Dennis S. Reison

Management of lymphoproliferative disorders after cardiac transplantation

We conducted a retrospective study of 516 cardiac recipients who underwent transplantation between April 1983 and April 1992, 19 of whom had development of post-transplantation lymphoproliferative disorders (PTLDs). These 19 patients presented with involvement of lung (5), gastrointestinal tract (5), disseminated disease (6), and adenoids and lymph nodes (3). B-cell proliferations ranging from an atypical hyperplasia to malignant lymphoma developed in 18 patients, and mixed cellularity Hodgkins disease developed in 1 patient. The 19 patients with PTLD displayed a predominance of both women and cardiomyopathy as the indication for transplantation when compared with two separate control populations. No correlation was found between demographic criteria analyzed and (1) early versus late diagnosis of PTLD after transplantation, (2) the site of PTLD involvement, or (3) the histopathologic category of the PTLD lesion. Patients with gastrointestinal tract and lung PTLD involvement enjoyed an improved survival after both transplantation and PTLD diagnosis when compared with patients with PTLD involvement of all other extranodal sites. We report a high incidence of PTLD involving the lung and gastrointestinal tract in our cohort study. These sites of involvement responded better to a reduction in immunosuppression than did the other extranodal sites of involvement.

The effect of captopril on renal, coronary, and systemic hemodynamics in patients with severe congestive heart failure

The effects of captopril (CPT), an oral angiotensin-converting enzyme (ACE) inhibitor, on systemic failure (CHF). In 15 patients, CPT decreased mean arterial pressure from 75 +/- 3 to 60 +/- 3 mm Hg associated with a 16% increase in cardiac output, a 24% reduction in systemic vascular resistance, and a 36% decrease in pulmonary capillary wedge pressure (all p less than 0.01). Despite the improved cardiac output, renal blood flow, creatinine clearance, and sodium excretion did not rise during the first 2 days of CPT therapy. In eight patients, coronary sinus blood flow diminished from 98 +/- 11 to 82 +/- 9 ml/min (p less than 0.01) following drug administration in association with a fall in arterial pressure and heart rate but no change in coronary sinus oxygen inhibitor failed to improve renal hemodynamics. In addition, initial CPT administration produced a decrease in coronary blood flow that was related to a decrease in myocardial oxygen requirements.

Cinevideodensitometric analysis of the effect of coronary angioplasty on coronary stenotic dimensions

The accuracy and reproducibility of caliper and cinevideodensitometric measurements of coronary stenotic dimensions were compared in radiographic phantom models and in coronary arteriograms of 28 patients undergoing coronary angioplasty. Projected, single-plane coronary cine frames were analyzed by a computer-assisted videodensitometric method, which measures stenotic cross-sectional area without assumptions about lesion geometry. The accuracy (2.4%) and precision (+/- 1.9%) of cinevideodensitometry for measuring percent area stenosis in Plexiglas models of eccentric stenotic lesions was superior to the accuracy (24.7%) and precision (+/- 5.4%) of caliper measurements. Interobserver variability was significantly (p less than 0.05) better for cinevideodensitometric (r = 0.98; SEE = 6.4%) than for caliper measurements (r = 0.87; SEE = 13.1%). After angioplasty, percent diameter stenosis measured by calipers fell from 70 +/- 12% to 30 +/- 15%. Mean percent area reduction measured by cinevideodensitometry fell from 89.1 +/- 8% to 40.1 +/- 22% and stenotic area increased five-fold, from 0.59 +/- 0.5 to 3.47 +/- 1.6 mm2. Pre and post PTCA gradients did not correlate with lesion dimensions. Cinevideodensitometric measurements of absolute stenotic dimensions were more reproducible than relative measurements expressed as a percentage, due to the tapered caliber of normal arterial segments. Thus, cinevideodensitometric measurements were more accurate and reproducible than caliper measurements. The angiographic effects of coronary angioplasty are best measured by cinevideodensitometry, because residual lesions post PTCA are often eccentric, have indistinct margins, and are better characterized by changes in area than by changes in diameter.

