-22, -18, and -16%, respectively) while their vascular resistances remained close to control values. By the time measurements were made, blood flow and vascular resistance of cerebral and renal tissues remained normal. For each organ studied, blood perfusion was uniform. These results indicate that nitroglycerin elicits both central and peripheral hemodynamic changes and that local reflex adjustments modify the vasodilator effect of the drug in most vascular beds that we have studied.

Animals↗
PubMed1981

Gentamicin: use of a programmable calculator to determine dosages from pharmacokinetic data for individual patients.

Gentamicin, an antibiotic frequently used in the treatment of gram-negative infections, has a narrow therapeutic index, so the correct prediction of its serum concentrations is important. Recent studies have emphasized the dubious accuracy of commonly used formulas, and computer programs that provide pharmacokinetic data for individual patients from multiple blood samples have helped to adjust dosages but are expensive. This study tested the applicability of a method using only two blood samples and a programmable calculator to estimate pharmacokinetic parameters for individual patients and adjust dosages to aim at peak and trough serum levels of 6 and 1 micrograms/ml respectively. In the 48 patients with normal renal function this method produced peak serum concentrations of gentamicin within 1 microgram/ml of the desired level in 22 (46%) and therapeutic peak concentrations (between 4 and 10 micrograms/ml) in all the patients. In 10 patients with renal failure it produced peak serum concentrations within 1 microgram/ml of the desired value in 4 and therapeutic serum concentrations in 7. Two patients had peak concentrations below 4 micrograms/ml and one had a peak concentration above 10 micrograms/ml. Two of the three patients whose serum levels were outside the therapeutic range had unstable renal insufficiency. Thus, patients with renal insufficiency need continued monitoring of the serum level of gentamicin, particularly when their renal function is changing.

Bacterial Infections↗
PubMed1981

Effects of cardiopulmonary bypass on the dynamics and coronary circulation of the normal heart.

This study observed the consequences of total normothermic cardiopulmonary bypass (CPB) on cardiac function, myocardial blood flow, and its regional distribution. To determine the potential effects of CPB per se on hemodynamic performance of the heart from the concomitant interfering influences of anesthesia, surgical procedure, and preexisting disease, myocardial function and blood flow were investigated in two groups of normal animals submitted to identical experimental conditions, except for two hours of total CPB, which was performed in only one group. Myocardial blood flow distribution was studied immediately before and after CPB, and the hemodynamic studies were performed 3, 24, and 48 hours postoperatively in the awake resting animal. Coronary blood flow and its distribution were similar before and after CPB. Three hours postoperatively, the hemodynamic status of the perfused dogs seemed to be slightly inferior compared with control subjects; however, there was no statistically significant difference between the two groups. Twenty-four and 48 hours after surgery, the cardiovascular dynamics were similar in both groups. These results demonstrate that two hours of total normothermic cardiopulmonary bypass have no significant deleterious effect on the performance, coronary perfusion, and its regional distribution, of the normal beating empty heart.

Animals↗
PubMed1981

Effect of water deprivation and rehydration on gentamicin disposition in the rat.

To study the effect of dehydration on gentamicin (G) kinetics, a group of rats was deprived of water for 4 days and then received a single i.v. dose of 3 mg/kg of G. Compared to control rats, the plasma and tissue concentration of G in dehydrated rats were increased and the elimination rate of the drug decreased. Higher G concentrations were found in plasma, spleen, renal cortex and medulla. These changes in G disposition consisted in a decrease of 33 and 22% of the apparent volume of distribution of the peripheral and central compartments, respectively, and, furthermore, in a decrease of 40% in the G apparent total body clearance. Another group of rats, after a similar period of water deprivation and i.v. administration of 3 mg/kg of G, were rehydrated with water or received a solution of NaCl and dextrose followed by water during 24 hr. In plasma and most tissues, rehydration did accelerate G washout without clear differences between the two modes of rehydration. It is concluded that a dehydration state will increase plasma and tissue G accumulation and might increase the risk of renal or ototoxicity. Rehydration will partially prevent and reverse G concentration. In a clinical setting, this event could very well occur. G tissue concentration cannot be predicted by changes in G plasma elimination half-life. The calculation of total body clearance and volume of distribution are necessary to predict the occurrence and estimate the extent of this tissue concentration.

