Out of hospital extracorporeal life support (ECLS) implantation in cardiogenic shock after cardiac arrest.

We report the use of out-of-hospital extracorporeal life support (ECLS) in a 62-year-old patient with severe cardiogenic shock after cardiac arrest. The patient was successfully stabilized using the ECLS system in the pre-hospital setting. Hospital discharge with a good neurological outcome was possible after 23days.

Expansion of the Multi-Link Frontier™ coronary bifurcation stent: micro-computed tomographic assessment in human autopsy and porcine heart samples.

BACKGROUND: Treatment of coronary bifurcation lesions remains challenging, beyond the introduction of drug eluting stents. Dedicated stent systems are available to improve the technical approach to the treatment of these lesions. However dedicated stent systems have so far not reduced the incidence of stent restenosis. The aim of this study was to assess the expansion of the Multi-Link (ML) Frontier™ stent in human and porcine coronary arteries to provide the cardiologist with useful in-vitro information for stent implantation and selection. METHODOLOGY/PRINCIPAL FINDINGS: Nine ML Frontier™ stents were implanted in seven human autopsy heart samples with known coronary artery disease and five ML Frontier™ stents were implanted in five porcine hearts. Proximal, distal and side branch diameters (PD, DD, SBD, respectively), corresponding opening areas (PA, DA, SBA) and the mean stent length (L) were assessed by micro-computed tomography (micro-CT). PD and PA were significantly smaller in human autopsy heart samples than in porcine heart samples (3.54±0.47 mm vs. 4.04±0.22 mm, p = 0.048; 10.00±2.42 mm(2) vs. 12.84±1.38 mm(2), p = 0.034, respectively) and than those given by the manufacturer (3.54±0.47 mm vs. 4.03 mm, p = 0.014). L was smaller in human autopsy heart samples than in porcine heart samples, although data did not reach significance (16.66±1.30 mm vs. 17.30±0.51 mm, p = 0.32), and significantly smaller than that given by the manufacturer (16.66±1.30 mm vs. 18 mm, p = 0.015). CONCLUSIONS/SIGNIFICANCE: Micro-CT is a feasible tool for exact surveying of dedicated stent systems and could make a contribution to the development of these devices. The proximal diameter and proximal area of the stent system were considerably smaller in human autopsy heart samples than in porcine heart samples and than those given by the manufacturer. Special consideration should be given to the stent deployment procedure (and to the follow-up) of dedicated stent systems, considering final intravascular ultrasound or optical coherence tomography to visualize (and if necessary optimize) stent expansion.

Enhanced expression of platelet CD40-ligand by in vitro lipopolysaccharide-challenge in patients with ventricular fibrillation complicating acute myocardial infarction.

BACKGROUND: Acute myocardial infarction can be complicated by ventricular arrhythmias due to electrophysiological changes in the ischemic myocardium, but the exact predisposing factors causing ventricular fibrillation during myocardial infarction still remain unclear. A role of inflammatory stimulation on platelets as a potential risk factor for ventricular fibrillation during acute myocardial infarction has not been described yet. METHODS AND RESULTS: Whole blood samples of 21 patients with a history of acute myocardial infarction (AMI) and ventricular fibrillation (VF) were incubated with lipopolysaccharide (LPS). As a control group, we studied 19 patients without VF during AMI. CD40-ligand and CD62P expression on platelets and tissue factor binding on monocytes were measured by flow cytometry. Platelet-monocyte aggregates were measured by CD41 expression on platelets adherent to monocytes. Soluble CD40-ligand plasma levels were measured with an ELISA. Without LPS, no significant difference between the patient groups concerning CD40L expression on platelets was observed, but plasma levels of soluble CD40L were significantly higher in patients with a history of AMI with VF. After LPS stimulation, patients with a history of VF showed a significantly increased expression of CD40L in comparison to the patients without ventricular fibrillation, based on a significantly higher increase of CD40L expression. CD62P expression on platelets was significantly increased in patients with a history of VF. CONCLUSIONS: Patients with a history of VF complicating AMI show an enhanced expression of CD40L on platelets after in vitro lipopolysaccharide-challenge with an enhanced platelet activation.

