Endothelial progenitor cells (EPCs) are known to play a significant role in reendothelialization and vascular repair. Recently, a mineralocorticoid receptor was demonstrated to be expressed by EPCs. The study aimed to evaluate a potential influence of eplerenone treatment on the total number of EPCs in patients with chronic heart failure.Eighty-seven male patients with chronic heart failure were included (age: 23-83 years; body mass index 29.1 ± 5.1 kg/m²; New York Heart failure classification (NYHA) I: 29 patients, NYHA II: 32 patients, NYHA III: 26 patients). Numbers of circulating EPCs were quantified immediately using flow cytometry. Twenty-eight patients received therapy with eplerenone. Patients were further characterized by echocardiography, spirometry and laboratory markers.Patients with ongoing eplerenone administration showed higher levels of circulating cells expressing CD34+ (p<0.05) and CD34+KDR+ (p<0.05) and CD34+CD133+KDR+ cells (p<0.05). The effects of eplerenone treatment could be shown to be independent of NYHA status, genesis of the underlying cardiovascular morbidity, left ventricular function and co-medication.Patients with chronic heart failure treated with eplerenone show higher numbers of EPCs. The clinical benefit for treatment with eplerenone has been demonstrated even for patients with mild heart failure and might be partially mediated by EPCs.
Intra-aortic counterpulsation (IABP) is frequently applied to provide hemodynamic support in patients with refractory cardiogenic shock (CS) of ischemic and non-ischemic cause. However, clinical data comparing outcomes are lacking for both indications. The purpose of this analysis was to evaluate outcome and safety of IABP support in patients with ischemic and non-ischemic CS and to identify predictors of early mortality in this severely ill patient population.For the period between 1998 to 2010, data from 489 consecutive patients (age, 67.2 ± 12.2 years; 65.9% male) who had received IABP support for CS at the University Heart Center Jena were retrospectively analyzed. The primary endpoint was overall mortality at 7 and 30 days. Secondary endpoints included the incidence of vascular and neurologic complications as well as long-term survival. Follow-up data on current health status of the patients were acquired either from health insurance records or based on patient and physician interviews. After data compilation, patients were assigned to one of the following subgroups: ST-elevation myocardial infarction (STEMI; n = 368; 75.3%), non-STEMI (n = 75; 15.3%) and congestive heart failure (CHF; n = 46; 9.4%). Of the 489 patients enrolled, 422 (86.4%) were successfully weaned from IABP support. However, a significantly lower proportion of patients were weaned successfully in the STEMI group (n = 310; 84.1%) compared to the other two groups (non-STEMI: n = 70, 92.4%; CHF: n = 45, 97.8%; P=.041). Overall mortality at 30 days was 36.4% (n = 178) and was not significantly different between the subgroups. Significant predictors of 30-day mortality included age >70 years (odds ratio [OR], 16.81; confidence interval [CI], 1.241-227.54), ejection fraction <40% (OR, 36.33; CI, 2.93-451.05) and mechanical ventilation (OR, 12.42; CI, 1.21-127.17). Long-term follow-up was 803 ± 1061 days (range, 0-1380 days), with a long-term survival rate of 38.3%.IABP represents a safe technology for hemodynamic support and is associated with low complication rates. Parameters relating to early mortality include age >70 years, respiratory failure requiring mechanical ventilation, and left ventricular function <40%, which represent an additional risk of death. However, the etiology of CS had no effect on mortality in this analysis. This observation should encourage physicians to apply IABP for hemodynamic support in patients with nonischemic left ventricular failure.
Obesity and the metabolic syndrome are dramatically increasing problems. Red blood cell distribution width (RDW), the variability in size of circulating red blood cells, has been demonstrated to be altered in different clinical settings. This analysis aimed to investigate the relationship between RDW and obesity in adolescents and in an animal model of diet-induced obesity (DIO).Seventy-nine male adolescents (aged 13-17 years) were studied. Thirty-seven of them were overweight (body mass index ≥ 90th percentile). RDW, markers of inflammation and stem cell factor (SCF) were determined. In an animal study, mice were fed with different diets for 15 weeks. RDW was determined using an animal blood count machine.RDW differed significantly between normal-weight adolescents (13.07 ± 0.09) and overweight adolescents (13.39 ± 0.10, P = 0.015), whereas erythrocyte counts and haematocrit did not differ. RDW correlated to markers of inflammation and inversely to SCF. In the mice animal model, nutritional changes increased RDW, whereas overweight per se did not change RDW.RDW is elevated in overweight and reflects the inflammatory state. RDW potentially represents an additional and cost-effective tool to indicate inflammation. Future studies are needed to understand the differential influences of nutrition and overweight on RDW.
