Electromechanical effects of urea on the isolated rat heart

Langendorff-perfused isolated hearts and left ventricle papillary muscles from 3-month old albino rats of both sexes were studied before and after a 30-min treatment with 17 mM urea added to the medium, a of urea were produced by an increase in tonicity, the study was repeated using 17 mM sucrose. Mechanical studies on the papillary muscles showed that isometric force development and its first time derivative decreased after washing out urea from the bath (F=9.73 ñ 1.02 g/mm2 to 7.47 ñ 0.72 and dF/dt=66.8 ñ 6.43 to 56.7 ñ 4.60 g (mm2)-1 s-1, respectively; P<0.05). Inotropic responses to isoproterenol and increased extracellular calcium after urea treatment reached values similar to those obtained before urea treatment. Thus, the effect of isoproterenol and calcium was stronger than that obtained before urea treatment. In Langendorff-perfused hearts, the spontaneous heart rate did not change after urea or sucrose treatment. Urea promoted a decrease in the left ventricle isovolumetric systolic pressure (39.7 ñ 4.05 to 26.1 ñ 2.69 mmHg, P<0.05) and a reduction of total QRS amplitude. In both papillary muscles and isovolumetric perfused hearts, contractile responses resulting from changes in extracellular sodium concentration were reduced after urea treatment. The increased osmolarity due to sucrose did not produce any changes in electromechanical activities. Although 17 mM, which reduces isometric force and isovolumic pressure development and modifies the ECG, is well below the concentration required to modify protein conformation in vitro, the present results suggest that its action could be explained by an effect at the sarcolemmal level

Activation of the langendorff perfused rat heart under depolarizing conditions

Myocardial activation under depolarized conditions was studied in spontaneoustly beating Langendorff perfused hearts from albino rats. Depolarization was obtained incrasing external potassium concentration in steps (5.4, 7.4, 10, 10.5, 11, 11.5 mM) in the perfusisng solution. Left ventricular isovolumic systolic pressure and coronary flow did not change as external potassium increased, but the atrial and ventricular beat rates decreased, the latter showing a larger decline. In the electrocardiogram, the P-R interval increased as a function of external potassium and the amplitude of the ORS complex diminished as its duration invreased. The mamjority of perfused hearts stopped punping when external potassium was raised to 11.5 mM

The relationship between extracellular calcium and isovolumic systolic pressure in the Langendorff-perfused rat heart

The relationship between extracelular calcium concentration and isovolumic systolic pressure developed by left ventricles was studied in Langendorff-perfused rat hearts. At diastolic pressure lower than 15 mmHg the isovolumic systolic pressure increased when external calcium was changed from 0.5 to 1.25 mM. Pressure stabilized when external calcium was increased to 3.5 mM but then declined at 5 mM Ca**2+. At higher diastolic pressures (20 and 25 mmHg) systolic pressure increased only up to 1.25 mM Ca**2+, and declined with further increases in external calcium concentration. This behavior is probably related to "calcium overload" of the preparations at external calcium concentrations greater than 3.5 mM associated with a decreased perfusion pressure gradient at higher diastolic pressures

Effect of urea on the mechanical and electrical activity of the perfused rat heart

The mechanical and electrical activities of Langendorff perfused isolated hearts from albino female rats were studied before and after the addition of 17 mM urea to the medium. The effect of urea on the osmolarity of the perfusing solution was evaluated by also carrying out the measurement in 17 mM saccharose. The rate of the spontaneously beating hearts did not change after urea or saccharose treatment. However, urea promoted a decrease in the left ventricle isovolumic systolic pressure and a reduction of the total QRS amplitude. Saccharose did not alter mechanical or electrical characteristics. Although the concentration of urea which reduced systolic isovolumic pressure development and altered the ECG is well below that required to modify protein conformation in vitro, our results suggest that its action could be at the sarcolemmal level

Depression of myocardial force development after urea treatment

Left ventricle papillary muscles from /wistar male rats were studied before, during and after urea treatment, Urea was used at a concentration (17 mM) equivalent to a plasma level of 100 mg/dl. To verify whether these effects were produced by an increase in osmolarity, the study was repeated using 17 mM saccharose. The results showed that isometric force development decreased after washing out urea from the bath but inotropic responses to isoproterenol (IPA) and increased extracellular calcium attained values similar to those obtained before urea treatment. Thus, the percentual increments due to IPA and calcium were enhanced after urea treatment. The increased osmolarity due to saccharose did not produce any change in contraction or in the responses to intropic interventions. It suggested that urea modifies the excitation-contraction coupling mechanism in heart muscle, reducing the force developed at the steady state control level without reducing the responses to the inotropic interventions