Arterial expression of the plasminogen activator system early after cardiac transplantation.

OBJECTIVES: Recent studies suggest that alterations in tissue thrombolysis as well as the inward migration of cells may be specific events that contribute to coronary artery narrowing after cardiac transplantation. Plasminogen activators and inhibitors play a central role in governing not only tissue thrombolysis, but also vascular cell migration. The purpose of this study was to examine arterial wall expression of the plasminogen activation system in coronary arteries during graft vascular disease initiation and progression. METHODS: Using in situ hybridization and immunocytochemistry, the expression patterns of uPA and PAI-1 in coronary arteries from cardiac allografts were compared to those of young individuals without disease. RESULTS: Both PAI-1 and uPA were over-expressed early after transplantation and as late as 27 months post grafting. Over-expression of these molecules preceded morphological evidence of graft vascular disease. Of special note was the adventitial expression of uPA and PAI-1 in microvessels and myofibroblasts. In contrast, the expression of uPA and PAI-1 in normal coronary arteries was confined to endothelial cells of the central lumen, as well as low levels of expression in intimal and medial smooth muscle cells. CONCLUSIONS: Despite morphologic similarities between normal and transplant coronary arteries, differences were noted in the vascular expression pattern of uPA and PAI-1. The exact role of these molecules in graft vascular disease requires further study; however, it is intriguing to consider that a local imbalance in the plasminogen system may contribute to arterial wall thrombosis and/or excessive cell migration and the genesis of complex vascular lesions.

Tissue fragments recovered at cardiac surgery masquerading as tumoral proliferations. Evidence suggesting iatrogenic or artefactual origin and common occurrence.

The entity described in the literature as a "distinctive cardiovascular lesion" resembling histiocytoid hemangioma and more recently referred to as "mesothelial/monocytic incidental cardiac excrescence" may not be a true proliferative lesion. Rather, it may represent an artefact produced by suctioning of the pericardial cavity during cardiac surgery. This hypothesis was explored by comparing two index cases of cardiac histiocytoid hemangioma-like lesions (HLLL) to (a) the contents of extracorporeal bypass pump (ECBP) filters in 22 random cardiac surgical cases, and (b) material adherent to mediastinal and pericardial drains in 15 random post-cardiac surgery cases. In 18 of the 22 ECBP filter cases (82%) and two of the 15 postsurgery cases (13%), tissue fragments indistinguishable from the HHLL index cases were identified. These filter and drain fragments had light microscopic, immunohistochemical, and ultrastructural features identical to those of the index cases, as well as to the HHLLs described in the literature. In neither index case, nor in the study patients, were any proliferative lesions identified at surgery. Three study cases subsequently came to autopsy, and no proliferative lesions were found. This and other evidence strongly suggest that these lesions not only are artefactual, but also are a common occurrence. They are likely produced during cardiac surgery by the cardiotomy suction, with compaction of friable mesothelial strips, other tissue debris, and fibrin into tumor-like fragments that may be transported around the operative site on the suction tip.

Anatomic correlations of the long-axis views in biplane transesophageal echocardiography.

The number of views obtainable during transesophageal echocardiography (TE) has been limited by the fixed position of the transducer at the end of the probe. This has confined standard TE studies to short-axis tomography of the heart and aorta. Recently, a biplane TE probe has become available that is capable of both long- and short-axis imaging. This study prospectively assessed the application of the long-axis plane of the biplane probe in providing complementary long-axis views in ambulatory patients. Six standard long-axis views could be obtained and were compared with corresponding anatomic sections to illustrate anatomic relations and facilitate structure identification. The long-axis views provide a better appreciation of the 3-dimensional nature of cardiac anatomy and function, especially in demonstrating the relation of vertically aligned structures.

Brief clinical report: short rib-polydactyly syndrome, Majewski type.

We describe a baby with external and internal anomalies of the Majewski form of the short rib-polydactyly (SRP) syndromes. Previously unreported abnormal vertebral bodies, delayed ossification of the sternum and fibulae, and a diencephalic hamartoma are noted. These abnormalities and minimal histologic abnormality at the chondro-osseous junction suggest that this syndrome may be heterogeneous or more variable than previously known.

Tamm-Horsfall protein: unusual, large perinephric deposits.

A case in which unusually large deposits of Tamm-Horsfall protein were identified in perinephric adipose tissue is presented. The deposition around the kidney in this case was most likely due to calyceal rupture, secondary to distal ureteric obstruction. The peculiar gross and microscopic appearance of these deposits, their intense staining with the periodic acid--Schiff technique, and their association microscopically with epithelial fragments raised the possibility of infiltration by mucin-producing adenocarcinoma. The localization of Tamm-Horsfall protein in the deposits by the immunoperoxidase technique helped to confirm their true nature.

