Analyses of coronary graft patency after aprotinin use: results from the International Multicenter Aprotinin Graft Patency Experience (IMAGE) trial.

OBJECTIVE: We examined the effects of aprotinin on graft patency, prevalence of myocardial infarction, and blood loss in patients undergoing primary coronary surgery with cardiopulmonary bypass. METHODS: Patients from 13 international sites were randomized to receive intraoperative aprotinin (n = 436) or placebo (n = 434). Graft angiography was obtained a mean of 10.8 days after the operation. Electrocardiograms, cardiac enzymes, and blood loss and replacement were evaluated. RESULTS: In 796 assessable patients, aprotinin reduced thoracic drainage volume by 43% (P < .0001) and requirement for red blood cell administration by 49% (P < .0001). Among 703 patients with assessable saphenous vein grafts, occlusions occurred in 15.4% of aprotinin-treated patients and 10.9% of patients receiving placebo (P = .03). After we had adjusted for risk factors associated with vein graft occlusion, the aprotinin versus placebo risk ratio decreased from 1.7 to 1.05 (90% confidence interval, 0.6 to 1.8). These factors included female gender, lack of prior aspirin therapy, small and poor distal vessel quality, and possibly use of aprotinin-treated blood as excised vein perfusate. At United States sites, patients had characteristics more favorable for graft patency, and occlusions occurred in 9.4% of the aprotinin group and 9.5% of the placebo group (P = .72). At Danish and Israeli sites, where patients had more adverse characteristics, occlusions occurred in 23.0% of aprotinin- and 12.4% of placebo-treated patients (P = .01). Aprotinin did not affect the occurrence of myocardial infarction (aprotinin: 2.9%; placebo: 3.8%) or mortality (aprotinin: 1.4%; placebo: 1.6%). CONCLUSIONS: In this study, the probability of early vein graft occlusion was increased by aprotinin, but this outcome was promoted by multiple risk factors for graft occlusion.

[Clinical results after en block double lung transplantation with direct bronchial revascularization. The first three and a half years' experience in Denmark]. / Kliniske resultater efter en bloc dobbeltlungetransplantation med direkte bronkial revaskularisering. De første tre et halvt års erfaring i Danmark.

En-bloc double lung transplantation with tracheal anastomosis and direct revascularization of the bronchial arteries to the left internal mammary artery has been carried out in Denmark since June 1992. Forty-seven patients (32 with alfa-1 antitrypsin deficiency, 11 with chronic obstructive pulmonary disease, two with cystic fibrosis and two with primary pulmonary hypertension), 25 men and 22 women, average age 39 years (17-64 years), have received their first double-lung transplant with bronchial artery revascularization. Arteriography of the internal mammary artery and bronchial arteries was performed in 42 (89%) of the patients from 1-150 days after the operation. Successful bronchial artery revascularization was demonstrated arteriographically in 40 patients, in two patients the arteriography failed to show bronchial artery revascularization. Arteriography was not performed in five patients due to early complications and death. Bronchoscopy showed rapid, uncomplicated airway healing in 42 patients. Mucosal necrosis under the tracheal anastomosis was found in three patients, and severe obstructive endobronchial growth of the fungus Aspergillus fumigatus was diagnosed in the last two patients. The one- and two-year survival is 83% (Kaplan-Meier). Eleven patients are dead, five due to pulmonary causes and six due to extra-pulmonary causes. Pulmonary function became normal in nearly all surviving patients between three to six months after the transplantation. In conclusion, en-bloc double-lung transplantation with bronchial artery vascularization has shown good short-term results, and the one- and two-year survival gives hope that a successful bronchial artery revascularization will improve the long-term survival following lung transplantation.

Direct bronchial artery revascularization and en bloc double lung transplantation--surgical techniques and early outcome.

