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Biomedical subjects

M T Márquez

Publications and source records attributed to M T Márquez.

18 recordsLinked to original sources
PubMed1999

The heart extrasystole: an energetic approach.

The consequences of an extrasystole (ES) on cardiac muscle's energetics and Ca2+ homeostasis were investigated in the beating heart. The fraction of heat release related to pressure development (pressure dependent) and pressure-independent heat release were measured during isovolumic contractions in arterially perfused rat ventricle. The heat release by a contraction showed two pressure-independent components (H1 and H2) of short evolution and a pressure-dependent component (H3). The additional heat released by ES was decomposed into one pressure-independent (H'2) and one pressure-dependent (H'3) component with time courses similar to those of control components H2 and H3. ES also induced the potentiation of pressure development (P) and heat release during the postextrasystolic (PES) beat. The slope of the linear relationship between pressure-dependent heat and pressure maintenance was similar in control, ES, and PES contractions (0.08 +/- 0.01, 0.10 +/- 0.02, and 0.08 +/- 0.01 mJ. g-1. mmHg-1. s-1, respectively). The potentiation of H2 (heat component related with Ca2+ removal processes) in PES was equal to H'2 at 0.3, 0.5, 1, and 2 mM Ca2+, suggesting that the extra amount of Ca2+ mobilized during ES was recycled in PES. Pretreatment with 1 mM caffeine to deplete sarcoplasmic reticulum Ca2+ content inhibited both the mechanical and energetic potentiation of PES. However, the heat released and the pressure developed during ES were not changed by sarcoplasmic reticulum depletion. The results suggest that 1) the source of Ca2+ for ES would be entirely extracellular, 2) the Ca2+ entered during ES is accumulated in the sarcoplasmic reticulum, and 3) the Ca2+ stored by the sarcoplasmic reticulum during ES induces an increased contribution of this organelle during PES compared with the normal contraction.

Animals↗
PubMed1997

Energetics of heart muscle contraction under high K perfusion: verapamil and Ca effects.

Tension-dependent (TDH) and tension-independent heat (TIH) release were measured during single isovolumetric contractions in the arterially perfused rat ventricle. Under perfusion with 7 mM K-0.5 mM Ca, TDH showed only one component (H3), whereas TIH could be divided into two components (H1 and H2) of short evolution (similar to the classically identified activation heat) and one component (H4) of long duration (dependent on mitochondrial respiration). Under 25 mM K, TIH components (i.e., H1, H2, and H4) increased with the increase in extracellular Ca concentration ([Ca]o) from 0.5 to 4 mM, and H3 correlated with pressure at all [Ca]o, with regression parameters similar to those observed under 7 mM K. Under 25 mM K-2 mM Ca, peak pressure development (P), H1, H2, and H3, plotted against the number of beats under 0.4 microM verapamil, exponentially decreased, but H4 decreased to 5.5 +/- 2.9% in the first contraction and remained constant thereafter. Under hypoxia, P, H1, H2, and H3 progressively decreased for about six contractions, but H4 was not detectable from the second contraction. The results suggest that increasing extracellular K concentration decreases contractile economy mainly by increasing energy expenditure related to a Ca-dependent (verapamil-sensitive) mitochondrial activity that is not related to force generation.

Animals↗
PubMed1995

Tension-dependent and tension-independent energy components of heart contraction.

Heat production and isovolumetric pressure development (P) were measured simultaneously in the arterially perfused rat ventricle. The time course of the calorimetric signal that follows a contraction could be decomposed into four components of energy released. Three of these components (H1, H2, and H4) were pressure independent, only H3 correlated with either P or the pressure-time integral (PtI) (r > 0.78, n = 36, P < 0.01). The dimensionless slope of the regression of H3 on P was 0.24 (an index of muscle economy) and the absence of O2 (N2 replacement) decreased it to 0.178 suggesting that 26% of H3 is related to oxidative metabolism. H4 was the most affected by the lack of O2 in the perfusate. It decreased to 16% in the first beat under N2 without change in P or in H1, H2 or H3, and disappeared (1.6 +/- 1.0 mJ.g-1) in the fourth contraction under N2 (while P, H1, H2 and H3 remained over 64% of their control values). H4 was activated during the first 1-3 beats after a quiescent period and remained active for several seconds (even in the absence of subsequent stimulation) as if the basal metabolism had been increased to a new steady level. H1 and H2 were dependent on the extracellular Ca. The magnitudes of both H1 (1.8 +/- 0.2 mJ.g-1) and H2 (2.7 +/- 0.2 mJ.g-1) were similar to those reported for the fast and slow components of activation heat in skeletal muscle. If twin stimuli are applied (200 ms apart), additional energy is released (+3.0 +/- 0.3 mJ.g-1) that can be decomposed in two components similar to those identified as H2 and H3. The magnitude of H1, its absence in the twin contraction and its Ca dependency suggest an association with Ca-binding processes (mainly Troponin C). The presence of an H2 component during the twin contraction, its magnitude and Ca dependence gives support to a relationship between H2 and Ca removal processes.