Contraction bands in visceral and vascular smooth muscle.

Smooth muscle contraction bands (SMCBs) have been described in the gastrointestinal tract, subsequent to acute ischemia, and in the coronary arteries of animals and individuals with a sudden death; in these circumstances SMCBs have been postulated to serve as a premortem marker, and suggested as diagnostically useful. The present investigation was undertaken to determine whether the presence of SMCBs could be correlated with a premortem clinical condition. Retrospectively, the routinely prepared histological sections from 76 autopsy and 93 surgical cases were screened semiquantitatively for the presence of SMCBs. The autopsy sections examined included the gastrointestinal tract, the prostate, and the coronary arteries, as well as all other smooth muscle-containing tissues; the surgical specimens included: coronary artery endarterectomies; saphenous vein bypass grafts; temporal artery biopsies; prostatic curettings; colectomies; varicose veins; leiomyomas of uterus, bowel, and skin; and, leiomyosarcomas. The clinical and pathology reports were reviewed for patient demographics, major clinical diagnoses, presence of shock, details of any resuscitation attempts, time interval to postmortem, and the cause of death. SMCBs were evident in 100% of the gastrointestinal and prostate, and in 96% of the coronary artery autopsy sections examined. All surgical specimens were positive for SMCBs, the exceptions being leiomyomas (positive in 13 of 22; 60%) and leiomyosarcomas (4 of 5; 80%); SMCBs in surgical specimens were less prominent when compared with those observed in autopsy tissue. No correlation was found between the presence of SMCBs and any clinical or demographic parameter assessed, because of the virtual universal occurrence of the SMCBs. The presence of less distinct SMCBs in surgical specimens may very well be artifactual, akin to myocardial and skeletal muscle contraction bands. The observation that SMCBs at autopsy are virtually ubiquitous suggests that they are best considered an agonal phenomenon, and a nonspecific pathological finding.

Patterns of failure in Ionescu-Shiley bovine pericardial bioprosthetic valves.

The experience of the University of Ottawa Heart Institute with valvular replacement by Ionescu-Shiley bovine pericardial bioprostheses has been recently reviewed. The focus of the present study is to examine the patterns of valve failure in a subgroup of these prostheses, those that required explanation for valve failure caused specifically by cusp wear and tears. A total of 22 aortic and six mitral standard-profile valves failed in this way. Twenty-five of these valves were reassessed and are the subject of this paper. Twenty-eight holes and 56 cusp tears occurred in these valves in locations which, along with coexistent pathologic findings, suggested that the cusp commissural suture/alignment stitch was the point of their origin. The importance of this observation and postulation about the genesis of these cases of valve failure lies in the potential for improvement of this valve's performance by modifications of its manufacture.

Paradoxic air embolism in the absence of an intracardiac defect.

A 58-year-old man experienced paradoxic air embolism with passage of air from the systemic venous to the systemic arterial circulation with subsequent stroke and death. No intracardiac shunt was present. Pulmonary fibrosis concomitant with severe pulmonary arterial hypertension appears to have been responsible for the air traversing the pulmonary capillary bed. This unusual outcome of a complicated central venous catheterization must be borne in mind and guarded against in similar patients.

A study of the sequential morphologic changes after manual coronary endarterectomy.

Manual coronary endarterectomies heal in the long-term by a poorly understood process of myofibrointimal proliferation. A retrospective analysis of detailed cardiovascular pathologic examinations of 51 patients dying at varying intervals after endarterectomy provides insight into the sequence of this proliferative response. Twenty-one patients died within 7 days, 6 at 8 to 30 days, 3 at 31 days to 6 months, 4 at 6 months to 5 years, and 17 at more than 5 years after endarterectomy. The observations made suggest that the denuded arterial surface heals after the fibrin-platelet mural thrombus that covers it is organized and is replaced by fibrosis and myofibroblast proliferation. In unusual cases proliferation is exuberant, resulting in significant restenosis, an outcome in which recurrent atherosclerosis contributes to only a minor degree. This is the first series in which the sequential reparative changes at varying times after manual coronary endarterectomy have been studied.

Valve failure caused by cusp tears in low-profile Ionescu-Shiley bovine pericardial bioprosthetic valves.

The pathologic findings in two low-profile Ionescu-Shiley bioprostheses that failed because of cusp tears are presented. Both valves were in the mitral position, one in place 28 months and the other 40 months. Observation of the valves and their tears suggests that stress at the cusp alignment stitches may be important in the genesis of the tears.

Retrograde dissection of the left main coronary artery after endarterectomy: a rare complication.

The case of a 72-year-old woman who died after bypass grafting and endarterectomy of the left anterior descending coronary artery is described. At autopsy a large intramural dissection of the left anterior descending artery that extended proximally to the left main ostium from the endarterectomy site was found. The dissection was associated with clotting of the false lumen and of the graft, and with a myocardial infarct that precipitated this woman's intraoperative death.

