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Biomedical subjects

R Santamaria

Publications and source records attributed to R Santamaria.

At least 37 records · Page 2Linked to original sources

Electrophysiological effects of carocainide (770207) on the dog heart.

The electrophysiological effects of carocainide (770207) were assessed in "in vivo" and "in vitro" experiments on dogs' hearts. Intravenous administration of 5 mg/kg body weight of carocainide significantly lengthened the following: A-H interval, the shortest atrial pacing cycle length maintaining 1:1 atrioventricular (A-V) nodal conduction, H-V interval, left bundle-ventricle (LB-V) interval, the shortest His bundle pacing cycle length maintaining 1:1 His-Purkinje conduction, QRS duration, right atrial and right ventricular effective refractory periods. In Purkinje fiber-papillary muscle junction preparations driven at a constant cycle length of 1000 msec, perfusion of carocainide at the concentration of 1.25 10(-5) M and 2.5 10(-5) M, increased conduction time between Purkinje and muscle fibers and decreased the rate of depolarization of Purkinje fibers and papillary muscle. These results suggest that carocainide depresses conduction and lengthens refractory periods at atrial and ventricular levels and provide an explanation for the positive effect of this compound against experimental cardiac arrhythmias.

Animals↗

Isolation and characterization of a tRNA(guanine-7-)-methyltransferase from Salmonella typhimurium.

The tRNA modifying enzyme, S-adenosylmethionine:tRNA(guanine-7-)-methyltransferase, has been extensively purified from Salmonella typhimurium. A rapid and efficient purification method using phosphocellulose chromatography followed by ammonium sulfate precipitation and Sephadex G-100 gel filtration is described. The enzyme appears to be a single polypeptide chain with a molecular weight of approximately 25 000--30 000 daltons. The Km for S-adenosylmethionine and for undermethylated tRNA is 53 microM and 3.4 microM, respectively. The methylation reaction is dependent on added monovalent or divalent cations; 5 mM spermidine, 3 mM MgCl2 and 1 mM spermine are the most effective. The enzyme, though not homogeneous, is free from contaminating ribonucleases and other tRNA methyltransferases.

Chromatography, Gel↗

Electrophysiological effects of carocainide (770207) on canine ventricular muscle and Purkinje fibers.

Carocainide is a new benzofuran derivative showing antiarrhythmic properties in animal models. In isolated papillary muscles and Purkinje fibers it decreases the maximum rate of rise of the action potential and in Purkinje fibers it decreases the plateau amplitude and the duration of the action potential. Carocainide increases the ratio of the effective refractory period to the action potential duration at 90% of repolarization, shifts the membrane responsiveness curve towards more negative membrane potentials and slows down the recovery of the maximum rate of rise of the action potentials of the Purkinje fibers. Carocainide also increases the conduction time at the Purkinje papillary muscle junction.

Action Potentials↗

Effects of MD770207 (carocainide) on experimental ventricular arrhythmias.

Administered by intravenous or oral route, carocainide, MD770207, abolished experimental ventricular arrhythmias in anaesthetized and conscious dogs. Slow rate intravenous infusion (0.5 mg/kg/min) studies in conscious coronary ligated dogs demonstrated a good arrhythmia conversion as well as a wide margin of safety; mean conversion to 95% of normal sinus rhythm was achieved at 10.5 +/- 2.1 mg/kg while first signs of reversible neuro and cardio-toxicity occurred at 37.8 +/- 8 mg/kg. The reference agents disopyramide and lidocaine showed less favourable safety margin. Carocainide reduced epicardial ST-segment elevation produced by short coronary artery occlusion and prevented the occurrence of ventricular fibrillation resulting from reperfusion after acute coronary artery ligation. At antiarrhythmic dose levels there were no undesirable effects noted on cardiovascular function. Given intravenously the compound increased the ventricular fibrillation threshold in spontaneously hypertensive rats.

Administration, Oral↗

Functional assay of tRNA molecules transcribed from a purified gene.

Purified tRNA genes are expressed when microinjected into the nucleus of X.laevis oocytes. In this paper we describe a method to assay the capacity to be aminoacylated of the tRNA transcribed in the frog oocytes. The method exploits the radiochemical purity of the transcript and relies on the binding of aminoacyl-tRNA but not of uncharged tRNA to purified elongation factor EF-Tu. We also present some preliminary results on several single point mutants of tRNAPro from Caenorhabditis elegans. We show that nucleotide 73 of tRNAPro can be substituted by any other nucleotide without loss of acceptor activity. A double mutant, causing transition from G45G46 to A45A46 has lost acceptor activity. Also inactive is a mutant carrying an insertion of a single base in the anticodon loop.

Amino Acyl-tRNA Synthetases↗

Effects of 5-hydroxytryptamine on canine isolated coronary arteries.

The effects of 5-hydroxytryptamine (5-HT) were studied in vitro on proximal and distal portions of canine interventricular and circumflex coronary arterial strips. 5-HT produced concentration-related contractions in the proximal portion whether contracted previously with KCl or not. These responses were still present after either chemical sympathetic denervation or release of noradrenaline induced by K+-free salt solution. In contrast, the distal portions of coronary arteries did not respond to 5-HT. Concentration-response curves to 5-HT exhibited a classical hyperbolic shape with a calculated Hill-coefficient of approximately 1. Methysergide and phentolamine but not morphine shifted to the right and depressed the maximum of the dose-response curves to 5-HT. It is concluded that the contractions produced by 5-HT in the proximal portion of the interventricular and circumflex coronary arteries are not due to the release of endogenous noradrenaline. The vessels appear to possess separate receptors for 5-HT and noradrenaline and the 5-HT responses belong to neither the M nor the D type.

Animals↗

[Thermodynamic analysis of oxygen/transport to the turtle heart].

Isolated turtle hearts were perfused, at constant flow, with human erytrocytes suspensions containing different levels of 2,3-DPG. PO2 measurements, in the blood leaving the heart, resulted in lower figures when the tissue was perfused with low affinity blood compared with perfusion of high affinity blood. Thermodynamic analysis was, also, carried out at four different levels of temperature. The results suggest that, in severe hypoxia, oxygen delivery to the tissue is increased when perfusion is performed with high oxygen affinity blood.

Animals↗