Myocardial contraction bands in transplant biopsies.
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Biomedical subjects
Publications and source records attributed to A Haverich.
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Double-velour woven Dacron prostheses were investigated both experimentally and clinically. In 6 mongrel dogs, a tandem conduit between the right ventricle and the pulmonary artery was implanted, consisting of a plain woven and a double-velour woven graft. Following explanation after 2, 4, and 6 months, superior healing properties of the double-velour woven prostheses could be assessed by microscopy, as represented by an increase of tissue ingrowth, as well as by a thin and densely adherent inner healing capsule. Double-velour woven grafts were implanted in 50 patients undergoing open heart surgery. All grafts were presealed with fibrin glue and no bleeding could be detected at the time of implantation, even under the adverse influence of full heparinization and extracorporeal circulation.
Vascular grafts with primary zero porosity are desirable in surgery for aortic aneurysms with intraoperative partial or total systemic heparinization of the patient. The present study describes the clinical application and results of a new knitted Dacron double-velour prosthesis (primary porosity: 1,400 cc/min/cm2), coated with cross-linked bovine collagen; the resulting porosity for implantation is O cc/min/cm2. Such grafts were implanted in 111 patients between 12/83 and 11/84: for replacement of the infrarenal aorta in 74 aneurysms, for replacement of the thoraco-abdominal aorta in 4 instances, and for replacement of 13 aneurysms of the descending aorta. In 20 patients with arterial occlusive disease, the prosthesis was employed as bifurcation graft. In 43 cases (38%) the underlying disease was a ruptured (26) or symptomatic aortic aneurysm requiring emergency operation. There was no leakage from any of the implanted grafts regardless of whether partial (100 units/kg BW) or total (300 units/kg BW) systemic heparinization was administered. The overall mortality rate was 11.7% (13/111). For cases of ruptured abdominal aortic aneurysm the mortality rate was 22.7% (5/22). There was no graft-related complication either in the early postoperative course or during the follow-up period (1 to 10 months, mean: 6.2 months). It is concluded that this new type of graft combines the advantages of knitted Dacron prostheses in respect to healing and incorporation with primary zero porosity, and is therefore the graft of choice in surgery for ruptured aortic aneurysm.
Satisfactory extended preservation of the lung has been difficult to obtain. This study investigated the influence of different total volumes and flow rates during flush-perfusion of the lung, and their effect on pulmonary artery pressure, flow distribution, regional lung temperature and functional performance of the lungs following transplantation after 24 hours. Fifteen mongrel dogs served as donors of the heart and lung block. Cold modified Euro-Collins solution was used as flush perfusate. Pulmonary artery and perfusion-line pressures were measured. The regional lung temperature was measured at one minute intervals with 5 myocardial temperature probes. Flow distribution was determined with micro-aggregated albumin labelled with Technetium 99. The heart-lung block was harvested, the right lung removed, and samples taken for gamma-counting. The left lung was stored in cold Euro-Collins solution and then transplanted. The inspired oxygen fraction (FiO2) was set at 0.4 and was kept constant throughout the procedure and the entire postoperative course. There were 3 groups of 5 animals each. In group A, the flush perfusate was administered at a total volume of 20 cc/kg over a period of 6 minutes. In group B the same volume of perfusate was administered at a pulmonary artery pressure (PAP) of 18 to 20 mmHg, resulting in a considerably shorter perfusion time (1.3 minutes). In group C 60 cc/kg of perfusate were given at the same flow rate as in group B, also resulting in PAP of 18 to 20 mmHg, but the perfusion time was increased to 4 minutes. Thus, groups B and C investigated the effect of increased pressure and volume of perfusate, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
A 37-year-old man underwent cardiac transplantation for diffuse coronary artery disease and malignant arrhythmias. During the harvesting of the donor heart slight distention of the left ventricle was present due to insufficiency of the aortic valve. After explantation of the graft, fusion of 2 cusps was found and a commissurotomy of the aortic valve was performed and the graft transplanted. Despite maximum inotropic support immediate graft failure and aortic insufficiency was present and discontinuation of cardiopulmonary bypass (CPB) was impossible. After replacement of the aortic valve using a bioprosthesis and implantation of an intraaortic balloon-pump, low cardiac output persisted and CPB had to be continued. After 11 hours of normothermic cardiopulmonary bypass and intraaortic balloon-pumping a second graft became available and was retransplanted successfully. The postoperative course was uneventful and the patient remains well 3 months after the operation.
