Natural innate cytokine response to immunomodulators and adjuvants in human precision-cut lung slices.

Prediction of lung innate immune responses is critical for developing new drugs. Well-established immune modulators like lipopolysaccharides (LPS) can elicit a wide range of immunological effects. They are involved in acute lung diseases such as infections or chronic airway diseases such as COPD. LPS has a strong adjuvant activity, but its pyrogenicity has precluded therapeutic use. The bacterial lipopeptide MALP-2 and its synthetic derivative BPPcysMPEG are better tolerated. We have compared the effects of LPS and BPPcysMPEG on the innate immune response in human precision-cut lung slices. Cytokine responses were quantified by ELISA, Luminex, and Meso Scale Discovery technology. The initial response to LPS and BPPcysMPEG was marked by coordinated and significant release of the mediators IL-1ß, MIP-1ß, and IL-10 in viable PCLS. Stimulation of lung tissue with BPPcysMPEG, however, induced a differential response. While LPS upregulated IFN-γ, BPPcysMPEG did not. This traces back to their signaling pathways via TLR4 and TLR2/6. The calculated exposure doses selected for LPS covered ranges occurring in clinical studies with human beings. Correlation of obtained data with data from human BAL fluid after segmental provocation with endotoxin showed highly comparable effects, resulting in a coefficient of correlation >0.9. Furthermore, we were interested in modulating the response to LPS. Using dexamethasone as an immunosuppressive drug for anti-inflammatory therapy, we found a significant reduction of GM-CSF, IL-1ß, and IFN-γ. The PCLS-model offers the unique opportunity to test the efficacy and toxicity of biological agents intended for use by inhalation in a complex setting in humans.

[100 years Heidehaus--from sanatorium for tuberculosis to a modern chest hospital]. / 100 Jahre Heidehaus--vom Tuberkuloseheim zum modernen Lungenzentrum.

When the sanatorium "Heidehaus" was founded on June 1, 1907 in the northern countryside of Hannover with Dr. Otto Ziegler as head about 120 beds for patients with tuberculosis were available. By 1914 about 200 patients were being treated by 4 physicians and 10 nurses. An operating theatre and a modern radiology unit were added in 1927. Shortly after the 2nd World War 400 patients with tuberculosis were hospitalised simultaneously. With the introduction of antituberculous triple drug treatment the number of patients dropped significantly. During this period many traditional facilities, used to care for patients with tuberculosis lost their financial basis and closed. However in the 1960s Prof. Schindler, the head of Heidehaus, widened the spectrum of the hospital into a modern chest hospital, focused on lung and airway diseases. In particular in the 1980s and 1990s this trend continued and 2 independent departments, i. e., pneumology and thoracic surgery were founded. In 2005 due to restructuring by the community of Hannover the "Heidehaus" moved completely and merged with another traditional hospital to become the new "Oststadt-Heidehaus". In its new surroundings both departments for pulmonary medicine and thoracic surgery offer a broad spectrum of modern thoracic medicine in cooperation with other disciplines.

Future horizons of lung preservation by application of a platelet-activating factor antagonist compared with current clinical standards. Euro-Collins flush perfusion versus donor core cooling.

With the introduction of platelet-activating factor antagonists, a direct inhibition of ischemia-induced reperfusion injury can be achieved by prevention of platelet activation, reduction of microvascular leakage, and platelet-activating factor-induced bronchoconstriction. At present, two preservation methods are established for clinical lung preservation: (1) donor core cooling by extracorporeal circulation and (2) pulmonary artery flush with Euro-Collins solution and prostacyclin. We compared the quality of organ preservation obtained with these methods to the application of a platelet-activating factor antagonist (WEB 2170; 0.3 mg/kg) for the donor, perfusion solution, and throughout the first 6 hours of reperfusion in combination with prostacyclin (20 ng/kg/min) and Euro-Collins solution (60 ml/kg). Eighteen heterotopic heart and orthotopic left lung transplants were performed in three groups of six dogs each after 6 hours of cold ischemia (group I, donor core cooling; group II, Euro-Collins flush and prostacyclin; group III, Euro-Collins flush, prostacyclin, and WEB 2170). Myocardial preservation was achieved with St. Thomas' Hospital solution (20 ml/kg) in all groups. After transplantation, cardiorespiratory function was assessed at an inspired oxygen fraction of 0.4. After transplantation, superior results were observed in group III, as expressed by significantly improved oxygenation, while cardiac output and pulmonary artery pressures were similar in all groups. We concluded that the use of the platelet-activating factor antagonist WEB 2170 resulted in better lung preservation than current clinical standards.

