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Biomedical subjects

L Merlo

Publications and source records attributed to L Merlo.

At least 37 records · Page 2Linked to original sources

Effects of ibopamine on systemic, pulmonary and regional hemodynamics. Experimental investigations in anesthetized dogs.

The effects of a new orally effective dopamine-like derivative, ibopamine (SB-7505), the 3,4-diisobutyryl ester of N-methyldopamine, on the cardiovascular system were investigated in anesthetized dogs. Ibopamine increased dose-dependently stroke volume index, cardiac index, left ventricular pressure, its first derivative: dP/dt, peak velocity left ventricular ejection and renal blood flow. After beta-blockade the positive inotropic effect of ibopamine is inhibited. Total peripheral resistance and renal vascular resistance decreased after ibopamine. Urine output was increased dose-dependently, reaching 115% after ibopamine 8 mg/kg intraduodenally. Coronary and femoral flows and resistance did not change after administration of 4 and 8 mg/kg. Only very high doses (24 mg/kg) caused an increase in flow and resistance. Mesenteric flow decreased transiently and then returned to the previous level or increased considerably over the basal figures when a high dose was used. No significant changes or fall in heart rate were observed with doses up to 16 mg/kg and no significant changes in pulmonary resistance were noted. The data obtained from the present investigation show, however, that oral ibopamine is capable of producing most of the effects induced by intravenously given dopamine in anesthetized dogs. Ibopamine's cardiac and renal effects may open new prospects for the long-term treatment of chronic heart failure in human subjects.

Anesthesia↗

Effects of ibopamine on acute cardiac failure following experimental coronary occlusion in dogs.

The activity of ibopamine (SB-7505), the 3,4-diisobutyryl ester of N-methyldopamine, on myocardial contractility and systemic and renal hemodynamics was investigated in the anesthetized dog with experimental infarction, instrumented with catheters and electromagnetic flowmeters. Ibopamine, given by the intraduodenal route at a dose of 24 mg/kg, was effective in improving the hemodynamic parameters depressed by myocardial infarction, in particular myocardial contractility and renal hemodynamics. In eliciting such activity which resembles that developed by dopamine in similar experimental conditions, ibopamine seems to meet the requirements of an orally active pharmacological agent useful in the therapy of acute heart failure.

Animals↗

[Effects of dopamine, noradrenaline and isoproterenol on pulmonary circulation in anesthetized dogs].

Experiments were performed on 19 anaesthetized open-chest dog instrumented with polyethylene catheters inserted: into the aorta, in pulmonary artery and in left atrium and with an electromagnetic flow-transducer placed around the ascending aorta in order to record : systemic arterial and pulmonary pressures, mean left auricular pressure and phasic aortic flow. Heart rate, stroke volume, total systemic and pulmonary resistance, cardiac work were moreover calculated. Each dog was given intravenously by slow infusione : Dopamine (micrograms 5--10--20/kg/min/ 5 min), Isoproterenol (microgram 0.125--0.25--0.5/kg/min/5 min) and Norepinephrine (microgram 0.25--0.5--1 /kg/min/5 min). Results obtained on systemic hemodynamics agree with those reported by many other investigators. On pulmonary circulation : Isoproterenol, at the tested doses, elicited vasodilator effects, Norepinephrine increased total pulmonary resistance but not pulmonary vascular resistance, while Dopamine did not modify or slightly reduced vascular pulmonary tone.

Animals↗

Acute clinical tolerance of creatinol O-phosphate.

Acute clinical tolerance to N-methyl-N-(beta-hydroxyethyl) guanidine O-phosphate (creatinol O-phosphate, COP) was investigated in volunteer human subjects without heart or renal disease and without other serious illness. COP was administered i.v. at three different dosages, 1020 mg (group A), 2040 mg (group B) and 3060 mg (group C), in comparison with a placebo (group D). Arterial pressure, heart rate, ECG pattern and a complete blood analysis showed no change at any COP dosage, with the exception of blood phosphate, which increased in groups B and C. Cumulative urinary excretion of phosphate and creatinine and diuresis increased, whereas other urine parameters did not change. The phosphate and creatinine increases derived from the COP molecule and the increase in diuresis from a simple osmotic process required to dilute the phosphate in the tubular fluid. All these alterations were statistically significant and dose-related with COP and had been expected. COP proved to be a very well tolerated drug without any evident side effect.

Adolescent↗

The action of creatinol 0-phosphate on the inotropic effect of isoprenaline in isolated rat atria and in anesthetized dogs.

The action of N-methyl-N-(beta-hydroxyethyl) guanidine O-phosphate (creatinol O-phosphate) was studied on the contractility of the heart, in vitro on isolated rat atria and in vivo in anesthetized dogs. Creatinol O-phosphate was without action on the contractility of isolated rat atria stimulated by isoprenaline 10(-8) mol/l which produced the maximum inotropic effect. Creatinol O-phosphate increased the contractility evoked by isoprenaline 10(-5) mol/l and impaired the development of the negative inotropic effect evoked by prolonged treatment with this large dose. In dogs, creatinol O-phosphate pretreatment increased the positive inotropic effect of large but not low isoprenaline dosages. It is concluded that creatinol O-phosphate increased the contractile efficiency of the heart submitted to the action of an excess of catecholamines.

Animals↗

Hemodynamic and metabolic changes induced by temporary clamping of the thoracic aorta.

Numerous authors reported a significant deterioration of heart function induced by aortic cross-clamping. Nevertheless, the aorta has been clamped during various surgical procedures without any complication. We studied the hemodynamic and metabolic variations induced by 20 min thoracic aorta cross-clamping in 6 open-chest dogs. During clamping the most striking modifications were an increase in coronary blood flow of over 65%, an increase in cardiac work of over 77% and an increase in total peripheral resistances of over 68% compared to base values. No significant variations were found in the heart rate and cardiac index. Metabolic parameters, such as O2 consumption and lactate consumption increased significantly during the clamping period. The increase in lactate consumption and the progressive and continuous improvement in oxygenation indexes (lactate/pyruvate, redox potential, excess of lactate) proved the absence of any myocardial anoxia during this period. Within 15--30 min after declamping all hemodynamic and metabolic parameters reverted to values close to basal values. These data strongly suggest that the mammalian heart can tolerate this procedure satisfactorily for a limited period of time. In clinical settings, one should consider the base conditions of the cardiovascular system before transposing these conclusions.

Animals↗

Effects of creatinol-O-phosphate (COP) on haemodynamics and cardiac metabolism in conscious and anaesthetized dogs.

The effects of creatinol-O-phosphate (COP, Aplodan) have been studied on haemodynamics and cardiac metabolism of virtually normal heart (conscious dogs with electromagnetic probes chronically implanted) and progressively failing heart (open chest anaesthetized dogs). The results obtained show that COP in both series of experiments increased cardiac work and improved some myocardial metabolic parameters (delta redox potential across the heart, lactate/pyruvate ratio, excess lactate) probably by enhancing the myocardial O2 supply-consumption ratio, and consequently increasing the amount of O2 available for energetic reactions in the cardiac muscle and possibly in other tissues as well.

Animals↗