Short- and long-term survival after isolated coronary artery bypass grafting, the impact of gender and age.

Objectives. Assess the short- and long-term survival for patients who underwent isolated coronary artery bypass grafting (CABG) and evaluate the impact of gender and age. Furthermore to assess the long-term survival in the CABG group compared to the general population. Design. This study included 4044 consecutive patients who underwent isolated CABG at Oslo University Hospital, Ullevål, in Oslo, Norway in the time period from 01 January 2003 to 31 December 2015. Patient data was collected retrospectively from the quality register at the department. Information on survival status was obtained from the Norwegian National Registry. Life expectancy data for the general population was gained from Statistics Norway. Results. Female patients were significantly older than male patients at the time of surgery (mean age 67.0 and 63.9 years, respectively, p < .001), and had significantly lower 30-day survival (mortality was 1.4% and 0.6%, respectively, p = .017). Male gender was independently associated with lower long-term survival (p = .0037) in a multivariate analysis. Male patients aged less than 60 years also showed significantly lower long-term survival (SMR = 1.84, 95% CI = 1.49-2.25) compared to the age-matched general population. Among patients older than 60 years, survival was similar to survival in the age-matched general population. Conclusions. Survival was excellent for patients undergoing surgery. Despite increased age and operative mortality, female patients had better adjusted long-time survival than male patients. There was lower long-term survival among male patients aged less than 60 compared to the general population. Our findings may help clinicians in selecting appropriate patients for surgery.

First Experience With Rectus Sheath Block for Postoperative Analgesia After Pancreas Transplant: A Retrospective Observational Study.

BACKGROUND: Standard of care for postoperative analgesia after pancreas transplant has been thoracic epidural analgesia (TEA). A high incidence of venous graft thrombosis necessitated a change to a more aggressive anticoagulation protocol. To minimize the risk of epidural hemorrhages, we changed from TEA to rectus sheath block (RSB) in 2017. METHODS: From June 2016 to December 2017, a total of 29 consecutive pancreas transplant recipients were included. Sixteen were treated with TEA and 13 were treated with RSB. In the TEA group, the catheter was inserted before induction of general anesthesia, and an epidural infusion was started intraoperatively. An ultrasound-guided RSB was performed bilaterally, and a bolus of local anesthetic was administered before an 18G catheter was inserted. The patients received intermittent local anesthetic boluses every 4 hours in addition to an intravenous patient-controlled analgesia with oxycodone. Both groups received oral acetaminophen and additional rescue opioids. RESULTS: The administered amount of intravenous morphine equivalents (MEQ) was not significantly different between the RSB and TEA groups. The median MEQ consumption per day during the stay at the surgical ward was 23 mg MEQ/d (interquartile range [IQR], 14-33 mg MEQ/d) in the TEA group compared with 19 mg MEQ/d (IQR, 14-32 mg MEQ/d) in the RSB group (P = .4). The duration of the pain catheters was significantly longer in the RSB group. We had no complications related to insertion, use, or removal of the RSB or the TEA catheters, and overall patient satisfaction and comfort was good. CONCLUSION: Compared with TEA, RSB was equally effective and safe for postoperative analgesia in heavily anticoagulated pancreas transplant patients.

Complement factor 5 blockade reduces porcine myocardial infarction size and improves immediate cardiac function.