Intravenous DSA was performed in 53 patients with suspected dissection of the thoracic aorta and in 13 patients following surgery for aortic dissection. In 36 patients, the suspected diagnosis could be excluded definitely and, in 14 cases out of 17, a dissection was correctly diagnosed. All 11 type B dissections were correctly diagnosed. Of six type A dissections, only three were adequately demonstrated by IV DSA. In type B dissections, IV DSA is reliable, but in type A dissection with massive aortic insufficiency or pericardial tamponade the findings are not reliable. In all 13 patients who had surgery for dissection, IV DSA proved suitable for showing the anastomosis and progress of the disease.
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To investigate the long-term histologic consequences of combined heart and lung transplantation, heart and lung biopsies were obtained from six rhesus monkeys; two had undergone heart-lung autotransplantation 3.5 and 4.5 years previously, two were the recipients of heart-lung allografts 4.1 and 4.5 years previously, and the results were compared with two normal control animals. Cyclosporine had been used as maintenance immunosuppression in the allograft group. The heart and lung biopsies in the autograft animals were essentially normal. Dense adhesions were noted in the allografts, adn in one the visceral pleura was grossly thickened. Cardiac biopsies in the allografts were unimpressive, with a normal myocardium in one, and minimal interstitial fibrosis in the other. Intimal hyperplasia was present in the pulmonary arterioles of one of the allografted animals. Focal scarring was present in the lung of one allograft recipient, and the other animal showed severe thickening and fibrosis of the alveolar septae, as well as marked interstitial fibrosis such that large areas of the specimen were replaced by connective tissue. Histologic abnormalities in the allografted lungs correlated with the abnormal hemodynamics in these animals reported in a previous study. It is suggested that the histologic appearances in the lung are a consequence of chronic rejection, and that these findings may become a significant problem in human heart-lung transplant recipients.
Preservation of the lung remains a major challenge and hinders the development of distant lung and heart-lung block procurement, limiting the clinical application of these modalities. The progress made in the field of lung preservation is reviewed and the many unanswered problems are presented here.
To assess the long-term hemodynamic consequences of combined heart and lung transplantation, we investigated six rhesus monkeys 2.6 to 4.6 years (mean 4.0) after operation. Total follow-up was 24.0 primate-years. Autotransplantation had been carried out in four animals and allotransplantation in two, and the hemodynamic results were compared with those in three normal monkeys of similar size. Each animal underwent simultaneous right and left heart catheterization and pulmonary arteriography. Hemodynamic measurements were made at three levels of inspired oxygen. Arterial oxygen tension was within normal limits in all animals, and pulmonary artery pressure and pulmonary vascular resistance index did not change significantly with changes in the levels of inspired oxygen. Indices of left ventricular systolic function were normal in all animals. Values for pulmonary artery pressure and pulmonary vascular resistance index were similar in the autograft and normal groups: in the allograft group, the average pressure was 30/17 mm Hg (mean 24) and the index was 5.6 units . m2--both levels significantly higher than normal (pressure was 16/10 mm Hg, mean 13, [p less than 0.001] and index was 2.5 units . m2 [p less than 0.02]). Pulmonary arteriography in the allograft group with the highest pulmonary vascular resistance index (6.1 units . m2) was compatible with pulmonary vascular disease. Pulmonary arteriograms in the remaining eight monkeys were normal. Prolonged survival following combined heart and lung transplantation is possible in primates. Autotransplantation (and probable persisting denervation of the cardiopulmonary axis) does not necessarily result in abnormal long-term hemodynamics. The elevation in pulmonary artery pressure and pulmonary vascular resistance index in the allograft group may be related to previous episodes of pulmonary rejection, infection, or drug reaction.
