| hilcrlcukin-2 (IL-2) is known to have various effects outside the frame of the immune system. The heart has also been proved to be a target of IL-2 action. While the effects of IL-2 on heart tissue are variable depending on the regions of the myocardium studied, mammalian species used, the doses of IL-2, and the intensity of the pacing stimulus, it is well known that IL-2 play a biological role in the mammalian heart. On the other side, systemic administration of IL-2 to patient may result in cadiovascular toxicity including arrhythmias, myocarditis, and cardiomyopathy. Cytokinc activities as IL-2 could be important locally in certain immunological and inflammatory environment following cardiac transplantation, cardiomyopathy, myocarditis, and ischacmia-reperfusion injury, in which various cytokines have implicated, and cytokine-induced myocyte dysfunction is thought to be play a role in the pathophysiology of cardiac disease.Accordingly, the objectives of this study were as follows: first, we sought to define the effect of IL-2 on active and passive electrical properties as well as myocardial contraction duration in isolated rat papillary muscle. Second, in order to evaluate the role of nitric oxide in the effects of IL-2 on myocardium, we determined the impact of nitric oxide synthase (NOS) on myocardiac effect of IL-2. Finally, we observed the effect of IL-2 on the force-frequency relation (FFR) and post-rest potentiation of contractile force, an index of the capacity of SR to store and release Ca2+.METHODSI. Papillary muscle preparationMale sprague-Dawley rats weighing 250-300g were stunned with a blow to the neck. The heart was rapidly removed and transferred to a Petri dish containing Tyrode solution. The papillary muscle was excised from the right ventricle and mounted in a tissue bath. The preparation was superfuscd with warmed (36-37癈) Tyrode solution oxygenated with 95% O2 and 5% CO2. at pH of 7.3-7.4. 1.Standard microclcctrodc technique. The papillary muscles were stimulated through bipolar wires isolated except at the tips at 1 Hz with duration of 1ms and intensity of twice threshold. Glass microelectrode with DC resistance 10-20MQ was used to record transmembrane potentials. The signals were displayed on oscilloscope and delivered to PcLab system, a computer system for data acquisition and analysis. After stabilization of the preparations for 1 hr, the action potentials were recorded as control. Then the papillary muscles were exposed to IL-2 with increasing concentrations from 0.5 to 2.5, 10, 50 and 200 u/ml, 10 min for each concentration. Intracellular impalements were maintained at the same sites for all measurements.2. Determination of passive electrical properties.The passive electrical properties of the papillary muscles were analy/cd according to the one-dimensional under cable model. One end of the muscle was pinned down to the base of bath, other extremity was led to a glass suction pipette with an inner diameter of ~600 y m and filled with Tyrode solution. The pipette was connected to stimulator of PC Lab system. The total current injected through the system was measured from the voltage drop across a resistor of 10 k Q . Experimental recordings were stated 60 min after the suction electrode was applied to the preparation. Subthreshold rectangular current was injected through suction electrode. The intensity of current was approximately 10 y A with the duration of 50 msec. The decay of transmembrane electrotonic potentials along the axis of the muscle was measured by electronic subtraction of the intracclluar microelectrode signal from the extracellular one. The extracellular electrode was positioned as close as possible to the intraccllular one in such a way that no voltage deflection was observed when intracellular electrode was withdrawn to immediately neighboring extracellular space. Records were started at a distance of 300 u m from the center of the suction electrode. The space constant, A,, membrane time constant, t ?. and input resistance, RIN were c...
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