Effects of Hyperthyroidism on Contractility and Na+/Ca2+ Exchanger Activity in the Isolated Papillary Muscle of Rats

Abstract Background: Hyperthyroidism (Hy) is an endocrine disorder, in which the thyroid hormones markedly alter the cardiac function. Increased myocardial contractility and cardiac output, improvement in diastolic relaxation, changes in electrical activity, increments in ventricular mass, and arrhythmias have been reported. However, the influences of thyroid hormones upon molecular mechanisms of cardiac functions have not yet been fully understood. Objectives: To evaluate changes in cardiac contractile parameters and the Na+/Ca2+ exchanger (NCX) function in induced hyperthyroid rats. Methods: Hy was induced by intraperitoneal injections of T3 (15 μg/100 g) for 10 days. Contractile parameters and NCX function were evaluated in the isolated papillary muscle. Data normality was confirmed by the Shapiro-Wilk test. The comparison between groups was performed through an unpaired Student's t-test. Results are expressed as mean ± SD. The accepted significance level was p < 0.05. Results: Our data revealed, in the Hy group, an increase of 30.98% in the maximum speed of diastolic relaxation (-284.64 ± 70.70 vs. -217.31 ± 40.30 mN/mm2/sec (p = 0.027)) and a boost of 149% in the NCX function in late phase of relaxation (20.17 ± 7.90 vs. 50.22 ± 11.94 minutes (p = 0.002)), with no changes in the maximum twitch force (p = 0.605) or maximum speed of systolic contraction (p = 0.208) when compared to the control. Conclusion: The improvement in relaxation parameters is hypothetically attributed to an increase in Sarco-Endoplasmic Reticulum Ca2+ATPase isoform 2 (SERCA2) expression and an increased calcium flow through L-type channels that boosted the NCX function.

Myocardial contractility impairment with racemic bupivacaine, non-racemic bupivacaine and ropivacaine. A comparative study

PURPOSE: To study racemic bupivacaine, non-racemic bupivacaine and ropivacaine on myocardial contractility. METHODS: Isolated Wistar papillary muscles were submitted to 50 and 100 mM racemic bupivacaine (B50 and B100), non-racemic bupivacaine (NR50 and NR100) and ropivacaine (R50 and R100) intoxication. Isometric contraction data were obtained in basal condition (0.2 Hz), after increasing the frequency of stimulation to 1.0 Hz and after 5, 10 and 15 min of local anesthetic intoxication. Data were analyzed as relative changes of variation. RESULTS: Developed tension was higher with R100 than B100 at D1 (4.3 ± 41.1 vs -57.9 ± 48.1). Resting tension was altered with B50 (-10.6 ± 23.8 vs -4.7 ± 5.0) and R50 (-14.0 ± 20.5 vs -0.5 ± 7.1) between D1 and D3. Maximum rate of tension development was lower with B100 (-56.6 ± 38.0) than R50 (-6.3 ± 37.9) and R100 (-1.9 ± 37.2) in D1. B50, B100 and NR100 modified the maximum rate of tension decline from D1 through D2. Time to peak tension was changed with NR50 between D1 and D2. CONCLUSIONS: Racemic bupivacaine depressed myocardial contractile force more than non-racemic bupivacaine and ropivacaine. Non-racemic and racemic bupivacaine caused myocardial relaxation impairment more than ropivacaine. .

