Abstract-In cardiomyocytes, generation of restoring forces (RFs) responsible for elastic recoil involves deformation of the sarcomeric protein titin in conjunction with shortening below slack length. At the left ventricular (LV) level, recoil and filling by suction require contraction to an end-systolic volume (ESV) below equilibrium volume (Veq) as well as large-scale deformations, for example, torsion or twist. Little is known about RFs and suction in the failing ventricle.We undertook a comparison of determinants of suction in open-chest dogs previously subjected to 2 weeks of pacing tachycardia (PT) 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 diastoles, allowing measurement of fully relaxed pressure at varying volumes. We quantified twist with sonomicrometry. We also assessed transmural ratios of N2B to N2BA titin isoforms and total titin to myosin heavy chain (MHC) protein. In PT, the LV did not contract below Veq, even with marked reduction of volume (end-diastolic pressure [EDP], 1 to 2 mm Hg), whereas in controls ESV was less than Veq when EDP was less than Ϸ5 mm Hg. In PT, both systolic twist and diastolic untwisting rate were reduced, and there was exaggerated transmural variation in titin isoform and titin-to-MHC ratios, consistent with the more extensible N2BA being present in larger amounts in the subendocardium. Thus, in PT, determinants of suction at the level of the LV are markedly impaired. The altered transmural titin isoform gradient is consistent with a decrease in RFs and may contribute to these findings. Key Words: suction Ⅲ restoring forces Ⅲ diastole Ⅲ heart failure Ⅲ tachycardia D iastolic suction results from compression and/or deformation of elastic elements in the wall of the ventricle, with storage of potential energy generated during systole in the form of a restoring force (RF) that is converted to recoil and ultimately kinetic energy (mitral inflow) during filling. [1][2][3][4][5][6][7] Inherent in this definition is the requirement that the ventricle be the source of energy driving mitral flow, ie, it must actively lower its pressure below the atrium. Ventricular filling can also occur as a result of an atrioventricular pressure gradient dictated by the level of atrial pressure at the time the mitral valve opens. In this case, atrial pressure is higher than diastolic ventricular pressure whether or not suction is present.In the cardiomyocyte, deformation of the sarcomeric protein titin during contraction below slack length is the source of a RF. 8 Titin is a large, filamentous protein extending from Z-to M-line of the sarcomere, with the segment spanning from near the Z-line to the A-band acting as a molecular spring. Titin is the major determinant of passive mechanical properties of the cardiomyocyte in sarcomeres stretched above and shortened below slack length. 8,9 In large mammals, titin exists as 2 isoforms with differing mechanical properties. 9 The smaller, N2B, isoform is st...

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Physical activity energy expenditure (PAEE) is a determinant of prognosis and fitness in older patients with coronary heart disease (CHD). PAEE and total energy expenditure (TEE) are closely related to fatness, physical function, and metabolic risk in older individuals. The goal of this study was to assess effects of resistance training on PAEE, TEE, and fitness in older women with chronic CHD and physical activity limitations (N = 51, mean age: 72 + 5 yr). The study intervention consisted of a progressive, 6-mo program of resistance training vs. a control group condition of low-intensity yoga and deep breathing. The study interventions were completed by 42 of the 51 participants. The intervention group manifested a 177 +/- 213 kcal/day (+9%) increase in TEE, pre- to posttraining, measured by the doubly labeled water technique during a nonexercise 10-day period (P < 0.03 vs. controls). This was due to a 50 +/- 74 kcal/day (4%) increase in resting metabolic rate measured by indirect calorimetry (P < 0.01, P < 0.05 vs. controls) and a 123 +/- 214 kcal/day (9%) increase in PAEE (P < 0.03, P = 0.12 vs. controls). Resistance training was associated with significant increases in upper and lower body strength, but no change in fat-free mass, measured by dual X-ray absorptiometry, or left ventricular function, measured by echocardiography and Doppler. Women in the control group showed no alterations in TEE or its determinants. There were no changes between groups in body composition, aerobic capacity, or measures of mental depression. These results demonstrate that resistance training of 6-mo duration leads to an increase in TEE and PAEE in older women with chronic CHD.

The oral glycoprotein IIb/IIIa antagonist sibrafiban achieved effective, long-term platelet inhibition with a clear dose-response but at the expense of a relatively high incidence of minor bleeding. Oral IIb/IIIa inhibition deserves further study as a new treatment strategy in patients after acute coronary syndromes.