Animals↗
PubMed1992

Influence of extracellular potassium on energetics of resting heart muscle.

The effects of various extracellular K concentrations ([K]e) on energy expenditure and their relationship to ionic exchange mechanisms under quiescent conditions were investigated in the arterially perfused rat heart. The increase in [K]e (from 6 to 12, 24, or 50 mM K) leads to a rapid increase (results are given per gram dry weight) in resting energy expenditure (+5.9 +/- 0.9, +13.6 +/- 1.1, and +30.0 +/- 2.0 mW/g, respectively) followed by a slow decrease toward a new steady rate of heat production but higher (+2.8 +/- 0.7, +6.3 +/- 0.6, and +10.5 +/- 1.1 mW/g) than that observed under control conditions (21.1 +/- 0.7 mW/g). The increase in [K]e from 6 to 50 mM also induced an increase in K influx (calculated from 86Rb uptake and efflux experiments) of approximately 0.25 mumol.g-1.s-1. If this increased K influx is driven by the Na-K pump, an increase in steady resting heat production of approximately 10 mW/g would be expected. This represents 95% of the increase in steady heat production measured for 50 mM K intervention. The simultaneous increase in the cellular Ca flux (+0.1 mumol.g-1.min-1) can only explain (if driven by the sarcolemmal Ca pump) less than 1% of the steady increase in heat production. The work also shows that the initial, transitory increase in resting heat production induced by increasing [K]e is caffeine sensitive and may be at least partially attributable to a transitory enhanced activity of the sarcoplasmic reticulum.

Animals↗
PubMed1992

Caffeine effects on heart muscle energetics: species differences.

The effects of caffeine (1mM) on energy expenditure and mechanical parameters in rat and toad perfused heart ventricles were examined at various stimulation frequencies. While in rat muscles caffeine significantly depressed developed tension and maximal rates of contraction and relaxation at all frequencies tested, in toad ventricle a slight positive inotropic effect was observed. Even though caffeine did not alter total contraction time in both preparations, in the rat ventricle the last part of relaxation was prolonged. In rat ventricle in the presence of caffeine, the ratios between active heat production per beat and either developed tension or tension time integral increased at all frequencies tested (+303 +/- 47 microJ.mN-1 x g-1 and +1.21 +/- 0.13 mJ.mN-1 x s-1 x g-1 respectively) indicating a decrease in contractile economy. In toad ventricle no changes on these ratios were observed. The fact that only in rat ventricle caffeine decreased muscle economy suggests that caffeine affects a system that is active in rat ventricle but it is not operative in toad ventricle. This gives support to the hypothesis that if in rat ventricle SR-Ca pump (1 ATP hydrolyzed/2 Ca transported) is inhibited by caffeine cytosolic Ca would have to be removed by alternative mechanisms such as Na-Ca exchanger or sarcolemmal Ca pump both with a higher rate of ATP hydrolysis (1 ATP hydrolyzed/Ca transported) with the consequent decrease in muscle economy. Resting heat production was increased by caffeine in both preparations and the magnitude of the increment (+3.0 +/- 0.6 mW.g-1 and +0.75 +/- 0.21 mW.g-1 for rat and toad ventricle respectively) also correlates with the different degree of SR activity in both species.

Animals↗
PubMed1991

Mechanisms underlying post-rest potentiation in isolated left rat atria.