Efeito do treinamento físico em alterações induzidas pelo envelhecimento no músculo papilar do rato / Effect of exercise training on aging-induced changes in rat papillary muscle / Efecto del entrenamiento físico en alteraciones inducidas por el envejecimiento en el músculo papilar de la rata

FUNDAMENTO: Os efeitos do envelhecimento no músculo papilar têm sido amplamente demonstrados, mas não há dados disponíveis sobre os efeitos do exercício nas alterações relacionadas à idade. OBJETIVO: Analisar os efeitos do envelhecimento nas propriedades morfológicas e quantitativas do músculo papilar e investigar se um programa contínuo de exercícios moderados pode exercer um efeito protetor contra as conseqüências do envelhecimento. MÉTODOS: Microscopia eletrônica foi utilizada para estudar a densidade dos miócitos, capilares e tecido conectivo e área transversal dos miócitos do músculo papilar no ventrículo esquerdo de ratos Wistar de 6 e 13 meses, não-treinados e submetidos a exercícios. RESULTADOS: Como esperado, a densidade de volume dos miócitos diminui significantemente (p<0,05) com a idade. A densidade de comprimento dos capilares também diminui com a idade, mas não de forma significante. A fração de volume intersticial do tecido do músculo capilar aumenta significantemente com a idade (P<0,05). O número de perfis de miócitos mostrou uma redução de 20% que foi acompanhada de hipertrofia dos miócitos no envelhecimento (P<0,05). Animais submetidos a uma sessão diária de 60 minutos, 5 dias/semana a 1,8 km.h-1 de corrida moderada em esteira ergométrica durante 28 semanas mostraram uma reversão de todos os efeitos do envelhecimento observados no músculo papilar. CONCLUSÃO: O presente estudo apóia o conceito de que treinamento físico de longo prazo impede as mudanças deletérias relacionadas à idade no músculo capilar.

BACKGROUND: The effects of aging on papillary muscle have been widely demonstrated, but no data on the effects of exercise on the age-related changes are available. OBJECTIVE: To analyze the effects of aging on the morphological and quantitative properties of papillary muscle and investigate whether a long-term moderate exercise program would exert a protective effect against the effects of aging. METHODS: We used electron microscopy to study the density of myocytes, capillaries and connective tissue and the cross-sectional area of myocytes of the papillary muscle of the left ventricle of 6- and 13-month-old untrained and exercised Wistar rats. RESULTS: As expected, the volume density of myocytes declined significantly (p<0.05) with aging. The length density of myocardial capillaries also declined with aging, but not significantly. The interstitial volume fraction of the papillary muscle tissue increased significantly (P<0.05) with age. The number of myocyte profiles showed a reduction of 20% that was accompanied by myocyte hypertrophy in the aged rats (P<0.05). Animals submitted to a 60-minute daily session,, 5 days/wk at 1.8 km.h-1 of moderate running on a treadmill for 28 weeks showed a reversion of all the observed aging effects on papillary muscle. CONCLUSION: The present study supports the concept that long-term exercise training restrains the aging-related deleterious changes in the papillary muscle.

FUNDAMENTO: Los efectos del envejecimiento en el músculo papilar han sido demostrados de modo amplio, pero no hay datos disponibles sobre los efectos del ejercicio en las alteraciones relacionadas a la edad. OBJETIVO: Analizar los efectos del envejecimiento en las propiedades morfológicas y cuantitativas del músculo papilar e investigar si un programa continuo de ejercicios moderados puede ejercer un efecto protector contra las consecuencias del envejecimiento. MÉTODOS: Se utilizó microscopia electrónica para estudiar la densidad de los miocitos, capilares y tejido conectivo, así como el área transversal de los miocitos del músculo papilar en el ventrículo izquierdo de ratas Wistar de 6 y 13 meses, no entrenadas y sometidas a ejercicios. RESULTADOS: Como se esperaba, la densidad de volumen de los miocitos disminuye significantemente (p<0,05) con el avance de la edad. La densidad de longitud de los capilares también disminuye con la edad, pero no de forma significante. La fracción de volumen intersticial del tejido del músculo capilar aumenta significantemente con el avance de la edad (P<0,05). El número de perfiles de miocitos mostró una reducción del 20%, seguida de su hipertrofia en el envejecimiento (P<0,05). Sometidos a una sesión diaria de 60 minutos, 5 días/semana a 1,8 km.h-1 de corrida moderada en estera ergométrica durante 28 semanas, los animales mostraron una reversión de todos los efectos del envejecimiento observados en el músculo papilar. CONCLUSIÓN: El presente estudio apoya el concepto de que entrenamiento físico de largo plazo impide los cambios letales en el músculo capilar relacionados a la edad.

