Effects of Combined Milrinone and Levosimendan Treatment on Systolic and Diastolic Function During Postischemic Myocardial Dysfunction in a Porcine Model.

It is not known whether there are positive or negative interactions on ventricular function when a calcium-sensitizing inotrope is added to a phosphodiesterase inhibitor in the clinical setting of acute left ventricular (LV) dysfunction. We hypothesized that when levosimendan is added to milrinone treatment, there will be synergetic inotropic and lusitropic effects. This was tested in an anesthetized porcine postischemic global LV injury model, where ventricular pressures and volumes (conductance volumetry) were measured. A global ischemic injury was induced by repetitive left main stem coronary artery occlusions. Load-independent indices of LV function were assessed before and after ventricular injury, after milrinone treatment, and finally after addition of levosimendan to the milrinone treatment. Nonparametric, within-group comparisons were made. The protocol was completed in 12 pigs, 7 of which received the inotrope treatment and 5 of which served as controls. Milrinone led to positive lusitropic effects seen by improvement in tau after myocardial stunning. The addition of levosimendan to milrinone further increased lusitropic state. The latter effect could however not be attributed solely to levosimendan, since lusitropic state also improved spontaneously in time-matched controls at the same rate during the corresponding period. When levosimendan was added to milrinone infusion, there was no increase in systolic function (preload recruitable stroke work) compared to milrinone treatment alone. We conclude that in this model of postischemic LV dysfunction, there appears to be no clear improvement in systolic or diastolic function after addition of levosimendan to established milrinone treatment but also no negative effects of levosimendan in this context.

Central venous oxygen saturation during cardiopulmonary bypass predicts 3-year survival.

OBJECTIVES: Long-term survival after cardiac surgery is determined by a number of different risk factors. Central venous oxygen saturation (S(v)O(2)) measures the balance between oxygen delivery and demand. S(v)O(2) levels in the intensive care situation are reported to be associated with patient outcome. The present report explores the connection between S(v)O(2) during cardiopulmonary bypass (CPB) and survival after cardiac surgery. METHODS: Retrospective analysis of one thousand consecutive cardiac surgical patients was undertaken. S(v)O(2) during CPB was monitored online. Registry data combining specific risk factors with S(v)O(2) were selected for Kaplan-Meier and Cox regression analysis to examine the influence on 30-day and 3-year survivals. RESULTS: Nine-hundred and thirty-two patient records were eligible for analysis. S(v)O(2) below 75% during CPB was associated with significantly shorter 30-day and 3-year survivals. Based on Kaplan-Meier statistics, the survival rate decreased by 3.1% (98.1-95.0), P = 0.011 and 6.1% (92.7-86.6), P = 0.003, respectively. The influence of S(v)O(2) on 3-year survival remained statistically significant after controlling for a series of risk factors in the Cox regression analysis. Patients with S(v)O(2) <75% carried a 2-fold (odds ratio 2.1) increased relative risk of shortened 3-year survival (P = 0.003). Other risk factors statistically significantly associated with 3-year survival were age, gender, duration of CPB, blood temperature, hypertension, haematocrit and type of surgical procedure. CONCLUSIONS: We report decreased 30-day and 3-year survival expectancy for patients experiencing S(v)O(2) lower than 75% during CPB.

Serum markers are not reliable measures of renal function in conjunction with cardiopulmonary bypass.

The present study explored the influence of haemodilution on estimates of the glomerular filtration rate (GFR) in conjunction with cardiopulmonary bypass (CPB) and cardiac surgery. Ninety-eight patients (n = 98) undergoing coronary artery bypass grafting with the aid of CPB were examined. The serum concentration of cystatin C and creatinine was analysed prior to surgery, after completion of CPB and in the intensive care the day after surgery. The estimated GFR was calculated using standard equations based on the serum concentration of cystatin C and creatinine. It was found that haemodilution induced by CPB had significant effects on the estimated GFR. For cystatin C, the GFR increased by 50.5 ± 2.5 ml/min (P = 0.000) and for creatinine based GFR with 22.5 ± 0.9 ml/min (P = 0.000) using the 4-variable modification of diet renal disease formula and with 22.1 ± 0.93 ml/min (P = 0.000) for the Cockcroft-Gault formula, respectively. Similar effects of haemodilution on GFR were also detected postoperatively. Haemodilution induced by CPB may therefore significantly overestimate the renal function as indicated by GFR based on serum markers.

Static blood-flow control during cardiopulmonary bypass is a compromise of oxygen delivery.