BACKGROUND: Lung transplantation including direct bronchial artery revascularization (BAR) has produced promising early results in small clinical series. METHODS: In Copenhagen primary en bloc double lung transplantation with BAR, with the left mammary artery used as conduit, has been performed in 47 patients from 1992 to the end of 1995. After introduction of the bloc into the recipient, the mammary-to-bronchial artery anastomosis is performed as the first anastomosis, allowing perfect exposure and early reperfusion. Internal mammary-bronchial artery arteriography has been performed routinely after operation. RESULTS: Bronchoscopic examination performed in all patients documented normal airway healing in 42, disturbed in two, and complicated in three. Arteriography performed in 42 patients demonstrated complete BAR in 25, incomplete in 15, and failed BAR in 2. Failed BAR was associated with complicated airway healing. The 1- and 2-year survival rate (Kaplan-Meyer) is 83%. Eleven patients have died, only one within 30 days. The total incidence of bronchiolitis obliterans syndrome at 3 years (with Kaplan-Meier technique) is 33%. Successful BAR has also been performed with an adjusted technique in a limited number of heart-lung and single lung transplantations. Our total experience of BAR in any type of lung transplantation includes 65 patients with an arteriographic BAR success rate of 94% (50 of 53 examined patients). CONCLUSIONS: Experience has improved the surgical technique and has made BAR reliable and safe, be it double lung, single lung, or heart-lung transplantation. Early results are good, but only follow-up will show if long-term results after lung transplantation will be improved by BAR. Already today, en bloc double lung transplantation with BAR is a viable alternative to sequential bilateral lung transplantation.

[Coronary bypass surgery at the Rigshospitalet 1993-1995. Results after 1.000 consecutive operations]. / Koronar bypass-kirurgi på Rigshospitalet 1993-1995. Resultater efter 1.000 konsekutive operationer.

During 1993-95 1000 consecutive patients were admitted for coronary bypass surgery. The total 30-day mortality of 1.9% was 0.9% for elective cases, 0.8% for reoperations and 0.2% for urgent cases. Perioperative myocardial infarction occurred in 44 patients of whom 25% had infarction at the start of the operation. Respiratory insufficiency occurred in 1.4% of the patients, 3.6% developed renal insufficiency and 1.8% had neurological defects postoperatively. Reoperation for bleeding occurred in 6%, and 0.2% developed sternal or mediastinal infection. This study demonstrates that the results of coronary bypass surgery at Rigshospitalet, Copenhagen are fully comparable to similar results in our neighbouring countries. The results can probably be further improved by more intensive treatment of perioperative ischaemia, especially in reoperations and urgent cases.

Significance and management of early graft failure after coronary artery bypass grafting: feasibility and results of acute angiography and re-re-vascularization.

UNLABELLED: Perioperative ischaemia and infarction after CABG are associated with increased morbidity and mortality. OBJECTIVE: To study causes of perioperative ischaemia and infarction by acute re-angiography and to treat incomplete re-vascularization caused by graft failure or any other cause. METHODS: Between 1990 and 1995, 2003 patients underwent an isolated CABG operation. Myocardial ischaemia was suspected if one or more of the following criteria were present: New changes in the ST-segment in the ECG; a CKMB value greater than 80 U/L; new Q-waves in the ECG; recurrent episodes of, or sustained ventricular tachyarrhythmia; ventricular fibrillation; haemodynamic deterioration and left ventricular failure. Acute coronary angiography was performed in stable patients, while haemodynamically severely compromised patients were rushed to the operating room. RESULTS: A total of 71 (3.5%) patients of all CABGs with suspected graft failure were identified and included in the study. Patients were grouped according to whether they had an acute re-angiography (n = 59; group 1) or an immediate re-operation (n = 12; group 2) performed. In group 1, the acute re-angiography demonstrated graft failure/incomplete re-vascularization in 43 patients (73%). The angiographic findings were: Occluded vein graft(s) in 19 (32%); poor distal run-off to the grafted coronary artery in ten (17%); internal mammary artery stenosis in four (7%); internal mammary artery occlusion in three (5%); vein graft stenoses in three (5%); left mammary artery subclavian artery steal in two (3%); and the wrong coronary artery grafted in one (2%). Based on the angiography findings, 27 patients were re-operated and re-grafted. At the time of re-operation, 18 patients (67%) had evolving infarction documented by ECG or CKMB. Two patients (3%) experienced stroke in immediate relation to the re-angiography. The 30-day mortality was three (7%). In group 2, graft occlusions were found in 11 patients (92%). The 30-day mortality was six (50%). CONCLUSION: An acute re-angiography demonstrated graft failure or incomplete re-vascularization in the majority of patients with myocardial ischaemia early after CABG. Re-operation for re-re-vascularization was performed with low risk. Few patients with circulatory collapse could be saved by an immediate re-operation without preceding angiography.

