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Background. Donor-specific tolerance induction remains an attractive objective that generates much research in the field of transplantation. Unfortunately, most of the protocols available involve pregraft conditioning, making these treatments incompatible with clinical applications. Methods. LEW.1A rats were grafted with histoincompatible LEW.1W hearts. On the day of transplantation, recipients were treated with anti-CD40L combined with donor splenocytes. The hearts were evaluated for graft survival; cellular infiltrate and intragraft cytokines were determined using real-time reverse transcriptase-polymerase chain reaction. Tolerance induction was assessed by skin grafting and adoptive transfers. Results. The combination of a single injection of anti-CD40L and donor splenocytes, given on the day of surgery, allowed 40% of cardiac allografts to survive long-term (mean survival time=66.3 day). The cellular composition or the extent of graft infiltrate was not modified but was associated with a massive decrease of proinflammatory cytokines expression within the graft. Long-term survivors accepted donor-matched skin grafts, and leukocytes harvested from these animals transferred tolerance into irradiated freshly grafted recipients. Conclusion. A combination of costimulation blockade and donor cells, given once at the time of transplantation, is sufficient to induce allograft tolerance in rats.

Objectives: Heart-type fatty acid binding protein (hFABP) is an intracellular molecule engaged in the transport of fatty acids through myocardial cytoplasm and has been used as a rapid marker of myocardial infarction. However, its value in the evaluation of perioperative myocardial injury has not yet been assessed. Methods: 32 consecutive patients undergoing coronary artery bypass grafting were included in a prospective, randomized study using standardized operative procedures and myocardial protection. Three patients with perioperative myocardial infarction were added. Serial blood samples were taken preoperatively, before ischemia, 5 and 60 min after declamping, 1 and 6 h postoperatively and on postoperative days 1, 2 and 10 and were tested for hFABP, creatin kinase isoenzyme MB (CKMB) and troponin I (TnI). Results: Hospital mortality was zero. The kinetics of the biochemical parameters revealed a typical pattern for each marker. In routine patients, hFABP levels peaked as early as 1 h after declamping, whereas CKMB and TnI peaked only 1 h after arrival in the intensive care unit. Patients with perioperative infarction displayed peak levels some hours later in all marker proteins. Peak serum levels of hFABP correlated significantly with peak levels of CKMB (ra 0:436, Pa 0:011) and TnI (ra 0:548, Pa 0:001), indicating the degree of myocardial damage. Conclusions: hFABP is a rapid marker of perioperative myocardial damage and peaks earlier than CKMB or TnI. The kinetics of marker proteins in serial samples immediately after reperfusion is more suitable for the detection of perioperative myocardial infarction than a fixed cut-off level. q 2001 Elsevier Science B.V. All rights reserved.

Since it is of great importance to distinguish between a systemic inflammatory response syndrome (SIRS) and an infection caused by microbes especially after heart transplantation (HTX), we examined patients following heart surgery by determining procalcitonin (PCT), because PCT is said to be secreted only in patients with microbial infections.Sixty patients undergoing coronary artery bypass grafting (CABG) and 14 patients after heart transplantation were included in this prospective study. In the CABG group we had 30 patients without any postoperative complications (group A). Furthermore we took samples of 30 patients who suffered postoperatively from a sepsis (group B, n=15) or a systemic inflammatory response syndrome (C, n=15). In addition we measured the PCT-levels in 65 blood samples of 14 patients after heart transplantation (Group I: rejectionIIa, II: viral infection (CMV), III: bacterial/fungal infection, IV: controls).In all patients of group A the pre- and intraoperative PCT-values and the measurement at arrival on intensive care unit (ICU) were less than 0.2 ng/ml. On the second postoperative day the PCT-value was 0.33+/-0.15 ng/ml in the control group. At the same time it was 19.6+/-6.2 ng/ml in sepsis and 0.7+/-0.4 ng/ml in systemic inflammatory response syndrome patients (P0.05). In transplanted patients we could find the following PCT-values: Gr.I: 0.18+/-0.06 II: 0.30+/-0.09 III: 1.63+/-1.16 IV: 0.21+/-0.09 ng/ml (P0.05 comparing group III with I, II and IV).These results show that extracorporeal circulation (ECC) and systemic inflammatory response syndrome do not initiate a PCT-secretion. Septic conditions cause a significant increase of PCT. In addition, PCT is a reliable indicator concerning the essential differentiation of bacterial or fungal--not viral--infection and rejection after heart transplantation.