BACKGROUND: Blood-flow control during cardiopulmonary bypass (CPB) is by tradition based on the patient's body surface area. Emergence of new techniques enables dynamic blood-flow control based on online measurement of venous oxygen saturation and oxygen consumption. Present investigation aimed to compare static versus dynamic blood-flow control with respect to use of oxygen and effects upon organ function. METHODS: In this study, 100 coronary-artery-bypass surgical patients were prospectively randomised to static or dynamic hypothermic blood-flow control during CPB. In the static group, pump flow was set to 2.4 (litres per minute) times the patient's body surface area (m(2)) throughout the procedure. Pump flow in the dynamic group was varied according to the reading of the venous oxygen saturation and maintained at >75%. CPB-specific information was collected online. Blood samples were collected for analysis of haemoglobin, lactate, amylase, creatinine and C-reactive protein: pre-CPB, at weaning from CPB and on day 1 postoperatively. RESULTS: Randomisation formed two uniform groups. Choice of static or dynamic blood-flow control during CPB had no significant effects on organ function as judged by lactate, amylase or creatinine levels. On increasing oxygen demand, oxygen balance was maintained by increasing venous oxygen extraction rates in the static flow mode and by increasing the pump flow rate in the dynamic group. CONCLUSIONS: Independent of the blood-flow control mode, oxygen balance remained preserved. However, the dynamic mode provided higher oxygen delivery, which may increase margins of safety and protection of organ function.

ST changes and temporal relation to the J point during heart rate increase and myocardial ischemia.

There is no concensus concerning where in the ST segment to measure. We studied the relation between different J point intervals to ST results during tachycardia and ischemia. Symptomatic (anesthetized) patients with coronary artery disease were paced at ascending incremental levels until they became ischemic. ST vector magnitude and ST vector change from baseline (STC-VM) as well as the sum of ST changes from all 12 electrocardiogram (ECG) leads (ECG ST sum) were measured at J point 0 millisecond, J + 20, J + 60, and J + 80 milliseconds for 34 patients. ST segments increased in similar fashion during pacing and ischemia. There was no difference in ST results when measurement was performed at different time intervals for both STC-VM and ECG ST sum. We conclude that ST assessment by ST change from baseline is not affected by different J point intervals during increased heart rate and ischemia in this clinical model of pacing-induced ischemia and vectorcardiographic ST analysis.

What is a normal lactate level during cardiopulmonary bypass?

Blood lactate levels during cardiopulmonary bypass are often used to verify adequacy of perfusion. The present investigation aimed to propose a threshold for hyperlactatemia. Blood lactate levels in 5 121 cardiac surgical patients were retrospectively analysed by a review of database records. Hyperlactatemia was defined as a value equal to the 90th percentile of the identified lactate distribution at weaning from cardiopulmonary bypass. Patient demographics, background and outcome statistics were performed stratified on presence of hyperlactatemia. The threshold for hyperlactatemia was found to equal 2 mmol/l. Significant predictors of hyperlactatemia based on logistic regression modelling were age, complex surgery, duration of cardiopulmonary bypass, blood transfusion, acid base level, emergency operations, diabetes, vasoactive intervention, venous-blood-return to the heart-lung machine and renal function. Patients with hyperlactatemia required longer intensive care and postoperative ventilatory support. Complications were more frequent, especially: renal dysfunction, infections, respiratory and circulatory disorders. Hospital mortality was 13.3% compared to an overall level at 2.2%. The threshold for hyperlactatemia during cardiopulmonary bypass attained 2 mmol/l and predicted increased morbidity and mortality.

Vectorcardiographic ST deviations related to increased heart rate in the absence of ischemia in an experimental pig model.

The electrocardiographic ST segment may change when heart rate (HR) increases. We aimed to analyze vectorcardiographic ST relation and myocardial conditions during controlled HR increases in anesthetized pigs. The relative parameters ST change vector magnitude and ST change vector angle were calculated at paced HRs ranging from 85 to 175 beats per minute. ST change vector magnitude increased from baseline 6.3 +/- 1.3 to 26.0 +/- 3.1 microV (P < .01; range, 4-50 microV) at HR 175 beats per minute with similar changes in ST change vector angle, whereas the absolute parameter ST vector magnitude demonstrated a heterogeneous pattern without any systematic relation to HR changes. Microdialysis results from left ventricular wall, with analysis of glucose, lactate, and pyruvate, showed no sign of ischemia during pacing. Potassium concentrations did not change during pacing. We conclude that significant HR-related ST vector changes can occur in the absence of myocardial ischemia.

Myocardial systolic function increases during positive pressure lung inflation.

