Tumor necrosis factor-alpha production in whole blood after cardiopulmonary bypass: downregulation caused by circulating cytokine-inhibitory activities.

OBJECTIVES: Cardiopulmonary bypass is associated with the release of proinflammatory cytokines (tumor necrosis factor alpha, interleukin 1beta, interleukin 6, and interleukin 8) and anti-inflammatory cytokines (interleukin 10 and transforming growth factor beta(1)). On the one hand this cytokine release is related to the postoperative systemic inflammatory response syndrome, and on the other hand it is related to deterioration of the immune system, for example in monocyte or polymorphonuclear neutrophil function, leading to an increased susceptibility to infections. To gain further insight into the alterations of immune cell reactivity and possible regulatory mechanisms, we studied lipopolysaccharide-induced tumor necrosis factor alpha synthesis in whole blood from cardiac surgical patients. METHODS: Fifteen patients undergoing elective heart surgery with cardiopulmonary bypass were included in the study. Ex vivo lipopolysaccharide-induced tumor necrosis factor alpha synthesis was measured in a whole blood assay before, during, and after bypass. Corresponding tumor necrosis factor alpha messenger RNA levels were determined by semiquantitative reverse transcriptase-polymerase chain reaction. In addition, the influence of patient serum on whole blood responsiveness and its relationship to anti-inflammatory cytokines were evaluated in vitro. RESULTS: Tumor necrosis factor alpha synthesis was significantly reduced after 30 minutes of cardiopulmonary bypass and showed the lowest values at the end of bypass (mean +/- SD 0.109 +/- 0.105 ng/10(6) white blood cells after 30 minutes of bypass and 0.050 +/- 0.065 ng/10(6) white blood cells at the end of bypass, vs 0.450 +/- 0.159 ng/10(6) white blood cells preoperatively, P <.001). As a further indication of reduced cytokine biosynthesis, diminished messenger RNA levels for tumor necrosis factor alpha were detected. Serum withdrawn from patients at the end of cardiopulmonary bypass reduced tumor necrosis factor alpha synthesis in heterologous blood from healthy volunteers highly significantly to 39.93% +/- 23.18% relative to control serum (P =.005) and preoperatively drawn serum (P =.024). This effect was dose dependent and was not specific for lipopolysaccharide-induced tumor necrosis factor alpha synthesis. Anesthesia and heparin administration did not influence tumor necrosis factor alpha production significantly. Ex vivo tumor necrosis factor alpha synthesis was negatively related to interleukin 10 serum levels, positively but weakly related to interleukin 4, and was not related to transforming growth factor beta(1) (Spearman correlation coefficients -0.565, P <.001, 0.362, P <.001, and -0.062, P =.460, respectively). However, interleukin 10 levels in patient serum after cardiopulmonary bypass were 300-fold below the quantities needed for half-maximal inhibition of tumor necrosis factor alpha synthesis in vitro. Moreover, the inhibitory activity could not be removed by immune absorption of interleukin 10. CONCLUSIONS: These results suggest that during cardiac operations cytokine-inhibitory serum activities are released or newly formed. These activities could not be explained by the actions of interleukins 4 and 10 or transforming growth factor beta(1). Although their exact nature remains undetermined, these substances may contribute to the diminished immune cell functions after cardiopulmonary bypass and thus need further characterization.

Ischemic pre-conditioning of 5 minutes but not of 10 minutes improves lung function after warm ischemia in a canine model.

BACKGROUND: Protection from reperfusion injury by ischemic pre-conditioning (IPC) before prolonged ischemia has been proven for the heart and the liver. We now assess the efficacy of IPC to protect lungs from reperfusion injury. METHODS: Eighteen foxhounds (25 to 30 kg) were anesthetized, intubated, and ventilated with a fraction of inspired oxygen of 0.3 at a volume-controlled mode to maintain arterial pCO2 of 30 to 40 mm Hg. After left thoracotomy, we performed warm ischemia for 3 hours by clamping the left hilus, and followed with 8 hours of reperfusion (control, n = 6). In the treated groups, IPC was performed either for 5 minutes followed by 15-minute reperfusion (n = 6, IPC-5), or by 2 successive cycles of 10-minute ischemia, followed by 10-minute reperfusion (n = 6, IPC-10) before prior to the 3-hours warm-ischemia period. Pulmonary compliance and gas exchange were determined separately for each lung, and we recorded pulmonary and systemic hemodynamics. We performed bronchoalveolar lavage (BAL) at the end of the experiment and determined total protein concentration as well as tumor necrosis factor alpha (TNF-alpha) mRNA expression in cell-free supernatant and in BAL cells, respectively. We also assessed the wet/dry ratio of the lung. RESULTS: In the controls, on reperfusion, we encountered a progressive deterioration of gas exchange, especially of the reperfused left lung, which we could largely avoid using the IPC-5 protocol. Similarly, pulmonary compliance steadily declined but was much better in the ICP-5 group. Parallel to the improvement of gas exchange and lung mechanics, we found less total alveolar protein content and TNF-alpha mRNA expression in BAL cells in the IPC-5 than in the controls. However, we did not find IPC-10 to be paralleled by a significant improvement of lung function. Neither IPC-5 nor IPC-10 influenced the pulmonary vascular resistance index or the fluid accumulation in the lung. CONCLUSION: The major finding of the present study was that 5 minutes of IPC improved lung function after 3 hours of warm ischemia of the lung.

