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Biomedical subjects

A Berdeaux

Publications and source records attributed to A Berdeaux.

At least 91 records · Page 5Linked to original sources
PubMed1989

[Vasodilator agents and the vascular endothelium].

The recent discovery of endothelium-derived relaxation factor (EDRF) has altered the traditional classification of vasodilators used in angina pectoris and heart failure. If a vasodilator induces release of EDRF from the epithelium it is classified as endothelium-dependent, if not it is independent. Sodium nitroprusside and SIN-1 (active metabolite of molsidomine) are the main independent vasodilators since the endothelium relaxation factor appears to be principally a nitric oxide radical in these synthetic vasodilators. In contrast, calcium-channel blockers and a good number of endogenous chemical mediators (acetylcholine, bradykinin, serotonin, etc.) are endothelium-dependent. Furthermore, simple increase in blood flow through the large vessels can result in endothelium-dependent vasodilation (flow rate-dependence) the extent of which depends on the drug examined. The fact that the pharmacologic response of a vasodilator can be altered under certain pathologic conditions (atherosclerosis, hypertension, diabetes, etc.) further increases the importance of the role of the vascular endothelium in the action of vasodilators since endothelial modulation may then be completely diverted to secretion of endothelium-derived contracting factors (EDCFS).

Endothelium, Vascular↗
PubMed1989

Cardiac and hemodynamic profile of the new cardiotonic agent, DPI 201-106, in the conscious dog.

The cardiac and hemodynamic effects of increasing doses (0.1-3 mg/kg i.v.) of the novel cardiotonic agent, DPI 201-106 (DPI), were investigated over a 60 min period in conscious dogs chronically instrumented for the measurement of arterial pressure, heart rate, left ventricular pressure (LVP), LV (+) dP/dtmax and cardiac output. LV (+) dP/dtmax, cardiac output and stroke volume were significantly increased by DPI whereas the total peripheral resistance was significantly decreased. These effects were dose-dependent in intensity and in duration. The mean arterial pressure and heart rate remained unaffected, except by the 3 mg/kg dose, which increased them slightly. Autonomic blockade with hexamethonium, atropine and propranolol did not alter the positive inotropic properties of DPI but unmasked its intrinsic bradycardic effect. At equipotent positive inotropic doses, DPI (0.3 mg/kg), milrinone (40 micrograms/kg) and dobutamine (5 micrograms/kg per min) induced similar increases in cardiac output and similar decreases in total peripheral resistance, but only dobutamine and milrinone accelerated the heart rate, whereas ouabain (17.5 micrograms/kg) induced a strong rise in the total peripheral resistance and markedly lowered the heart rate and cardiac output. After coadministration of DPI and ouabain, LV (+) dP/dtmax was further increased whereas the ouabain-induced bradycardia, the rise in the total peripheral resistance and the decrease in cardiac output were reinforced, halved and unaltered, respectively. We conclude that (a) DPI exhibits potent and direct positive inotropic properties, associated with a peripheral vasodilating action, and almost no positive chronotropic effects, and (b) coadministration of DPI and ouabain results in synergistic positive inotropic effects.

Animals↗
PubMed1989

Arterial baroreceptor reflex and calcium antagonists.

The tachycardia elicited by decreases in aortic pressure produced by various calcium antagonists, regardless of their chemical structures, is not always simply related to the reduction in pressure. Several experimental and clinical experiments have clearly demonstrated that some of these compounds interfer with the baroreceptor reflex control of heart rate. The voltage-dependent calcium channel blockade induced by these antagonists is probably not involved in the baroreceptor mechanotransduction, but central modulation of the baroreceptor reflex is probably an important site for action of these drugs at therapeutic levels. During chronic treatment of hypertension with calcium antagonists, a resetting of the reflex occurred with parallel shift of the set-point and of the baroreceptor reflex-response curve towards lower pressures, thus explaining the lack of change in heart rate despite a permanent reduction in blood pressure under these conditions. However, these effects of calcium antagonists on the baroreceptor reflex do not provide evidence that such interactions could play a role in their antihypertensive action during chronic therapy.

Animals↗
PubMed1988

Relationship between parietal blood flow studies in the left colon and the rectum in dogs. Colonic pressure and blood flow.

