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In the clinical setting great efforts have been made with contradictory results to operate upon acutely myocardial ischaemic patients. The reasons for the absence of clear-cut results are not well understood nor are they scientifically explored. To resolve this problem further, we attempted to design an experimental in vivo model to mimic acute myocardial ischaemia followed by extracorporeal circulation (ECC) and reperfusion. One of the main targets of our protocol was monitoring of myocardial energy metabolism by microdialysis (MCD) during the periods of coronary occlusion (60 min), hypothermic (30 degrees C) ECC and cardioplegia (45 min), followed by reperfusion with (30 min) and without (60 min) ECC. In eight anaesthetized, open-chest pigs, myocardial lactate, pyruvate, adenosine, taurine, inosine, hypoxanthine and guanosine were sampled with MCD in both ischaemic and non-ischaemic areas. Myocardial area at risk and infarct size were quantified with the modified topographical evaluation methods. The principal finding with this experimental setup was a biphasic release pattern of lactate, adenosine, taurine, inosine, hypoxanthine and guanosine from ischaemic myocardium. Lactate levels were equally high in reperfused ischaemic and non-ischaemic myocardial tissue. Pyruvate demonstrated consistently higher values in non-ischaemic myocardium throughout the experiment. A pattern was discernible, lactate being a marker of compromised cell energy metabolism, and taurine being a marker of disturbed cell integrity. Of special interest was the increased level of pyruvate in microdialysates of non-ischaemic myocardium as compared with its ischaemic counterpart. In conclusion, we found disturbances in energy metabolism and cell integrity not only in ischaemic but also in non-ischaemic tissue during reperfusion implying that non-ischaemic myocardium demonstrated an unexpected accumulation of lactate and pyruvate. These new findings could at least partly be explicatory to the i

The basic idea of retroperfusion of the coronary sinus (RCS) is to ameliorate detrimental consequences of myocardial ischaemia. Several experimental models of RCS have been introduced, most with an emphasis on functional myocardial status. Since only few studies have been devoted to energy metabolic considerations and none to continuous monitoring of energy-related metabolites of myocardium during RCS, we here present such a study using microdialysis. This study comprised the following components: Coronary occlusion and drainage on the beating heart with RCS-assist (60 min), hypothermic (30 degrees C) extracorporeal circulation (ECC) and cardioplegia (45 min), reperfusion and rewarming to 38 degrees C on ECC (30 min). The microdialysis analytical outcome mainly reflected anaerobic energy metabolism in potentially ischaemic myocardium. Additionally, a pronounced increase of microdialysate content of lactate, pyruvate and guanosine was observed in non-ischaemic myocardium especially during the reperfusion phase. The planimetric calculation revealed an infarct size reduction from 69% to 19% and was not correlated to clear-cut improvements of potentially ischaemic myocardial energy metabolism. We conclude that prolonged (60 min) anaerobic energy metabolism does not pose an immediate threat to cell viability but could even sustain myocyte survival.

Children are sensitive to the inflammatory side effects of cardiopulmonary bypass (CPB). Our intention was to investigate if the biocompatibility benefits of heparin-coated CPB circuits apply to children. In 20 operations, 19 children were randomized to heparin-coated (group HC, n = 10) or standard (group C, n = 10) bypass circuits. Plasma levels of acute phase reactants, interleukins, granulocytic proteins and complement factors were measured. All were significantly elevated after CPB. Levels of complement factor C3a (851 (791-959)ng/ml [median with quartiles] in group C, 497 (476-573)ng/ml in group HC, p < 0.001), Terminal Complement Complex (114 (71-130) AU/ml in group C, 35.5 (28.9-51.4) AU/ml in group HC, p < 0.001), and interleukin-6 (570 (203-743) pg/ml in group C, 168 (111-206)pg/ml in group HC, p = 0.005), were significantly reduced in group HC. Heparin-coated CPB circuits improve the biocompatibility of CPB during heart surgery in the paediatric patient population, as reflected by significantly reduced levels of circulating complement factors and interleukin-6.

