The effect of lathyrogen beta-amino proprionitrile (BAPN) on the mechanical properties of experimentally hypertrophied rat cardiac muscle.

Abstract

SUMMARY yS-Amino proprionitrile (BAPN) at dietary concentrations of 1, 5, and 10 g BAPN/kg rat chow was administered to rats for 14-21 days following surgical constriction of the ascending aorta. Five and 10 g BAPN/kg rat chow prevented the increase in left ventricular collagen content which occurred with cardiac hypertrophy in rats following aortic constriction. In spite of this block in the increase in collagen in the ventricles, isolated trabecular muscles from hypertrophied hearts showed a decrease in maximum velocity of shortening at a preload of 0.5 g/mm 2 (max V) and an increase in time to peak tension as compared with values for sham-operated animals. Max V for rats with aortic constriction was decreased 0.57 muscle length/sec as compared with sham-operated animals (P< 0.01) whereas time to peak tension was prolonged by 12 msec (P < 0.05). In rats with aortic constriction receiving 10 g BAPN/kg rat chow, max V was decreased 0.66 muscle length/sec (P < 0.05), and time to peak tension was prolonged by 21 msec (P < 0.001). Resting tension was increased to 1.70 ± 0.18 (mean ± SEM) g/mm 2 as compared with shams (1.22 ± 0.10 g/mm 2 ; P < 0.002) in cardiac hypertrophy without BAPN. However, the increase in resting tension was not seen when animals with aortic constriction received 10 g BAPN/kg rat chow [1.23 ± 0.9 g/mm 2 as compared with shams, 1.15 ± 0.09 g/mm 2 (not significant)]. We conclude that the decrease in maximum velocity of shortening and prolongation of time to peak tension in experimental cardiac hypertrophy occur independently of elevated collagen content, whereas elevations in resting tension appear to depend upon an increase in collagen content of these hearts.IN THE past decade, numerous studies have attempted to characterize the mechanical performance of hypertrophied cardiac muscle. Several investigators 1 " 6 have reported a decrease in maximum shortening velocity of hypertrophied cardiac muscle when the hypertrophy was induced by a pressure overload. Whether the decrease in shortening velocity reflects a depression of cardiac "contractility" is a matter of controversy. 7 " 9 It seems clear, nonetheless, that an abnormality of cardiac performance follows acute experimental pressure overload. Additional mechanical changes have been described to accompany cardiac hypertrophy induced by pressure overload. These include a prolongation of contraction 2 ' 4l 6 and a change in passive compliance. 2 ' 5 In addition to the increase in RNA 10 ' n and protein synthesis, 12 ' 13 which accompanies experimental cardiac hypertrophy, enhanced thymidine incorportion into DNA has been demonstrated primarily in fibroblasts. 11 ' 14 ' lb Also, increased quantities of collagen are found in hypertrophied heart muscle. 2 ' 16 " 18 /?-amino proprionitrile (BAPN) is a lathyrogen which has been shown in vivo and in tissue culture to inhibit the cross-linking of collagen 19 ' 20 and elastin 21 probably by blocking the initial step in the enzymatic conversion of lysyl residues in peptide linkages to their aldehyde de...

Hydroxyproline and passive stiffness of pressure-induced hypertrophied kitten myocardium.

“…Furthermore, the constant hydroxyproline concentration as hypertrophy developed also is opposite that observed by others in pressure-induced cardiac hypertrophy (3,5,6). Comparison of this and previous studies revealed that these differences could not be attributed to differences in species studied (2,4,5) or extent of hypertrophy (1,2,4).…”

“…The anatomic determinants of passive stiffness have not been elucidated completely although there is considerable evidence that the connective tissue matrix and its collagen component play a major role (3,28). Many authors have measured collagen as hydroxyproline since traditionally it has been believed that hydroxyproline formed a constant fraction of mammalian collagen (29).…”

“…An increase in passive stiffness of pressure-induced hypertrophied myocardium in the experimental animal has been observed by several investigators (1)(2)(3) including ourselves (4). Furthermore, the increase in passive stiffness would appear to be due at least in part to a concomitant increase in collagen that accompanies the hypertrophic process (3,(5)(6)(7).…”

“…Furthermore, the increase in passive stiffness would appear to be due at least in part to a concomitant increase in collagen that accompanies the hypertrophic process (3,(5)(6)(7). However, it is unclear whether these changes represent a fundamental characteristic of pressure-induced hypertrophy or a peculiarity of the experimental model.…”

The isolated working heart model in infarcted rat hearts

“…Due to impaired CO and loss of heart contractility (Pfeffer et al 1979, Fellenius et al 1985, Pfeffer & Pfeffer 1987, the arterial mean BP could not be reached. In case of an increase of left ventricular filling pressure (Pfeffer et al 1979, Pfeffer & Pfeffer 1987, an increase of myocardial stiffness and wall tension due to fibrosis (Bing et al 1978, Hess et al 1981, Thiedemann et al 1983, Carroll et al 1989, Jalil et al 1989, there is no increase in LVPs because of the loss of heart contractility and therefore loss of pressure in the systole of the infarcted rat heart (Bing et al 1995).…”