The importance of pharmacokinetics, pharmacodynamic and repetitive use of levosimendan.

Levosimendan was introduced into routine clinical practice in 2000, obtaining approval for the treatment of decompensation of severe chronic heart failure. Levosimendan increases the calcium sensitivity of contractile proteins by binding to myocardial troponin C (cTnC) in a calcium dependent manner. Apart from the mechanism of action of levosimendan, resulting directly in the improvement of heart function, a number of pleiotropic mechanisms have also been identified, including anti-inflammatory, antioxidant and anti-apoptotic effects. Pharmacokinetics of levosimendan is linear in a therapeutic dose range i.e. from 0.05 to 0.2 µg/kg/min. Therapeutic concentration of levosimendan is reached approximately 1 h after the start of intravenous infusion, and steady state is reached within 5 h after continuous infusion initiation. OR-1855 and OR-1896 are the only significant metabolites detected in the systemic circulation after administration of levosimendan. After a 24-hour infusion of levosimendan, the pharmacodynamic effect of the drug is observed for at least one week. Repetitive levosimendan infusions are safe and multiple infusions of levosimendan show a number of benefits. However, experience with multiple doses of levosimendan is scarce. The protocols of clinical trials conducted so far on repeated and intermittent infusions of levosimendan were developed subjectively and were based on the opinion of experts forming a given research team. There is still a need for more clinical research on the multidirectional effect of levosimendan in the group of patients with heart failure. The aim of this review was to summarize most relevant and up-to-date scientific data on pharmacokinetic and pharmacodynamic basis of levosimendan repetitive use in clinical practice that may assist in bedside decision making.

[Successful therapy and rehabilitation following stroke in a pregnant woman with prosthetic aortic valve]. / Pomyslna terapia i rehabilitacja udaru u ciezarnej ze wszczepiona sztuczna zastawka aortalna.

This report describes a case of a 40 year-old woman with implanted aortic prosthetic valve, who experienced thrombo-embolic complication in a form of ischaemic stroke in 15 week of pregnancy. At the beginning of the event, the patient suffered from mixed aphasia, right-side paresis and depressive syndrome. Thanks to cooperation of many specialists, especially rehabilitation team, she restored overall physical efficiency, speaking ability, delivered a healthy child, and returned to normal family and social activity. Problems of anti-thrombotic therapy during pregnancy in patients with prosthetic valves are discussed.

[Severe, thromboembolic pulmonary hypertension with recurrent pulmonary embolism and right heart thrombi in a patient with past myocardial infarction, cerebral ischaemic stroke and small intestine necrosis]. / Ciezkie, zakrzepowo−zatorowe nadcisnienie plucne z nawracajaca zatorowoscia plucna i skrzeplinami w prawych jamach serca u pacjenta z przebytymi zawalami serca, udarem pnia mózgu oraz martwica jelita cienkiego.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a chronic progressive disease of pulmonary circulation characterised by indistinct ethiopathogenesis. We present a case of a 50 year-old male with thrombophilia of unknown origin leading to the formation of multiple thrombi within venous circulation followed by episodes of acute pulmonary embolism resulting ultimately in acute heart failure in the course of developing CTEPH. Unfortunately, despite the wide range of haemostasis laboratory tests we were not able to define the type of coagulation abnormality. Owing to the efficient cooperation between cardiologists and cardiosurgeons it was possible to save patient's life.