RESUMO
INTRODUCTION: Lumbar disc hernias are a common cause of spinal surgery. Hernia recurrence is a prevalent complication. OBJECTIVE: To analyse the risk factors associated with hernia recurrence in patients undergoing surgery in our institution. MATERIALS AND METHODS: Lumbar microdiscectomies between 2010 and 2014 were analysed, patients with previous surgeries, extraforaminales and foraminal hernias were excluded. Patients with recurrent hernia were the case group and those who showed no recurrence were the control group. RESULTS: 177 patients with lumbar microdiscectomy, of whom 30 experienced recurrence (16%), and of these 27 were reoperated. Among the risk factors associated with recurrence, we observed a higher rate of disc height, higher percentage of spinal canal occupied by the hernia and presence of degenerative facet joint changes; we observed no differences in sex, body mass index or age. DISCUSSION: Previous studies show increased disc height and young patients as possible factors associated with recurrence. CONCLUSION: In our series we found that the higher rate of disc height, the percentage of spinal canal occupied by the hernia and degenerative facet joint changes were associated with hernia recurrence.
Assuntos
Discotomia , Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Deslocamento do Disco Intervertebral/etiologia , Complicações Intraoperatórias/epidemiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Recidiva , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
Ca(2+) influx via Ca(2+) current (I(Ca)) during the action potential (AP) was determined at 25 degrees C and 35 degrees C in isolated rabbit ventricular myocytes using AP clamp. Contaminating currents through Na(+) and K(+) channels were eliminated by using Na(+)- and K(+)-free solutions, respectively. DIDS (0.2 mmol/L) was used to block Ca(2+)-activated chloride current (I(Cl(Ca))). When the sarcoplasmic reticulum (SR) was depleted of Ca(2+) by preexposure to 10 mmol/L caffeine, total Ca(2+) entry via I(Ca) during the AP was approximately 12 micromol/L cytosol (at both 25 degrees C and 35 degrees C). Similar Ca(2+) influx at 35 degrees C and 25 degrees C resulted from a combination of higher and faster peak I(Ca), offset by more rapid I(Ca) inactivation at 35 degrees C. During repeated AP clamps, the SR gradually fills with Ca(2+), and consequent SR Ca(2+) release accelerates I(Ca) inactivation during the AP. During APs and contractions in steady state, total Ca(2+) influx via I(Ca) was reduced by approximately 50% but was again unaltered by temperature (5.6+/-0.2 micromol/L cytosol at 25 degrees C, 6.0+/-0.2 micromol/L cytosol at 35 degrees C). Thus, SR Ca(2+) release is responsible for sufficient I(Ca) inactivation to cut total Ca(2+) influx in half. However, because of the kinetic differences in I(Ca), the amount of Ca(2+) influx during the first 10 ms, which presumably triggers SR Ca(2+) release, is much greater at 35 degrees C. I(Ca) during a first pulse, given just after the SR was emptied with caffeine, was subtracted from I(Ca) during each of 9 subsequent pulses, which loaded the SR. These difference currents reflect I(Ca) inactivation due to SR Ca(2+) release and thus indicate the time course of local [Ca(2+)] in the subsarcolemmal space near Ca(2+) channels produced by SR Ca(2+) release (eg, maximal at 20 ms after the AP activation at 35 degrees C). Furthermore, the rate of change of this difference current may reflect the rate of SR Ca(2+) release as sensed by L-type Ca(2+) channels. These results suggest that peak SR Ca(2+) release occurs within 2.5 or 5 ms of AP upstroke at 35 degrees C and 25 degrees C, respectively. I(Cl(Ca)) might also indicate local [Ca(2+)], and at 35 degrees C in the absence of DIDS (when I(Cl(Ca)) is prominent), peak I(Cl(Ca)) also occurred at a time comparable to the peak I(Ca) difference current. We conclude that SR Ca(2+) release decreases the Ca(2+) influx during the AP by approximately 50% (at both 25 degrees C and 35 degrees C) and that changes in I(Ca) (and I(Cl(Ca))), which depend on SR Ca(2+) release, provide information about local subsarcolemmal [Ca(2+)].
