Persistently elevated troponin I in paracetamol hepatotoxicity: Association with liver injury,organ failure,and outcome

Abstract

Context. An elevated troponin I (TnI) is associated with a poorer prognosis during critical illness. Objective. Our aims were to determine whether significant paracetamol-induced hepatotoxicity was associated with an elevated TnI; if this elevation was persistent and was associated with worse clinical outcomes. Materials and methods. In this retrospective cohort study, the requirement for orthotopic liver transplantation (OLT) or death and/or the development of multiorgan failure (MOF) was evaluated for 48 consecutive patients admitted to the Royal Infirmary of Edinburgh (a university tertiary referral centre) with acute liver injury or acute liver failure secondary to paracetamol overdose. Results. TnI was elevated (≥ 0.05 ng/L) in 13/48 patients (27%). This appeared to be sustained for at least 6 days which has not been shown previously in the context of Acute Liver Injury (ALI). Elevated TnI was strongly associated with MOF, with the requirement for inotropic support being the strongest predictor (p = 0.003, OR 9.00, 95% CI 2.13–37.98). TnI elevations also correlated strongly with Acute Physiology and Chronic Health Evaluation (APACHE) II scores (p = 0.0006, r = 0.482, 95% CI 0.22–0.68) and with interleukin 6 (IL-6) levels (p = 0.0001, r = 0.55, 95% CI 0.29–0.73). Although a raised TnI was associated with a markedly increased risk of death or orthotopic liver transplant (p = 0.005, OR 7.73, 95% CI 1.87–32.05) on univariate analysis, this was primarily seen in the context of MOF (SOFA score p = 0.003, OR 1.23, 95% CI 1.07–1.41) and was not an independent predictor of death. There was no correlation between TnI or outcome with other cardiac biomarkers and markers of cardiovascular risk. Discussion and Conclusion. An elevated TnI in the context of acute liver injury or liver failure following paracetamol overdose is associated with a significantly worse patient outcome but it is not an independent prognostic factor. Further studies should be undertaken to investigate the mechanism behind this elevated troponin association.     

浅低温心脏不停跳瓣膜置换手术中监测与护理进展

使心脏在有节律的空跳状态下完成心脏瓣膜替换手术,是90年代初期在国内兴起的一种较接近生理的心肌保护技术,在心脏外科手术领域应用的又一进展。该方法避免了传统的低温停跳心肌保护技术,无法避免的心肌缺血性损害及再灌注损伤等缺点[1],有效地防止了术后低心排血量综合征和严重心律失常,明显降低术后死亡率[2]。     

Taking a Byte of the Apple:

No abstract available for this article.     

Inhibitory effects of sigma‐1 ligands on handling‐induced tachycardia in conscious tethered rats

We used conscious tethered Sprague‐Dawley rats to evaluate the cardiovascular effects of four sigma‐1 (σ₁) agonists and five antagonists, given alone or in combination. All drugs were administered as a single intraperitoneal dose. The agonists were given at doses reported as efficacious in rodent cognition models, while the antagonists were administered at doses neutralizing agonist effects in vivo. Systolic blood pressure (SBP) and heart rate (HR) were continuously recorded for 20 min before and 60 min postadministration. Immediately after injection, a sudden, transitory increase in HR and SBP was noted in all animals, because of the stress induced by handling. For both parameters, a peak value (ΔHR_max and ΔSBP_max) and an area under the curve of changes from baseline over the period 5–20 min postinjection (ΔHR_AUC_{5–20 min} and ΔSBP_AUC_{5–20 min}) were calculated. Three of the four σ₁ agonists (SKF‐10,047, dehydroepiandrosterone (DHEAS), Compound 14) significantly reduced ΔHR_AUC_{5–20 min} value without changing ΔHR_max, while the fourth one, SA‐4503, had no significant effect. None of the antagonists (haloperidol, rimcazole, NE‐100, and BD1047) reduced, and even one (progesterone) enhanced the stress‐induced effects on HR. No changes in SBP were noted with any compound. When the antagonist NE‐100 was administered just before SKF‐10,047, it completely reversed the inhibitory effects of the σ₁ agonist on HR increase. In conclusion, we demonstrated for the first time the involvement of σ₁ receptors in the regulation of handling‐induced tachycardia in the conscious rat. Although additional investigations are needed to fully understand this role, it might offer new therapeutic perspectives to σ₁ ligands in the cardiovascular sphere.     

Rheumatic heart disease and risk of incident heart failure among community-dwelling older adults: A prospective cohort study

Abstract

Background. Little is known about the association of rheumatic heart disease (RHD) with incident heart failure (HF) among older adults.

Design. Cardiovascular Health Study, a prospective cohort study.

