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Aims Competitive flow from native coronary vessels is considered a major factor in the failure of coronary bypass grafts. However, the pathophysiological effects are not fully understood. Low and oscillatory wall shear stress (WSS) is known to induce endothelial dysfunction and vascular disease, like atherosclerosis and intimal hyperplasia. The aim was to investigate the impact of competitive flow on WSS in mammary artery bypass grafts. Methods and results Using computational fluid dynamics, WSS was calculated in a left internal mammary artery (LIMA) graft to the left anterior descending artery in a three-dimensional in vivo porcine coronary artery bypass graft model. The following conditions were investigated: high competitive flow (non-significant coronary lesion), partial competitive flow (significant coronary lesion), and no competitive flow (totally occluded coronary vessel). Time-averaged WSS of LIMA at high, partial, and no competitive flow were 0.3–0.6, 0.6–3.0, and 0.9–3.0 Pa, respectively. Further, oscillatory WSS quantified as the oscillatory shear index (OSI) ranged from (maximum OSI = 0.5 equals zero net WSS) 0.15 to 0.35, <0.05, and <0.05, respectively. Thus, high competitive flow resulted in substantial oscillatory and low WSS. Moderate competitive flow resulted in WSS and OSI similar to the no competitive flow condition. Conclusion Graft flow is highly dependent on the degree of competitive flow. High competitive flow was found to produce unfavourable WSS consistent with endothelial dysfunction and subsequent graft narrowing and failure. Partial competitive flow, however, may be better tolerated as it was found to be similar to the ideal condition of no competitive flow. [ABSTRACT FROM PUBLISHER]

OBJECTIVES Levosimendan is a novel inotropic agent claimed to improve myocardial contractility by a calcium-sensitizing effect. Our aim was to evaluate dose-dependent effects of levosimendan on left ventricular (LV) contractility and energetic properties in an acute, ischaemic heart failure porcine model. METHODS Six pigs were used in an anaesthetized in vivo open-chest model. The time points of measurements were: baseline, after heart failure induction and after dose 1–4 (D1–D4). Heart failure was induced by microembolization of the left coronary artery before infusion of four different doses (D1: 2.5 µg/kg, D2: 10 µg/kg, D3: 40 µg/kg, D4: 80 µg/kg) of levosimendan. Haemodynamics were assessed by the pressure-conductance catheter technique. LV oxygen consumption was calculated from coronary flow measurements and coronary sinus blood gases. Mitochondrial respiration was studied in biopsies of the LV. RESULTS Levosimendan had no significant, load-independent effect on contractile force (slope of preload recruitable stroke work was 34 mmHg immediately following failure and 39 (P = 0.406), 42 (P = 0.219), 46 (P = 0.067) and 41 (P = 0.267) at D1–D4), although the more load-dependent contractility indicator of dP/dtmax was slightly increased at dose 4 (P < 0.05). LV energy conversion efficiency (PVA–MVO2 relationship) remained unaltered at all doses. Maximal mitochondrial respiration decreased after induction of failure and remained at an unaltered low level during levosimendan infusion. CONCLUSIONS Surprisingly, levosimendan had no significant effect on contractility, energy efficiency and mitochondrial respiration of the LV, in a porcine model of acute heart failure. At high doses, levosimendan induced vasodilatation and increased heart rate and cardiac output. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To assess whether coronary graft flow patterns are affected differently by native coronary competitive flow or by stenosis of the coronary anastomosis. Methods: Nine pigs (65–70kg) underwent off-pump grafting of the left internal mammary artery to the left anterior descending artery (LAD). Transit-time flow patterns in the mammary grafts were recorded under four different conditions: (1) baseline flow (proximal LAD occluded), (2) full competitive flow, (3) partial competitive flow and (4) after creation of a stenosis in the anastomosis. Competitive flow was achieved by an adjustable occluder on the left anterior descending artery. The mean luminal stenosis of the anastomosis was 75±11%, calculated by epicardial ultrasound. Mean flow, systolic and diastolic antegrade and retrograde flow during different flow conditions were calculated as ratios of baseline flow and compared. Different derived flow indexes were calculated and compared in the same manner. Friedman''s test and post hoc analyses by Wilcoxon signed-ranks were performed without correction for multiple comparisons. Results: Mean graft flow was more reduced by competitive flow than by a stenotic anastomosis of 75±11%. Competitive flow significantly decreased diastolic antegrade flow and both diastolic and systolic maximum peak flows, but increased retrograde flow, compared with baseline and stenosis. Furthermore, competitive flow and stenosis could be distinguished by analysis of several derived indexes. Pulsatility index (maximum−minimum flow/mean flow) and insufficiency percent (retrograde flow as fraction of total flow) was increased significantly more by competitive flow than by stenosis. Diastolic filling percent was significantly reduced at competitive flow compared with stenosis and baseline. Conclusions: The mammary graft flow was significantly reduced by native coronary competitive flow, but marginally decreased by a stenotic anastomosis of 75% mean luminal stenosis. Reduction of graft flow due to competition was particularly evident in diastole. A detailed flow pattern analysis may differentiate between competitive flow and stenosis of the anastomosis. [Copyright &y& Elsevier]

