Temperature-dependent inotropic effects of lignocaine and ethanol on rat heart papillary muscles.

1. The main objective of the present study was to investigate the temperature dependence of the cardiac inotropic effects of lignocaine and ethanol (EtOH). 2. We studied the in vitro inotropic actions and interactions of EtOH (2.4 g/L) and lignocaine (25 mg/L) on rat papillary muscles superfused with Tyrode's solution and stimulated at 1 Hz at either 37 or 30 degrees C. Peak tension developed (PTD), maximum velocity of development of tension (VmaxT) and time to peak tension (TPT) were measured. 3. At 37 degrees C, EtOH depressed PTD, while VmaxT and TPT remained unchanged. At 37 degrees C, lignocaine alone or in combination with EtOH depressed all three parameters. 4. At 30 degrees C, EtOH did not modify PTD or VmaxT, whereas TPT decreased. At 30 degrees C, lignocaine decreased TPT, but VmaxT did not change and the effect of lignocaine on PTD was smaller at 30 degrees C than at 37 degrees C. Ethanol and lignocaine in combination decreased all three parameters at 30 degrees C. However, the depression of VmaxT by the combination of lignocaine and EtOH was less at 30 degrees C than at 37 degrees C. 5. Hypothermia (30 degrees C) protected the myocardium against the depressant actions of EtOH and lignocaine, alone or in combination. With EtOH alone, the protection resulted in no change in PTD. When lignocaine was involved, the protection resulted in a weaker action on PTD and VmaxT. The temperature dependence of the action of lignocaine may explain, at least in part, the development of ventricular failure in cardiac surgical patients exposed to lignocaine during hypothermia and rewarming.

Actions and interactions of ethanol and imipramine on the rat sinus node.

We studied the actions and interactions of ethanol and imipramine on the sinus node. Strips of the right rat atrium including the sinus node were superfused with Tyrode's solution at 37 degrees C while beating spontaneously. The preparations were exposed to imipramine or ethanol alone as well as to the two drugs in combination while recording membrane potentials with standard intracellular microelectrodes. The results obtained show that ethanol 0.8 and 2.4 g/l exerted a positive chronotropic action. On the other hand, imipramine 0.25 mg/l did not modify the sinus node rate. However, it reduced significantly the positive chronotropic action of ethanol. The sinus node rate decreased under the action of a higher concentration of imipramine (1 mg/l). When ethanol was tested in combination with this concentration of imipramine, the effect of the latter prevailed. In conclusion, a concentration of imipramine that did not affect the sinus node rate antagonized the positive chronotropic action of ethanol. In addition, the negative chronotropic action of a higher concentration of imipramine prevailed over the positive action of ethanol. The results obtained provide additional support to the notion that the use of ethanol and cardioactive drugs in combination may result in significant changes in the actions of either of the two, or both. This is of clinical relevance, since at least some of the individuals under treatment with cardioactive drugs will be alcoholics and/or social drinkers.

[Comparison between digoxin and atenolol in chronic atrial fibrillation]. / Comparación de digoxina y atenolol en fibrilación auricular crónica.

The benefits of digoxin in patients with atrial fibrillation may be reduced due to its limited effect on atrioventricular conduction. The aim of this work was to compare digoxin and atenolol on functional class, resting and exercise heart rate and exercise capacity in patients with atrial fibrillation. Thirteen subjects with this condition, normal echocardiographic left ventricular function and size, a resting heart rate less than 80 beats/min and with no contraindication for beta blocker or digoxin use were studied. Patients were randomly assigned to receive initially digoxin 0.25 mg o.d. or atenolol 100 mg o.d. in a double blind fashion. The doses were adjusted to obtain a heart rate between 60 and 80 beats/min at the end of the first week of treatment. After two weeks of treatment, outcomes were assessed, patients were left without treatment for one week and crossed over to the other drug after that. Resting heart rates achieved with digoxin and atenolol were similar (67 +/- 11 and 65 +/- 23 beats/min respectively). However, maximal exercise heart rates and maximal exercise time were higher during digoxin treatment (166 +/- 23 vs 135 +/- 27 beats/min and 9.95 +/- 1.68 vs 8.5 +/- 2 min respectively). NYHA functional class deteriorated in three patients receiving atenolol. We conclude that atenolol achieves a better control of heart rate during exercise but also reduces maximal exercise capacity.