Assuntos
Potenciais de Ação , Canais de Cálcio/metabolismo , Cálcio/metabolismo , Miocárdio/metabolismo , Função Ventricular , Animais , Ventrículos do Coração/metabolismo , Coelhos , TemperaturaRESUMO
Normally the sarcoplasmic reticular calcium pump and sarcolemmal Na/Ca exchange compete and are the primary mechanisms responsible for reducing [Ca]i during cardiac relaxation. The sarcolemmal calcium pump and mitochondrial calcium uptake are much slower, but may also participate in [Ca]i regulation. The aim of this study was to provide a clearer understanding of the interaction of these mechanisms. Myocyte shortening and [Ca]i transients (using indo-1 fluorescence) were measured in rabbit ventricular myocytes, with similar results. The t1/2 of twitch relaxation was 0.17(SEM 0.03) s. Contractures induced by 10 mM caffeine (caffeine contraction) relaxed more slowly [t1/2 = 0.54(0.07) s] due to prevention of sarcoplasmic reticular calcium uptake. When the Na/Ca exchange was also blocked by perfusion with 0Na,0Ca solution, the peak of the caffeine contraction was increased (by 44%) and relaxation was slowed about 16-fold [t1/2 = 8.8(0.8) s]. Blocking mitochondrial calcium uptake by including 1 microM FCCP + 1 microM oligomycin in the 0Na,0Ca solution slowed the relaxation of the caffeine contraction further [t1/2 = 19.7(3.2) s]. Inhibition of the sarcolemmal calcium pump by perfusion with 0Na, 10 mM Ca during caffeine contraction also increased the relaxation t1/2 to 27.5(6.9) s. Inhibition of all four calcium transport systems almost abolished relaxation. It is also shown that calcium which was taken up by the mitochondria during relaxation of the caffeine contraction in 0Na,0Ca gradually redistributed (with tau = 41 s) back to the sarcoplasmic reticulum after caffeine was removed. A second caffeine contraction could then be elicited.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Cálcio/metabolismo , Miocárdio/metabolismo , Animais , Transporte Biológico Ativo/fisiologia , Cafeína/farmacologia , ATPases Transportadoras de Cálcio/metabolismo , Proteínas de Transporte/metabolismo , Mitocôndrias Cardíacas/metabolismo , Contração Miocárdica/efeitos dos fármacos , Contração Miocárdica/fisiologia , Miocárdio/citologia , Coelhos , Sarcolema/metabolismo , Retículo Sarcoplasmático/metabolismo , Sódio/metabolismo , Trocador de Sódio e CálcioRESUMO
In this work we present a theoretical analysis of the ratio method, a widely used technique for measuring intracellular calcium concentration, [Ca2+]i, in isolated cells. From the ratio of fluorescence measured at two different excitation or emission wavelengths, [Ca2+]i may be estimated from the equation: [Ca2+]i = Kd.beta.(R-Rmin)/(Rmax-R). From this equation we determined the method sensitivity showing that its maximum is located at [Ca2+] = Kd.beta.(Rmin/Rmax)1/2, i.e. for [Ca2+] < Kd.beta. We also analyzed the error propagation due to inaccuracies in the calibration parameters. The fluorescence phenomenon was described, aiming at providing a basis for the microscopic interpretation of the method and giving physical meaning to the calibration parameters. In this sense beta, is shown to depend not only on the set-up, but also on the spectrum of the indicator for the particular sample studied. A new approach to estimate beta with higher accuracy is also proposed. Experimentally obtained beta values using this approach were not statistically different from those determined as Fmin2/Fmax2. A graphical interpretation of the method is presented to provide users of fluorescence systems with a simple technique to help understand equipment performance and design.
