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Biomedical subjects

M Leeman

Publications and source records attributed to M Leeman.

At least 91 records · Page 5Linked to original sources
PubMed1987

Inhibition of angiotensin-converting enzyme by perindopril diacid in canine oleic acid pulmonary edema.

To test the hypothesis that angiotensin II could be a mediator of acute lung injury, we studied the effects of perindopril diacid, a new angiotensin-converting enzyme inhibitor, on hemodynamics, blood gases, lung mechanics, and extravascular lung water (EVLW). Twenty-four dogs were anesthetized, paralyzed and ventilated with a fraction of inspired oxygen of 0.4 in which pulmonary edema was induced by 0.1 ml/kg iv oleic acid. Perindopril diacid (1 mg/kg) was administered iv either before (eight dogs) or 100 min after (eight dogs) oleic acid injection. In the control group (eight dogs) not treated with perindopril diacid, 150 min after oleic acid injection, PaO2 changed from 193 +/- 7 (mean +/- SEM) to 55 +/- 4 torr, venous admixture from 3 +/- 1% to 52 +/- 5%, cardiac index from 4.1 +/- 0.3 to 3.1 +/- 0.3 L/min X m2, mean pulmonary artery pressure from 13 +/- 1 to 17 +/- 1 mm Hg, dynamic compliance from 90 +/- 8 to 46 +/- 7 ml/cm H2O, and EVLW from 165 +/- 25 to 750 +/- 92 ml/m2. Administration of perindopril diacid reduced systemic BP by 20% but did not affect other hemodynamic variables, blood gases, or dynamic compliance. Maximum increases in EVLW were from 169 +/- 16 to 615 +/- 54 ml/m2 in the pretreated group and from 188 +/- 23 to 675 +/- 56 ml/m2 in the treated group (no significant difference from the control group). However, pretreatment with perindopril diacid significantly (p less than .05) slowed the rise in EVLW, which was lower 60 and 90 min after oleic acid injection compared to untreated dogs. Plasma renin activity and angiotensin I concentration increased after oleic acid injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1987

Pulmonary arterial pressure-flow plots in dogs: effects of isoflurane and nitroprusside.

We investigated the effects of nitroprusside and isoflurane on multipoint pulmonary arterial pressure (PAP)/cardiac index (Q) plots in pentobarbital sodium-anesthetized dogs ventilated alternatively in hyperoxia (fraction of inspired O2, FIO2, 0.4) and hypoxia (FIO2 0.1). Over the entire range of Q studied, 2-5 l.min-1.m-2, hypoxia increased PAP in 16 dogs ("responders") and did not affect PAP in 16 other dogs ("nonresponders"). A hypoxic pulmonary vasoconstriction (HPV) was restored in the nonresponders by intravenous administration of 1 g of acetylsalicylic acid (ASA). Nitroprusside (5 micrograms.kg-1.min-1) inhibited HPV in responders (n = 8) and nonresponders treated with ASA (n = 8). End-tidal 1.41% isoflurane (a minimal alveolar concentration equal to one for dogs) did not affect HPV in responders (n = 8) and nonresponders treated with ASA (n = 8). In the latter group isoflurane increased PAP at the highest Q studied (3-5 l.min-1.m-2) in hyperoxia and hypoxia. In a final group of eight dogs with Q kept constant, PAP remained unchanged during two consecutive sequences of alternated 30-min periods (maximum time to generate a PAP/Q plot) successively at FIO2 0.4 and 0.1, and the hypoxia-induced increase in PAP was reproducible. Thus the present experimental model appeared suitable for the study of the effects of hypoxia and drugs on pulmonary vascular tone of intact dogs. At the given doses HPV was inhibited by nitroprusside and not affected by isoflurane. Products of arachidonic acid metabolism possibly could be implicated in the pulmonary vascular effects of isoflurane.

