BackgroundIn heart failure, the heart does not pump out enough blood to satisfy the body tissues with oxygen. Well-established lines of evidence suggest that chronical activation of the â-adrenergic system plays a major role in the pathogenesis of this condition. Betablocker therapy is now standard treatment for all degrees of heart failure, and it is well known that this therapy reduces hospitalizations, total morality, cardiac mortality and sudden death in these patients.However, betablockers were originally contraindicated in patients with congestive heart failure. Logically, as does heart failure represent a condition with diminished heart contractility, and â-adrenoceptors increase the contractility and rate of the heart. I wanted to find out which processes take place in the myocardial cell in heart failure, and further what happens after treatment with betablockers.
MethodsI did a litterature overview based on articles found in the largest medical databases and publications. I focused on articles about receptor signalling and calcium handling in myocardial cells in the condition of heart failure - and after betablocker intervention.
DiscussionMany ions are involved in the workings of the heart, and calcium is believed to be the most important. It is crucial to the process that enables the chambers of the heart to contract and relax, from the very beginning to the end of the contraction. The cycling of calcium is mainly controlled by activity in the â-receptor system, for instance by regulation of ion pump activity, ion channel opening and phosphatase activity. Overwhelming evidence suggest today that chronical activation of the â-adrenergic system plays a major role in the pathogenesis of heart failure. The sympathetic system is activated, cardiac â-receptor number and function are decreased, and downstream mechanisms are altered. Calcium cycling is defective, showing a decreased concentration during systole and a increased concentration during diastole, which lead to a diminished heart work and an increased oxygen use.Betablockers are now standard treatment in heart failure, as they reduce morbidity and mortality among the patients. It is believed that they normalize the pathological signalling in the heart myocytes, but much is still not clear when it comes to why they do have beneficial effects.
ResultsChronical stimulation of the â-adrenergic receptor system plays a main role in the pathoetiology of heart failure. The sympathetic system is activated, cardiac â-receptor number and function are decreased, and downstream mechanisms are altered.The subsequent alterations in the calcium handle system lead to dysfunction of the heart muscle, with following energy depletion and increased oxygen demand of the myocardium. Betablockers resensitize the â-adrenergic receptor system, normalize the calcium cycling and improve the energy use of the heart. Thereby they make the heart work better, and they reduce the morbidity and mortality of the patients with heart failure.