Dag Nordhaug

Impact of competitive flow on wall shear stress in coronary surgery: computational fluid dynamics of a LIMA–LAD model

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.

Different graft flow patterns due to competitive flow or stenosis in the coronary anastomosis assessed by transit-time flowmetry in a porcine model,

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 (65-70 kg) 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. Friedmans 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.

The pressure-volume loop revisited: Is the search for a cardiac contractility index a futile cycle?

ABSTRACT Our previous studies indicate that left ventricular end-systolic pressure-volume relations (ESPVRs) or elastance (Ees) are not reduced in studies where expected reductions of contractility should be found (i.e., heart failure, stunning, and endotoxemia). The present study was done to assess whether this phenomenon is due to a particular load sensitivity of elastance, rendering this index inappropriate as a measurement of contractility in pathologic states in vivo. Methods and Results Analysis of previously generated data revealed an increased ESPVR in stunned hearts, in pigs made endotoxemic, and in hearts rapidly paced. After inducing acute heart failure by microembolization, the ESPVR was increased when assessed using linear relations but reduced when assessing ESPVR by a curvilinear algorithm. To further evaluate the effect of different load alterations on ESPVR, this relation was generated by (i) inferior vena caval occlusions (VCOs); (ii) gradually occluding the descending aorta (pressure interventions); and (iii) rapidly infusing blood (120 mL) into the left atrium (volume increments). The load protocol was applied in 5 pigs, before and after the left ventricle was stunned by 11 brief left main coronary artery occlusions/reperfusions (accumulated ischemia 20 min affecting 81% of the left ventricle). Correlation coefficients for left ventricular elastance ranged from 0.93 to 0.99 in all the 3 types of loading interventions. Despite significant reductions in stroke volume, stroke work, and dP/dtmax, VCO-calculated linear and curvilinear Ees increased 90 min after stunning (55% ± 4% and 94% ± 6%, respectively). Linear Ees during pressure interventions decreased 36% ± 1%, whereas curvilinear Ees decreased 33% ± 3%. During volume infusions, linear Ees decreased 27% ± 2%. We achieved the same results after blocking the baroreceptor reflexes using hexamethonium. Conclusions The Ees is particularly load dependent and will reflect load interventions more than the inotropic state of thecardiac muscle. A VCO-generated Ees increase could be an unmasking of a pronounced preload sensitivity in failing myocardium.

Prophylactic treatment with levosimendan: a retrospective matched-control study of patients with reduced left ventricular function

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 < or =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) (l min(-1)m(-2)), stroke volume index (SVI) (mlm(-2)), mixed venous O(2)-saturation (SvO(2)) (%) 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, SvO(2)) compared to controls. Levosimendan reduced MAP and increased the need for norepinephrine postoperatively.

E. coli sepsis induces profound mechanoenergetic inefficiency in the porcine left ventricle

Myocardial dysfunction is believed to be a central part of septic multiorgan manifestations. The aim of the present study was to assess whether E. coli sepsis in an in vivo model would induce a dysfunction in the relationship between mechanical work and energy consumption in the left ventricle (LV). Accordingly, we measured hemodynamics, left ventricular pressure–volume area (PVA), and myocardial oxygen consumption (MVo2) in deeply anesthetized pigs. Eight pigs received 2.0 ± 0.5 × 109E. coli bacteria intravenously, and seven served as controls. Compared with baseline and the control group, no alternations were observed in LV diastolic function or indices of contractility in the septic group. The MVo2–PVA relationship was highly linear in both groups (all r2 = 0.96–0.99). At 5 h, the y-axis intercept of the MVo2–PVA relationship (nonmechanical MVo2) had increased in the sepsis group by 70% compared with baseline (P = 0.004) and by 60% compared with the control group (P = 0.003). Contractile efficiency (the inverse of the MVo2–PVA slope) remained unchanged over time and between groups. The study demonstrates a profound increase in nonmechanical oxygen consumption during E. coli sepsis in the LV.

Levosimendan improves contractility in vivo and in vitro in a rodent model of post‐myocardial infarction heart failure

As few studies have presented a thorough analysis of the effect of levosimendan (LEV) on contractility, our purpose was to investigate in vivo cardiac function as well as in vitro cardiomyocyte function and calcium (Ca2+) handling following LEV treatment.

Cardiac power integral: a new method for monitoring cardiovascular performance

Cardiac power (PWR) is the continuous product of flow and pressure in the proximal aorta. Our aim was to validate the PWR integral as a marker of left ventricular energy transfer to the aorta, by comparing it to stroke work (SW) under multiple different loading and contractility conditions in subjects without obstructions in the left ventricular outflow tract. Six pigs were under general anesthesia equipped with transit time flow probes on their proximal aortas and Millar micromanometer catheters in their descending aortas to measure PWR, and Leycom conductance catheters in their left ventricles to measure SW. The PWR integral was calculated as the time integral of PWR per cardiac cycle. SW was calculated as the area encompassed by the pressure–volume loop (PV loop). The relationship between the PWR integral and SW was tested during extensive mechanical and pharmacological interventions that affected the loading conditions and myocardial contractility. The PWR integral displayed a strong correlation with SW in all pigs (R2 > 0.95, P < 0.05) under all conditions, using a linear model. Regression analysis and Bland Altman plots also demonstrated a stable relationship. A mixed linear analysis indicated that the slope of the SW‐to‐PWR‐integral relationship was similar among all six animals, whereas loading and contractility conditions tended to affect the slope. The PWR integral followed SW and appeared to be a promising parameter for monitoring the energy transferred from the left ventricle to the aorta. This conclusion motivates further studies to determine whether the PWR integral can be evaluated using less invasive methods, such as echocardiography combined with a radial artery catheter.

A dose–response study of levosimendan in a porcine model of acute ischaemic heart failure

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/dt(max) 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.

Learning endobronchial ultrasound transbronchial needle aspiration – a 6-year experience at a single institution

Endobronchial ultrasound with transbronchial needle aspiration (EBUS‐TBNA) has become an important diagnostic tool for the pulmonologist. Learning this procedure and maintaining technical skills requires continuous practice and evaluation.

Learning EBUS‐TBNA – a 6‐year experience at a single institution

Endobronchial ultrasound with transbronchial needle aspiration (EBUS‐TBNA) has become an important diagnostic tool for the pulmonologist. Learning this procedure and maintaining technical skills requires continuous practice and evaluation.