Improvement of currently used methods for lung preservation with prostacyclin and University of Wisconsin solution.

After 6 hours of cold ischemia the quality of lung preservation was assessed in a canine heart-lung transplant model comparing three clinically used methods for lung preservation: donor core cooling by means of extracorporeal circulation (group I); pulmonary artery flush perfusion with either Euro-Collins solution after prostacyclin application (group II); or University of Wisconsin solution after donor pretreatment with prostacyclin (group III). In all cases St. Thomas Hospital solution was used for myocardial protection. Heterotopic heart and orthotopic left lung allotransplantation was performed in three groups of six mongrel dogs each according to the method of lung preservation. After transplantation cardiorespiratory function was assessed at FiO2 of 0.4 for a maximum of 12 hours. After surgery, significantly improved oxygenation of the donor lung was observed in groups II and III, compared to group I (p less than 0.01). Between groups II and III, no significant differences were found in the oxygenation during the first 5 hours, but in the later postoperative course pO2 values decreased in group II although they remained stable on a higher level during the entire postoperative course in group III (p less than 0.05). University of Wisconsin solution for lung preservation in combination with prostacyclin donor pretreatment provides superior postoperative oxygenation of the transplanted lung compared to currently used clinical standards represented by donor core cooling and Euro-Collins flush perfusion.

Donor heart-related variables and early mortality after heart transplantation.

Impaired donor heart function after heart transplantation results in the necessity for prolonged catecholamine and ventilatory support of the patient. Subsequently the risk of multiorgan impairment, infection, and rejection will be increased. In this retrospective analysis we tried to identify donor-related risk factors in patients who died early after transplantation. Of 174 patients undergoing heart transplantation from October 1985 through October 1988, 22 (12.6%) died early. Of the total, 39 cases were evaluated retrospectively for donor-related logistic and metabolic factors. All donors were analyzed with respect to the early mortality for age, weight, height, maximum dopamine concentration, thyroid hormone levels, and the duration from brain death until explantation and ischemia. Thirty patients were survivors (group A); nine patients died early (group B). By multiple regression analysis a significant influence (group A vs group B) of donor age, dopamine support, and ischemic time on early mortality could be demonstrated, whereas donor weight and height, hormone levels of triiodothyronine and thyroxine, and duration of brain death showed no correlation. From this limited experience we conclude that use of hearts from older donors with higher catecholamine support and longer ischemic times will result in an increased early mortality. In contrast, no influence of prolonged brain death times and metabolic factors could be demonstrated.

Preventive treatment of coronary vasculopathy in heart transplantation by inhibition of smooth muscle cell proliferation with angiopeptin.

