In normal coronary arteries, several different mechanisms of blood flow regulation exist, acting at different levels of the coronary tree: endothelial, nervous, myogenic and metabolic regulation. In addition, physiologic blood flow regulation is also dependent on the activity of several coronary ion channels, including ATP-dependent K(+) channels, voltage-gated K(+) channels and others. In this context, ion channels contribute by matching demands for homeostatic maintenance. They play a primary role in rapid response of both endothelium and vascular smooth muscle cells of larger and smaller arterial vessels of the coronary bed, leading to coronary vasodilation. Consequently, an alteration in ion channel function or expression could be directly involved in coronary vasomotion dysfunction.

Aims The cardio‐renal syndrome plays a critical role in acute heart failure (HF). Levosimendan, an inodilator drug, has a positive but controversial effect on kidney. Our aim was to evaluate its effects on both renal and systemic haemodynamic parameters as well as on renal function, explaining the possible mechanisms involved. Methods and results Patients with acute decompensated HF, moderate renal impairment, wedge pressure >20 mmHg and EF <40% were eligible. Twenty‐one patients were randomized to infusion of levosimendan or placebo, on top of standard therapy. Systemic haemodynamic parameters (wedge and cardiac output) were evaluated at baseline and at 8, 16, 24, 48, and 72 h. An intravascular renal artery Doppler exam was performed at baseline, after levosimendan bolus, and 1 h thereafter. Renal blood flow, glomerular filtration rate (GFR), cystatin C, blood urea nitrogen (BUN), urinary output, sodium excretion, and plasma sodium were measured. The effect of levosimendan was beneficial and significantly different from placebo on several renal and cardiac parameters. Specifically, the levosimendan and placebo group exhibited significantly different changes over time in GFR (P = 0.037), renal blood flow (P = 0.037), and renal artery diameter (P = 0.033), with ensuing improvements in serum levels of BUN (P = 0.014), creatinine (P = 0.042), and cystatin C (P = 0.05). Concomitantly, levosimendan provided a significant increase in urine output up to 72 h (P = 0.02). These beneficial results on renal parameters were accompanied by similarly significant and favourable changes in cardiac index (P = 0.029) and PCWP (P < 0.001). Conclusion Levosimendan, in acute decompensated HF, has an immediate renoprotective effect, mediated by an increase in renal blood flow, due to a selective renal arterial and venous vasodilating action. Trial registration NCT00527059.

There is an established tradition of cardiovascular simulation tools, but the application of this kind of technology in the e-Learning arena is a novel approach. This paper presents an e-Learning environment aimed at teaching the interaction of cardiovascular and lung systems to health-care professionals. Heart-lung interaction must be analyzed while assisting patients with severe respiratory problems or with heart failure in intensive care unit. Such patients can be assisted by mechanical ventilatory assistance or by thoracic artificial lung.“In silico” cardiovascular simulator was experimented during a training course given to graduate students of the School of Specialization in Cardiology at ‘Sapienza’ University in Rome.The training course employed CARDIOSIM©: a numerical simulator of the cardiovascular system. Such simulator is able to reproduce pathophysiological conditions of patients affected by cardiovascular and/or lung disease. In order to study the interactions among the cardiovascular system, the natural lung and the thoracic artificial lung (TAL), the numerical model of this device has been implemented. After having reproduced a patient’s pathological condition, TAL model was applied in parallel and hybrid model during the training course.Results obtained during the training course show that TAL parallel assistance reduces right ventricular end systolic (diastolic) volume, but increases left ventricular end systolic (diastolic) volume. The percentage changes induced by hybrid TAL assistance on haemodynamic variables are lower than those produced by parallel assistance. Only in the case of the mean pulmonary arterial pressure, there is a percentage reduction which, in case of hybrid assistance, is greater (about 40%) than in case of parallel assistance (20-30%).At the end of the course, a short questionnaire was submitted to students in order to assess the quality of the course. The feedback obtained was positive, showing good results with respect to the degree of students’ learning and the ease of use of the software simulator.

Heart failure is a major public health problem because of its high prevalence and impact on mortality, morbidity, quality of life, and social costs. The aim of this analysis was to estimate the effects of the novel inodilator levosimendan versus standard inotropic therapy (ST) of dobutamine in acute heart failure. A study population of 292 patients with acute heart failure was derived from an observational registry of patients referred to our department. Of these, 147 patients received iv levosimendan (0.05-0.1 μg·kg·min for 24 hours), and 145 patients were treated with ST. Duration of hospitalization, survival at 1 month, and the rehospitalization rate during the year after the index hospitalization were evaluated. Cost-effectiveness analysis was performed. The mean length of hospitalization was 12.08 and 13.57 days in the levosimendan and ST groups, respectively (P < 0.05). Rehospitalization rates were lower in the levosimendan group at 6 months (1.44% vs. 2.3%; P < 0.05) and 12 months (7.6% vs. 14.3%; P < 0.05). Mortality rate at 1 month was 2.1% versus 6.9% in the levosimendan and ST groups, respectively (P < 0.05). The per-capita cost of treatment with levosimendan was €78.86 higher than that with ST during the first hospitalization but €280.22 lower when the rehospitalization rate was considered.