Myocardial hypertrophy and enhanced left ventricular contractility in Zucker diabetic fatty rats.

Heart failure is known to be a complication of insulin-dependent (IDDM) and noninsulin-dependent diabetes mellitus (NIDDM) even in the absence of coronary heart disease or hypertension. The mechanisms leading to diabetic cardiomyopathy are unknown. The aim of the study was to characterize structural and functional alterations in hyperinsulinemic Zucker diabetic fatty (ZDF) rats treated with or without insulin. Diabetic animals showed a twofold increase in cardiomyocyte volume with increased left ventricular ANP but not BNP mRNA levels in spite of a reduced plasma renin activity (PRA) 2 months after onset of diabetes compared to nondiabetic littermates. These changes were associated with an increase in left ventricular performance as assessed by echocardiography. Insulin treatment led to a significant increase in body weight (BW), total heart weight, myocardial protein content, and left ventricular mass (LVM). Perivascular fibrosis and laminin thickness were significantly augmented in diabetic rat myocardium irrespective of insulin treatment, whereas interstitial collagen I and fibronectin were similarly found in diabetic and control myocardium. Initial stages of diabetic cardiomyopathy in hyperinsulinemic rats are characterized by cardiomyocyte hypertrophy and enhanced cardiac contractility. It is suggested that hyperinsulinemia may be involved in cardiac hypertrophy.     

Effect of diurnal variability of heart rate on development of arrhythmia in patients with chronic obstructive pulmonary disease

We examined the possible effect of diurnal variability of heart rate on the development of arrhythmias in patients with chronic obstructive pulmonary disease (COPD). Forty-one COPD patients (M/F: 39/2, mean age: 59+/-8.5 years) and 32 (M/F: 27/5, mean age: 57+/-11 years) healthy controls were included. Twenty-four hour ECG recordings were analyzed for atrial fibrillation (AF) or ventricular premature beats (VPB), and circadian changes in heart rate variability (HRV) were assessed by dividing the 24-h period into day-time (08:00-24:00 h) and night-time (24:00-08:00 h) periods. Night-time total (TP), low frequency (LF) and high frequency (HF) powers were similarly lower from day-time parameters in AF(-) COPD patients (HF 3.91+/-1 vs. 4.43+/-1.04 ms(2), P=0.001) and controls (HF 3.95+/-0.72 vs. 4.82+/-0.66 ms(2), P<0.001). The LF/HF ratios were also significantly reduced in the same patient groups (AF(-) COPD 1.35+/-0.21 vs. 1.27+/-0.19, P=0.04, controls 1.43+/-0.14 vs. 1.24+/-0.09, P<0.001). Night-time TP and LF were increased, HF unchanged and LF/HF significantly increased (1.11+/-0.25 vs. 1.19+/-0.27, P<0.05) in AF(+) COPD patients. Frequency of VPB was correlated with corrected QT dispersion (QTc(d)) (r=0.52, P=0.001) and the day-time/night-time HF ratio (r=0.43, P=0.02). Patients with QTc(d)>or=60 ms did not have the expected increase in night-time HF and had a statistically insignificant increase in LF/HF ratio. In COPD patients with QTc(d)<60 ms, circadian changes in HRV parameters were parallel with the controls. We concluded that COPD patients with arrhythmia had circadian HRV disturbances such as unchanged night-time parasympathetic tone and disturbed sympatho-vagal balance in favor of the sympathetic system all day long, which may explain the increased frequency of arrhythmia.     

Early assessment of percutaneous coronary interventions for chronic total occlusions analyzed by novel echocardiographic techniques

OBJECTIVE:

Successful revascularization of chronic total occlusions has been associated with improved left ventricular systolic function, reduced anginal symptoms, increased exercise capacity, and increased survival. This study was conducted to determine the impact of revascularization in chronic total occlusion on left ventricular function using novel echocardiographic techniques.

METHODS:

A total of 129 patients with chronic total occlusion who underwent revascularization between April 2011 and November 2012 were included in this study. Echocardiographic assessments with two-dimensional speckle tracking echocardiography and real-time three-dimensional echocardiography were performed before the procedure and one month after the procedure. The left ventricular ejection fraction, left ventricular volumes, and three-dimensional systolic dyssynchrony index were quantified.

RESULTS:

An immediate procedural success was obtained in 118 patients (91.5%). There were no acute or subacute stent thromboses during follow-up. The mean left ventricular ejection fraction significantly increased (p<0.001), while the left ventricular end-diastolic and end-systolic volumes significantly decreased (p = 0.001 and p<0.001, respectively). The three-dimensional systolic dyssynchrony index also decreased significantly (p<0.001). The global longitudinal strain showed a significant increase after successful revascularization (p<0.001). An increase in the global longitudinal strain was correlated with an increase in the left ventricular ejection fraction (r = 0.27, p = 0.02). The patients with a left ventricular ejection fraction ≥50% displayed a greater improvement in the global longitudinal strain, and the patients with diabetes showed less improvement.

CONCLUSIONS:

Using novel echocardiographic techniques, our results showed that restoring the coronary blood flow in chronic total occlusion patients reduces the left ventricular volumes and improves the left ventricular ejection fraction and the global longitudinal strain of hibernating myocardium.     