[Lung transplantation. Indications, preoperative evaluation and postoperative treatment]. / Lungetransplantation. Indikationer, proeoperativ bedømmelse og postoperativ behandling.

Thirty-six heart-lung and lung transplantations have been performed in Denmark from January 1992 to January 1994. Heart-lung transplantations was initially carried out in patients with pulmonary vascular diseases. Single lung, double lung and heart-lung transplantation have become therapeutical alternatives and the indications have been expanded to terminal patients with pulmonary diseases. Careful selection of patients and donors, careful surgical techniques and a stringent immunosuppressive treatment have minimized the perioperative mortality. Daily lung function measurements, transbronchial biopsies and bronchoalveolar lavage have created possibilities for an early and safe diagnosis of infections and rejections. A high frequency of obliterative bronchiolitis with loss of pulmonary function is still a serious and unsolved problem. Intensive investigations with the aim of understanding, preventing and treating obliterative bronchiolitis are going on.

Early experience of double-lung transplantation with bronchial artery revascularization using mammary artery.

En-bloc double-lung transplantation with tracheal and bronchial revascularization using the left internal mammary artery has been performed in 14 Danish patients. Primary healing of the tracheal anastomosis was observed in 12 patients, in 10 of whom a successful revascularization has been verified by angiography. Two patients have been operated recently and not yet examined by angiography. Mucosal necrosis and subsequent development of bronchial stenosis had to be treated by left-sided pneumonectomy in two patients with failed revascularization. All patients were early survivors (1-14 months). We conclude that bronchial revascularization with the internal mammary artery is possible with an acceptable success rate and is associated with primary healing of the tracheal anastomosis. The impact on long-term results remains to be seen.

Preparation of autologous fibrin glue from pericardial blood.

To salvage patients' blood and improve hemostasis in cardiac operations, autologous fibrin glue was prepared in a new way by means of ethanol from pericardial blood. The yield from 44 mL of blood was 2.1 +/- 0.7 mL (mean +/- standard deviation) of fibrinogen concentrate with a concentration of 25.1 +/- 7.5 mg/mL; 2.7 mL of two-component glue was obtained after the addition of thrombin solution. The glue has the advantages of safety from transmission of viral diseases and from immunologic reactions.

Intra-aortic balloon counterpulsation in Denmark 1988-1991. Early results and complications.

During the years 1988-1991 6319 patients underwent cardiac surgical procedures in Denmark. In 183 patients (2.9%) with left ventricular failure intra-aortic balloon counterpulsation (IABP) was used. Four percent of the IABP were placed preoperatively, 86% intraoperatively and 10% postoperatively. Severe complications occurred in 16 patients (8.7%) and were mainly vascular due to limb ischemia. The incidence of complications was independent of the duration of balloon pumping. Sixty percent of the patients were weaned from IABP. The 30-day mortality rate was 54%. During the observation period we found a gradual decrease in the use of IABP as well as a reduction in mortality.

Composite graft replacement of the aortic valve and ascending aorta with Cabrol technique.