Study of the traction resistance of mitral valve chordae tendineae

OBJECTIVE: To determinate the extension and the resistance of the primary mitral valve chordae tendineae when submitted to traction. The importance of keeping the integrity of papillary muscle, chordae tendineae, and mitral valve cuspid when the replacement of this valve occurs is clear, but the knowledge of the maximum resistance that a primary tendinea chorda can withstand is not known. METHODS: Eight hearts were dissected, and one hundred and thirty two primary human chordae tendineae were measured (length and thickness) and submitted to traction under controlled conditions so that the absolute resistance, resistance relative to thickness (relative resistance), and elongation could be measured. RESULTS: The correlation between the elongation at the moment of rupture and the thickness was equal to 1.54 + 17.02 x thickness (P = 0.026); and to absolute resistance was equal to 0.95 + 1.42 x resistance (P < 0.001); and to the resistance relative to thickness (relative resistance) was equal to 1.95 + 0.08 x relative resistance (P = 0.009). The correlation between the absolute resistance and the thickness was equal to 0.26 + 14.53 x thickness (P < 0.001). CONCLUSION: The resistance of primary mitral valve chordae tendineae is associated with its thickness and elongation at the moment of rupture, but is not associated with the length. The elongation at the moment of rupture shows a relationship with the resistance relative to thickness (relative resistance) and with the thickness of the primary chordae tendineae, but not with the length of the chordae tendineae.

OBJETIVO: Determinar o alongamento e a resistência à tração das cordas tendíneas primárias humanas da valva mitral cardíaca. Sabe-se da importância de se manter a integridade do músculo papilar, corda tendínea e cúspide da valva mitral, quando da substituição desta valva, mas não se tem conhecimento da resistência máxima que uma corda tendínea primaria pode sofrer resistência máxima que uma corda tendínea apresenta. MÉTODO: Foram dissecados 8 corações que permitiram a tração de cento e trinta e duas cordas tendíneas primárias humanas. Foram dissecados 8 corações que permitiram a tração de cento e trinta e duas cordas tendíneas primárias humanas, as quais foram medidas (comprimento e espessura) e submetidas a trações em condições controladas, e assim a resistência absoluta, a resistência relativa a espessura (resistência relativa) e o alongamento puderam ser medidos. RESULTADOS: A correlação entre alongamento no momento da ruptura e espessura foi igual a 1,54 + 17,02*espessura (p=0,026); e à resistência absoluta foi igual a 0,95 + 1,42*resistência (p<0,001); e à resistência relativa à espessura foi igual a 1,95 + 0,08*resistência relativa (p=0,009). A correlação entre resistência absoluta e espessura foi igual a 0,26 + 14,53*espessura (p<0,001). CONCLUSÃO: A resistência da corda tendínea primaria humana da valva mitral está relacionada com sua espessura e com o alongamento no momento da ruptura à tração, não estando relacionada ao seu comprimento; e que o alongamento no momento da ruptura apresenta correlação com a resistência relativa à espessura e com a espessura da corda tendínea primaria humana, não estando relacionada com o comprimento da mesma.