An animal model was proposed to clarify the difference in occurrence of enterocolitis in congenital aganglionosis. When gaseous distention of the colon was localized to the rectosigmoid area, enterocolitis never occurred. On the contrary, when it involved the left colon, enterocolitis occurred in 13 of 15 patients. Intestinal blood flow rates were simultaneously measured in the left colon and rectum of six dogs by using labeled microspheres and expressed in function of the intraluminal pressure. Results show that for elevated values of intraluminal pressure, blood flow was significantly lower in the left colon than in the rectum. These results may explain why ischemia and necrosis occurred more frequently in the left colon than in the rectum.

Animals↗
PubMed1988

Comparison of the effects of Bay K 8644 and aortic constriction on regional myocardial blood flow and function in canine nonischemic and ischemic myocardium.

The effects of Bay K 8644, aortic constriction, and a placebo on regional myocardial blood flows (RMBFs) and contractile function (RCF) were compared in three groups of open-chest anesthetized dogs during coronary stenosis. Bay K 8644 was investigated in two doses: 0.1 micrograms/kg, which exhibited no systemic hemodynamic effect, and 1 microgram/kg, which significantly increased arterial pressure. Aortic constriction was performed to raise afterload to the same extent as Bay K 8644 1 microgram/kg. As compared with placebo, Bay K 8644 0.1 microgram/kg, significantly increased coronary resistance, decreased RMBFs without changing RCF in nonischemic myocardial zones, and affected neither RMBFs nor RCF in ischemic zones. In nonischemic myocardium, Bay K 8644 1 microgram/kg increased RMBFs without affecting RCF, whereas aortic constriction did not modify RMBFs but decreased RCF. In ischemic myocardium, both Bay K 8644 1 microgram/kg and aortic constriction increased RMBFs but did not affect RCF. Thus, the low dose of Bay K 8644 exerts a direct and selective coronary vasoconstrictor effect that has no deleterious consequences on nonischemic RCF. Despite this intrinsic coronary vasoconstrictor effect, the high dose of Bay K 8644 increases RMBFs and maintains RCF in both ischemic and nonischemic zones in relation with the drug-induced increases in coronary perfusion pressure (both zones) and in contractility (nonischemic zones).

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1988

Evaluation of the natriuretic and beta-adrenoceptor-blocking effects of tienoxolol in normal volunteers.

The beta-adrenoceptor blocking and diuretic properties of tienoxolol (150 mg and 300 mg) were investigated and compared to those of a placebo in a double-blind, cross-over trial in six healthy volunteers. Heart rate (HR), systolic and diastolic blood pressures, peak expiratory flow rate (PEFR) at rest and during vigorous exercise, plasma renin activity (PRA) and aldosterone levels at rest, and diuresis and urinary electrolyte excretion values were measured before and at intervals up to 24 h after oral administration of the drugs. In addition, the clearances of electrolytes, uric acid, and creatinine were calculated, as well as the fractional sodium excretion (Fe Na%) before and 4 h and 24 h after drug intake. Finally, tienoxolol plasma levels were measured. Tienoxolol significantly and dose-dependently reduced exercise-induced tachycardia. This effect started 1 h after drug administration, peaked between 4 h and 6 h (-12% and -17% from control values at 150 mg and 300 mg, respectively), and lasted at least 12 h. Resting HR was decreased at 300 mg (P less than 0.05), PRA was decreased at both doses (P less than 0.05), but PEFR was not drug-affected. 24-h cumulative sodium excretion was increased (+24% at 150 mg [NS], +38% at 300 mg [P less than 0.01]) as compared to placebo, and Fe Na% did not change, regardless of the dose administered. 24-h cumulative diuresis was moderately increased by tienoxolol (NS), whereas creatinine clearance rose after the 300-mg dose, suggesting that tienoxolol might increase glomerular filtration rate. Plasma aldosterone levels remained unchanged. Finally, the elimination half-life of tienoxolol was 7.5 h. Thus, in healthy volunteers, tienoxolol behaves as an early acting and relatively long-lasting selective beta 1-adrenoceptor blocking drug endowed with significant natriuretic properties.

Adrenergic beta-Antagonists↗
PubMed1988

Effects of amiodarone therapy on thyroid iodine content as measured by x-ray fluorescence.