Animals↗
PubMed1977

Effect of norepinephrine on intramyocardial distribution of blood flow in normal and ischemic myocardium.

Using labelled microspheres, the effect of norepinephrine (NE) infusions (15 microgram and 30 microgram/min) on coronary blood flow and its intramyocardial distribution during ischemia was studied. The results reported here show that in the ischemic myocardium, the ratio of endocardial to epicardial flow was 0.67. This value became 1.0 in dogs receiving NE at a dose of 30 microgram/min. Since an adrenergic discharge is known to accompany angina in man, these data suggest that an imbalance between the endocardial and epicardial blood flow might not be present in this clinical condition.

Animals↗
PubMedDate not supplied

Decreased digitalis receptor activity in acute rejecting canine transplanted heart.

In the course of acute rejection, myocardial tissue undergoes massive transformation and we hypothetized that for digitalis-like substances, receptor binding characteristics might be altered. Ten canine heterotopic cardiac allografts were carried out and were harvested once rejection had developed (8-10 days post-transplant). Microsomal membrane fractions of those grafts and of native hearts were isolated. Radioligand binding studies were carried out in a medium containing 5 mM Tris PO4, 50 mM Tris HCl, 5 mM MgCl2, pH 7.4 at 37 degrees C, using 3H-ouabain as the ligand. Saturation experiments (n = 10) indicate the presence of one homogeneous population of high affinity binding sites with an affinity constant (Kd) of 8-13 nM and a maximum binding capacity (Bmax) of 47 +/- 3.5 pmol/mg protein. Both saturation and competition binding studies illustrate the fact that acute rejection resulted in a significant decrease in Bmax (43%) without significant alteration in Kd value. These studies indicate that digitalis-like substances might not exert significant inotropic activity during rejection, but this hypothesis must be confirmed by in vivo haemodynamic experiments.

Animals↗
PubMedDate not supplied

Characteristics of the phenylalkylamine binding site in canine cardiac sarcolemmal membranes.

We have investigated the phenylalkylamine binding site in canine cardiac sarcolemmal preparations using (-)-[3H]-desmethoxyverapamil as the labeled ligand. Radioligand binding experiments were carried out in 10 mM Hepes (Na+) buffer and 1 mM EGTA, at pH 7.4 and 20 degrees C. A single high affinity binding site for (-)-[3H]-desmethoxyverapamil was identified both by saturation and competition binding experiments. Several phenylalkylamine derivatives such as (-)-D600, (+)-D600, verapamil and (+)-desmethoxyverapamil completely inhibited (-)-[3H]-desmethoxyverapamil binding with the following order of potency: (-)-desmethoxyverapamil greater than (-)-D600 greater than verapamil greater than (+)-desmethoxyverapamil = (+)-D600. In contrast to this, ronipamil, a new long acting phenylalkylamine derivative, produced only a 70% inhibition. Diltiazem also completely inhibited (-)-[3H]-desmethoxyverapamil binding to canine cardiac sarcolemma while nifedipine displaced only 70% of binding. (-)-[3H]-desmethoxyverapamil binding was also inhibited by Ca++ and Mg++. These data suggest the presence of a saturable, reversible and stereoselective phenylalkylamine binding site in canine cardiac sarcolemmal preparations which may be a receptor for the phenylalkylamine Ca++ channel inhibitors.

Aniline Compounds↗
PubMedDate not supplied

Sensory block extension during combined spinal and epidural.

