Assessment of mitochondrial respiratory capacity in relation to cardiac contractile performance in patients with normal to mildly decreased cardiac systolic function.

Chronic heart failure (CHF) with reduced left ventricular ejection fraction (LVEF) is associated with remodeling of cardiac energy metabolism; however, experimental data from human hearts that are still in early stages of contractile decline are very sparse. In the current study, we probed the association between LV contractility and myocardial capacity for fatty acid and carbohydrate oxidation in patients having normal-to-mildly decreased systolic function. In patients undergoing coronary artery bypass grafting surgery (n=40, EF ≥40%), a sample of left ventricular myocardium was obtained by subepicardial needle biopsy. Mitochondrial respiratory capacity, as well as oxidation of individual fatty acid and carbohydrate substrates (palmitoyl-carnitine and pyruvate, respectively), were assessed by measuring the rate of oxygen consumption. Also, expression of key mitochondrial metabolic factors and tissue accumulation of ceramide were evaluated, and correlation analysis was performed. Maximal mitochondrial respiration, and expression of mitochondrial biogenesis and remodeling factors (PGC-1α and mitofusin-2) were positively correlated with LVEF (r=0.37-0.50; P<0.05). Although there was no relationship between LVEF and respiration driven by individual metabolic substrates, LVEF was positively correlated with expression of key ß-oxidation enzymes. Finally, LVEF was inversely correlated with accumulation of cardiotoxic ceramide (r=0.89, P<0.05). In patients with coronary artery disease exhibiting normal-to-mildly decreased LVEF, cardiac systolic function is associated with mitochondrial respiratory capacity and levels of fatty acid oxidation enzymes, pointing to them as factors involved in early phases of myocardial pathological remodeling.

The use of systematic reviews to justify anaesthesiology trials: A meta-epidemiological study.

AIMS: New randomized clinical trials (RCTs) should be initiated if previous systematic reviews (SRs) indicate that new trials are needed. We analysed whether RCTs published in anaesthesiology journals mentioned previous SRs as a rationale for conducting trial and for discussing results. METHODS: This was a meta-epidemiological, descriptive cross-sectional study. We analysed RCTs published in the seven first-quartile anaesthesiology journals between 2014 and 2016. We studied text and bibliography of the RCTs to assess whether the authors made a reference to previous SRs when justifying the need for their own clinical trial and discussing the results. RESULTS: In the 622 studied RCTs 126 (20%) mentioned verbatim or cited one or more SRs as justification for conducting a trial, most commonly in introduction of a manuscript. Almost half of the included RCTs (44%) did not cite a single systematic review. There was no significant difference between the years in the number of explicitly mentioned SRs as justification for conducting a trial (F = 0.540, p = 0.583). Trials citing, mentioning or explicitly using SRs as a justification were published in journals with significantly higher impact factor and included significantly higher number of participants, while there was no difference in using SRs in trials in terms of funding type, type of intervention or positive versus negative results. CONCLUSIONS: Trialists should use evidence from existing SRs for planning a trial, while ethics committees, peer-reviewers and editors should require authors to provide evidence that a new trial is indeed necessary. SIGNIFICANCE: Since less than a fifth of trials published in high-impact journals in the field of anaesthesiology explicitly mention previous systematic review as a justification for conducting the trial, authors, ethics committees, editors and peer-reviewers need to increase their awareness of the need for proper justification regarding the necessity for a new trial.

Trimetazidine does not alter metabolic substrate oxidation in cardiac mitochondria of target patient population.

BACKGROUND AND PURPOSE: Trimetazidine, known as a metabolic modulator, is an anti-anginal drug used for treatment of stable coronary artery disease (CAD). It is proposed to act via modulation of cardiac metabolism, shifting the mitochondrial substrate utilization towards carbohydrates, thus increasing the efficiency of ATP production. This mechanism was recently challenged; however, these studies used indirect approaches and animal models, which made their conclusions questionable. The goal of the current study was to assess the effect of trimetazidine on mitochondrial substrate oxidation directly in left ventricular myocardium from CAD patients. EXPERIMENTAL APPROACH: Mitochondrial fatty acid (palmitoylcarnitine) and carbohydrate (pyruvate) oxidation were measured in permeabilized left ventricular fibres obtained during coronary artery bypass grafting surgery from CAD patients, which either had trimetazidine included in their therapy (TMZ group) or not (Control). KEY RESULTS: There was no difference between the two groups in the oxidation of either palmitoylcarnitine or pyruvate, and in the ratio of carbohydrate to fatty acid oxidation. Activity and expression of pyruvate dehydrogenase, the key regulator of carbohydrate metabolism, were also not different. Lastly, acute in vitro exposure of myocardial tissue to different concentrations of trimetazidine did not affect myocardial oxidation of fatty acid. CONCLUSION AND IMPLICATIONS: Using myocardial tissue from CAD patients, we found that trimetazidine (applied chronically in vivo or acutely in vitro) had no effect on cardiac fatty acid and carbohydrate oxidation, suggesting that the clinical effects of trimetazidine are unlikely to be due to its metabolic effects, but rather to an as yet unidentified intracardiac mechanism.

Predictors of competitive achievement among pubescent synchronized swimmers: an analysis of the solo-figure competition.

AIM: This study examined the applicability of sport-specific fitness tests (SSTs), anthropometrics, and respiratory parameters in predicting competitive results among pubescent synchronized swimmers. METHODS: A total of 25 synchronized swimmers (16-17 years; 166.2 ± 5.4 cm; and 58.4 ± 4.3 kg) volunteered for this study. The independent variables were body mass, body height, Body Mass Index (BMI), body fat percentage (BF%), lean body mass percentage, respiratory variables, and four SSTs (two specific power tests plus one aerobic- and one anaerobic-endurance test). The dependent variable was competitive achievement in the solo figure competition. The reliability analyses, Pearson's correlation coefficient and forward stepwise regression were calculated. RESULTS: The SSTs were reliable for testing fitness status among pubescent synchronized swimmers. The forward stepwise regression retained two SSTs, BF% and forced vital capacity (FVC, relative for age and stature) in a set of predictors of competitive achievement. Significant Beta coefficients are found for aerobic-endurance, SST and FVC. CONCLUSION: The sport-specific measure of aerobic endurance and FVC appropriately predicted competitive achievement with regard to the figures used in the competition when competitive results (the dependent variable) were obtained. Athletes and coaches should be aware of the probable negative influence of very low body fat levels on competitive achievement.