Sarcomere length-tension relationship in failing human myocardium

Abstract

The Starling relationship is a fundamental component of cardiac muscle physiology. Although many researchers have studied the length-tension relationship in human myocardium, none have done it at the sarcomere level. The present study examined the effects of sarcomere length (SL) on contractile parameters in cardiac trabeculae from ischemic and non-ischemic failing human hearts, as well as those mechanically unloaded by a left ventricular assist device (LVAD).Methods:Using laser diffraction techniques, resting SLs were measured in right ventricular cardiac trabeculae (n 10: Average dimensions (mm): 0.33 0.05 Width, 0.19 0.01 Thickness, 2.94 0.32 Length) from failing human hearts. As muscle length was incremented in a stepwise manner (25.0 um/step), resting SL and isometric contractile tension were assessed. Based on the SL-tension relationship, we determined the SLs that produced a developed tension of 20, 50, and 80% of maximal developed tension (Tmax) for each trabeculae. Results: For all groups, developed tension, rate of maximal tension rise, and rate of maximal tension decline all increased linearly as SL was increased. Diastolic tension increased minimally between SLs of 1.7 um to 2.0 um, and in some cases at SLs beyond 2.0 um, it increased in a nonlinear fashion. The SL associated with a particular percent of Tmax was remarkably consistent across all trabeculae: 1.92 0.02 um 20%(Tmax-To); 2.09 0.02 um 50%(Tmax-To); and 2.25 ± 0.01 um 80%(Tmax-To); (To represents the minimal developed tension). These relationships did not seem to be affected by etiology or prior LVAD support. Conclusion: SL can be reliably measured in very thin cardiac trabeculae from human hearts. Although the shapes of the active SL-tension relationships are quite similar, there is substantial heterogeneity in the shapes of the passive SL-tension relationships. Our study also shows that Tmax, often used as a starting point during in vitro analysis, is achieved at non-physiological SLs ( 2.35 um). Therefore, in studies where SL cannot be measured, using a percent of the tension between Tmax and To one can reliably set the preload at a more physiologic SL.