BACKGROUND AND OBJECTIVES: During a combined spinal and epidural technique, extension of sensory block by epidural injection of saline or bupivacaine has been demonstrated and attributed to a volume effect or to the combination of a volume effect with a local anesthetic effect. This two-part study was designed to evaluate the time dependency of the volume effect and the local anesthetic effect on the mechanism of spinal block extension. METHODS: We performed two prospective studies. Thirty patients were randomized in each study. A combined spinal and epidural was performed in a sitting position in all groups. The patients in the first study received 15 mg hyperbaric bupivacaine intrathecally and were placed supine 2 minutes after spinal injection. They received 10 mL epidural saline either 5 minutes after spinal (group A) or 20 minutes after spinal (group B) compared to a control group (group C). The patients in the second study received 12.5 mg hyperbaric bupivacaine intrathecally and were placed supine 5 minutes after spinal injection. They then received epidurally either 10 mL saline 7 minutes after spinal (group D) or 10 mL bupivacaine 7 minutes after spinal (group E) or nothing (group F). Sensory block levels were assessed by a loss of sensation to cold using ether. RESULTS: In the first portion of this study, in group A, area under the curve of sensory block levels by time from 10 to 40 minutes after spinal injection, and maximum sensory block levels were significantly higher (P < .05) compared to groups B and C. In the second portion of the study, sensory block levels were comparable at all times in the three groups. CONCLUSIONS: During a combined spinal and epidural technique with the use of hyperbaric bupivacaine, the volume effect is time dependent and is seen when epidural top up is done soon after spinal injection. This volume effect is abolished when patients are left seated for 5 minutes after spinal injection. The local anesthetic effect is not demonstrated when high sensory block levels are achieved by spinal injection.

Adult↗
PubMedDate not supplied

Effects of PGE1 in experimental vasoconstrictive pulmonary hypertension.

The pulmonary vascular and systemic effects of PGE1 were studied in a canine model of pulmonary hypertension. Systemic arterial, central venous and pulmonary arterial pressures were monitored and an electromagnetic flow probe was placed around the ascending aorta for continuous cardiac index (CI) measurements. Through a laparotomy, an arteriovenous fistula was created between the abdominal aorta and inferior vena cava. Gradual opening of this fistula significantly affected CI and these values were used to generate pressure-flow curves (pulmonary arterial pressure (PAP)/CI). Following PGF2 alpha infusion (5-10 micrograms/kg/min) significant pulmonary hypertension was observed (2- to 3-fold increase in PAP). PGF2 alpha infusion also resulted in a significant rise in heart rate and systemic vascular resistance (SVR) while CI was reduced. PGF2 alpha significantly increased both the line slope (vascular resistance) and intercept (outflow pressure) of the pressure-flow curves. Intravenous PGE1 infusion in doses ranging from 40 to 320 ng/ml/min elicited a dose-dependent reduction of both pulmonary and systemic vascular resistances, the former being slightly more affected. With PGE1 infusions only the intercept of the pressure-flow curve was affected suggesting that specific components of the pulmonary vascular bed modulating the outflow pressure were involved. High doses of PGE1 significantly decreased arterial PO2, indicating that this prostaglandin derivative deteriorates pulmonary gas exchanges.

Alprostadil↗
PubMedDate not supplied

Efficacy of dobutamine in the failing transplanted heart.

Acute rejection often leads to severe myocardial failure and death. Surprisingly, no systematic study on the efficacy of beta-adrenergic pharmacologic agents have been reported to the present. Because of all the pathophysiologic alterations documented during rejection, we expected an inappropriate response to inotropic drugs, so we have questioned the value of dobutamine during those circumstances. Twelve dogs underwent orthotopic transplantation and were prepared with implantable devices for serial hemodynamic studies to be performed on the resting unanesthetized subject. Of this number, six dogs were studied while they were in immediate postoperative heart failure (3 hours after operation), and the same study was performed when myocardial failure secondary to rejection occurred (5 to 7 days). After basal state measurement, 5 and 10 micrograms.kg-1.min-1 of dobutamine were infused continuously, and the hemodynamic response during the two phases was compared. The baseline cardiac index in the immediate postoperative period was 1.4 +/- 0.4 L.min-1.m2 and 1.8 +/- 1.0 L.min-1.m2 during rejection, showing a similar degree of heart failure. Dobutamine (5 micrograms.kg-1.min-1) increased cardiac index by 97% 3 hours after transplantation and by 35% during rejection (p < 0.05). With 10 micrograms.kg-1.min-1 of dobutamine, the difference between increments was not significant (99% versus 79%). Raising the infusion rate of the drug to 15 and 20 micrograms.kg-1.min-1 during rejection increased cardiac index by 97% and 118%, respectively. Interestingly, no detrimental tachycardia occurred with this increased dosage. Heart failure secondary to acute rejection can therefore be improved by dobutamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