Abstract: Objective: Levosimendan is a calcium-sensitising inotropic agent and a vasodilator used in the treatment of heart failure. Post-cardiotomy cardiac failure is more common in patients with a low preoperative left ventricular ejection fraction (LVEF). We aim at investigating how prophylactic treatment with levosimendan before weaning from cardiopulmonary bypass (CPB) affects postoperative haemodynamics and outcome in patients with low preoperative LVEF. Methods: Patients with a preoperative LVEF ≤30% treated with levosimendan before weaning from CPB were included in the study. Each patient was matched to a control patient with respect to the following criteria: surgical procedure, EuroSCORE, age, gender and the use of intra-aortic balloon pump. We investigated postoperative haemodynamics in the intensive care unit (ICU) at time points: 1, arrival; 2, approximately 7h after arrival; and 3, the first postoperative morning. In addition, mortality was evaluated. Results: Thirty patients treated with levosimendan and 30 matched controls were enrolled in the study. No statistically significant differences in cardiac index (CI) (lmin−1 m−2), stroke volume index (SVI) (mlm−2), mixed venous O2-saturation (SvO2) (%) or heart rate (HR) (beats per minute) between the two groups measured at the three time points 1–3 were registered. Mean arterial blood pressure (MAP) (mmHg) was lower in the levosimendan group both at time points 2 (68, range: 65–71 vs 75, range: 72–78; p =0.009) and 3 (72, range: 69–74 vs 78, range: 74–82; p =0.01), despite a higher dose of norepinephrine in the treatment group (p =0.021). A significantly higher number of control patients were treated with classic adrenergic inotropes both in the operating room (p =0.013) and in the ICU (p <0.001). Thirty days mortality was the same in both groups (7%). Conclusions: Prophylactic infusion of levosimendan initiated before weaning from CPB did not lead to superior haemodynamic parameters (CI, SVI, SvO2) compared to controls. Levosimendan reduced MAP and increased the need for norepinephrine postoperatively. [Copyright &y& Elsevier]

Objectives: The use of cardiopulmonary bypass in coronary artery bypass grafting (CABG) may contribute to the postoperative inflammatory response. The molecular chaperone heat-shock protein (HSP) 70 may be induced by ischemia, and has been detected both in the myocardium and in the circulation after CABG. In vitro, extracellular HSP70 may activate both innate and adaptive immunity. Hypothesizing that use of cardiopulmonary bypass (CPB) leads to more circulating HSP70, we explored the release of it in 10 patients undergoing CABG with the use of CPB, and in 10 patients undergoing off-pump surgery CABG (OPCAB). Methods: Blood samples were taken preoperatively, twice peroperatively, 2 and 6 h postoperatively and the next day. Serum analyses were performed by means of immunoassays. Results: We detected a significant difference in postoperative circulating HSP70 between on-pump and off-pump patients (median peaks of 2849 and 756 pg/ml, respectively, P<0.01, 2 h postoperatively). Interleukin-6 and -8 increased in all patients, without significant differences between the groups. Serum interleukin-10 increased at the end of the operation in 7 of 10 patients operated with cardiopulmonary bypass (median 51.7 pg/ml), but in none of the off-pump patients. Furthermore, in the first group, interleukin-10 correlated with the HSP70 concentration at the end of the operation, r=0.75, P<0.05. Serum markers of myocardial damage were higher in conventional than off-pump patients on day 1 postoperatively: median cardiac Troponin T was 0.358 and 0.126 μg/l, respectively, P<0.01. Correspondingly, median creatine kinase-MB was 23.6 and 7.8 μg/l in on-pump and off-pump patients, respectively, P<0.01. Peak HSP70 correlated with both Troponin T and creatine kinase-MB measured on day 1. Conclusions: Significantly more HSP70 was released into the circulation following conventional than following off-pump CABG. Circulating HSP70 may indicate cellular stress or damage. Furthermore, HSPs are suggested as immunoregulatory agents, and may be important in the host defence postoperatively. [Copyright &y& Elsevier]