BACKGROUND: The underlying mechanism of accelerated coronary vasculopathy in cardiac allografts still remains unclear. Our hypothesis was that inhibition of smooth muscle cell proliferation with the somatostatine analogue Angiopeptin may reduce vasculopathy. METHODS: Fifty-four patients received Angiopeptin injections (1500 micrograms x three times daily subcutaneously) for 21 days after the operation and three additional injections with every rejection treatment. Angiography was performed yearly, and data were compared with a matched historic control group. RESULTS: Actuarial survival was 85% at 1 year and 80% at 2 years, comparable with our results in general (80%/77%). Forty-six long-term survivors could be followed by coronary angiography. At 1 year, vasculopathy was assessed in nine patients (17%). Of the 18 patients investigated at 2 years thus far, an additional three patients were found to have vasculopathy. In the control group vasculopathy was comparable, being 13% after 1 year and 20% after 2 years. A significantly lower incidence of rejections and lower creatinine values were found in the study group within the entire observation period (p < 0.05). CONCLUSIONS: We conclude that Angiopeptin treatment appears to be safe without significant side effects; it may reduce the number of acute rejections, at least during the first year after heart transplantation. However, the results of the 2-year follow-up in the remaining patients would have to be included in assessing the effect of Angiopeptin. Long-term follow-up will be necessary to decide whether Angiopeptin will be helpful in reducing the incidence of transplant vasculopathy.

Heterotopic heart-unilateral left lung transplantation in dogs.

A technique is presented for transplantation of the heart and left lung in the canine model. Preservation of the recipient's heart and right lung allowed heterotopic en bloc transplantation of the donor organs, thus preserving the normal respiratory pattern and obviating the need for cardiopulmonary bypass. Four experiments were performed to develop the surgical technique. The mean survival of the remaining 10 dogs studied was 23 +/- 28 days (range 3 to 91 days). The transplanted heart and lung could be investigated as in orthotopic heart-lung transplantation; bronchoscopy with bronchoalveolar lavage and endobrachial biopsy as well as endomyocardial biopsy were performed by standard approaches. This model is suitable for physiological and immunological long-term observations of cardiopulmonary transplantation in dogs.

Long-term follow up of patients with implantable cardioverter-defibrillators and mild, moderate, or severe impairment of left ventricular function.

OBJECTIVE: To determine whether patients with life threatening ventricular tachyarrhythmias, impaired left ventricular function, and severe heart failure will benefit from implantable cardioverter-defibrillator (ICD) treatment. DESIGN: 410 patients were followed up after ICD implant. Left ventricular function was assessed by the New York Heart Association (NYHA) functional class of heart failure: 50 patients (12%) were in NYHA I-II, 151 (37%) in NYHA II, 117 (29%) in NYHA II-III, and 92 (22%) in NYHA III. Epicardial ICD implantation was performed in 209 patients (51%) and 201 patients (49%) received non-thoracotomy ICDs. RESULTS: Perioperatively, 12 patients (3%) died, more often after epicardial ICD implant (11/209 patients, 5%) than after transvenous implant (1/201 patients, < 1%) (P < 0.05). During a mean (SD) follow up of 28 (24) months (range < 1 to 114 months), 90 patients (23%) died: nine (2%) died from sudden arrhythmia; five (1%) also died suddenly but probably not from arrhythmic causes; 55 (14%) died from cardiac causes (congestive heart failure, myocardial reinfarction); 21 (5%) died from non-cardiac causes. The three year, five year, and seven year survival was 92-96% for arrhythmic mortality in NYHA class I, II and III, compared to a three year survival of 94% and a five year and seven year survival of 84% for patients in NYHA class II-III. 338 patients (82%) received ICD shocks (21 (SD 43) shocks per patient); patients in NYHA class II (83%), class II-III (84%), and class III (90%) received ICD discharges more often than those in class I-II (64%) (P < 0.05). The mean (SD) time interval between ICD implant and the first ICD shock was shorter in NYHA class II (16 (17) months), class II-III (19 (27) months), and class III (16 (19) months) than in class 0-I (22 (24) months) (P < 0.05). CONCLUSIONS: Patients with mild, moderate, and severe left ventricular dysfunction benefit from ICD treatment and these patients survive for a considerable time after the first shock. Survival is influenced by the degree of left ventricular dysfunction; aggressive treatment of heart failure is necessary as well as ICD therapy.

Age dependent efficacy of implantable cardioverter-defibrillator treatment: observations in 450 patients over an 11 year period.

