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Background: The novel coronavirus disease 2019 (COVID-19) pandemic has become a global health crisis affecting over 200 countries worldwide. Extracorporeal membrane oxygenation (ECMO) has been increasingly used in the management of COVID-19-associated end-stage respiratory failure. However, the exact effect of ECMO in the management of these patients, especially with regards to complications and mortality, is unclear. Methods: This is the largest retrospective study of ECMO treated COVID-19 patients in China. A total of 50 ECMO-treated COVID-19 patients were recruited. We describe the main characteristics, the clinical features, ventilator parameters, ECMO-related variables and management details, and complications and outcomes of COVID-19 patients with severe acute respiratory distress syndrome (ARDS) that required ECMO support. Results: For those patients with ECMO support, 21 patients survived and 29 died (mortality rate: 58.0%). Among those who survived, PaO2 (66.3 mmHg [59.5-74.0 mmHg] and PaO2/FiO2 (68.0 mmHg [61.0-76.0 mmHg]) were higher in the survivors than those of non-survivors (PaO2: 56.8 mmHg (49.0-65.0 mmHg), PaO2/FiO2 (58.2 mmHg (49.0-68.0 mmHg), all P < 0.01) prior to ECMO. Patients who achieved negative fluid balance in the early resuscitation phase (within 3 days) had a higher survival rate than those who did not (P = 0.0003). Conclusions: In this study of 50 cases of ECMO-treated COVID-19 patients, a low PO2/FIO2 ratio before ECMO commencement may indicate a poor prognosis. Negative fluid balance in the early resuscitation phase during ECMO treatment was a predictor of increased survival post-ECMO treatment.

Remote ischemic conditioning has been convincingly shown to render the myocardium resistant to a subsequent more severe sustained episode of ischemia. Compared with other organs, little is known regarding the effect of transient liver ischemic conditioning. We proposed the existence of cardioprotection induced by remote liver conditioning. Male Sprague-Dawley rats were divided into sham-operated control (no further hepatic intervention) and remote liver ischemic conditioning groups. For liver ischemic conditioning, three cycles of 5 min of liver ischemia-reperfusion stimuli were conducted before-(liver preconditioning), post-myocardial ischemia (liver postconditioning), or in combination of both (liver preconditioning + liver postconditioning). Rats were exposed to 45 min of left anterior descending coronary artery occlusion, followed by 3 h of reperfusion thereafter. ECG and hemodynamics were measured throughout the experiment. The coronary artery was reoccluded at the end of reperfusion for infarct size determination. Blood samples were taken for serum lactate dehydrogenase and creatine kinase-MB test. Heart tissues were taken for apoptosis measurements and Western blotting. Our data demonstrate that liver ischemic preconditioning, postconditioning, or a combination of both, offered strong cardioprotection, as evidenced by reduction in infarct size and cardiac tissue damage, recovery of cardiac function, and inhibition of apoptosis after ischemia-reperfusion. Moreover, liver ischemic conditioning increased cardiac (not hepatic) glycogen synthase kinase-3β (GSK-3β) phosphorylation. Accordingly, inhibition of GSK-3β mimicked the cardioprotective action of liver conditioning. These results demonstrate that remote liver ischemic conditioning protected the heart against ischemia and reperfusion injury via GSK-3β-dependent cell-survival signaling pathway.NEW & NOTEWORTHY Remote ischemic conditioning protects hearts against ischemia and reperfusion (I/R) injury. However, it is unclear whether ischemic conditioning of visceral organs such as the liver, the largest metabolic organ in the body, can produce cardioprotection. This is the first study to show the cardioprotective effect of remote liver ischemic conditioning in a rat model of myocardial I/R injury. We also, for the first time, demonstrated these protective properties are associated with glycogen synthase kinase-3β-dependent cell-survival signaling pathway.

Ultrasound shear wave elastography (SWE) is a non-invasive, low risk technology allowing the assessment of tissue stiffness. Used clinically for nearly two decades to diagnose and stage liver fibrosis and cirrhosis, it has recently been appreciated for its ability to differentiate between more subtle forms of liver dysfunction. In this review, we will discuss the principle of ultrasound shear wave elastography, its traditional utilization in grading liver cirrhosis, as well as its evolving role in identifying more subtle degrees of liver injury. Finally, we will show how this capacity to distinguish nuanced changes may provide an opportunity for its use in perioperative risk stratification. [ABSTRACT FROM AUTHOR]

Introduction For the past 30 years or more, the quest to develop treatments that directly improve systolic performance of the failing heart while also conferring long-term survival benefits has been [...], Cardiac resynchronization therapy (CRT), the application of biventricular stimulation to correct discoordinate contraction, is the only heart failure treatment that enhances acute and chronic systolic function, increases cardiac work, and reduces mortality. Resting myocyte function also increases after CRT despite only modest improvement in calcium transients, suggesting that CRT may enhance myofilament calcium responsiveness. To test this hypothesis, we examined adult dogs subjected to tachypacing-induced heart failure for 6 weeks, concurrent with ventricular dyssynchrony ([HF.sub.dys]) or CRT. Myofilament force-calcium relationships were measured in skinned trabeculae and/or myocytes. Compared with control, maximal calcium-activated force and calcium sensitivity declined globally in HFdys; however, CRT restored both. Phosphatase PP1 induced calcium desensitization in control and CRT-treated cells, while [HF.sub.dys] cells were unaffected, implying that CRT enhances myofilament phosphorylation. Proteomics revealed phosphorylation sites on Z-disk and M-band proteins, which were predicted to be targets of glycogen synthase kinase-3β (GSK-3β ). We found that GSK-3β was deactivated in [HF.sub.dys] and reactivated by CRT. Mass spectrometry of myofilament proteins from [HF.sub.dys] animals incubated with GSK-3β confirmed GSK-3β -dependent phosphorylation at many of the same sites observed with CRT. GSK-3β restored calcium sensitivity in HFdys, but did not affect control or CRT cells. These data indicate that CRT improves calcium responsiveness of myofilaments following [HF.sub.dys] through GSK-3β reactivation, identifying a therapeutic approach to enhancing contractile function.