[Cholinergic action of Bay K-8644 on the rat heart sinus node automaticity]. / Acción colinergica de Bay K-8644 sobre el automatismo sinusal en corazon de rata.

The actions of different concentrations of a dihydropyridine agonist (Bay K-8644) on rat heart sinus node automaticity and their interactions with atropine, were studied. The experiments were performed using a portion of the right atrium that contained the sinus node, perfused with Tyrode's solution at 37 degrees C and registering the action potentials with intracellular microelectrodes (Ag-KCL). The series of Bay K with or without atropine were perfused during 10 min. Atropine, 1 x 10(-5) M, did not change sinus frequency after 30 min of perfusion (237 +/- 6 to 229 +/- 7 action potentials/min; n = 24). Bay K, 2.8 x 10(-8) M (10 ug/L) did not change sinus frequency (240 +/- 9 to 246 +/- 12; n = 8, but in the presence of atropine, caused an increment (225 +/- 7 to 256 +/- 12 p < 0.05). Bay K, 7 x 10(-8) M (25 ug/L) and 1.4 x 10(-7) M (50 ug/L, caused an increase in sinus frequency (237 +/- 5 to 279 +/- 15; n = 9 p < 0.05 and 254 +/- 6 to 291 +/- 6; n = 6 p < 0.05 respectively) that occurred sooner in the presence of atropine. It is concluded that Bay-K has a cholinergic effect that interferes with its positive chronotropic action, specially at low concentrations.

Cardiac beta-adrenergic mediated chrono- and inotropic effects of imipramine in vitro.

Clinical and experimental studies show that tricyclic antidepressants in "therapeutic plasma concentrations" can increase heart rate, myocardial contractility and blood pressure. Our study was undertaken to analyze the role of beta-adrenergic stimulation in the chronotropic and inotropic effects of imipramine. Strips of rat right atrium including the sinus node, which were beating spontaneously, were used to study chronotropism. Strips of the left atrium, electrically stimulated to beat at 1 Hz, were used to study inotropism. The preparations were superfused in vitro with Tyrode's solution at 37 degrees C and exposed to imipramine while recording membrane potentials or force of contraction. Imipramine exerted dose-dependent biphasic actions. Imipramine 0.8 microM produced positive chronotropic and inotropic actions which were blocked by propranolol. Imipramine 1.6 microM depressed the sinus node automaticity, but it did not modify the force of contraction. Imipramine 3.2 microM depressed both the sinus node automaticity and the myocardial contractility. In conclusion, imipramine in "therapeutic plasma concentrations" produces beta-adrenergic mediated cardiac positive chronotropic and inotropic actions. The possible mechanisms of the depressant effects of imipramine itself on automaticity and contractility are still not clear. The results presented can explain stimulatory and depressant cardiac effects of therapeutic doses and overdoses of tricyclic antidepressants.

Cardiac inotropic effects of ethanol and calcium-channel modulators.

Our objective was to analyze the influence of ethanol ingestion on the in vitro inotropic effects of dihydropyridines alone, or in combination with ethanol, on atrial muscle from rats offered a liquid diet with ethanol ("ethanol rats," ER) or without ethanol ("normal rats," NR). Left atria from NR or ER were superfused with Tyrode's solution (36 degrees C) and driven at 1.5 Hz while recording tension. Bay K 8644 (BAYK) increased, while nimodipine or ethanol decreased, the tension developed and the velocity of development of tension. The preparations recovered rapidly from the effects of ethanol, but not from those of the dihydropyridines. The effects of ethanol and dihydropyridines in combination were the result of the additive or counteractive actions of the drugs. The effects of ethanol and nimodipine on ER preparations were not different from those observed in NR. The action of BAYK was significantly smaller in ER than in NR. In other words, chronic ingestion of ethanol reduced the positive inotropic effect of BAYK, but it did not modify the negative inotropic action of nimodipine or ethanol.

Actions and interactions of calcium modulators and ethanol on rat atrial membrane potentials.