Patterns of failure in Hancock pericardial bioprostheses.

A series of Hancock pericardial valve bioprostheses was reviewed for cases of primary valve failure. Thirteen mitral and 10 aortic valve explants were recovered from 21 adult patients. Mitral valves had been in place for a mean of 56.4 months, and aortic valves for 53.8 months. All valves failed with cusp tears from stents (with a mean of 1.7 for mitral valves and 2.6 for aortic valves) in a predictable pattern, suggesting that wear and stress at cusp stitch sites are important in their pathogenesis. The topography of these tears is illustrated as are the less common associates of primary failure, such as calcification, fibrosis, and thrombosis. Similarities and differences of this valve's failure compared with that of the Ionescu-Shiley pericardial valve are discussed.

Are temperatures attained by donor hearts during transport too cold?

Excessive myocardial cooling may have detrimental effects on donor heart integrity. This study assessed the standard technique for donor myocardial preservation using hearts from seven mongrel dogs (mean weight 192.7 gm), which were arrested, excised, and placed in a cooler containing saline and ice. Temperature probes placed in both the left and right ventricular free walls and the septum revealed that, after cardioplegia, temperatures fell to 10.3 degrees, 7.5 degrees, and 7.6 degrees C, respectively. Temperature decreased to below 1 degree C after 75, 75, and 60 minutes for the left ventricle, right ventricle, and septum, respectively, independent of the size of the heart (range = 104 to 322 gm). After 4 hours of cooling, temperature was below 0 degrees C throughout the myocardium. Examination with an electron microscope showed similar serial changes over 4 hours in all hearts, including moderate-to-severe cytoplasmic and nuclear swelling and mitochondrial calcium deposits. Cell membranes remained intact, which suggests that the damage was not irreversible. We conclude that current donor heart preservation techniques may result in unacceptably low myocardial temperatures that cause reversible myocardial injury.

Comparative results with the St. Jude Medical and Medtronic Hall mechanical valves.

This study compared the clinical performance of the St. Jude Medical and Medtronic Hall mechanical valves in isolated aortic or mitral valve replacement. From 1984 to 1993, 349 St. Jude Medical valves (aortic 237, mitral 112) and 465 Medtronic Hall valves (aortic 272, mitral 193) were implanted in 814 patients at the University of Ottawa Heart Institute. The patients had similar preoperative characteristics. The hospital mortality rate for aortic valve replacement was 3.4% with the St. Jude Medical valve and 5.8% with the Medtronic Hall valve (p = 0.26) and the rate for mitral valve replacement was 8.9% with the St. Jude Medical valve and 11.9% with the Medtronic Hall valve (p = 0.54). Actuarial estimates of survival and freedom from complications were calculated. At 5 years the actuarial probability of survival (including hospital deaths) for aortic valve replacement was 86% +/- 3% with the St. Jude Medical valve and 68% +/- 4% with the Medtronic Hall valve (p = 0.0001) and for mitral valve replacement was 75% +/- 7% with the St. Jude Medical valve and 70% +/- 4% with the Medtronic Hall valve (p = 0.54). The most common cause of late death was cardiac failure and no deaths were caused by structural failure. The 5-year probability of freedom from bleeding after aortic valve replacement was 99% +/- 1% with the St. Jude Medical valve and 95% +/- 2% with the Medtronic Hall valve (p = 0.06) and after mitral valve replacement 99% +/- 1% with the St. Jude Medical valve and 97% +/- 2% with the Medtronic Hall valve (p = 0.37). The 5-year probability of freedom from thromboembolism after aortic valve replacement was 88% +/- 4% with the St. Jude Medical valve and 81% +/- 3% with the Medtronic Hall valve (p = 0.08) and after mitral valve replacement was 85% +/- 7% with the St. Jude Medical valve and 77% +/- 5% with the Medtronic Hall valve (p = 0.17). Reoperation was uncommon and there were no cases of structural valve failure. The 5-year actuarial estimate of freedom from reoperation therefore for aortic valve replacement was 99% +/- 1% with the St. Jude Medical valve and 96% +/- 2% with the Medtronic Hall valve (p = 0.09) and for mitral valve replacement was 98% +/- 2% with the St. Jude Medical valve and 95% +/- 3% with the Medtronic Hall valve (p = 0.40).(ABSTRACT TRUNCATED AT 400 WORDS)

The surgical anastomoses after orthotopic heart transplantation: clinical complications and morphologic observations.

