Jiri Mandak

Impact of cardiopulmonary bypass on peripheral tissue metabolism and microvascular blood flow.

The aim of this study was to monitor and compare the changes in metabolism and blood flow in the skeletal muscles during cardiac operations performed with cardiopulmonary bypass (CPB) and operations without CPB (off-pump) by means of interstitial microdialysis (Figure 1). Surgical revascularization, coronary artery bypass grafting (CABG), was performed in 40 patients randomized to two groups. Twenty patients (On-Pump Group) were operated on using CPB, 20 patients (Off-Pump Group) were operated on without CPB. Interstitial microdialysis was performed by 2 probes of a CMA 60 (CMA Microdialysis AB, Solna, Sweden) inserted into the patient’s deltoid muscle. Microdialysis measurements were performed at 30-minute intervals. Glucose, lactate, pyruvate and glycerol as markers of basic metabolism and tissue perfusion were measured in samples from the first probe, using a CMA 600 Analyzer (CMA Microdialysis AB). Blood flow through the interstitium was monitored by means of dynamic microdialysis of ethanol as a flow-marker in the dialysates taken from the second probe (ethanol dilution technique). Results in both the groups were statistically processed and compared. Both the groups were similar in respect of preoperative characteristics. Dynamic changes of interstitial concentrations of the measured analytes were found in both the patient groups (on-pump vs. off-pump) during the operation. There was no significant difference in dialysate concentrations of glucose and lactate between the groups. Significant differences were detected in pyruvate and glycerol interstitial concentrations, lactate/pyruvate ratio and lactate/glucose ratio between the on-pump vs. off-pump patients. In the Off-Pump Group, pyruvate concentrations were higher and the values of concentrations of glycerol lower. The lactate/pyruvate ratio and the lactate/glucose ratio, indicating the aerobic and anaerobic tissue metabolism status, were lower in the Off-Pump Group. There was no significant difference in dialysate concentrations of ethanol as a flow-marker during the surgery in either of the groups. There was no statistically significant difference between the groups (On-Pump Group vs. Off-Pump Group) comparing the postoperative clinical outcome (ICU stay, ventilation duration, length of hospital stay). The dynamic changes in the interstitial concentrations of the glucose, glycerol, pyruvate and lactate were found in both the groups of patients (On-Pump Group and Off-Pump Group), but there was no difference in local blood flow when the ethanol dilution technique was used. These results showed significantly higher aerobic metabolic activity of the peripheral tissue of patients in the Off-Pump Group vs. the On-Pump Group during the course of cardiac revascularization surgery. Results suggest that extracorporeal circulation, cardiopulmonary bypass, compromises peripheral tissue (skeletal muscles) energy metabolism. These changes have no impact on the postoperative clinical outcome; no significant difference between the groups was found.

The long pentraxin 3 in cardiac surgery: distinct responses in "on-pump" and "off-pump" patients.

Objective. Pentraxin 3 (PTX3) is a newly identified acute phase reactant with non-redundant functions in innate immunity. The purpose of this study was to assess the kinetics of release of PTX3 in cardiac surgical patients, operated on either with or without the use of cardiopulmonary bypass (CPB). Design. Thirty-four patients, seventeen in each group, were randomly assigned to CABG surgery performed either with (“on-pump”) or without (“off-pump”) CPB. Blood samples were collected both during and after the operation up to the 7th day. Results. In patients operated on with the use of CPB, PTX3 levels increased throughout the operation. Compared to baseline levels the highest PTX3 value (p<0.000) was attained on the 1st postoperative day in both “on-pump” and “off-pump” patients. In contrast to CPB patients, however, PTX3 levels in the latter group declined slowly, remaining elevated as long as the 3rd postoperative day (p<0.042). Conclusions. Operations performed with the use of CPB are associated with a more pronounced release of PTX3 immediatelly after operation.

