Insights into the pathogenesis of vein graft disease: lessons from intravascular ultrasound

The success of coronary artery bypass grafting (CABG) is limited by poor long-term graft patency. Saphenous vein is used in the vast majority of CABG operations, although 15% are occluded at one year with as many as 50% occluded at 10 years due to progressive graft atherosclerosis. Intravascular ultrasound (IVUS) has greatly increased our understanding of this process. IVUS studies have shown that early wall thickening and adaptive remodeling of vein grafts occurs within the first few weeks post implantation, with these changes stabilising in angiographically normal vein grafts after six months. Early changes predispose to later atherosclerosis with occlusive plaque detectable in vein grafts within the first year. Both expansive and constrictive remodelling is present in diseased vein grafts, where the latter contributes significantly to occlusive disease. These findings correlate closely with experimental and clinicopathological studies and help define the windows for prevention, intervention or plaque stabilisation strategies. IVUS is also the natural tool for evaluating the effectiveness of pharmacological and other treatments that may prevent or slow the progression of vein graft disease in clinical trials

The poly-omics of ageing through individual-based metabolic modelling

Abstract Background Ageing can be classified in two different ways, chronological ageing and biological ageing. While chronological age is a measure of the time that has passed since birth, biological (also known as transcriptomic) ageing is defined by how time and the environment affect an individual in comparison to other individuals of the same chronological age. Recent research studies have shown that transcriptomic age is associated with certain genes, and that each of those genes has an effect size. Using these effect sizes we can calculate the transcriptomic age of an individual from their age-associated gene expression levels. The limitation of this approach is that it does not consider how these changes in gene expression affect the metabolism of individuals and hence their observable cellular phenotype. Results We propose a method based on poly-omic constraint-based models and machine learning in order to further the understanding of transcriptomic ageing. We use normalised CD4 T-cell gene expression data from peripheral blood mononuclear cells in 499 healthy individuals to create individual metabolic models. These models are then combined with a transcriptomic age predictor and chronological age to provide new insights into the differences between transcriptomic and chronological ageing. As a result, we propose a novel metabolic age predictor. Conclusions We show that our poly-omic predictors provide a more detailed analysis of transcriptomic ageing compared to gene-based approaches, and represent a basis for furthering our knowledge of the ageing mechanisms in human cells

The Relationship Between Coronary Pressure During Reperfusion and Myocardial Recovery After Hypothermic Cardioplegia

The aim of this study was to document the relationship between coronary pressure during reperfusion and myocardial recovery after hypothermic cardioplegia. Isolated canine hearts perfused by a support dog were subjected to 2 hours of cardioplegia at 20°C. Three hearts were reperfused at each of the following pressures: 20, 40, 60, 80, 100, and 150 mm Hg. The reperfusion period lasted 30 minutes, with the pressure being raised gradually from zero to the test level over the first 2 minutes, then being held constant until the end of the period. The results showed that the normal dog heart after 2 hours of hypothermic cardioplegia is tolerant to a wide range of coronary pressures during reperfusion. Hearts reperfused at pressures between 40 and 100 mm Hg had similar values for coronary blood flow, coronary sinus oxygen saturation, myocardial oxygen consumption, lactate flux, contractility, and myocardial adenosine triphosphate content. If coronary reperfusion pressure was 10 mm Hg, myocardial rewarming was delayed, myocardial oxygen consumption was decreased, and myocardial ischemia was manifested by marked lactate efflux, high myocardial lactate concentration, and depletion of adenosine triphosphate. If pressure was 150 mm Hg, coronary flow was excessive. To place these results in the context of coronary artery disease, we measured reperfusion pressure in coronary arteries distal to a stenosis in 10 patients studied at the time of coronary bypass grafting. In 13 arteries with major stenoses, distal mean coronary pressure averaged 31 mm Hg while the simultaneously measured mean aortic or radial artery pressure averaged 66 mm Hg. Thus the average gradient across the stenoses was 35 mm Hg (range 15 to 60 mm Hg). We concluded that in normal hearts without ischemic damage, reperfusion can be conducted satisfactorily at mean coronary pressures from 40 to 100 mm Hg. In setting the tolerable limits for reperfusion pressure in patients with severe coronary artery disease, one should make allowance for pressure gradients of up to 60 mm Hg between the aorta and the distal coronary artery

Impact of coenzyme Q-10 on parameters of cardiorespiratory fitness and muscle performance in older athletes taking statins

Many older athletes take statins, which are known to have potential for muscle toxicity. The adverse effects of statins on muscles and the influence thereof on athletic performance remain uncertain. Coenzyme Q-10 (CoQ10) may improve performance and reduce muscle toxicity in older athletes taking statins. This trial was designed to evaluate the benefits of CoQ10 administration for mitochondrial function in this population. Twenty athletes aged ≥ 50 years who were taking stable doses of statins were randomized to receive either CoQ10 (200 mg daily) or placebo for 6 weeks in a double-blind, placebo-controlled, crossover study to evaluate the impact of CoQ10 on the anaerobic threshold (AT). Several secondary endpoints, including muscle function, cardiopulmonary exercise function, and subjective feelings of fitness, were also assessed. The mean (SD) change in AT from baseline was -0.59 (1.2) mL/kg/min during placebo treatment and 2.34 (0.8) mL/kg/min during CoQ10 treatment (P = 0.116). The mean change in time to AT from baseline was significantly greater during CoQ10 treatment than during placebo treatment (40.26 s vs 0.58 s, P = 0.038). Furthermore, muscle strength as measured by leg extension repetitions (reps) increased significantly during CoQ10 treatment, with a mean (SD) increase from baseline of 1.73 (2.9) reps during placebo treatment versus 3.78 (5.0) reps during CoQ10 treatment (P = 0.031). Many other parameters also tended to improve in response to CoQ10 treatment. Treatment with CoQ10 improved AT in comparison with baseline values in 11 of 19 (58%) subjects and in comparison with placebo treatment values in 10 of 19 (53%) subjects. Treatment with CoQ10 (200 mg daily) did not significantly improve AT in older athletes taking statins. However, it did improve muscle performance as measured by time to AT and leg strength (quadriceps muscle reps). Many other measures of mitochondrial function also tended to improve during CoQ10 treatment