INTRODUCTION: Heart failure (HF) can occur as a consequence of a number of cardiovascular diseases, and consists of left ventricle (LV) dysfunction, characterized by a reduction of myocardial contractility and cardiac output, with an increase in LV end diastolic volume combined with the reduction of the cardiac reserve. In rats, HF is usually induced by acute myocardial infarction (AMI). Rats with AMI affecting 40-50% of the LV present, 2-6 weeks after the coronary artery ligation, functional and anatomical cardiac alterations combined with hemodynamic, autonomic and humoral derangements, typical of the HF. The sympathetic hyperactivity, the hallmark of HF, can be detected six weeks after AMI and is associated with the reduction of the baroreflex reflex sensitivity. The baroreflex is responsible for maintaining the arterial pressure (AP) within a relatively narrow range. The baroreflex control is of great importance over the autonomic cardiovascular modulation, but in HF it is attenuated. The attenuation of the baroreflex may involve the derangement of the afferences, the central integration or the efferences of the baroreflex arch.Several studies have shown the reduction of the AP and heart rate (HR) after due to a decrease in sympathetic activity. Moreover, chronic electrical stimulation of the baroreflex caused an increase in the survival in dogs with HF. For the time being, there is no report of electrical stimulation of the baroreceptors in conscious rats with HF, looking at the baroreflex control in this pathological condition, as well as the hemodynamic responses due to the baroreflex attenuation. In rats, the electrical stimulation of the aortic depressor nerve (ADN) has been used currently in our laboratory as a mechanism for baroreflex activation. OBJECTIVES: To examine, in conscious freely moving rats with HF, the hemodynamic responses elicited by electrical stimulation of the AND, and these responses them with those of obtained healthy rats, in order to evaluate the attenuation of the baroreflex. Particularly it will look at: 1) The bradycardic and hypotensive responses under the muscarinic receptor blockade by methylatropine, in order to evaluate the role played by the reflex bradycardia in the hypotensive response;2) The bradycardic and hypotensive responses under the ²1-adrenergic blockade with atenolol, in order to evaluate the role played by the sympathetic withdraw combined with the simultaneous parasympathetic activation during the bradycardic response. METHODS: The rats will be anesthetized with sodium thiopental, the hearts exposed and the anterior descending branch of the left coronary artery will be ligated. Control rats will be submitted to similar procedures, except for the coronary ligation. Only animals with infarcted area greater than 40% of the left ventricle will be included in the study. Six weeks after the coronary ligation, the animals will be anesthetized, and the AND will be dissected, isolated and positioned over a pair of electrodes, whose extremities will be exteriorized in the nape of the neck. The femoral artery and vein will be cannulated and exteriorized in the same area. On the day following the surgical procedures, the femoral artery cannula will be connected to a pressure transducer and the electrodes connected to an electrical stimulator. The experimental protocol will consist of a sequence of electrical stimulations (1 mA and 2 ms) of the ADN with frequencies of 5, 15, 30, 60 and 90 Hz, applied randomly, with a 5 minutes interval between stimuli, applied during 20s. At the end of the stimulation trend, the autonomic blockade will be achieved by means of methylatropine (2 mg/kg, iv) or atenolol (2 mg/kg, iv). After the blockade, another stimulation trend will be applied, with the same parameters used before.
News published in Agência FAPESP Newsletter about the scholarship: