Study protocol - Prospective case-control trial - Impact of significant carotid stenosis on retinal perfusion measured with automated retinal oximetry.

BACKGROUND: Large vessel carotid stenosis is a significant cause of ischaemic stroke. Indications for surgical revascularisation depend on the severity of the stenosis and clinical symptoms. However, mild symptoms such as TIA (Transient ischaemic attack), amaurosis fugax or minor stroke precede large strokes in only 15% of cases. AIM: The aim of this prospective study is to evaluate whether retinal perfusion is impacted in significant carotid stenosis. Automated retinal oximetry will be used to better assess perfusion in the post-stenotic basin. We presume the more stenotic the blood vessel, the more reduced the retinal perfusion is, resulting in adaptive changes such as greater arteriovenous saturation difference due to greater oxygen extraction. This could broaden the indication spectrum for revascularisation for carotid stenosis. METHODS: We plan to enroll yearly 50 patients with significant carotid stenosis and cross-examine them with retinal oximetry. The study group will provide stenotic vessels and, non-stenotic vessels will form the control group. Patients with significant carotid stenosis will undergo an MRI (Magnetic Resonnance imaging) examination to determine the presence of asymptomatic recent ischaemic lesions in the stenotic basin, and the correlation to oximetry parameters. STATISTICS: The stenosis severity and retinal oximetry parameters will be compared for study and control groups with a threshold of 70%, respectively 80% and 90% stenosis. Results will be then reevaluated with emphasis on MRI findings in the carotid basin. CONCLUSION: This prospective case control study protocol will be used to launch a multicentre trial assessing the relationship between significant carotid stenosis and retinal perfusion measured with automated retinal oximetry. Despite these differences, the findings indicate the potential of retinal oximetry for noninvasive real-time measurements of oxyhaemoglobin saturation in central nervous system vessels. Following calibration upgrade and technological improvement, verification retinal oximetry may potentially be applied to critically ill and anaesthesia care patients. The study on combined scanning laser ophthalmoscope and retinal oximetry supports the feasibility of the technique for oximetry analysis in newly born babies. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT06085612.

Arterio-venous balance studies of skeletal muscle fatty acid metabolism: What can we believe?

The arterio-venous balance (A-V balance/difference) technique has been used by a number of groups, including ours, to study skeletal muscle fatty acid metabolism. Several lines of evidence indicate that, like glycogen, intramyocellular triglycerides (imcTG) are an energy source for local use. As such, the report that increased release of free fatty acids (FFA) via lipolysis from skeletal muscle, but not from adipose tissue, is responsible for the increased systemic lipolysis during IL-6 infusion in healthy humans is somewhat unexpected (26). It appears that given the complex anatomy of human limbs, as to be discussed in this review, it is virtually impossible to determine whether any fatty acids being released into the venous circulation of an arm or leg derive from the lipolysis of intermuscular fat residing between muscle groups, intramuscular fat residing within muscle groups (between epimysium and perimysium, or bundles), or the intramyocellular triglyceride droplets (imcTG). In many cases, it may even be difficult to be confident that there is no contribution of FFA from subcutaneous adipose tissue. This question is fundamentally important as one attempts to interpret the results of skeletal muscle fatty acid metabolism studies using the A-V balance technique. In this Perspectives article, we examine the reported results of fatty acid kinetics obtained using the techniques to evaluate the degree of and how to minimize contamination when attempting to sample skeletal muscle-specific fatty acids.

Ruminal tissue uptake of amino acids in Holstein cows when supply of nutrients within the rumen differs.

Characterisation of amino acid (AA) use by the ruminal vein-drained viscera (RDV) has not been assessed in vivo in dairy cattle, and thus, the extent of ruminal AA use from arterial and postabsorptive blood supplies is unclear. Understanding the complete use of AA by the splanchnic bed may lead to alternative feeding programmes that maximise animal N efficiency. The objective of this work was to determine how different nutritional manipulations affect RDV net appearance and apparent affinity for arterial AA in lactating dairy cattle. Data from two arterio-venous (A-V) difference studies, that used a common set of multicatheterised lactating Holstein cows, assigned to different nutritional treatments, were used to assess ruminal metabolism. Study 1 consisted of three dietary treatments at calving [an alfalfa-glucogenic diet, a glucogenic diet (GLCG), or a ketogenic diet (KETO)] to investigate the effects of dietary nutrients and increasing intake postpartum on RDV metabolism of AA at -14, +4, +15, and +29 days relative to calving (DRTC). Study 2 consisted of two dietary levels of CP (17 or 13%) and three ruminal buffers (ammonia, butyrate, and control) to investigate the level of dietary CP and ruminal fermentation products on RDV metabolism of AA. Blood was collected at 9, 20, and 30 min after buffer administration. Regardless of dietary nutrients or fermentation products present in ruminal fluid, net RDV uptake was positive for most AA, excepting Asp, Cys, Glu, and Ser, which were consistently negative. The general positive net uptakes indicate that any AA potentially absorbed from the rumen were not adequate to meet apparent needs. Ruminal plasma flow and net RDV uptake of Trp, Ala, Gly, and Pro increased linearly with increased DRTC. Feeding KETO or GLCG diets increased ruminal plasma flow, and net RDV uptake of Thr and Gly. Feeding high CP diets increased ruminal uptake of Leu, Phe, and Val. The increased AA uptakes were partially driven by increased plasma flow, however, tissue affinity as reflected in clearance rates also increased or tended to for Met, Trp, Ala, Gly, Pro, and Tyr suggesting that changes in RDV uptake were regulated and not due solely to mass action. In conclusion, splanchnic tissue bed responses to dietary and washed rumen conditions were in part driven by changes in RDV nutrient demand and metabolic activity. The adaptive responses alter the fraction of absorbed AA utilised for non-productive purposes and thus the efficiency of conversion of those AA to product.

Signals from the Circle: Tricarboxylic Acid Cycle Intermediates as Myometabokines.

Regular physical activity is an effective strategy to prevent and ameliorate aging-associated diseases. In particular, training increases muscle performance and improves whole-body metabolism. Since exercise affects the whole organism, it has countless health benefits. The systemic effects of exercise can, in part, be explained by communication between the contracting skeletal muscle and other organs and cell types. While small proteins and peptides known as myokines are the most prominent candidates to mediate this tissue cross-talk, recent investigations have paid increasing attention to metabolites. The purpose of this review is to highlight the potential role of tricarboxylic acid (TCA) metabolites as humoral mediators of exercise adaptation processes. We focus on TCA metabolites that are released from human skeletal muscle in response to exercise and provide an overview of their potential auto-, para- or endocrine health-promoting effects.