OBJECTIVE: To determine whether implantable cardioverter-defibrillator (ICD) treatment is beneficial in elderly patients with life threatening ventricular tachyarrhythmias. DESIGN: Since January 1984, ICDs were implanted in 450 patients to evaluate surgical risk, complications and mean survival in relation to patient age; 81 patients (18%) were < or = 50 years at the time of ICD implant, 254 patients (56%) were between 51 and 64 years, and the remaining 115 (26%) were > or = 65 years. Epicardial lead systems were implanted in 209 patients (46%), while transvenous lead systems were implanted in 241 (54%). RESULTS: 13 patients (3%) died perioperatively, more often after epicardial (11 of 209 patients, 5%) than after transvenous ICD implantation (one of 241 patients, < 1%) (p < 0.05). During a mean (SD) follow up of 28 (24) months (range < 1 to 114 months), 90 patients (20%) died. Of these, nine (2%) died from sudden arrhythmic death; five (1%) died suddenly, probably as a result of non-arrhythmic causes; 55 (12%) died from other cardiac causes (congestive heart failure, myocardial infarction); and 21 (5%) died from non-cardiac causes. The three, five, and seven year survival for arrhythmic mortality was 95% in patients < or = 50 years compared with a three year survival of 93% and a five and seven year survival of 91% in patients of 51 to 64 years, and a three, five, and seven year survival of 99% in patients > or = 65 years. 362 patients (80%) received ICD discharges (21 (43) shocks per patient), with a similar incidence among all three patient groups (< or = 50 years, 80%; 51 to 64 years, 81%; > or = 65 years, 79%). The time interval between ICD implant and the first ICD treatment was shorter in patients > or = 65 years (8 (8) months) than in patients between 51 and 64 years (11 (14) months) or < or = 50 years (11 (11) months) (p < 0.05). Survival time following first appropriate shock was 30 (24) months in patients < or = 50 years, 30 (26) months in patients of 51 to 64 years, and 19 (20) months in patients > or = 65 years. CONCLUSIONS: Elderly patients benefit from ICD treatment, and survive for a considerable time after the first treatment. Therefore, elderly patients should be considered candidates for ICD implantation if life threatening ventricular tachy-arrhythmias are present.

Ten year survival after heart transplantation: palliative procedure or successful long term treatment?

OBJECTIVE: To investigate the long term outcome and prognostic factors after heart transplantation. SETTING: University hospital. SUBJECTS: 120 heart transplant patients (98 male, 22 female; underlying disease: dilated cardiomyopathy in 69, coronary artery disease in 42, miscellaneous in nine) who had undergone heart transplantation between October 1984 and October 1987. Immunosuppressive treatment was comparable in all patients and rejection episodes were treated in a uniform manner. METHODS: Functional status, quality of life, and potential predictors for long term survival were investigated. RESULTS: Actuarial survival rates were 65% at five years and 48% at 10 years; 58 patients survived > 10 years. The major causes of death were cardiac allograft vasculopathy (39%), acute rejection (18%), infection (11%), and malignancy (11%). Long term survivors had good exercise tolerance assessed by the New York Heart Association classification: 47 (81%) in grade I/II; 11 (19%) in grade III/IV. Echocardiography showed good left ventricular function in 48 patients. On angiography, severe allograft vasculopathy was present in only 16 patients (28%). Renal function was only slightly impaired, with mean (SD) serum creatinine of 148.5 (84.9) micromol/l. Multiple potential predictors of long term survival were analysed but none was found useful. CONCLUSIONS: Heart transplantation represents a valuable form of treatment. Survival for more than 10 years with a good exercise tolerance and acceptable side effects from immunosuppression can be achieved in about 50% of patients.

Hyperimmuneglobulin for cytomegalovirus prophylaxis following heart transplantation.

