Developed pressure data may provide misinformation when used alone to evaluate systolic function in isovolumetric left ventricle preparations

We report data showing that developed pressure (DPmax) may lead to opposite conclusion with respect to maximal developed circumferential wall stress (smax) when used to assess contractile function in left ventricle isovolumic preparations. Isovolumetric left ventricle preparations of rats with cardiac hypertrophy (H; N = 10) induced by isoproterenol administration showed higher DPmax (174 ± 14 mmHg) than control (C; N = 8) animals (155 ± 12 mmHg) or rats with regression (R; N = 8) of hypertrophy (144 ± 11 mmHg). In contrast, the estimated smax for C (145 ± 26 kdynes/cm2) and R (133 ± 17 kdynes/cm2) was higher than for H (110 ± 13 kdynes/cm2). According to Laplace's law, the opposite results of DPmax and smax may depend on the increased mass/volume left ventricle ratio of the hypertrophied hearts, which favored pressure generation. These results clearly show that DPmax should be used with caution to analyze systolic function.Universidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

Caracterização funcional da hipertrofia miocárdica induzida pelo isoproterenol e de sua regressão

OBJETIVO: Analisar as disfunções da hipertrofia miocárdica induzida pelo isoproterenol e de sua regressão. Corações isolados hipertrofiados por isoproterenol (ISO) (8 dias) e após 22 dias de sua suspensão (regressão) foram distendidos. MÉTODOS: Até pressão de repouso (Pr) de 60mmHg, analisaram-se: pressão desenvolvida máxima (PDmáx.); estresse sistólico (sigmamáx); inclinação da reta estresses/deformações; constante de relaxamento; rigidez da câmara e rigidez miocárdica. RESULTADOS: Nos corações hipertrofiados (H) as variações de volume (deltaV) necessárias para Pr=60mmHg foram heterogêneas. Em alguns (H1; n=10) deltaV equivaleu à dos controle (C) enquanto em outros (H2; n=10) foi inferior, e também diferiram quanto ao peso seco, complacência ventricular, rigidez miocárdica, constante de relaxamento,e sigmamáx. PDmáx dos grupos H1 e H2 foram superiores às de C (n=8) e Regressão (R) (n=8). Contudo, sigmamáx de H2 foi menor que C, H1 e R. O mecanismo de Frank-Starling foi deprimido nos corações hipertrofiados. A constante de relaxamento de H2 indicou retardo no decaimento da pressão associado a menor complacência ventricular e rigidez miocárdica acentuada. CONCLUSÃO: Hipertrofia miocárdica induzida pelo ISO não é homogênea. Alguns corações têm alterações pouco expressivas; outros têm comprometimento das funções sistólica e diastólica. A hipertrofia miocárdica reduz a capacidade de gerar força e aprimora a capacidade em variar pressão por aumento da relação massa/volume. Há, também, comprometimento da complacência ventricular e da rigidez muscular.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo (UNIFESP) Laboratório de Fisiologia CardíacaUNIFESP, Laboratório de Fisiologia CardíacaSciEL

Electric Countershock and Cold Stress Effects on Liver and Adrenal Gland

OBJECTIVES: Cold exposure induces glycogen and lipid depletion in the liver and the adrenal gland, respectively. However, no previous study has determined the effects of electrical countershock on those tissues. We aimed to evaluate the effects of electrical countershock on lipid depletion in the adrenal gland and on glycogen depletion in the liver. METHODS: We used 40 male Wistar rats divided into four groups: the control group, in which the animals were subjected to a resting period of seven days; the electrical discharge group, in which the animals were subjected to a resting period followed by administration of ten 300-mV electrical discharges; the electrical post-discharge group, in which the animals received ten electrical shocks (300 mV) followed by rest for seven consecutive days; and the cold stress group, in which the animals were subjected to a resting period and were then exposed to -8ºC temperatures for four hours. All animals underwent a laparotomy after treatment. The lipid and glycogen depletions are presented using intensity levels (where + = low intensity and ++++ = high intensity, with intermediate levels in between). RESULTS: The rats exposed to the cold stress presented the highest glycogen and lipid depletion in the liver and the adrenal gland, respectively. Furthermore, we noted that the electrical countershock significantly increased lipid depletion in the adrenal gland and glycogen depletion in the liver. One week after the electrical countershock, the liver and adrenal gland profiles were similar to that of the control group. CONCLUSION: Electrical countershock immediately increased the glycogen depletion in the liver and the lipid depletion in the adrenal gland of rats

Memantine Prevents Cardiomyocytes Nuclear Size Reduction in the Left Ventricle of Rats Exposed to Cold Stress

