Programmed death of myocytes occurs in the decompensated human heart in spite of the enhanced expression of BCL2; this phenomenon may contribute to the progression of cardiac dysfunction.

PTX3 is present in the intact myocardium, increases in the blood of patients with AMI, and disappears from damaged myocytes. We suggest that PTX3 is an early indicator of myocyte irreversible injury in ischemic cardiomyopathy.

To determine the effects of aging on the human myocardium, 67 O ne of the major difficulties encountered in the study of the effects of age on the cardiovascular system is the differentiation of the aging process itself from the presence of specific disease states. Atherosclerosis, diabetes, and ischemic heart disease are common events in humans, and the severity of these pathological conditions increases with age. Because the contribution of these variables to the alterations of the aged myocardium cannot easily be separated from the aging phenomenon alone, the changes of the heart throughout life are therefore the result of multifactorial events in which aging plays an important but indistinguishable role.1 There is no temporal reference point that can be used to distinguish between maturational changes beyond sexual maturity and the aging changes per se, since they are both controlled by time as a critical factor.'-3 Thus, the issue of whether aging of the heart has to be regarded as a successful adaptation or as a progressive disease state remains a matter of controversy, with data being accumulated in support of the former1-4 and the latter.5-9 However, it is well established that in both humans and animals myocyte proliferation occurs shortly after birth'0-13 and that the growth of the heart, during the relatively early phases of postnatal life and long before sexual maturity is reached, is controlled by hypertrophy of myocytesl213 and hyperplasia of capillary endothelial cells and interstitial fibroblasts.13 Although DNA synthesis with ploidy formation in adult human cardiac myocytes has been described,14-17 this phenomenon does not alter the number of muscle cells and/or muscle cell nuclei in the tissue, so that the total number of myocytes or myocyte nuclei in the ventricle can be used as an absolute reference parameter for the evaluation of the effects of aging on the myocardium. This approach was used in the present investigation to determine whether myocyte cell loss accompanies the life span of humans and may constitute the underlying cause for the occurrence of congestive heart failure in the elderly. Materials and Methods Study Design and Selection CriteriaSixty-seven human hearts were collected from a total number of 1,176 autopsies performed at the University Hospital of Parma Medical School during 1988 and 1989. All 67 hearts were collected within 24 hours after death. These cases were assumed to represent normal aging according to preautopsy criteria, autopsy criteria, and histological criteria, which are listed below.Preautopsy criteria for inclusion in the study. These criteria were as follows: 1) sudden death associated

Aging does not lead to myocyte cell loss and myocyte cellular reactive hypertrophy in women, indicating that gender differences may play a significant role in the detrimental effects of the aging process on the heart.

To determine the effects of loading on active and passive tensions, programmed cell death, superoxide anion formation, the expression of Fas on myocytes, and side-to-side slippage of myocytes, papillary muscles were exposed to 7-8 and 50 mN/mm2 and these parameters were measured over a 3-h period. Overstretching produced a 21-and a 2.4-fold increase in apoptotic myocyte and nonmyocyte cell death, respectively. Concurrently, the generation of reactive oxygen species increased 2.4-fold and the number of myocytes labeled by Fas protein 21-fold. Moreover, a 15% decrease in the number of myocytes included in the thickness of the papillary muscle was found in combination with a 7% decrease in sarcomere length and the inability of muscles to maintain stable levels of passive and active tensions. The addition of the NO-releasing drug, C87-3754, prevented superoxide anion formation, programmed cell death, and the alterations in active and passive tensions with time of overloaded papillary muscles. In conclusion, overstretching appears to be coupled with oxidant stress, expression of Fas, programmed cell death, architectural rearrangement of myocytes, and impairment in force development of the myocardium. (J. Clin. Invest. 1995. 96:2247-2259