For the testing of heart assist devices most animal models of acute cardiac failure that are usually used show certain disadvantages. We therefore developed a new method using the β-adrenoceptor antagonist carazolol. We administered a bolus injection of 1 mg/kg followed by a continuous infusion of 1 mg/kg/h in adult German 'Landrasse' pigs. Blood pressure, heart rate, cardiac output and maximum left ventricular pressure rise time showed a significant ( P

BACKGROUND In order to optimize regional utilization of transplantable thoracic organs, the seven university hospitals in North-Rhine-Westfalia have formed a transplant cooperation meanwhile approved by Eurotransplant. METHODS Heart transplant and organ donation activities of the cooperating hospitals in the year before the foundation of the cooperation (period A, 7/95 - 6/96) and in the year thereafter (period B, 7/96 - 6/97) were retrospectively analysed. RESULTS In period A, a total of 39 heart transplants and 74 heart donations were performed, whereas in period B 67 heart transplantations and 78 heart donations could be achieved. The regional utilization of the donor organs increased from 4% to 30% with a significantly shorter ischemia time of regionally or locally allocated donor hearts than of nationally or internationally allocated ones. CONCLUSIONS A high rate of regional or local heart transplant procedures with short ischemia times clearly demonstrate the benefits of a regionalization of heart transplant medicine for medical as well as economical reasons.

Background: The reasons for a systemic inflammatory response syndrome (SIRS) following ECC are not yet fully understood. Procalcitonin (PCT) blood levels may distinguish between bacterial infections and a non-bacterial systemic inflammation. We investigated the influence of ECC, ECC modified by application of aprotinin, systemic inflammation, and bacterial infection on the PCT values. Methods: 20 CABG patients were randomized and divided in two groups. Group A served as the control group, while group B perioperatively received a high dose of aprotinin. Blood samples for measurement of PCT were taken 6 times perioperatively. Furthermore, blood samples were taken from 20 preoperatively comparable patients who suffered from bacterial infection (n = 10) (group C) or a SIRS (n = 10) (group D) after ECC; in these groups PCT was determined daily after the onset of inflammation. Results: There was no significant elevation of PCT in group A or B at any time. In sepsis patients a significant elevation of PCT was seen, with the peak level of 18.6 ± 6.3 ng/ml on the second day after diagnosis; the PCT level of SIRS patients remained constantly low (< 0.9 ng/ml). Conclusions: In this study it was demonstrated that ECC and the use of aprotinin did not have any influence on the secretion of PCT. A systemic bacterial infection caused a significant increase of PCT, whereas PCT values remained normal in case of a SIRS. So it seems to be possible to distinguish between a primary SIRS and a bacterial sepsis by means of PCT.

The number of patients with ischemic cardiomyopathy and accompanying chronic pump failure of the left and/or right ventricle has tripled within the last 10 years. Ischemic cardiomyopathy represents numerically the greatest share as the reason for illness in heart transplantation today; their results are not different for patients following cardiac transplantation due to primary cardiomyopathy. Since heart transplantation has become a clinical routine method today, the discrepancy between the number of the available donor organs and the number of the needed organs becomes more and more obvious. The longer waiting lists and the longer waiting times are responsible for the increased use of bridging systems. Today the long-term results after heart transplantation are not worse in patients after bridging. With more experience in the field of mechanical support, better devices, and proved indications, frequent improvement of prerequisites for transplantation can be achieved in this group of patients. The implantable ventricles give the patient the change of full mobilization and, therefore, high clinical acceptance of this management can be registered.

This paper presents a new cardiac support device for left ventricular failure which consists of two inflatable bellows positioned dorsally and ventrally to the left ventricle. The implantable multichamber pump system (IMPS) is driven by a pneumatic pump system and controlled by a microcomputer using ECG-trigger and pacemaker modules. It was implanted via thoracotomy in 8 pigs. The circulatory parameters were measured in the animals on β-blockers, with cardiac failure and in ventricular fibrillation with an activated (IMPS on) and deactivated (IMPS off) system. IMPS significantly increased the left ventricular pressure (LVPsys IMPS off: 63 ∓ 6 mmHg vs IMPS on: 96 ∓ 8 mmHg) and the blood pressure in the common carotid artery (Bpca' IMPS off: 69/38 mmHg vs IMPS on: 95/40 mmHg). The IMPS proved to be highly efficient in the therapy of animals with acute cardiac failure and in ventricular fibrillation in the experimental model. Apart from its efficiency the advantages with this system are the ease of handling and its high biocompatibility due to the lack of contact with circulating blood.