Animals↗
PubMed1987

Effects of dopamine and dobutamine on hyperoxic and hypoxic pulmonary vascular tone in dogs.

The pulmonary vascular effects of dopamine and of dobutamine have been reported variably in the literature. We investigated the effects of dopamine and of dobutamine, at doses of 10 and 20 micrograms/kg/min, on the relationships of overall mean pulmonary arterial pressure (Ppa) to cardiac index (Cl) in 14 dogs ventilated alternatively in hyperoxic (FIO2, 0.4) and in hypoxic (FIO2, 0.1) conditions. Five-point Ppa/Cl plots were constructed by opening an arteriovenous femoral fistula or by stepwise inflations of a balloon in the inferior vena cava. These Ppa/Cl plots were rectilinear in all experimental conditions. Hypoxia was associated with an increase in Ppa over the entire range of Cl studied (2 to 5 L/min/m2). A deterioration in arterial oxygenation and an increase in O2 consumption constantly occurred after dopamine as well as after dobutamine administration. At 10 micrograms/kg/min (n = 6 dogs) neither drug affected Ppa over the entire range of Cl at both 0.4 and 0.1 FIO2. At 20 micrograms/kg/min (n = 8 dogs), dopamine and dobutamine increased Ppa at the lowest Cl (2 to 4 and 2 to 3 L/min/m2, respectively) at 0.4 FIO2, and attenuated hypoxia-induced increases in Ppa over the entire range of Cl. Two repetitions of alternated 0.4 and 0.1 FIO2 exposures had no effect on Ppa/Cl plots in 6 additional dogs given no drug. We concluded that at dosages as great as 20 micrograms/kg/min, as generally given in clinical practice, dopamine and dobutamine exerted similar effects upon the pulmonary circulation of intact dogs; either no change or an increase in hyperoxic pulmonary vascular tone and either no change or an attenuation of hypoxic pulmonary vasoconstriction.

Animals↗
PubMed1987

Reduction in pulmonary hypertension and in airway resistances by enoximone (MDL 17,043) in decompensated COPD.

Hemodynamics, blood gas values, and lung mechanics were investigated in 19 patients with decompensated COPD before and 30 and 60 minutes after a slow (15 minute) intravenous administration of 3 mg/kg enoximone (MDL 17,043). In the first 11 patients who were spontaneously breathing, enoximone significantly decreased pulmonary arterial wedge pressure, right atrial pressure, mean systemic arterial pressure, and mean pulmonary arterial pressure. Cardiac output remained unchanged, while heart rate increased slightly. Lung resistance decreased and dynamic lung compliance increased. Blood gas values remained unchanged. Similar effects were observed in the next eight patients who were artificially ventilated, except for an increase in cardiac output. These results show that enoximone has bronchodilating and pulmonary vasodilating properties.

Aged↗
PubMed1986

Acute central and renal haemodynamic responses to tertatolol and propranolol in patients with arterial hypertension following head injury.

We compared the central and renal haemodynamic effects of tertatolol, a new non-cardioselective beta-adrenergic blocking drug without partial agonist activity, with those of an equipotent dosage of propranolol in two groups of 10 patients each with acute cerebral injury who had developed systemic hypertension. After tertatolol, 5 mg orally, mean arterial pressure was unchanged, heart rate decreased by 22% (P less than 0.01) and cardiac index by 24% (P less than 0.01), while renal blood flow remained unchanged (-5%, NS). After 160 mg propranolol orally, mean arterial pressure was unchanged, heart rate decreased by 12% (P less than 0.01), cardiac index by 16% (P less than 0.01) and renal blood flow by 17% (P less than 0.01). There was a moderate rise in norepinephrine levels after tertatolol only. Thus in this particular model of acute hypertension, tertatolol acted as a potent beta-blocking agent but differed from propranolol by preserving renal perfusion.

Adolescent↗
PubMed1986

Cardiovascular and blood gas responses to inhaled anaesthetics in normoxic and hypoxic dogs.