From May 1984 through June 1993, 162 patients have undergone orthotopic heart transplantation at the University of Ottawa Heart Institute. Thirty-three deaths occurred, and postmortem examinations were performed in 29 of these cases. This study evaluated the surgical anastomoses of these patients' hearts, an aspect of orthotopic heart transplantation that has not been well described in the literature. The major findings encountered were two cases of stenosis at the left atrial anastomosis, one case of aortic anastomotic tear, one case of pulmonary artery anastomotic kinking, one case of left atrial suture line mural thrombus and possible coronary embolism, and one case of extramural compression of a coronary artery by an anastomotic suture. Other findings when the suture lines were examined included residual native valve remnants, protruding tissue tags or other tissue remnants, mural thrombi, and protruding free suture ends. These findings are described, illustrated, and discussed in the context of the published literature on the subject.

Analysis of deaths after heart transplantation: the University of Ottawa Heart Institute experience.

This study reviews the clinical outcome of the 132 orthotopic heart transplantations performed at our institute from 1984 through 1991 and focuses on the pathology of those patients who died. The study comprised 124 adults (mean age, 45.6 +/- 0.9 years) and eight children. Twenty-six adult and one pediatric deaths occurred. Operative mortality (within 30 days) was 10.6%, with 84.8% of patients surviving to discharge. Actuarial probabilities of survival at 1 and 5 years were 84% +/- 3% and 71% +/- 6%, respectively. Of the 27 deaths, six (22.2%) occurred in the operating room (from hemorrhage, graft failure, and hyperacute rejection); 14 (51.9%) occurred in-hospital after surgery (from sepsis, rejection, cytomegalovirus disease, or myocardial infarct), and seven (25.9%) occurred after discharge (from rejection and/or recurrent coronary artery disease). Two groups of patients were at higher risk: patients in cardiogenic shock requiring pretransplantation mechanical support, with in-hospital mortality of 39.1%; and patients with previous valve replacement who were taking oral anticoagulants, with intraoperative mortality of 50.0%. Pathologic examination revealed occasional instances of unsuspected coronary artery disease in the donor hearts with more than 50% stenoses of the left anterior descending coronary arteries in three of 21 (14.3%) of cases. Complications of the transplantation or related therapeutic procedures were common among those who died. The complications ranged from functionally insignificant anatomic curiosities to life-threatening problems. These complications are tabulated and shown.

Complications of cardiac valve surgery and their autopsy investigation.

This review describes the broad spectrum of complications that may attend cardiac valve replacement surgery. Patient morbidity and mortality may be a consequence of preoperative condition or care, operative complications, or postoperative course. Careful autopsy examination of patient deaths, correlated with clinical information, will usually reveal an explanation for a patient's demise, as well as precipitating or contributing factors. The autopsy is particularly valuable if it can demonstrate technical, prosthetic, or other unexpected findings whose communication to clinicians and manufacturers can serve to improve the care of subsequent patients, or the development of improved prostheses.

Thyroid heterotopia as a rare cause of intrapericardial tumoral mass case report and review of the literature.

This article describes the interesting discovery of a large tumoral mass formed of heterotopic thyroid tissue inside the pericardial cavity of an elderly man who died of unrelated causes. Heterotopic thyroid tissue may be found in many locations throughout the body. Intracardiac and intrapericardial locations, however, are exceptionally rare-this is only the second report of intrapericardial thyroid heterotopia. Such cases may be explained by the proximity of the developing cardiac structures and the foregut, the latter containing thyroid primordia during early embryogenesis.

Coronary artery erosion and dissection: an unusual complication of mitral annular calcification.

This article describes a 42-year-old male patient with a longstanding history of insulin-dependent diabetes mellitus, systemic arterial hypertension, and chronic renal failure. The patient had severe mitral annular calcification (MAC) identified at autopsy. This MAC was of an amorphous, caseous-appearing type; it displaced the posterior mitral valve leaflet and extruded into the myocardium of the lateral and posterolateral left ventricle to involve the epicardial surface. The MAC produced extramural erosion of the wall, and dissection into the media, of the first left/obtuse marginal coronary artery. This coronary artery involvement by, and other complications of, MAC are discussed.

Amyloid and the cardiovascular system: A review of pathogenesis and pathology with clinical correlations.

The process of amyloidogenesis may complicate diverse disease states. It may be systemic and have serious clinical sequelae; in other circumstances, it is a localized phenomenon and functionally insignificant. In many cases its manifestations may be predictable, with knowledge of the responsible protein. Perhaps no organ system better exemplifies this than the cardiovascular one in which amyloid may form from precursor proteins as varied as immunoglobulin light chains, serum amyloid-A protein, transthyretin and its variants, atrial natriuretic factor, ß2-microglobulin, and others. This review describes the state of knowledge in relation to cardiovascular amyloidosis, with particular emphasis on what is currently known about the pathogenesis of the process and the related pathology of the various anatomic components of the cardiovascular system.