No description available.

Left Ventricular Hypertrophy (LVH) is common in Type 2 Diabetes (T2DM) and despite optimal treatment of blood pressure can still persist. We know LVH is a cardiovascular (CV) risk factor in its own right and contributes to high CV event rates in patients with T2DM. Apart from hypertension, other factors contribute to the development of LVH in patients with T2DM, in particular oxidative stress (OS) has been implicated in LVH development. Allopurinol is a potent anti-oxidant, acting by blocking the enzyme Xanthine Oxidase, and has been previously shown to reduce vascular OS. Therefore the main aim of this thesis was to investigate whether allopurinol regresses LVH in patients with T2DM. The trial design was a randomised, double blind, placebo controlled study in 66 patients with T2DM with echocardiographic evidence of LVH. Allopurinol 600mg/day or placebo was given for nine months over the study period. The primary outcome was reduction in left ventricular mass (LVM) as calculated by cardiac magnetic resonance imaging (CMR) at baseline and at nine months follow-up. The secondary end-points were change in flow mediated dilatation (FMD) and augmentation index (AIx). Allopurinol significantly reduced absolute LVM (-2.65 ± 5.91g and placebo group +1.21 ± 5.10g (p=0.012)) and LVM indexed to body surface area (-1.32 ± 2.84g/m2 and placebo group +0.65 ± 3.07g/m2 (p=0.017)). When analysis was made of high and low baseline LVM then the effects of allopurinol were exaggerated in the high LVM mass group. No significant change was seen in either FMD or AIx. This thesis shows that allopurinol regresses LVM in patients with T2DM and LVH and controlled blood pressure. Regressing LVH has been shown previously to improve CV mortality and morbidity. Therefore allopurinol may become a useful therapy to reduce CV events in T2DM patients with LVH.

Hokkaido University (北海道大学) / 博士 / 医学

The contribution of left ventricular (LV) torsion and recoil in augmenting stroke volume during exercise is poorly understood. This study examined the effects of aging on LV torsion and recoil at rest and during sub-maximal exercise in 11 young (YU) and 9 older, untrained males (OU), and 12 age-matched older, endurance-trained males (OT) in upright and supine body positions. LV torsion increased from rest to exercise in YU in upright and supine body positions (9.9±2.3 to 13.2±5.2 degrees, p=.03, and 8.8±3.8 to 12.8±6.6 degrees, p=.02, respectively), but not in OU. LV torsion increased with exercise in the supine body position only in OT (p=.046). There were no differences in EDV or change in ESV with supine exercise across groups suggesting that once the Frank-Starling mechanism is fully recruited, the young heart, and that of older, endurance-trained subjects may augment SV by increasing LV torsion and contractility rather than contractility alone.

The contribution of left ventricular (LV) torsion and recoil in augmenting stroke volume during exercise is poorly understood. This study examined the effects of aging on LV torsion and recoil at rest and during sub-maximal exercise in 11 young (YU) and 9 older, untrained males (OU), and 12 age-matched older, endurance-trained males (OT) in upright and supine body positions. LV torsion increased from rest to exercise in YU in upright and supine body positions (9.9±2.3 to 13.2±5.2 degrees, p=.03, and 8.8±3.8 to 12.8±6.6 degrees, p=.02, respectively), but not in OU. LV torsion increased with exercise in the supine body position only in OT (p=.046). There were no differences in EDV or change in ESV with supine exercise across groups suggesting that once the Frank-Starling mechanism is fully recruited, the young heart, and that of older, endurance-trained subjects may augment SV by increasing LV torsion and contractility rather than contractility alone.

Diss. (sammanfattning) Umeå : Univ., 2004. / Härtill 4 uppsatser.

Background: Adrenomedullin has been demonstrated to cause systemic vasodilation, and increased plasma adrenomedullin levels have been observed in cardiovascular disease states such as heart failure. While adrenomedullin receptors have been localized to the myocardium, the effects of adrenomedullin on human myocyte contractility remained unknown. Methods and Results: Left ventricular myocytes were isolated from myocardial biopsies of patients (n = 16) undergoing elective coronary artery bypass surgery with normal left ventricular ejection fractions (51 ± 1%). A total of 233 left ventricular myocytes were studied by videomicroscopy. Myocyte shortening velocity (μm/s) was measured at baseline and following the addition of either 3 nM, 30 nM, or 60 nM of adrenomedullin. The change in myocyte shortening velocity with increasing concentrations of adrenomedullin was computed. At all concentrations, adrenomedullin reduced myocyte shortening velocity from baseline values (P < 0.05). Next, the potential interaction of adrenomedullin with the β-adrenergic receptor system was examined using 25 nM isoproterenol. The β-adrenergic receptor-mediated increase in the myocyte shortening velocity was blunted with adrenomedullin (29 ± 7 vs 63 ± 13 μm/s, P < 0.05). Conclusions: These unique findings demonstrate that adrenomedullin reduced contractility in isolated human left ventricular myocytes and exhibited a negative interaction with the β-adrenergic receptor system. Past studies have shown that adrenomedullin induces nitric oxide synthesis and that nitric oxide can uncouple myocyte metabolism. Thus, while adrenomedullin causes systemic vasodilation, this peptide can also exert a negative contractile effect in human left ventricular myocytes.

