1 Evaluation of Isovolumic Relaxation Phase in the Process of Ventricular Remodeling following Myocardial Infarction A. Kheradvar 1 , R.C. Gorman 2 , J.H. Gorman, III 2 , A. Zeeshan 2 , M. Gharib 1 1 Cardiovascular Research Laboratory, California Institute of Technology, Pasadena, CA 2 Harrison Department of Surgical Research, University of Pennsylvania, Philadelphia, PA Abstract- The course of cardiac remodeling after an acute cardiac MI, might affect the orientation of the cardiac muscle fibers as well as their contraction behavior. This may result in alteration of the untwisting during isovolumic relaxation phase, which might have effects on rapid early filling phase. In the present article, the variation of the time constant of isovolumic pressure drop (τ) has been studied during the course of cardiac remodeling after different types of induced myocardial infarction (MI) in sheep. The results for each group show different patterns of change in τ. The normalized τ curve in all three groups of anteroapical, anterobasal and posterobasal MI group show a rise 30 minutes after infarction. Two weeks later, the pressure drop constants decline to a lower level than baseline and by eight weeks after infarction, the time constant reached around the baseline level. Keywords-Isovolumic relaxation, pressure drop time constant, twisting, ventricular remodeling I. INTRODUCTION Nowadays, it has been widely accepted that left ventricular (LV) diastolic dysfunction may proceed to congestive heart failure [1]. Therefore, evaluation of diastolic function is crucial with the aim of early detection of dysfunctions. End stage LV dysfunction is generally associated with abnormal LV relaxation. The process of relaxation occurs mostly during the isovolumic relaxation phase of the cardiac cycle. Isovolumic relaxation time is described as the time between aortic valve closure and mitral valve opening when ventricular pressure drops rapidly. One of the representatives of the relaxation time is the time constant of isovolumic pressure drop (τ) [2], which is the time that pressure has fallen to approximately one-third (1/e≈1/3) of the end-systolic pressure. Since the duration of diastole is limited, particularly during tachycardia, early filling has to be both rapid and large magnitude. Thus the rate of development of pressure difference must also be rapid and of large amplitude [3]. Untwisting, which occurs largely during isovolumic relaxation, is associated with the release of restoring forces that had been accumulated during systole and is thought to contribute to diastolic suction [4,5,6]. It has been also believed that the extent of LV torsion is correlated with the cavity pressure and its recoil rate is related to the rate of pressure drop [7]. Several mathematical models have been developed based on empirical data for describing the course of pressure drop in isovolumic relaxation phase. One of the models, which is frequently used, is the mono-exponential equation: ∞ − + = P e P P t τ 0 Where P is the LV pressure, is the pressure at minimal dP/dt [8], t is the time thereafter, τ is the pressure drop time constant and represents the pressure asymptote. 0 P ∞ P The course of cardiac remodeling after an acute cardiac MI, might affect the orientation of the cardiac muscle fibers as well as their contraction behavior. This may result in alteration of the untwisting during isovolumic relaxation phase, which might have effects on rapid early filling phase. In the present article, the variation of the time constant of isovolumic pressure drop (τ) has been studied during the course of cardiac remodeling after different types of induced myocardial infarction (MI) in sheep. II. METHODOLOGY Twenty Dorsett hybrid sheep between 35 and 45 kg were anesthetized and underwent left thoracotomy and ligation of two major coronary arteries. Six sheep had ligation of the distal left anterior descending and second diagonal arteries. This infarction involves 22±3 % of the left ventricular mass and leads to the development LV aneurysms