The effects of ethanol and dihydropyridines on atrial membrane potentials (MP) were studied. Rat atrial strips superfused with Tyrode's solution (36 degrees C) were driven at 5 Hz while recording MP with intracellular microelectrodes. Bay K 8644 7 X 10(-7) M (BAYK) increased the amplitude of the action potential (AAP) without affecting the resting membrane potential (RMP) or the Vmax of phase 0 (Vmax 0). The velocity of change in voltage decreased at the beginning of the repolarization, causing an increase in the action potential duration (APD), but it was not modified at negative voltages. Nimodipine 4.2 X 10(-6) M reduced the AAP without affecting RMP or Vmax 0. The velocity of change in voltage increased at the beginning of the repolarization, causing a decrease in the APD, but was not modified at negative voltages. Ethanol 5.3 X 10(-2) M exerted actions similar to those of nimodipine. Simultaneous exposure to ethanol and nimodipine resulted in changes not different from those obtained with each of the two compounds. The MP remained unchanged when the preparations were exposed to ethanol and BAYK simultaneously. In summary, ethanol and nimodipine exerted similar actions on the atrial MP while BAYK had opposite actions. The effects of ethanol and BAYK cancelled each other.

Inotropic effects of ethanol and dihydropyridines on the guinea pig heart atrial muscle.

The effects of ethanol and/or dihydropyridines (DHPs) on force of contraction of atrial muscle were studied. Guinea pig atrial strips superfused with Tyrode's solution (36 degrees C) were driven (1.5 Hz) while recording muscle tension. Bay K 8644 (BAYK) increased, while nimodipine or ethanol reduced, the peak tension developed and the maximum velocity of development of tension. The effects of ethanol were readily reversible, but those of the DHPs were not. The combined actions of ethanol and DHPs were the result of the synergism or antagonism of the drugs tested. The shorter duration of the action of ethanol resulted in the effect of DHPs being still evident well after the exposure to the drugs ended. In summary, ethanol and nimodipine exerted depressant actions on atrial contractile force, while BAYK had opposite effects. The different mechanisms of action may explain the different duration of the effects of ethanol (physical agent) and DHPs (receptor-binding chemicals).

Estudio de la utilidad de la estimulación aurículo-ventricular secuencial en pacientes con marcapasos e insuficiencia cardíaca / Auriculo-ventricular stimulation study in patients with pacemaker and heart failure

Con el fin de evaluar la importancia de la contracción auricular en pacientes (pac.) con Marcapaso (MP) ventricular en pacientes con Insuficiencia Cardíaca (IC), se efectuó cateterismo cardíaco derecho y medición de Presión Arterial (PA) directa en 11 pac. con bloqueo a-v total y MP: 4 pac. sin IC y 7 con IC. Se efectuó medición de presiones y débito (DC): 1.- Basal (B); 2.- Con estimulación auricular secuencial (ES) con estimulador externo Medtronic 5325 y 3.- Con estimulación auricular intra QRS (EI). El DC. B. de 3.86 ñ 0.30 lt/min. aumentó a 4.53 ñ0.48 lt/min., con 17.3% de incremento en relación a DC.B (p< 0.0025). Con EI. el DC. bajó a 3.60 ñ 0.14 lt/min. que es 6.7% inferior a DC.B y 20.5% inferior a ES. (p.< 0.01). En los pacientes con IC. el aumento del DC con ES fue de 0.36 ñ 0.4 lt./min. (8% mayor que DC.B.), significativamente menor que el aumento de los pacientes sin IC.: 0.93 ñ 0.4 lt/min. que equivale a 23% (p <0.025). Al pasar de ES a EI la PA. descendió en promedio de 171/78 a 149/75 mm. de Hg. La PA. diferencial descendió 47% en los pac. sin IC y 15% en los pac. con IC., (diferencia significativa: p < 0.005). Hubo correlación lineal entre el cambio de presión y cambio de débito. Se concluye que la relación temporal P-QRS determina importantes cambios de DC y PA. Los pac. con IC tuvieron menor mejoría con ES, explicable en la IC avanzada en porción horizontal de curva de función ventricular. Ello y la amplia variación individual, justifican la metódica de estudio seguida antes de un implante de M.P. Secuencial