Beat-to-beat regulation of left ventricular function in the intact cardiovascular system

A variety of regulatory mechanisms have evolved to control the heart's pump function because the cardiovascular system must continually adapt to the changing demands that body functions place on it. This regulation takes place through many physiological systems; however, fine adjustments in cardiac pumping probably require adaptations more quickly than external control mechanisms (such as the autonomic nervous system) can compensate. Thus cardiac pumping is also regulated by mechanisms intrinsic to the heart. To better understand these intrinsic control mechanisms, we studied the beat-to-beat response of left ventricular function to continually varying changes in loading conditions produced by transiently occluding the pulmonary artery, venae cavae, and aorta. We used multiple linear regression to identify and quantify the important beat-to-beat determinants of left ventricular systolic function, quantified as stroke work. We could not adequately explain or predict beat-to-beat changes in stroke work with traditional determinants of ventricular function, preload, afterload, and heart rate, because a large systematic error remains after taking these traditional determinants of function into account. To eliminate this systematic error, we had to include some function of previous beat stroke volume and end-systolic size and pressure. This additional information significantly improved both our ability to model the observed transient changes in left ventricular stroke work and to predict additional observations that were not used to develop our model. We conclude that previous beat contraction history is an important determinant of left ventricular function and implies an important regulatory mechanism whereby the left ventricle can fine tune its function from beat to beat in response to continually changing loading conditions.