In the isolated rat left atria the influence of rest intervals on the force developed by the first post rest beat (PRB) was studied. Under control conditions the force developed by the PRB increased (respect to previous steady state at 0.5 Hz) with the increase of the rest interval until 20 sec of pause and decreased with longer intervals. In the presence of caffeine (1 or 4 mM plus high [Ca]0) there was a monotonous fall of the PRB as a function of the rest interval. When extracellular calcium was replaced by Sr the tension developed by PRB vs. rest interval curve rose with a slope lower than the control one and reached the peak at 60 sec. At saturation levels of [Ca]0 the PRB tension development did not vary up to 20 sec pause but the decreasing phase observed after 20 sec of rest interval was still present. At 0.5 mM [Ca]0 the response was similar to control curve. The results in the presence of caffeine and strontium suggest that, in rat atria, the rest potentiation appears to be dependent on the release of calcium from intracellular stores (sarcoplasmic reticulum). This is consistent with the hypothesis proposing that longer resting periods provide a longer interval for the transfer of Ca from uptake to release sites in the sarcoplasmic reticulum.

Analysis of Variance↗
PubMed1986

Papaverine-induced positive inotropism with failure to increase cyclic AMP in rat atria.

Phosphodiesterase inhibition by papaverine is likely to play a minor role in the rat atrial inotropic response because non-significant changes in cyclic AMP were obtained. Isoprenaline however raised the nucleotide levels three-fold and up to seventeen-fold when papaverine was added in a similar preparation. A prominent effect of papaverine was to lengthen relaxation instead of shortening it as did isoprenaline. The results suggest different sites of action, although overlapping effects cannot be excluded.

Animals↗
PubMed1986

Effects of papaverine on calcium efflux and contractility in superfused rat left atria.

The effects of papaverine upon force of contraction, maximal rate of contraction, maximal rate of relaxation and 45Ca efflux were studied in isolated superfused rat left atria electrically driven at 1 Hz. Papaverine (3 X 10(-5) mol/l, increased developed tension (from 5.35 +/- 1.17 mN to 7.18 +/- 1.51 mN) by 1.8 +/- 0.41 mN (+33%, p less than 0.01) and maximal rate of contraction (+T) by 34.5 +/- 13% (p less than 0.05). In all experimental conditions tested, papaverine increased the rate of 45Ca efflux. The amount by which papaverine increased 45Ca efflux was 175 +/- 41 nmoles . g wet wt-1 and 304 +/- 76 nmoles . g wet wt-1, in the presence and in the absence of caffeine, respectively. The plot of changes in 45Ca efflux versus changes in developed tension fitted to a straight line (r = +0.56, n = 17, p less than 0.05), with a slope and intercept of 42 nmoles Ca . mN-1 . g wet wt-1 and -0.47 mN respectively, suggesting an association between the changes induced by papaverine in force development and increased 45Ca efflux.

Animals↗
PubMed1984

Simultaneous analyses of Ca exchange and mechanical parameters in the rat atria.

In the rat left atrium, electrically driven, a superfusion dropping method was developed. The device essentially consisted of a pair of platinum wire electrodes which held one end of the tissue, while the other end was attached to an isometric tension transducer. Either normal or isotopically labeled solutions were poured on the preparation at preset flow rates by means of a minipump. Effluent was collected fractionally in vials for measurement of radioactivity. Several perfusion flows tested led us to the conclusion that higher rates than 2.26 ml/min did not improve contractile performance. Stability of the preparation was found similar to the classical isolated organ-bath method during a 180 min period of observation. Set-up of the superfused atria reproduced paired determinations of 45Ca efflux, together with the contractile parameters. In addition, the frequency of sampling (intervals of 1 min or less) allowed us to detect changes in the washout pattern of exchangeable 45Ca even during early phases of Ca efflux. Therefore, the method reported herein seems to overcome the serious handicap of the scanty tissue employed.

Animals↗
PubMed1983

Antagonism and supersensitivity to phenylephrine-induced chronotropic responses.

Right atria from rats were analyzed for chronotropic responses to phenylephrine in face of various drugs and procedures. Propranolol, 10(-8) M, produced a competitive antagonism against the agonist which concentration-effect curve was closely similar to that obtained from reserpinized animals. Prazosin, but not phentolamine (both 10(-6) M) showed inhibition of the phenylephrine-induced changes in heart rate, as judged by their -log EC50. Either of the alpha-adrenoceptor antagonists exhibited a greater steepness in the curve slope with respect to control. The simultaneous exposure of tissues to phentolamine and propranolol proved to effectively antagonize the chronotropic effect of the agonist. This held true for phentolamine assayed in atria from reserpine-pretreated rats. Previous incubation of tissues with papaverine, 10(-5) M, brought about supersensitivity to phenylephrine which was thoroughly inhibited by either phentolamine or propranolol. These results strongly suggest that beta-adrenoceptor stimulation of heart rate by phenylephrine takes place indirectly via norepinephrine release. There is also alpha 1-adrenoceptor stimulation (blocked by prazosin). Finally, it is hypothesized that supersensitivity develops by papaverine-enhanced Ca2+ influx, since numerous evidences are against a phosphodiesterase inhibition-dependent cAMP accumulation mechanism triggered by papaverine in the presence of phenylephrine.