Thyroid iodine content (TIC) was measured by x-ray fluorescence in 68 patients who had received amiodarone treatment for varying intervals (1 g/week for 1-120 months). Thirty-six patients were euthyroid; the mean TIC of the patients (n = 15), who had been treated for less than 12 months was 30 +/- 19 (+/- SD) mg, twice the normal mean value (14.6 +/- 5.0 mg), and it was 39 +/- 17 mg in those (n = 16) who had been treated for 12-60 months and 29 +/- 6 mg in those (n = 5) who had been treated longer (greater than 60 months). Nineteen patients were hyperthyroid and had elevated TIC values. Of them, 6 patients had a goiter; their TIC (50 +/- 19 mg) was not significantly different from that of the hyperthyroid patients with no goiter (55 +/- 29 mg), but they became hyperthyroid more rapidly. Thirteen patients were hypothyroid; none had TIC values above the normal range, and it was below 2.5 mg in 5 patients. A sequential study was undertaken in 11 euthyroid patients who had no detectable antithyroid antibodies. TIC did not increase during treatment in 2 patients; both developed hypothyroidism, which was transient in 1 despite continuation of amiodarone treatment. The TIC initially increased during amiodarone treatment in the other 9 patients, leveling off at the end of the first year. The TIC rose well above the upper limit of the normal range in 4 patients, of whom 2 became hyperthyroid during the second year of treatment. TIC remained within the normal range in the other 5 patients, of whom 3 became hypothyroid after 12-24 months of treatment (1 subclinical, 2 overt). Although the TIC was significantly higher in the patients with hyperthyroidism than in the patients who remained euthyroid, the TIC test cannot be used to predict the occurrence of hyperthyroidism. The latter must be diagnosed on the basis of clinical symptoms and a frank elevation of serum thyroid hormone levels. Conversely, patients whose TIC values do not increase during treatment or remain within the normal range should be considered at risk for hypothyroidism.

Adult↗
PubMed1988

Pharmacokinetics of bupivacaine after short and prolonged infusions in conscious dogs.

A conscious dog model was used to study pharmacokinetics of bupivacaine after a short infusion (SI) (15 min) and a prolonged infusion (PI) (24 hours). Bupivacaine was infused in six mongrel dogs at least 10 days after implantation of femoral arterial and venous catheters. Each dog received both the SI and the PI in a random crossover design at a one week interval. Bupivacaine concentration was measured in serum sampled during the SI, during the last hour of the PI, and at frequent intervals during eight hours after cessation of infusion. Indocyanine green (ICG) clearance also was measured during the last hour of the PI and 90 min after cessation of both the SI and the PI. The terminal half-life (T1/2Z) of bupivacaine increased after the PI compared with the SI, 167 +/- 86 vs 53 +/- 13 min, respectively (mean +/- SD; P less than 0.05), and total body clearance (Cl) decreased, 3.4 +/- 1.2 vs 9.5 +/- 4.5 ml.min-1.kg-1, (P less than 0.05), although the volumes of distribution (VZ and VSS) did not change. A decrease in hepatic blood flow did not cause the decrease in Cl because ICG clearance did not change during the three sets of measurements. Thus, the observed increase in T1/2Z and decrease in Cl after the PI as compared with the SI are due to a decrease in hepatic intrinsic clearance of bupivacaine. Differences in the kinetic profile of the two enantiomers of bupivacaine cannot be excluded as a cause. We conclude that the extrapolation of kinetic data of bupivacaine obtained after a short infusion (or a bolus injection) to prolonged dosage must be done with care.

Anesthetics, Local↗
PubMed1987

Ketanserin and the arterial baroreceptor reflex in normotensive subjects.

The effects of oral ketanserin 40 and 120 mg on the responses to baroreflex activation and deactivation by phenylephrine and nitroglycerin, respectively, were investigated in normotensive subjects. Plasma catecholamine levels were measured at the same times. Two hours after the administration of ketanserin, and regardless of its effect on arterial pressure (no change after 40 mg, decrease after 120 mg), there was no alteration either in resting heart rate or baroreflex sensitivity during baroreceptor activation or deactivation. The lack of reflex tachycardia in response to the drug-induced hypotension may be related to the alpha 1-adrenoceptor blockade-mediated sympathoinhibitory effect of ketanserin, which leaves unaffected both plasma catecholamines and the normal reactivity of the sympathetic system.

