Inotropic therapy for cardiac low output syndrome: comparison of hemodynamic effects of dopamine/dobutamine versus dopamine/dopexamine.

OBJECTIVE: To examine the effects of a therapy with dopexamine/dopamine in comparison with a regimen of dobutamine/dopamine on the outcome of patients with profound cardiogenic shock. MATERIAL AND METHODS: Twenty patients presenting with an acute cardiogenic shock assisted with mechanical ventilation, being refractory to a therapy with dopamine alone were analyzed. After persistence of low cardiac output syndrome (cardiac index <2.5 l/min/m2) was confirmed, patients were treated either with receiving dopexamine (2 microg/kg/min) (group 1) or dobutamine (6 microg/kg/min) (group 2) in combination with dopamine (6 microg/kg/min) for 24 hrs. Hemodynamic parameters, urine production and clinical outcome were measured at intervals throughout the study. The groups were similar with respect to demographics and risk factors and there were no significant differences in the supportive treatment and hemodynamics at baseline. RESULTS: The dopexamine treated patients had lower myocardial oxygen consumption (9310+/-2243 mmHg O2/sec vs. 10621+/-2552 mmHg O2/sec) and lower mean arterial pressure (66+/-11 mmHg vs. 71+/-10 mmHg) after the 24 hrs treatment interval, but no one of the changes reached statistical significance. No differences were found between the two groups for other variables and the overall clinical outcome. CONCLUSION: The present study revealed that neither substance is superior in the treatment of cardiogenic shock, even if the effect on myocardial consumption and the reported beneficial effects on renal and splanchnic functions might favour the use of dopexamine under certain circumstances.

The FCGR2A--Arg131 variant is no major mortality factor in the elderly--evidence from a German centenarian study.

The functional single nucleotide polymorphism rs1801274 in the FCGR2A gene (His131Arg) influences the efficiency of hIgG2 binding, the main isotype produced in response to encapsulated bacteria like Streptococcus pneumoniae and Haemophilus influenzae. In contrast to the receptor with the His131 allele, FcgammaRIIa-Arg131 binds hIgG2 poorly and carriers of this variant have been shown to be much more susceptible to succumb to bacterial pneumonia or meningitis. As bacteraemic pneumonia is one of the leading causes of death in elderly individuals, we hypothesized that the Arg131 variant could be a major mortality factor in the old. We analysed the FCGR2A-His131Arg polymorphism in a group of 408 German centenarians and two samples of younger Germans aged 60-75 and 18-49 years, respectively. No statistically significant differences were observed between the three age groups, neither at the allele nor at the genotype level. Apparently, the ability to reach old age is largely unaffected by the genetically determined efficacy of the FCGR2A-based immune response. However, the severely reduced ability of FCGR2A-131Arg carriers to eliminate encapsulated bacteria must apparently be compensated by an alternative mechanism, possibly involving other genetic survival factors.

A functional variant in the CARD4 gene and risk of premature coronary heart disease.

Infection and innate immunity have been suggested as playing an important role in the pathogenesis of atherosclerosis. The recently discovered pattern-recognition receptor (PRR) proteins initiate signalling after host-pathogen interactions and several PRRs, especially the Toll-like receptor 4 (TLR4), have been shown to be involved in the development and progression of atherosclerosis. A new addition to the PRRs is CARD4, a gene that encodes the protein nucleotide-binding oligomerization domain 1 (NOD1) and that seems to be associated with barrier function in chronic inflammatory disorders. Recently, a functional variant in the CARD4 gene, the insertion-deletion polymorphism ND(1)+32656, has been associated with inflammatory barrier diseases (inflammatory bowel diseases and asthma). We analysed the frequencies of this known functional mutation in the CARD4 gene and of the two adjacent variants, rs2075822 and rs2907748, in a German sample of 1440 unrelated early onset coronary heart disease (CHD) patients and healthy controls. Genotype and haplotype data showed no evidence for a significant association of these CARD4 variants with CHD. Our results suggest that the analysed CARD4 mutations do not play a major role in the aetiology of CHD.