[Changes in heart surgical strategies: a word of caution]. / Herzchirurgische Strategien im Wandel: Ein Wort der Vorsicht.

The introduction of minimally invasive coronary artery bypass surgery has expanded the technical armementarium for operative treatment of coronary artery disease. Minimal access surgery using partial sternotomy or anterior intercostal minimal thoracotomy can be combined with videoscopic techniques or port-access-methods. Either atrio-aortal cannulation, femoro-femoral or jugular-femoral connections to the pump are possible for extracorporal circulation (ECC). Even endoluminar occlusion of the aorta and application of cardioplegia into the aortic root can be considered and applied. Extracorporal circulation has developed into a safe standardized method. As far as pathophysiology is concerned, the decision to use ECC or not is of much more importance than the grade of invasiveness. Fundamentally we therefore need to distinguish between minimally invasive methods with and without ECC. Video-assisted coronary surgery in hearts under hypothermia and fibrillation with ECC is also recommended occasionally. Minimally invasive coronary artery procedures on beating hearts without ECC have to be done in a stabilized and bloodless operative field to allow the construction of high standard anastomoses between bypass grafts and coronary arteries. In practice, silicon occluders, epicardial and myocardial suture occlusion and fixation, mechanical stabilization devices, and pharmacologic induction of bradycardia are used. In principle a skilled surgeon should be familiar with all these methods to select the most suitable solution for the special clinical problem. A final judgement about each method is not possible up to now. High patients numbers have to be recruited in the groups and subgroups due to low mortality (1%) and morbidity (5%), otherwise statistical significance of the results cannot be gained.

Mediastinitis after cardiac surgery--epidemiology and current treatment.

Mediastinal infection is a feared complication observed after 0.4%-5% of cardiac operations. Even today the mortality remains as high as 20%-40%. We discuss the aetiology, mechanisms, prevention, diagnosis, and medical management. The staging system for mediastinal wound infections developed at a joint conference of German cardiac surgical centres is presented. The use of parenteral polyvalent immunoglobulins is also discussed.

[Measurement of the humidity of inspired air in ventilated patients with various humidifer systems]. / Messungen des Feuchtigkeitsgehaltes der Inspirationsluft bei beatmeten Patienten bei Verwendung verschiedener Befeuchtungssysteme.

INTRODUCTION: Humidification of inspired gas in artificially ventilated patients positively influences mucociliary function and secretolysis. We performed this study to examine the properties of heat and moisture exchangers in comparison with hot water humidifiers and dry artificial ventilation. METHODS: We measured inspired humidity with a special sensor in 41 patients after coronary artery bypass grafting with cardiopulmonary bypass. Three Heat and Moisture Exchangers (HME) and a hot water humidifier were used to humidity the inspired gas of artificially ventilated patients. Humidity measurements were compared. RESULTS: Hot water humidifiers produced the highest humidification (average of 38.4 mg/l, 37-43 mg/l); lowest humidification was produced by dry artificial ventilation (average of 8.7 mg/l, 6-11 mg/l). Heat and moisture exchangers (HME) produced humidity between 24 and 36 mg/l. Highest humidification was produced by HME hygrobac s (average of 32.2 mg/l, 31-36 mg/l) and hygrovent s (average of 31.4 mg/l, 29-35 mg/l); lowest humidification was produced by HME hygroster (average of 28.6 mg/l, 24-31 mg/l). Multifactorial analysis shows a significant impact of the humidification method on the humidity of inspired gas. The multiple comparison procedure (Tukey) shows significant differences (alpha = 0.05) between all humidification techniques on inspired gas except the heat and moisture exchangers hygrobac s and hygrovent s. CONCLUSIONS: Hygrobac s and hygrovent s may be an alternative to hot water humidifiers. Further clinical studies of HMEs and hot water humidifiers will be necessary to evaluate the influence of inspired gas humidity on the outcome of artificially ventilated patients.

