Biomedical subjects
Publications and source records attributed to Wim K Lagrand.
Infective endocarditis remains a serious and complex disease with significant morbidity and mortality. The aim of this study was to demonstrate the clinical usefulness of 3-dimensional transesophageal echocardiography for the spatial assessment of aortic valve endocarditis. This case showed severe destruction of the aortic valve with perforations by endocarditis.
Circulating levels of C-reactive protein (CRP) constitute a cardiovascular risk marker. Immunohistochemical studies have revealed co-localization of CRP and activated complement in human infarcted myocardium suggesting CRP to enhance inflammation in ischemic myocardium by inducing local complement activation. The aim was to establish whether CRP activates complement in infarcted human myocardium and to assess the relationship between this activation and the duration of infarction. Myocardial tissue samples from 56 patients that had died from acute myocardial infarction were evaluated. Specimens were taken from infarcted as well as noninfarcted sites of the heart. CRP-mediated complement activation was assessed by immunohistochemistry and by measuring levels of complement, CRP, and CRP-complement complexes, specific markers for CRP-mediated activation, in homogenates of the heart. Infarctions of 12 hours to 5 days had significantly more extensive depositions of complement and CRP and contained significantly more CRP, activated complement, and CRP-complement complexes than infarctions that were less than 12 hours old. Levels of CRP complexes correlated significantly with CRP and complement concentrations in the infarctions, as well as with the extent of complement and CRP depositions as measured via immunohistochemistry. Specific activation products of CRP-mediated activation of complement are increased in infarcts of more than 12 hours in duration and correlate with the extent of complement depositions. Hence, CRP seems to enhance local inflammatory reactions ensuing in human myocardial infarcts of more than 12 hours duration.
OBJECTIVE: An increase of circulating secretory Phospholipase A(2) (sPLA(2)) is a risk factor for coronary artery disease. We hypothesized that this reflects participation of sPLA(2) in local inflammatory reactions ensuing in ischemic myocardium. Therefore, we studied the course of circulating sPLA(2), in patients with acute myocardial infarction (AMI) or unstable angina pectoris (UAP), and investigated the presence of sPLA(2) in infarcted myocardial tissue. METHODS: Plasma samples of 107 patients with AMI or UAP, collected on admission and at varying intervals thereafter, were tested for the presence of sPLA(2) and C-reactive protein (CRP). Cumulative release values of these parameters were calculated, which allowed for comparison of the results rearranged in time according to the onset of symptoms. By immunohistochemistry we studied the presence of sPLA(2) and CRP in myocardial tissue of 30 patients who died subsequent to AMI. RESULTS: Levels of sPLA(2) became elevated during the disease course in 66 of the 87 patients with AMI, and were higher than those of the patients with UAP of whom 8 of the 20 had elevated levels. By immunohistochemistry sPLA(2) was found to be localized in the infarcted myocardium, particularly in its borderzone, from 12 h after the onset of AMI. Positive staining for sPLA(2) was more extensive than that for CRP. CONCLUSIONS: The localization pattern of sPLA(2) in infarcted myocardium as well as its plasma course, in relation to those of CRP, are in line with a supposed pro-inflammatory role during AMI for sPLA(2) as a generator of lysophospholipids serving as ligands for CRP.
OBJECTIVES: C1-inhibitor protein (C1-INH) purified from pooled human plasma is used for the treatment of patients with hereditary angioedema. Recently, the beneficial effects of high-dose C1-INH treatment on myocardial ischemia or reperfusion injury have been reported in various animal models and in humans. We investigated the pharmacokinetic behavior of C1-INH in patients with acute myocardial infarction to calculate the amount of C1-INH required for optimal efficacy. METHODS: Twenty-two patients received an intravenous loading dose, followed by 48 hours of continuous infusion of C1-INH. Changes in the endogenous production of C1-INH were evaluated in 16 control patients with acute myocardial infarction. A 2-compartment model was used to estimate the fractional catabolic rate constant (FCR), transcapillary escape rate constant (TER), and extravascular return rate constant (ERR) of C1-INH. Software designed to analyze and fit measured data to unknown parameters in a system of differential equations was used to fit the experimental data against the 3-parameter model. RESULTS: With fixed TER and ERR values (0.014 h(-1) and 0.018 h(-1), respectively), 20 of the 22 cases yielded well-determined FCR values, and simultaneous fitting resulted in a median FCR of 0.011 h(-1) (95% confidence interval, 0.010 to 0.012 h(-1)) versus 0.025 h(-1) as reported in healthy control patients. Simultaneous estimation of TER, ERR, and FCR demonstrated weakly defined TER and ERR values, whereas the median FCR value remained unchanged. The use of a 2-compartment model resulted in a significantly better fit compared with the 1-compartment model. Physiologic explanations are offered for discrepancies in the literature. CONCLUSIONS: Dose calculation of C1-INH in patients treated with massive doses of C1-INH requires turnover parameters that differ from those found in healthy subjects, possibly because of suppression of continuous C1-INH consumption by target proteases.