Simple approach to an apparently chaotic arrhythmia.

Deciphering complex arrhythmias requires a strict, systematic approach. In a step-by-step analysis of an electrocardiogram recorded from a patient with severe metabolic disturbances, we present a few simple suggestions that may often be helpful in electrocardiographic interpretation.

Severe symptomatic atrioventricular block induced by pilocarpine eye drops.

An 89-year-old man with chronic glaucoma received hourly pilocarpine eye drops for seven hours, when he developed third-degree atrioventricular block with a slow idioventricular escape rate. After discontinuing the pilocarpine, the atrioventricular block gradually disappeared. The site of pilocarpine-related block was most likely within the His-Purkinje system.

A study of modulated ventricular parasystole by programmed stimulation.

To analyze the phase-dependent sensitivity of the parasystolic pacemaker to nonparasystolic beats, 11 patients with modulated ventricular parasystole were studied using the ventricular extrastimulus method. The intrinsic parasystolic cycle lengths ranged from 1,100 to 1,800 ms. Premature stimuli altered the duration of the parasystolic cycle lengths by amounts that depended on timing of the test impulses within the parasystolic cycles. Premature impulses delivered during the first part of the parasystolic cycles prolonged the parasystolic cycle lengths to 107 to 151% of the intrinsic parasystolic cycle lengths and impulses applied during the second part abbreviated them to 70 to 81% of the intrinsic parasystolic cycle lengths. In 10 patients the accelerating effects were of greater magnitude than the decelerating effects. Transition from the accelerating to slowing phases was progressive or unstable in 9 patients and abrupt in 2. Changes induced by individual stimuli were short-lived and the parasystolic pacemakers returned immediately to their original rates. In 1 patient the biphasic sensitivity of parasystole to premature stimuli was shown to sustain for 21 days.

Effect of beta-adrenoceptor blocking compounds (propranolol, practolol and LB 46) on isoprenaline induced changes in regional blood flow in the rat.

1. The effects of three beta-adrenoceptor blocking agents on isoprenaline induced changes in systemic and regional blood flow have been investigated in rats anaesthetized with pentobarbitone. The blood flow to the principal vascular beds was measured by the (86)Rb fractionation method.2. Isoprenaline infusion at a rate of 0.3 (mug/kg)/min intravenously caused an increase in cardiac output and a decrease in peripheral resistance which affected different vascular fields unevenly. The coronary and carcass fractions of cardiac output increased while the cutaneous, renal and splenic fractions decreased.3. Pretreatment with propranolol (2 mg/kg intravenously) blocked all isoprenaline effects. Practolol (8 mg/kg intravenously) lessened the effect on cardiac output but did not prevent the vascular effects except those on the coronary circulation. LB 46 (0.2 mg/kg) had less marked beta-adrenoceptor blocking activity than propranolol (2.0 mg/kg).

Assessment of selective beta-adrenoceptor blockade in man.

1. Selective antagonism of the cardiac beta(1)-adrenoceptors has been studied in normal human volunteers.2. Practolol and UK 6558 produced greater antagonism of the chronotropic and inotropic responses to i.v. isoprenaline than of the vasodilator response to either i.v. or intra-arterial isoprenaline. A third drug, M&B 17,803A, produced non-selective beta-adrenoceptor blockade in 2 of 3 subjects studied.3. Practolol, UK 6558 and M&B 17,803A, produced an attenuation of the responses to Valsalva's manoeuvre.4. A substantial reduction in blood pressure was seen in 3 of 4 normotensive subjects given UK 6558.

Anticoagulant-related skin reactions.

Cutaneous reactions have been reported during anticoagulant therapy with coumarin derivatives, unfractionated and low molecular weight heparins, heparinoids, danaparoid and hirudins. Anticoagulant-induced skin reactions vary from local allergic manifestations to skin necrosis. In patients with allergic reactions, diagnosis and crossreactions between anticoagulants can be confirmed by intracutaneous testing. Coumarin- and heparin-induced skin necrosis are rare, but are important side effects due to their high morbidity and occasional mortality. Cutaneous tests are contraindicated in these patients. In the future, anticoagulant strategies may include direct synthetic thrombin inhibitors (argatroban and melagatran/ximelagatran) and the Factor Xa inhibitor, pentasaccharide (fondaparinux).

