Continuous monitoring of left ventricular function in postoperative intensive care patients using artificial intelligence and transesophageal echocardiography.

BACKGROUND: Continuous monitoring of mitral annular plane systolic excursion (MAPSE) using transesophageal echocardiography (TEE) may improve the evaluation of left ventricular (LV) function in postoperative intensive care patients. We aimed to assess the utility of continuous monitoring of LV function using TEE and artificial intelligence (autoMAPSE) in postoperative intensive care patients. METHODS: In this prospective observational study, we monitored 50 postoperative intensive care patients for 120 min immediately after cardiac surgery. We recorded a set of two-chamber and four-chamber TEE images every five minutes. We defined monitoring feasibility as how often the same wall from the same patient could be reassessed, and categorized monitoring feasibility as excellent if the same LV wall could be reassessed in ≥ 90% of the total recordings. To compare autoMAPSE with manual measurements, we rapidly recorded three sets of repeated images to assess precision (least significant change), bias, and limits of agreement (LOA). To assess the ability to identify changes (trending ability), we compared changes in autoMAPSE with the changes in manual measurements in images obtained during the initiation of cardiopulmonary bypass as well as before and after surgery. RESULTS: Monitoring feasibility was excellent in most patients (88%). Compared with manual measurements, autoMAPSE was more precise (least significant change 2.2 vs 3.1 mm, P < 0.001), had low bias (0.4 mm), and acceptable agreement (LOA - 2.7 to 3.5 mm). AutoMAPSE had excellent trending ability, as its measurements changed in the same direction as manual measurements (concordance rate 96%). CONCLUSION: Continuous monitoring of LV function was feasible using autoMAPSE. Compared with manual measurements, autoMAPSE had excellent trending ability, low bias, acceptable agreement, and was more precise.

Automatic assessment of left ventricular function for hemodynamic monitoring using artificial intelligence and transesophageal echocardiography.

We have developed a method to automatically assess LV function by measuring mitral annular plane systolic excursion (MAPSE) using artificial intelligence and transesophageal echocardiography (autoMAPSE). Our aim was to evaluate autoMAPSE as an automatic tool for rapid and quantitative assessment of LV function in critical care patients. In this retrospective study, we studied 40 critical care patients immediately after cardiac surgery. First, we recorded a set of echocardiographic data, consisting of three consecutive beats of midesophageal two- and four-chamber views. We then altered the patient's hemodynamics by positioning them in anti-Trendelenburg and repeated the recordings. We measured MAPSE manually and used autoMAPSE in all available heartbeats and in four LV walls. To assess the agreement with manual measurements, we used a modified Bland-Altman analysis. To assess the precision of each method, we calculated the least significant change (LSC). Finally, to assess trending ability, we calculated the concordance rates using a four-quadrant plot. We found that autoMAPSE measured MAPSE in almost every set of two- and four-chamber views (feasibility 95%). It took less than a second to measure and average MAPSE over three heartbeats. AutoMAPSE had a low bias (0.4 mm) and acceptable limits of agreement (- 3.7 to 4.5 mm). AutoMAPSE was more precise than manual measurements if it averaged more heartbeats. AutoMAPSE had acceptable trending ability (concordance rate 81%) during hemodynamic alterations. In conclusion, autoMAPSE is feasible as an automatic tool for rapid and quantitative assessment of LV function, indicating its potential for hemodynamic monitoring.

Wrist ballistocardiography and invasively recorded blood pressure in healthy volunteers during reclining bike exercise.

Objective: Ballistocardiogram (BCG) features are of interest in wearable cardiovascular monitoring of cardiac performance. We assess feasibility of wrist acceleration BCG during exercise for estimating pulse transit time (PTT), enabling broader cardiovascular response studies during acute exercise and improved monitoring in individuals at risk for cardiovascular disease (CVD). We also examine the relationship between PTT, blood pressure (BP), and stroke volume (SV) during exercise and posture interventions. Methods: 25 participants underwent a bike exercise protocol with four incremental workloads (0 W, 50 W, 100 W, and 150 W) in supine and semirecumbent postures. BCG, invasive radial artery BP, tonometry, photoplethysmography (PPG) and echocardiography were recorded. Ensemble averages of BCG signals determined aortic valve opening (AVO) timings, combined with peripheral pulse wave arrival times to calculate PTT. We tested for significance using Wilcoxon signed-rank test. Results: BCG was successfully recorded at the wrist during exercise. PTT exhibited a moderate negative correlation with systolic BP (ρSup = -0.65, ρSR = -0.57, ρAll = -0.54). PTT differences between supine and semirecumbent conditions were significant at 0 W and 50 W (p < 0.001), less at 100 W (p = 0.0135) and 150 W (p = 0.031). SBP and DBP were lower in semirecumbent posture (p < 0.01), while HR was slightly higher. Echocardiography confirmed association of BCG features with AVO and indicated a positive relationship between BCG amplitude and SV (ρ = 0.74). Significance: Wrist BCG may allow convenient PTT and possibly SV tracking during exercise, enabling studies of cardiovascular response to acute exercise and convenient monitoring of cardiovascular performance.