Inhibition of complement factor 5 (C5) reduced myocardial infarction in animal studies, while no benefit was found in clinical studies. Due to lack of cross-reactivity of clinically used C5 antibodies, different inhibitors were used in animal and clinical studies. Coversin (Ornithodoros moubata complement inhibitor, OmCI) blocks C5 cleavage and binds leukotriene B4 in humans and pigs. We hypothesized that inhibition of C5 before reperfusion will decrease infarct size and improve ventricular function in a porcine model of myocardial infarction. In pigs (Sus scrofa), the left anterior descending coronary artery was occluded (40 min) and reperfused (240 min). Coversin or placebo was infused 20 min after occlusion and throughout reperfusion in 16 blindly randomized pigs. Coversin significantly reduced myocardial infarction in the area at risk by 39% (p = 0.03, triphenyl tetrazolium chloride staining) and by 19% (p = 0.02) using magnetic resonance imaging. The methods correlated significantly (R = 0.92, p < 0.01). Tissue Doppler echocardiography showed increased systolic displacement (31%, p < 0.01) and increased systolic velocity (29%, p = 0.01) in coversin treated pigs. Interleukin-1ß in myocardial microdialysis fluid was significantly reduced (31%, p < 0.05) and tissue E-selectin expression was significantly reduced (p = 0.01) in the non-infarcted area at risk by coversin treatment. Coversin ablated plasma C5 activation throughout the reperfusion period and decreased myocardial C5b-9 deposition, while neither plasma nor myocardial LTB4 were significantly reduced. Coversin substantially reduced the size of infarction, improved ventricular function, and attenuated interleukin-1ß and E-selectin in this porcine model by inhibiting C5. We conclude that inhibition of C5 in myocardial infarction should be reconsidered.

In vivo characterization of ischemic small intestine using bioimpedance measurements.

The standard clinical method for the assessment of viability in ischemic small intestine is still visual inspection and palpation. This method is non-specific and unreliable, and requires a high level of clinical experience. Consequently, viable tissue might be removed, or irreversibly damaged tissue might be left in the body, which may both slow down patient recovery. Impedance spectroscopy has been used to measure changes in electrical parameters during ischemia in various tissues. The physical changes in the tissue at the cellular and structural levels after the onset of ischemia lead to time-variant changes in the electrical properties. We aimed to investigate the use of bioimpedance measurement to assess if the tissue is ischemic, and to assess the ischemic time duration. Measurements were performed on pigs (n = 7) using a novel two-electrode setup, with a Solartron 1260/1294 impedance gain-phase analyser. After induction of anaesthesia, an ischemic model with warm, full mesenteric arterial and venous occlusion on 30 cm of the jejunum was implemented. Electrodes were placed on the serosal surface of the ischemic jejunum, applying a constant voltage, and measuring the resulting electrical admittance. As a control, measurements were done on a fully perfused part of the jejunum in the same porcine model. The changes in tan δ (dielectric parameter), measured within a 6 h period of warm, full mesenteric occlusion ischemia in seven pigs, correlates with the onset and duration of ischemia. Tan δ measured in the ischemic part of the jejunum differed significantly from the control tissue, allowing us to determine if the tissue was ischemic or not (P < 0.0001, F = (1,75.13) 188.19). We also found that we could use tan δ to predict ischemic duration. This opens up the possibility of real-time monitoring and assessment of the presence and duration of small intestinal ischemia.

Effect of Perfusion Fluids on Recovery of Inflammatory Mediators in Microdialysis.

Microdialysis is an excellent tool to assess tissue inflammation in patients, but in vitro systems to evaluate recovery of inflammatory mediators have not been standardized. We aimed to develop a reference plasma preparation and evaluate different perfusion fluids with respect to recovery of metabolic and inflammatory markers. The reference preparation was produced by incubation of human blood with lipopolysaccharide and cobra venom factor to generate cytokines and activate complement, respectively. Microdialysis with 100 kDa catheters was performed using different colloid and crystalloid perfusion fluids (hydroxyethyl starch (HES) 130/0.4, HES 200/0.5, hyperosmolar HES 200/0.5, albumin 200 g/l, T1 perfusion fluid and Ringer's acetate) compared to today's recommended dextran 60 solution. Recovery of glucose, glycerol and pyruvate was not significantly different between the perfusion fluids, whereas lactate had lower recovery in HES 200/0.5 and albumin perfusion fluids. Recovery rates for the inflammatory proteins in comparison with the concentration in the reference preparation differed substantially: IL-6 = 9%, IL-1ß = 18%, TNF = 0.3%, MCP-1 = 45%, IL-8 = 48%, MIG = 48%, IP-10 = 25%, C3a = 53% and C5a = 12%. IL-10 was not detectable in microdialysis dialysate. HES 130/0.4 and HES 200/0.5 yielded a recovery not significantly different from dextran 60. Hyperosmolar HES 200/0.5 and albumin showed significantly different pattern of recovery with increased concentration of MIG, IP-10, C3a and C5a and decreased concentration of IL-1ß, TNF, MCP-1 and IL-8 in comparison with dextran 60. In conclusion, microdialysis perfusion fluid dextran 60 can be replaced by the commonly used HES 130/0.4, whereas albumin might be used if specific immunological variables are in focus. The present reference plasma preparation is suitable for in vitro evaluation of microdialysis systems.