Early Expression of FcRI (CD64) on Monocytes of Cardiac Surgical Patients and Higher Density of Monocyte Anti-Inflammatory Scavenger CD163 Receptor in “On-Pump” Patients

Objective. Activation of innate immunity cells is inseparably linked to cardiac surgical operation. The aim of this study was to assess the kinetics in the expression of receptor for Fc part of IgG, FcγRI (CD64), and scavenger receptor CD163 on peripheral blood cells of cardiac surgical patients and to examine the effect of cardiac bypass as a separable influence on the systemic acute inflammatory response. Methods. Forty patients, twenty in each group, were randomly assigned to CABG surgery performed either with “on-pump” or without “off-pump” cardiopulmonary bypass. Standardized quantitative flow cytometry method was used to determine the expression of surface markers. Results. The density of CD64 molecule on monocytes reached maximum on the 1st postoperative day (P<.001) whereas the peak for CD64 molecule expression on granulocytes was postponed to the 3rd postoperative day (P<.001). The expression of CD163 scavenger molecule on monocytes reached maximum on the 1st postoperative day (P<.001). The density of CD163 molecule on monocytes on the 1st postoperative day is significantly higher in “on-pump” patients in comparison with “off-pump” patients (P<.001). Conclusion. In cardiac surgical patients the expression of activation marker FcγR1 (CD64) on monocytes is increased earlier in comparison with granulocytes in both “on-pump” and “off-pump” patients. The expression of scavenger molecule CD163 on monocytes is significantly higher in “on-pump” patients.

Tissue and plasma concentrations of cephuroxime during cardiac surgery in cardiopulmonary bypass — a microdialysis study

Aim: Wound and mediastinal infections are still very serious complications of open-heart surgery, in spite of the use of prophylactic antibiotics. The use of cardiopulmonary bypass (CPB) is associated with profound physiological changes affecting the pharmacokinetic behaviour of antibiotics. The aim of this pilot study was to monitor the tissue concentrations of cephuroxime (prophylactic antibiotic) in skeletal muscle during cardiac surgery using CPB by interstitial microdialysis. These concentrations were compared with plasma concentrations of cephuroxime. Material and methods: Nine adult patients operated on using CPB were enrolled in this study. Cephuroxime was used as a prophylactic antibiotic (1st dose — 3 g of cefuroxime i.v. with anesthesia induction, 2nd dose — 1.5 g i.v. after CPB with protamine sulphate, 3rd dose — 1.5 g i.v. 8 hours after the surgery). Interstitial microdialysis was performed by probe CMA 60 (CMA Microdialysis AB, Sweden) inserted into the patients deltoid muscle. Concentrations of cephuroxime in dialysates and in plasma were determined by the modified fluid chromatography method. The unbound cephuroxime fraction in plasma was obtained by using an ultrafiltration method. Samples of dialysates were collected at the following intervals: before CPB, each 30 minutes of CPB, at the end of CPB. Samples of blood were collected at these intervals: incision, start of CPB, each 30 minutes of CPB, at the end of CPB, at the end of surgery. Concentrations of cephuroxime in tissue were corrected by in vivo recoveries of the microdialysis probes. Results: Plasma concentrations of cephuroxime were 163.5 ± 40.1, 79.3 ± 17.4, 73.7 ± 16.8, 66.1 ± 18.3, 57.0 ± 10.9, 120.7 ± 29.9 (mg . L — 1) and concentrations of free plasma fraction of cephuroxime were 119.5 ± 35.2, 67.8 ± 15.5, 66.0 ± 12.5, 54.8 ± 12.2, 49.6 ± 9.8, 102.6 ± 26.0 (mg . L — 1). The concentrations of cephuroxime in dialysates were 44.3 ± 15.7, 36.1 ± 11.6, 31.9 ± 9.3, 34.6 ± 12.3, 27.6 ± 12.9, 56.7 ± 17.6 (mg . L — 1). The mean in vivo recovery of cephuroxime in this study was 30%. Corrected concentrations (calculated by in vivo recovery) of cephuroxime in skeletal muscle were 148, 120, 106, 115, 92, 189 (mg . L — 1). Conclusion: Our preliminary results show that CPB can modify the time course of cephuroxime plasma and tissue concentrations. A decrease in plasma drug concentrations occurred at the start of CPB and lasted until CPB ended. An increase in plasma concentrations corresponds to the second drug dose after CPB. The concentrations of cephuroxime in skeletal muscle (corrected by recovery) during CPB are higher than plasma concentrations. It is influenced by important changes during CPB; closely associated with hemodilution, a shift of intravascular volume, solutes and albumin to the extravascular space and inconstant protein binding of cephuroxime during operation. Perfusion (2007) 22, 129—136.