Assuntos
Cálcio/análise , Fluorescência , Matemática , Potenciais da MembranaRESUMO
There are four cellular Ca transport systems which compete to remove Ca from the myoplasm in mammalian ventricular myocytes. These are 1) the SR Ca-ATPase, 2) the sarcolemmal Na-Ca exchange, 3) the sarcolemmal Ca-ATPase and 4) the mitochondrial Ca uniporter. Using multiple experimental approaches we have evaluated the dynamic interaction of these systems during the normal cardiac contraction-relaxation cycle. The SR Ca-ATPase and Na-Ca exchange are clearly the most important, quantitatively; however, the relative roles vary in a species-dependent manner. In particular, the SR is much more strongly dominant in rat ventricular myocytes, where approximately 92% of Ca removal is via SR Ca-ATPase and only 7% via Na-Ca exchange during a twitch. In other species (rabbit, ferret, cat, and guinea pig) the balance is more in the range of 70% SR CA-ATPase and 25-30% Na-Ca exchange. Ferret ventricular myocytes also exhibit an unusually strong sarcolemmal Ca-ATPase. During the steady state the same amount of Ca must leave the cell as enters over a cardiac cycle. This implies that 25-30% of the Ca required to activate contraction must enter the cell, and experiments demonstrate that this amount of Ca may be supplied by the L-type Ca current.
Assuntos
Cálcio/metabolismo , Proteínas de Transporte/metabolismo , Contração Miocárdica/fisiologia , Miocárdio/metabolismo , Sódio/metabolismo , Animais , Cafeína/farmacologia , ATPases Transportadoras de Cálcio/metabolismo , Sarcolema/enzimologia , Trocador de Sódio e Cálcio , Temperatura , Função VentricularRESUMO
This paper presents a novel optical approach for the study of spreading depression in isolated retina. The method makes it possible to register the laser light scattered from each layer of the tissue, yielding a functional image of the retina during spreading depression. The tissue is kept intact, since histological cuts are not necessary. Measurements of other variables, such as extracellular potential, are also allowed by the described method. This is done simultaneously with the functional image in a high spatial resolution, with the positioning of the microelectrode tip being easily monitored. The information about temporal and spatial evolution of light was compacted in a single image. The image-processing technique used here enables the visualization of the light scattered by the inner plexiform layer (IPL), which is the most prominent scatter layer during spreading depression. The wavefront velocity and its increase as two wavefronts approach each other can then be determined, and it is also possible to observe the thickness variation of the tissue during the wave travel. The relationship between two peaks of light-scattering sequence during the phenomenon was studied at two wavelengths (632.8 and 543.5 nm). This relationship is shown to be dependent on the wavelength.
Assuntos
Depressão Alastrante da Atividade Elétrica Cortical/fisiologia , Diagnóstico por Imagem/métodos , Lasers , Óptica e Fotônica , Retina/fisiologia , Animais , Galinhas , Diagnóstico por Imagem/instrumentação , Estimulação Elétrica/métodosRESUMO
The chronotropic responsiveness to norepinephrine (NE) and isoproterenol (ISO) was determined in right atria isolated from rats submitted to repeated escapable or inescapable foot-shock. Significant postjunctional supersensitivity to ISO, but not to NE, was observed in both groups. No significant change in the pA2 value of metoprolol (a selective beta 1-adrenoceptor antagonist) was detected. However, a decrease of the maximum response to soterenol, a partial agonist at beta 1-adrenoceptors, occurred only after inescapable foot-shock. The enhanced sensitivity to ISO was abolished by butoxamine (a selective beta 2-adrenoceptor antagonist) and accompanied by a marked increase in the pA2 value of this antagonist. We conclude that the ability to control the shock prevented the down-regulation of the pacemaker beta 1-adrenoceptors but not the increased participation of beta 2-adrenoceptors in the response of the rat sinoatrial node to catecholamines after repeated foot-shock.
