Search

New Findings: What is the topic of this review?Lactate is considered an important substrate for mitochondria in the muscles, heart and brain during exercise and is the main gluconeogenetic precursor in the liver and kidneys. In this light, we review the (patho)physiology of lactate metabolism in sepsis and coronavirus disease 2019 (COVID‐19).What advances does it highlight?Elevated blood lactate is strongly associated with mortality in septic patients. Lactate seems unrelated to tissue hypoxia but is likely to reflect mitochondrial dysfunction and high adrenergic stimulation. Patients with severe COVID‐19 exhibit near‐normal blood lactate, indicating preserved mitochondrial function, despite a systemic hyperinflammatory state similar to sepsis. In critically ill patients, elevated plasma lactate is often interpreted as a sign of organ hypoperfusion and/or tissue hypoxia. This view on lactate is likely to have been influenced by the pioneering exercise physiologists around 1920. August Krogh identified an oxygen deficit at the onset of exercise that was later related to an oxygen 'debt' and lactate accumulation by A. V. Hill. Lactate is considered to be the main gluconeogenetic precursor in the liver and kidneys during submaximal exercise, but hepatic elimination is attenuated by splanchnic vasoconstriction during high‐intensity exercise, causing an exponential increase in blood lactate. With the development of stable isotope tracers, lactate has become established as an important energy source for muscle, brain and heart tissue, where it is used for mitochondrial respiration. Plasma lactate > 4 mM is strongly associated with mortality in septic shock, with no direct link between lactate release and tissue hypoxia. Herein, we provide evidence for mitochondrial dysfunction and adrenergic stimulation as explanations for the sepsis‐induced hyperlactataemia. Despite profound hypoxaemia and intense work of breathing, patients with severe coronavirus disease 2019 (COVID‐19) rarely exhibit hyperlactataemia (> 2.5 mM), while presenting a systemic hyperinflammatory state much like sepsis. However, lactate dehydrogenase, which controls the formation of lactate, is markedly elevated in plasma and strongly associated with mortality in severe COVID‐19. We briefly review the potential mechanisms of the lactate dehydrogenase elevation in COVID‐19 and its relationship to lactate metabolism based on mechanisms established in contracting skeletal muscle and the acute respiratory distress syndrome. [ABSTRACT FROM AUTHOR]

Background: Augmented skeletal muscle metaboreflex activation may accompany chronic obstructive pulmonary disease (COPD). The maintained metaboreflex control of mean arterial pressure (MAP) that has been reported may reflect limited evaluation using only one moderate bout of static handgrip (HG) and following postexercise ischaemia (PEI). Objective: We tested the hypothesis that cardiovascular and respiratory responses to high‐intensity static HG and isolated metaboreflex activation during PEI are augmented in COPD patients. Methods: Ten patients with moderate to severe COPD and eight healthy age‐ and BMI‐matched controls performed two‐minute static HG at moderate (30% maximal voluntary contraction; MVC) and high (40% MVC) intensity followed by PEI. Results: Despite similar ratings of perceived exertion, arm muscle mass and strength, COPD patients demonstrated lower MAP responses during both HG intensities compared with controls (time × group interaction, p <.05). Indeed, during high‐intensity HG at 40% MVC, peak MAP responses were significantly lower in COPD patients (ΔMAP: COPD 41 ± 9 mmHg vs. controls 56 ± 14 mmHg, p <.05). Notably, no group differences in MAP were observed during PEI (e.g. 40% MVC PEI: ΔMAP COPD 33 ± 9 mmHg vs. controls 33 ± 6 mmHg, p >.05). We found no between‐group differences in heart rate, respiratory rate, or estimated minute ventilation during HG or PEI. Conclusion: These results suggest that the pressor response to high‐intensity HG is blunted in COPD patients. Moreover, despite inducing a strong cardiovascular and respiratory stimulus, skeletal muscle metaboreflex activation evoked similar responses in COPD patients and controls. [ABSTRACT FROM AUTHOR]

Type 2 diabetes is associated with microvascular dysfunction, but little is known about how capillary ultrastructure is affected by exercise training. To investigate the effect of two types of exercise training on skeletal muscle capillary ultrastructure and capillarization in individuals with type 2 diabetes, 21 individuals with type 2 diabetes were allocated (randomized controlled trial) to 11 weeks of aerobic exercise training consisting of either moderate‐intensity endurance training (END; n = 10) or low‐volume high‐intensity interval training (HIIT; n = 11). Skeletal muscle biopsies (m vastus lateralis) were obtained before and after the training intervention. At baseline, there was no difference in capillarization, capillary structure, and exercise hyperemia between the two groups. After the training intervention, capillary‐to‐fiber ratio increased by 8% ± 3% in the END group (P < 0.05) and was unchanged in the HIIT group with no difference between groups. Endothelium thickness increased (P < 0.05), basement membrane thickness decreased (P < 0.05), and the capillary lumen tended (P = 0.07) to increase in the END group, whereas these structural indicators were unchanged after HIIT. In contrast, skeletal muscle endothelial nitric oxide synthase (eNOS) increased after HIIT (P < 0.05), but not END, whereas there was no change in vascular endothelial growth factor (VEGF), superoxide dismutase (SOD)‐2, or NADPH oxidase after both training protocols. In contrast to END training, HIIT did not alter capillarization or capillary structure in individuals with type 2 diabetes. In conclusion, HIIT appears to be a less effective strategy to treat capillary rarefaction and reduce basement thickening in type 2 diabetes. [ABSTRACT FROM AUTHOR]