Antithrombin III is associated with acute liver failure in patients with end-stage heart failure undergoing mechanical circulatory support.

OBJECTIVE: There are few data on the role of liver dysfunction in patients with end-stage heart failure supported by mechanical circulatory support. The aim of our study was to investigate predictors for acute liver failure in patients with end-stage heart failure undergoing mechanical circulatory support. METHODS: A consecutive 164 patients with heart failure with New York Heart Association class IV undergoing mechanical circulatory support were investigated for acute liver failure using the King's College criteria. Clinical characteristics of heart failure together with hemodynamic and laboratory values were analyzed by logistic regression. RESULTS: A total of 45 patients (27.4%) with heart failure developed subsequent acute liver failure with a hospital mortality of 88.9%. Duration of heart failure, cause, cardiopulmonary resuscitation, use of vasopressors, central venous pressure, pulmonary capillary wedge pressure, pulmonary pulsatility index, cardiac index, and transaminases were not significantly associated with acute liver failure. Repeated decompensation, atrial fibrillation (P < .001) and the use of inotropes (P = .007), mean arterial (P = .005) and pulmonary pressures (P = .042), cholinesterase, international normalized ratio, bilirubin, lactate, and pH (P < .001) were predictive of acute liver failure in univariate analysis only. In multivariable analysis, decreased antithrombin III was the strongest single measurement indicating acute liver failure (relative risk per %, 0.84; 95% confidence interval, 0.77-0.93; P = .001) and remained an independent predictor when adjustment for the Model for End-Stage Liver Disease score was performed (relative risk per %, 0.89; 95% confidence interval, 0.80-0.99; P = .031). Antithrombin III less than 59.5% was identified as a cutoff value to predict acute liver failure with a corresponding sensitivity of 81% and specificity of 87%. CONCLUSIONS: In addition to the Model for End-Stage Liver Disease score, decreased antithrombin III activity tends to be superior in predicting acute liver failure compared with traditionally thought predictors. Antithrombin III measurement may help to identify patients more precisely who are developing acute liver failure during mechanical circulatory support.

Ultrasound-guided regional anesthesia for carotid endarterectomy induces early hemodynamic and stress hormone changes.

OBJECTIVE: Locoregional anesthesia is an effective method for evaluating cerebral function during carotid endarterectomy (CEA). Landmark-guided regional anesthesia (RA) is currently used for CEA and can provoke substantial perioperative hypertension. Ultrasound-guided RA (US-RA) is a new method for performing RA in CEA; however, the effect on sympathetic activity and blood pressure is uncertain. This study assessed early sympathetic activity during CEA in US-RA compared with general anesthesia (GA). METHODS: Patients were prospectively randomized to receive US-RA (n = 32) or GA (n = 28) for CEA. The primary end point was the change in systolic arterial blood pressure after induction of anesthesia (just before starting surgery) comparing US-RA with GA. We also recorded heart rate and analyzed concentrations of plasma blood hormones, including cortisol, metanephrine, and normetanephrine at five different times. Creatinine kinase, troponin I, and N-terminal pro-B-type natriuretic peptide were analyzed to detect potential changes in cardiac biomarkers during the procedure. RESULTS: Systolic arterial blood pressure (mean ± standard deviation) increased significantly in US-RA patients compared with GA patients even before surgery was initiated (180 ± 26 mm Hg vs 109 ± 24 mm Hg; P < .001), then remained elevated during the entire surgery and returned to baseline values 1 hour after admission to the postoperative anesthesia care unit. Heart rate (US-RA: 78 ± 16 beats/min, GA: 52 ± 12 beats/min; P < .001) and cortisol levels (US-RA: 155 ± 97 µg/L, GA: 99 ± 43 µg/L; P = .006) were also significantly higher in the US-RA group after induction of anesthesia. Other values did not differ. CONCLUSIONS: The US-RA technique for CEA induces temporary intraoperative hypertension and an increase in stress hormone levels. Nevertheless, US-RA is a feasible, effective, and safe form of locoregional for CEA that enables targeted placement of low volumes of local anesthesia under direct visualization.

Sphingosine-1-phosphate-dependent activation of p38 MAPK maintains elevated peripheral resistance in heart failure through increased myogenic vasoconstriction.

RATIONALE: Mechanisms underlying vasomotor abnormalities and increased peripheral resistance exacerbating heart failure (HF) are poorly understood. OBJECTIVE: To explore the role and molecular basis of myogenic responses in HF. METHODS AND RESULTS: 10 weeks old C57Bl6 mice underwent experimental myocardial infarction (MI) or sham surgery. At 1 to 12 weeks postoperative, mice underwent hemodynamic studies, mesenteric, cerebral, and cremaster artery perfusion myography and Western blot. Organ weights and hemodynamics confirmed HF and increased peripheral resistance after MI. Myogenic responses, ie, pressure-induced vasoconstriction, were increased as early as 1 week after MI and remained elevated. Vasoconstrictor responses to phenylephrine were decreased 1 week after MI, but not at 2 to 6 weeks after MI, whereas those to endothelin (ET)-1 and sphingosine-1-phosphate (S1P) were increased at all time points after MI. An antagonist (JTE-013) for the most abundant S1P receptor detected in mesenteric arteries (S1P(2)R) abolished the enhanced myogenic responses of HF, with significantly less effect on controls. Mice with genetic absence of sphingosine-kinases or S1P(2)R (Sphk1(-/-); Sphk1(-/-)/Sphk2(+/-); S1P(2)R(-/-)) did not manifest enhanced myogenic responses after MI. Mesenteric arteries from HF mice exhibited increased phosphorylation of myosin light chain, with deactivation of its phosphatase (MLCP). Among known S1P-responsive regulators of MLCP, GTP-Rho levels were unexpectedly reduced in HF, whereas levels of activated p38 MAPK and ERK1/2 (extracellular signal-regulated kinase 1/2) were increased. Inhibiting p38 MAPK abolished the myogenic responses of animals with HF, with little effect on controls. CONCLUSIONS: Rho-independent p38 MAPK-mediated deactivation of MLCP underlies S1P/S1P(2)R-regulated increases in myogenic vasoconstriction observed in HF. Therapeutic targeting of these findings in HF models deserves study.