Assuntos
Eletrochoque , Miocárdio/metabolismo , Receptores Adrenérgicos beta/fisiologia , Estresse Psicológico/fisiopatologia , Animais , Butoxamina/farmacologia , Etanolaminas/farmacologia , Átrios do Coração/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Isoproterenol/farmacologia , Masculino , Metoprolol/farmacologia , Norepinefrina/farmacologia , Oxidopamina , Ratos , Ratos Wistar , Receptores Adrenérgicos beta/efeitos dos fármacos , Simpatectomia QuímicaRESUMO
Studies on cardiac cell response to electric field stimulation are important for understanding basic phenomena underlying cardiac defibrillation. In this work, we used a model of a prolate spheroidal cell in a uniform external field (Klee and Plonsey, 1976) to predict the threshold electric field (ET) for stimulation of isolated ventricular myocytes of rats at different ages. The model assumes that ET is primarily determined by cell shape and dimensions, which markedly change during postnatal development. Neonatal cells showed very high ET, which progressively decreased with maturation (experimental mean values were 29, 21, 13, and 5.9 and 6.3 V/cm for 3-6, 13-16, 20-21, 28-35, and 120-180 day-old rats, respectively, P < 0.001; theoretical values were 24, 18, 11, 9, and 6 V/cm, respectively). Estimated maximum membrane depolarization at threshold (deltaVT approximately equals 35 mV, under our experimental conditions) was reasonably constant during development, except for cells from 1-mo-old animals, in which deltaVT was lower than at other ages. We conclude that the model reasonably correlates ET with cell geometry and size in most cases. Our results might be relevant for the development of efficient procedures for defibrillation of pediatric patients.
Assuntos
Animais Recém-Nascidos/fisiologia , Estimulação Elétrica , Ventrículos do Coração/citologia , Função Ventricular , Análise de Variância , Animais , Processamento de Imagem Assistida por Computador , Ratos , Ratos Wistar , Estatísticas não ParamétricasRESUMO
The influence of changes in the KCl concentration of the bath fluid ([KCl]o) on the corrected sinus node recovery time (CSNRT) was studied using the continuous pacing method (M1) and the method of stimulation with premature pulses (M2). M1 and M2 were compared in Krebs-Henseleit solution containing normal (4.6 mM), low (3.1 mM, LoKCl) and high (6.1 mM, HiKCl) [KCl]o. The results revealed that HiKCl increased CSNRT (P less than 0.01) and changed the prematurity-CSNRT relationship (P less than 0.01), whereas LoKCl did not change CSNRT. M1 and M2 were different (P less than 0.01) regardless of [KCl]o, except for pacing intervals near the spontaneous cycle length.
Assuntos
Cloreto de Potássio/farmacologia , Nó Sinoatrial/efeitos dos fármacos , Análise de Variância , Animais , Técnicas In Vitro , Masculino , Cloreto de Potássio/metabolismo , RatosRESUMO
The effects of osmolality (300 and 450 mOsm/l) and external calcium concentration ([Ca2+]o: 0.87, 1.13, 1.47 and 1.92 mM) on the inotropic response of isolated rat left atria to an increase of 97.8 mM in extracellular sodium concentration ([Na+]o) were studied. The evoked tensions developed during 30 min after the exposure to increased [Na+]o increased with increasing [Ca2+]o. In iso-osmotic solutions, tension was lower than in hyperosmotic solutions when [Ca2+]o was 0.87 and 1.13 mM, but not for higher [Ca2+]o, revealing a Ca2(+)-osmolality interaction in the determination of the inotropic response.
Assuntos
Cálcio/metabolismo , Contração Miocárdica , Sódio/metabolismo , Animais , Função Atrial , Masculino , Concentração Osmolar , Ratos , Ratos EndogâmicosRESUMO
This study analyzes the effects of hyperosmotic solutions on the sensitivity of the rat isolated right and left atria to the chronotropic and inotropic effects of noradrenaline (NA), respectively. Hyperosmotic NaCl solution caused subsensitivity to both effects of NA (pD2 values for NA, right atria: control 7.42 +/- 0.06, NaCl 6.83 +/- 0.18, P less than 0.05; left atria: control 7.67 +/- 0.22, NaCl 6.61 +/- 0.18, P less than 0.05). Hyperosmotic sucrose solution produced a similar effect in right atria (pD2 NA: 6.96 +/- 0.17, P less than 0.05), whereas in left atria it depressed the maximum inotropic response to NA by about 80%. All changes, except that of maximum inotropic response, were abolished following combined pretreatment with 6-hydroxydopamine, phenoxybenzamine, atropine and imipramine. These data suggest that the noradrenergic subsensitivity induced in atrial tissue by hyperosmolality is probably not due to changes of beta-adrenoceptor function and/or coupling of these receptors to the effector mechanisms.