Exercise-Induced myocardial ischemia in patients with coronary artery disease: Lack of evidence for platelet activation or fibrin formation in peripheral venous blood

The hypothesis that exercise-induced myocardial ischemia is associated with abnormal platelet activation and fibrin formation or dissolution was tested in patients with coronary artery disease undergoing upright bicycle stress testing. In vivo platelet activation was assessed by radioimmunoassay of platelet factor 4, beta-thrombo-globulin and thromboxane B2. In vivo fibrin formation was assessed by radioimmunoassay of fibrinopeptide A, and fibrinolysis was assessed by radioimmunoassay of thrombin-increasable fibrinopeptide B which reflects plasmin cleavage of fibrin I. Peripheral venous concentrations of these substances were measured in 10 normal subjects and 13 patients with coronary artery disease at rest and during symptom-limited peak exercise. Platelet factor 4, beta-thromboglobulin and thromboxane B2 concentrations were correlated with rest and exercise catecholamine concentrations to determine if exercise-induced elevation of norepinephrine and epinephrine enhances platelet activation. Left ventricular end-diastolic and end-systolic volumes, ejection fraction and segmental wall motion were measured at rest and during peak exercise by first pass radionuclide angiography. All patients with coronary artery disease had documented exercise-induced myocardial ischemia manifested by angina pectoris, ischemic electrocardiographic changes, left ventricular segmental dyssynergy and a reduction in ejection fraction. Rest and peak exercise plasma concentrations were not significantly different for platelet factor 4, beta-thromboglobulin, thromboxane B2, fibrinopeptide A and thrombin-increasable fibrinopeptide B. Peripheral venous concentrations of norepinephrine and epinephrine increased significantly (p less than 0.001) in both groups of patients. The elevated catecholamine levels did not lead to detectable platelet activation. This study demonstrates that enhanced platelet activation, thromboxane release and fibrin formation or dissolution are not detectable in peripheral venous blood of patients with coronary disease during exercise-induced myocardial ischemia.

Altered Rheological Properties of Blood following Administrations of Tissue Plasminogen Activator and Streptokinase in Patients with Acute Myocardial Infarction

Tissue blood flow is determined by rheological properties of blood as well as by vascular resistance. In acute myocardial infarction patients who participated in the TIMI I trial, we compared the effects of recombinant tissue plasminogen activator (rt-PA) and streptokinase (SK) on blood rheological properties and plasma fibrinogen concentration. Blood viscosity was determined by using a coaxial cylinder viscometer at shear rates, gamma, of 0.01-200 sec-1. Red blood cell (RBC) deformability was studied by filtration through polycarbonate microsieves with pore size of 3 and 5 microns. Therapy with rt-PA resulted in slight decreases but statistically significant in blood viscosity from 5.2 +/- 0.5 to 4.9 +/- 0.4 cP (gamma = 52 sec-1), plasma viscosity from 1.36 +/- 0.09 to 1.32 +/- 0.06 cP, and plasma fibrinogen from 0.26 +/- 0.04 to 0.21 +/- 0.03 g/dl. SK therapy resulted in reductions in blood viscosity from 5.1 +/- 0.5 to 4.6 +/- 0.3 cP, plasma viscosity from 1.26 +/- 0.10 to 1.16 +/- 0.03 cP, and fibrinogen from 0.26 +/- 0.06 to 0.10 +/- 0.05 g/dl. Changes observed with SK were significantly greater than those observed with rt-PA (all p less than 0.05), and the differences persisted at 10 days after thrombolytic therapy. RBC deformability was similar in the two groups. The greater reduction of blood viscosity after SK than rt-PA suggests that, for a given degree of arterial patency, myocardial blood flow may be better maintained with SK than rt-PA in patients with acute myocardial infarction.