OBJECTIVES: Memantine is an N-methyl-d-aspartate (NMDA) glutamate receptor antagonist used to treat Alzheimer's disease. Previous studies have suggested that receptor blockers act as neuroprotective agents; however, no study has specifically investigated the impact that these drugs have on the heart. We sought to evaluate the effects of memantine on nuclear size reduction in cardiac cells exposed to cold stress. METHOD: We used male EPM-Wistar rats (n=40) divided into 4 groups: 1) Matched control (CON); 2) Memantine-treated rats (MEM); 3) Rats undergoing induced hypothermia (IH) and 4) Rats undergoing induced hypothermia that were also treated with memantine (IHM). Animals in the MEM and IHM groups were treated by oral gavage administration of 20 mg/kg/day memantine over an eight-day period. Animals in the IH and IHM groups were submitted to 4 hours of hypothermia in a controlled environment with a temperature of - 8ºC on the last day of the study. RESULTS: The MEM group had the largest cardiomyocyte nuclear size (151 ± 3.5 &#956;m³ vs. CON: 142 ± 2.3 &#956;m³; p<0.05), while the IH group had the smallest mean value of nuclear size. The nuclear size of the IHM group was preserved (125 ± 2.9 &#956;m³) compared to the IH group (108 ± 1.7 &#956;m³; p<0.05). CONCLUSION: Memantine prevented the nuclear size reduction of cardiomyocytes in rats exposed to cold stress

Postischemic stunned myocardium does not alter cardiac response to an elevation in contractile frequency

OBJECTIVE:To assess the influence of the postischemia/reperfusion stunned myocardium (PIRSM) on the inotropic and lusitropic effects of heart rate (HR). METHODS: Nine preparations of isolated dog hearts in isovolumic contraction and nourished by the arterial blood of another dog underwent heart rate elevation from 60 bpm to 200 bpm, in 20-bpm stages. The following variables were assessed before (B) and after (A) ischemia (15 min) and reperfusion (30 min): the pressure developed during contraction (PD), its first positive (+dP/dt) and negative (-dP/dt) derivative, the time of maximum pressure (TMP), the pressure at rest (Pr), and the time necessary for the developed pressure to decrease by 90% of its maximum value (time for relaxation - TR90%). RESULTS: The stimulating effects of HR elevation on inotropism and relaxation were similar before and after ischemia/reperfusion as follows: +dP/dt values increased, TMP decreased, -dP/dt values were intensified, and TR90% decreased. The values of PD did not change, and Pr increased. CONCLUSION: The results confirmed the positive inotropic effect of HR elevation (Bowditch effect) and the depressive action of ischemia/reperfusion. They also evidenced that PIRSM does not alter the stimulating action of the Bowditch effect, in accordance with the current concept that PIRSM does not impair calcium myocardial kinetics, favoring the prevalent hypothesis that the decrease in the contractile capacity after ischemia/reperfusion depends on the reduction of the myofilament responsiveness to calcium.OBJETIVO: Analisar a influência da depressão miocárdica pós-isquemia/reperfusão (DMPIR) sobre os efeitos inotrópico e lusitrópico promovidos pela freqüência cardíaca (FC). MÉTODOS: Nove preparações de coração isolado de cães nutrido pelo sangue arterial de um outro cão e contraindo isovolumetricamente tiveram a freqüência cardíaca elevada de 60 bpm a 200 bpm, em etapas de 20 bpm. Foram avaliadas as variáveis antes (C) e depois (D) da isquemia (15 min) e reperfusão (30 min): a pressão desenvolvida durante a contração (PD), sua 1ª derivada positiva (+dP/dt) e negativa (-dP/dt), o tempo de pressão máxima (TPM), a pressão de repouso (Pr) e o tempo para a pressão desenvolvida regredir em 90% de seu valor máximo (TR90%). RESULTADOS: Os efeitos estimulantes da elevação da FC sobre o inotropismo e o relaxamento foram semelhantes em C e em D: houve aumento dos valores da +dP/dt, redução do TPM, acentuação da -dP/dt e diminuição do TR90%. A PD não sofreu alteração e a Pr se elevou. CONCLUSÃO: Os resultados confirmaram o efeito inotrópico positivo da elevação da FC (efeito Bowditch) e a ação depressora da isquemia/reperfusão. Evidenciaram ainda que a DMPIR não altera a ação estimulante do efeito Bowditch. Os resultados se adequam ao conceito vigente de que a DMPIR não compromete a cinética miocárdica do cálcio, favorecendo, a hipótese prevalente de que o decaimento da capacidade contrátil pós-isquemia/reperfusão depende de redução da responsividade dos miofilamentos ao cálcio.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Fisiologia CardiovascularUNIFESP, EPM, Fisiologia CardiovascularSciEL