Coronary artery bypass grafting in a patient with type II heparin associated thrombopenia.

Two types of heparin-associated thrombopenia can be distinguished. Patients with the type II condition present a particularly difficult management problem when they require full anticoagulation. There is no consensus about the proper anticoagulation management for type II patients who have to undergo cardiopulmonary bypass. The case is reported of a type II heparin-associated thrombopenia patient who underwent successful aortocoronary saphenous vein grafting. Sodium-danaparoid was used for anticoagulation. The anti-factor Xa level was kept below the value reported in the literature for patients undergoing cardiopulmonary bypass. No fibrin formation was observed during the time of cardiopulmonary bypass, nor was any severe postoperative haemorrhage seen, as is frequently described in the literature.

Cardiac surgery in patients with end-stage renal failure.

End-stage renal failure is commonly considered a significant factor for an increased risk after coronary artery bypass grafting. This holds true for patients who have received a kidney transplant (NTX group) as well as for patients who require chronic hemodialysis (HD group). To assess the risk in our population we performed a retrospective analysis of 22 patients with end-stage renal failure (HD group: 17, NTX group: 5) who underwent cardiac surgery. The perioperative course was compared to a normal population. In addition to standard data we assessed the following factors: renal failure etiology, risk factors, concurrent diseases, duration of renal failure, function of renal graft, ECG (paying special attention to signs of previous myocardial infarctions and rhythm disorders), results of cardiac catheterization and coronary angiography, NYHA class and urgency of operative intervention. Complications and mortality were the main measures of the perioperative course. We analyzed the hospital charts retrospectively and requested the patients' physicians to complete a questionnaire about the patient's present condition. All HD group patients were dialyzed on the day before surgery. The first postoperative HD was performed for hyperkalemia or signs of volume overload (pulmonary capillary wedge pressure > 20 mmHg) when signs of pulmonary function deterioration were seen. HD was successful in treating these conditions. 3 of the 17 patients on HD expired postoperatively, 4 died within 3 years, all of unrelated diseases. Mortality and morbidity was 0% in the NTX group. In one NTX patient who required intermittent HD preoperatively because of poor renal graft function, renal function improved postoperatively, presumably secondary to better renal perfusion, and he did not require HD after his cardiac surgery. By surgical intervention the NYHA class of all patients improved (by 1.6 on the average) as well as their quality of life. Because of these good short- and long-term results and relatively low operative risk we support an approach of prompt work-up and surgical intervention when necessary in HD and NTX patients.

Results of cardiac operations in five kidney transplant patients.

Because of the paucity of literature reports about cardiac operations in renal-transplant patients we performed a retrospective study encompassing all such patients operated upon in our institution in 1993 and 1994. During this time 5 renal transplant patients underwent cardiac surgical procedures between 1 and 9 years after transplantation: in 4 patients coronary artery bypass grafting (CABG) was carried out and in one patient aortic valve replacement. We analyzed pre-, peri-, and postoperative data. Late results were obtained by questionnaire from the patients' primary physicians. Short- and long-term results were excellent. Mortality was 0%. At late follow-up (8-23 months) all patients were in NYHA class II or better. Postoperatively all patients experienced a clear improvement of their cardiac symptoms. None of the transplanted kidneys deteriorated. One patient who had to undergo intermittent hemodialysis preoperatively improved so much that she did not require any dialysis postoperatively. Although the total number of patients in this study is limited we believe it can be stated that renal transplant patients can undergo cardiac operations with generally good results.

Impact of particulate contamination in crystalloid cardioplegic solutions: studies by scanning and transmission electron microscopy.