No description available.

Increasing diastolic dysfunction (DD) grade is associated with increased heart failure (HF). Patients with preserved ejection fractions and grade 1 DD may have left atrial dilatation, e′ < 8 cm/sec, increased left ventricular (LV) mass, or variable E/e′ ratios. The aim of this study was to test the hypothesis that LV hypertrophy or E/e′ ratio > 8 may be associated with a greater incidence of HF. Methods Two hundred twelve patients with grade 1 DD and ejection fractions > 50% were retrospectively studied. Group 1 comprised 108 patients with E/A ratios < 0.8, without LV hypertrophy, e′ < 8 cm/sec, and E/e′ ratios < 8. Group 2 comprised 104 patients with LV hypertrophy or E/e′ ratios > 8. Patients with incident HF and valvular or coronary disease were excluded. Using two-dimensional Doppler echocardiography, LV and left atrial volumes and transmitral spectral and tissue Doppler were analyzed. Medical records were examined for laboratory data, HF admissions, and all-cause mortality from 2004 to 2012. Results Despite similar ejection fractions, patients in group 2 had greater LV and left atrial volumes, LV mass index values, and E/e′ ratios (P < .01 for all). HF incidence was greater in group 2 (30 vs 4, P < .001). Combined HF or all-cause mortality was greater in group 2 (46 vs 14, P < .001). Multivariate analysis revealed that HF was associated with E/e′ ratio (P < .0001), systolic blood pressure (P = .0123), and LV mass index (P = .042). Combined HF or all-cause mortality was associated with E/e′ ratio (P < .0001), LV mass index (P = .009), and lower calcium channel blocker use (P = .0011). Conclusions HF alone or HF and all-cause mortality were increased in patients with grade 1 DD in the presence of LV hypertrophy or elevated LV filling pressures.

Background: Chronic aortic regurgitation (AR) patients demonstrate left ventricular (LV) remodeling with increased LV mass and volume but may have a preserved LV ejection fraction (EF). We hypothesize that in chronic AR, global longitudinal systolic and diastolic function will be reduced despite a preserved LV EF. Methods: We studied with Doppler echocardiography 27 normal subjects, 87 patients with chronic AR with a LV EF > 50% (AR + PEF), 66 patients with an EF < 50% [AR + reduced LV ejection fraction (REF)] and 82 patients with hypertensive heart disease. LV volume, transmitral spectral and tissue Doppler were obtained. Myocardial velocities and their timing and longitudinal strain of the proximal and mid wall of each of the 3 apical views were obtained. Results: As compared to normals, global longitudinal strain was reduced in AR + PEF (13.8 ± 4.0%) and AR + REF (11.4 ±4.7%) vs. normals (18.4 ± 3.6%, both p < 0.001). As an additional comparison group for AR + PEF, global longitudinal strain was reduced as compared to patients with hypertensive heart disease (p = 0.032). The average peak diastolic annular velocity (e’) was decreased in AR + PEF (6.9 ± 3.3 cm/s vs. 13.4 ± 2.6 cm/s, p < 0.001) and AR + REF (4.8 ± 2.1 cm/s, p < 0.001). Peak rapid filling velocity/e’ (E/e’) was increased in both AR + PEF (14.4 ± 6.2 vs. 6.2 ± 1.3, p < 0.001) and AR + REF (18.8 ± 6.4, p <0.001 vs. normals). Independent correlates of global longitudinal strain (r = 0.6416, p < 0.001) included EF (p < 0.0001), E/e’ (p < 0.0001), and tricuspid regurgitation velocity (p = 0.0176). Conclusion: With chronic AR, there is impaired longitudinal function despite preserved EF. Moreover, global longitudinal strain was well correlated with noninvasive estimated LV filling pressures and pulmonary systolic arterial pressures.