Enhanced coagulation activation by in vitro lipopolysaccharide challenge in patients with ventricular fibrillation complicating acute myocardial infarction.

BACKGROUND: Indicators of coagulation and inflammation are elevated in patients with coronary heart disease. A role of coagulation activation in ventricular fibrillation during acute myocardial infarction has not been described. METHODS AND RESULTS: Whole blood samples of 21 patients with a history of acute myocardial infarction complicated by ventricular fibrillation and whole blood samples of 18 patients without ventricular fibrillation were incubated with lipopolysaccharide (LPS). In both groups, the in vitro blood coagulation time was measured with the ReoRox, a viscometric whole blood coagulometer. CD62P expression on platelets, tissue-factor binding on monocytes, and platelet-monocyte aggregates were measured with flow cytometry. Without LPS, no difference in the coagulation times were observed in both patient groups. After incubation with LPS, patients with a history of ventricular fibrillation showed a significantly decreased coagulation time compared to patients without ventricular fibrillation. The decrease of coagulation time after incubation with LPS also differed significantly in both groups. Expression of CD62P on platelets was significantly higher in patients with a history of ventricular fibrillation after incubation with LPS. Although in each patient group incubation with LPS induced a significantly increased amount of tissue factor on monocytes and a significantly increased the number of platelet-monocyte aggregates, the two groups did not differ significantly concerning tissue factor binding on monocytes and the amount of platelet-monocyte aggregates. CONCLUSIONS: After in vitro LPS challenge, patients with a history of ventricular fibrillation during myocardial infarction show an enhanced coagulation activation, which may partly be due to an enhanced platelet activation.

Magnetic resonance imaging findings in patients with Brugada syndrome.

INTRODUCTION: Cardiac magnetic resonance imaging (CMR) is a powerful diagnostic tool for evaluating cardiac structure and function. Recently, right ventricular wall-motion abnormalities were described using electron beam tomography in patients with Brugada syndrome. In the present study, we prospectively evaluated CMR findings in patients with Brugada syndrome compared to matched controls. METHODS AND RESULTS: CMR was performed on 20 consecutive patients with proven Brugada syndrome. The imaging protocol included breath-hold dark blood prepared T1-weighted multislice turbo spin-echo and gradient-echo images. Ventricular volumes and dimensions were compared to age- and sex-matched normal volunteers. The right ventricular outflow tract area was significantly enlarged in patients with Brugada syndrome compared to controls (11 vs 9 cm2, P = 0.018). There was a trend to larger right ventricular end-diastolic and end-systolic volumes and lower right ventricular ejection fraction in patients with Brugada syndrome compared to controls. However, none of the differences reached significance (P = 0.3, P = 0.08, and P = 0.06, respectively). There was no statistically significant difference in the left ventricular parameters between patients and controls. High intramyocardial T1 signal similar to fat signal was observed in 4 (20%) of the 20 patients compared to none of the controls. CONCLUSION: The findings support the view that subtle structural changes, such as right ventricular outflow tract dilation may point to a localized arrhythmogenic substrate in patients with Brugada syndrome.

Anti-hirudin antibodies alter pharmacokinetics and pharmacodynamics of recombinant hirudin.