The aim was to study impacts of mild to severe hypoxia on human red blood cell (RBC)-nitric oxide synthase (NOS)-dependent NO production, protein S-nitrosylation and deformability.Ambient air oxygen concentration of 12 healthy subjects was step-wisely reduced from 20.95% to 16.21%, 12.35%, 10% and back to 20.95%. Additional in vitro experiments involved purging of blood (±sodium nitrite) with gas mixtures corresponding to in vivo intervention.Vital and hypoxia-associated parameters showed physiological adaptation to changing demands. Activation of RBC-NOS decreased with increasing hypoxia. RBC deformability, which is influenced by RBC-NOS activation, decreased under mild hypoxia, but surprisingly increased at severe hypoxia in vivo and in vitro. This was causatively induced by nitrite reduction to NO which increased S-nitrosylation of RBC α- and β-spectrins -a critical step to improve RBC deformability. The addition of sodium nitrite prevented decreases of RBC deformability under hypoxia by sustaining S-nitrosylation of spectrins suggesting compensatory mechanisms of non-RBC-NOS-produced NO.The results first time indicate a direct link between maintenance of RBC deformability under severe hypoxia by non-enzymatic NO production because RBC-NOS activation is reduced. These data improve our understanding of physiological mechanisms supporting adequate blood and, thus, oxygen supply to different tissues under severe hypoxia.
Aims Conventional parameters of right ventricular (RV) function are load‐dependent and therefore do not accurately reflect contractility in patients with relevant tricuspid regurgitation (TR). RV adaptability to load has been characterized using the Dandel's index in patients with heart failure, but its prognostic value in patients undergoing tricuspid transcatheter edge‐to‐edge repair (T‐TEER) has not been investigated so far. Methods and results From the EuroTR registry (2019 to 2022), patients with complete datasets and a minimum of 2‐years of follow‐up were included. RV functional parameters (i.e. tricuspid annular plane systolic excursion [TAPSE], fractional area change [FAC], TAPSE/systolic pulmonary arterial pressure [sPAP]), as well as a echocardiographic RV load adaptation index (Dandel's index) were assessed and their predictive value in terms of all‐cause mortality evaluated using logistic multivariate logistic regression. The majority of the 364 patients had secondary TR (96%) and were severely symptomatic (New York Heart Association class ≥III; 92%). At 2‐year follow‐up, 36% of patients had died. Functional RV parameters (TAPSE: hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.62–0.84; FAC: HR 0.73, 95% CI 0.59–0.91), coupling index (TAPSE/sPAP: HR 0.8, 95% CI 0.65–0.99) and Dandel's index (HR 0.67, 95% CI 0.53–0.85) were all associated with mortality at 2 years in univariable analyses. In a multivariate logistic regression model, the Dandel's index maintained its predictive value ( p < 0.001), along with TAPSE and absence of signs of right heart failure, with an optimal threshold of 20.5 determined by the receiver‐operating characteristic analysis. This threshold also successfully predicted cardiac hospital readmission. A multivariate analysis was conducted to identify parameters linked to RV function and predicting clinical outcomes. Conclusion Assessment of the RV capacity to adjust for changes in loading conditions predicted mortality in patients with severe symptomatic TR undergoing T‐TEER. The use of a multiparametric approach including the Dandel's index to assess RV function had an incremental value for the stratification of patients into subgroups with different prognosis.
Hypoxia frequently associated with certain physiologic and pathologic conditions influences numerous cellular functions. Because the effects of short-term hypoxia are incompletely understood, we examined phagocytosis and cytokine production as well as the activation of the transcription factors HIF-1 and NFκB in peripheral blood cells of healthy volunteers exposed to an oxygen concentration equivalent to that found at a height of 5500 m. Furthermore, we analysed plasma HIF-1 and serum concentrations of various HIF-1-dependent genes. Results showed that short-term hypoxia increased phagocytosis in neutrophils without affecting monocyte phagocytosis. Hypoxia decreased basal TNFα concentration in monocytes and basal interferon γ concentration in CD4 + T lymphocytes. In contrast, plasma HIF and serum VEGF concentrations were not affected by hypoxia, although serum EPO concentration was raised. In PBMC, hypoxia increased cytosolic HIF-1 concentration without affecting nuclear HIF-1 concentration and led to a rise in the nuclear NFκB in PBMC. Our results show that short-term hypoxia affects immune functions in healthy individuals. Furthermore, we speculate that the effects of hypoxia are not due to HIF-1, but are caused by the activation of NFκB .