Myocardial tissue CO2 tension detects coronary blood flow reduction after coronary artery bypass in real-time†.

BACKGROUND: Coronary stenosis after coronary artery bypass grafting (CABG) may lead to myocardial ischaemia and is clinically difficult to diagnose. In a CABG model, we aimed at defining variables that detect hypoperfusion in real-time and correlate with impaired regional ventricular function by monitoring myocardial tissue metabolism. METHODS: Off-pump CABG was performed in 10 pigs. Graft blood flow was reduced in 18 min intervals to 75, 50, and 25% of baseline flow with reperfusion between each flow reduction. Myocardial tissue Pco2 (Pt(CO2)), Po2, pH, glucose, lactate, and glycerol from the graft supplied region and a control region were obtained. Regional cardiac function was assessed as radial strain. RESULTS: In comparison with baseline, myocardial pH decreased during 75, 50, and 25% flow reduction (-0.15; -0.22; -0.37, respectively, all P<0.05) whereas Pt(CO2) increased (+4.6 kPa; +7.8 kPa; +12.9 kPa, respectively, all P<0.05). pH and Pt(CO2) returned to baseline upon reperfusion. Lactate and glycerol increased flow-dependently, while glucose decreased. Regional ventricular contractile function declined significantly. All measured variables remained normal in the control region. Pt(CO2) correlated strongly with tissue lactate, pH, and contractile function (R=0.86, R=-0.91, R=-0.70, respectively, all P<0.001). New conductometric Pt(CO2) sensors were in agreement with established fibre-optic probes. Cardiac output was not altered. CONCLUSIONS: Myocardial pH and Pt(CO2) monitoring can quantify the degree of regional tissue hypoperfusion in real-time and correlated well with cellular metabolism and contractile function, whereas cardiac output did not. New robust conductometric Pt(CO2) sensors have the potential to serve as a clinical cardiac monitoring tool during surgery and postoperatively.

Reduced visfatin levels in aortic stenosis increase after aortic valve replacement and may contribute to reverse left ventricular remodelling.

AIM: Visfatin may play a part in reverse left ventricular remodelling. Using a mouse model of reversible left ventricle pressure overload, we examined if visfatin was altered in the myocardium. Furthermore, we addressed this issue in patients with aortic stenosis (AS) and examined whether visfatin levels are related to reverse remodelling following aortic valve replacement (AVR). METHODS: Myocardial visfatin was analysed after aortic banding (AB) and debanding (DB) in mice and compared to sham operated animals. Myocardial visfatin was measured in biopsies from patients undergoing AVR and compared to controls. Serum visfatin was measured before and after AVR in patients with AS and correlated with echocardiographic measurments of cardiac morphology and function. RESULTS: Four weeks after AB, myocardial visfatin protein was reduced by 50% compared to sham. Three days after DB, myocardial protein levels increased significantly. Myocardial visfatin and serum visfatin levels were reduced by 23% and 64%, respectively, in patients with AS compared to controls. Twelve months after AVR, serum visfatin levels increased compared to preoperative values and correlated negatively with degree of left ventricular hypertrophy. CONCLUSION: Myocardial visfatin and serum visfatin levels are reduced by cardiac pressure overload. Visfatin levels increase after correction of pressure overload and may play a part in postoperative reverse remodelling.

