ity of myocytes consistent with cell prolif-

long-term mechanical stress (51. When hemodynamic load is chronically elevated, cardiac

mass may reach levels that far exceed normal, in which case, further cell enlargement (or hypertrophy) rather than cell proliferation (or hyperplasia) is responsible for this increase in weight beyond that of normal growth 03. consistent observations of myocyte ~y~~ropbic, but not pro~i~~rat~v~. growth have led to the concept that adult my “terminally differentiated” and are devoid of the capacity of FU

mo~hornet~~ anAy& of the myoca autopsy series of elderly subjects, w increases in ventricular weight. The in the total number of myocyte nuclei as well as the cell size per nucleus in the senescent, hy~~rophied ventricles chal-

ma of the terminally differentiated myocyte. They conclude that the marked increase in ven- tricular weight is a consequence of an expansion of intersti- tial area and an increase in the number of myocyaes as well as an increase in myocytc volume (7). The authors appropri- ately acknowledge the limitations of their study, particularly

ii: assessment of the ave volume per nucleus i tion of binucleated conclude that at least a component of the increase in the

*Editorials published in Journal of the American College of Cardiology rs and do not necessarily represent the views of

, Harvard Medical School. Brigham and

. Marc A. Pfeffer, Cardiovascular Divi- sion. Bri&am and Women’s Hospital, 75 Francis Street, Boston, Massachu- setts 02115.

strated that under pathologic co

structural dilation requires a major reorientation (remodel- ing) of both the myocyte and interstitial components. In the aged myocardium under stress, the interaction between the interstitium and the myocyte may lead to an alteration in the genetic expression of the myocytes. Reciprocal cell- to-cell interactions between the microvascular endothe~ium and adult myocytes in coculture (20) may provide a clue for the unusual finding of latent mitotic activity of ahe myocyte under a major mechanicall stress.

The coupling of cell size and cardiac chamber configura- tion during normal growth and the compensated phase of hypertrophy underscore the feedback control between me- chanical stress and growth. Several possible transducers of mechanical load and myocyte growth have been proposed (21-23). This important work, however, focuses on the acute

a 1994 by the Americrn College of Cardiology 073%1097/94/$7.00

3.

4.

5.

6.

7.

pro~~fe~tioa dut ing cardiac growth. Am J Cardiol 1973;3 I :

phic senebcent heart in humans. J Am Colt Cardiol 1994:24:146-Y.

ajstura 4. Zhsng X, Reiss K. et al. Myocyte celhlar hyperplasia and rtrophy cor~t~bute to chronic ventricular remodel-

ing in coroa~y artery ~~owia~~nduce~ cardiomyopathy in rats. Circ

kiss K, ~ajst~~ J, Capasso JM. arino TA. Anversa P. Impairment of

myocyte conIractility fol~ow~Rg coronary artery narrowing is associated with activation of the myocyte RX1 autocrine system, ea~aaced expres- sion of late growth related genes, DNA synthesis, and myocyte nuclear

10. Lanzbach Al.

CJ. Left vent~c~~ar ens-svst~lic volume as the maior determinant fir survival after recovery fro& myocardi

V.

infarction. ~~rc~~at~o~ P987;76: 44-51.

Ot!en TW. Plod& Qariables prediclive of survival in pat~eats with coronary disease: ction by univariate and rna~t~va~~ate analyses from the chnical, e~ect~card~o~mphic, exercise, ~e~~~ra~~~c, and quantitative a~~io~~p~ic evaluations. Circulation

deter MA, Plappert T, et al. Quaniitative two- rdiographic aleas~reme~ts are major predictors of

adverse cardiovascular events after acute myocardial infarction: the sits of captopril. Circulation ~~4~8~68-75. o~o~~ca~ significance of cardiac ~~y~~ro~hy. Am 3 Cardiol

McLaurin LD. Wall stress and patterns of n left ventricle. J Clin invest l975;56:56-64.

Weber RT. Janicki JS. The heart as a ~~~sc~e~p~rnp system and the concept of heart failure. Am Heart J 1979;98:371-84. Pord LE. Heart size. Circ Res ~976;39:299-3~3. Pfetfer MA, Bwunwal E. Ventricular remodeling after myocardial ~ofa~ctioa: experimental observations and clinical implications. Circula- tion 1 ;81:1161-72. Ross J Jr, So~~enblic~ ED., Taylor RR, Spotnitz NM, Cove11 J Diastolic geometry and sarcomere lengths in the chronically dilated canine left ventricle. Circ Res 1971;28:49-61.

Sprinebora JP, Kelly RA, Smith TW. Cell-cell signaliug between adult rat ventricular myocy?es and cardiac microvascular endo-

21.

22.

23.

24.

thelial cells in hete~otypic primary culture. 9 Clin Invest 1993;91: 1934-41. Rent RL, Rozich JD, cCollam Pt.. et al. Rapid expression of the Na+-Ca’+ exchanger i response to cardiac pressure overload. Am J Pkysiol 1993:265:H1024-9. Sadoshima I, Xu Y, Slayter HLS. lzumo S. Autocrine release ofangioten- sin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell 1993;7.5:977-84. Chien RR. Knowlton KU, Zhu M. Chien S. Regulation of cardiac gene expression during myocardial growth and hyy rtropby: molecular studies of al adaptiv Schwartz 14. Lompre AM, Mercadier 35. Switches in cardiac muscle gene expression as a result of pressure and volume overload. Am J Physiol 1992;262:R364-9.