Postoperative Pulmonary Complications After Cardiac Surgery: The VENICE International Cohort Study.

OBJECTIVE: Postoperative pulmonary complications (PPC) remain a main issue after cardiac surgery. The objective was to report the incidence and identify risk factors of PPC after cardiac surgery. DESIGN: An international multicenter prospective study (42 international centers in 9 countries). PARTICIPANTS: A total of 707 adult patients who underwent cardiac surgery under cardiopulmonary bypass. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: During a study period of 2 weeks, the investigators included all patients in their respective centers and screened for PPCs. PPC was defined as the occurrence of at least 1 pulmonary complication among the following: atelectasis, pleural effusion, respiratory failure, respiratory infection, pneumothorax, bronchospasm, or aspiration pneumonitis. Among 676 analyzed patients, 373 patients presented with a PPC (55%). The presence of PPC was significantly associated with a longer intensive care length of stay and hospital length of stay. One hundred ninety (64%) patients were not intraoperatively ventilated during cardiopulmonary bypass. Ventilation settings were similar regarding tidal volume, respiratory rate, inspired oxygen. In the regression model, age, the Euroscore II, chronic obstructive pulmonary disease, preoxygenation modality, intraoperative positive end-expiratory pressure, the absence of pre- cardiopulmonary bypass ventilation, the absence of lung recruitment, and the neuromuscular blockade were associated with PPC occurrence. CONCLUSION: Both individual risk factors and ventilatory settings were shown to explain the high level of PPCs. These findings require further investigations to assess a bundle strategy for optimal ventilation strategy to decrease PPC incidence.

Postoperative pulmonary complications after cardiac surgery: the VENICE international cohort study

OBJECTIVE: Postoperative pulmonary complications (PPC) remain a main issue after cardiac surgery. The objective was to report the incidence and identify risk factors of PPC after cardiac surgery. DESIGN: An international multicenter prospective study (42 international centers in 9 countries). PARTICIPANTS: A total of 707 adult patients who underwent cardiac surgery under cardiopulmonary bypass. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: During a study period of 2 weeks, the investigators included all patients in their respective centers and screened for PPCs. PPC was defined as the occurrence of at least 1 pulmonary complication among the following: atelectasis, pleural effusion, respiratory failure, respiratory infection, pneumothorax, bronchospasm, or aspiration pneumonitis. Among 676 analyzed patients, 373 patients presented with a PPC (55%). The presence of PPC was significantly associated with a longer intensive care length of stay and hospital length of stay. One hundred ninety (64%) patients were not intraoperatively ventilated during cardiopulmonary bypass. Ventilation settings were similar regarding tidal volume, respiratory rate, inspired oxygen. In the regression model, age, the Euro score II, chronic obstructive pulmonary disease, preoxygenation modality, intraoperative positive end-expiratory pressure, the absence of pre- cardiopulmonary bypass ventilation, the absence of lung recruitment, and the neuromuscular blockade were associated with PPC occurrence. CONCLUSION: Both individual risk factors and ventilatory settings were shown to explain the high level of PPCs. These findings require further investigations to assess a bundle strategy for optimal ventilation strategy to decrease PPC incidence.

No evidence of cardiac stunning or decoupling immediately after cardiopulmonary bypass for elective coronary surgery.