Cytomegalovirus continues to be an important cause of morbidity and mortality following organ transplantation. In a series of 75 heart transplant patients, we have compared two protocols for prophylactic administration of CMV hyperimmuneglobulin. The first group of patients received immunoglobulin on the operative and on the tenth postoperative days. The second group of patients received immunoglobulins on the operative day, and repeatedly with each period of increased immunosuppression. With repeated doses of immunoglobulin prophylaxis, the incidence of CMV reactivation and the clinical severity of CMV infection were both significantly reduced. A reduction in the incidence of CMV infection in recipients who were seronegative preoperatively was also observed. (5/8 vs. 7/25 patients; P = 0.06). We conclude that repeated administration of specific hyperimmuneglobulin with each period of increased immunosuppression following heart transplantation has a beneficial effect on both CMV reactivation and infection.

Inhibition of atrial fibrillation by pulmonary vein isolation and auricular resection--experimental study in a sheep model.

OBJECTIVE: The MAZE procedure has proven effective for surgically treating atrial fibrillation, but its acceptance has been limited due to the complex dissection pattern. A new simplified operative technique, that comprises two important components of the MAZE procedure, has been evaluated in an established animal model of induced sustained atrial fibrillation. METHODS: In eight sheep, median sternotomy was performed for cardiopulmonary bypass via femoral and bicaval cannuiation. Bipolar atrial and ventricular electrodes (16) were applied for computerized EKG-sampling. Atrial fibrillation was induced during continuous theophylline infusion (0.5 mg/kg/min) by repetitive (10x) biatrial stimulation. Atrial response was monitored and mapped. The operative procedure was accomplished in induced ventricular fibrillation: Right and left atrial appendices were resected and a circumferential transmural incision around all pulmonary veins was performed and closed. After defibrillation, the atria were stimulated again using the above protocol and EKGs were sampled. RESULTS: Sustained atrial fibrillation was inducible in all animals (80 stimulation episodes, median duration 31 s, 6 incessant episodes) prior to dissection. Post resection of the atrial appendices and pulmonary vein isolation, atrial fibrillation was not inducible in any of the eight animals (80 stimulation episodes). A significant interatrial (104 +/- 13 ms) and atrioventricular (208 +/- 19 ms) conduction delay was observed post dissection. CONCLUSION: We conclude that the described procedure is effective for the inhibition of sustained atrial fibrillation in morphologically unaltered atria. The operative approach involves less dissection than the MAZE procedure, which could facilitate its use in concomitant mitral procedures. The clinical significance of the observed AV-Delay has to be evaluated.

Surgical interventions in ischemic ventricular tachyarrhythmias--endocardial resection or implanted cardioverter/defibrillator.

The surgical therapy of ventricular tachyarrhythmias (VTA) in ischemic heart disease is attracting attention, since current medical therapies are showing limited long-term efficacy. The curative concept of electrophysiologically guided endocardial resection (ER) and palliation with the implantable cardioverter/defibrillator (ICD) are compared retrospectively. From 1980-1992, 121 patients (55 +/- 9 years, 108 males, 13 females) underwent ER and 203 patients (59 +/- 9 years, 195 males, 8 females) received an ICD for ischemic VTA. Concomitant coronary revascularization was performed in 38/121 patients with ER (31%) and in 62/203 patients (31%) with ICD. Perioperative mortality was 8% (10/121 patients) for ER and 5% (10/203 patients) for ICD (P = n.s.). Hundred eleven patients with ER (mean follow-up 41 +/- 37 months) and 193 with ICD (mean follow-up 22 +/- 20 months) were available for survival analysis: freedom from sudden death was comparable for the two groups at 1 year (99% for ICD, and 94% for ER) and at 5 years (90% for ICD and 90% for ER) (P = n.s.). Freedom from cardiac death also showed no differences between the groups at 1 year (94% for ICD, and 84% for ER) and at 5 years (74% for ICD and 74% for ER) (P = n.s.). Left ventricular function, indicated by left ventricular ejection fraction, was comparable (34 +/- 9% in ER, 30 +/- 11% with ICD) (P = n.s.) in the two groups. The linearized incidence of DC-shocks was 10.3/year in ICD patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Pneumocystis carinii pneumonia following heart transplantation.