Recent studies have found that selective stimulation of troponin (Tn)I protein kinase A (PKA) phosphorylation enhances heart rate-dependent inotropy and blunts relaxation delay coupled to increased afterload. However, in failing hearts, TnI phosphorylation by PKA declines while protein kinase C (PKC) activity is enhanced, potentially augmenting TnI PKC phosphorylation. Accordingly, we hypothesized that these site-specific changes deleteriously affect both rate-responsive cardiac function and afterload dependence of relaxation, both prominent phenotypic features of the failing heart. A transgenic (TG) mouse model was generated in which PKA-TnI sites were mutated to mimic partial dephosphorylation (Ser22 to Ala; Set23 to Asp) and dominant PKC sites were mutated to mimic constitutive phosphorylation (Ser42 and Ser44 to Asp). The two highest-expressing lines were further characterized. TG mice had reduced fractional shortening of 34.7 [+ or -] 1.4% vs. 41.3 [+ or -] 2.0% (P = 0.018) and slight chamber dilation on echocardiography. In vivo cardiac pressure-volume studies revealed near doubling of isovolumic relaxation prolongation with increasing afterload in TG animals (P < 0.001), and this remained elevated despite isoproterenol infusion (PKA stimulation). Increasing heart rate from 400 to 700 beats/rain elevated contractility 13% in TG hearts, nearly half the response observed in nontransgenic animals (P = 0.005). This blunted frequency response was normalized by isoproterenol infusion. Abnormal TnI phosphorylation observed in cardiac failure may explain exacerbated relaxation delay in response to increased afierload and contribute to blunted chronotropic reserve. contractility

Decreased [Ca.sup.2+] responsiveness of the myofilaments underlies myocardial stunning. Given that cross-bridge cycling is a major determinant of myofilament behavior, we quantified cross-bridge cycling rate in stunned myocardium. After stabilization, rat hearts were subjected to 20 min of no-flow global ischemia and 30 min of reperfusion at 37[degrees]C. Control hearts were perfused continuously at 37[degrees]C for 60 min. Trabeculae were dissected and chemically skinned with 1% Triton X-100. The muscles were then activated with solutions of varied [Ca.sup.2+] concentration ([[Ca.sup.2+]]). Force-[[Ca.sup.2+]] relations, rate of force redevelopment after release ([k.sub.tr]), muscle stiffness ([k.sub.m]), and myofilament ATP consumption were determined. Maximal [Ca.sup.2+]-activated force ([F.sub.max]) was depressed in stunned myocardium (49 [+ or -] 5 vs. 82 [+ or -] 5 mN/[mm.sup.2], P < 0.01). Western immunoblotting showed degradation of troponin I in stunned myocardium. The [k.sub.tr] at [F.sub.max] was significantly increased in stunned muscles (19.82 [+ or -] 2.74 vs. 13.19 + 0.96 [s.sup.-1], 22[degrees]C, P < 0.01; 7.49 [+ or -] 0.52 vs. 5.81 [+ or -] 0.54 [s.sup.-1], 10[degrees]C, P < 0.05). The ratio of km measured at 100 Hz over that at 1 Hz, during [F.sub.max], is lower in stunned muscles (8.22 [+ or -] 1.56 vs. 12.94 [+ or -] 0.71, P < 0.05). In comparison with [k.sub.m] at rigor, [k.sub.m] at [F.sub.max] is significantly lower in the stunned group (78.82 [+ or -] 6.11 vs. 93.27 [+ or -] 3.03%, P < 0.05). Myofilament ATP consumption at [F.sub.max] did not change in stunned muscles (5,901 [+ or -] 952 vs. 5,596 [+ or -] 972 pmol*[micro][l.sup-1]*[min.sup.-1], p = 0.49). These results show that cross-bridge cycling is increased in stunned myocardium. Such increases are likely the result of increased transition rate from force-generating states to non-force-generating states. Thus stunned myocardium still maintains ATP consumption in spite of lower force development, rationalizing the long-standing paradox of decreased force but unchanged oxygen consumption in the postischemic heart. cross-bridge cycling; contraction; myocardial stunning

A study was conducted on whether pretreatment with adenosine (Ado) could mimic the effect of phorbol ester phorbol 12-myristate 13-acetate in isolated rabbit ventricular myocytes. The results suggest that Ado plays dual role to initiate and to mediate ischemic preconditioning. Moreover, Ado connects the roles of Ado receptors, protein kinase C and I (sub K,ATP) in ischemic preconditioning.

Analysis of the correlation between intracellular Ca2+ ((Ca2+)i) and contractile force in intact cardiac trabeculae of rat injected with fura-2 salt reveals that 0.65 plus or minus 0.19 micromoles of (Ca2+)i stimulates the steady state force-(Ca2+)i relationship during ryanodine tetanization. The Ca2+-ATPase inhibitor, cyclopiazonic acid (CPA), attenuates the rate of decay of (Ca2+)i and enables the force to reach a steady state with (Ca2+)i. However, the force-(Ca2+)i relationship is insufficient for predicting the steady state relationship during physiological twitch contractions.