No clear clinical benefit of using mini-invasive extracorporeal circulation in coronary artery bypass grafting in low-risk patients.

Background: Current research is engaged in innovative technologies of extracorporeal circulation (ECC) systems in an effort to eliminate negative effetcs. Some studies have shown that, due to the complexity of technical settings of mini-ECC, they invoke a weaker immune response compared to classic ECC. The clinical benefits of using these systems have not been clearly proven yet. Methods: A group of 54 patients who were indicated for elective coronary surgery were randomised into two groups — Group A (patients operated on using classic ECC - open modification) and Group B (patients operated on using mini-ECC). The concentrations of IL-6, PMN elastase and MCP-1 in both groups were monitored per- and postoperatively, along with the postoperative clinical course. Results: The groups did not differ in the basic pre- and peroperative characteristics. We recorded a lower priming for mini-ECC (p < 0.001) and significantly reduced hemodilution during ECC. There were no differences in the clinical outcome in either group. Serum concentrations of monitored markers of immune reaction towards ECC showed higher activity during standard ECC. Conclusion: New technologies used in mini-systems have proven to lower activation of the immune system, which can be monitored using kinetics of proinflammatory mediators. In spite of these comparable laboratory results, we did not find differences in short-term clinical results when comparing both these groups of low-risk patients.

Neutrophil Apoptosis by Fas/FasL: Harmful or Advantageous in Cardiac Surgery?

Polymorphonuclear leukocytes or neutrophils are the main executors of cellular death, both in septic inflammation during bacterial infection and in sterile inflammation during trauma or surgery. Whereas in septic inflammation neutrophils perform a useful function to fortify the hosts defense against infection, in sterile inflammation, by contrast, they contribute to unwelcome tissue damage. Regardless of the situation, activated neutrophils exhibit a prolonged lifespan and delayed apoptotic death which, under normal conditions, is a prerequisite for their natural renewal. Traditionally, delayed neutrophil apoptosis was considered to promote trauma or surgical injury. According to the results of recent studies, however surprising they may appear, the reverse might be in keeping with what happens IN VIVO. Apoptotic signaling in neutrophils could, by contrast, contribute to intrinsic protection of the hosts tissues. This review article, aimed preferentially but not exclusively at the cardiac surgeon, presents some new information in support of this viewpoint, which fits in with our own observations.

Serum level of sCD163, a soluble receptor for hemoglobin, is influenced by cardiac surgery

Background:The scavenger receptor for complexes hemoglobin-haptoglobin (CD163), which is expressed on monocytes/ macrophages, is shed to the body fluids in a soluble form (sCD163). Objectives: To evaluate the dynamics of sCD163 in the blood of patients undergoing cardiac surgery. Patients and Methods: Sixty-one adult patients who underwent coronary artery bypass grafting (CABG) were enrolled in the study. They were assigned to undergo CABG using either cardiopulmonary bypass (CPB), “on-pump”, (22 patients), modified CPB, mini “on-pump”, (17 patients) or without CPB, “off-pump”, (22 patients) surgery. Serum levels of sCD163 in venous blood samples taken before and after surgery, and during an early postoperative period, were evaluated by Macro 163TM diagnostic kit (IQ Products, Groningen, NL). Results: Compared to the preoperative levels (“on-pump”; 344 ng/mL, “off-pump”; 314.5 ng/mL, mini-invasive “on-pump”; 336.5 ng/mL) serum levels were elevated at the finish of surgery, reaching maximum at the 1st postoperative day (“onpump”; 658 ng/mL; p<0.05, “off-pump”; 810.5 ng/mL; p<0.01; mini-invasive “on-pump”; 663 ng/mL; non-significant). No significant differences regarding the serum levels of sCD163 between different surgical approaches were found. Conclusion: Serum level of sCD163 scavenger molecule for hemoglobin is elevated at the end of surgery and at the 1st postoperative day, being little influenced by cardiopulmonary bypass.