Multipotent cells of monocytic origin improve damaged heart function.

Recently, we generated cells with multipotent properties from blood monocytes that in vitro differentiate into various somatic cell types. This experimental study investigated whether these programmable cells of monocytic origin (PCMO) succeed to restore left ventricular function after myocardial infarction (MI). PCMO were generated from monocytes by exposition to RPMI medium containing M-CSF and IL-3 for 6 days. MI was induced in female Lewis rats ligating the left coronary artery. PCMO of male Lewis donors were injected either intramyocardially (i.my.) or intravenously (i.v.) 24 h or 6 days post-infarction. Hemodynamic assessment after 60 days demonstrated significant improvement of left ventricular function following i.my. transplantation of PCMO as well as early (24 h post-infarction) i.v. application while nonmodulated monocytes failed to restore heart function. The Y-chromosome-specific SRY gene of male donor PCMO was detected exclusively in infarcted hearts of animals, which demonstrated improved cardiac function. Subdivision of infarcted hearts by microdissection localized the SRY gene-containing department to the left ventricle adjacent to the infarcted area whereas the right ventricle remained negative. Successful generation of PCMO in access numbers allows their autologous use as a new additive treatment for early restoration of cardiac function after MI.

Matrix metalloproteinase-9 in bronchiolitis obliterans syndrome after lung transplantation.

Bronchiolitis obliterans syndrome (BOS) is a severe complication after lung transplantation (LTX). In a retrospective cohort study 12 stable healthy recipients (non-BOS) and eight patients with BOS were enrolled after LTX and matrix metalloproteinases (MMP)-9, TIMP-1 and cell characteristics in bronchoalveolar lavage (BAL) samples (n = 145) were analysed. BALs from patients with BOS were further divided according to whether they were obtained before (pre-BOS) or after manifestation of BOS (BOS group). The MMP-9/TIMP-1 ratio was significantly increased in the BOS group compared with non-BOS or pre-BOS; furthermore, the ratio was negatively correlated with forced expiratory volume in one second. In zymography, the active form of MMP-9 was detected predominantly in the BOS group. In addition, zymography showed the banding pattern of neutrophil-derived MMP-9, indicating that polymorphonuclear neutrophils (PMNs) were the main source of MMP-9. According to that, MMP-9 was significantly correlated with the number of PMN. In immunocytochemistry, MMP-9 was also associated predominantly with PMN. This is the first study to evaluate the expression of matrix metalloproteinase-9 and tissue inhibitors of metalloproteinases-1 over time during manifestation of a fibroproliferative lung disease in patients. It demonstrates development of bronchiolitis obliterans syndrome after lung transplantation is associated with an imbalance of matrix metalloproteinases-9/tissue inhibitors of metalloproteinase-1 ratio.

Heterogeneity of noninvasive arrhythmic risk indicators in patients with ischemic cardiomyopathy.

Noninvasive electrocardiographic variables for arrhythmic risk stratification in chronic heart failure are of great clinical interest but remain highly controversial. This study analyzed repolarization dispersion, heart rate variability, ventricular ectopic activity, and hemodynamic parameters in 30 patients with ischemic heart failure and in 20 normal control subjects. The values for all parameters were distinctly separated between the failure and control group. Left ventricular ejection fraction had a strong relation to ventricular ectopic activity (r = .54), a weak association with repolarization dispersion (r = .29), and seemingly no parallels with heart rate variability (r = .12). However, no linear association could be detected between any of the arrhythmic risk indicators (r = .10-.22), whereas a number of linearly related angiographic-hemodynamic variables readily defined the mechanical risk profile. Thus, alterations of noninvasive arrhythmic risk indicators in heart failure are not uniform, which confounds approaches for a composite ECG risk score in individual patients.