Replacement of the aortic valve, root and ascending aorta with the technique first described by Cabrol was performed on 17 patients. In five cases the aortic arch was also replaced. The indications were type A aortic dissection with aortic insufficiency (8 cases, with acute dissection in 7), native endocarditis with severe aortic insufficiency and aortic root abscess (3 cases), prosthetic endocarditis (3), and true aneurysm of the ascending aorta with aortic insufficiency (3). Acute surgery was performed in 15 cases (88%). The overall operative mortality was 41%. For the patients discharged from hospital the mean observation time was 30 months. None died, but in one case the right leg of the interposition graft became occluded and reoperation was required 40 months after the primary operation for acute type A dissection. The described technique of aortic valve and root displacement can be used in all cases in which use of a composite graft is indicated, except in situations where the coronary ostia and arteries are damaged by acute dissection.

[Autologous fibrin glue--preparation and clinical use]. / Autolog fibrinklaeber--fremstilling og klinisk anvendelse.

Fibrin tissue adhesive is a tissue adhesive in which the two components are fibrinogen concentrate and a thrombin solution, respectively. In autologous fibrin tissue adhesive, the fibrinogen is prepared from the patient's own blood in contrast to the fibrin adhesive available commercially where the fibrinogen is prepared from pooled donor plasma. In 42 heart and lung operations, autologous fibrin tissue adhesive prepared by a new method was employed in which the fibrinogen is separated from the patient's own plasma by precipitation with ethanol. Either 44 or 88 ml blood was employed for concentration of the fibrinogen. This resulted in 2.5 ml and 4.9 ml fibrinogen concentrate which was mixed with 0.3 parts of thrombin solution containing calcium and aprotinin (fibrolysis inhibitor) so that the total volumes of tissue adhesive were 3.3 ml and 6.4 ml. Production of autologous fibrin tissue adhesive is uncomplicated and takes less than 90 minutes. A new method of production of autologous tissue adhesive based on ethanol is described. The fibrin tissue adhesive prepared in this manner has a high concentration of fibrinogen and is effective as a haemostatic and as an adhesive in surgical operations and it has the further advantage that it is not associated with the risk of transmission of viral or for immunological reactions.

[Heart transplantation in Denmark. Therapeutic routines and preliminary results]. / Hjertetransplantation i Danmark. Behandlingsrutiner og praeliminaere resultater.

When the criterion of brain-death was introduced in Denmark on 1.7.1990, the possibility for heart transplantation and other interventions was opened. The first heart transplantation was carried out 3.10.1990 and, during the first year, 28 transplantations were carried out on 27 patients. The therapeutic routines in the department are reviewed and the results obtained after the first year are presented. A total of 33 donors who fulfilled the donor criteria were available. Of these, 28 came to Rigshospitalet, two were sent abroad and suitable recipients could not be found for two. The recipient group consisted of four women and 23 men with an average of 46 years. At the time of writing, on an average 169 days after operation (13-330), 23 out of 27 patients survived in good health and with normal cardiac function. Three patients are still in hospital.

[Patient related diagnostic delay in breast tumor. A prospective study]. / Patientrelateret diagnoseforsinkelse ved tumor mammae. En prospektiv undersøgelse.

In 209 patients referred with the diagnosis of tumour of the breast, the patient delay (PD) was registered together with the demographic and clinical conditions concerning the patient according to a meticulous questionnaire. In addition, the histological diagnosis and possible regional spread were registered. A total of 126 patients (60%) sought advice within one month of the commencement of symptoms. No statistically significant connection could be demonstrated between PD and age, marital status, education and occupational situation. No significant connection could be demonstrated between the size of the tumour, time of seeking advice and PD. A total of 115 patients (55%) had malignant tumours. The frequency of regional spread was found to be significantly greater in patients with PD longer than four weeks. Regular self-examination of the breast was undertaken by 92 (46%) of the patients and this was significantly more frequent in married or cohabiting patients, in patients with long education and in patients with employment outside the home. It did not prove possible to demonstrate briefer PD, lesser size of tumour and fewer cases of regional spread in patients who undertook self-examination of the breast but further research is required here.