Activation of coagulation and platelets by candidate membranes of implantable devices in a whole blood model without soluble anticoagulant.

Implantable devices are challenged with thrombus formation at their biomaterial interface. Thus the importance of identifying compatible biomaterials that will help to improve the performance of these devices are becoming increasingly paramount. The aim of this study was to evaluate the activation of coagulation and platelets by candidate membranes considered for use in implantable devices on the basis of an adapted whole blood model without soluble anticoagulants. Evaluated materials were incubated with whole blood without soluble anticoagulant in wells coated with heparin. Prothrombin fragment 1+2 (PTF 1+2), thrombin-antithrombin complex (TAT), and ß-thromboglobulin (BTG) were analyzed in plasma samples using enzyme immunoassays. The C5 inhibitor eculizumab was used to evaluate the role of complement. Incubation of two of the polyamide membranes PAR and PATF led to an increase in concentration of PTF 1+2 and TAT (p < 0.01 for PAR, ns for PATF). The BTG concentration was significantly increased for five materials [PAR, PATF, polycarbonate (PC), and two polyarylethersulphone membranes PAES-1 and PAES-2]. Complement inhibition had no effect on coagulation or platelet activation induced by PAR and PATF. In conclusion, PAR and PATF were not compatible with blood and should be avoided for use in implantable devices.

Tissue gas tensions and tissue metabolites for detection of organ hypoperfusion and ischemia.

BACKGROUND: The aim of this study was to evaluate how tissue gas tensions and tissue metabolites measured in situ can detect hypoperfusion and differentiate between aerobic and anaerobic conditions during hemorrhagic shock. We hypothesized that tissue PCO(2) (PtCO(2)) would detect hypoperfusion also under aerobic conditions and detect anaerobic metabolism concomitantly with or earlier than other markers. METHODS: Prospective experimental animal study with eight anesthetized pigs subjected to a continuous blood loss ∼8% of total blood volume per hour until death. We measured cardiac index, organ blood flows, and tissue levels of PO(2), PCO(2), glucose, pyruvate, lactate, and glycerol in intestine, liver, kidney, and skeletal muscle. RESULTS: With reduction in blood flow to the organs under aerobic conditions, PtCO(2) increased ∼1-4 kPa from baseline. With the onset of tissue hypoxia there was a pronounced increase of PtCO(2), lactate, lactate-pyruvate (LP) ratio, and glycerol. Tissue pH and bicarbonate decreased significantly, indicating that metabolic acid was buffered by bicarbonate to generate CO(2). CONCLUSION: Moderate tissue hypoperfusion under aerobic conditions is associated with increased PtCO(2), in contrast to metabolic parameters of ischemia (lactate, LP ratio, and glycerol) which remain low. From the onset of ischemia there is a much more rapid and pronounced increase in PtCO(2), lactate, and LP ratio. PtCO(2) can be used as a marker of hypoperfusion under both aerobic and anaerobic conditions; it gives an earlier warning of hypoperfusion than metabolic markers and increases concomitantly with or earlier than other markers at the onset of tissue anaerobiosis.

A mouse model of reverse cardiac remodelling following banding-debanding of the ascending aorta.