The effects of Pilates on metabolic control and physical performance in adolescents with Type 1 diabetes mellitus

Physical activity is a substantial method in the management of children and adolescents with Type 1 diabetes mellitus but it is not considered as a treatment for diabetes. The aim of this study was to investigate the effects of Pilates exercises on metabolic control and physical performance in patients with type 1 diabetes mellitus. Thirty one sedentary patients with type 1 diabetes mellitus, ranging in age from 12 to 17 (experimental group, n=17 and control group, n=14) were submitted to 12 weeks of Pilates training. Participants underwent tests to determine the physical performance and metabolic control before and after 12 weeks of Pilates session. At the end of study, there were significant alterations in physical performance of the study group. Peak power, mean power, vertical jump and flexibility of study group increased. There were no alterations for this parameters in the control group. There was no significant difference for glycated hemoglobin (HbA1c) in both groups. Conclusions: Physical performance increased via Pilates exercises in the patients with type 1 DM. However there were no changes in metabolic control. In the present study, the positive effects of exercise on metabolic control could not be shown in patients with Type 1 DM.     

Pannexin‐1 and P2X7‐Receptor Are Required for Apoptotic Osteocytes in Fatigued Bone to Trigger RANKL Production in Neighboring Bystander Osteocytes

Osteocyte apoptosis is required to induce intracortical bone remodeling after microdamage in animal models, but how apoptotic osteocytes signal neighboring “bystander” cells to initiate the remodeling process is unknown. Apoptosis has been shown to open pannexin‐1 (Panx1) channels to release adenosine diphosphate (ATP) as a “find‐me” signal for phagocytic cells. To address whether apoptotic osteocytes use this signaling mechanism, we adapted the rat ulnar fatigue‐loading model to reproducibly introduce microdamage into mouse cortical bone and measured subsequent changes in osteocyte apoptosis, receptor activator of NF‐κB ligand (RANKL) expression and osteoclastic bone resorption in wild‐type (WT; C57Bl/6) mice and in mice genetically deficient in Panx1 (Panx1KO). Mouse ulnar loading produced linear microcracks comparable in number and location to the rat model. WT mice showed increased osteocyte apoptosis and RANKL expression at microdamage sites at 3 days after loading and increased intracortical remodeling and endocortical tunneling at day 14. With fatigue, Panx1KO mice exhibited levels of microdamage and osteocyte apoptosis identical to WT mice. However, they did not upregulate RANKL in bystander osteocytes or initiate resorption. Panx1 interacts with P2X₇R in ATP release; thus, we examined P2X₇R‐deficient mice and WT mice treated with P2X₇R antagonist Brilliant Blue G (BBG) to test the possible role of ATP as a find‐me signal. P2X₇RKO mice failed to upregulate RANKL in osteocytes or induce resorption despite normally elevated osteocyte apoptosis after fatigue loading. Similarly, treatment of fatigued C57Bl/6 mice with BBG mimicked behavior of both Panx1KO and P2X₇RKO mice; BBG had no effect on osteocyte apoptosis in fatigued bone but completely prevented increases in bystander osteocyte RANKL expression and attenuated activation of resorption by more than 50%. These results indicate that activation of Panx1 and P2X₇R are required for apoptotic osteocytes in fatigued bone to trigger RANKL production in neighboring bystander osteocytes and implicate ATP as an essential signal mediating this process. © 2016 American Society for Bone and Mineral Research.     

Structural and Mechanical Repair of Diffuse Damage in Cortical Bone In Vivo

Physiological wear and tear causes bone microdamage at several hierarchical levels, and these have different biological consequences. Bone remodeling is widely held to be the mechanism by which bone microdamage is repaired. However, recent studies showed that unlike typical linear microcracks, small crack damage, the clusters of submicron‐sized matrix cracks also known as diffuse damage (Dif.Dx), does not activate remodeling. Thus, the fate of diffuse damage in vivo is not known. To examine this, we induced selectively Dif.Dx in rat ulnae in vivo by using end‐load ulnar bending creep model. Changes in damage content were assessed by histomorphometry and mechanical testing immediately after loading (ie, acute loaded) or at 14 days after damage induction (ie, survival ulnae). Dif.Dx area was markedly reduced over the 14‐day survival period after loading (p < 0.02). We did not observe any intracortical resorption, and there was no increase in cortical bone area in survival ulnae. The reduction in whole bone stiffness in acute loaded ulnae was restored to baseline levels in survival ulnae (p > 0.6). Microindentation studies showed that Dif.Dx caused a highly localized reduction in elastic modulus in diffuse damage regions of the ulnar cortex. Moduli in these previously damaged bone areas were restored to control values by 14 days after loading. Our current findings indicate that small crack damage in bone can be repaired without bone remodeling, and they suggest that alternative repair mechanisms exist in bone to deal with submicron‐sized matrix cracks. Those mechanisms are currently unknown and further investigations are needed to elucidate the mechanisms by which this direct repair occurs. © 2014 American Society for Bone and Mineral Research