Barth syndrome is an X-linked cardiac and skeletal mitochondrial myopathy. Barth syndrome may be due to lipid alterations because the product of the mutated gene is homologous to phospholipid acyltransferases. Here we document that a single mitochondrial phospholipid species, tetralinoleoyl-cardiolipin, was lacking in the skeletal muscle (n = 2), right ventricle (n = 2), left ventricle (n = 2), and platelets (n = 6) of 8 children with Barth syndrome. Tetralinoleoyl-cardiolipin is specifically enriched in normal skeletal muscle and the normal heart. These findings support the notion that Barth syndrome is caused by alterations of mitochondrial lipids.

LVAD support can improve contractile strength of intact myocardium and reverse the negative FFR associated with end-stage heart failure. The expression of genes encoding for proteins involved in Ca(2+) cycling is upregulated (reverse molecular remodeling), but only the protein content of SERCA2a is increased.

Background Some Coronavirus disease 2019 (COVID-19) patients who have recovered from their acute infection after experiencing only mild symptoms continue to exhibit persistent exertional limitation that is often unexplained by conventional investigative studies. Research question What is the patho-physiological mechanism of exercise intolerance that underlies the post-COVID-19 long haul syndrome following COVID-19 in patients without cardio-pulmonary disease? Study Design and Methods This study examined the systemic and pulmonary hemodynamics, ventilation, and gas exchange in 10 post-COVID-19 patients without cardio-pulmonary disease during invasive cardiopulmonary exercise testing (iCPET) and compared the results to 10 age- and sex matched controls. These data were then used to define potential reasons for exertional limitation in the post-COVID-19 cohort. Results Post-COVID-19 patients exhibited markedly reduced peak exercise aerobic capacity (VO 2 ) compared to controls (70±11%predicted vs. 131±45%predicted; p<0.0001). This reduction in peak VO 2 was associated with impaired systemic oxygen extraction (i.e., narrow CaVO 2 /CaO 2 ) compared to controls (0.49±0.1 vs. 0.78±0.1, p<0.0001) despite a preserved peak cardiac index (7.8±3.1 vs. 8.4±2.3 L/min, p>0.05). Additionally, post-COVID-19 patients demonstrated greater ventilatory inefficiency (i.e., abnormal VE/VCO 2 slope: 35±5 vs. 27±5, p=0.01) compared to controls without an increase in dead space ventilation. Interpretation Post-COVID-19 patients without cardiopulmonary disease demonstrate a marked reduction in peak VO 2 from a peripheral rather than a central cardiac limit along with an exaggerated hyper-ventilatory response during exercise.

Abnormal cardiolipin is a specific diagnostic marker of cardiomyopathies caused by TAZ mutations. These mutations lead to alterations in the fatty acid composition of several phospholipids, supporting the idea that TAZ encodes a human acyltransferase.

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The brain is one of the most metabolically active organs in the body. The brain’s high energy demand associated with wakefulness persists during rapid eye movement sleep, and even during non–rapid eye movement sleep, cerebral oxygen consumption is only reduced by 20%. The active bioenergetic state parallels metabolic waste production at a higher rate than in other organs, and the lack of lymphatic vasculature in brain parenchyma is therefore a conundrum. A common assumption has been that with a tight blood–brain barrier restricting solute and fluid movements, a lymphatic system is superfluous in the central nervous system. Cerebrospinal fluid (CSF) flow has long been thought to facilitate central nervous system tissue “detoxification” in place of lymphatics. Nonetheless, while CSF production and transport have been studied for decades, the exact processes involved in toxic waste clearance remain poorly understood. Over the past 5 years, emerging data have begun to shed new light on these processes in the form of the “glymphatic system,” a novel brain-wide perivascular transit passageway dedicated to CSF transport and metabolic waste drainage from the brain. Here, we review the key anatomical components and operational drivers of the brain’s glymphatic system, with a focus on its unique functional dependence on the state of arousal and anesthetic regimens. We also discuss evidence for why clinical exploration of this novel system may in the future provide valuable insight into new strategies for preventing delirium and cognitive dysfunction in perioperative and critical care settings.

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