Atrial pacing to suppress ventricular arrhythmias in the critically ill patients: a case report.

Background: Atrial and ventricular arrhythmias are common in the critically ill due to a variety of factors including sepsis, myocardial ischaemia, renal dysfunction, and electrolyte disturbances. Anti-arrhythmic medications can be useful to control arrhythmias but can result in bradycardia and haemodynamic compromise. A paced atrial rhythm alongside normal atrioventricular conduction can be helpful to treat bradycardia, prevent arrhythmias, and support cardiac output. Case summary: A 55-year-old gentleman with pseudomonas pneumonia, respiratory failure necessitating mechanical haemodynamic support, and subsequent coronary ischaemia presented to the intensive care unit. Paroxysms of atrial fibrillation and ventricular arrhythmias caused haemodynamic embarrassment and presented an ongoing clinical challenge as anti-arrhythmic medications resulted in bradycardia and Torsade de Pointes. Atrial pacing mediated intrinsic conduction via the His-Purkinje system inhibited ventricular ectopy and further arrhythmia breaking the tachycardia-bradycardia cycle; this stabilized the patient, facilitated ongoing intensive therapy unit care and promoted recovery. Conclusion: Atrial pacing mediated intrinsic conduction via the His-Purkinje system is an effective approach to suppress ventricular ectopy and sustained arrhythmias whilst protecting the patient from haemodynamically compromising bradycardia.

Utility of echocardiographic right ventricular subcostal strain in critical care.

AIMS: Right ventricular (RV) strain is a known predictor of outcomes in various heart and lung pathologies but has been considered too technically challenging for routine use in critical care. We examined whether RV strain acquired from the subcostal view, frequently more accessible in the critically ill, is an alternative to conventionally derived RV strain in intensive care. METHODS AND RESULTS: RV strain data were acquired from apical and subcostal views on transthoracic echocardiography (TTE) in 94 patients (35% female), mean age 50.5 ± 15.2 years, venovenous extracorporeal membrane oxygenation (VVECMO) (44%). RV strain values from the apical (mean ± standard deviation; -20.4 ± 6.7) and subcostal views (-21.1 ± 7) were highly correlated (Pearson's r -0.89, P < 0.001). RV subcostal strain correlated moderately well with other echocardiography parameters including tricuspid annular plane systolic excursion (r -0.44, P < 0.001), RV systolic velocity (rho = -0.51, P < 0.001), fractional area change (r -0.66, P < 0.01), and RV outflow tract velocity time integral (r -0.49, P < 0.001). VVECMO was associated with higher RV subcostal strain (non-VVECMO -19.6 ± 6.7 vs. VVECMO -23.2 ± 7, P = 0.01) but not apical RV strain. On univariate analysis, RV subcostal strain was weakly associated with survival at 30 days (R2 = 0.04, P = 0.05, odds ratio =1.08) while apical RV was not (P = 0.16). CONCLUSION: RV subcostal deformation imaging is a reliable surrogate for conventionally derived strain in critical care and may in time prove to be a useful diagnostic marker in this cohort.

Vascular cell adhesion molecule 1 expression by biliary epithelium promotes persistence of inflammation by inhibiting effector T-cell apoptosis.

UNLABELLED: Chronic hepatitis occurs when effector lymphocytes are recruited to the liver from blood and retained in tissue to interact with target cells, such as hepatocytes or bile ducts (BDs). Vascular cell adhesion molecule 1 (VCAM-1; CD106), a member of the immunoglobulin superfamily, supports leukocyte adhesion by binding α4ß1 integrins and is critical for the recruitment of monocytes and lymphocytes during inflammation. We detected VCAM-1 on cholangiocytes in chronic liver disease (CLD) and hypothesized that biliary expression of VCAM-1 contributes to the persistence of liver inflammation. Hence, in this study, we examined whether cholangiocyte expression of VCAM-1 promotes the survival of intrahepatic α4ß1 expressing effector T cells. We examined interactions between primary human cholangiocytes and isolated intrahepatic T cells ex vivo and in vivo using the Ova-bil antigen-driven murine model of biliary inflammation. VCAM-1 was detected on BDs in CLDs (primary biliary cirrhosis, primary sclerosing cholangitis, alcoholic liver disease, and chronic hepatitis C), and human cholangiocytes expressed VCAM-1 in response to tumor necrosis factor alpha alone or in combination with CD40L or interleukin-17. Liver-derived T cells adhered to cholangiocytes in vitro by α4ß1, which resulted in signaling through nuclear factor kappa B p65, protein kinase B1, and p38 mitogen-activated protein kinase phosphorylation. This led to increased mitochondrial B-cell lymphoma 2 accumulation and decreased activation of caspase 3, causing increased cell survival. We confirmed our findings in a murine model of hepatobiliary inflammation where inhibition of VCAM-1 decreased liver inflammation by reducing lymphocyte recruitment and increasing CD8 and T helper 17 CD4 T-cell survival. CONCLUSIONS: VCAM-1 expression by cholangiocytes contributes to persistent inflammation by conferring a survival signal to α4ß1 expressing proinflammatory T lymphocytes in CLD.

Differential induction of nuclear factor-kappaB and activator protein-1 activity after CD40 ligation is associated with primary human hepatocyte apoptosis or intrahepatic endothelial cell proliferation.

CD40, a tumor necrosis factor receptor superfamily member, is up-regulated on intraheptatic endothelial cells (IHEC) and epithelial cells during inflammatory liver disease, and there is evidence that the functional outcome of CD40 ligation differs between cell types. Ligation of CD40 on cholangiocytes or hepatocytes results in induction of Fas-mediated apoptosis, whereas ligation of IHEC CD40 leads to enhanced chemokine secretion and adhesion molecule expression. We now report that differential activation of two transcription factors, nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1), in primary human hepatocytes or IHEC, is associated with and may explain, in part, the different responses of these cell types to CD40 ligation. CD40 ligation induced a rise in NF-kappaB activity in hepatocytes,which peaked at 2 h and returned to baseline by 24 h; however, IHEC CD40 ligation resulted in a sustained up-regulation of NF-kappaB (>24 h). In hepatocytes, CD40 ligation led to sustained up-regulation of AP-1 activity >24 h associated with increased protein levels of RelA (p65), c-Jun, and c-Fos, whereas no induction of AP-1 activity was observed in IHECs. Analysis of mitogen-activated protein kinase phosphorylation (phospho-extracellular signal-regulated kinase 1/2 and phospho-c-Jun NH(2)-terminal kinase 1/2) and expression of inhibitor kappaBalpha were entirely consistent, and thus confirmed the profiles of NF-kappaB and AP-1 signaling and the effects of the selective inhibitors assessed using electrophoretic mobility shift assay or Western immunoblotting. CD40 ligation resulted in induction of apoptosis in hepatocytes after 24 h, but on IHECs, CD40 ligation resulted in proliferation. Inhibition of (CD40-mediated) NF-kappaB activation prevented IHEC proliferation and led to induction of apoptosis. Selective extracellular signal-regulated kinase and c-Jun NH(2)-terminal kinase inhibitors reduced levels of apoptosis in (CD40-stimulated) hepatocytes by approximately 50%. We conclude that differential activation of these two transcription factors in response to CD40 ligation is associated with differences in cell fate. Transient activation of NF-kappaB and sustained AP-1 activation is associated with apoptosis in hepatocytes, whereas prolonged NF-kappaB activation and a lack of AP-1 activation in IHECs result in proliferation.