Animals↗
PubMed1982

Papaverine-induced changes on cardiac inotropism with special reference to a D-propranolol antagonism.

Contractile responses were analyzed in the rat paced left atrium. Positive inotropic effects were papaverine dose-dependent with an increase in rate of tension development (dT/dt) and time to peak tension, with prolongation in the total duration of contraction. Reserpinized preparations did not modify papaverine response but several treatments inhibited it, i.e., either doubling or halving [Ca2+]0, as well as the addition of D-propranolol. Incubation of tissues with papaverine (1 hr) changed the usual dose-response curve to isoproterenol into a low, monotonous effect, independent of the agonist dose. Neither high nor low [Ca2+]0 could correct this action. D-propranolol restored the isoproterenol response but significantly blocked it. Under the same conditions, phenylephrine showed similar qualitative effects as above, though no significant differences were found in control vs. the various procedures tested. These results strongly suggest that papaverine provokes an initial calcium release followed by a sustained inhibition. In addition its site of action is the same as that of D-propranolol.

Animals↗
PubMed1979

Effect of the frequency of stimulation on the blocker action of propranolol in isolated rat left atria.

The beta-blocking activity of propranolol was studied on the positive inotropic effect of norepinephrine, epinephrine, isoproterenol, dopamine and ethylephrine, in the left atrium driven at different rates. Dose of the antagonist of 10(-8) and 10(-7) M did not block the norepinephrine dose-response curve at 1 and 2.8 Hz, but a shift to the right was observed at 1.6 Hz. Although epinephrine showed a significant increase in its pD2 (p less than 0.001) at the lower stimulation frequency, the blockade increased progressively the higher the rates. On the other hand, propranolol antagonized isoproterenol at all the frequencies tested, in spite of an increase in the maxima at 2.8 Hz. This latter behavior was also true for dopamine and ethylephrine. Both sympathomimetic amines were blocked by propranolol at 1 and 1.6 Hz. The complex effect of propranolol on Ca2+ movements and its effects on cAMP and ATPase seem to be superimposed to the beta-blocking activity. Thus, the various actions on the sympathomimetic amines change according to the agonist considered and the stimulation frequency employed.

Adrenergic beta-Antagonists↗
PubMed1977

Response of the atrial pacemaker to dobutamine.

The action of dobutamine, (+/-)-4- [2- [[3-(p-hydroxyphenyl)-1-methylpropyl]amino]ethyl] pyrocatechol hydrochloride was studied on the pacemaker of the isolated rat atria. The dose-chronotropic response curve showed a typical bell-dome shape of the sympathomimetic amines. Reserpinization of the animals did not change the curve of the agonist. Cocaine (6.7 microgram/ml) induced a decrease of the sensitivity of the rat atria pacemaker for dobutamine (p less than 0.001). Propranolol (3 X 10(-8) and 10(-7) M) provoked a shift to the right of the dose-response curve for dobutamine. Also, the last concentration of the antagonist depressed the maxima (p less than 0.01). Phentolamine failed to prove a possible alpha-adrenergic action of the drug on the pacemaker. The response to dobutamine was not affected when monoaminoxidase was inhibited by pretreatment with pargyline, or when catechol-O-methyltransferase was inhibited by exposure to U-0521 (3,4 dihydroxy-alpha-methylpropiophenone). These results indicate that dobutamine: a) is a beta-adrenergic agent, b) is not a good substrate of MAO, c) is a direct-acting sympathomimetic amine.

Adrenergic beta-Antagonists↗
PubMed1977

Effects of ethylephrine on the rat atrial pacemaker.

Ethylephrine, assayed in isolated rat atria, as a dose-chronotropic response curve showed a typical bell-dome shape of the sympathomimetic amines. Yet, on the same basis, it was less powerful than epinephrine, norepinephrine or isoproterenol. Pretreatment with reserpine provoked supersensitivity and increase in the maximum. As well, previous administration of pargyline to the animals resulted in augmented accelerating effects, either in normal or reserpinized preparations. Cocaine or phentolamine shifted the dose-response curve to the left. On the contrary, propranolol, produced a marked action, decelerating the effects of ethylephrine and also decreased the maxima with higher doses. It is concluded that ethylephrine: a) is a direct-acting sympathomimetic amine; b) it brings beta-receptor stimulation; c) a certain degree of alpha-receptor decelerating effect is also involved; d) it is a good substrate of monoaminoxidase.