Efeitos da fluoxetina sobre a ultraestrutura mitocondrial no ventrículo direito de ratos expostos ao estresse pelo frio

OBJECTIVE: To assess fluoxetine effects on mitochondrial structure of the right ventricle in rats exposed to cold stress. METHODS: The experimental study procedures were performed in 250-300g male EPM-Wistar rats. Rats (n=40) were divided into four groups: 1) Control group (CON); 2) Fluoxetine (FLU); 3) Induced hypothermia (IH) and; 4) Induced hypothermia treated with fluoxetine (IHF). Animals of FLU group were treated by the administration of gavages containing 0.75 mg/kg/day fluoxetine during 40 days. The induced hypothermia was obtained by maintaining the groups 3 and 4 in a freezer at -8ºC for 4 hours. The animals were sacrificed and fragments of the right ventricle (RV) were removed and processed prior to performing electron microscopic analysis. RESULTS: The ultrastructural changes in cardiomyocytes were quantified through the number of mitochondrial cristae pattern (cristolysis). The CON (3.85%), FLU (4.47%) and IHF (8.4%) groups showed a normal cellular structure aspect with preserved cardiomyocytes cytoarchitecture and continuous sarcoplasmic membrane integrity. On the other hand, the IH (34.4%) group showed mitochondrial edema and lysis in cristae. CONCLUSION: The ultrastructural analysis revealed that fluoxetine strongly prevents mitochondrial cristolysis in rat heart, suggesting a protector effect under cold stress condition.OBJETIVO: Analisar os efeitos da fluoxetina sobre a estrutura mitocondrial do ventrículo direito de ratos expostos ao estresse pelo frio. MÉTODOS: Os procedimentos do estudo foram realizados em ratos Wistar-EPM (250-300g) machos. Os ratos (n=40) foram divididos em quatro grupos: 1) Controle (CON); 2) Fluoxetina (FLU); 3) Induzidos à hipotermia (IH) e; 4) Induzidos à hipotermia tratados com fluoxetina (IHF). O grupo FLU foi tratado com gavagem contendo 0,75 mg/kg/dia de fluoxetina durante 40 dias. O estresse induzido pelo frio foi realizado mantendo os grupos 3 e 4 em um freezer (-8ºC) por quatro horas. Os animais foram sacrificados e fragmentos do ventrículo direito (VD) foram removidos e processados antes de serem conduzidos para a microscopia eletrônica. RESULTADOS: As alterações ultraestruturais dos cardiomiócitos foram quantificadas pelo número padrão de cristas mitocondriais (cristólises). Os grupos CON (3,85%), FLU (4,47%) e IHF (8,4%) mostraram aspecto normal de suas estruturas celulares com a citoarquitetura dos cardiomiócitos preservada com integridade sarcoplasmática contínua. Por outro lado, o grupo IH (34,4%) apresentou edema mitocondrial e lise nas cristas. CONCLUSÃO: A análise ultraestrutural revelou que a fluoxetina previne fortemente cristólises mitocondriais em miocárdio de ratos, sugerindo possível efeito protetor na condição de estresse induzido pelo frio.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo (UNIFESP)Faculdade de Medicina do ABCFaculdade de Medicina do ABC Departamento de Morfologia e FisiologiaUniversidade Federal de São Paulo (UNIFESP) Departamento de MedicinaUNIFESP, Depto. de MedicinaSciEL

Prior exercise training does not prevent acute cardiac alterations after myocardial infarction in female rats

OBJECTIVE: This study aimed to investigate whether previous exercise training could prevent or attenuate acute cardiac alterations after myocardial infarction. METHODS: Female rats were submitted to swim training (1 h/day; 5 days/week) or allowed to remain sedentary for 8 weeks. Afterwards, they were randomly assigned to left coronary artery occlusion or sham surgery. After this procedure, the rats remained sedentary for one week until euthanasia. Cardiac structural and functional analyses were performed using Doppler echocardiography. The rats that had a moderate or large infarct size were included in the evaluations. The data (mean + SEM) were analyzed using a two-way ANOVA model followed byTukey's post-hoc test. RESULTS: After the surgery, no significant difference between the exercise and sedentary groups was observed in the left ventricular infarct sizes (34.58 + 3.04 vs. 37.59 + 3.07). In another group of rats evaluated with Evans blue 1 h after myocardial infarction, no siginificant difference in the area at risk was observed between the exercised and sedentary rats (49.73 + 1.52 vs. 45.48 + 3.49). The changes in the left ventricular fractional areas for the exercised and sedentary myocardial infarction groups (36 + 2% and 39 + 3%, respectively) were smaller than those for the exercise sham surgery (ES, 67+1%) and sedentary sham surgery (SS, 69 + 2%) groups. The E/A was higher in the sedentary myocardial infarction (4.4 + 0.3) and exercised myocardial infarction (5.5 + 0.3) rats than in the SS (2.4 + 0.1) and ES (2.2 + 0.1) rats. CONCLUSION: Previous swim training of female rats does not attenuate systolic and diastolic function alterations after myocardial infarction induced by left coronary artery occlusion, suggesting that cardioprotection cannot be provided by exercise training in this experimental model

