Tamás Maros

High-dose glucose-insulin-potassium after cardiac surgery: a retrospective analysis of clinical safety issues

Background: Metabolic treatment with insulin or glucose‐insulin‐potassium (GIK) has received attention in association with myocardial infarction, cardiac surgery and critical care. As a result of insulin resistance during neuroendocrine stress, doses of insulin up to 1 IU kg−1 b.w.*h are required to achieve maximal metabolic effects after cardiac surgery. The clinical experience with regard to safety issues of such a high‐dose GIK regime in critically ill patients after cardiac surgery is reported.

Radial artery grafts: surgical anatomy and harvesting techniques

At present more and more surgeons are using the radial artery as a graft for coronary bypass. The statistics until now show that the patency of radial grafts exceeds that of the venous grafts used up to the present. In our department we used radial artery for coronary bypass in 515 patients between January 1990 and December 2000. The radial artery harvesting with minimally invasive technique developed by us was applied in 50 of these patients while the rest were performed with the traditional method. No ischemic complications occurred in forearm or hand following either of the methods. One year after the operation we carried out control examinations on 197 consecutive patients. Our surveys showed that following the traditional technique of radial artery harvesting neurological complications (temporary dysaesthesia) occurred in 16.5% of the patients. After the minimally invasive procedure, temporary dysaesthesia occurred in one case (2%). These complaints ceased within 1-12 months (an average of 3.8 months). Definitive neurological complications did not occur in any of the patients. In summation, we experienced that both operating techniques can be safely applied. The proportion of temporary neurological complications is higher following the traditional procedure, therefore, further development and application of the minimally invasive procedure should be considered.

Low Tidal Volume Ventilation during Cardiopulmonary Bypass Reduces Postoperative Chemokine Serum Concentrations

BACKGROUND Open-heart surgery with cardiopulmonary bypass (CPB) is associated with a generalized immune response and postoperative lung dysfunction. Chemokines are involved in the pathogenesis of postoperative lung dysfunction. We investigated whether continued mechanical ventilation during CPB has an impact on chemokine serum concentrations. METHODS A total of 30 patients undergoing coronary artery bypass graft operation were randomized to either continuous ventilated group (n=15) or nonventilated group (n=15). Blood samples were drawn at the beginning and at the end of surgery and on the 5 consecutive days. Serum CCL2, CCL4, and CCL20 concentrations were measured and given as mean ± standard deviation. RESULTS Chemokine concentrations were elevated at the end of surgery in both groups. CCL2 and CCL4 levels returned to baseline on postoperative day (POD)-1 in the ventilation group and stayed elevated in the nonventilation group. CCL4 serum levels were significantly lower in ventilated-group patients on POD-1 (10.9 [39.0] vs. 153.2 [168.1]; p=0.005), POD-2 (16.8 [36.8] vs. 147.9 [165.4]; p=0.019), POD-3 (14.2 [24.0] vs. 97.9 [87.1]; p=0.005), and POD-5 (6.5 [25.0] vs. 33.6 [38.4]; p=0.045). CONCLUSION Continued mechanical ventilation during CPB results in reduced CCL4 concentrations on POD-1 to -5.

New Perspectives in the Renin-Angiotensin-Aldosterone System (RAAS) II: Albumin Suppresses Angiotensin Converting Enzyme (ACE) Activity in Human

About 8% of the adult population is taking angiotensin-converting enzyme (ACE) inhibitors to treat cardiovascular disease including hypertension, myocardial infarction and heart failure. These drugs decrease mortality by up to one-fifth in these patients. We and others have reported previously that endogenous inhibitory substances suppress serum ACE activity, in vivo, similarly to the ACE inhibitor drugs. Here we have made an effort to identify this endogenous ACE inhibitor substance. ACE was crosslinked with interacting proteins in human sera. The crosslinked products were immunoprecipitated and subjected to Western blot. One of the crosslinked products was recognized by both anti-ACE and anti-HSA (human serum albumin) antibodies. Direct ACE-HSA interaction was confirmed by binding assays using purified ACE and HSA. HSA inhibited human purified (circulating) and human recombinant ACE with potencies (IC50) of 5.7±0.7 and 9.5±1.1 mg/mL, respectively. Effects of HSA on the tissue bound native ACE were tested on human saphenous vein samples. Angiotensin I evoked vasoconstriction was inhibited by HSA in this vascular tissue (maximal force with HSA: 6.14±1.34 mN, without HSA: 13.54±2.63 mN), while HSA was without effects on angiotensin II mediated constrictions (maximal force with HSA: 18.73±2.17 mN, without HSA: 19.22±3.50 mN). The main finding of this study is that HSA was identified as a potent physiological inhibitor of the ACE. The enzymatic activity of ACE appears to be almost completely suppressed by HSA when it is present in its physiological concentration. These data suggest that angiotensin I conversion is limited by low physiological ACE activities, in vivo.