AIM: Myocardial remodelling during pressure overload might contribute to development of heart failure. Reverse remodelling normally occurs following aortic valve replacement for aortic stenosis; however, the details and regulatory mechanisms of reverse remodelling remain unknown. Thus, an experimental model of reverse remodelling would allow for studies of this process. Although models of aortic banding are widely used, only few reports of debanding models exist. The aim of this study was to establish a banding-debanding model in the mouse with repetitive careful haemodynamic evaluation by high-resolution echocardiography. METHODS: C57Bl/6 mice were subjected to ascending aortic banding and subsequent debanding. Cardiac geometry and function were evaluated by echocardiography, and left ventricular myocardium was analysed by histology and quantitative real-time polymerase chain reaction. RESULTS: The degree of aortic banding was controlled by non-invasive estimation of the gradient, and we found a close correlation between left ventricular mass estimated by echocardiography and weight at the time of killing. Aortic banding led to left ventricular hypertrophy, fibrosis and expression of foetal genes, indicating myocardial remodelling. Echocardiography revealed concentric left ventricular remodelling and myocardial dysfunction. Following debanding, performed via a different incision, there was rapid regression of left ventricular weight and normalization of both cardiac geometry and function by 14 days. CONCLUSIONS: We have established a reproducible and carefully characterized mouse model of reverse remodelling by banding and debanding of the ascending aorta. Such a model might contribute to increased understanding of the reversibility of cardiac pathology, which in turn might give rise to new strategies in heart failure treatment.

Osteoprotegerin levels predict mortality in patients with symptomatic aortic stenosis.

OBJECTIVES: To examine the prognostic value of osteoprotegerin (OPG) levels in relation to all-cause mortality in patients with symptomatic severe aortic stenosis (AS). DESIGN: We measured plasma OPG levels in 136 patients with symptomatic severe AS and investigated associations with transvalvular gradients, valve area, valve calcification (using ultrasonic backscatter analysis as an estimate) and measures of heart failure. Then, we assessed the prognostic value of elevated plasma OPG in determining all-cause mortality (n = 29) in these patients. RESULTS: Elevated OPG was poorly correlated with the degree of AS but was associated with increased backscatter measurements and impaired cardiac function. Furthermore, OPG was associated with all-cause mortality in patients with symptomatic AS, even after adjustment for conventional risk markers. The strongest association was obtained by using a combination of high levels of both OPG and N-terminal pro-brain natriuretic peptide (NT-proBNP), suggesting that these markers may reflect distinct pathways in the development and progression of AS. CONCLUSION: The level of circulating OPG is significantly associated with all-cause mortality alone and in combination with NT-proBNP in patients with severe symptomatic AS.

New biomarkers in an acute model of live Escherichia coli-induced sepsis in pigs.

We developed a live Escherichia coli model of acute sepsis in pigs with emphasize on biomarkers reflecting the early inflammatory response of sepsis. Healthy pigs, 25-35 kg, were challenged intravenously (IV) (n = 12) or intrapulmonary (n = 6) with live E. coli and observed for 3 and 5 h respectively. Control pigs received culture medium (n = 6 + 3). Haemodynamic parameters and a broad panel of inflammatory mediators were measured. The dose of bacteria was carefully titrated to obtain a condition resembling the early phase of human septic shock. The IV group displayed a pro-inflammatory response [significant increase in tumour necrosis factor-alpha, interleukin (IL)-6 and IL-8] and an early anti-inflammatory response (significant increase in IL-10). For the first time, we demonstrate a significant increase in IL-12 and matrix metalloproteinase-9 (MMP) early in pig sepsis. Coagulation was activated (significant increase in thrombin-antithrombin complexes) and there was a significant decrease in the serum proteins suggesting capillary leakage. Haemodynamic parameters reflected a septic condition with significant decrease in systemic blood pressure, increases in heart rate, pulmonary artery pressure and base deficit. None of these changes was observed in the control group. Interleukin-1beta and vascular endothelial growth factor increased in both groups. Nitric oxide measurements suggested an initial pulmonary vascular endothelial inflammatory response. The intrapulmonary group, which did not resemble septic condition, showed a substantial increase in MMP-9. In this porcine model of sepsis, IL-12 and MMP-9 were detected for the first time. These biomarkers may have an impact in the understanding and future treatment of sepsis.

Continuous cardiac output during off-pump coronary artery bypass surgery: pulse-contour analyses vs pulmonary artery thermodilution.