Actividad rítmica del músculo papilar inducida por estimulación de alta frecuencia: ritmos n:1, formas de transición e histéresis / Arrhytmic actiitty of the papilary muscle induced by high frecuency stimulatiion: rhythm n:1, transition forms and hysteresis

Los tejidos cardíacos son capaces de trabajar en un amplio intervalo de frecuencias con el fin de atender las distintas demandas que el organismo impone al sistema cardiovascular. Sin embargo, bajo un régimen de cambios de frecuencia y con ciertas condiciones patológicas, pueden desarrollarse arritmias, como bloqueos, taquicardias, fibrilaciones, etc. de posibles consecuencias fatales. Esto motiva la realización de diversos arreglos experimentales en los cuales se explora el comportamiento del corazón, o de regiones de éste. En este artículo reportamos diversos fenómenos que ocurren en el músculo papilar de cobayo cuando se le estimula eléctricamente, desde una frecuencia basal de un pulso por segundo (pps) hasta frecuencias muy altas, de varias decenas de pps, pero incrementando paulatinamente la frecuencia de estimulación. Describimos que en nuestras condiciones experimentales, el músculo despliega sucesivamente ritmos tipo n:1 (una respuesta cada n estímulos) con n creciente; encontramos también que entre uno y otro de estos ritmos aparecen diversas formas de transición, entre las cuales describimos una totalmente nueva en este sistema, que hemos denominado por "ráfagas"; finalmente mostramos que este sistema exhibe de manera generalizada histéresis en la frecuencia, siendo el primer reporte que se hace para esta especie y además el primer reporte en el que se muestran varias "asas" o regiones de histéresis por frecuencia dentro de una misma excursión experimental. Debido al gran volumen de datos generados, hemos introducido una forma de presentación y análisis concisa y eficiente, basada en los espectros de potencia de los datos obtenidos a través de la transformada rápida de Fourier. Este método también se describe brevemente en el artículo.

Cardiac tissues are able to work within a wide range of frequencies to respond to the changing requirements an organism may have. However, during these frequency variations and under certain pathologic conditions arrhythmias such as blocks, tachycardia, fibrillation, etc, may arise some with fatal consequences. For this reason several experimental procedures have been developed that have shown to be useful in studying whole heart properties, or as an alternative from portions of it when changes in its work rate are imposed. This study reports different phenomena occurring in the papillary muscle of the guinea pig heart when stimulated at very high frequency, of several tens of pps, while analyzing its responses during gradual increments starting at 1 (pulses per second). We found that in our conditions papillary muscles display N:1 rhythms with progressive higher N; further more we found that between one and the next rhythm diverse transition patterns appear, among them a new one that we have named "burst pattern". Finally we show that our system exhibits a generalized process of hysteresis by frequency, being this the first report for guinea pig cardiac tissue and the first one to show also the presence of several hysteresis loops in the same experiment. Due to the large volume of generated data we used a faster and easier way to analyze and display them, based on the fast Fourier transform (FFT). The method is briefly described. (Arch Cardiol Mex 2004; 74:11-24).

The blood of the papillary muscle of the right ventricle of human heart and its relationship with the ventricular arterial segments

The frequency of the blood supply of the right ventricle papillary muscles was studied in 41 humans heartsinjected with a vinyl acetate solution. The anterior interventricular branch (AIV), right marginal branch (RM) and posterior interventricular branch (PIV) were injected with different colors and correlated with the arterial segments of the heart (I SV, II DV and III DV) supplied by each one of those arteries. The anterior and posterior papillary muscles received blood from the three arterial segments. The artery of the segment I SV supplied the anterior papillary muscle in 56.09 (per cent) of the cases. The posterior papillary muscle was supplied by the artery of the segment II DV in 34.14 (per cent) of the cases. The anterior group of the septal papillary muscle was supplied by the artery of the segment I SV in all cases. When the posterior group of septal papillary muscle was present (29 cases), the blood supply came from the arteries of the three segments, with major contribution from the arteries of the segments I SV (31.03 per cent) and III DV (51.72 per cent). The most frequent associations observed were the segments I SV and II DV supplying the anterior papillary muscle (24.39 per cent) and segments II DV and III DV supplying the posterior papillary muscle (24.39 per cent).

