Due to their negative inotropic properties, beta-blockers have generally been contraindicated in patients with heart failure. More recently, however, there has been a shift in the management of heart failure from a hemodynamic to a neurohormo-nal approach . This has led to an emphasis on pharmacological therapy aimed at counteracting these neurohormonal compensatory mechanisms, such as the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS). Initially, when there is a reduction in cardiac output as a result of heart failure, both the SNS and RAAS become activated. Activation of the SNS results in the release of catecholamines such as adrenaline and noradrenaline, resulting in several beneficial effects including an increase in myocardial contractility and heart rate, improved venous return, and enhanced perfusion to cerebral and coronary vessels. The net result of these effects is an improvement in cardiac output, and maintenance of blood pressure and perfusion to essential organs. buy asthma inhaler
There is increasing evidence, however, that prolonged activation of these compensatory mechanisms may actually be detrimental, producing adverse hemodynamic consequences and contributing to the progression of heart failure . Long term activation of the SNS may lead to direct myocardial injury (resulting from intracellular calcium overload and production of free-oxygen radicals), increased afterload, increased sodium and fluid retention (through up-regulation of the RAAS and increased vasopressin release), decreased diastolic function, down-regulation of beta-receptors (which leads to desensitization of the myocardium), increased myocardial oxygen consumption and potential for increased arrhythmias. In fact, in patients with moderate to severe heart failure, there is a correlation between plasma noradrenaline levels and mortality.