BACKGROUND: There is significant uncertainty regarding the timing of onset of cardiovascular stunning after cardiac surgery. Cardiovascular stunning is affecting both contractility (Ees) and arterial load. Arterial load may be represented by arterial elastance (Ea) and participates in ventriculo-arterial coupling through the Ea/Ees ratio, giving information on efficiency and performance. An alternative approach to ventriculo-arterial interaction is oscillatory power fraction (OPF). The aim of this study was to investigate the immediate beat-to-beat effects of on-pump coronary artery bypass graft (CABG) surgery on contractility, cardiac power parameters, arterial load and ventriculo-arterial coupling as well as classical haemodynamic parameters. METHODS: We included 41 patients scheduled for fast-track CABG surgery. Measurements were taken before and after cardiopulmonary bypass. A flow and pressure curve were recorded from transoesophageal pulsed wave Doppler and a radial artery catheter, respectively. This enabled the calculation of stroke work, total cardiac energy delivery, OPF and Ea/Ees ratio. Routine haemodynamic monitoring provided the classical haemodynamic parameters. RESULTS: Immediately after cardiopulmonary bypass there was no firm evidence for alterations in contractility, stroke work, stroke volume or arterial elastance. Ea/Ees ratio and OPF remained unchanged. CONCLUSIONS: There was no evidence for clinically relevant cardiac stunning or altered arterial load immediately after cardiopulmonary bypass for CABG surgery. The unchanged Ea/Ees ratio and OPF are indicating unchanged cardiac efficiency before and after cardiopulmonary bypass. This indicates that in elective CABG patients cardiovascular stunning is perhaps a phenomenon of inflammation and not immediate ischaemia-reperfusion injury or mechanical handling.

Ventriculo-arterial interaction may be assessed by Oscillatory Power Fraction.

The rate of energy transfer from the left ventricle to the aorta is viewed in terms of mean power (MP) and total power (TP). The difference between MP and TP is due to the pulsatility of the circulation and is known as oscillatory power (OP). OP is considered the energy spent to accelerate the blood flow. The aim of this study was to investigate the baseline left ventricular oscillatory power fraction (OP/TP) and how this was affected by acute cardiovascular dysfunction and altered preload. Twenty-eight patients undergoing elective coronary artery bypass graft surgery were included. Before administration of anaesthesia, we simultaneously recorded an arterial pressure curve and instantaneous cardiac outflow with pulsed wave Doppler. Postoperatively, prior to extubation, these measurements were repeated in neutral, Trendelenburg and reverse-Trendelenburg position. The final measurements were taken on the awake patient the day after the operation. TP is the mean of the instantaneous product of the flow and pressure curves. MP was calculated by multiplying mean arterial pressure with mean cardiac output. The oscillatory power fraction is therefore calculated as (TP-MP)/TP. The oscillatory power fraction in neutral position decreased from 23% preoperatively to 16% immediately postoperatively (P<0·001) and increased again to 19% the first postoperative day (P = 0·001). The oscillatory power fraction also increased from 16% in neutral to 19% in Trendelenburg (P = 0·001) and decreased comparing to neutral, to 14% in reverse-Trendelenburg (P = 0·04). The oscillatory power fraction is situation-dependent and is influenced by both the operation and the altered preload.

Post cardiac surgery stunning reduces stroke work, but leaves cardiac power output unchanged in patients with normal ejection fraction.

This study assesses positional changes in cardiac power output and stroke work compared with classic hemodynamic variables, measured before and after elective coronary artery bypass graft surgery. The hypothesis was that cardiac power output was altered in relation to cardiac stunning. The study is a retrospective analysis of data from two previous studies performed in a tertiary care university hospital. Thirty-six patients scheduled for elective coronary artery bypass graft surgery, with relatively preserved left ventricular function, were included. A pulmonary artery catheter and a radial artery catheter were placed preoperatively. Cardiac power output and stroke work were calculated through thermodilution both supine and standing prior to induction of anesthesia and again day one postoperatively. Virtually all systemic hemodynamic parameters changed significantly from pre- to postoperatively, and from supine to standing. Cardiac power output was maintained at 0.9-1.0 (±0.3) W both pre- and postoperatively and from supine to standing on both days. Stroke work fell from pre- to postoperatively from 1.1 to 0.8 J (P < 0.001), there was a significant fall in stroke work with positional change preoperatively from 1.1 to 0.9 J (P < 0.001). Postoperatively the stroke work remained at 0.8 J despite positional change. Cardiac power output was the only systemic hemodynamic variable which remained unaltered during all changes. Stroke work appears to be a more sensitive marker for temporary cardiovascular dysfunction than cardiac power output. Further studies should explore the relationship between stroke work and cardiac performance and whether cardiac power output is an autoregulated intrinsic physiological parameter.

