These findings suggest that circulating cTnT may reflect left ventricular hypertrophy and/or myocardial ischaemia in dialysis patients, and indicate that ET-1 and big ET-1 might be associated with these conditions.
Reference values are usually based on blood samples from healthy men or non-pregnant women. Blood samples from pregnant women may be compared with these reference values. Correct references for pregnancy can be extremely important for clinical decisions such as ablatio placentae, appendicitis, premature rupture of membranes and preeclampsia. Previous studies of normal variations during third-trimester pregnancy are incomplete. Blood samples during pregnancy weeks 33, 36 and 39 as well as 1-3 h postpartum were collected from pregnant women with dietary iron supplement and at least one previous pregancy without a history of hypertension or preeclampsia. When the sampled values were compared with the present reference values from men and non-pregnant women, the following differences were found during normal pregnancy: Haemoglobin and ferritin were reduced, CRP was slightly elevated, WBC (white blood cell count) and HNL (human neutrophilic lipocalin) were elevated during pregnancy and significantly increased postpartum. Albumin was reduced. ALT and AST were slightly elevated and GGT was unchanged during pregnancy. ALP, D-dimer and fibrinogen were elevated. Uric acid increased during the third trimester and thrombocyte count decreased. Separate reference values for pregnant women are essential for correct diagnostic decisions during third-trimester pregnancy. Elevated levels of D-dimer do not necessarily indicate ablatio placentae. A diagnosis of progressive preeclampsia cannot be based on increasing uric acid levels and reduced platelet count in a stable clinical condition. HNL signals activation of neutrophilic granulocytes and can thereby offer a helpful tool for diagnosing infection during pregnancy and postpartum.
Abstract. Löwbeer C, Stenvinkel P, Pecoits-Filho R, Heimbü rger O, Lindholm B, Gustafsson SA, Seeberger A (Karolinska Institutet at Huddinge University Hospital; Capio Diagnostik, St Görans Hospital, Stockholm, Sweden). Elevated cardiac troponin T in predialysis patients is associated with inflammation and predicts mortality. J Intern Med 2003; 253: 153-160.Objectives. Cardiac troponin T (cTnT) is a highly sensitive and specific marker of myocardial damage. It has been shown that elevated serum concentrations of cTnT in haemodialysis (HD) patients are associated with poor prognostic outcome. The aim of the present study was to investigate the predictive value of cTnT in samples from predialysis patients and to investigate associations between cTnT and inflammatory markers, such as C-reactive protein (CRP) and interleukin-6 (IL-6). Design. Cohort, follow-up study. Setting. Huddinge University Hospital, Sweden. Subjects. A total of 115 (62% males, 28% diabetic patients) end-stage renal disease (ESRD) patients (52 ± 1 years), of which 29% had cardiovascular disease (CVD), were studied shortly before the onset of dialysis therapy. Sixty-four patients started peritoneal dialysis (PD) as renal replacement therapy, whilst 49 started HD during the follow-up. Main outcome measures. The cTnT was analysed with the third generation TnT assay on Elecsys 2010. The prognostic value was calculated for cTnT, IL-6, age, CVD, malnutrition, diabetes mellitus (DM) and gender. Survival analyses were made with Kaplan-Meier and Cox regression analyses, with all-cause mortality as the clinical end point (mean follow-up period 2.7 ± 0.1 years). Results. Significant correlations were found between cTnT and CKMB (q ¼ 0.52, P < 0.0001), IL-6 (q ¼ 0.23, P < 0.05), CRP (q ¼ 0.30, P < 0.05), and serum albumin (q ¼ )0.31, P < 0.001), respectively. Diabetic patients had higher median serum cTnT level (0.09 lg L )1 ; range <0.01-0.51 vs. 0.04 lg L )1 ; range <0.01-0.67 lg L )1 ; P < 0.005) compared with nondiabetic patients. Likewise, patients with CVD had a significantly higher median level (0.08 lg L )1 ; range <0.01-0.67 lg L )1 vs. 0.04 lg L )1 ; range <0.01-0.61 lg L )1 ; P < 0.01) of cTnT compared with patients without CVD. Patients with cTnT ‡0.10 lg L )1 had a higher cumulative mortality rate than patients with cTnT < 0.10 lg L )1 (v 2 ¼ 7.04; P < 0.01). Whilst age, CVD, malnutrition, DM, IL-6, cTnT and male gender were associated with poor outcome in the univariate analysis, only DM (P < 0.05) and cTnT (P < 0.05) were independently associated with mortality in a multivariate analysis. Conclusions. The present study demonstrates that serum concentrations of cTnT ‡0.10 lg L )1 is a significant predictor of mortality in patients starting dialysis. Moreover, the positive correlations between cTnT and IL-6, and CRP, respectively, suggest an association between inflammation and cTnT levels. Finally, the results of the present study suggest that cTnT is an independent predictor of mortality in ESRD patients starting dialysis.
Abstract-To investigate if spontaneous ischemic events in mice with severe multi-organ atherosclerosis could adapt to ischemia, apolipoprotein E/LDL receptor knockout mice were fed an atherogenic diet for 7 to 9 months. Signs of spontaneous ischemia occurred. One to two days later, hearts were excised, Langendorff-perfused with induced global ischemia, and compared with mice without signs of disease. In vivo heart or brain infarctions were verified by heart histology and/or increased serum levels of cardiac troponin T and S100B. Hearts of mice with spontaneous ischemic events had improved function and reduced Langendorff-induced infarctions. To investigate the remote preconditioning effect of brain ischemia, bilateral ligation of the internal carotid arteries was performed in C57BL6 mice. Twenty-four hours later, their isolated hearts were protected against induced global ischemia. A possible role of inducible NO synthase (iNOS) was studied in iNOS knock out mice, who were not preconditioned by induced brain ischemia. Cardiac iNOS was unchanged 24 hours after preconditioning, suggesting that NO is a trigger rather than a mediator of protection. These findings suggest that spontaneous ischemic events in the brain and heart adapt the heart to ischemia. This can be mimicked by induced brain ischemia, with iNOS as a key factor of protection. Key Words: ischemic preconditioning Ⅲ remote preconditioning Ⅲ atherosclerosis Ⅲ brain ischemia Ⅲ inducible nitric oxide synthase C ardiac adaptation to ischemia can be achieved experimentally by ischemic preconditioning, transient episodes of ischemia and reperfusion before sustained ischemia.
Acute administration of glucocortiocoids reduces inflammation. Increasing knowledge of the mechanisms of action indicate that pretreatment with glucocorticoids could have organ-protective effects. We investigated whether pretreatment with methylprednisolone (MP) protected the heart against ischemia-reperfusion dysfunction, and we hypothetized that this protection might be due to induction of the cardioprotective heat shock protein 72 (HSP72). Rats were given vehicle or MP-40 mg/kg im as a double injection starting either 24 or 120 h (5 days) before their hearts were excised for Langendorff perfusion (n = 6-11 hearts in each group). MP improved left ventricular function and coronary flow during reperfusion after 30 min of global ischemia and reduced infarct size. Cardiac HSP72 gradually increased in a 24-h time course after MP treatment, and the increase was sustained 5 days afterward (immunoblotting). HSP72 mRNA was either reduced or unchanged, indicating a posttranscriptional regulation. Pretreatment with hydrocortisone or dexamethasone (n = 7-8 hearts of each) similarily increased cardiac HSP72 24 h afterward. This paper demonstrates that glucocorticoids increase cardiac HSP72 and protect organ function against ischemia-reperfusion injury.
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