Digitalis: a dangerous drug in atrial fibrillation? An analysis of the SPORTIF III and V data.

OBJECTIVE: In heart failure, digitalis increases exercise capacity and reduces morbidity, but has no effect on survival. This raises the suspicion that the inotropic benefits of digitalis may be counteracted by serious adverse effects. Patients with atrial fibrillation (AF) were studied to clarify this. DESIGN: In the Stroke Prevention using an ORal Thrombin Inhibitor in atrial Fibrillation (SPORTIF) III and V studies, 7329 patients with AF at moderate-to-high risk were randomised to preventive treatment of thromboembolism, either with warfarin or the oral direct thrombin inhibitor ximelagatran. The survival of users and non-users of digitalis was investigated. RESULTS: At baseline, 53.4% of the study population used digitalis, and these patients had a higher mortality than non-users (255/3911 (6.5%) vs 141/3418 (4.1%), p<0.001; hazard ratio (HR) = 1.58 (95% CI 1.29 to 1.94)). Digitalis users also had more baseline risk factors. After multivariate risk factor adjustment, the increased mortality persisted (p<0.001; HR = 1.53 (95% CI 1.22 to 1.92 vs 1.23 to 1.92)). CONCLUSIONS: The results suggest that digitalis, like other inotropic drugs, may increase mortality. This may be concealed in heart failure, but be revealed in patients with AF, who need the rate-reducing effect of digitalis, but do not benefit much from an increased inotropy. Cautious interpretation of the data is mandatory since the patients were not randomised with respect to digitalis use.

[Magnetic tomography--new imaging techniques and future perspectives]. / Magnettomografi--nyere bildeteknikker og fremtidsperspektiver.

BACKGROUND: From the very introduction of MRI into medicine, the modality has presented the user a long list of theoretical tissue contrast parameters. The development of MRI has been aimed at turning these theoretical possibilities into practical options. MATERIAL AND METHODS: We give an overview of the new MRI techniques and perspectives for the future based on a literature search and our own experience. RESULTS: Today, the modality offers state-of-the-art anatomical details as well as visualisation of several functional parameters such as perfusion, diffusion, blood oxygen saturation, and tissue temperature. In the near future, MRI may provide absolute quantification of regional perfusion and rate of oxygen consumption in a clinical setting. New vascular and gastrointestinal contrast media will further increase the sensitivity and specificity of MRI. A continuous increase in imaging speed has made MRI capable of providing adequate "fluoroscopic" guidance during interventional procedures, and real-time diagnostic imaging is only few years ahead. INTERPRETATION: The spread of MRI installations will increase as a result of increasing demand for the best and least harmful diagnostic procedure. The main challenge to the MRI community will be to exploit the vast diagnostic possibilities.

Vitamin E restores endothelium dependent vasodilatation in cholesterol fed rabbits: in vivo measurements by photoplethysmography.

OBJECTIVE: Pulse curve plethysmography was used to examine the effect of vitamin E on endothelium dependent and independent vasodilatation in unanaesthetised cholesterol fed rabbits in vivo. The height of the dicrotic notch was used as an index of general arterial vasodilatation. METHODS: Twenty eight rabbits were divided into three study groups; a control group (group 1, n = 8), a group fed 1% cholesterol (group 2, n = 10), and a group fed 1% cholesterol with the addition of 0.2% vitamin E after four weeks (group 3, n = 10). After six weeks on diet the vasodilator responses to acetylcholine and glyceryl trinitrate were measured by photoplethysmography of the rabbit ear. Recordings were made during light sedation at baseline and during infusion of acetylcholine (1.5, 3.0, 6.0, and 12 micrograms.min-1) and glyceryl trinitrate (3.75, 7.5, and 15.0 micrograms.min-1). In a second set of experiments with control fed rabbits (n = 5), acetylcholine infusions were given before and after infusion of L-nitro-arginine (15 mg). RESULTS: The relative height of the dicrotic notch (which predominantly indicates arterial tone in the larger vessels) was reduced by acetylcholine in a dose dependent manner, but in cholesterol fed rabbits (group 2) this response was significantly decreased. Rabbits receiving concomitant dietary vitamin E responded in a similar manner to controls. The difference was most prominent using acetylcholine at a dose of 3.0 micrograms.min-1, where the mean change from baseline was 11(SEM 4)% in group 2, compared to 31(6)% in group 1 (p = 0.01), and to 26(5)% in group 3 (p = 0.02). Similar differences between the groups were observed for the increase in heart rate during acetylcholine infusions. In contrast, the responses to glyceryl trinitrate were similar in all groups. After infusions of L-nitro-arginine, the responses to acetylcholine were blunted. CONCLUSIONS: Supplementation with vitamin E restored the otherwise reduced vascular response to acetylcholine in cholesterol fed rabbits. Analysis of photoplethysmographic pulse curves is a simple non-invasive method of evaluating arterial vasodilator effects. However, the nature of the measured dilator response needs to be characterised further.

Increased plasma noradrenaline during severe sodium restriction does not stimulate platelet release in essential hypertension.

Seventeen 50-year old hypertensive men, previously untreated with blood pressure 157 +/- 4/110 +/- 2 mmHg (means +/- SE) were given a low sodium diet for 2 weeks. During the second week, the diet was supplemented with potassium. The urinary Na+/K+ excretion ratio changed from 2:1 to 1:4 and 1:11, respectively. Sympathetic noradrenergic tone increased considerably during the first week. Thus, venous plasma noradrenaline increased from 254 +/- 22 to 347 +/- 28 pg/ml (p less than 0.001) and arterial concentration from 253 +/- 36 to 317 +/- 42 pg/ml (n = 10, p less than 0.001). No significant change was observed in sympathetic adrenal tone as reflected by normal plasma adrenaline in venous (42 +/- 5 vs 43 +/- 6 pg/ml, ns) or arterial blood (71 +/- 10 vs 82 +/- 15 pg/ml, n = 10, ns) or in venous plasma concentration of the blood platelet release product beta-thromboglobulin (BTG) (50 +/- 8 vs 43 +/- 5 ng/ml, ns). During the second week sympathetic noradrenergic tone remained highly significantly elevated compared to baseline but still no change in plasma adrenaline or plasma BTG was found. Thus, whereas sodium depletion did increase plasma noradrenaline concentration markedly in these hypertensive men, no change in adrenaline concentration was observed, and blood platelet release reaction was unchanged. Plasma noradrenaline within the physiological concentration range does not seem to serve as a regulator of in vivo platelet function.