TY - JOUR
T1 - Effects of captopril on contractility after myocardial infarction
T2 - Experimental observations
AU - Litwin, Sheldon E.
AU - Raya, Thomas E.
AU - Warner, Alberta
AU - Litwin, Christine M.
AU - Goldman, Steven
N1 - Funding Information:
From the Departments of Internal Medicine and Pathology, Tucson Veterans Administration Medical Center, and the University of Arizona Heart Center, Tucson, Arizona. Supported by grants from the Arizona Afhliate of the American Heart Association, National American Heart Association, Arizona Disease Control Research Commission, Veterans Administration, and the National Institutes of Health (HL-20984). The data in this article have been published previously in part in Circulation (1988;77:1424-1431) Circulation Research (1989;64:330-338) and Circulation (1991;83:1028-1037). Address for reprints: Steven Goldman, MD, Cardiology lllC, Tucson Veterans -4dministration Medical Center, Tucson, Arizona 85723.
PY - 1991/11/18
Y1 - 1991/11/18
N2 - After large myocardial infarction, compromised left ventricular (LV) function and changes in the peripheral circulation result in the syndrome of chronic congestive heart failure. Although treatment with angiotensin-converting enzyme inhibitors improve cardiovascular function, it is difficult to determine whether this benefit is due to changes in organ versus muscle function. The rat model of heart failure, created by ligating the left coronary artery, results in pathophysiology that is similar to that seen in patients, i.e., increased LV end-diastolic pressure and volume, hypertrophy of the noninfarcted myocardium, prolongation of the time constant of LV relaxation, decreased venous compliance, and increased total blood volume. In noninfarcted papillary muscles, isolated from rats with heart failure, maximal developed tension and peak rate of tension rise ( +dT dt) are decreased, time to peak tension is prolonged, and myocardial stiffness is increased. Morphologic changes include an increase in papillary muscle myocyte cross-sectional area and an increase in myocardial hydroxyproline content. Captopril (2 g/liter drinking water) alters LV loading by decreasing arterial pressure, increasing venous compliance, and decreasing blood volume. This results in a decrease in LV end-diastolic pressure and volume. In the noninfarcted myocardium, time to peak tension is shortened, whereas developed tension, +dT dt, and muscle stiffness remain abnormal. Captopril decreases myocyte cross-sectional area, but collagen content remains elevated. Thus, in the rat infarct model of heart failure, treatment with captopril alters LV remodeling and hypertrophy but produces only modest improvement in muscle function. In this model, after treatment for 3 weeks, it appears that the major benefit from angiotensin-converting enzyme inhibition is due to improvements in organ function resulting from changes in loading conditions, whereas muscle function remains compromised.
AB - After large myocardial infarction, compromised left ventricular (LV) function and changes in the peripheral circulation result in the syndrome of chronic congestive heart failure. Although treatment with angiotensin-converting enzyme inhibitors improve cardiovascular function, it is difficult to determine whether this benefit is due to changes in organ versus muscle function. The rat model of heart failure, created by ligating the left coronary artery, results in pathophysiology that is similar to that seen in patients, i.e., increased LV end-diastolic pressure and volume, hypertrophy of the noninfarcted myocardium, prolongation of the time constant of LV relaxation, decreased venous compliance, and increased total blood volume. In noninfarcted papillary muscles, isolated from rats with heart failure, maximal developed tension and peak rate of tension rise ( +dT dt) are decreased, time to peak tension is prolonged, and myocardial stiffness is increased. Morphologic changes include an increase in papillary muscle myocyte cross-sectional area and an increase in myocardial hydroxyproline content. Captopril (2 g/liter drinking water) alters LV loading by decreasing arterial pressure, increasing venous compliance, and decreasing blood volume. This results in a decrease in LV end-diastolic pressure and volume. In the noninfarcted myocardium, time to peak tension is shortened, whereas developed tension, +dT dt, and muscle stiffness remain abnormal. Captopril decreases myocyte cross-sectional area, but collagen content remains elevated. Thus, in the rat infarct model of heart failure, treatment with captopril alters LV remodeling and hypertrophy but produces only modest improvement in muscle function. In this model, after treatment for 3 weeks, it appears that the major benefit from angiotensin-converting enzyme inhibition is due to improvements in organ function resulting from changes in loading conditions, whereas muscle function remains compromised.
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U2 - 10.1016/0002-9149(91)90258-M
DO - 10.1016/0002-9149(91)90258-M
M3 - Article
C2 - 1746417
AN - SCOPUS:0026331894
SN - 0002-9149
VL - 68
SP - 26
EP - 34
JO - The American Journal of Cardiology
JF - The American Journal of Cardiology
IS - 14
ER -