A total of 135 survivors of surgical treatment of aortic dissection was followed for up to 15 years after surgery. Actuarial survival rates were 82 +/- 4% at 5 years and 64 +/- 6% at 10 years. There were no significant differences in long-term survival rates of patients in four subsets based on type and acuity of dissections. The incidence of late reoperation (dissection-related) was 13 +/- 4% at 5 years and 23 +/- 6% at 10 years; again, there was no significant difference among patients with different types or acuity of dissection. Multiple variables were investigated by multivariate discriminant analysis. Significant independent risk factors for late death included stroke, chronic renal dysfunction, remote myocardial infarction, and operation in the early years of this study. Younger age, site of intimal tear (arch), and cardiac tamponade portended a significantly higher likelihood of late reoperation. Except for stroke, no complication of the dissection or intraoperative factor significantly influenced late survival. Patients in whom the intimal tear was located in the aortic arch had the highest probability of late reoperation. Thus, dissection type, acuity, and distal extent, whether or not the tear was resected or concomitant aortic valve replacement performed, and a host of patient-related characteristics had no significant influence on the generally excellent long-term prognosis after surgical treatment. Indefinite surveillance of the remaining natural aorta is imperative (with reoperation when indicated) to attain such results.
The influence of 35 preoperative and intraoperative characteristics on operative mortality risk after 1,479 isolated aortic valve replacement procedures (1967 to 1981) was investigated utilizing univariate and multivariate logistic regression analyses. Mean age at operation was 58 +/- 13 years; 72% of patients were men. Physiology was classified as aortic stenosis (58%), regurgitation (30%), or both (9%). The overall operative mortality rate was 7% +/- 1%, but there were substantial differences in operative mortality rates among physiological subgroups (aortic regurgitation, 10% +/- 2%; aortic stenosis, 6% +/- 1%; stenosis/regurgitation, 5% +/- 2%). Independent determinants of operative mortality rate in the entire group were advanced New York Heart Association functional class, renal dysfunction, physiological subgroup, atrial fibrillation, and older age. In the aortic regurgitation subgroup, functional class, atrial fibrillation, and operative year were independent predictors. In the aortic stenosis subgroup, the significant determinants were functional class, renal dysfunction, age, prosthetic valve dysfunction, and absence of angina. Concomitant coronary bypass grafting, previous operation, endocarditis, and ascending aortic replacement had no independent predictive effect on operative mortality rate. Thus, the early results of aortic valve replacement can be related to several specific variables describing the functional and physiological status of the patient. Operative mortality rate is not independently related to previous operation or concomitant operative procedures. Specific differences in risk factors exist among the various physiological subgroups, probably reflecting the pathophysiology of the different hemodynamic lesions. This information should provide for a more rational approach to aortic valve replacement, at least in terms of early risk/benefit deliberations.
The influence of 34 variables on the operative mortality rate for isolated mitral valve replacement (MVR) was assessed by univariate and multivariate logistic regression analysis. The physiologic lesions were classified as stenosis (20%, operative mortality rate 8 +/- 1%), regurgitation (44%, operative mortality rate 13 +/- 2%), and mixed (34%, operative mortality rate 8 +/- 1%). Functional class (NYHA), previous myocardial infarction, and hepatic dysfunction were powerful independent clinical determinants of operative mortality (p less than .001), along with age at operation and emergency operation (p = .001, p = .04). Concomitant coronary artery bypass grafting or tricuspid annuloplasty, angina, ischemic etiology, and physiologic lesion were not significant independent determinants of operative risk. Interestingly, year of operation, prosthetic valve dysfunction, and previous cardiac surgery had no important effect on operative mortality. Early operative risk for MVR was related to preoperative cardiac and hepatic function. Prior myocardial infarction substantially increased the risk even if the mitral valve disease was not ischemic in origin. Increased operative mortality rate in the subgroup with mitral regurgitation was related to advanced left ventricular failure and myocardial infarction rather than the etiology of the mitral regurgitation. These clinical factors coupled with more refined measurements of left ventricular systolic pump function (independent of loading conditions) should permit more intelligent decision making regarding the optimal timing of MVR, at least in terms of early operative risk.