Pneumocystis carinii pneumonia represents a rare complication that is associated with a high mortality following heart transplantation. The cases of two heart transplant recipients who developed Pneumocystis pneumonia within the first 3 postoperative months are reported. Both patients had severe clinical symptoms of the disease; the diagnosis was confirmed by bronchoalveolar lavage, and the patients were treated with a combination of trimethoprim and sulfamethoxazole. Both patients recovered and are well at the time of this report.

Retransplantation of the lung. A single center experience.

While lung retransplantation remains the only therapeutic option in early or late graft failure, its value is viewed controversially. Of 134 patients undergoing pulmonary transplantation in our institution, 13 patients underwent 14 redos following heart-lung transplantation (n = 3), bilateral lung transplantation (n = 5), and unilateral lung transplantation (n = 5). Indications for retransplantation were acute graft failure (n = 2), persistent graft dysfunction (n = 3), airway complications (n = 2), and chronic graft failure (n = 7). Prior to retransplantation, six patients had been in stable respiratory failure, the remaining eight patients were on mechanical ventilation or extracorporeal membrane oxygenation (n = 2). Four patients died, 19, 43, 142, and 683 days following retransplantation due to pneumonia (n = 2), early onset of obliterative bronchiolitis (n = 1), and pulmonary embolism (n = 1). There was no correlation between mortality and intubation prior to re-operating, timing of operation, donor cytomegalovirus (CMV) status, or type of operation. Postoperative need for intensive care treatment was prolonged in patients undergoing acute retransplantation (P < 0.05). Actuarial 1- and 2-year survival rates were calculated at 77 and 64%. This was slightly lower than in the overall population following primary isolated lung transplantation (83 and 80%). Actuarial freedom from obliterative bronchiolitis (stage 3) at 1 and 2 years was calculated at 88 and 27% (primary grafts: 88% vs 72%; P < 0.05). Retransplantation is a realistic option in early and late graft failure after lung transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic rejection following lung transplantation. Incidence, time pattern and consequences.

UNLABELLED: The long-term prognosis following lung transplantation (LTX) depends mainly on the development of chronic rejection which appears clinically as deterioration of the lung function while, histologically, obliterative bronchiolitis (OB) is found. However, it still remains questionable whether heart-lung (HL), double or single lung (DL/SL) transplants behave similarly with regard to incidence and time pattern. Eighty-two patients, transplanted until August 92, were analyzed. Early and late deaths within 180 days postoperatively were excluded. A total of 64 patients at risk could be evaluated. By repeated lung function tests, obstructive airway disease was defined by a drop of 25% or more of the forced expiratory volume in one second (FEV1) in percent of the inspiratory vital capacity. RESULTS: The functional optimum after transplantation was reached after a comparable time-span postoperatively in all groups. Chronic deterioration of the lung function developed earlier following DLTX compared to HLTX and SLTX. Obstructive airway disease was diagnosed in 9/20 (45%) HL, 7/19 (37%) DL, and 7/25 (28%) SL patients. Of these, 4 died and 4 had to be retransplanted for the disease while an additional 15 patients are currently under investigation. It is concluded that the development of obstructive airway disease represents a serious problem in all types of lung transplantation. There is a tendency to earlier development following DLTX--perhaps caused by the greatest immunological potential in this group of patients.

Distant organ procurement in clinical lung- and heart-lung transplantation. Cooling by extracorporeal circulation or hypothermic flush.