The effects of probucol on QT/QS2 relation and systolic time intervals.

The QT, QTc, QS2 intervals, pre-ejection period-left ventricular ejection time ratios and serum lipoprotein levels were measured in 8 patients with primary hypercholesterolemia before and after a 3-month therapy with probucol, 1 g/day. Both QT and QTc intervals increased significantly, whereas no significant changes were observed between the pre- and post-treatment QT/QS2 and pre-ejection period-left ventricular ejection time ratios. These results help to explain why treatment with probucol, while effecting a prolongation of the QTc interval, does not result in serious arrhythmias in man.

[Heparin, thrombin and Factor Xa inhibitors]. / Heparine, thrombin- und faktor-Xa-inhibitoren.

Direct and indirect coagulation inhibitors are used to inhibit the activity of the serine proteases of the coagulation system. Indirect inhibitors act via antithrombin and heparin cofactor II. The main representatives are heparins, lowmolecular-weight heparins, fondaparinux, idraparinux and danaparoid. They bind to antithrombin and potentiate the inactivation of factor Xa and other serine proteases. Direct thrombin inhibitors bind reversibly to thrombin without cofactor. Anticoagulants are determined by global and specific anticoagulant methods. New anticoagulants are developed such as oral factor Xa inhibitors, oral thrombin inhibitors, antibody against activated factor VII, recombinant tissue pathway inhibitor to improve inhibition of blood coagulation or to induce nonanticoagulant effects (e. g. activated protein C in septicaemia). New anticoagulant methods are developed to improve and specify the anticoagulant effect of anticoagulants in thromboembolic diseases.

[Ximelagatran for treatment of venous thromboembolism]. / Ximelagatran zur Therapie thromboembolischer Erkrankungen.

Acute venous thromboembolism including asymptomatic and symptomatic pulmonary embolism without respiratory or cardiac failure is currently treated for 6 months, initially with subcutaneous low-molecular-weight heparin followed by oral anticoagulation. The main drawback of oral anticoagulation is caused by severe bleeding complications. Oral Ximelagatran has shown to be as effective and safe for the initial treatment of acute deep venous thrombosis compared to subcutaneous low-molecular-weight heparin followed by oral warfarin over a period of 4 weeks. Currently, oral ximelagatran is investigated versus subcutaneous low-molecular-weight heparin and oral warfarin over 6 months to demonstrate an almost equal efficacy and safety. The study is performed on a double blind and double dummy basis. Six months after oral anticoagulation of patients with acute deep venous thrombosis, recurrent venous thromboembolism may occur in up to 25% within 2 years. Ximelagatran is currently investigated versus placebo to demonstrate a reduced recurrence rate of venous thromboembolism over a period of 18 months.

[Lepirudin for therapeutic use in heparin-induced thrombocytopenia]. / Lepirudin bei heparininduzierter Thrombozytopenie. Grundlagen und aktueller Erkenntnisstand zur klinischen Anwendung.

Heparin-induced thrombocytopenia (HIT) type II is an antibody mediated severe adverse event to heparin with a paradoxical decrease of platelet count and an increased risk for thromboembolic complications. The antibodies are directed against a neoepitop of platelet factor 4 after its binding to heparin. The incidence of HIT type II is lower with low-molecular-weight heparin compared to unfractionated heparin and lower in not operated patients compared to those after major surgery. In patients with HIT type II alternative anticoagulation has to be performed immediately due to the high thrombogenicity of the antibodies. The recombinant hirudin lepirudin (Refludan) is the anticoagulant drug of choice. A long-term anticoagulation has to be performed depending on the concomitant risk factors, intravenous administration followed by subcutaneous lepirudin overlapping with vitamin K antagonists.