Human cardiomyocyte calcium handling and transverse tubules in mid-stage of post-myocardial-infarction heart failure.

AIMS: Cellular processes in the heart rely mainly on studies from experimental animal models or explanted hearts from patients with terminal end-stage heart failure (HF). To address this limitation, we provide data on excitation contraction coupling, cardiomyocyte contraction and relaxation, and Ca2+ handling in post-myocardial-infarction (MI) patients at mid-stage of HF. METHODS AND RESULTS: Nine MI patients and eight control patients without MI (non-MI) were included. Biopsies were taken from the left ventricular myocardium and processed for further measurements with epifluorescence and confocal microscopy. Cardiomyocyte function was progressively impaired in MI cardiomyocytes compared with non-MI cardiomyocytes when increasing electrical stimulation towards frequencies that simulate heart rates during physical activity (2 Hz); at 3 Hz, we observed almost total breakdown of function in MI. Concurrently, we observed impaired Ca2+ handling with more spontaneous Ca2+ release events, increased diastolic Ca2+ , lower Ca2+ amplitude, and prolonged time to diastolic Ca2+ removal in MI (P < 0.01). Significantly reduced transverse-tubule density (-35%, P < 0.01) and sarcoplasmic reticulum Ca2+ adenosine triphosphatase 2a (SERCA2a) function (-26%, P < 0.01) in MI cardiomyocytes may explain the findings. Reduced protein phosphorylation of phospholamban (PLB) serine-16 and threonine-17 in MI provides further mechanisms to the reduced function. CONCLUSIONS: Depressed cardiomyocyte contraction and relaxation were associated with impaired intracellular Ca2+ handling due to impaired SERCA2a activity caused by a combination of alteration in the PLB/SERCA2a ratio and chronic dephosphorylation of PLB as well as loss of transverse tubules, which disrupts normal intracellular Ca2+ homeostasis and handling. This is the first study that presents these mechanisms from viable and intact cardiomyocytes isolated from the left ventricle of human hearts at mid-stage of post-MI HF.

Reduced reactive hyperemia may explain impaired flow-mediated dilation after on-pump cardiac surgery.

In previous studies, Flow Mediated Dilation (FMD) was used to study the effect of cardiac surgery on endothelial function. This study investigated the effect of on-pump cardiac surgery on FMD and reactive hyperemia. The FMD-response and reactive hyperemia were measured in 25 patients the morning before- and the first morning after cardiac surgery. Brachial artery diameter and blood flow were measured with ultrasound at baseline before 5 min occlusion of the blood flow to the forearm, and continuously for 3 min after release of the occlusion. An exponential wash-out model was fitted to the blood flow over time. Nineteen patients remained for final data analysis. Data are mean ± SEM The FMD response was reduced after surgery from 3.3 ± 0.5% to 1.4 ± 0.6% (P = 0.02). Max blood flow after cuff release was reduced from 342 ± 30 mL preoperatively to 305 ± 30 mL postoperatively (P < 0.00) and fell toward baseline significantly quicker; preoperative half-life was 36 ± 2.4 sec. versus 29 ± 1.9 sec postoperatively (P < 0.00). Resting blood flow was reduced from 84 ± 9 mL/min to 66 ± 9 mL/min, (P < 0.00). Brachial artery baseline diameter was unaffected by coronary artery bypass surgery (P = 0.3). The observed reduction in brachial artery FMD after surgery, by previous authors taken to represent endothelial dysfunction, may at least partly be due to reduced hyperemic flow postoperatively. In studies where FMD is measured on multiple occasions, flow data should also be included. Reduced postoperative blood flow to the arm may indicate regional differences in vascular resistance after cardiac surgery.

Minimally invasive beat-by-beat monitoring of cardiac power in normal hearts and during acute ventricular dysfunction.