BACKGROUND: Nitric Oxide (NO) is reported to possess anti-inflammatory properties. The aim of this study was to investigate if nitric oxide affects leukocyte response during simulated extracorporeal circulation (SECC). METHODS: Human blood was circulated for 23 hours through SECC circuit. Control group C (n = 5) was ventilated with an oxygen/air mixture, and NO was added in the study group (n = 5). Leukocyte response was determined by release of myeloperoxidase (MPO) and human neutrophil lipocalin (HNL) and by oxygen free radical production, estimated using chemiluminescence. RESULTS: Addition of NO significantly increased MPO at 30 minutes and 120 minutes of SECC and HNL at 120 minutes of SECC. Oxygen free radical production in whole blood was generally not affected by NO. Similarly, no significant differences were observed between the groups with regard to the chemiluminescence in isolated granulocytes. CONCLUSIONS: Nitric oxide increased release of leukocyte granule derived proteins; MPO and HNL at an early stage of simulated extracorporeal circulation. At the same time, nitric oxide did not affect the whole blood and leukocyte capacity to produce oxygen free radicals.

Blood conservation during cardiac surgery is critically important because of the inherent risks in homologous blood transfusions. Two techniques for the intraoperative conservation of blood--retransfusion of the red cells using a cell-saver (CS), or retransfusion of the blood using a cardiotomy suction (CTR) system--were compared using biocompatibility markers, granulocyte activation, and production of oxygen-free radicals (OFR). In the CTR group, heparin coated circuits with an uncoated cardiotomy reservoir were used. For the CS group, identical heparin coated cardiopulmonary bypass (CPB) sets, without a cardiotomy reservoir but with a CS, were used. In each group, eight patients had coronary artery bypass grafting performed. The capacity of the whole blood and the granulocytes to produce OFR was estimated by a chemiluminescence, and granulocyte activation was measured as release of the granulocyte granule proteins myeloperoxidase (MPO) and lactoferrin. A significantly reduced capacity to produce OFR by the whole blood was noted at 45 minutes of CPB in the CTR group (68% +/- 17% vs 94% +/- 16% in the CS group). MPO release was higher after 3 hours (p = 0.05) and 20 hours (p < 0.05), postoperatively, in the CTR group (417 +/- 77 micrograms/L and 257 +/- 31 micrograms/L vs 246 +/- 25 micrograms/L and 164 +/- 12 micrograms/L, respectively, in the CS group). We conclude that the heparin coated CPB circuit with the uncoated cardiotomy reservoir may be less biocompatible than the identical CPB set used together with the CS.

OBJECTIVE: Blood activation during extracorporeal circulation is associated with morbidity and mortality in cardiac surgery. This activation can be diminished by usage of heparin-coated circuits. Nitric oxide has also been reported to influence humoral and cellular components of blood. This study was performed to determine biomaterial-dependent part of blood activation. DESIGN: Fresh, whole human blood mixed with Ringer's solution was circulated through a heart-lung machine for two and half hours. Five circuits were heparin-coated (group HC), whilst five other circuits were uncoated (group NC). During the last half hour NO was added to the oxygen/air mixture. METHODS: Blood activation was estimated by measuring following parameters: interluekin 6, complement activation products C3a and terminal complement complex, and oxygen free radicals (OFR) production capacity, which was determined using chemiluminescence enhanced by serum opsonized zymosan (SOZ) and phorbol myristate acetate (PMA). Granulocyte activation was measured as release of myeloperoxidase (MPO) and human neutrophil lipocalin (HNL). RESULTS: OFR in granulocyte suspension stimulated by SOZ and PMA were significantly lower in the NC group, mostly later during ECC. Similarly, lower neutrophil and monocyte counts were observed in this group. NO increased superoxide production in the whole blood in heparin-coated circuits, but did not change OFR in isolated granulocytes. MPO was also affected by heparin-coating. NO supply seemed to increase release of MPO and HNL. It is concluded that heparin-coating contributed to reduction of biomaterial-dependent blood activation. An addition of NO at late stage of ECC tended to influence this activation.