Peri-operative Levosimendan in Patients Undergoing Cardiac Surgery: An Overview of the Evidence.

Levosimendan, a calcium sensitiser, has recently emerged as a valuable agent in the peri-operative management of cardiac surgery patients. Levosimendan is a calcium-sensitising ionodilator. By binding to cardiac troponin C and reducing its calcium-binding co-efficient, it enhances myofilament responsiveness to calcium and thus enhances myocardial contractility without increasing oxygen demand. Current evidence suggests that levosimendan enhances cardiac function after cardiopulmonary bypass in patients with both normal and reduced left ventricular function. In addition to being used as post-operative rescue therapy for low cardiac output syndrome, a pre-operative levosimendan infusion in high risk patients with poor cardiac function may reduce inotropic requirements, the need for mechanical support, the duration of intensive care admissions as well as post-operative mortality. Indeed, it is these higher-risk patients who may experience a greater degree of benefit. Larger, multicentre randomised trials in cardiac surgery will help to elucidate the full potential of this agent.

Differential effects of inhaled methacholine on circumferential wall and vascular smooth muscle of third-generation airways in awake sheep.

Evolution and natural selection ensure that specific mechanisms exist for selective airway absorption of inhaled atmospheric molecules. Indeed, nebulized cholinoceptor agonists used in asthma-challenge tests may or may not enter the systemic circulation. We examined the hypothesis that inhaled cholinoceptor agonists have selective access. Six sheep were instrumented under general anesthesia (propofol 5 mg/kg iv, 2-3% isoflurane-oxygen), each with pulsed-Doppler blood flow transducers mounted on the single bronchial artery and sonomicrometer probes mounted on the intrapulmonary third-generation lingula lobe bronchus. Continuous measurements were made of bronchial blood flow (Q(br)), Q(br) conductance (C(br)), bronchial hemicircumference (CIRC(br)), and bronchial wall thickness (WALL TH(br)) in recovered, standing, awake sheep. Methacholine (MCh; 0.125-2.0 µg/kg iv), at the highest dose, caused a 233% rise in Q(br) (P < 0.05) and a 286% rise in C(br) (P < 0.05). CIRC(br) fell to 90% (P < 0.05); WALL TH(br) did not change. In contrast, nebulized MCh (1-32 mg/ml), inhaled through a mask at the highest dose, caused a rise in ventilation and a rise in Q(br) proportional to aortic pressure without change in C(br). CIRC(br) fell to 91% (P < 0.01), and WALL TH(br) did not change. Thus inhaled MCh has access to cholinoceptors of bronchial circumferential smooth muscle to cause airway lumen narrowing but effectively not to those of the systemic bronchovascular circulation. It is speculated that the mechanism is selective neuroparacrine inhibition of muscarinic acetylcholine receptors (M3 bronchovascular cholinoceptors) by prostanoids released by intense MCh activation of epithelial and mucosal cells lining the airway.