Cardiac power, the product of aortic flow and blood pressure, appears to be a fundamental cardiovascular parameter. The simplified version named cardiac power output (CPO), calculated as the product of cardiac output (CO) in L/min and mean arterial pressure (MAP) in mmHg divided by 451, has shown great ability to predict outcome in a broad spectrum of cardiac disease. Beat-by-beat evaluation of cardiac power (PWR) therefore appears to be a possibly valuable addition when monitoring circulatory unstable patients, providing parameters of overall cardiovascular function. We have developed a minimally invasive system for cardiac power measurement, and aimed in this study to compare this system to an invasive method (ttPWR). Seven male anesthetized farm pigs were included. A laptop with in-house software gathered audio from Doppler signals of aortic flow and blood pressure from the patient monitor to continuously calculate and display a minimally invasive cardiac power trace (uPWR). The time integral per cardiac cycle (uPWR-integral) represents cardiac work, and was compared to the invasive counterpart (ttPWR-integral). Signals were obtained at baseline, during mechanically manipulated preload and afterload, before and after induced global ischemic left ventricular dysfunction. We found that the uPWR-integral overestimated compared to the ttPWR-integral by about 10% (P < 0.001) in both normal hearts and during ventricular dysfunction. Bland-Altman limits of agreement were at +0.060 and -0.054 J, without increasing spread over the range. In conclusion we find that the minimally invasive system follows its invasive counterpart, and is ready for clinical research of cardiac power parameters.

Cardiac power parameters during hypovolemia, induced by the lower body negative pressure technique, in healthy volunteers.

BACKGROUND: Changes in cardiac power parameters incorporate changes in both aortic flow and blood pressure. We hypothesized that dynamic and non-dynamic cardiac power parameters would track hypovolemia better than equivalent flow- and pressure parameters, both during spontaneous breathing and non-invasive positive pressure ventilation (NPPV). METHODS: Fourteen healthy volunteers underwent lower body negative pressure (LBNP) of 0, -20, -40, -60 and -80 mmHg to simulate hypovolemia, both during spontaneous breathing and during NPPV. We recorded aortic flow using suprasternal ultrasound Doppler and blood pressure using Finometer, and calculated dynamic and non-dynamic parameters of cardiac power, flow and blood pressure. These were assessed on their association with LBNP-levels. RESULTS: Respiratory variation in peak aortic flow was the dynamic parameter most affected during spontaneous breathing increasing 103 % (p < 0.001) from baseline to LBNP -80 mmHg. Respiratory variation in pulse pressure was the most affected dynamic parameter during NPPV, increasing 119 % (p < 0.001) from baseline to LBNP -80 mmHg. The cardiac power integral was the most affected non-dynamic parameter falling 59 % (p < 0.001) from baseline to LBNP -80 mmHg during spontaneous breathing, and 68 % (p < 0.001) during NPPV. CONCLUSIONS: Dynamic cardiac power parameters were not better than dynamic flow- and pressure parameters at tracking hypovolemia, seemingly due to previously unknown variation in peripheral vascular resistance matching respiratory changes in hemodynamics. Of non-dynamic parameters, the power parameters track hypovolemia slightly better than equivalent flow parameters, and far better than equivalent pressure parameters.

Cardiac function assessed by exercise echocardiography on the first morning after coronary artery bypass grafting.

Cardiac surgery patients are urged to resume light physical activity on the first postoperative day, even if cardiac function may not have recovered fully after the operation. To elucidate the postoperative recovery process, we examined cardiac surgery patients with exercise echocardiography before and on the first day after the operation. Patients undergoing on-pump coronary artery bypass grafting were examined with echocardiography during semirecumbent cycle exercise. Patients exercised for five minutes at 10 W intensity and five minutes at 30 W intensity in bed with the upper body supported to approximately 30°. Fourteen patients were studied. Mitral annulus excursion and pulsed wave Doppler from the left ventricular outflow tract indicated postoperatively reduced cardiac stroke volume. Early diastolic tissue velocities of the mitral annulus were reduced, and early trans-mitral flow velocity was increased. The ratio between early mitral flow velocity and early diastolic mitral tissue velocity was increased postoperatively, indicating impaired left ventricular relaxation and increased left atrial pressure. Postoperative systolic mitral annulus tissue velocities were similar to preoperative velocities, indicating maintained systolic function. Postoperative exercise was associated with improvements in myocardial function indices and cardiac stroke volume similar to preoperative improvements. There were no signs of further deterioration in myocardial function during 30 W exercise. In summary, reduced left ventricular diastolic function after surgery resulted in reduced cardiac stroke volume, increased left atrial pressure and a higher rate of perceived exertion on the first postoperative day.

The Precision of Pulmonary Artery Catheter Bolus Thermodilution Cardiac Output Measurements Varies With the Clinical Situation.