Adult↗
PubMed1987

Effects of four angiotensin I converting enzyme inhibitors on regional myocardial blood flow and ischemic injury during coronary artery occlusion in dogs.

The effects of 4 angiotensin I converting enzyme inhibitors (ACEI), captopril, enalapril, ramipril, and trandolapril, were investigated on regional myocardial blood flow (RMBF, radioactive microspheres) distribution in ischemic and nonischemic zones and on ST-segment elevation in ischemic zones during intermittent coronary artery occlusion in anesthetized dogs. The 4 ACEI inhibited plasma ACE activity to an almost similar extent. All similarly reduced systemic blood pressure, an effect related to a decrease in systemic vascular resistance. Heart rate and myocardial contractility were not affected, but myocardial oxygen consumption presumably decreased because of the reduction in afterload. RMBF and their distribution (between epicardial and endocardial layers and between nonischemic and ischemic zones) were not modified by ACEI. Coronary vascular resistance was slightly decreased in nonischemic zones. ACEI had no effect on ST-segment elevation in ischemic zones. Thus, in this experimental model, all ACEI exhibited the same profile, including no change in RMBF and affording no protection against ischemic injury.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1987

Antihypertensive drugs and baroreceptor reflex control of heart rate and blood pressure.

The arterial baroreceptor reflex (BR; aortic and carotid sinus BR) and the cardiopulmonary BR are the most important reflexes acting as buffer systems for the maintenance of arterial pressure around a fixed physiologic value. They act as permanent inhibitory systems on the central cardiovascular structures and they can be either activated or deactivated by using selective techniques. During chronic hypertension there are structural alterations of the peripheral and/or central components of the BR that become "reset", with a shift in the function curve relating BR activity to blood pressure (BP) in the direction of higher pressure values. As a consequence of the hypertension-induced resetting phenomenon, both the threshold pressure and sensitivity of BR are disturbed. However, if BR resetting during hypertension clearly decreases the sensitivity of BR control of heart rate (HR), BR control of peripheral resistance and arterial pressure as a whole is preserved and even increased when hypertension develops. Thus, this apparent discrepancy between BR control of HR and BP during hypertension demonstrates that evaluation of an antihypertensive therapy on reflex control of HR alone cannot predict what will happen to BR control of the whole cardiovascular system. Regarding BR control of HR, in contrast to the classical arteriolar vasodilators such as hydralazine and its derivatives, the majority of the modern antihypertensive drugs do not evoke reflex tachycardia in response to lowering of BP in normotensive or hypertensive subjects. Although the intrinsic pharmacologic mechanisms of action of these drugs on BR may be quite different (e.g., alpha 1-or beta-adrenoreceptor blocking agents, converting enzyme inhibitors, certain calcium-channel blockers of the phenyldihydropyridine group, and so on), they all shift in a parallel manner the set-point of the BR response curve towards lower pressures, with no change in HR or R-R interval. Generally, this resetting phenomenon occurs after several weeks or months of antihypertensive therapy, but it can also occur acutely (e.g. after IV injection) after administration of drugs such as prazosin or ketanserin. Finally, antihypertensive agents such as clonidine and methyldopa can simultaneously reset the BR and increase its sensitivity, thus leading to almost complete restoration of control of HR response despite the concomitant decrease in BP. Regarding BR control of blood pressure, only captopril and especially celiprolol (a beta 1-adrenoreceptor blocking drug with vasodilating properties) are able to restore almost normal BR control of arterial pressure.

Antihypertensive Agents↗
PubMed1987

Bupivacaine accentuates the cardiovascular depressant effects of verapamil in conscious dogs.

