H Halbrook — Page 2 | PubMed Health

PubMedDate not supplied

Laboratory-clinical correlates of time-associated lesions in the vascular immunopathology of human cardiac allografts.

Ninety cardiac allograft recipients were studied for clinical and functional parameters during a 40-month period. Baseline histologic and immunocytochemical data were obtained from donors' hearts before transplantation, and serial endomyocardial biopsy specimens were studied histologically for cellular infiltrates and immunocytochemically for complement and immunoglobulin deposits and for components of the hemostatic, fibrinolytic, and natural anticoagulant pathways. Results were grouped according to the time from transplantation: the first 3 months, 4 to 21 months, and 22 to 40 months. Each group was evaluated for most frequently obtained immunocytochemical findings and results relevant to clinical-laboratory cooperation in patient management. During the first 3 months, findings of biopsy specimens from allografts that subsequently were going to be problem cases revealed depleted tissue plasminogen activator in arteriolar smooth muscle cells, and recipient IgM that was deposited on donor endothelium of stable grafts was diminished or absent in unstable allografts. In addition, vascular deposits of activated complement components were identified in 50 of 70 allografts. From 4 through 21 months after transplantation, vascular deposits of complement rarely were identified (even in patients who previously had positive biopsy specimens), and the principal vascular lesion was fibrin deposits with impaired anticoagulant pathways and inadequate fibrinolysis, usually without associated cellular infiltrates. From 22 through 40 months after transplantation, the principal vascular lesion was graft-induced atherosclerosis. These immunocytochemically defined qualitative and quantitative changes in unstable or failing allografts form a time-related spectrum of lesions that encompasses the emerging diagnostic entity of vascular rejection.

Biopsy↗

PubMedDate not supplied

Vascular lesions in biopsy specimens devoid of cellular infiltrates: qualitative and quantitative immunocytochemical studies of human cardiac allografts.

Biopsy specimens from 80 cardiac allografts were studied immunocytochemically with nine antibodies selected to identify cellular, immunologic, and vascular aspects of rejection. Results from these experiments were converted to a numeric base and used to calculate rejection indexes for each of these aspects of rejection. Pretransplantation biopsy specimens of donor hearts were studied to determine normal values, and clinical, catheterization, and conventional biopsy findings were used to classify patients as stable or unstable. The standard deviation of cellular and immunologic reaction indexes were overlapping for stable and unstable patients, but the vascular indexes for these patient groups were significantly different, suggesting that vascular damage defines clinical instability in cardiac allograft recipients. To study the vascular index in the absence of cellular infiltrates, biopsy specimens from 80 allografted hearts were selected to represent 40 patients with cellular infiltrates and 40 patients devoid of infiltrates. The results of this analysis revealed no difference in the vascular index between hearts that contained or did not contain infiltrates; the spectrum of vascular damage between the groups ranged from trivial to severe, suggesting that vascular damage was not dependent on cellular infiltrates. Concluding that these were independent events was not possible, however, because none of the hearts continuously were devoid of cellular infiltrates. Two groups of patients with significantly different vascular indexes then were studied for a systemic manifestation of coagulation by measurement of their thrombin times. The group with low vascular index was found to have significantly prolonged thrombin times compared to the group with high vascular index, and a trend to less prolongation of thrombin times was observed in another group with high cellular index. The relation of these results with cardiac allograft vasculopathy is not established, but the results suggest hitherto unexplored roles for quantitative expressions of hemostasis, fibrinolysis, and anticoagulation in the pathophysiology of vascular disease in allografts.

Adult↗