Assuntos
Contração Miocárdica/efeitos dos fármacos , Norepinefrina/farmacologia , Solução Salina Hipertônica/farmacologia , Acetilcolina/metabolismo , Animais , Átrios do Coração/efeitos dos fármacos , Contração Isométrica , Masculino , Concentração Osmolar , Ratos , Ratos Endogâmicos , Sacarose/farmacologiaRESUMO
Relaxation in the mammalian ventricle is initiated by Ca2+ removal from the cytosol, which is performed by three main transport systems: sarcoplasmic reticulum Ca2+-ATPase (SR-A), Na+-Ca2+ exchanger (NCX) and the so-called slow mechanisms (sarcolemmal Ca2+-ATPase and mitochondrial Ca2+ uptake). To estimate the relative contribution of each system to twitch relaxation, SR Ca2+ accumulation must be selectively inhibited, usually by the application of high caffeine concentrations. However, caffeine has been reported to often cause changes in membrane potential due to NCX-generated inward current, which compromises the reliability of its use. In the present study, we estimated integrated Ca2+ fluxes carried by SR-A, NCX and slow mechanisms during twitch relaxation, and compared the results when using caffeine application (Cf-NT) and an electrically evoked twitch after inhibition of SR-A with thapsigargin (TG-TW). Ca2+ transients were measured in 20 isolated adult rat ventricular myocytes with indo-1. For transients in which one or more transporters were inhibited, Ca2+ fluxes were estimated from the measured free Ca2+ concentration and myocardial Ca2+ buffering characteristics. NCX-mediated integrated Ca2+ flux was significantly higher with TG-TW than with Cf-NT (12 vs 7 M), whereas SR-dependent flux was lower with TG-TW (77 vs 81 M). The relative participations of NCX (12.5 vs 8% with TG-TW and Cf-NT, respectively) and SR-A (85 vs 89.5% with TG-TW and Cf-NT, respectively) in total relaxation-associated Ca2+ flux were also significantly different. We thus propose TG-TW as a reliable alternative to estimate NCX contribution to twitch relaxation in this kind of analysis.
Assuntos
Cálcio/metabolismo , Inibidores Enzimáticos/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Retículo Sarcoplasmático/efeitos dos fármacos , Tapsigargina/farmacologia , Animais , Cafeína/farmacologia , ATPases Transportadoras de Cálcio , Estimulação Elétrica , Ventrículos do Coração/citologia , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/enzimologia , Masculino , Contração Miocárdica/efeitos dos fármacos , Miócitos Cardíacos/enzimologia , Ratos , Ratos Wistar , Retículo Sarcoplasmático/enzimologia , Trocador de Sódio e Cálcio/efeitos dos fármacos , Trocador de Sódio e Cálcio/metabolismoRESUMO
The chronotropic and inotropic effects of hyperosmotic solutions (HS) on isolated rat atria were studied to determine the influences of solute, time and blockade of autonomic receptors. NaCl and sucrose HS (450 mOsm/1) exerted a time-dependent negative chronotropic effect on right atria. NaCl decreased whereas sucrose increased peak tension of the left atria. Phenoxybenzamine and propranolol did not change the chronotropic effects of hyperosmolality, but increased the peak tension of left atria exposed to HS. We conclude that chronotropic effects of HS seem to be non-specific while inotropic effects depend on the solute and may involve neurotransmitter release, probably acetylcholine.
Assuntos
Frequência Cardíaca/efeitos dos fármacos , Contração Miocárdica/efeitos dos fármacos , Solução Salina Hipertônica/farmacologia , Cloreto de Sódio/farmacologia , Sacarose/farmacologia , Acetilcolina/metabolismo , Análise de Variância , Animais , Solução Hipertônica de Glucose/farmacologia , Átrios do Coração/efeitos dos fármacos , Masculino , Bloqueadores Neuromusculares/metabolismo , Ratos , Ratos Endogâmicos , Receptores Adrenérgicos/metabolismoRESUMO
We describe a microprocessor-based programmable triggering instrument designed to control the distribution in time of electrical stimuli delivered to a heart muscle preparation. Sequences of stimuli may be selected among those stored in the non-volatile memory of the instrument and new sequences may be programmed using a repertory of 25 commands. The instrument was used to study the inotropic effects of three irregular sequences of stimuli applied to the isolated rat left atrium. The mean peak tension developed by the tissue was unaltered by stimulus sequence, provided the mean stimulatory frequency (2 or 5 Hz) was maintained. The instrument may be useful to study the effect of different stimulatory patterns on cardiac inotropism, as well as for controlling the electrical stimulation of other biological preparations.