Composite extracardiac conduits consisting of a low-porosity woven graft and a high-porosity knitted double-velour Dacron graft presealed with fibrin glue were implanted between the right ventricle and the pulmonary artery in 6 dogs under partial heparinization. Two grafts were explanted after 6 weeks, 2 after 12 weeks, and 2 after 6 months. The healing properties of both types of prosthesis were studied macroscopically, under light microscopy, and with scatter electron microscopy. Spontaneous peeling of both the inner and outer capsules of the graft occurred in 3 of 6 woven prostheses during transection. In the remaining 3, peeling could be easily induced by blunt dissection; this was impossible in the knitted grafts. Microscopically, in a comparison of the different weaves after identical time intervals, the inner capsule was noticeably thicker in woven than in knitted grafts. Transtitial ingrowth of fibroblastic tissue could be observed in knitted grafts after 6 weeks; only poor transmural tissue bridging was detectable in woven prostheses after 6 months. Neovascularization of the inner capsule was detectable earlier and was more advanced toward the luminal surface of highly porous grafts. In conclusion, knitted grafts in the position of extracardiac right ventricular conduits showed firmer attachment of both inner and outer capsules to the prosthetic material. Also, the inner capsule remained thinner and revealed a higher degree of neovascularization than in the woven Dacron grafts.
The finding of mycotic aneurysms creates a major problem in surgery for both active bacterial endocarditis and prosthetic valve endocarditis. The value of local treatment of such aneurysms by a suspension of fibrin glue and an antibiotic was examined in an animal study since a previous in vitro investigation had indicated that such a suspension may discharge sufficient quantities of the antibiotic for up to 12 days. In 3 groups of 6 rabbits each, the entrance to the left atrial appendage was occluded subtotally. The endothelium within the cavity thus created was mechanically injured and the tip of a thin transthoracic catheter was placed in the cavity. In all animals, aliquots of staphylococcus aureus were injected through the catheter. All rabbits developed fever, and positive blood cultures were obtained in 16. The animals in group 1 were left without treatment. All 6 animals lost weight progressively, 4 animals died from sepsis, 2 rabbits were sacrificed after 6 days. Active endocarditis was demonstrated by histology and bacteriology in each animal. In group 2, 12.5 mg cephalotin were injected via the catheter 24 hours after the infection. Four animals died from sepsis, one rabbit had a positive tissue culture, and only one animal was free of infection on postoperative day 10. In group 3, 12.5 mg cephalotin suspended in fibrin glue was injected via the catheter 24 hours after the infection. All animals survived, became afebrile and resumed gain of weight. At autopsy after 10 days no infection was detectable. We conclude that a suitable antibiotic suspended in fibrin glue may allow for the sterilization of mycotic aneurysms in bacterial endocarditis.
This paper presents experimental investigations to evaluate fibrin seal for bleeding control under systemic heparinization as well as some of the benefits and limits of fibrin-presealing vascular prostheses. Local hemostasis using fibrin seal plus collagen fleece was achieved in 3 standardized sources of bleeding produced in mongrel dogs under full heparinization. Water porosity was measured in 3 standard prosthetic materials of different porosity. It could be shown that all graft types investigated were sufficiently sealed up to a pressure of 600 mmHg. The influence of fibrinolysis on the stability of the fibrin network in vascular grafts was tested by in vitro experiments using urokinase incubation. While water permeability increased in fibrin-sealed fabric without aprotinin added, no fibrinolysis-induced leakage was observed in those exposed to aprotinin. Surface thrombogenicity of the fibrin-sealed grafts was higher than in blood-preclotted prostheses, if not rinsed with isotonic saline. After rinsing, thrombogenicity decreased below values obtained in grafts preclotted conventionally. Survival studies in animals show no difference between blood-preclotted and fibrin-presealed prostheses both 3 and 7 days after implantation.
This report concerns our clinical experience with fibrin glue for local bleeding control and for sealing of vascular prostheses. Hemostasis could be achieved in 90% of 124 applications of the glue under different indications. Local application of fibrin adhesive is recommended in all types of bleeding difficult either to approach or control by conventional surgical technique. Complete sealing of low pore vascular grafts could be obtained in all operations under extracorporeal circulation and full heparinization. Highly porous grafts sealed with fibrin glue also were explored under conditions thus far requiring tightly woven grafts.