Cardiomiopatia hipertrófica felina

A Cardiomiopatia Hipertrófica (CMH) é uma doença é a doença cardíaca primária mais comum em gatos causada por uma mutação genética autossómica de dominância incompleta com apresentações clínicas variadas que apresenta uma grande dispersão mundial e racial. O carácter hereditário desta doença cardíaca resulta de uma mutação genética autossómica dominante com penetração incompleta, sendo mais exuberante em situações de homozigotia. A mutação mais comum ocorre em genes que codificam para a Proteína C3 de Ligação à Miosina, com alterações estruturais do mesmo e consequente hipertrofia concêntrica parcial ou total do ventrículo esquerdo. Com o aumento do septo interventricular, dos músculos papilares e/ou da parede do ventrículo esquerdo, ocorre comprometimento tanto do enchimento ventricular como do seu relaxamento, o que por sua vez contribui para a progressão da hipertrofia. A diminuição da câmara cardíaca, a diminuição do débito cardíaco, o aumento compensatório do ritmo, o aumento da pressão de enchimento diastólico e o aumento do átrio esquerdo predispõem para uma insuficiência cardíaca congestiva, formação trombos e até morte súbita. A avaliação clínica de um gato com suspeita de Cardiomiopatia Hipertrófica deve ser exaustiva, mesmo que o diagnóstico definitivo apenas possa ser confirmado através de ecocardiografia e de métodos de biologia molecular no sentido de identificar a mutação genética. A ecocardiografia pode ainda ser útil para direcionar a terapêutica em função do grau de hipertrofia estabelecer prognóstico. Atualmente, em medicina humana, existem outras formas de terapêutica, como o novo MYK 461, que se revelam bastante promissores.The Hypertrophic Cardiomyopathy is the heart disease more common in cats caused by a genetic autossomic mutation with imcomplete penetrance, having several clinic findings worldwide and inbreed. This disease assumes an hereditary character associated with a genetic mutation autossomic dominant with incomplete penetrance, being more exuberant in homozigotic. It’s a common mutation in genes that codify for the Myosin Binding Protein C (MYBPC3), with structural alteration of itself and leading to the partial or total concentric hypertrophy os left ventricule. With the increase of the interventricular septum and/or papillary muscles and/or left ventricle hall there is a compromise of the ventricular filling and it’s relaxation, which in other hand contributes to the progression of the hypertrophy. The decrease of the cardiac chamber, the decrease of cardiac output, the compensatory increase of rhythm, the increase of pressure in diastolic filling and the increase of the left atrium predispose to congestive heart failure and even sudden death. Cats clinical evaluation under the suspect of Hypertrophic Cardiomyopathy should be exhaustive, even if the definite diagnostic can only be confirmed throght Ultrasound and bio molecular methods looking for identification of genetic mutations. Ultrasound can also be useful to direct the therapeutics accordingly to the level of Hypertrophy, and better prognostics. Nowadays, there are other new therapeutic drugs, like MYK 461, that are showing promissing results

Silymarin Constituent 2,3-Dehydrosilybin Triggers Reserpine-Sensitive Positive Inotropic Effect in Perfused Rat Heart

<div><p>2,3-dehydrosilybin (DHS) is a minor flavonolignan component of <i>Silybum marianum</i> seed extract known for its hepatoprotective activity. Recently we identified DHS as a potentially cardioprotective substance during hypoxia/reoxygenation in isolated neonatal rat cardiomyocytes. This is the first report of positive inotropic effect of DHS on perfused adult rat heart. When applied to perfused adult rat heart, DHS caused a dose-dependent inotropic effect resembling that of catecholamines. The effect was apparent with DHS concentration as low as 10 nM. Suspecting direct interaction with β-adrenergic receptors, we tested whether DHS can trigger β agonist-dependent gene transcription in a model cell line. While DHS alone was unable to trigger β agonist-dependent gene transcription, it enhanced the effect of isoproterenol, a known unspecific β agonist. Further tests confirmed that DHS could not induce cAMP accumulation in isolated neonatal rat cardiomyocytes even though high concentrations (≥ 10 μM) of DHS were capable of decreasing phosphodiesterase activity. Pre-treatment of rats with reserpine, an indole alkaloid which depletes catecholamines from peripheral sympathetic nerve endings, abolished the DHS inotropic effect in perfused hearts. Our data suggest that DHS causes the inotropic effect without acting as a β agonist. Hence we identify DHS as a novel inotropic agent.</p></div

Effect of DHS on cAMP accumulation.

<p>Isolated neonatal rat cardiomyocytes were subjected to treatments with DMSO (control), NE or various concentrations of DHS alone or in combination for 5 min followed by measurement of intracellular cAMP level using ELISA based assay. Data are average ± SD for three independent experiments. Values are significantly different from control values * (p < 0.05).</p

Effect of propranolol on perfusion treatments.

<p>Isolated adult rat hearts were perfused with Krebs-Henseleit buffer for 10 min followed by 15 min perfusion with DHS or DHS + PRO and concluded by 10 min perfusion (wash-out) with Krebs-Henseleit buffer. Data presented were obtained for hearts treated with 1 μM DHS (◆, dotted line) and 200 μM PRO together with 1 μM DHS (■, dashed line). Individual panels are: A—LVP; B—contractility; C–heart rate. The same perfusion protocol was used for ISO treatment. Data presented were obtained for hearts treated with 1 μM ISO (▲, dashed line) and 200 μM PRO together with 1 μM ISO (●, full line). Individual panels are: D—LVP; E—contractility; F—heart rate.</p

Effect of DHS on biomechanical parameters in perfused adult rat heart.

<p>Isolated adult rat hearts were perfused with Krebs-Henseleit buffer for 10 min followed by 15 min perfusion with DHS or Krebs-Henseleit buffer in control hearts, and concluded by 10 min perfusion (wash-out) with Krebs-Henseleit buffer. Data presented were obtained for control hearts (●, full line) and hearts treated with: 10 nM DHS (■, dotted line); 100 nM DHS (◆, dashed line); 1 μM DHS (*, dash-and-dot line) and 10 μM DHS (▲, dashed line). Individual panels are: A—LVP; B—contractility; C—heart rate. Each point represents an average for three experiments.</p

Effect of DHS on phosphodiesterase activity.

<p>Phosphodiesterase activity was evaluated in the presence of various DHS concentrations or in the presence of 50 μM IBMX. Data are average ± SD for three independent experiments, each experiment was performed as triplicates. Values are significantly different from control values * (p < 0.05).</p