Assuntos
Estimulação Cardíaca Artificial , Frequência Cardíaca , Microcomputadores , Software , Animais , Contração Miocárdica , RatosRESUMO
Evidence has indicated that the sarcoplasmic reticulum (SR) might be involved in the generation of spontaneous electrical activity in atrial pacemaker cells. We report the effect of disabling the SR with ryanodine (0.1 microM) on the sinus node recovery time (SNRT) measured in isolated right atria from 4-6-month-old male Wistar rats. Electrogram and isometric force were recorded at 36.5 degree C. Two methods for sinus node resetting were used: a) pulse: a single stimulus pulse interpolated at coupling intervals of 50, 65 or 80% of the regular spontaneous cycle length (RCL), and b) train: a 2-min train of pulses at intervals of 50, 65 or 80% of RCL. Corrected SNRT (cSNRT) was calculated as the difference between SNRT (first spontaneous cycle length after stimulation interruption) and RCL. Ryanodine only slightly increased RCL (<10%), but decreased developed force by 90%. When the pulse method was used, cSNRT ( approximately 40 ms), which represents intranodal/atrial conduction time, was independent of the coupling interval and unaffected by ryanodine. However, cSNRT obtained by the train method was significantly higher for shorter intervals between pulses, indicating the occurrence of overdrive suppression. In this case, ryanodine prolonged cSNRT in a rate-dependent fashion, with a greater effect at shorter intervals. These results indicate that: a) a functional SR, albeit important for force development, does not seem to play a major role in atrial automaticity in the rat; b) disruption of cell Ca2+ homeostasis by inhibition of SR function does not appear to affect conduction; however, it enhances overdrive-induced depression of sinusal automaticity.
Assuntos
Rianodina/farmacologia , Retículo Sarcoplasmático/efeitos dos fármacos , Nó Sinoatrial/efeitos dos fármacos , Animais , Estimulação Elétrica , Masculino , Ratos , Ratos Wistar , Fatores de TempoRESUMO
In the present paper we describe a method to estimate mitochondrial Ca2+ uptake during the declining phase of Ca2+ transients (cell relaxation) in intact isolated myocardial cells. This method is based on inhibition of sarcoplasmic reticulum (SR) Ca2+ accumulation by caffeine, blockade of Ca2+ transport via sarcolemmal Ca(2+)-ATPase by treatment with carboxyeosin and inhibition of sarcolemmal Na+/Ca2+ exchange by removal of extracellular Na+ and Ca2+.Ca2+ transients were evoked in rabbit ventricular myocytes by quick and sustained caffeine application (10 mM) after a 5-min period of electrical stimulation to load the SR with Ca2+. Mitochondrial Ca2+ transport was estimated using a model described by Sipido and Wier (Journal of Physiology (1991), 435: 605-630), which was originally proposed to describe Ca2+ fluxes during excitation-contraction coupling in cardiac cells. Our results indicate that, in intact rabbit myocytes, the Ca2+ flux due to net mitochondrial Ca2+ uptake may attain a value close to 1 microM/sec.
Assuntos
Cálcio/metabolismo , Mitocôndrias Cardíacas/fisiologia , Contração Miocárdica/fisiologia , Animais , ATPases Transportadoras de Cálcio , Transporte de Íons , Masculino , Miocárdio/citologia , Miocárdio/metabolismo , Coelhos , Ratos , Ratos Endogâmicos , Retículo SarcoplasmáticoRESUMO
The effects of pacing frequency, overdrive duration and stimulus amplitude on the sinus node recovery time (SNRT) were studied in the isolated right atrium of the rat. A positive relationship between pacing frequency and the SNRT was observed, whereas overdrive duration and stimulus amplitude did not affect SNRT. There was no significant interaction among the factors studied. The effect of frequency upon SNRT probably does not involve neurotransmitter release due to stimulation, since in vitro pretreatment with atropine plus propranolol does change the SNRT-frequency relation.
