Disease-associated QT-shortage versus quinine associated QT-prolongation: age dependent ECG-effects in Ghanaian children with severe malaria.

BACKGROUND: While several anti-malarials are known to affect the electric conduction system of the heart, less is known on the direct effects of Plasmodium falciparum infection. Some earlier studies point to a direct impact of Plasmodium falciparum infection on the electric conduction system of the heart. The aim of this study was to analyse infection- and drug-induced effects on the electric conduction system. METHODS: Children aged 12 months to 108 months with severe malaria were included in Kumasi, Ghana. In addition to basic demographic, clinical, biochemical and parasitological, biochemical data were measured data upon hospitalization (day 0) and 12-lead electrocardiograms were recorded before (day 0) and after (day 1) initiation of quinine therapy as well as after 42 (±3) days. RESULTS: A total of 180 children were included. Most children were tachycardic on day 0 but heart rate declined on day 1 and during follow up. The corrected QT intervals were longest on day 1 and shortest on day 0. Comparison of QT intervals with day 42 (healthy status) after stratification for age demonstrated that in the youngest (<24 months) this was mainly due to a QT shortage on day 0 while a QT prolongation on day 1 was most pronounced in the oldest (≥48 months). Nearly one third of the participating children had measurable 4-aminoquinoline levels upon admission, but no direct effect on the corrected QT intervals could be shown. CONCLUSION: Severe P. falciparum infection itself can provoke changes in the electrophysiology of the heart, independent of anti-malarial therapy. Especially in young - thus non immune - children the effect of acute disease associated pre-treatment QT-shortage is more pronounced than quinine associated QT-prolongation after therapy. Nevertheless, neither malaria nor anti-malarial induced effects on the electrophysiology of the heart were associated with clinically relevant arrhythmias in the present study population.

BIBN4096BS and CGRP(8-37) antagonize the relaxant effects of alpha-CGRP more than those of beta-CGRP in human extracranial arteries.

We hypothesize that dilatation of extracranial arteries during migraine could be caused by CGRP. We compared the relaxant effects of alpha-calcitonin gene-related peptide (alpha-CGRP) and beta-calcitonin gene-related peptide (beta-CGRP) and the antagonism by BIBN4096BS and CGRP(8-37) on rings of human temporal and occipital arteries precontracted with KCl. beta-CGRP relaxed temporal (-logEC50M = 8.1) and occipital arteries (-logEC50M = 7.6) with 19-fold and 29-fold lower potencies respectively than alpha-CGRP. Nearly maximal effective concentrations of alpha-CGRP (4 nM) and beta-CGRP (50 nM) caused stable relaxations of the temporal artery for 4 h without fading. BIBN4094BS antagonized the effects of alpha-CGRP (pK(B) = 10.1 and 9.9, respectively) more than beta-CGRP (pK(B) = 9.3 and 9.2 respectively) on both temporal and occipital arteries. CGRP(8-37) antagonized the effects of alpha-CGRP (pK(B) = 6.6 and 6.4 respectively) more than beta-CGRP (pK(B) = 5.7 and 5.5 respectively) on both temporal and occipital arteries. Antagonism of the relaxant effects of alpha-CGRP (4 nM) and beta-CGRP (50 nM) by BIBN4096BS (10 and 100 nM) was reversible for beta-CGRP, but irreversible for alpha-CGRP, 1 h after BIBN4096BS washout. We conclude that alpha-CGRP and beta-CGRP interact either at different binding sites of the same CGRP receptor system or all together with different receptor systems in human extracranial arteries. BIBN4096BS binds more firmly to the receptor activated by alpha-CGRP than to the receptor activated by beta-CGRP.

Cardiac function in Ghanaian children with severe malaria.

PURPOSE: The aim was to assess whether impaired cardiac function contributes to symptoms of severe malaria in general or to metabolic acidosis in particular in children living in endemic regions. METHODS: In a prospective observational investigation, 183 children with severe malaria were investigated for hemodynamic status and cardiac function upon admission (day 0) and after recovery (day 42). Cardiac function parameters were assessed by cardiac ultrasonography. Blood gas analyses and cardiac enzymes were measured at hospitalization and follow-up. Differences in subgroups with and without metabolic acidosis as well as other severe malaria-defining symptoms and conditions were assessed. RESULTS: Cardiac index (CI) was significantly increased on day 0 compared to day 42 (5.8 ml/m(2), SD ± 1.8 ml/m(2), versus 4.7 ml/m(2), SD ± 1.4 ml/m(2); P < 0.001). CI correlated negatively with hemoglobin levels but not with parameters indicating impaired tissue perfusion or metabolic acidosis. Parasite levels had a significant influence on metabolic acidosis but not on CI. Alterations related to cardiac function, hemoglobin levels and metabolic acidosis were most prominent in children younger than 2 years. CONCLUSION: Increased CI reflecting high output status is associated with low hemoglobin levels while metabolic acidosis is linked to parasite levels.