Methods. Of the 4,751 community-dwelling adults ≥ 65 years, free of prevalent HF at baseline, 140 had RHD, defined as self-reported physician-diagnosed RHD along with echocardiographic evidence of left-sided valvular disease. Propensity scores for RHD, estimated for each of the 4,751 participants, were used to assemble a cohort of 720, in which 124 and 596 participants with and without RHD, respectively, were balanced on 62 baseline characteristics.

Results. Incident HF developed in 33% and 22% of matched participants with and without RHD, respectively, during 13 years of follow-up (hazard ratio when RHD was compared to no-RHD 1.60; 95% confidence interval 1.13–2.28; P = 0.008). Pre-match unadjusted, multivariable-adjusted, and propensity-adjusted hazard ratios (95% confidence intervals) for RHD-associated incident heart failure were 2.04 (1.54–2.71; P < 0.001), 1.32 (1.02–1.70; P = 0.034), and 1.55 (1.14–2.11; P = 0.005), respectively. RHD was not associated with all-cause mortality (HR 1.09; 95% CI 0.82–1.45; P = 0.568).

Conclusion. RHD is an independent risk factor for incident HF among community-dwelling older adults free of HF, but has no association with mortality.     

Brain natriuretic peptide-guided therapy for heart failure

The drug treatment of heart failure, once simple, has become complex. Apart from a loop diuretic and digoxin, most patients should now be receiving an angiotensin-converting enzyme inhibitor (or angiotensin II receptor blocker), a beta-blocker and spironolactone. Newer drugs, such as endothelin-receptor antagonists and combined blockers of converting-enzyme and neutral endopeptidase, might soon become available. When to introduce these drugs and what dose is optimal for any individual, are questions that currently vex clinicians. We proposed that plasma levels of the cardiac hormone brain natriuretic peptide (BNP, or better, its 1-76 amino-acid N-terminal fragment, N-BNP), would provide an objective index for guiding drug treatment in patients with established, stable cardiac failure. In a pilot study, 69 patients were randomized to drug treatment based on clinical criteria, or based on plasma levels of N-BNP. After a median follow-up of 9.6 months, those in the N-BNP group had fewer clinical end-points than those in the group managed by clinical criteria alone (19 vs 54; P= 0.02). These preliminary data encourage the concept that the increasingly complex pharmacotherapy for heart failure, both chronic (as in this trial) and acute, might best be guided by an objective measure such as plasma levels of BNP or N-BNP.     

Role of angiogenic growth factors in transplant coronary artery disease

Transplant coronary artery disease (TxCAD) as a manifestation of chronic rejection is a major limitation to long‐term survival of heart transplant recipients. Although the exact molecular and cellular mechanisms contributing to neointimal formation are unknown, it has been generally believed that smooth muscle cells (SMC) of donor origin migrate from the media into the subendothelial layer of the vascular wall, where SMC proliferate and synthesize extracellular matrix resulting in intimal thickening. However, recent observations indicate that hematopoietic and vascular progenitor cells derived from recipient bone marrow may contribute to the arteriosclerotic lesion formation in the coronary arteries of the transplant. On the other hand, studies on postnatal hematopoiesis indicate that angiogenic growth factors such as vascular endothelial growth factor (VEGF) and angiopoietin‐1 (Ang1) may regulate the recruitment of these cells into distant organs. Furthermore, embryonic VEGFR‐2 ⁺ /CD34 ⁺ stem cells may serve as vascular progenitor cells and their differentiation into endothelial cells and SMC may be regulated by VEGF and platelet‐derived growth factor (PDGF), respectively. In this review, we discuss the role of angiogenic growth factors such as VEGF, Ang, and PDGF in the recruitment of hematopoietic and vascular progenitor cells in TxCAD and suggest novel therapies targeted at homing, differentiation and proliferation of these cells in the allograft.     

Cardiovascular Risk in Young Finns

This report describes the general outline and progress of a multicentre study on risk factors of coronary heart disease and their determinants in children and adolescents. “Cardiovascular Risk in Young Finns” comprises a cross-sectional study of 3 to 18-year old subjects in 1980, and follow-up studies in 1983 and 1986 in various parts of Finland, and in 1989 in one of the study areas (Turku). The number of participants in 1980 was 3596 (83.1%) of those invited. In 1983 and 1986 83.2% and 77.8% of them, respectively, participated. The study programme has comprised questionnaire data on, for example, general health and living conditions, physical activity, eating habits, smoking, and psychological variables. The physical examination covered height, weight, skinfold thickness, pubertal stages and blood pressure. Blood specimens were obtained to assess concentrations of serum lipids and insulin, and in 1986 also for possible genetic markers of hypercholesterolemia. A 48 hour recall on nutrient intake was obtained from some of the subjects. The follow-up studies have enabled a study of the tracking phenomenon. Other important questions under study include, for example, the possible clustering of risk factors and their determinants. The cohorts studied provide a valuable research basis for the future, with emphasis on enabling a long-term follow-up of the subjects.