Evaluación de la función barorrefleja en ratas jóvenes espontáneamente hipertensas

BACKGROUND: The literature describes contradictory data regarding the onset of the baroreflex reduction in spontaneously hypertensive rats. OBJECTIVE:This investigation was undertaken to evaluate the baroreflex function in 13-week-old spontaneously hypertensive rats. METHODS:Male Wistar Kyoto (n=15) and spontaneously hypertensive rats (n=15) aged 13 weeks were studied. Cannulas were inserted in the abdominal aortic artery through the right femoral artery to measure mean arterial pressure and heart rate. Baroreflex function was calculated as the derivative of the variation of HR in function of the MAP variation (Δheart rate/Δmean arterial pressure) tested with a depressor dose of sodium nitroprusside (50µg/kg) and with a pressor dose of phenylephrine (8µg/kg) in the right femoral venous approach through an inserted cannula in awake spontaneously hypertensive rats and Wistar-Kyoto. Differences with p values < 0.05 were considered statistically significant. RESULTS:Spontaneously hypertensive rats: Δmean arterial pressure=43.5mmHg±5.2, Δheart rate=-59.7ppm±17.9 and Δheart rate/Δmean arterial pressure=1.3ppm/mmHg±0.1 tested with phenylephrine; Wistar Kyoto: Δmean arterial pressure=&56mmHg±3, Δheart rate=*-114.9ppm±11.3 and Δheart rate/Δmean arterial pressure=#1.9ppm/mmHg±0.3 tested with phenylephrine; spontaneously hypertensive rats: Δmean arterial pressure=-45.6mmHg±8.1, Δheart rate=40.1ppm±11.6 and Δheart rate/Δmean arterial pressure=0.9ppm/mmHg±0.5 tested with sodium nitroprusside; Wistar Kyoto: Δmean arterial pressure=-39.8mmHg±6.2, Δheart rate=51.9ppm±21.8 and Δheart rate/Δmean arterial pressure=1.4ppm/mmHg±0.7 tested with sodium nitroprusside (*p<0.05; #p<0.01; &p<0.001). CONCLUSION: Our results showed that 13-week-old spontaneously hypertensive rats presented reduced baroreflex function when tested with phenylephrine.FUNDAMENTO: La literatura ha descrito datos contradictorios con relación al inicio de la disminución de la función barorrefleja en ratas espontáneamente hipertensas. OBJETIVO: Se realizó este estudio con el objetivo de evaluar la función barorrefleja en ratas jóvenes de 13 semanas, espontáneamente hipertensas. MÉTODOS: Se estudiaron ratas machos Wistar Kyoto (WKY) (n=15) y ratas espontáneamente hipertensas (REH) de 13 semanas de edad (n=15). Se insertaron cánulas en la arteria aorta abdominal -a través de la arteria femoral derecha- para medir la presión arterial media (PAM) y la frecuencia cardiaca (FC). Se calculó la función barorrefleja como la derivada de la variación de la FC en función de la variación de la PAM (ΔFC/ΔPAM). Dicho cálculo se efectuó tras prueba con una dosificación depresora de nitroprusiato de sodio (50µg/kg) y también con una dosificación para presión arterial de fenilefrina (8µg/kg) a través de una cánula insertada en la vena femoral derecha tanto de ratas espontáneamente hipertensas como de WKY. Se consideraron estadísticamente significantes diferencias con un valor de p < 0.05. RESULTADOS: Ratas espontáneamente hipertensas sometidas a prueba con fenilefrina: ΔPAM=43,5 mmHg±5,2, ΔFC=-59,7 ppm±17,9 y ΔFC/ΔPAM=1,3 ppm/mmHg±0,1; Wistar Kyoto probadas con fenilefrina: ΔPAM=&56mmHg±3, ΔFC=*-114,9ppm±11,3 y ΔFC /ΔPAM =#1,9ppm/mmHg±0,3. Ratas espontáneamente hipertensas probadas con nitroprusiato de sodio: ΔPAM=-45,6mmHg±8,1, ΔFC=40,1ppm±11,6 y ΔFC/ΔPAM=0,9ppm/mmHg±0,5; Wistar Kyoto sometidas a prueba con nitroprusiato de sodio: ΔPAM =-39,8mmHg±6,2, ΔFC=51,9ppm±21,8 y ΔFC /ΔPAM =1,4ppm/mmHg±0,7 (*p<0,05; #p<0,01; &p<0,001). CONCLUSIÓN: Nuestros resultados muestran que ratas espontáneamente hipertensas de 13 semanas de edad presentaron reducción de la función barorrefleja cuando probadas con fenilefrina.FUNDAMENTO: A literatura tem descrito dados contraditórios em relação ao início da diminuição da função barorreflexa em ratos espontaneamente hipertensos. OBJETIVO:Este estudo foi realizado para avaliar a função barorreflexa em ratos jovens de 13 semanas espontaneamente hipertensos. MÉTODOS:Foram estudados ratos machos Wistar Kyoto (WKY) (n=15) e ratos espontaneamente hipertensos (REH) de 13 semanas (n=15). Cânulas foram inseridas na artéria aorta abdominal através da artéria femoral direita para medir a pressão arterial média (PAM) e a freqüência cardíaca (FC). A função barorreflexa foi calculada como a derivada da variação da FC em função da variação da PAM (ΔFC/ΔPAM), quando submetida a teste com uma dose depressora de nitroprussiato de sódio (50µg/kg) e com uma dose pressora de fenilefrina (8µg/kg) através de cânula inserida na veia femoral direita em ratos espontaneamente hipertensos e WKY. Diferenças com um valor de p < 0.05 foram consideradas estatisticamente significantes. RESULTADOS:Ratos espontaneamente hipertensos: ΔPAM=43,5 mmHg±5,2, ΔFC=-59,7 ppm±17,9 e ΔFC/ΔPAM=1,3 ppm/mmHg±0,1 testados com fenilefrina; Wistar Kyoto: ΔPAM=&56mmHg±3, ΔFC=*-114,9ppm±11,3 e ΔFC /ΔPAM =#1,9ppm/mmHg±0,3 testados com fenilefrina; ratos espontaneamente hipertensos: ΔPAM=-45,6mmHg±8,1, ΔFC=40,1ppm±11,6 e ΔFC/ΔPAM=0,9ppm/mmHg±0,5 testados com nitroprussiato de sódio; Wistar Kyoto: ΔPAM=-39,8mmHg±6,2, ΔFC=51,9ppm±21,8 e ΔFC/ΔPAM=1,4ppm/mmHg±0,7 testados com nitroprussiato de sódio (*p<0,05; #p<0,01; &p<0,001). CONCLUSÃO: Nossos resultados mostram que ratos espontaneamente hipertensos de 13 semanas apresentaram redução da função barorreflexa quando testados com fenilefrina.Universidade Federal de São Paulo (UNIFESP)Faculdade de Medicina do ABCUNIFESPSciEL

