VENTRICULAR PERFORMANCE Myocardial relaxation : effects of preload on the time course of isovolumetric relaxation

We studied the effect of an isolated increase in preload on isovolumetric relaxation in the intact dog heart and isometric relaxation in isolated cardiac muscle (dog and rat) preparations. In eight anesthetized dogs, 8 to 12 ml of blood was infused into the left ventricle during a single diastole. The exponential time constant (T) of isovolumetric relaxation was measured in single-beat experiments in which the left ventricular systolic pressure increased (112 ± 2 to 128 ± 3 mm Hg; p < .05, n = 62). In a second series of experiments, left ventricular systolic pressure was held constant (109 ± 2 to 107 + 2 mm Hg; p = NS, n = 23) by simultaneous ventricular infusion and aortic unloading. In the first protocol, T increased from 28.0 ± 0.4 to 30.7 ± 0.4 msec (p < .05), whereas in the second protocol (constant systolic pressure) there was no change in T. The time course of isometric relaxation was also studied in six rat left ventricular papillary muscles and four dog right ventricular trabecular muscles. Preload was varied from 30% to 100% of the peak of the isometric length-tension curve in each muscle. Over this wide range of preload, the isometric force decline recordings were superimposable as long as the comparisons were made at equal levels of total load. Thus an isolated increase in preload does not influence the time course of isovolumetric relaxation. Circulation 73, No. 5, 1037-1041, 1986. THE TIME COURSE of left ventricular isovolumetric pressure decline is determined by a series of interacting factors, including loading conditions, the inactivation rate of individual fibers, and the degree of fiber inhomogeneity within the wall of the ventricle.1 These factors are continuously modulated by autonomic tone and metabolic events, and for these reasons it is difficult to interpret some of the reported changes in left ventricular isovolumetric relaxation rate. For example, angina pectoris is associated with an apparent stiffening of the left ventricular chamber, which is widely thought to be caused by impaired or slowed myocardial relaxation.2 Because ischemia also produces changes in several of the factors that may independently influence the time course of left ventricular relaxation, Raff and Glantz3 reasoned that changes in relaxation "could have been due to the changes in the load the heart faces rather than any direct effect on the relaxing system." From the Department of Medicine (Cardiology), Tufts University School of Medicine, and the Veterans Administration Medical Center, Boston. Supported by grant HL28377 from the NHLBI and by Medical Research Funds from the Veterans Administration. Address for correspondence: William H. Gaasch, M.D., Cardiology Section, Veterans Administration Medical Center, 150 South Huntington Ave., Boston, MA 02130. Received Dec. 30, 1985; accepted Jan. 30, 1986. Vol. 73, No. 5, May 1986 These investigators then went on to assess whether an increase in left ventricular preload could be responsible for an increase in the time constant of left ventricular isovolumetric pressure decline (T). They found that volume loading slows T in the intact dog heart and, on the basis of a multivariate analysis, concluded that this effect was a reflection of the dependence of relaxation on both left ventricular end-diastolic pressure and aortic systolic pressure. In conscious dogs, however, Karliner et al.4 found that primary changes in afterload produced changes in T, but volume infusion did not produce such changes. We also found that modest changes in left ventricular preload did not influence T, but when volume loading was sufficient to produce an increase in aortic pressure, T increased.5 To date, there are no published studies that define the effects of an isolated increase in left ventricular preload on isovolumetric relaxation. Accordingly, we designed the present series of experiments to assess the effect of a pure increase in preload on isovolumetric relaxation in the intact dog heart and isometric relaxation in isolated cardiac muscle preparations.