The rate of force generation by the myocardium is not influenced by afterload

The influence of afterload on the rate of force generation by the myocardium was investigated using two types of preparations: the in situ dog heart (dP/dt) and isolated papillary muscle of rats (dT/dt). Thirteen anesthetized, mechanically ventilated and thoracotomized dogs were submitted to pharmacological autonomic blockade (3.0 mg/kg oxprenolol plus 0.5 mg/kg atropine). A reservoir connected to the left atrium permitted the control of left ventricular end-diastolic pressure (LVEDP). A mechanical constriction of the descending thoracic aorta allowed to increase the systolic pressure in two steps of 20 mmHg (conditions H1 and H2) above control values (condition C). After arterial pressure elevations (systolic pressure C: 119 + 8.1; H1: 142 + 7.9; H2: 166 + 7.7 mmHg; P<0.01), there were no significant differences in heart rate (C: 125 + 13.9; H1: 125 + 13.5; H2: 123 + 14.1 bpm; P>0.05) or LVEDP (C:6.2 + 2.48; H1: 6.3 + 2.43; H2: 6.1 + 2.51 mmHg; P>0.05). The values of dP/dt did not change after each elevation of arterial pressure (C:3,068 + 1,057; H1: 3,112 + 996; H2: 3,086 + 980 mmHg/s; P>0.05). In isolated rat papillary muscle, an afterload corresponding to 50 percent and 75 percent of the maximal developed tension did not alter the values of the maximum rate of tension development (100 percent: 78 + 13; 75 percent: 80 + 13; 50 percent: 79 + 11 g mm-2 s-1, P>0.05). The results show that the rise in afterload per se does not cause changes in dP/dt or dT/dt.

Action potential duration and contraction after rest at room temperature in guinea pig papillary muscle

Simultaneous recordings of action potential and isometric tension of right papillary muscles were performed. After regular stimulation at 1 Hz, pauses of 10 min were allowed. In the first beat after rest, we measured action potential duration at the 90 percent of the repolarization (APD90), maximal twitch tension (T), time to peak of contraction (TTP), and rate of development of tension (+dT/dt) and relaxation (-dT/dt). Values were normalized against pre-rest ones. No significative changes were observed after rest at 35 degrees Celsius. After rest at 25 degrees Celsius APD90 and TTP were prolonged but T was reduced. Post-rest+dT/dt were shower, dT/dt did not shown significative changes. Nifedipine 10 muM prevented post-rest APD90 tengthening, and produced a further reduction of mechanical response. Substitution of external Na+ by Li+ shortened APD90, increased T of either regular or post-rest beats and led to calcium overload signs. When pause were allowed during Na+ substitution, calcium overload signs were attenuated. We conclude that the combination of rest and room temperature diminished [Ca++]i mainly by Na+/Ca++ mechanism. The reduction of [Ca++]i in turn could delay the inactivation of iCa. As a consequence, longer APs were obtained, accompanied by weaker and slower mechanical responses. Changes in TTP and +dT/dt could suggest that post-rest contractions in room temperature, are dependent of extracellular Ca++ rather than a deplected RS.

The blood supply of the papillary muscles of the right ventricle

Because of the functional importance of the Papillary Muscles (PM) we conducted this study on the blood supply of these structures in the right ventricle. The main vessels of the musculli papillares parvi are the ramus septalis of the ramus interventricularis subsinuosus (RSSS), helped by the ramus septalis of the arteria coronaria dextra (RSCD) and the first ramus septalis of theramus interventricularis paraconalis (RSPC). Themusculi papillares magnus receives vessels mainly from theramus ventricularis of the a. coronaria dextra (RVCD) associated with the RSPC, or RSSS. Themmusculus papillaris subarteriosus receives vessels only from the RSCD. In each papillary muscle there is an arterial circle (a double blood supply), which is an anatomical arrangement protecting these structures against vascular problems.