OBJECTIVE: To investigate the effects of ventilatory mode, injectate temperature, and clinical situation on the precision of cardiac output measurements. DESIGN: Randomized, prospective observational study. SETTING: Single university hospital. PARTICIPANTS: Forty patients undergoing planned cardiac surgery, receiving a pulmonary artery catheter according to institutional routine. INTERVENTIONS: Cardiac output was measured at 4 predefined time points during the perioperative patient course, twice during controlled and twice during spontaneous ventilation, using 2 blocks of 8 measurement replications with cold and tepid injectate in random order. MEASUREMENTS AND MAIN RESULTS: The data were analyzed using a hierarchical linear mixed model. Clinical precision was determined as half the width of the 95% confidence interval for the underlying true value. The single-measurement precision measured in 2 different clinical situations for each temperature/ventilation combination was 8% to 10%, 11% to 13%, 13% to 15%, and 23% to 24% in controlled ventilation with cold injectate, controlled ventilation with tepid injectate, spontaneous breathing with cold injectate, and spontaneous breathing with tepid injectate, respectively. Tables are provided for the number of replications needed to achieve a certain precision and for how to identify significant changes in cardiac output. CONCLUSIONS: Clinical precision of cardiac output measurements is reduced significantly during spontaneous relative to controlled ventilation. The differences in precision between repeated measurement series within the temperature/ventilation combinations indicate influence of other situation-specific factors not related to ventilatory mode. Compared with tepid injectate in patients breathing spontaneously, the precision is 3-fold better with cold injectate and controlled ventilation.

Elevated arterial lactate concentrations early after coronary artery bypass grafting are associated with increased anaerobic metabolism in skeletal muscle.

OBJECTIVE: To assess the effect of coronary artery bypass grafting with cardiopulmonary bypass on muscle perfusion, oxygen extraction, and lactate release during postoperative rest and exercise. DESIGN: Prospective observational study. SETTING: University hospital. PARTICIPANTS: Patients undergoing planned coronary artery bypass grafting. INTERVENTION: Knee-extensor exercise before and after coronary artery bypass grafting. MEASUREMENTS AND MAIN RESULTS: Femoral artery blood flow was measured with ultrasound. Femoral vein blood and arterial blood were sampled at rest and during light exercise and were analyzed for hemoglobin, lactate, oxygen saturation, and oxygen partial pressure. Fourteen patients were tested before and after surgery. The arterial lactate concentrations were increased after surgery, both at rest and during light exercise. Resting arterial lactate increased from 0.65 (0.5-0.8) to 1.0 (0.9-1.3) mmol/L (p=0.01) (median and interquartile range). Furthermore, lactate was released from the leg even during postoperative rest, and the release of lactate was increased during postoperative exercise. There were no significant differences between the preoperative and postoperative femoral artery blood flow. Femoral vein oxygen partial pressure was reduced significantly after surgery, indicating reduced muscle cell oxygen partial pressure. CONCLUSIONS: The patients had elevated anaerobic metabolism in skeletal muscle after surgery to compensate for anemia. Lactate was released from the leg into the general circulation during postoperative rest and exercise. The postoperatively reduced hemoglobin concentration of 11.4 mg/dL (10.6-12.3) resulted in increased anaerobic metabolism and release of lactate from skeletal muscle. The authors concluded that coronary artery bypass grafting patients are susceptible to anaerobic metabolism even with maintained peripheral blood flow.

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 (R (2) > 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.

High-intensity knee extensor training restores skeletal muscle function in COPD patients.

Improving reduced skeletal muscle function is important for optimising exercise tolerance and quality of life in chronic obstructive pulmonary disease (COPD) patients. By applying high-intensity training to a small muscle group, we hypothesised a normalisation of muscle function. Seven patients with COPD performed 6 weeks (3 days·week(-1)) of high-intensity interval aerobic knee extensor exercise training. Five age-matched healthy individuals served as a reference group. Muscle oxygen uptake and mitochondrial respiration of the vastus lateralis muscle were measured before and after the 6-week training programme. Initial peak work and maximal mitochondrial respiration were reduced in COPD patients and improved significantly after the training programme. Peak power and maximal mitochondrial respiration in vastus lateralis muscle increased to the level of the control subjects and were mainly mediated via improved complex I respiration. Furthermore, when normalised to citrate synthase activity, no difference in maximal respiration was found either after the intervention or compared to controls, suggesting normal functioning mitochondrial complexes. The present study shows that high-intensity training of a restricted muscle group is highly effective in restoring skeletal muscle function in COPD patients.

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.

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.

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.