Severe myocardial dysfunction induced by ventricular remodeling in aging rat hearts.
To determine if aging engenders alterations in the functional properties of the myocardium and ventricular remodeling, the hemodynamic performance and structural characteristics of the left ventricle of male Fischer 344 rats at 4, 12, 20, and 29 mo of age were studied by quantitative physiology and morphology. In vivo assessment of cardiac pump function showed no change up to 20 mo, whereas left ventricular end-diastolic pressure was increased at 29 mo. Moreover, peak rates of pressure rise and decay, stroke volume, ejection fraction, and cardiac output were depressed at the later age interval, demonstrating the presence of ventricular failure at this time. The measurements of chamber size and wall thickness showed that ventricular end-diastolic and end-systolic volumes progressively increased with age with the greatest change occurring at 20-29 mo. Aging was also accompanied by a marked augmentation in the volume fraction of fibrotic areas in the ventricular myocardium that was due to an increase in their number and cross-sectional area with time. These architectural rearrangements, in combination with the abnormalities in ventricular function, resulted in an elevation in the volume of wall stress throughout the cardiac cycle. Wall stress increased by 64, 44, and 50% from 4 to 12, 12 to 20, and 20 to 29 mo of age. In conclusion, aging leads to a continuous rise in wall stress that is not normalized by ventricular remodeling. These two independent processes appear to be responsible for the onset of heart failure in the senescent rat.
Capasso
J M
JM
Department of Pathology, New York Medical College, Valhalla 10595.
Palackal
T
T
Olivetti
G
G
Anversa
P
P
D000375:Aging / Q000502:physiology*; D000818:Animals; D001835:Body Weight; D009202:Cardiomyopathies / Q000503:physiopathology*; D006321:Heart / Q000033:anatomy & histology / Q000254:growth & development*; D006352:Heart Ventricles; D006439:Hemodynamics; D008297:Male; D009929:Organ Size; D051381:Rats; D011916:Rats, Inbred F344; D013314:Stress, Mechanical; D013318:Stroke Volume; D014655:Vascular Resistance