Efeitos da inibição prolongada da enzima de conversão da angiotensina sobre as características morfológicas e funcionais da hipertrofia ventricular esquerda em ratos com sobrecarga pressórica persistente

Abstract

Left ventricular hypertrophy (LVH) is an adaptive response of the heart to sustained work overload. Data in the literature 1 have shown that the load conditions and neurohumoral systems, among which the renin-angiotensin-aldosterone system (RAAS) stands out, modulate the characteristics of left ventricular hypertrophy that develop in the presence of chronic pressure overload. Clinical studies 2,3 have shown that angiotensin-converting enzyme inhibitors (ACEI) improve the survival of patients with heart failure, delay heart decompensation in patients with asymptomatic left ventricular dysfunction, and attenuate the progression of left ventricular dilation and dysfunction after myocardial infarction. Experimental studies [4][5][6] have shown that ACEIs attenuate ventricular remodeling, improve survival, and delay the progression of left ventricular dysfunction in rats with myocardial infarction and hamsters with cardiomyopathy. Angiotensin-converting enzyme inhibitors have also been proved to decrease left ventricular hypertrophy in human beings 7 and in experimental animals with chronic pressure overload 8,9 . The favorable effects of ACEI on survival and regression of left ventricular hypertrophy in heart failure and arterial hypertension are frequently attributed to interference with the RAAS, resulting in a reduction in blood pressure and peripheral vascular resistance with a consequent reduction in cardiac overload 10 . However, several studies [10][11][12] have reported that the angiotensin-converting enzyme (ACE) and the myocardial tissue RAAS are activated in animal models of heart failure and cardiac hypertrophy. Although the efficacy of the ACEI in prolonging survival, delaying the development of ventricular dysfunction, and reversing cardiac hypertrophy is widely recognized, it has been difficult to dissociate the hemodynamic effects of those agents on systemic blood pressure from the effects of the myocardial tissue ACE blockade. Therefore, the use of ACEI in arterial hypertension, acute myocardial infarction, and cardiomyopathy is clearly justified, because those drugs block RAAS activity, reduce cardiac load, and reverse left ventricular hypertrophy. The validity of that strategy is controversial when the increase in cardiac load is relatively fixed, as in the case of aortic valvular stenosis. In that circumstance, the reduction in left ventricular hypertrophy may be seen as a loss of the adaptive mechanism that can result in maladjustment of the afterload, and dilation and impairment of left ventricular function. Alternati- Original Article Effects of the Prolonged Inhibition of the Angiotensin-Converting Enzyme on the Morphological and Functional Characteristics of Left Ventricular Hypertrophy in Rats with ObjectiveTo assess the effects of lisinopril (L) on mortality (M) rate and congestive heart failure (CHF), and the characteristics of geometrical myocardial remodeling and left ventricular function in rats with supravalvular aortic stenosis (SAS). MethodsSome Wistar rats underwent SAS or the sim...

Papel relativo da remodelação geométrica do ventrículo esquerdo, morfológica e funcional do miocárdio na transição da hipertrofia compensada para a falência cardíaca em ratos com estenose aórtica supravalvar

“…Morphological alterations of the myocardium were assessed by determining the degree of LVH and quantification of myocardial collagen content. Contractility was studied in papillary muscle preparations that enable the assessment of the contractile status regardless of loading conditions, chamber geometry and neurohormonal disorders 20 .…”

“…After the recordings were concluded, muscle length at Lmax was measured and the muscle was weighed. The cross-sectional area (SA, mm 2 ) was calculated assuming a cylindrical geometry and specific density of 1.0 20 . All variables of the mechanical study of the papillary muscles were normalized for SA.…”

Critérios ecocardiográficos para definição de graus de disfunção ventricular em ratos portadores de estenose aórtica

“…Induction of heart failure through aortic stenosis -Aortic stenosis was induced according to the method previously described in our laboratory 5,13,14 . In summary, the animals were submitted to median thoracotomy and trichotomy after anesthesia with ketamine hydrochloride (50 mg/kg intraperitoneally) and xylazine hydrochloride (10 mg/kg intraperitoneally).…”

“…Other criteria to diagnose heart failure (HF) are based on the presence of clinical and anatomical changes such as tachypnea, pleural effusion, ascitis, thrombus in the left atrium and right ventricle hypertrophy; most of these changes are identifi ed after the animal is sacrifi ced [2][3][4][5] .…”

“…In small animals, the transthoracic echocardiogram is one of the most frequently used methods to assess the size of heart structures, and the contractile performance of the LV [4][5][6][7][8][9][10] . The identification of ventricular dysfunction is generally carried out by comparing the muscular shortening indexes with those obtained in the control group.…”