Nipradilol Can Prevent Left Ventricular Systolic and Diastolic Dysfunction After Myocardial Infarction in Rats.

Abstract

n the process of cardiac remodeling after myocardial infarction (MI), infarct expansion occurs as an acute dilatation and thinning of the infarcted region, and is followed by ventricular dilatation and myocardial hypertrophy in the non-infarcted regions. This cardiac remodeling is associated with progressive systolic and diastolic dysfunction, and an increased incidence of congestive heart failure and sudden death. [1][2][3][4] The changes in the myocardial tissue are related to structural rearrangement in the infarcted and non-infarcted regions, characterized by myocardial cell damage, hypertrophy and expression of extracellular matrix components. It is well known that the angiotensin blockade can prevent cardiac remodeling and has prolonged survival in both experimental models of MI and in patients after MI. 5-9 Beta-adrenergic blockers are also used in the treatment of MI and have been shown to reduce morbidity and mortality, presumably by preventing myocardial ischemia and arrhythmia. [10][11][12] However, the effects of -adrenergic blockers on left ventricular (LV) remodeling after MI are still unclear. Previous experimental studies have suggested that propranolol promotes LV dilation following MI, which would adversely affect LV function 13,14 and we have reported that 100 mg·kg -1 ·day -1 of atenolol facilitated LV remodeling after MI. 15 However, other -adrenergic block- Circulation Journal Vol.66, March 2002ers, which have a vasodilating action, do not have clear beneficial effects on ventricular remodeling after MI. Nipradilol (3,4-dihydro-8-(2-hydroxy-3-isopropylamino) propoxy-3-nitroxy-2H-1-benzopyran) is a non-selectiveadrenergic blocker that has a vasodilating action partly mediated by a nitrate moiety of its chemical structure. 16,17 Experimentally, nipradilol prevents the increase in heart weight, LV end-diastolic pressure (LVEDP) and LV enddiastolic volume index after MI, 18,19 but it is still unclear whether nipradilol prevents the progressive systolic and diastolic dysfunction that accompanies the change in the non-infarcted myocardial tissue during cardiac remodeling after MI. To elucidate the effects of nipradilol on cardiac remodeling in a rat model of MI, LV geometry and cardiac function were assessed by Doppler echocardiography and the cardiac gene expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), which are markers of the hypertrophic response of cardiomyocytes, and collagen I and III, which are markers of fibrosis, in non-infarcted areas of the left and right ventricles were investigated by northern blot analysis. Methods Experimental ProtocolMI was produced, as described previously, 20 in male Wistar rats, weight 290-310 g (Clea Japan, Osaka, Japan). Briefly, the rats were anesthetized by injection of pentobarbital sodium (35 mg/kg ip) and a left thoracotomy was performed under volume-controlled mechanical ventilation (tidal volume, 3.0 ml; respiration rate, 60 cycles/min). A ligature of 6-0 prolene was placed around the proximal left anterior descending c...

Dipeptidyl peptidase‐4 inhibitor improves cardiac function by attenuating adverse cardiac remodelling in rats with chronic myocardial infarction

“…The fact that these drugs could improve cardiac sympathovagal balance and decrease oxidative stress may also provide a long-term benefit on the progression of heart failure in this chronic MI model. In rats with chronic MI, cardiac systolic and diastolic dysfunction is commonly found (Bauersachs et al 2001;Izutani et al 2002). Given that the infarct size in our rats with chronic MI was not different among different treatment groups, the improved LV function observed with both enalapril and vildagliptin, but not metformin, treatment could contribute to the improved cardiac remodelling by these drugs.…”

“…; Izutani et al . ). Given that the infarct size in our rats with chronic MI was not different among different treatment groups, the improved LV function observed with both enalapril and vildagliptin, but not metformin, treatment could contribute to the improved cardiac remodelling by these drugs.…”

Effects of Cellular Cardiomyoplasty on Ventricular Remodeling Assessed by Doppler Echocardiography and Topographic Immunohistochemistry

“…Ejection fraction was measured by modifying Simpson's method, which uses 4-chamber views (Fig 1). 10 If the left ventricular chamber could not be gained clearly, we used contrast echocardiography. The contrast agent, optison, was injected into the left ventricular cavity via the femoral vein (Fig 2).…”

Long-Term Beneficial Effect of Infarct-Related Artery Patency in Acute Anterior Myocardial Infarction in Patients With Poor Myocardial Viability in the Region-at-Risk

“…Further, we suspect that the mechanism may be based on differences in the structure of connective tissue and microvasculature; in other words, on differences in the healing process such as collagen metabolism, morphological changes in necrotic tissue, the number of residual capillaries, and the resulting inflammation at the infarct site. Although -blocking agents and angiotensin-converting enzyme inhibitors inhibit remodeling and improve neurohormonal conditions, 20,[27][28][29][30] there were no differences in the medical regimens of the 2 groups and therefore we do not consider that these agents had a great influence. The primary mechanism of the benefit to be gained from IRA patency is inhibition of LV remodeling, and residual myocardial viability is not a major factor in this.…”