Efeito potencial cardioprotetor da espironolactona em coração isolado de rato

Abstract

Spironolactone is a drug that have been widely used for many decades in clinical practice to heart failure treatment, often in association to digitalis. However, there are few reports about its effects directly in the heart tissue as well as the cardioprotection against digitalis toxicity. Thus, experimental protocols were carried out using isolated male rat hearts (Wistar) mounted in Langendorff apparatus perfused with Krebs-Henseleit nutrient solution (32 ± 0,5ºC) under constant flow (10 mL. mim-1) in wich were evaluated the acute effects of spironolactone (10 μmol L-1) to electrocardiographic parameters (ECG) and left ventricular pressure using a latex cuff inflated at 150 mmHg and coupled to transducer. Protocols were performed in absence or presence of potassium channels blockers as tetraethylammonium (20 m.mol L-1) or glibenclamide (100 μ.mol L-1) or ouabain (100 μ.mol L -1), an Na+/K+-ATPase inhibitor. Data shown that spironolactone have increased PR interval of ECG and reduced QT and QTc in same time without QRS duration change. To presence of potassium channel inhibitors, TEA showed, but no glibenclamide, the reduction of PRi lengthening spironolactone-induced, in same time, QT and QTc shortening promoted by spironolactone were reduced. Spironolactone rises the left ventricular pressure increased by ouabain and ameliorates the electrocardiographic changes ouabain-induced, such as QTi prolongation, bradycardia and fist degree blockade (PRi prolongation). Diastolic ventricular relaxation was improved to spironolactone presence while it is one of goals to heart failure treatment. The spirolonactone-induced contractile response is double: earliest is inotropic positive however reduces the left ventricular pressure along the perfusion. The first derivative of ventricular relaxation is reduced by spironolactone. Having in hands these data we can prove that spironolactone acts directly in the heart tissue shortening the ECG repolarization time by means of potassium currents facilitation and ameliorates the diastolic ventricular relaxation, also prevents alterations at ECG shape digitalis-induced without impairment its inotropic positive effect.