Effects of Apelin on Left Ventricular-Arterial Coupling and Mechanical Efficiency in Rats with Ischemic Heart Failure

Abstract

Apelin plays important roles in cardiovascular homeostasis. However, its effects on the mechanoenergetics of heart failure (HF) are unavailable. We attempted to investigate the effects of apelin on the left ventricular-arterial coupling (VAC) and mechanical efficiency in rats with HF. HF was induced in rats by the ligation of the left coronary artery. The ischemic HF rats were treated with apelin or saline for 12 weeks. The sham-operated animals served as the control. The left ventricular (LV) afterload and the systolic and diastolic functions, as well as the mechanoenergetic indices were estimated from the pressure-volume loops. Myocardial fibrosis by Masson's trichrome staining, myocardial apoptosis by TUNEL, and collagen content in the aorta as well as media area in the aorta and the mesenteric arteries were determined. Our data indicated that HF rats manifested an increased arterial load (Ea), a declined systolic function (reduced ejection fraction, +dP/dt_max, end-systolic elastance, and stroke work), an abnormal diastolic function (elevated end-diastolic pressure, τ, and declined -dP/dt_max), and decreased mechanical efficiency. Apelin treatment improved those indices. Concomitantly, increased fibrosis in the LV myocardium and the aorta and enhanced apoptosis in the LV were partially restored by apelin treatment. A declined wall-to-lumen ratio in the mesenteric arteries of the untreated HF rats was further reduced in the apelin-treated group. We concluded that the rats with ischemic HF were characterized by deteriorated LV mechanoenergetics. Apelin improved mechanical efficiency, at least in part, due to the inhibiting cardiac fibrosis and apoptosis in the LV myocardium, reducing collagen deposition in the aorta and dilating the resistant artery.

Figure 1

Representative short-axis echocardiographic images at midpapillary muscle level before treatment, gross left ventricular morphology, and pressure-volume loops at the study termination.

Figure 2

The morphological changes as illustrated by hematoxylin and eosin staining and Masson's trichrome staining. For Masson's trichrome staining, fibrosis was stained blue, whereas cytoplasm red. Untreated HF animals displayed disorder structure and fibrotic myocardium, which were ameliorated by apelin treatment.

Figure 3

Representative TUNEL staining slices for left ventricular myocardium. TUNEL: terminal dUTP nick end labeling. Apoptotic nuclei were stained brown. Apelin alleviated myocardial apoptosis induced by coronary artery ligation.

Figure 4

The media cross-sectional area in thoracic and mesenteric arteries depicted by hematoxylin and eosin staining and the collagen density in thoracic aorta indicated by Masson's trichrome staining. Representative transverse sections of the complete mesenteric arteries (a, b, and c) and aortas (d, e, and f) stained with hematoxylin and eosin. Aortic collagen deposition was shown by Masson's trichrome staining. Collagen was stained green while muscle and cytoplasm were red (g, h, and i). Quantitative analysis of media cross-sectional area in the mesenteric and thoracic arteries (j, k) and collagen in the aortas (l). CSA: media cross-sectional area. Apelin reduced media CSA and wall-to-lumen ratio in the mesenteric arteries and alleviated aorta collagen accumulation, but it did not affect media CSA and wall-to-lumen ratio in the aortas.