The amount of particulate matter present in Bretschneider's cardioplegic solution (HTK) was assessed by laser-mediated particle counting. Permissible levels of contaminant particles with a distribution of diameters between 0.2 and 20 microns were found. A significant further increase in the particle count was observed when the fluid was administered for clinical use, which resulted in the additional release of particles from, for example, the infusion kit, which included an in-line filter with pores of 270 microns. Filtration of the HTK solution by a terminal inline filter (0.2 micron) significantly reduced the number of particles. In order to determine the chemical composition and the potential hazards of the particulate material we used scanning electron microscopy in combination with energy dispersive X-ray analysis and transmission electron microscopy to examine specimens taken from heart tissue obtained from Göttinger minipigs after cardioplegia and from humans undergoing mitral valve replacement after cardioplegia and reperfusion. Particles of various diameters were found either to be plugging coronary capillaries, to be adherent to the endothelial layer, or to be engulfed by polymorphonuclear (PMN) granulocytes, which appeared to be activated. Some of the PMN granulocytes were apparent in the endothelial layer. It is recommended, therefore, that a terminal in-line filter (0.2 micron) should be routinely used.

Bilateral inferior vena cava with azygos continuation but without congenital heart disease complicates routine venous cannulation for cardiopulmonary bypass in an adult.

Attempted venous cannulation with a dual-stage cannula for cardiopulmonary bypass in routine coronary revascularization led to the discovery of an abnormal inferior vena cava in a 65-year-old patient. The operative and postoperative course of the patient were not affected by the inferior caval anomaly. The detailed infradiaphragmatic venous anatomy was elucidated later by MRI and showed bilateral inferior caval veins with azygos continuation. Although this malformation of the inferior cava is rare in adults, the occurrence should be known. Quick recognition and handling should be achieved if detected during cannulation for cardiopulmonary bypass.

[Direct coronary bypass operation in complicated coronary dissection]. / Direkte koronare Bypassoperation bei komplizierter koronarer Dissektion.

Improvement of interventional techniques, sophisticated patient selection, and individual experience has decreased the probability of emergency operative revascularization of increasing numbers of PTCA cases in recent years. This rate is now between 0.5 to 3%, including highrisk dilatations. Dissection is the most common complication of PTCA, while perforation is rare. Patients with high risk for PTCA-procedures (age, concomittant diseases, female gender) are, in general, risk patients for operative revascularization. The postoperative course of emergency bypass surgery after PTCA-complication (infarction rate, mortality) is dependent on duration and severity of the myocardial ischemia and preoperative circulatory function. Complete revascularization in cases of multi-vessel disease and the use of the internal mammary artery as a graft vessel is being achieved in increasing numbers.

The efficacy of amrinone or adrenaline on low cardiac output following cardiopulmonary bypass in patients with coronary artery disease undergoing preoperative beta-blockade.

We examined 20 patients undergoing coronary bypass grafting for coronary artery disease with NYHA classifications of II and III who had been treated with beta-blocking agents. Patients were randomised for administration of either adrenaline (0.1 microgram/kg/min) or amrinone (bolus 1 mg/kg, continuous infusion of 5-10 micrograms/kg/min), if following cardiopulmonary bypass their cardiac index was < 2.4 L/min/m2 with normal peripheral resistance and normal or increased right- or left-ventricular filling pressures. Over a period of 1 hour, the hemodynamic parameters mean arterial pressure (MAP), cardiac index (CI), heart rate (HR), coronary perfusion pressure (CPP), total peripheral resistance (TPR), as well as the pressure-work index (PWI) were registered or calculated. By means of a coronary sinus catheter myocardial arterio-venous oxygen content difference (AVDO2cor), myocardial blood flow (MBF), using the thermodilution method, and myocardial oxygen consumption (MVO2) could be measured or calculated. Simultaneously, arterial and myocardial lactate concentrations and, using the arterio-venous lactate ratio, myocardial lactate extraction or production were quantified. Using a transseptal approach, the left-ventricular pressure curve was measured and used to differentiate for myocardial contractility (dp/dtmax). Following induction of anesthesia and after cardiopulmonary bypass, plasma levels of the used beta-blocking agent were determined. Both substances caused a significant increase in myocardial contractility, with adrenaline showing a more potent effect than amrinone. Both substances caused a significant increase in CI with a mild increase in HR. Amrinone caused a significant drop in TPR, while MAP remained practically constant.(ABSTRACT TRUNCATED AT 250 WORDS)

[Concept for therapy of heart failure in heart surgery]. / Konzept zur Therapie der Herzinsuffizienz in der Herzchirurgie.

