Morphometric analysis of collagen network and plasma perfused capillary bed in the myocardium of rats during evolution of cardiac hypertrophy

Abstract

In order to investigate the consequences of different types of cardiac hypertrophy on myocardial capillary and fibrosis density in rats we describe here, in the same hearts, the pattern of capillary bed density visualized by fluorescein isothiocyanate dextran (FITC-dextran) and the pattern of fibrosis density as determined by automated image analysis. Pressure overload was induced by clipping one renal artery in rats (one-clip, two-kidney Goldblatt hypertension, RHV). Volume overload was induced by creation of an arteriovenous shunt between the abdominal aorta and the vena cava (aorto-caval fistula model ACF). Animals were sacrified at 1, 3 and 6 months following surgical procedure. Immediately prior to sacrifice, FITC-dextran (MW 150,000) was injected with the animal under ether anesthesia. Five minutes later, cardiac diastolic arrest was induced by the i.v. injection of potassium chloride. The heart was rapidly excised and placed in a formaldehyde solution. The degree of cardiac hypertrophy was calculated after measurement of cardiac weight. Left ventricular wall thickness and cavity area were measured by microscopic methods. Capillary density and geometry were determined by morphometric methods, under ultraviolet light microscopy, using a graphic tablet connected to a microcomputer. The degree of myocardial fibrosis, visualized with Sirius Red, was estimated by the use of automated image analysis using light microscopy. In renovascular hypertension, cardiac hypertrophy was maximum at one month (36%) and persisted through the six months of the study. This increase in cardiac mass was concentric, due to a significant increase in ventricular wall thickness and was associated with a marked increase in fibrosis and a significant decrease in subendocardial capillary density. These effects existed already one month and did not change with time. In the aorto-caval fistula model, cardiac hypertrophy was also maximum at one month (+56%), but this eccentric increase in cardiac mass was associated with no significant change in left ventricular wall thickness, but rather with a significant increase in the surface area of the left ventricular cavity. This volume overload hypertrophy was associated with a decrease in subendocardial capillary density which was negatively correlated with time. In contrast to concentric hypertrophy there was no increase in the fibrosis density compared to the sham-operated groups. Despite the identical degrees of hypertrophy, pressure and volume cardiac overload differed in a significant manner in both left ventricular wall thickness and cavity surface area.(ABSTRACT TRUNCATED AT 400 WORDS)

Myocardial Fibrosis in Chronic Aortic Regurgitation

“…However, our data are consistent with the lack of increase in LV collagen during short-term (Յ2 months) LV volume loading from aortocaval fistulae in dogs 22 and rats. [23][24][25] Also, although AR was not studied, recent reports suggest stress-induced variant expression of genes involved in ECM metabolism. 26 Our results contrast with those reported in the pressureloaded LV in which collagen hyperproduction frequently has been identified 27 and noncollagen ECM usually is not assessed.…”

Angiotensin and the remodelling of the myocardium.

“…This same perivascular and streaky fibrosis was found in the rat myocardium following systemic microsphere embolization and the appearance of sclerotic glomeruli (Carroll et al, 1989). The collagen concentration of the myocardium in renovascular hypertension, as measured by either its concentration of hydroxyproline or its morphometrically determined collagen volume fraction, is elevated (Averill et al, 1976;Bartosova etal., 1969;Doering etal., 1988;Jalil et al, 1988;Michel et al, 1986b;Sen & Bumpus, 1979;Thiedemann etal., 1983;Weber et al, 1988b). Thus, there is little question that collagen accumulation and its structural remodelling are an integral component of the pressure overload state that accompanies renovascular hypertension and which, in some yet undefined manner, may be related to elevated circulating angiotensin II.…”

Structural remodeling in hypertensive heart disease and the role of hormones.

“…45 It likewise does not appear with either the volume-overload hypertrophy associated with uninephrectomy and a high Na + diet, 45 a compensated arteriovenous fistula, 46 -51 chronic anemia, 52 atrial septal defect, 53 or the hypertrophy induced by chronic thyroxine administration. 52 - 54 In each of these latter circumstances the RAAS is not activated.…”