To investigate the potential risk of regional anaesthesia in a verapamil-treated patient, the cardiovascular effects of a combined intravenous infusion of bupivacaine and verapamil were studied in seven conscious and chronically instrumented dogs and were compared to those obtained when each drug was infused separately in the same animals. During verapamil infusion, the decrease in arterial pressure and myocardial contractile force, and the increase in heart rate were constant during the infusion. The lengthening of PR interval correlated with the plasma level of verapamil. During infusion of bupivacaine alone, there was an increase in heart rate and arterial pressure at the end of infusion, whereas the initial depression of myocardial contractile force was compensated. PR interval remained unchanged throughout the infusion of bupivacaine. During combined infusion of bupivacaine and verapamil, there was a time-dependent decrease in heart rate, arterial pressure and myocardial contractile force. A further increase in PR interval correlated with verapamil plasma concentrations which were higher than when verapamil was infused alone; bupivacaine plasma levels were in the same range as during bupivacaine infusion alone. Short periods of second-degree atrioventricular block developed in three out of the seven dogs but no relation was found between QT interval and heart rate in the whole group. Calcium chloride during bupivacaine-verapamil returned heart rate, arterial pressure and myocardial contractile force to their control values within 5 min. Atrioventricular block disappeared and PR interval was shortened following administration of calcium. Bupivacaine and verapamil have additive cardiovascular effects which lead to atrioventricular conduction dysfunction. The effects, at these doses, are reversed by calcium chloride.

Animals↗
PubMed1986

Influence of venous return on baroreflex control of heart rate during lumbar epidural anesthesia in humans.

The role of variation of venous return on baroreflex control of heart rate during lumbar epidural anesthesia was investigated in 12 unpremedicated patients. Group 1 patients (n = 6) received 8 ml of 0.5% plain bupivacaine in the epidural space (L3-4) (mean upper level of analgesia at T10). Group 2 patients (n = 6) received 8 ml of saline at the same level in the epidural space. Following the epidural injection, phenylephrine (PHE) and nitroglycerin (NTG) were employed to alter the stimulation of baroreceptor sites before and during application of lower body positive pressure (LBPP). Plasma bupivacaine, catecholamines, renin activity, and vasopressin were assayed. In contrast to saline, epidural bupivacaine induced a decrease in systolic arterial and right atrial pressures (-11 +/- 4 and -3.2 +/- 0.7 mmHg, respectively, mean +/- SEM) without change in heart rate, an increase in baroreflex slopes during PHE and NTG injections (+5.9 +/- 1.6 ms/mmHg and +2.8 +/- 0.9 ms/mmHg, respectively), and a decrease in plasma norepinephrine (-248 +/- 89 pg/ml). The application of LBPP restored hemodynamic and reflex variables to preepidural analgesia values, whereas plasma catecholamines decreased further. Plasma renin activity and vasopressin were not modified at any time in either groups. This study indicates that lumbar epidural anesthesia enhances cardiac vagal tone mainly through a decrease in venous return.

Adult↗
PubMed1986

Effects of lidocaine on myocardial contractility and baroreflex control of heart rate in conscious dogs.

The effects of intravenous lidocaine (30 and 60 micrograms X kg-1 X min-1 during 30 min) at steady-state plasma levels (1.9 +/- 0.2 and 3.5 +/- 0.2 micrograms/ml, respectively) were investigated in conscious dogs, previously instrumented for measurements of arterial and left ventricular (LV) pressures, isometric myocardial contractility indexes (LV peak rate of tension development [dP/dt] and LV [dP/dt]/DP40), and heart rate. In addition, before and at the end of lidocaine infusions, arterial baroreflex responses were tested by bolus injections of nitroglycerin and phenylephrine. Whereas LV peak dP/dt and LV (dP/dt)/DP40 were significantly decreased after the low dosage of lidocaine, these indexes returned to control values after the 10th min of infusion of the high dosage. Moreover, eight out of 14 dogs exhibited continuous tremors, tachycardia, hypertension, and increase in contractility after the 10th min of lidocaine infusion (60 micrograms X kg-1 X min-1), although their lidocaine plasma levels (3.7 +/- 0.2 micrograms/ml) did not differ from those of the whole group. When these dogs were pretreated by combined alpha- and beta-adrenoceptor blocking drugs, none of them had tremors, and there was a constant depressant effect on cardiac chronotropism and inotropism. A specific enhancement of baroreflex sensitivity after phenylephrine injection was observed at the high lidocaine dosage. It is concluded that a central stimulation of both components of the autonomic nervous system modulates the direct effects of therapeutic plasma levels of lidocaine on cardiac chronotropism and inotropism in conscious dogs.

Animals↗