Changes in haemodynamics and blood gases were investigated before and after administration of 0.5, 1 and 1.5 MAC of halothane, enflurane and isoflurane in respectively 7, 7 and 9 dogs ventilated alternatively with a fraction of inspired O2 in N2 (FiO2) of 0.4 and with brief periods (10 min) of FiO2 of 0.1. Anaesthesia was induced with pentobarbital and the animals were paralysed with pancuronium. Acute hypoxic challenges with FiO2 of 0.1 consistently decreased arterial PO2 to 3.5-4.5 kPa and increased pulmonary vascular resistances by 60-100%. At identical inspired concentrations, as expressed in MAC units, all three inhaled anaesthetics induced a broadly comparable dose-related decrease in systemic blood pressures, due to a depression in cardiac performance as well as a reduction in systemic vascular resistances. Enflurane was the most potent myocardial depressor and isoflurane the most potent vasodilator, halothane being intermediate. Oxygen deprivation was associated with some enhancement of the cardiovascular depressant effects of the inhaled anaesthetics but, in spite of this, matching of O2 transport to tissue O2 demand appeared to be improved, probably in relation to a concomitant reduction in metabolic rate. Only isoflurane inhibited the hypoxic pulmonary pressor response, and this was associated with a slight deterioration in arterial oxygenation in both normoxic and hypoxic conditions.

Adaptation, Physiological↗
PubMed1986

Tertatolol preserves renal perfusion in patients with arterial hypertension after head injury.

Tertatolol is a noncardioselective beta-adrenergic blocking agent without partial agonist activity. Its central and renal hemodynamic effects were compared to those of an equipotent dosage of propranolol in two groups of 10 patients each who developed arterial hypertension and a hyperdynamic circulatory state after head injury. After tertatolol, 5 mg orally, mean arterial blood pressure was unaffected, heart rate decreased by 22% (p less than 0.01) and cardiac index by 24% (p less than 0.01) while renal blood flow remained unchanged (-5%; not significant) so that the renal fraction of cardiac index was increased by 22% (p less than 0.05). After propranolol, 160 mg orally, mean arterial blood pressure was not modified, heart rate decreased by 12% (p less than 0.01), cardiac index by 16% (p less than 0.01) and renal blood flow by 17% (p less than 0.01) so that the renal fraction of cardiac index remained unchanged (-3%; not significant). Tertatolol is a potent beta-blocking agent comparable to propranolol apart from the fact that it preserves renal perfusion; this peculiar effect is related to a redistribution of the reduced cardiac output to the benefit of the kidney.

Adolescent↗
PubMed1986

Discrepancy between thermodilution and radionuclide right ventricular ejection fraction measurements: the importance of tricuspid regurgitation.

Measurement of right ventricular ejection fraction (RVEF) by the thermodilution technique has become routinely available at the bedside of the critically ill. We describe 2 patients with tricuspid regurgitation in whom RVEF values were considerably lower by thermodilution than by radionuclide techniques. Discrepancies could be due to the regurgitation of the thermodilution signal and possibly to the different nature of the two measurements (forward stroke volume with the thermodilution technique and total stroke volume with the radionuclide technique). We suggest that lower RVEF measurement by the thermodilution technique could be related to unrecognized tricuspid regurgitation. Measurement of an unexpectedly low RVEF by the thermodilution technique should suggest the presence of tricuspid regurgitation.

Heart↗
PubMed1985

Administration of dazoxiben, a selective thromboxane synthetase inhibitor, in the adult respiratory distress syndrome.