AMP-Activated Kinase (AMPK) Activation by AICAR in Human White Adipocytes Derived from Pericardial White Adipose Tissue Stem Cells Induces a Partial Beige-Like Phenotype.

Beige adipocytes are special cells situated in the white adipose tissue. Beige adipocytes, lacking thermogenic cues, morphologically look quite similar to regular white adipocytes, but with a markedly different response to adrenalin. White adipocytes respond to adrenergic stimuli by enhancing lipolysis, while in beige adipocytes adrenalin induces mitochondrial biogenesis too. A key step in the differentiation and function of beige adipocytes is the deacetylation of peroxisome proliferator-activated receptor (PPARγ) by SIRT1 and the consequent mitochondrial biogenesis. AMP-activated protein kinase (AMPK) is an upstream activator of SIRT1, therefore we set out to investigate the role of AMPK in beige adipocyte differentiation using human adipose-derived mesenchymal stem cells (hADMSCs) from pericardial adipose tissue. hADMSCs were differentiated to white and beige adipocytes and the differentiation medium of the white adipocytes was supplemented with 100 μM [(2R,3S,4R,5R)-5-(4-Carbamoyl-5-aminoimidazol-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate (AICAR), a known activator of AMPK. The activation of AMPK with AICAR led to the appearance of beige-like morphological properties in differentiated white adipocytes. Namely, smaller lipid droplets appeared in AICAR-treated white adipocytes in a similar fashion as in beige cells. Moreover, in AICAR-treated white adipocytes the mitochondrial network was more fused than in white adipocytes; a fused mitochondrial system was characteristic to beige adipocytes. Despite the morphological similarities between AICAR-treated white adipocytes and beige cells, functionally AICAR-treated white adipocytes were similar to white adipocytes. We were unable to detect increases in basal or cAMP-induced oxygen consumption rate (a marker of mitochondrial biogenesis) when comparing control and AICAR-treated white adipocytes. Similarly, markers of beige adipocytes such as TBX1, UCP1, CIDEA, PRDM16 and TMEM26 remained the same when comparing control and AICAR-treated white adipocytes. Our data point out that in human pericardial hADMSCs the role of AMPK activation in controlling beige differentiation is restricted to morphological features, but not to actual metabolic changes.

Continued mechanical ventilation during coronary artery bypass graft operation attenuates the systemic immune response

OBJECTIVES Cardiopulmonary bypass (CPB) is known to induce a short pro- and long-lasting anti-inflammatory immune response. The anti-inflammatory protein soluble ST2 (sST2) may be involved in the pathogenesis of postoperative immune dysfunction. We investigated whether continued mechanical ventilation during CPB has an impact on postoperative serum sST2 and cytokine release. METHODS Thirty patients undergoing conventional coronary artery bypass graft (CABG) operation were randomized into a ventilated on CPB (VG; n = 15) and non-ventilated on CPB group (NVG; n = 15). Blood samples were drawn at the beginning and at the end of surgery, and at the 5 consecutive days. sST2, IL-4, IL-10, IgM, IgG, IL-6 and endotoxin were measured by ELISA. Data are given as mean standard deviation (SD). A Mann-Whitney U-test was used for statistical analysis. RESULTS Serum levels of sST2 and IL-10 were significantly higher in the NVG when compared with the VG at the first postoperative day (POD-1) [sST2 pg/ml: 1366.4 (433) (VG) vs 2296.3 (1795.5) (NVG) P = 0.029; IL-10 pg/ml: 10.7 (4.0) (VG) vs 15.4 (6.8) (NVG) P = 0.038]. In addition, the secretion of proinflammatory IL-6 was slightly reduced in the VG at POD-1 [IL-6 pg/ml: 83.1 (52.5) (VG) vs 110.2 (42.3) (NVG) P = 0.033]. IL-4, endotoxin, IgM and IgG showed no differences between groups. CONCLUSION These data suggest that continued mechanical ventilation during CABG attenuates inflammatory and anti-inflammatory immune responses after CPB. Continued mechanical ventilation may have beneficial effects in the attenuation of the CPB-induced immune activation.

