Effects of Captopril on Contractility After Myocardial Infarction: Experimental Observations Sheldon E. Litwin, MD, Thomas E. Raya, MD, Alberta Warner, MD, Christine M. Litwin, MD, and Steven Goldman, MD After large myocardial infarction, compromised left ventricular (LV) function and changes in the peripheral circulation result in the syndrome of chronic congestiie heart failure. Although treat- ment with angitiensin-converting enzyme inhibi- tors improve cardiovascular function, it is diicult to determine whether thii benefit is due to changes in organ versus muscle functiin. The rat model of heart failure, created by ligating the left coronary artery, results in pathophysiology that is similar to that seen in patkmts, i.e., increased LV end-diastolic: pressure and volume, hypettro- phy of the noninfarcted myocardium, prolonga- tion of the time constant of LV relaxation, de- creased venous compliance, and increased total blood volume. In noninfarcted papillary muscles, isolated from rats with heart failure, maximal de- veloped tension and peak rate of tension rise (sdT/c/t) are decreased, time to peak tension is prolonged, and myocardial stiiess is increased. Morphologic changes include an increase in pap- illary muscle myocyte cross-sectional area and an increase in myocardial hydroxyproline con- tent. Captopril(2 g/liter drinking water) atters LV loading by decreasie arterial pressure, increas- ing venous compliance, and decreasing blood volume. This results in a decrease in LV end-dias- tolii pressure and volume. In the noninfarcted myocardium, time to peak tension is shortened, From the Departments of Internal Medicine and Pathology, Tucson Veterans Administration Medical Center, and the Univer- sity of Arizona Heart Center, Tucson, Arizona. Supported by grants from the Arizona Afhliate of the American Heart Associa- tion, 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. whereas developed tension, +dT/dt, and muscle sttt remain abnormal. Captopril decreases myocyte cross-sectional area, but collagen con- tent remains elevated. Thus, in the rat infarct model of heart failure, treatment with captopril alters LV remodeling and hypertrophy but pro- duces only modest improvement in muscle func- tion. In thii model, after treatment for 3 weeks, it appears that the major benefit from angiotensin- converting enzyme inhibition is due to improve- ments in organ function resulting from changes in loadiN condiiins, whereas muscle function re- mains compromised. (Am J Cardiil1991;68:26D44D) arge L myocardial infarction frequently pro- duces progressive left ventricular (LV) dila- tion and hypertrophy of myocytes in the noninfarcted myocardium. These changes in LV geometry, referred to as LV remodeling, may contribute to development of the syndrome of chronic congestive heart failure. Laboratory and clinical studies have shown that treatment of heart failure with angiotensin-converting enzyme (ACE) inhibitors, such as captopril, can improve LV function and survival.‘-9 Although it is commonly believed that the beneficial effects of captopril are due to improvement in ventricular loading condi- tions, this explanation may be too simplistic. We hypothesized that following large myocardial infarc- tion, functional impairment of noninfarcted myo- cardium would occur due to the increased load borne by the residual myocytes. Unloading these myocytes might be expected to result in a gradual improvement in their function. Because of the complex effects of simultaneous changes in myocar- dial function, ventricular geometry, and ventricular- vascular coupling on global LV function, it is difficult to assess the relative importance of changes in each area. This report focuses on our efforts to 26D THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 68 NOVEMBER 18, 1991