Mitral valve replacement (MVR) is still associated with a relatively high mortality. To investigate the influence of chordal preservation in MVR on left ventricular size and function, we studied a series of 82 patients who underwent MVR either with (group A n = 50) or without (group B n = 32) preservation of the subvalvular structures and compared the two groups. Echocardiography was performed preoperatively, and 7 days and 3 months postoperatively. Echocardiographic investigations included left atrial and ventricular diameters, right ventricular diameters and left ventricular length. Preoperatively there were no difference between the two groups of patients. Intraoperative and postoperative management was similar in the groups. Three months postoperatively echocardiographic examinations demonstrated that chordal preservation in MVR resulted in smaller left ventricular systolic and diastolic diameters (LVESD: gr. A 43.4 +/- 7.8 mm vs gr. B 48.8 +/- 9.2 mm P < 0.05, LVEDD: 57.3 +/- 7.8 mm vs 62.9 +/- 10.5 mm P < 0.05) and a significantly decreased left ventricular length (87.1 +/- 4.2 mm in gr. A vs 97.5 +/- 5.7 mm in gr. B P < 0.05). In addition, left ventricular ejection fraction in group A was significantly improved compared to group B (54.2 +/- 11.2% vs 48.1 +/- 12.4%, P < 0.05). We conclude that chordal preservation in MVR improves left ventricular function and reduces left ventricular diameters and volumes compared to resection of the mitral subvalvular appartus and that these beneficial effects can be maintained in the postoperative course.

To reduce blood consumption in cardiac surgery, aprotinin has been widely used for years. Because aprotinin is metabolized in the kidney, damage of the renal system has been discussed.To study these possibly unfavorable effects of aprotinin, a prospective, randomized, placebo-controlled study of 20 patients undergoing aortocoronary bypass operations was performed. A placebo group P was compared with group A, in which patients received high-dose aprotinin according to the "Hammersmith" regimen. Renal function was assessed for 5 postoperative days using sodium dodecyl sulfate gel electrophoresis and quantitative protein analysis of the urine.During and after the operation, temporary renal dysfunction was found in all patients, with a substantial increase of all investigated indices. The alpha 1-microglobulin level in the urine was significantly increased in the aprotinin group for 5 days in comparison with the placebo group, with a maximum on the third postoperative day (64.8 +/- 13.7 versus 21.0 +/- 6.5 mg/L; p0.05). Similarly, after sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the bands of proteins filtrated in the renal tubular system were almost tripled in the aprotinin group 5 days postoperatively (5.0 +/- 0.8 versus 2.1 +/- 0.2; p0.05). Although urine production was significantly increased in group A (4789 +/- 580 versus 3653 +/- 492 mL/24 h postoperatively; p0.05), no relevant changes in serum or urine creatinine levels could be observed in either group.Patients undergoing aortocoronary bypass operations demonstrate a temporary renal dysfunction. Aprotinin impairs renal function in addition by overloading the tubular reabsorption mechanisms. Patients with normal renal function preoperatively--as were included in this study--are able to compensate for both the perioperative renal dysfunction caused by the extracorporeal circulation and the additional tubular damage due to aprotinin.

The results of orthotopic heart transplantation (OHTx) are still burdened with considerable early mortality due to graft rejection or infection. Sternum osteomyelitis is an infrequent postoperative complication. We report a case of deep sternal wound infection (2 months after OHTx) that was treated with hyperbaric oxygen therapy in addition to local surgical treatment.

