Remodelling and functional alterations of the rabbit coronary artery in volume overloaded heart.

OBJECTIVE: The aim was to study the contractility of the conduit coronary artery to vasoactive agents in developing and established volume overload cardiac hypertrophy and to compare it with structural alterations in the artery. METHODS: Aortic valve insufficiency in rabbits was used to produce a volume overloaded heart. One month (developing hypertrophy), and four months (stabilised hypertrophy) after inducing aortic insufficiency, the isometric contraction of the coronary artery to acetylcholine, serotonin, and potassium chloride was recorded. For transmission electron microscopy, the coronary arteries were perfused via the ascending aorta with glutaraldehyde fixative under constant pressure. The point counting method was used for quantitative evaluation. Semithin sections were used to determine the geometry (ie, the inner diameter and wall thickness) of the coronary artery by light microscopy. RESULTS: A significant increase in heart weight and heart weight to body weight ratio was found after one month and four months of volume overload. Concentration-response relations of the coronary artery to all three agents were shifted to the right; in developing hypertrophy the shift was non-significant, in stabilised hypertrophy it was significant. The contractions were weakened by up to one fifth of the control values. An associated increase in wall thickness of the coronary artery was found, due to a significant expansion of the intercellular space. The internal diameter did not change significantly. Ultrastructural findings (an increase of the area occupied by organelles in myocytes) suggested a transition from "contractile" to more "synthetic" type of smooth muscle cells. CONCLUSIONS: In cardiac hypertrophy due to volume overload, the structure of the coronary arteries reflects the long term haemodynamic alterations, particularly through an increase in the non-cellular component. In parallel, the contraction efficiency to vasoactive drugs decreases markedly.

[The effect of long-term administration of metipranolol on passive diastolic properties of the hypertrophic ventricle]. / Vplyv dlhodobého podávania metipranololu na pasívne diastolické vlastnosti hypertrofovanej komory.

In the course of adaptation of the rabbit heart to volume load passive diastolic properties of the hypertrophic ventricle and myocardium were changing significantly. On day 30 following perforation of the aortic valve stiffness of the ventricle was reduced, yet normalized ventricular stiffness and myocardial stiffness were increased. These changes were prevented by beta adrenergic blockade during development of adaptation of the heart to volume load. Although ventricular stiffness was reduced, normalized ventricular stiffness and myocardial stiffness remained at the level of control values. The demonstrated effect of beta adrenergic blockade on passive diastolic properties of the ventricle and myocardium may be of value in preventing heart failure due to chronic hemodynamic load. (Tab.3,Ref.15.).

[Quantitative ultrastructural characteristics of mitochondria and myofibrils in the myocardium in chronic hemodynamic overload]. / Kvantitatívne ultrastruktúrne charakteristiky mitochondrií a myofibríl v myokarde pocas chronickej hemodynamickej zátaze.

Stereological morphometry was used to determine ultrastructural changes of the myocardium in the course of well defined chronic hemodynamic overload. Overload was induced in the hearts of rabbits by perforation of aortic valves. Relative volumes of mitochondria, myofibrils were measured in tissue samples taken from subendocardial and subepicardial region of the left ventricle. In the course of developing hypertrophy relative volume of mitochondria significantly increased as well as volume ratio Mi/Mf, while those of myofibrils decreased. Increased volume of mitochondria prolonged during the period of developed hypertrophy and its normalization occurred in the hypertrophy regression. Failure of the heart was characterized by increased volume of mitochondria and decrease those of myofibrils. Comparison of given morphometric data in subendocardium and subepicardium of the left ventricle did not find regional differences in subcellular composition of cardiomyocytes in the course of chronic hemodynamic overload.

[Passive diastolic properties of the left ventricle during development of cardiac hypertrophy]. / Pasívne diastolické vlastnosti l'avej komory v období vyvíjajúcej sa hypertrofie srdca.

Induced insufficiency of the aortal valve in rabbits is followed by gradual adaptation of the heart to volume load. In the period of developing hypertrophy, we studied the changes in the passive diastolic properties of the ventricle. By analyzing the passive relationship between the volume of the ventricular cavity and the intraventricular pressure, the stiffness of the ventricle, normalized ventricular stiffness, and myocardial stiffness were determined. On day 30 after inducing the volume verload, the stiffness constant of the ventricle was statistically significantly reduced, whereas the constant of normalized ventricular stiffness and the constant of myocardial stiffness were statistically significantly increased. The increased stiffness of the myocardium, which characterizes the volume verloaded, left ventricle in the period of developing hypertrophy, may represent one of the changes causing reversal of the adaptive response of the heart to hemodynamic verload after a certain period of time, gradually resulting in the development of the syndrome of heart failure.

Constriction ability of coronary artery in volume overload cardiac hypertrophy.

The constrictor response of the rabbit conduit coronary artery from hypertrophied heart (volume-overload stabilized hypertrophy) was studied to vasoactive substances. The heart/body weight ratio was 2.67 +/- 0.95 in the experimental group and 1.90 +/- 0.09 in the controls. The responses to acetylcholine, serotonin and potassium chloride was dose-dependent in the controls: the maximum amounted to 9.07 +/- 2.03 mN, 6.00 +/- 1.79 and 10.94 +/- 1.64 mN, respectively. Remarkably lower responses were detected in coronary arteries from hypertrophied hearts in the whole range of concentrations applied; the maximum was only 22.34 +/- 8.32% of the control response to acetylcholine, 17.83 +/- 11.37% to serotonin, and 21.74 +/- 5.50% to potassium chloride. A disbalance between stabilized cardiac hypertrophy and the remarkably low constrictor ability of the conduit coronary artery has been described.

Calcium transport by intracellular membrane structures in the myocardium of hypertrophied and failing hearts.

After inducing haemodynamic cardiac overload in rabbits, the authors studied in several stages (1-14 months) the calcium transport activity of the mitochondrial and sarcoplasmic myocardial fractions using labelled 45CaCl2. A coincidence was found between changes in myocardial contractility and changes in calcium transport activity of intracellular organelles. A possible important role of mitochondria in this adaptive process was also documented. Since the calcium transport capacity of the sarcoplasmic reticulum progressively decreases (with the exception of the earliest stages following overload induction), it seems that increased myocardial contractility ensures enhanced Ca transport activity of the mitochondria. Myocardial contractility drops only at the time when the Ca transport activity of the mitochondria decreases. Since these changes occur already at the time of regression of myocardial hypertrophy, which precedes heart failure, it can be assumed that they are causally connected with the reduced contractility of a failing heart.

Respiratory and oxidative phosphorylation of myocardial mitochondria in hypertrophied and failing hearts.

Respiratory and oxidative phosphorylation activity of mitochondria was studied in the course of the adaptation of the heart to haemodynamic overload in rabbit due to aortic valve insufficiency. In the period of developing cardiac hypertrophy, the rate of oxygen consumption in stage 3, i.e. in the stage of ATP formation, and the phosphorylation rate significantly increase. In the period of regression of cardiac hypertrophy, which precedes heart failure, the respiratory and oxidative phosphorylation activity does not significantly change. In a failing heart, the respiratory rate in stage 3 returns to normal and the phosphorylation rate increases in comparison with normal rabbits. The results of the study show that in the myocardium of hypertrophied non-failing as well as failing heart after prolonged haemodynamic overload, the primary function of mitochondria, i.e. energy production is sufficiently preserved.