Recombinant hirudin (r-hirudin) is a potent direct thrombin inhibitor with immunogenic properties. Anti-hirudin antibodies (aHAb) are detected in up to 74% of patients treated with r-hirudin for more than 5 days. aHAb may alter the pharmacokinetics and pharmacodynamics of r-hirudin. The effects of aHAb on the pharmacokinetics of r-hirudin were investigated in rats receiving r-hirudin intravenously either without aHAb (controls), 15 min after intravenous administration of non-specific antibodies or aHAb, and after pre-incubation with aHAb. When both were compared to controls and pre-treatment with non-specific antibodies, aHAb significantly altered the pharmacokinetics of r-hirudin with similar effects in both approaches: In the presence of aHAb, the volume of distribution in a steady state and total plasma clearance were diminished, while the half-life of elimination was prolonged. Both the maximum r-hirudin plasma concentration and the area under the curve were increased. In addition, r-hirudin filtration by high-flux hemodialyzer membranes (polysulfone, AN69) was investigated 1) in the absence of aHAb, 2) in the presence of non-specific mouse antibodies, and 3) in the presence of three monoclonal aHAb. In the absence of aHAb, both hemodialyzers allowed for significant r-hirudin filtration. Non-specific mouse antibodies did not markedly affect r-hirudin filtration. By contrast, all three aHAb almost completely hindered r-hirudin filtration. aHAb varied in their capacity to neutralize r-hirudin. In conclusion, aHAb markedly alter the pharmacokinetics of r-hirudin leading to r-hirudin accumulation. In the presence of aHAb, hemofiltration does not allow for rapid reduction of r-hirudin concentration. aHAb are capable of modifying pharmacodynamics of r-hirudin. Close monitoring of aHAb-positive patients treated with r-hirudin is considered mandatory.

Biological relevance of anti-recombinant hirudin antibodies--results from in vitro and in vivo studies.

This article provides an overview of the clinically relevant characteristics of antibodies directed toward recombinant (r) hirudin, with emphasis on the different ways in which these antibodies may influence pharmacokinetics and pharmacodynamics of r-hirudin. A high incidence of anti-hirudin antibody (AHAb) formation, mainly of the immunoglobulin G (IgG) subclass, was reported in up to 74% of patients treated with r-hirudin for more than 5 days. Like other drug-induced antibodies, AHAb may be responsible for accumulation or neutralization of the drug. Current clinical data support this assumption with reports on reduced metabolism, enhanced activity, and accumulation and neutralization of r-hirudin in the presence of AHAb. By examining AHAb developed in patients, we were able to demonstrate that AHAbs are capable of neutralizing r-hirudin in vitro. In addition, the anticoagulant activity of r-hirudin administered to Sprague-Dawley rats was almost completely abolished when a monoclonal mouse AHAb with known r-hirudin neutralizing capacity in vitro was injected intravenously. Because r-hirudin is mainly eliminated via the kidneys, formation of r-hirudin-AHAb complexes may, due to their size, result in accumulation of r-hirudin. We investigated filtration of r-hirudin incubated with monoclonal mouse AHAb by using high-flux hemodialyzers in a suitable in vitro model. Whereas sieving coefficients (SC) were high in the absence of AHAb, they were minimal (SC < 0.05) in the presence of AHAb. These findings may also be important when AHAb-positive patients treated with r-hirudin undergo hemofiltration procedures, which have recently been described as a rescue measure in case of r-hirudin overdosage. In vivo, the influence of a non-neutralizing monoclonal mouse AHAb on r-hirudin pharmacokinetics was examined in rats. Pharmacokinetic data compared with those of a control group without AHAb administration revealed that r-hirudin elimination half-life was significantly prolonged (59 +/- 25 minutes versus 142 +/- 25 minutes). This was accompanied by a decrease of total plasma clearance of r-hirudin. The volume of distribution of r-hirudin was significantly decreased (275 +/- 112 mL/kg versus 35 +/- 3 mL/kg), indicating that r-hirudin bound by AHAb is mainly distributed to the intravascular compartment. Taken together, both the half-life prolongation and the decrease of the volume of distribution contribute to r-hirudin accumulation and may explain respective findings in patients. In summary, two different effects of AHAbs seem to be clinically relevant: decreasing anticoagulant activity of r-hirudin by neutralization and accumulation of r-hirudin by reducing renal clearance. Formation of AHAbs has not yet been correlated with enhanced major bleeding complications. However, close monitoring of coagulation parameters is recommended in AHAb-positive patients during r-hirudin treatment.