BACKGROUND: No gold standard method exists for monitoring continuous cardiac output (CO). In this study, the agreement between the two most frequently used methods, PiCCO pulse-contour analysis (PCCO) and STAT pulmonary artery thermodilution (STAT-CO), was assessed during multiple-vessel off-pump coronary artery bypass (OPCAB) surgery. METHODS: Thirty patients were enrolled in the study. Two time periods were defined during surgery; Period 1 included positioning of the heart and stabilizer device and Period 2 included the coronary occlusion. Measurements were obtained every minute during both periods. The agreement for the continuous CO and the change in CO (DeltaCO) was estimated using the Bland-Altman method. RESULTS: Significant changes in mean arterial pressure (DeltaMAP), central venous saturation, PCCO and STAT-CO were seen only during Period 1. DeltaMAP correlated only with changes in PCCO, (P < 0.001, r = 0.60). The mean difference (2sd) between PCCO and STAT-CO ranged from - 0.29 (1.82) to - 0.71 (2.57) litre min(-1), and the percentage error varied from 32 to 50%. For the CO measurements, the limits of agreements did not differ between Period 1 and Period 2. In contrast, for the DeltaCO measurements, the limits of agreements were wider in Period 1 than in the more haemodynamically stable Period 2. CONCLUSIONS: CCO and STAT-CO show large discrepancies in CO during OPCAB surgery. Clinically acceptable agreement was seen only for trends in CO during haemodynamically stable periods.

Agreement between PiCCO pulse-contour analysis, pulmonal artery thermodilution and transthoracic thermodilution during off-pump coronary artery by-pass surgery.

BACKGROUND: Haemodynamic instability during off-pump coronary artery bypass surgery (OPCAB) may appear rapidly, and continuous monitoring of the cardiac index (CI) during the procedure is advisable. With the PiCCO monitor, CI can be measured continuously and almost real time with pulse-contour analysis and intermittently with transthoracic thermodilution. The agreement between pulmonal artery thermodilution CI (Tpa), transthoracic thermodilution CI (Tpc) and pulse-contour CI (PCCI) during OPCAB surgery has not been evaluated sufficiently. METHODS: In 30 patients scheduled for OPCAB surgery, a pulmonary artery catheter and a PiCCO catheter were inserted. At different time points during surgery, Tpa, Tpc and PCCI were compared. Measurements were performed after induction of anesthesia (T1), after pericardiothomy (T2), after grafting on the anterior (T3), posterior (T4) and lateral (T5) walls and after chest closure (T6). The PCCI was recalibrated at time point T2-T6. RESULTS: Mean difference and the limits of agreements (percentage error) between Tpa and Tpc were: -0.14 +/- 0.60 (22.0%) l/min/m2, between Tpa and PCCI: -0.07 +/- 0.92 (33.5%) l/min/m2 and between Tpc and PCCI: 0.10 +/- 1.00 (35.5%) l/min/m2. For changes in CI from one time point to the next (DeltaCI), the limits of agreements between DeltaCI Tpa and DeltaCI Tpc were 0.04 +/- 0.90 l/min/m2, between DeltaCI Tpa and DeltaCI PCCI: -0.02 +/- 1.22 l/min/m2 and between DeltaCI Tpc and DeltaCI PCCI: -0.08 +/- 1.32 l/min/m2. CONCLUSION: In OPCAB surgery, limits of agreement comparing thermodilution methods were smaller than comparing PCCI with thermodilution. Recalibration of PCCI is therefore advisable.

Microdialysis for monitoring inflammation: efficient recovery of cytokines and anaphylotoxins provided optimal catheter pore size and fluid velocity conditions.