Influência da pós-carga sobre a taxa de variação da tensão desenvolvida (dT/dt). Estudo em músculo cardíaco isolado / Effects of afterlood on peak rate of tension rise (dT/dt). Study in isolated cardiac muscles

PURPOSE: To evaluate the effects of afterload on peak rate of tension rise (dT/dt) in the isolated muscle. METHODS: Left ventricular papillary muscles from Wistar rats were studied in isometric and isotonic afterloaded contractions. Muscles were analised in Krebs-Henseleit solution with calcium concentration of 2.52mM at 28 degrees C. The resting muscle length (preload) was maintained constant. The peak isometric developed tension (DT) and dT/dt were measured during increases of afterload (25, 50, 75 and 100 from DT). RESULTS: A rise in afterload corresponding to 50, 75 and 100 of DT, did not cause an increase in dT/dt values (p > 0.05). The dT/dt value decreased (p < 0.05) when afterload was changed from 75 to 25 of DT. CONCLUSION: The data suggest that an increase in the afterload from 50 of the DT did not promote changes in the dT/dt

Objetivo - Avaliar a influência da pós-carga sobre a taxa de variação da tensão desenvolvida (dT/dt) em músculo isolado.Métodos - Músculos papilares isolados de ventrículo esquerdo de ratos Wistar foram estudados em contrações isométrica e isotônicas contra pós-carga, em solução de Krebs-Henseleit, com concentração de cálcio de 2,52mM, frequência de estímulos de 0,2Hz e temperatura de 28o C. O comprimento diastólico da fibra (pré-carga) foi mantido constante. A tensão máxima desenvolvida (TD) e dT/dt foram medidas durante elevações progressivas da pós-carga (25, 50, 75 e 100% da TD). Resultados - Não ocorreu variação significante (p> 0,05) na dT/dt entre as alterações de pós-carga correspondentes a 50, 75 e 100% da tensão máxima desenvolvida. O valor da dT/dt foi significantemente menor (p < 0,05) em pós-carga de 25%, comparativamente à de 75% da TD. Conclusão - Os resultados sugerem que elevações isoladas da pós-carga, a partir de 50% da tensão máxima desenvolvida, não acarretam variações nos valores da dT/dt.

Influence of the sarcoplasmic reticulum on the inotropic responses of the rat myocardium resulting from changes in rate and rhythm

1. The role of the sarcoplasmic reticulum (SR) in the inotropic responses produced by changes in stimulation rate and rhythm and resting tension was investigated in the rat myocardium. 2. Rat papillary muscles contracting isometrically (basic stimulation rate = 30/min) were superfused in vitro with normal Krebs solution and after addition of ryanodine (1 microM). Post-rest potentiation was obtained after pauses of 5, 10, 15, 30, 60 and 120 s, and the stimulation rate was changed from 6 to 90 bpm. Post-extrasystolic potentiation was induced by interpolating an extra stimulus after an interval of 413 +/- 15 ms. NiCl2 (2 mM) was used to confirm that contractions obtained after SR blockade with ryanodine were activated only by sarcolemmal calcium influx. 3. In the presence of ryanodine, the post-rest potentiation phenomenon disappears and the force-frequency relationship changes from the typical force decrease produced by rate increase to force increase. Under the effect of ryanodine, resting tension increased with the increase in stimulation rate. This behavior was enhanced by reducing extracellular KCl from 5.4 mM to 1 mM. This maneuver decreases Na(+)-K(+)-ATPase and increases intracellular Na+ activity, which reduces Ca2+ extrusion through the Na(+)-Ca2+ exchange mechanism. 4. SR participation in the post-extrasystolic potentiation phenomenon is also suggested because ryanodine treatment reversed the extrasystolic force depression into potentiation. In the presence of ryanodine, blockade of Ca2+ influx with NiCl2 (2 mM) abolished isometric contractions indicating that after SR blockade contractions are mainly dependent on sarcolemmal Ca2+ influx. 5. The results suggest that the SR is involved in the genesis of post-rest potentiation and contributes to the typical force-frequency relationship of the rat myocardium and to the post-extrasystolic potentiation phenomenon. Moreover, SR activity seems to be important for the maintenance of low resting tension in the cardiac muscle, which may represent a safety factor against contractures during inotropic changes produced in rate and rhythm.