Lung inflation with positive airway pressure may have rapid and dynamic effects on myocardial contractile function. We designed this study to assess the magnitude and time to onset of myocardial function changes during the initiation of single positive pressure lung inflation at clinically relevant inflation pressures. In 8 anesthetized 40-kg pigs, left ventricular pressures and volumes were measured directly (conductance volumetry). A 15 cm H2O airway pressure plateau with lung inflation (PPLI-15) was performed, and 2 single beats from that sequence, one from resting apnea at zero airway pressure and the second from the point when the lungs were first maximally inflated, were selected for analysis. Systolic function variables for zero airway pressure and PPLI-15 were analyzed. Systolic elastance, derived from bilinear time-varying elastance curves, increased approximately 15% during PPLI-15 from zero airway pressure. This agreed with other systolic function variables that identified an increase in left ventricular contractile function for the lung inflation beat. Serial measurements of myocardial function should be conducted with constant airway pressure and lung inflation conditions.

ST-segment deviations during pacing-induced increased heart rate in patients without coronary artery disease.

INTRODUCTION: In order to interpret ST-segment changes as an indicator of ischemia in patients with higher heart rates (HRs), the relation between ST-segment levels and HR needs to be well defined in subjects without coronary artery disease. METHODS: Eighteen patients with normal ECGs in the catheterization laboratory, after radiofrequency ablation of AV nodal re-entry tachycardia or an accessory pathway were included. Computerized online vectorcardiography (VCG) was performed during step-wise atrial pacing-induced increases in HR up to 150 beats min(-1) (bpm). The ST-vector magnitude (ST-VM) and the relative ST change vector magnitude (STC-VM) were analysed at the J point, J + 20 and J + 60 ms. RESULTS: There was no divergence in the course of ST-VM or STC-VM based on J point + 0, 20, or 60 ms during increasing HR. The STC-VM mean values increased progressively during increases in HR above 100 bpm, with an average increase in STC-VM of 15-20 microV per 10 bpm increases in HR. The ST-VM response during HR increases showed a heterogeneous and unpredictable pattern. CONCLUSION: The STC-VM increases linearly with rising HRs above 100 bpm. The STC-VM can exceed widely recognized ischemic thresholds during higher HRs in the absence of ischemia. The choice of J point time to ST-VM measurements as tested here is not important for the STC-VM relation to HR at these HR levels. Further clinical testing is needed to improve the diagnostic specificity of STC-VM measurements during increased HRs.

Intracoronary beta2 receptor activation induces dynamic local t-PA release in the pig.

To investigate beta2 -adrenergic agonist-mediated effects on coronary fluxes of local fibrinolytic factors, healthy anaesthetised and instrumented pigs (n=10) were studied during infusion of isoprenaline (IPR) into the left main coronary artery. Coronary net fluxes of total t-PA antigen, active t-PA and total PAI-1 antigen were determined at baseline and at 3, 5, 7 and 10 minutes of IPR infusion. During IPR, net release of total t-PA increased in a biphasic pattern with transiently high levels at 3 (+440 %) and 7 minutes (+620%) and returned towards baseline at 10 minutes. Net coronary release of active t-PA increased with maximum levels at 3 minutes (+50%). Baseline coronary net flux of total PAI -1 showed a decrease which was most pronounced at 10 minutes. To conclude, a fast beta2 agonist-mediated local release of t-PA into the coronary vasculature was demonstrated. For total t-PA, this response was characterised by a biphasic release profile.

Method of preload reduction during LVPVR analysis of systolic function: airway pressure elevation and vena cava occlusion.

BACKGROUND: A graded preload reduction during analysis of the left ventricular pressure-volume relationship (LVPVR) is required for derivation of end-systolic elastance (Ees) and preload recruitable stroke work (PRSW). The authors aimed to measure serial changes in these systolic function parameters before and during planned circulatory interventions using two different methods of preload alteration: a positive airway pressure plateau (APP) and inferior vena cava occlusion (IVCO). METHODS: In eight animals, measurements were made at 38 degrees, 30 degrees, 32 degrees, 34 degrees, and posthypothermia 38 degrees C. In an additional eight animals, isoflurane, adrenaline, and aorta occlusion (balloon catheter occluder) were administered in series, each with a preintervention control measurement. Left ventricular volume was measured by conductance. Paired measurements of the systolic function parameters Ees and PRSW, each derived with two preload methods, were analyzed for bias. RESULTS: Circulatory alterations were achieved with the temperature, isoflurane, adrenaline, and aorta occlusion interventions. Measured changes in Ees and PRSW from control to intervention showed a strong correlation and no significant bias for APP in relation to IVCO. The APP-derived absolute values for Ees and PRSW demonstrated a consistent positive bias compared with IVCO. CONCLUSION: The APP method for preload reduction during LVPVR analysis detected changes in Ees and PRSW during the circulatory interventions in this model that were not different than those detected using another preload reduction method, IVCO. APP and IVCO are not interchangeable methods for preload reductions during LVPVR absolute quantitation of systolic function, and each needs to be used serially.