Plasma homocysteine levels are related to medium-term venous graft degeneration in coronary artery bypass graft patients

Objective: Saphenous venous grafts (SVGs) are established choices for coronary artery bypass grafting (CABG); however, their lumen patency is limited. Our goal was to investigate the risk factors of SVG degeneration. Methods: Seventy-five patients (mean age, 57.5±10.4 years) with 133 SVG conduits who had cardiac catheterization ≥1 year after CABG were selected; follow-up period was 67.6±36.8 months. Patients were divided into 3 groups according to angiographic status at follow up [intact: <20% (n=23); narrowed: 20–99% (n=24); and occluded (n=28)]. Baseline clinical conditions were evaluated in relation to follow-up angiography. As onset date of chronic total occlusions is usually uncertain, they arise typically from thrombotic lesions; thus, their value in evaluation is limited. Results: There were no significant differences between the 3 groups in clinical parameters. Linear correlation analysis found significant (p<0.01) positive connection of SVG disease (luminal diameter reduction 20–99%) with C-reactive protein (CRP) and homocysteine (Hcy), as well as between CRP and Hcy. Multiple regression analysis showed plasma Hcy level to be significantly related to graft diameter reduction normalized to time elapsed until angiography in narrowed grafts: 1 µmol/L increase of Hcy was associated with 0.053%/month decrease in lumen diameter (p<0.01; R2=0.428); extrapolating: +10 µmol/L higher Hcy level during 5 years is associated with 32.1% lumen reduction. Conclusion: Medium- to long-term SVG degeneration is related to elevated plasma total Hcy in patients with sub-occlusive graft stenosis, while in cases with intact SVGs, the beneficial local flow conditions may protect the grafts from degeneration.

Incidence, survival and determinants of mortality following mesenteric angiography and continuous intra-arterial prostaglandin E1 perfusion for non-occlusive mesenterial ischaemia in cardiac surgery

Methods Our aim was to evaluate the incidence of NOMI, to analyze results of treatment and to identify variables associated with mortality. Hospital records and clinical data of patients treated for NOMI during the last 12 years were reviewed. Clinical outcomes and factors influencing mortality were studied. Statistical analysis was performed to determine the significance of risk factors on mortality with Fisher exact test or c2 test in categorical variables. Wilcoxon rank test was used to test the continuous variables.

Kiegészítő klinikai módszer a nyitott szívműtéteknél fellépő légembolisatio csökkentésére A complementary clinical method to minimize air embolism during open-heart surgery

Air from the left heart is ejected even up to several hours after cardiopulmonary bypass (CPB) despite the use of CO2. The following method is complementary in addition to surgical de-airing in order to further reduce the chance of air embolism, especially from the pulmonary veins. After re-expanding the lungs with standard bag inflation, the ventilation is restarted in consultation with the surgeon. The ventilator is set to the respiratory minute volume used before the CPB but at a respiratory frequency of 10/minutes whereas the regularly beating heart is filled from the heart lung machine. Transoesophageal echocardiography (TEE) reliably controls the effect.

[A complementary clinical method to minimize air embolism during open-heart surgery].

Air from the left heart is ejected even up to several hours after cardiopulmonary bypass (CPB) despite the use of CO2. The following method is complementary in addition to surgical de-airing in order to further reduce the chance of air embolism, especially from the pulmonary veins. After re-expanding the lungs with standard bag inflation, the ventilation is restarted in consultation with the surgeon. The ventilator is set to the respiratory minute volume used before the CPB but at a respiratory frequency of 10/minutes whereas the regularly beating heart is filled from the heart lung machine. Transoesophageal echocardiography (TEE) reliably controls the effect.