Alterations in the determinants of diastolic suction during pacing tachycardia

In cardiomyocytes, generation of restoring forces (RFs) responsible for ela stic recoil involves deformation of the sarcomeric protein titin in conjunc tion with shortening below slack length. At the left ventricular (LV) level , recoil and filling by suction require contraction to an end-systolic volu me (ESV) below equilibrium volume (Veq) as well as large-scale deformations , for example, torsion or twist. Little is known about RFs and suction in t he failing ventricle. We undertook a comparison of determinants of suction in open-chest dogs previously subjected to 2 weeks of pacing tachycardia (P T) and controls. To assess the ability of the LV to contract below Veq, we used a servomotor to clamp left atrial pressure and produce nonfilling dias toles, allowing measurement of fully relaxed pressure at varying volumes. W e quantified twist with sonomicrometry, We also assessed transmural ratios of N2B to N2BA titin isoforms and total titin to myosin heavy chain (MHC) p rotein. In PT, the LV did not contract below Veq, even with marked reductio n of volume (end-diastolic pressure [EDP], 1 to 2 mm Hg), whereas in contro ls ESV was less than Veq when EDP was less than approximate to 5 mm Hg. In PT, both systolic twist and diastolic untwisting rate were reduced, and the re was exaggerated transmural variation in titin isoform and titin-to-MHC r atios, consistent with the more extensible N2BA being present in larger amo unts in the subendocardium. Thus, in PT, determinants of suction at the lev el of the LV are markedly impaired. The altered transmural titin isoform gr adient is consistent with a decrease in RFs and may contribute to these fin dings.