Kenneth M. Moser

Assessment of Pulmonary Photoscanning and Angiography in Experimental Pulmonary Embolism

The diagnostic reliability and specificity of pulmonary angiography and perfusion photoscanning were examined by applying both technics in two series of dogs: one subjected to multiple small pulmonary emboli; the other, to massive embolization. Interpretations of the angiograms and photoscans by two observers were correlated with each other and autopsy data. Analysis disclosed a high degree of agreement between the two technics. Application of both technics, however, led to a greater incidence and accuracy of embolic detection than either method provided alone. Both technics were subject to interpretive errors leading to false positive and false negative diagnoses. The factors promoting such errors are discussed. It is concluded that the two technics are complementary, not competitive, and that each is least reliable in detecting emboli at the extremes of size.

Correlation of lung photoscans with pulmonary angiography in pulmonary embolism

Abstract Ten patients with clinical-laboratory evidence suggesting extensive acute or chronic pulmonary thromoboembolism were studied by pulmonary photoscan and by utilizing radiolabeled macroaggregates of human serum albumin (R-MAA) and by angiographic technics. A high degree of correlation between the inactive areas of the radioscan and the nonperfused areas of the angiogram was noted. The radioscan accurately reflected the pattern of arteriolarcapillary blood flow, whereas the angiogram provided precise information regarding the pulmonary vascular anatomy. The two procedures should be considered complementary rather than competitive. Lung radioscanning was found to offer a readily available, safe, rapid and reliable screening technic for definition of nonperfused pulmonary areas. Problems in radioscan interpretation, including “false positives,” lack of anatomic precision and limitations of resolution are discussed. Such problems underscore the basic tenet that accurate evaluation of the radioscan requires that it be viewed in proper clinical context.

Perfusion and ventilation radioisotope lung scans in stenosis of the pulmonary arteries and their branches

Abstract In ten patients with stenosis of the pulmonary arteries, the relative distribution of right and left pulmonary blood flow was related to the localization of the coarctation by angiography and the degree of stenosis. To evaluate the distribution of pulmonary blood flow, the scintillation lung scan after injection of 131 I macroaggregated albumin (MAA) was utilized. Scintillation scanning of the lungs after inhalation of xenon-133 gas was also performed to assess the distribution of ventilation. The relative right to left pulmonary arterial blood flow distribution showed a good correlation with the catheterization pressure gradients and the angiographic findings. The distribution of ventilation was relatively unaffected. In a patient with a precordial murmur that exhibits disproportionate radiation to the axilla and back, an altered distribution of right to left perfusion helps to substantiate the diagnosis of stenosis of the pulmonary arteries. However, if the obstruction is bilateral and of equal degree, the distribution of blood flow may be normal. In patients with isolated acyanotic left to right shunts, the right to left distribution of pulmonary blood flow is apparently unaltered so that a lateral shift from the normal pattern raises the question of stenosis of the pulmonary arteries as an additional lesion. The finding of patchy areas of decreased radioactivity in both perfusion and ventilation lung scans in four of ten patients suggest that there may be a high incidence of emphysema or other lung disease in these patients.

Clinical observations in thromboembolic disease treated with fibrinolysin.

* Instructor in Medicine, Georgetown University, Washington, D. C. The therapeutic challenge posed by the thromboembolic diseases has not yet been met adequately. Evidence indicates that the anticoagulant drugs will provide a satisfactory degree of protection against both the development of thrombosis and the extension of such a process once discovered. These agents, however, exert little effect upon intravascular clot which is present when anticoagulant therapy is begun. Since this original thrombus is often a source of morbidity and mortality, effective therapy should include some method for its acute removal. Enhancement of plasma fibrinolytic activity would appear to offer the most direct approach to this goal of rapid thrombolysis. Although acute clot dissolution plus prevention of rethrombosis is the basic aim of treatment in all of the thromboembolic states, the details of therapy will depend upon the particular form of thrombotic disorder involved. Not only dosage and duration of therapy, but also the possible complications of a lytic-anticoagulant regimen will be related to the location and extent of the

The combined use of fibrinolytic and anticoagulant agents: Laboratory and clinical considerations∗

Abstract The therapeutic goal in thromboembolism includes not only clot dissolution but also the maintenance of vascular patency. Clinical and experimental evidence, as well as theoretic considerations, suggest that a sequence of clot dissolution followed by a recurrence of thrombosis may occur when fibrinolytic therapy is relied upon exclusively. Concomitant use of anticoagulant drugs appears to offer the best current method for avoiding this sequence. Heparin, because of its mechanism of action, prompt onset of effect and easy reversibility, seems to provide the most desirable anticoagulant supplement to fibrinolytic therapy. To insure that no increased hemorrhagic risk attends this combined thrombolytic-anticoagulant program, the dosage-response characteristics of each type of fibrinolytic agent should be accurately defined. Evidence suggesting antagonism between thrombolytic and anticoagulant agents in vivo has not been encountered but several aspects of this problem require further study. Failure to provide protection against a recurrence of thrombosis after initial fibrinolytic therapy can not only lead to misinterpretation of experimental data regarding the efficacy of fibrinolytic drugs but also may prevent attainment of optimum clinical results in man. While further development of fibrinolytic agents may obviate or alter the need for combination therapy, the concurrent use of fibrinolytic and anticoagulant drugs appears to provide the optimum therapeutic approach to thromboembolism at the present time.

Intravenous Administration of Fibrinolysin: Its Systemic Toxicity and Effect Upon Components of the Coagulation Mechanism

are no drugs which guarantee successful treatment of all patients. Furthermore, both toxicity and therapeutic value are related to the problem of dosage which, in turn, is dependent upon that inconstant factor known as &dquo;response of the individual patient.&dquo; Therefore, in assessing any new agent, we are faced with an equation which contains multiple variables and few known constants. Such complexities have led most workers to express the clinical value of new materials in terms of a toxic-therapeutic ratio based on study of large groups of patients at different dosage levels. During the past 2 years, we have been engaged in an investigation designed to define the toxictherapeutic ratio of fibrinolysin in various forms of thromboembolism. These studies

Diurnal variation in plasma euglobulin activity and fibrinogen levels. Preliminary report.

The therapeutic potential of agents capable of achieving clot dissolution in vivo by influencing the intrinsic fibrinolytic mechanism is of considerable magnitude.1-5 This potential, however, will not be fully realized until a number of basic problems relating to the fibrinolytic agents have been resolved. One such problem is the development of pra.ctical methods for the accurate and reliable measurement of plasma fibrinolytic activity. Controversy presently exists regarding not only the changes induced in plasma fibrinolytic activity by various agents but also the correlation between such changes and therapeutic success.6 It has become increasingly apparent that much of this controversy is rooted in the methodologic differences which abound in this field. Therefore, critical examination of all methods being used to estimate fibrinolytic activity is currently underway in our laboratory and others This preliminary report deals with one facet of our multiphasic investigations in this area, namely, definition of the factors which may influence euglobulin methods for measuring changes in plasma fibrinolytic activity. The plasma euglobulin fraction has been used by a number of investigators9-13 to ascertain the status of fibrinolytic activity in vivo. This fraction is precipitated by some variant of the procedure involving dilution and acidification of the plasma which was described by :Milstone.14 The precipitate is then dissolved in an appropriate buffer and its fibrinolytic activity assayed by: (1) clotting the euglobulin solution with calcium or thrombin and observing the lysis time of the resultant clot, (2) adding the euglobulin solution to a fibrinogen-thrombin system and observing the lysis time or (3) adding the solution to heated