The scarcity of suitable donors for single lung and heart-lung transplantation calls for methods of medium-term pulmonary preservation to allow for distant organ procurement. At our institution, the first five grafts (four heart-lung, one single lung) were cooled by means of a transportable extracorporeal circulation unit, while the last eight grafts (four heart-lung, four single lung) were flush-perfused with modified cold Euro-Collins solution. The technique of extracorporated circulation included aortic and right atrial cannulation and cooling to 12 degrees-14 degrees C (rectal temperature) using a bubble oxygenator. Bypass times ranged between 41 and 52 min. Following excision, the organs were transported in ice-cold donor blood for ischemic times from 171 to 310 min. For cold flush preservation, simultaneous coronary (cold St. Thomas's solution) and pulmonary artery perfusion (Euro-Collins solution, 50 ml/kg over 4 min) were initiated simultaneously. The organs were transported in cold Euro-Collins solution for ischemic times of 175 to 270 min. In heart-lung transplantations the first postoperative arterial PO2 upon arrival at the intensive care unit was 120 +/- 38 Torr in the extracorporeal circulation and 140 +/- 38 Torr in the Euro-Collins solution group. Six of eight patients were extubated within 48 h after cardiopulmonary grafting. We conclude that pulmonary function following heart-lung or single lung preservation with simple hypothermic flush is as good or better than that following extracorporeal circulation. Since distant organ retrieval is much more convenient without the latter, preservation using Euro-Collins solution is preferred.

Results of orthotopic heart transplantation for ischaemic cardiomyopathy.

From July 1983 to May 1987, 172 orthotopic heart transplantations were performed in 165 patients. Of these, 46 recipients (39 male, 7 female), aged between 26 and 56 years (mean age 47), suffered from ischaemic cardiomyopathy. Postoperative immunosuppression consisted of a triple drug regimen of cyclosporine A, azathioprine and, in the last 31 patients, low-dose steroids. The actuarial survival in this group of patients at 1 year and at 2 years was 71.9%. There were five early deaths: three due to acute rejection and two from multiple-organ failure and sepsis. Of the eight late deaths, two could be attributed to acute cardiac rejection and four to bacterial infections. In two patients, sudden death occurred in the presence of accelerated graft atherosclerosis. Mild-to-moderate coronary artery lesions were seen in five other patients undergoing angiography one year after transplantation. Apart from the well-known postoperative risk factors in cardiac transplant recipients, accelerated graft atherosclerosis appears to be an additional hazard in the subgroup surgically treated for ischaemic cardiomyopathy.

Graft coronary vasculopathy in cardiac transplantation--evaluation of risk factors by multivariate analysis.

The development of coronary vasculopathy is the main determinant of long-term survival in cardiac transplantation. The identification of risk factors, therefore, seems necessary in order to identify possible treatment strategies. Ninety-five out of 397 patients, undergoing orthotopic cardiac transplantation from 10/1985 to 10/1992 were evaluated retrospectively on the basis of perioperative and postoperative variables including age, sex, diagnosis, previous operations, renal function, cholesterol levels, dosage of immunosuppressive drugs (cyclosporin A, azathioprine, steroids), incidence of rejection, treatment with calcium channel blockers at 3, 6, 12, and 18 months postoperatively. Coronary vasculopathy was assessed by annual angiography at 1 and 2 years postoperatively. After univariate analysis, data were evaluated by stepwise multiple logistic regression analysis. Coronary vasculopathy was assessed in 15 patients at 1 (16%), and in 23 patients (24%) at 2, years. On multivariate analysis, previous operations and the incidence of rejections were identified as significant risk factors (P < 0.05), whereas the underlying diagnosis had borderline significance (P = 0.058) for the development of graft coronary vasculopathy. In contrast, all other variables were not significant in our subset of patients investigated. We therefore conclude that the development of coronary vasculopathy in cardiac transplant patients mainly depends on the rejection process itself, aside from patient-dependent factors. Therapeutic measures, such as the administration of calcium channel blockers and regulation of lipid disorders, may therefore only reduce the progress of native atherosclerotic disease in the posttransplant setting.