Experimental studies suggest that thromboxane A2 could play a role in the pulmonary hypertension of the adult respiratory distress syndrome (ARDS). We therefore investigated the hemodynamic and gasometric effects of dazoxiben, a selective thromboxane synthetase inhibitor, in seven patients who had developed ARDS. The patients were studied for 120 minutes after a single intravenous bolus of 1.5 mg of dazoxiben per kilogram of body weight. During this period, there was no change in pulmonary hemodynamics, a moderate increase in arterial oxygen pressure, and a slight decrease in venous admixture. Therefore, administration of dazoxiben in patients with ARDS does not decrease pulmonary hypertension. This study does not support the role of thromboxane A2 as an important mediator in pulmonary hypertension in human ARDS, at least once the syndrome has been recognized.

Adult↗
PubMed1984

Prostaglandin-9-ketoreductase activity in erythrocytes of normal and hypertensive subjects.

The PGE2/PGF2 alpha balance, controlled in part by prostaglandin-9-ketoreductase, seems to be involved in the regulation of sodium excretion by the kidney. A decreased PGE2/PGF2 alpha ratio has been observed in the urine of hypertensive subjects. This suggests that an alteration of prostaglandin metabolism might be involved in the pathogenesis of essential hypertension. In order to test this hypothesis, prostaglandin-9-ketoreductase (PG-9-KR) and prostaglandin-15-dehydrogenase (PG-15-DH) activities were measured in erythrocytes of normotensive controls and patients with essential hypertension. The two enzyme activities were highly correlated in the two groups, supporting the hypothesis that they are alternate expressions of a single enzyme. These two enzyme activities were not significantly different in hypertensive subjects as compared to controls. Human essential hypertension does not appear to be linked to a generalized defect of prostaglandin catabolic enzymes.

Adult↗
PubMed1984

Administration of sulmazol in low-output states following cardiac surgery.

Sulmazol (AR-L 115BS), a phenylimidazopyridine derivative, which combines positive inotropic and vasodilating properties, was administered to nine patients who had a low cardiac output state (cardiac index below 2.0 L/min/m2) within 24 hours after cardiac surgery for valvular replacement (eight patients) or septal repair after myocardial infarction (one patient). Sulmazol, administered as a 60-minute infusion of 1.8 mg/min, resulted in significant increases in cardiac output and cardiac work, associated with significant decreases in cardiac filling pressures. Arterial pressure did not change notably, and systemic vascular resistance decreased significantly. A small but significant increase in heart rate was also observed. By its combined inotropic and vasodilating properties, sulmazol can be helpful in the management of low-output states after cardiac surgery.

Aged↗
PubMed1983

Serial lactate determinations during circulatory shock.

The time course of lactacidemia was studied prospectively in 17 patients during fluid resuscitation for an episode of noncardiogenic shock, in 5 patients after grand mal seizures, and in 5 patients after successful CPR for cardiac arrest. The 9 patients in whom shock was reversed with fluid administration demonstrated a regular decrease in lactate concentrations, which exceeded 5% of the initial value during the first 60 min of treatment. In the other patients who expired despite similar therapy, lactacidemia was not significantly affected. During circulatory shock, repeated lactate determinations represent a more reliable prognostic index than an initial value taken alone. Changes in lactate concentration can provide an early and objective evaluation of the patient's response to therapy.

Adult↗
PubMed1983

Value of lithium plasma concentration in severe lithium intoxication.

Lithium intoxication is a frequent condition with sometimes severe symptoms. Despite repeated plasma measurements, it is not always possible to prevent serious side effects because they can occur at therapeutic plasma levels. Several aspects of the lithium metabolism are reviewed and illustrated by two case reports.

Adult↗
PubMed1981

[Seizures due to lithium intoxication (author's transl)].

Lithium intoxication may present as seizures, which have been observed when plasma lithium concentrations were decreasing. The neurotoxic effect of lithium could be due to a rise in intra-/extra-cellular lithium ratio. Intracellular retention of lithium reflected in rapid fall of plasma concentrations during treatment would modify cell membrane properties and increase neuronal excitability. Such a mechanism would explain the occurrence of seizures despite therapeutic plasma lithium concentrations.

Adult↗