Abstract 652: Coronary Capillaries in Ischemic Congestive Heart Failure in Rats Exhibit Significant Morphological Disorder

In ischemic congestive heart failure (CHF), the heart is damaged and undergoes compensatory remodeling, a pathological process associated with harmful effects. The goal of this study is to explore the manifestation of CHF by examining the morphological changes occurring in the coronary microvasculature in CHF versus normal rat hearts. We tested the hypothesis that coronary capillaries in rats with CHF exhibit significantly more morphological disorder than those in control rats. Methods: CHF was induced by aortic banding, ischemia/reperfusion injury two months post-banding (left coronary artery ligation for 30 minutes) and aortic debanding one month post-injury. Resin polymer containing fluorescent dye was injected into coronary vasculature of excised hearts. Muscle tissue was digested using NaOH to reveal vascular casts that were sputter coated with gold for imaging under a Scanning Electron Microscope (SEM). A total of 93 SEM images from 14 rats (7 control, 7 CHF) were analyzed for structural alignment using an automated gradient detection algorithm and circular statistics implemented using MATLAB software; Mean Vector Length (MVL) was calculated for each image as a measure of capillary organization (0<MVL<0. MVL->1 perfect alignment, MVL->0 random disarray). Results: CHF capillaries exhibit significantly more structural disorder than control (MVL 0.35±0.02 for 61 CHF, 0.58±0.02 for 32 control. p<0.01). Conclusions: Coronary capillaries in CHF rats exhibit significant abnormal morphological disarray that may impair blood flow hemodynamics and material and oxygen exchange in myocytes. Such disordered capillary remodeling could have detrimental consequences for the progression and prognosis of heart failure.

Abnormalities of capillary microarchitecture in a rat model of coronary ischemic congestive heart failure

The aim of the present study is to explore the role of capillary disorder in coronary ischemic congestive heart failure (CHF). CHF was induced in rats by aortic banding plus ischemia-reperfusion followed by aortic debanding. Coronary arteries were perfused with plastic polymer containing fluorescent dye. Multiple fluorescent images of casted heart sections and scanning electric microscope of coronary vessels were obtained to characterize changes in the heart. Cardiac function was assessed by echocardiography and in vivo hemodynamics. Stenosis was found in all levels of the coronary arteries in CHF. Coronary vasculature volume and capillary density in remote myocardium were significantly increased in CHF compared with control. This occurred largely in microvessels with a diameter of ≤3 μm. Capillaries in CHF had a tortuous structure, while normal capillaries were linear. Capillaries in CHF had inconsistent diameters, with assortments of narrowed and bulged segments. Their surfaces appeared rough, potentially indicating endothelial dysfunction in CHF. Segments of main capillaries between bifurcations were significantly shorter in length in CHF than in control. Transiently increasing preload by injecting 50 μl of 30% NaCl demonstrated that the CHF heart had lower functional reserve; this may be associated with congestion in coronary microcirculation. Ischemic coronary vascular disorder is not limited to the main coronary arteries, as it occurs in arterioles and capillaries. Capillary disorder in CHF included stenosis, deformed structure, proliferation, and roughened surfaces. This disorder in the coronary artery architecture may contribute to the reduction in myocyte contractility in the setting of heart failure.

Abstract 16619: The Role of Capillary Disorder in Coronary Ischemic Congestive Heart Failure in Rats

The aim of present study is to explore the role of capillary disorder in coronary ischemic congestive heart failure (CHF). Methods: CHF was induced in rats by aortic banding plus ischemia/reperfusion followed by aortic de-banding. Coronary arteries were perfused with plastic polymer containing fluorescent dye. Multiple fluorescent images of casted heart sections and scanning electric microscope of coronary vessels were conducted to characterize changes in the heart. Cardiac function was assessed by echocardiography and in vivo hemodynamics. Results: Stenosis was found in all levels of coronary artery in CHF. Coronary vasculature volume and capillary density in remote myocardium were significantly increased in CHF compared with control. This occurred largely in micro-vessels with diameter ≤ 3 μm. Capillaries in CHF had a tortuous structure, while normal capillaries were linear. Capillaries in CHF had inconsistent diameters, with assortments of narrowed and bulged segments. Their surfaces appeared rough, likely indicating endothelial dysfunction in CHF. Segments of main capillaries between bifurcations were significantly shorter in CHF than in control. Transiently increasing preload by injecting 50 μl of 30% NaCl demonstrated that the CHF heart has lower functional reserve; this is likely associated with congestion in coronary microcirculation. Conclusions: Ischemic coronary vascular disorder is not limited to main arteries, but also occurs in arterioles and capillaries. Capillary disorder in CHF included stenosis, deformed structure, proliferation and roughened surfaces, and is perhaps a primary contributor to the energy starvation which leads to reduction of myocyte intrinsic contractility.

Separate mechanisms cause anemia in ischemic vs. nonischemic murine heart failure

In ischemic congestive heart failure (CHF), anemia is associated with poor prognosis. Whether anemia develops in nonischemic CHF is uncertain. The hematopoietic inhibitors TNF-α and nitric oxide (NO) are activated in ischemic CHF. We examined whether mice with ischemic or nonischemic CHF develop anemia and whether TNF-α and NO are involved. We studied mice ( n = 7–9 per group) with CHF either due to myocardial infarction (MI) or to overexpression of the Ca2+-binding protein calsequestrin (CSQ) or to induced cardiac disruption of the sarcoplasmic reticulum Ca2+-ATPase 2 gene (SERCA2 KO). Hematopoiesis was analyzed by colony formation of CD34+bone marrow cells. Hemoglobin concentration was 14.0 ± 0.4 g/dl (mean ± SD) in controls, while it was decreased to 10.1 ± 0.4, 9.7 ± 0.4, and 9.6 ± 0.3 g/dl in MI, CSQ, and SERCA2 KO, respectively ( P < 0.05). Colony numbers per 100,000 CD34+cells in the three CHF groups were reduced to 33 ± 3 (MI), 34 ± 3 (CSQ), and 39 ± 3 (SERCA2 KO) compared with 68 ± 4 in controls ( P < 0.05). Plasma TNF-α nearly doubled in MI, and addition of anti-TNF-α antibody normalized colony formation. Inhibition of colony formation was completely abolished with blockade of endothelial NO synthase in CSQ and SERCA2 KO, but not in MI. In conclusion, the mechanism of anemia in CHF depends on the etiology of cardiac disease; whereas TNF-α impairs hematopoiesis in CHF following MI, NO inhibits blood cell formation in nonischemic murine CHF.