Animals↗
PubMed1977

Positive inotropic effect of ethylephrine on the isolated rat atria.

Ethylephrine, a sympathomimetic amine which belongs to the phenolamine group, was assayed on the driven left rat atrium. The frequency response curve was performed for norepinephrine and ethylephrine. The maxima was attained for both compounds at 1 Hz. The agonist under study has an inotropic action less potent than the classical catecholamines. Propranolol (10(-8) and 10(-7) M) produced a parallel shift to the right in the log dose-response curves of ethylephrine with no decrease in the maximal response, indicating that the antagonism was competitive. In the presence of cocaine or with reserpine-pretreatment the sensitivity of the preparation to the amine did not vary. The alpha-blocker, phentolamine (10(-8) to 3.10(-5) M) did not possess an inotropic effect per se. In contrast, phentolamine, delivered to the bath beforehand, did not block the agonist. However at 10(-8) and 10(-7) M increase the maximal response both in normal and reserpinized preparations. It is suggested that ethylephrine is a direct inotropic preparation. It is suggested that ethylephrine is a direct inotropic agent on the driven left rat atrium and its effects are mediated by beta-receptors. The results also indicate the lack of evidence that ethylephrine has any action on the alpha-receptors.

Animals↗
PubMed1976

Metabolic responses to catecholamines.

Isoproterenol and propranolol, in a single dose, caused hyperglycemia after 15 and 30 min, either in the conscious rat or in the anesthetized dog. In this latter species no modifications of the serum potassium were observed. Adrenaline, 5 microgram/kg, iv provoked hyperglycemia at the same intervals and hyperkalemia at min 1st and 2nd with further hypokalemia until 90 min. The beta-adrenergic blocker, sotalol, 5 mg/kg, iv, administered prior to adrenaline suppressed the increase in glycemia and the late decrease in serum potassium, but not the early hyperkalemia. In the isolated hind limb of the dog the intra femoral artery administration of adrenaline, 3 microgram/kg, produced similar hyperglycemia either in the artery or in the femoral vein, starting from the 15 min. Contrarily, the serum concentration of potassium was significantly less in the vein than in the artery at the 1st min. These findings suggest that different receptors are involved in the glucose and potassium response to adrenaline, and the skeletal muscle plays an important role in the regulation of the early hyperkalemia.

Animals↗
PubMedDate not supplied

Interactions between sympathomimetic agonists and blocking agents: cardiac effects of phenylephrine and isoproterenol.

In the isolated rat atria the effects of phenylephrine (alpha-agonist) and isoproterenol (beta-agonist) on the contractile force and heart rate were studied either in presence or not of alpha- and/or beta-blockade. Phentolamine 10(-6) M and propranolol 10(-8) M were used as alpha- and beta-antagonists, respectively. The chronotropic dose-response curves were made in both spontaneously beating atria while inotropic effects were derived from left atria driven at 1 Hz, 5 msec and voltage about 20 percent above threshold. Both agonists induced an inotropic effect that could be significantly blocked by phentolamine, propranolol and both antagonists given together. The chronotropic dose-response curve of isoproterenol (pD2 = 10.70 +/- 0.11) was blocked by phentolamine (pD2 = 9.27 +/- 0.08, p less than 0.001) and propranolol (pD2 = 9.21 +/- 0.19, p less than 0.001). Contrarily, pentolamine was unable to shift to the right the chronotropic dose-response curve for phenylephrine (pD2 = 6.48 +/- 0.07 and 6.63 +/- 0.10, respectively). This action of phenylephrine on the heart rate was significantly blocked by propranolol (pD2 = 6.21 +/- 0.13, p less than 0.05) and by propranolol plus phentolamine (pD2 = 6.07 +/- 0.04, p less than 0.001). From the present results it is concluded that in the rat's atrial myocardium there exist alpha- and beta-adrenoceptors mediating the positive inotropic effect of isoproterenol and phenylephrine. Yet, the chronotropic action seems to behave in a different way: while isoproterenol triggered either type of receptors; phenylephrine is only mediated by beta-adrenoceptors.U

Animals↗