Assuntos
Estimulação Cardíaca Artificial , Contração Miocárdica , Nó Sinoatrial/fisiologia , Animais , Função Atrial , Atropina/farmacologia , Eletrofisiologia , Masculino , Neurotransmissores/metabolismo , Propranolol/farmacologia , Ratos , Ratos EndogâmicosRESUMO
BACKGROUND AND PURPOSE: Myocardial automatism and arrhythmias may ensue during strong sympathetic stimulation. We sought to investigate the relevant types of adrenoceptor, as well as the role of phosphodiesterase (PDE) activity, in the production of catecholaminergic automatism in atrial and ventricular rat myocardium. EXPERIMENTAL APPROACH: The effects of adrenoceptor agonists on the rate of spontaneous contractions (automatic response) and the amplitude of electrically evoked contractions (inotropic response) were determined in left atria and ventricular myocytes isolated from Wistar rats. KEY RESULTS: Catecholaminergic automatism was Ca(2+) -dependent, as it required a functional sarcoplasmic reticulum to be exhibited. Although both α- and ß-adrenoceptor activation caused inotropic stimulation, only ß(1) -adrenoceptors seemed to mediate the induction of spontaneous activity. Catecholaminergic automatism was enhanced and suppressed by ß(2) -adrenoceptor blockade and stimulation respectively. Inhibition of either PDE3 or PDE4 (by milrinone and rolipram, respectively) potentiated the automatic response of myocytes to catecholamines. However, only rolipram abolished the attenuation of automatism produced by ß(2) -adrenoceptor stimulation. CONCLUSIONS AND IMPLICATIONS: α- and ß(2) -adrenoceptors do not seem to be involved in the mediation of catecholaminergic stimulation of spontaneous activity in atrial and ventricular myocardium. However, a functional antagonism of ß(1) - and ß(2) -adrenoceptor activation was identified, the former mediating catecholaminergic myocardial automatism and the latter attenuating this effect. Results suggest that hydrolysis of cAMP by PDE4 is involved in the protective effect mediated by ß(2) -adrenoceptor stimulation.
Assuntos
Agonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Catecolaminas/farmacologia , Contração Miocárdica/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Receptores Adrenérgicos beta 1/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Animais , Relação Dose-Resposta a Droga , Átrios do Coração/efeitos dos fármacos , Ventrículos do Coração/efeitos dos fármacos , Masculino , Miócitos Cardíacos/metabolismo , Ratos , Ratos Wistar , Retículo Sarcoplasmático/efeitos dos fármacosRESUMO
BACKGROUND AND PURPOSE: Adding spironolactone to standard therapy in heart failure reduces morbidity and mortality, but the underlying mechanisms are not fully understood. We analysed the effect of canrenone, the major active metabolite of spironolactone, on myocardial contractility and intracellular calcium homeostasis. EXPERIMENTAL APPROACH: Left ventricular papillary muscles and cardiomyocytes were isolated from male Wistar rats. Contractility of papillary muscles was assessed with force transducers, Ca(2+) transients by fluorescence and Ca(2+) fluxes by electrophysiological techniques. KEY RESULTS: Canrenone (300-600 micromol L(-1)) reduced developed tension, maximum rate of tension increase and maximum rate of tension decay of papillary muscles. In cardiomyocytes, canrenone (50 micromol L(-1)) reduced cell shortening and L-type Ca(2+) channel current, whereas steady-state activation and inactivation, and reactivation curves were unchanged. Canrenone also decreased the Ca(2+) content of the sarcoplasmic reticulum, intracellular Ca(2+) transient amplitude and intracellular diastolic Ca(2+) concentration. However, the time course of [Ca(2+)](i) decline during transients evoked by caffeine was not affected by canrenone. CONCLUSION AND IMPLICATIONS: Canrenone reduced L-type Ca(2+) channel current, amplitude of intracellular Ca(2+) transients and Ca(2+) content of sarcoplasmic reticulum in cardiomyocytes. These changes are likely to underlie the negative inotropic effect of canrenone.