Microdialysis emerges as a useful tool to evaluate tissue inflammation in a number of clinical conditions, like sepsis and transplant rejection, but systematic methodological studies are missing. This study was undertaken to determine the recovery of relevant inflammatory mediators using the microdialysis system, comparing microdialysis membranes with two different molecular weight cut-offs at different flow rates. Twenty and 100 kDa pore sizes CMA microdialysis catheters were investigated using velocities of 0.3, 1.0 and 5.0 microl/min. Reference preparations for cytokines [tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and IL-10; m.w. 17-28 kDa] and chemokines (IL-8, MCP-1, IP-10 and MIG; m.w. 7-11 kDa) were prepared from plasma after incubating human whole blood with lipopolysaccharide. Reference preparation for complement anaphylatoxins (C3a, C4a, C5a; m.w. 9-11 kDa) was prepared by incubating human plasma with heat-aggregated immunoglobulin G. The reference preparations were quantified for the respective inflammatory molecules and used as medium for the microdialysis procedure. Through the 20 kDa filter only the four chemokines passed, but with low recovery (3-7%) and limited to the 1.0 microl/min velocity. The recovery with the 100 kDa filter was as follows: IL-1beta = 75%, MCP-1 = 55%, MIG = 50%, IL-8 = 38%, C4a = 28%, IP-10 = 22%, C5a = 20%, C3a = 16%, IL-6 = 11, IL-10 = 8% and TNF-alpha = 4%. The highest recovery for all chemokines and anaphylatoxins were consistently at velocity 1.0 microl/min, whereas IL-1beta and IL-10 recovered most efficiently at 0.3 microl/min. Thus, microdialysis using catheters with a cut-off of 100 kDa is a reliable method to detect inflammation as judged by a defined panel of inflammatory markers. These findings may have important implications for future clinical studies.

Postoperative pain and convalescence in living kidney donors-laparoscopic versus open donor nephrectomy: a randomized study.

The aim of the present study was to compare postoperative pain and convalescence in patients randomized to laparoscopic or open donor surgery in a prospective, controlled trial. The donors were randomly assigned to undergo laparoscopic (n = 63) or open (n = 59) donor nephrectomy. Our end points were amount of administered analgesics in the recovery period, postoperative pain on the second postoperative day and at one month after surgery and duration of sick leave. There was a significant difference in favor of the laparoscopic group regarding administered analgesics on day of surgery (p < 0. 02). No difference was observed between groups regarding self-reported pain on the second postoperative day. One month post donation, significantly fewer donors in the laparoscopic group reported pain (p < 0. 02) or had used analgesics (p < 0.05). The duration of sick leave was significantly shorter in the laparoscopic group (p = 0.01). The laparoscopic group experienced a more rapid convalescence and a shorter period of sick leave. Although immediate postoperative pain can be managed efficiently regardless of procedure, a lower consumption of opioids and incidence of pain in the convalescent period suggest a clinically relevant patient-experienced benefit from a successful laparoscopic procedure.

Regulation of neuronal type genes in congestive heart failure rats.

AIM: After myocardial infarction (MI), complex changes in the heart occur during progression into congestive heart failure (CHF). This study sought to identify regulated genes that could have a functional role in some of the changes seen in CHF. METHODS: Myocardial infarction was induced by ligation of the left anterior descending coronary artery (LAD) in Wistar rats. Gene expression changes in 1- and 7-day MI left ventricular myocardium was analysed using complementary DNA (cDNA) filter arrays. Regulated genes were identified by repeated measurements and a ranked ratio analysis method. RESULTS: A total of 135 genes were identified as differentially expressed. A few genes were robustly regulated at 1-day MI. In 7-day CHF hearts, changes in the expression of neuronal type genes was prominent (32%, n = 28). Eleven of these genes with no described association with CHF were selected for validation. One gene failed the validation. In CHF hearts, the expression of the muscarinic m4 (Chrm4) and nicotinic alpha4 (Chrna4) acetylcholin receptors, the ATP receptor P2rx4, nerve growth factor receptor (Ngfr), discoidin domain receptor 1 (Ddr1), neuronal pentraxin receptor (Nptxr), peripheral myelin protein Pmp-22, leukocyte type 12-lipoxygenase (Alox15), cytochrome P450 4F5 (Cyp4F5) and cardiac Kcne1 were all increased (range 1.6-6.0-fold, P < 0.01 for all genes). The lack of significant regulation of these genes at 1-day post-MI, suggests that the induction of these genes at 7-day post-MI is not a short-term response induced by the infarct itself. CONCLUSION: These neuronal type genes may participate in underlying processes that affect contractility, intracardiac nerve function and development of arrhythmias in CHF hearts.