Perioperative deterioration of the circulatory performance of patients undergoing heart surgery ranges from transitory impairment in cardiac output by deterioration of the compensation range of the oxygen transport system to manifest circulatory failure without previous myocardial damage and the acute decompensation of pre-existing chronic heart failure. On the basis of the current state of knowledge in this field, a concept for rational staged treatment should be based on the different myocardial beta-adrenoceptor conditions related to the type and stage of the individual underlying heart disease and on adrenoceptor subtype specific properties of positive inotropic drugs. 1. The therapy of perioperative "circulatory" insufficiency after extra-corporal circulation consists of the use of drugs to adapt the performance of the oxygen transport system to increased overall oxygen demand. Simultaneous volume loading (by CVP) and positive inotropic support with dobutamine are the best means of treating this (normally transitory) dysregulation. 2. In the case of manifest severe circulatory insufficiency (low cardiac output syndrome), sepsis or acute heart failure (e.g., following acute myocardial infarction), the use of a pulmonary artery catheter for determining perioperative cardiac output and resistance is essential. In such cases, positive inotropic therapy is based on catecholamines of medium (dobutamine) to high (adrenaline) efficacy, because it can be assumed that the beta-adrenoceptor pattern will remain normal with regular functioning and regulation of the (remaining) myocardium up to the onset of acute heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Sequential bilateral lung transplantation for pulmonary alveolar microlithiasis.

Lung transplantation has been successfully used in the treatment of patients with end-stage pulmonary disease and adequate cardiac function. We report about a 32-year-old man with pulmonary alveolar microlithiasis who underwent sequential bilateral lung transplantation. Preoperative hemodynamic studies revealed severe pulmonary hypertension; the right ventricular ejection fraction was 0.27. Eighteen months postoperatively, he continues to do well with normalized pulmonary and cardiac function and without clinical or histopathologic signs of graft rejection.

Transient outward current in human and rat ventricular myocytes.

OBJECTIVE: The aim was to investigate transient outward currents (I(to)) in single myocytes isolated from human heart muscle specimens which were obtained either from patients in terminal heart failure receiving a transplant or from multiorgan donors whose hearts were not suitable for transplantation. METHODS: Using the whole cell patch clamp technique, depolarisation dependent I(to) was investigated in these myocytes, and its electrophysiological characteristics compared to I(to) of rat myocytes. RESULTS: I(to) was observed in ventricular myocytes isolated from failing and non-failing human hearts. The current density of I(to) was similar in cells from failing and non-failing hearts [at +60 mV: 7.9(SEM 1.0) pA.pF-1, n = 9, and 8.7(1.2) pA.pF-1, n = 8, respectively], but smaller in human than in normal rat myocytes, ie, 8.2(0.7) pA.pF-1 (n = 17) v 19.9(2.8) pA.pF-1 (n = 12, six hearts), respectively. Half maximum activation was found at more positive potentials in human than in rat cells, at +21.2(2.0) v +6.4(1.3) mV. In human myocytes, the fraction of non-inactivating outward current at the end of 300 ms long clamp steps was smaller than in rat cells, ie, 22(5%) of peak I(to) in human (n = 17) and 39(5%) in rat cells (n = 12). The potential of half maximum steady state inactivation of rapidly inactivating I(to) in the presence of 0.1 mM Cd2+ was -21.4(0.7) mV in human (n = 15, five hearts), and -35.3(1.0) mV in rat cells (n = 12, six hearts). The late component of outward current showed no potential dependent inactivation in human cells, but underwent steady state inactivation at all potentials positive to -100 mV in rat myocytes. At -100 mV, recovery of I(to) from inactivation took place with a similar time constant, ie, 18(2) ms (n = 7), 24(2) ms (n = 6), and 25(2) ms (n = 4) in cells from three failing and two non-failing human hearts, and from two normal rat hearts, respectively. CONCLUSIONS: In a limited number of cells, I(to) in human ventricular myocytes shows no dramatic differences between cells derived from failing and non-failing hearts. The characteristics of I(to) in human cells were similar though not identical to I(to) in rat heart cells. This current may be a potential target for antiarrhythmic drug action.

Endothelial damage of the venous graft in CABG. Influence of solutions used for storage and rinsing on endothelial function.