Lipopolysaccharide Binding Protein and sCD14 are Not Produced as Acute Phase Proteins in Cardiac Surgery

Objectives. The changes in the serum levels of lipopolysaccharide binding protein (LBP) and sCD14 during cardiac surgery were followed in this study. Design. Thirty-four patients, 17 in each group, were randomly assigned to coronary artery bypass grafting surgery performed either with (“on-pump”) or without (“off-pump”) cardiopulmonary bypass. LBP and sCD14 were evaluated by ELISA. Results. The serum levels of LBP were gradually increased from the 1st postoperative day and reached their maximum on the 3rd postoperative day in both “on-pump” and “off-pump” patients (30.33±9.96 μg/mL; 37.99±16.58 μg/mL), respectively. There were no significant differences between “on-pump” and “off-pump” patients regarding LBP. The significantly increased levels of sCD14 from the 1st up to the 7th postoperative day in both “on-pump” and “off-pump” patients were found with no significant differences between these groups. No correlations between LBP and sCD14 and IL-6, CRP and long pentraxin PTX3 levels were found. Conclusions. The levels of LBP and sCD14 are elevated in cardiac surgical patients being similar in both groups. These molecules are not produced as acute phase proteins in these patients.

Expression of CD200/CD200R regulatory molecules on granulocytes and monocytes is modulated by cardiac surgical operation

Aims: Cardiac surgical operation is inseparably linked to the induction of an inflammatory response. Both humoral and cellular regulatory mechanisms are operating to maintain body homeostasis. We followed the changes in the expression of CD200/CD200R regulatory molecules on monocytes and granulocyte of cardiac surgical patients operated on using either standard (OP) or modified “mini-invasive” cardiopulmonary bypass (MOP). Methods: Expression of CD200/CD200R regulatory molecules was determined by flow cytometry. Results: The expression of CD200R on granulocytes was increased after surgery in both groups of patients, but the increase was statistically significant only in OP patients (p<0.01). At this time point, there was a significant difference in CD200R expression on granulocytes when comparing OP to MOP patients, being higher in the former group (p<0.01). The expression of CD200R on monocytes was diminished after surgery and during an early postoperative period in both groups of patients. The expression of CD200 on monocytes was significantly diminished after surgery in both groups (p<0.01). Nonetheless, we observed an increase in CD200 expression in OP patients at the 3rd postoperative day. There was a statistically significantly increased CD200 expression on monocytes of OP patients (p<0.001) at the 3rd postoperative day when we compared OP and MOP groups. The expression of CD200 on granulocytes was significantly higher after surgery and at the 3rd postoperative day in OP when compared to MOP patients. Conclusions: CD200R expression on granulocytes was significantly increased, while CD200 and CD200R expression on monocytes was decreased after cardiac surgery.

The Effect of Conventional and Mini-Invasive Cardiopulmonary Bypass on Neutrophil Activation in Patients Undergoing Coronary Artery Bypass Grafting

Interleukin-10 (IL-10) is considered to be a cytokine with potent anti-inflammatory properties, which have been previously linked to increased incidence of sepsis. The level of IL-10 is elevated by cardiac surgery when cardiopulmonary bypass (CPB) and methylprednisolone are used. In our study, we compare the level of IL-10, IL-10 Receptor (IL-10R), and percentage of neutrophils between two groups of cardiac surgical patients undergoing Coronary Artery Bypass Grafting, both of which were not given methylprednisolone. The first group was operated with conventional CPB, while the second group was operated with minimally invasive CPB (mini-CPB). We detected enhanced level of IL-10 during surgery and at the end of surgery in both groups of patients. While no correlation between IL-10 and IL10R was found, IL-10 was positively correlated with increased percentage of neutrophils at the time points when the level of IL-10 peaked.