Myocardium tissue changes caused by electrical transthoracic discharges in rats

<p>Abstract</p> <p>Background</p> <p>Cardiomyocytes cytoarchitecture changes caused by transthoracic countershocks have been focused recently. We aimed to evaluate the effects of electrical discharge application in the mitochondria structure in atrial myocardium of rats.</p> <p>Methods</p> <p>An electrical cardioverter was adapted to small rodent animals for our research. Electrical discharges were applied to the precordial region of 30 albino rats: (1) control group - animals that remained on resting period and were afterwards sacrificed; (2) electrical discharge group - animals that remained on resting period, followed by ten electrical discharges of 300 mV and sacrificed, and; (3) electrical post-discharge group - animals that remained on a resting period and received ten electrical discharges like the electrical discharge group, but were sacrificed seven days subsequently. We examined liver, adrenal and left atrium tissue fragments of the three groups.</p> <p>Results</p> <p>It was observed in control and post-discharge groups a normal cellular structure aspect with preserved architecture of cardiomyocytes and continuous sarcoplasmic membrane integrity. On the other hand, cardiac muscle fibers with mitochondrial edema and lysis occurred in the discharge group. Glycogen and adrenal lipids were not depleted in all groups.</p> <p>Conclusion</p> <p>These data suggest that transthoracic electrical discharges induce mitochondrial injuries in atrial cardiac cells of rats.</p