A significant proportion of early graft occlusions after aortocoronary revascularization using autologous saphenous vein grafts (SVG) are due to mechanical and/or metabolic or biochemical endothelial lesions. The morphological examination of the endothelium, usually carried out using light microscopy or by various types of scanning electron microscopy (SEM), does not give any indication of the functioning of the endothelium (E). Functionally intact E is capable of producing endothelium-derived relaxing factor (EDRF); a practicable in vitro test is the relaxation of pre-contracted vein segments (VS) in response to acetylcholine (ACh) application. To study the effect of the solution used to rinse and store the SVG between removal and implantation on the functional characteristics of the E, we performed in vitro tests on macroscopically intact VS removed from the saphenous vein of 30 male patients who underwent elective CABG surgery. Isolated VS rings were incubated for 60 min in heparinized whole blood (HWB), Bretschneider's cardioplegic solution (HTK), human albumin solution (HAS), or Ringer's solution (RS) and compared with the results obtained immediately after the removal of untreated control samples (C) taken from the same patients. After equilibration in carbogen aerated Krebs-Henseleit solution and precontraction by 3 x 10(-7) M noradrenaline (NE), relaxation induced by 10(-6) M ACh was measured. Only the samples stored in HWB (13.4 +/- 0.4 mN) showed similar maximal contractions with NE to those in the control group (14.4 +/- 0.5 mN), i.e. all those segments which showed both contractions with NE and relaxation with ACh.(ABSTRACT TRUNCATED AT 250 WORDS)

Low-output syndrome after heart surgery: is a monotherapy with phosphodiesterase-III inhibitors feasible? A comparative study of amrinone and enoximone.

In order to determine whether the primary use of a phosphodiesterase-III (PDE) inhibitor as monotherapy for severe cardiac low-output states (LOS) is in fact practicable, we investigated the haemodynamic effects of amrinone and enoximone in a prospective randomized study. After elective CABG, AVR, or MVR, patients with cardiac LOS were given amrinone (n = 10) or enoximone (n = 9). Following bolus saturation (1.0-2.0 mg/kg [XA = 1.4] or 0.5-1 mg/kg [XE = 0.9] in total), a dose of 5-10 microgram/kg/min was given by infusion. The standard monitoring program included discontinuous haemodynamic measurements (Swan-Ganz) over a maximum time period of 48 hours, arterial and venous blood-gas analyses, and clinical chemistry. The preoperative clinical and haemodynamic status of the enoximone (E) group (55% CABG patients; MPAP 27 +/- 2.5 mmHg, PCWP 20 +/- 2.9 mmHg, PVR 201 +/- 35 dyn.s.cm-5) was considerably worse than that of the amrinone (A) group (70% CABG patients; MPAP 23 +/- 2.3 mmHg, PCWP 16 +/- 3.5 mmHg, PVR 153 +/- 28 dyn.s.cm-5). Both PDE inhibitor preparations led to a significant increase in cardiac index (from 1.9 +/- 0.1 to 2.5 +/- 0.12 L/min/m2 (A) and from 1.98 +/- 0.1 to 2.6 +/- 0.18 L/min/m2 (E) within 30 minutes, accompanied by a simultaneous decrease in filling pressures and vascular resistances. For up to 2 hours, 3/10 (A) and 2/9 (E) patients required additional positive inotropic support with adrenaline. There were no significant differences between the two groups at any time.(ABSTRACT TRUNCATED AT 250 WORDS)

[The concept of lung and heart-lung preservation within the scope of multiple organ procurement]. / Konzept zur Lungen- und Herz-Lungen-Präservation im Rahmen der Multiorganentnahme.

Preservation of the lung is still one of the most challenging problems, because due to limited procurement time not all organs available can be used. The most common procurement technique is flush perfusion of the pulmonary artery system. Alternative methods in clinical use are either the autologous working heart-lung preparation or donor core-cooling (DCC). The own concept presented here, modified to the special demands of multi-organ-procurement, combines DCC and interstitial equilibration adapted to intracellular ion concentration. DCC is induced by extracorporeal circulation (ECC) using a transportable heart lung machine including a highly effective cooling system: cooling circuit based on two parallel heat exchangers with ice-water cooling produced by a high-pressure overflow of a low-temperature ice block (-40 degrees C). While cooling by ECC stepwise hemodilution is achieved by priming volume and incorporation of the cardioplegic solution (Bretschneider-HTK). The aim of equilibration is to lower the extracellular levels of sodium and calcium, and to increase the level of potassium. Additionally, the buffer capacity of donor blood is increased by the incorporated histidine-buffer system (alpha-stat). To avoid donor organ edema the time of ECC should be as short as possible. Using our system donor organ temperatures below 10 degrees C are reached within less than 30 min. In addition to ECC, lung surface cooling is achieved by external overflow with cold arterial blood (internal mammary artery). Besides lung preservation the main advantage of this concept is the profound precooling of all visceral organs before their individual flush perfusion.