Objective: C-Reactive protein (CRP) is known to be a sensitive indicator of infection. Since it is also involved in the acute phase reaction, it is of great interest, whether an isolated preoperative increase of CRP without further signs of infection is of any prognostic value for postoperative outcome after cardiac surgery with cardiopulmonary bypass (CPB), which itself is possibly causing a systemic inflammatory response syndrome (SIRS). Methods: Fifty patients with an isolated CRP-elevation (>5 mg/l) (from 6.2 to 93.3 mg/l) were operated using CPB (group A). A control group (group B) consisted of 50 cardiac surgery patients, matched in the patterns of age, gender and kind of disease. No preoperative CRP-elevation (from 0 to 4.8 mg/l) occurred in this group. Results: The postoperative course of both groups showed significant differences. Septic complications were seen more often in group A (20%) than in the controls (2%) (P < 0.01). Microbiology (blood culture, cultures from nose, tracheal aspirate and urine) was positive only in 10% of these patients. Catecholamine support (epinephrine, norepinephrine and/or doses of dopamine or dobutamine of more than 3 μg/kg per min) was needed in 26% of group A cases, whereas it was only needed in 10% of group B (P < 0.05). A significantly longer respiratory support was also necessary in patients with elevated CRP (25.2 ± 6.4 h vs. 6.6 ± 0.8 h) (P < 0.01). Furthermore there was a significant difference in the duration of intensive care (4.6 ± 0.8 days vs. 2.6 ± 0.3 days) (P < 0.05). Conclusions: These data show that patients without apparent infection or inflammation, who had elevated CRP-values preoperatively, face an increased risk of septic complications after extracorporeal circulation. As microbiology tests are negative in most cases, it may be speculated that the majority of septic complications are due to a SIRS.

Between 1975 and 1993, lung resections were performed in 1735 patients because of malignancies, with an early postoperative mortality of 7.2% (125 patients). Early postoperatively acute cardiorespiratory failure was experienced by 32 patients (1.85%), of whom 26 died despite immediate resuscitation measures. In 20/26 patients autopsy was performed revealing central pulmonary embolism as the cause of death in 19 of them. In one patient a rupture of the free posterior left ventricular wall following transmural myocardial infarction was found. Two patients who could be resuscitated successfully were operated on with extracorporeal circulation after pulmonary angiography had been performed to confirm the diagnosis; however they died 2 days later of right heart failure. Of the survivors three cases had myocardial infarctions, one patient had arrhythmias of unknown etiology. Immediate embolectomy with the use of extracorporeal circulation was performed in two patients, only on the ground of suspected pulmonary embolism and without further diagnostic measures. Both patients survived. Of the 23 cases, with proven pulmonary embolism 17 were still under postoperative prophylaxis with heparin. Six patients were already fully mobilized. We conclude that massive pulmonary embolism is a frequent early postoperative fatal complication after lung resections, which cannot be safely prevented by postoperative heparinization. The only successful life-saving measure in the case of central pulmonary embolism is immediate pulmonary embolectomy, if necessary without further diagnostic measures.

Puiser chez l'animal des organes qui permettraient a l'homme de survivre a des defaillances d'organes vitaux est un vieux reve que les progres de la biotechnologie ont rallume. Parallelement, les progres de la bio-compatibilite et de l'electronique ont produit des robots implantables de plus en plus performants. A cette date, les organes artificiels posent moins de problemes ethiques et leur progres procede d'un processus continu. Le succes eventuel des xenogreffes necessite encore des sauts cognitifs et technologiques importants. Cette breve revue cherche a faire le point sur ces deux strategies.

Although secondary data analyses have been established in recent years in health research, explicit recommendations for standardized, transparent and complete reporting of secondary data analyses do not exist as yet. Therefore, between 2009 and 2014, a first proposal for a specific reporting standard for secondary data analysis was developed (STROSA 1). Parallel to this national process in Germany, an international reporting standard for routine data analysis was initiated in 2013 (RECORD). Nevertheless, because of the specific characteristics of the German health care system as well as specific data protection requirements, the need for a specific German reporting standard for secondary data analyses became evident. Therefore, STROSA was revised and tested by a task force of 15 experts from the working group Collection and Use of Secondary Data (AGENS) of the German Society for Social Medicine and Prevention (DGSMP) and the German Society for Epidemiology (DGEpi) as well as from the working group Validation and Linkage of Secondary Data of the German Network for Health Services Research (DNVF). The consensus STROSA-2 checklist includes 27 criteria, which should be met in the reporting of secondary data analysis from Germany. The criteria have been illustrated and clarified with specific explanations and examples of good practice. The STROSA reporting standard aims at stimulating a wider scientific discussion on the practicability and completeness of the checklist. After further discussions and possibly resulting modifications, STROSA shall be implemented as a reporting standard for secondary data analyses from Germany. This will guarantee standardized and complete information on secondary data analyses enabling assessment of their internal and external validity.