Citations

Abstract Aims Heart failure (HF) patients breathe with a rapid shallow pattern during exercise. This study examined the relationship between cardiac size and tachypnoeic breathing in HF patients during exercise. Methods and results Thirty-seven HF patients [age = 55 ± 13 years, ejection fraction (EF) = 27 ± 10%, New York Heart Association (NYHA) class = 2.3 ± 1.2] and 42 controls (CTL) (age = 56 ± 14 years, EF = 63 ± 8%) were recruited. Participants underwent maximal exercise testing, pulmonary function testing, and chest radiography for calculation of total thoracic cavity volume (TTCV), diaphragm, heart, and lung volumes. Heart failure patients were divided into two groups: Group A = cardiac volume < median (n = 18) and Group B = cardiac volume ≥ median of the HF patients (n = 19). There was no difference between groups for TTCV (CTL = 8203 ± 1489 vs. Group A = 8694 ± 1249 vs. Group B = 8195 ± 1823 cm3). Cardiac volume was different between groups for both absolute (CTL = 630 ± 181 vs. Group A = 894 ± 186 vs. Group B = 1401 ± 382 cm3, P< 0.001 for all comparisons) and %TTCV (CTL = 8 ± 2 vs. Group A = 10 ± 1 vs. Group A = 18 ± 5%, P< 0.001 for all comparisons). Similarly, total lung volume as a %TTCV was significantly different among the groups (CTL = 70 ± 4 vs. Group A = 65 ± 5 vs. Group A = 58 ± 7%, P< 0.01 for all comparisons). In HF patients, there was a trend (P = 0.10) towards an independent association between cardiac size and tidal volume (VT) at 75% of VO2 peak whereas this relationship was statistically significant at VO2 peak (P = 0.02) as patients with larger cardiac size had reduced VT. Conclusion This study demonstrates the close relationship between cardiac size and breathing pattern during exercise in HF patients. These results suggest cardiac size may pose a significant constraint on the lungs during exercise and may contribute to tachypnoeic breathing.

Cdc20 is an activator of the anaphase-promoting complex/cyclosome that initiates anaphase onset by ordering the destruction of cyclin B1 and securin in metaphase. To study the physiological significance of Cdc20 in higher eukaryotes, we generated hypomorphic mice that express small amounts of this essential cell cycle regulator. In this study, we show that these mice are healthy and not prone to cancer despite substantial aneuploidy. Cdc20 hypomorphism causes chromatin bridging and chromosome misalignment, revealing a requirement for Cdc20 in efficient sister chromosome separation and chromosome–microtubule attachment. We find that cyclin B1 is newly synthesized during mitosis via cytoplasmic polyadenylation element–binding protein-dependent translation, causing its rapid accumulation between prometaphase and metaphase of Cdc20 hypomorphic cells. Anaphase onset is significantly delayed in Cdc20 hypomorphic cells but not when translation is inhibited during mitosis. These data reveal that Cdc20 is particularly rate limiting for cyclin B1 destruction because of regulated de novo synthesis of this cyclin after prometaphase onset.

SAGE-Journals-Accessible-Video-Player 10.1089/vid.2010.0114.M1 sj-vid-1-vid-10.1089_vid.2010.0114

Objective— To determine whether serum levels of N-terminal (NT) pro–B-type natriuretic peptide (pro-BNP) are higher in patients with poorly compressible arteries (PCA) than in patients with peripheral artery disease (PAD) and control subjects without PCA or PAD. Methods and Results— Medial arterial calcification in the lower extremities results in PCA and may be associated with increased arterial stiffness and hemodynamic/myocardial stress. PCA was defined as having an ankle-brachial index >1.4 or an ankle blood pressure >255 mm Hg, whereas PAD was defined as having an ankle-brachial index ≤0.9. Study participants with PCA (n=100; aged 71±10 years; 70% men) and age- and sex-matched patients with PAD (n=300) were recruited from the noninvasive vascular laboratory. Age- and sex-matched controls (n=300) were identified from a community-based cohort and had no history of PAD. NT pro-BNP levels were approximately 2.5-fold higher in patients with PCA than in patients with PAD and approximately 4-fold higher than in age- and sex-matched controls. In multivariable regression analyses that adjusted for age, sex, smoking, hypertension, history of coronary heart disease/stroke, systolic blood pressure, and serum creatinine, NT pro-BNP levels remained significantly higher in patients with PCA than in patients with PAD and controls ( P <0.001). Conclusion— Patients with medial arterial calcification and PCA have higher serum levels of NT pro-BNP than patients with PAD and controls, which is suggestive of an adverse hemodynamic milieu and increased risk for adverse cardiovascular outcomes.

Tendon disuse, or stress deprivation, frequently accompanies clinical disorders and treatments, yet the metabolism of tendons subject to stress deprivation has rarely been investigated systematically. The effects of stress deprivation on canine flexor tendon were investigated in this study. One adult canine forepaw was suspended for 21 or 42 days. Control forepaws were collected from dogs that had no intervention on their limbs and paws. The expression of collagen I and III was not significantly altered in the tendons disused for 21 days but was significantly decreased at 42 days ( P < 0.03). The expression of collagen II, aggrecan, decorin, and fibronectin was significantly decreased in the tendons in the suspended limbs at 21 days ( P < 0.002) and further reduced at 42 days. With stress deprivation, the expression of matrix metalloproteinase 2 (MMP2) was significantly increased ( P < 0.004) at 21 and 42 days. The expression of MMP3 was significantly decreased at 21 and 42 days ( P < 0.03). The expression of MMP13 was not altered with stress deprivation at 21 and 42 days. The expression of MMP14 was significantly increased at 21 days ( P = 0.0015) and returned to the control level at 42 days. Tissue inhibitor of metalloproteinase 1 (TIMP1) expression was decreased after the limbs were suspended for 42 days ( P = 0.0043), but not 21 days. However, TIMP2 expression was not significantly different from control at 21 or 42 days. Furthermore, the cross-sectional area of the stress-deprived tendons at 42 days was decreased compared with the control group ( P < 0.01). The intervention method in this study did not result in any alteration of stiffness of the tendon. Our study demonstrated that stress deprivation decreases the anabolic process and increases the catabolic process of extracellular matrix in flexor tendon.