Extracorporeal life support and digoxin-specific Fab fragments for successful management of Taxus baccata intoxication with low output and ventricular arrhythmia.

INTRODUCTION: Yew plants are evergreen shrubs which are widely spread throughout the northern hemisphere. Taxane alkaloid derivatives, mainly taxine B, represent the main toxins of Taxus baccata and are highly cardiotoxic. Due to the lack of randomized clinical trials, case reports on accidental or suicidal yew intoxications build the only source of knowledge of clinical treatment options. CASE REPORT: We report the case of a suicidal yew ingestion admitted to our hospital under prolonged cardiopulmonary resuscitation due to pulseless electrical activity. Extra-corporeal life support (ECLS) was established to maintain adequate organ perfusion. Repeated administration of digoxin-specific Fab antibody fragments, which cross-react with taxine, was associated with an immediate conversion from asystole to broad-complex bradycardia and a gradual normalization of the electrocardiogram (ECG). This was paralleled by a recovery of the cardiac function and weaning from the ECLS. The taxine metabolite 3,5-dimethoxyphenol could be detected by mass spectrometry before but not after the first Fab-fragment treatment. In contrast, the total amount of taxine (including the neutralized, Fab fragment-bound fraction) was increased after each Fab fragment administration, suggesting an accumulation of neutralized, since antibody-bound taxine in the blood by anti-digoxin Fab fragments. DISCUSSION: In conclusion, the successful clinical course of this case suggests a benefit of an early anti-digoxin Fab-fragment administration for the treatment of yew intoxication.

Deferoxamine, the newly developed iron chelator LK-614 and N-alpha-acetyl-histidine in myocardial protection.

During cold storage of donor hearts, reactive oxygen species produced by intracellular redox-active chelatable iron potentially alter myocardial function. To reduce this cold-induced injury we investigated the efficacy of two new modifications of the well established histidine-tryptophan-ketogluterate (HTK) solution (Custodiol) with the addition of N-alpha-acetyl-l-histidine and iron-chelators in a heterotopic rat heart transplantation model. The donor hearts were cardioplegically arrested with 20 ml cardioplegia and stored for 1 h. Then the hearts were anastomosed to the abdominal aorta and vena cava of the recipient (n=30). After 1 h reperfusion, myocardial function and energy charge potential were measured in three groups: HTK-1: addition of l-arginine and N-alpha-acetyl-l-histidine; HTK-2: addition of iron-chelators deferoxamine and LK-614; traditional HTK - control. After 1 h reperfusion, left ventricular systolic pressure (106+/-33 vs. 60+/-39, vs. 67+/-8 mmHg, P<0.05) and dP/dt minimal (-1388+/-627 vs. -660+/-446, vs. 871+/-188 mmHg/s, P<0.05) were significantly higher in the HTK-1 group. Energy charge potentials were not significantly different. This study showed that the novel modified HTK-1 solution improves myocardial contractility and relaxation after heart transplantation. Nevertheless, addition of the iron-chelators deferoxamine and LK-614 diminished these beneficial effects.

Inducible NO synthase expression in endomyocardial biopsies after heart transplantation in relation to the postoperative course.

OBJECTIVE: Ischemia and reperfusion during heart transplantation cause damage to cardiomyocytes and endothelial cells and may initiate later acute rejection. Free oxygen radicals generated by iNOS are widely accepted to be responsible for ischemic injury. Increased iNOS expression on cardiac tissue may represent a more intensive tissue injury during ischemia and reperfusion in heart transplantation. The aim of this study was, therefore, to test the hypothesis that increased iNOS expression in early postoperative endomyocardial biopsies correlates with rejection or infection episodes in the later postoperative course. PATIENTS AND METHODS: Right ventricular endomyocardial biopsies were obtained from heart transplantation recipients at transplantation and during the first 2 weeks postoperatively. The recipients were divided into three groups depending on the postoperative course during the first year after transplantation: patients in group 1 had an uncomplicated postoperative course, patients in group 2 developed significant signs of postoperative infection, while patients in group 3 presented with acute rejection (< or =grade 2R ISHLT). The expression was analyzed in a semi-quantitative score. RESULTS: iNOS expression was found in cardiomyocytes, endothelial cells, infiltrating cells, and vascular smooth muscle cells. At the time of heart transplantation, the expression was significantly increased in the rejection group compared to the other groups. This increase was even more pronounced in week 2. CONCLUSIONS: The present study shows that an increased iNOS expression at the time of heart transplantation could precede an acute rejection in the later postoperative course. Thus, measurements of iNOS expression may be of predictive value for an increased rejection risk and therefore offer the possibility of earlier therapeutic intervention.