Caracterização da perfusão miocárdica e remodelamento ventricular em modelo experimental de hipertensão arterial crônica

Abstract

Characterization of myocardial perfusion and ventricular remodeling in an experimental model of chronic high blood pressure. 2020. 76p Master's degree dissertation – Universidade Federal do Triângulo Mineiro, Uberaba, 2020. Introduction: High blood pressure (HBP) is a multifactorial clinical condition characterized by the sustained increase of pressure levels. It is considered one of the main risk factors for cardiovascular, cerebrovascular and renal diseases. Chronic HBP comes along with lesions in target organs, among which is the heart, which may develop into left ventricular concentric hypertrophy and, in some cases, into systolic dysfunction. Since myocardial perfusion defects, as well as alterations of the systolic ventricular function, are often associated to hypertrophic cardiopathy secondary to chronic high blood pressure, we originally expected to register the presence of perfusion defects in vivo through scintillography of myocardial perfusion, as well as remodeling of left ventricle, in an experimental model of HBP. Aims: To characterize myocardial perfusion and left ventricular morphological changes in an experimental model of chronic high blood pressure of Spontaneously hypertensive rat (SHR) and correlate alterations of myocardial perfusion to morphological alterations found in echocardiogram in SHR animals. Methods: rats of 22 weeks were used for the study, kept in refrigerated accommodation in the vivarium of Departamento de Clínica Médica da Faculdade de Medicina de Ribeirão Preto – USP, distributed in Control Group (CG, n = 10): normotensive, 12-week-old Kyoto Wistar Rats, and Investigational Group (SHR, n = 10): spontaneously hypertensive (SHR), 12-week-old rats. Within the time frame of 22 weeks of age of the groups studied, all animals underwent systolic arterial pressure (SAP) analysis through tail plethysmography, and afterwards each group underwent the following image exams in vivo: Doppler-Echocardiogram (ECO) and myocardial perfusion scintillography with Sestamibi-Tc-99m (mini-SPECT) at rest and under stress. Induction of cardiac stress was conducted through the infusion of dobutamine hydrochloride at a dose of 25 µg/Kg/min, for a minute of infusion. Morphologic parameters evaluated were final systolic and diastolic diameters of left ventricle, left ventricle posterior wall thickness at systole and diastole, interventricular septum thickness at systole and diastole, mass index of the left ventricle and relative thickness of ventricular wall. Functional parameters evaluated were fraction of ejections and shortening of left ventricle. Defects in caption of rest and stress images were semi-quantified, according to visual scores allocation (0 = normal; 1 = mild defect; 2 = moderate defect; and 3 = severe defect), in model of 17 segments of left ventricle wall. For each animal, scores were calculated and added in the images of rest, stress and difference between stress and rest, for the evaluation of global extension of reversibility (ischemia) and severity, which were measured through the difference score. Results: SHR group presented significantly higher values of HBP (160 ± 20,09 mmHg) comparing to CG (109,63 ± 20,53 mmHg); p=0,0001, similarly to heart rate (HR), with SHR (232,92 ± 18,82 bpm) comparing to CG (187,06 ± 19,64 bpm); p=0,0001. With dobutamine infusion, significant increase in HR was observed in both groups: for CG, an increase from 201,4 ± 22,6 bpm to 267,6 ± 17,9 bpm (p=0,001), and for SHR, from 203,0 ± 22,6 bpm to 255,8 ± 36,4 bpm (p=0,001). No significant difference was observed in HR increase due to dobutamine infusion between the groups studied. Morphologic parameters observed in ECO documented cardiac remodeling, with slight concentric-type left ventricle hypertrophy, in the SHR group compared to CG, presenting significantly different values in the following variables: left ventricle final systolic diameter (CG = 5,09 ± 0,45 mm vs SHR 4,57 ± 0,55 mm; p=0,03), interventricular septum at systole (CG = 2,73 ± 0,24 mm vsSHR 3,18 ± 0,19 mm; 0,0002), and interventricular septum at diastole (CG = 1,69 ± 0,17 mm vsSHR 1,98 ± 0,21 mm; p=0,003). There was no significant difference in systolic ventricular function between CG and SHR. Significant, higher value was observed in scores added under stress for SHR (14,3 ± 6,9) compared to CG (7,4 ± 4,9), p=0,01 and the added score of the difference SHR (8,9 ± 5,3) and CG (3,9 ± 3,5), p=0,02. Global extension of ischemia was significantly higher for SHR (7,0 ± 3,1 segments) than for CG (3,1 ± 2,6 segments), p=0,008. The number of segments with ischemic defects was significantly higher for SHR (71 segments) comparing to CG (30 segments), p=0,01. Severity of ischemic defects was documented through the presence of mild and moderate defects, stretching between basal, medial and apical ventricular segments in SHR, while in CG ischemic defects were more evident in basal and medial ventricular segments. There was no significant correlation between groups studied. Conclusions: The study conducted with spontaneously hypertensive rats showed morphologic alterations of cardiac remodeling, marking the initial stage of left ventricle hypertrophy, associated to preserved systolic ventricular function. Originally, myocardial perfusion defects in vivo were documented, characterized by diffuse ischemic defects, presented as mild and moderate defects. In the stage of disease evolution in which the groups were studied (22 weeks of age), it was not possible to document significant correlation between the defects of myocardial perfusion and ventricular remodeling.