Efeito do envelhecimento sobre o comportamento mecânico dos músculos papilares de ratos Wistar / Effects of Age on Mechanical Performance of Wistar Rat Papillary Muscles

Objetivo - Avaliar a influência do envelhecimento sobre o comportamento mecânico do músculo cardíaco. Métodos - Músculos papilares isolados de ventrículo esquerdo de ratos Wistar com 1,3,6 e 12 meses de idade foram estudados em contraçäo isométrica e isotônica, em soluçäo de Krebs-Henseleit, com concentraçäo de cálcio de 2.52 mM, freqüência de estímulos de 0,2 Hz e temperatura de 28ºC. Resultado - A tensäo máxima desenvolvida näo mostrou variaçäo significante a partir de 3 meses. A velocidade de variaçäo da tensäo desenvolvida decresceu significativamente entre 1, 3 e 12 meses. O tempo para a tensäo desenvolvida atingir o valor máximo elevou-se significativamente entre 1, 3 e 12 meses. O tempo para a tensäo desenvolvida decrescer 50// do seu valor máximo aumentou significativamente entre 3 e 6 e 3 e 12 meses. A velocidade de variaçäo de decréscimo da tensäo desenvolvida decresceu entre 3 e 6 e 3 e 12 meses (p < 0,05). A tensäo de repouso näo mostrou variaçäo entre grupos. O encurtamento máximo e o tempo para o pico do encurtamento aumentaram significantemente somente entre ratos com 1 e 3 meses. O tempo para o comprimento do músculo aumentar de 50// a partir do encurtamento máximo, elevou-se significativamente entre 3 e 6 e 3 e 12 meses. A variaçäo relativa de comprimento, a velocidade de encurtamento e de relaxamento näo mostraram variaçöes significantes entre os vários grupos. Conclusäo - Os resultados sugerem que o envelhecimento altera a funçäo mecânica do miocárdio. As modificaçöes funcionais exteriorizam-se por meio de parâmetros derivados de contraçöes isotônica e/ou isométrica

Purpose - To evaluate the effects of age on mechanical performance of rat myocardium. Methods - Left ventricular papillary muscles were isolated from male Wistar rats at 1, 3, 6 and 12 months of age. Muscles were studied isometrically and isotonically, stimulated at 0.2 Hz, perfused with KrebsHenseleit solution having an external calcium concentration of 2.52 mM, and maintained at 280C. Results - Peak isometric developed tension was significantly higher in 1 month than 3, 6 and 12 months. Peak rate of isometric tension rise decreased substantially between 1, 3 and 12 months. Time to peak isometric developed tension showed a significant increase of both 3 and 12 months of age. Time to half relaxation increased significantly from 3 to 6 and from 3 to 12 months. Maximum rate of tension decline decreased from 3 to 6 and from 3 to 12 months. No difference in resting tension was noted among any group. Isotonically, peak shortening and time to peak shortening increased from 1 to 3 months of age. Time to half relengthening increased from 3 to 6 and from 3 to 12 months of age. No difference in peak shortening velocity, peak relaxation velocity and relative change in muscle length was noted among any groups. Conclusion - The maturation affects the mechanical performance of cardiac muscle

Effects of mercury on the contractility of isolated rat cardiac muscle

The effects of increasing concentrations of mercury (Hg2+) chloride (1, 2.5, 5 and 10 microM) were studied on isometrically contracting papillary muscles from female rats (Wistar, EPM strain) weighing 150 to 180 g. Hg2+ promoted an increase of 12.7 +/- 2.2% in the developed force at 1 microM. At 2.5 microM, force values were similar to control, decreasing progressively as Hg2+ concentration increased to 5 (-13 +/- 6.4%) and 10 microM (-37 +/- 12.3%). Potentiated post-rest contractions (PRC) were also determined after 15-, 30- and 60-s pauses. There was a progressive reduction of the potentiated PRCs relative to their respective steady-state control contractions with increasing concentrations of HgCl2. Since in several tissues including myocardium Hg2+ inhibits the activity of Ca2+ and Na(+)-K(+)-ATPases the results described here suggest that Hg2+, at lower concentrations, could increase force by inhibiting Na(+)-K(+)-ATPase, while at higher concentrations Hg2+ would decrease relative PRC potentiation by inhibiting sarcoplasmic reticulum Ca(2+)-ATPase

Mechanical behavior of rest contractions in cardiac muscle

The effects of increasing trest periods on rest contractions and rest potentiation were analysed on isometric contractions of guinea pig papillary muscles at room temperature. Rest contraction amplitude is dependent on pause duration and potentiated for short pauses, which decreases as the rest period increases. Their inotropic state is also dependent on the inotropic state of steady state control contractions. This statement is validadted by the interdependence between control contractions and rest contractions aplitude and also because positive (5.0 mM CaCl2) and negative (0.5 mM NiCl2) inotropic interventions do not change the time course of dF/dt pause duration curves. The also show a slow activation characterized by a prolonged TTP that depends on pause duration being observed even in contractions occurring after short pauses. Rest contractions can be elicited under depolarized conditions produced by TKBa (Tyrode with high potassium and barium) and TKAdr (Tyrode with high potassium and adrenaline), showing that they are dependent on calciun influx occurring during the slow response of the cardiac action potential. The present study, carried out under depolarized conditions and in low extracellular Na+, shows that Na+ entry during the Na-dependent fast component of the action potential is necessary for the occurrence of rest potentiation. These findings suggest that the intracellular Na+, that can be exchanged by external clacium with the Na/Ca exchange mechanism, is necessary for the occurence of the rest potentiation and to avoid the accelerated depression of therest contraction with increasing pause duration

The Na+Ca2+ exchange mechanism as a regulator of post rest contractions in cardiac muscle

The effects of external Na+ concentration and stimulation rate changes on the post rest contraction of rat myocardium were studied. An increase in external Na+ concentration or in stimulation rate causes relative potentiation of the post rest contractions, suggesting that the sarcolemmal Na+-Ca2+ exchange mechanism affects the mafgnitude of the potentiation of post rest contractions

Mechanism of Low K+-induced Depolarization in Mammalian Cardiac Muscle

The membrane permeability to potassium at a resting state is greater than to any other ions and the maintenance of resting membrane potential is largely dependent on K+ concentration of outside medium (Hodgkin and Horowicz 1959), i.e. an increase of K+ concentration of medium induces a depolarization, vice versa. However, on the contrary to this prediction, in some mammalian heart muscle a reduction of external K+ concentration induces a depolarization of membrane potential rather than a hyperpolarization (Vassalle 1965). In this study it was aimed to elucidate the possible mechanism of spontaneous depolarization induced by low external K+ in canine Purkinje fibers. The membrane potential was constantly recorded while components of cations in the bathing medium were replaced one by one by equimolar sucrose until the low K+ induced depolarization was blocked. The results are summarized as follows; The membrane potential of canine Purkinje fibers was spontaneously depolarized by low external K+, and the magnitude of depolarization was not affected by verapamil TEA, and a partial replacement of external Na+ and Ca2+ with choline chloride. But the membrane potential was hyperpolarized only when the all external cations were substitued with sucrose; and this hyperpolarization was disappeared again by substitution of sucrose with choline chloride. From these results, it may be concluded that the depolarization induced by low external K+ in canine Purkinje fibers is due to the nonspecific increase of membrane permeability to external cations and/or combinations with decreased K+ conductance.