Detection of organ ischemia during hemorrhagic shock.

BACKGROUND: In a porcine hemorrhagic shock model we aimed to determine: (a) whether blood flow to the intestine and kidney was more reduced than cardiac output; (b) whether parameters of anaerobic metabolism correlated with regional blood flow; and (c) whether metabolic parameters in intestine, kidney and skeletal muscles detected a compromised metabolic state at an earlier stage than did systemic parameters. METHODS: In an animal research laboratory at a university hospital six domestic pigs were subjected to volume-controlled hemorrhage. Every 30 min samples of blood were withdrawn. Systemic and regional hemodynamic parameters and tissue levels of PCO2 were monitored. Whole body and organ-specific oxygen consumption (VO2) and veno-arterial (VA) differences of lactate, glucose, potassium (K+), PCO2, H+ and base excess (BE) were calculated every 30 min. RESULTS: With progressive hemorrhage, intestinal blood flow decreased to the same extent as cardiac output, whereas the reduction in renal blood flow was more pronounced. We found a concomitant reduction in VO2 (onset of supply dependent metabolism) in intestine, kidney and skeletal muscles. In muscular tissue PCO2 increased to levels three times higher than baseline, while renal and intestinal PCO2 increased eightfold. Supply dependency was associated with a concomitant increase in VA CO2 and VA H+. Also, VA lactate increased, mostly in intestine and least in skeletal muscle. Intestinal and renal VA K+ increased, while muscular VA K+ decreased. Arterial lactate and H+ increased considerably, whereas arterial BE decreased. CONCLUSION: With progressive hemorrhage, renal blood flow, but not intestinal and skeletal muscle blood flow, was reduced more than cardiac output. Supply dependent oxygen metabolism (VO2) and organ acidosis occurred simultaneously in the three organs, despite differences in blood flow reductions. Organ ischemia coincided with a pronounced change in arterial lactate and systemic acid base parameters.

Gene expression of colony-stimulating factors and stem cell factor after myocardial infarction in the mouse.

Recent studies have suggested that cytokines such as macrophage colony-stimulating factor (M-CSF) might be involved in the pathogenesis of ischaemic heart disease. Macrophage colony-stimulating factor, granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage-colony stimulating factor (GM-CSF), stem cell factor (SCF), interleukin-3 (IL-3) and interleukin-7 (IL-7) are potent cytokines belonging to the same structual class that may affect function, growth and apoptosis both in the heart and other organs. The aims of the present study were to characterize a post-infarction model in the mouse and to examine mRNA expression of M-CSF, GM-CSF, SCF, IL-3 and IL-7 during the development of heart failure. Myocardial infarction (MI) was induced in mice by ligation of the left coronary artery. Average infarct size was 40% and the mice developed myocardial hypertrophy and pulmonary oedema. Ribonuclease (RNAase) protection assays showed abundant cardiac expression of M-CSF and SCF. After MI, we measured down-regulation of cytokine mRNA expression in the heart (M-CSF, SCF), lung (M-CSF), liver (M-CSF) and spleen (M-CSF) compared with sham. Cardiac G-CSF, GM-CSF and IL-7 mRNAs were not detected. In conclusion, abundant cardiac gene expression of M-CSF and SCF was found. In our mouse model of MI, M-CSF and SCF were down-regulated in the heart and several other organs suggesting specific roles for these cytokines during development of ischaemic heart failure.