Pulmonary embolism: what have we learned since Virchow? Natural history, pathophysiology, and diagnosis.

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are distinct but related aspects of the same dynamic disease process known as venous thromboembolism (VTE). An estimated 200,000 new cases occur in the United States every year, including 94,000 with PE, resulting in an incidence of 23 per 100,000 patients per year-cases. Without treatment, pulmonary embolism is associated with a mortality rate of approximately 30%, causing nearly 50,000 deaths per year. Moreover, based on post-mortem studies, two-thirds of the patients with pulmonary emboli remain undiagnosed. Clinically, PE may present as (1) isolated dyspnea, (2) pleuritic pain and/or hemoptysis, and (3) circulatory collapse. However, clinical history and examination can be notoriously misleading in reaching a diagnosis. A number of acquired etiologic risk factors (predispositions) are associated with a tendency to develop VTE. These include increasing age, immobilization, surgery, trauma, hospital or nursing home confinement, malignancy, neurologic disease with extremity paresis, as well as certain types of oral contraception and hormone replacement therapy. In addition, a variety of genetic risk factors, such as factor V Leiden, protein S or C deficiency have also been identified. However, in at least half of the instances, no predisposing factors can be identified (idiopathic PE). In the majority of cases thromboemboli originate in the deep veins of the calf or pelvis. The pathogenic conditions for VTE comprise a triad of factors and include (1) venous stasis, (2) hypercoagulable states, and (3) vascular endothelium injury. Occlusion of pulmonary arteries has variable and transient clinical and pathophysiologic consequences, involving both mechanical and reflex effects of vascular occlusion with a consecutive perfusion defect as well as the release of vasoactive and other inflammatory mediators. The objectives of this article are to present an overview of the etiologic and pathogenic factors promoting VTE as well as the pathophysiologic and inflammatory processes following PE.

Principle mechanisms underlying venous thromboembolism: Epidemiology, risk factors, pathophysiology and pathogenesis

Seipin: from human disease to molecular mechanism.

Pulmonary embolism and infarction; a review of the physiologic consequences of pulmonary arterial obstruction.

Pulmonary Embolism: What Have We Learned Since Virchow?: Treatment and Prevention

PULMONARY infarction has never been produced consistently in experimental animals, although numerous investigators have attempted it. 1 Virchow, in 1856, 1k observed that obstruction of branches of the pulmonary artery was not in itself sufficient to result in infarction. Karsner in 1912, 1f using turnip seed emboli in dogs, concluded that some factor other than an embolus was necessary to cause infarctions. Most authors reported that obstruction of branches of the pulmonary artery is not sufficient to cause infarction, if infarction is defined as necrosis of pulmonary tissue. An exception is the work of Steinberg and Mundy, 1i who produced occasional infarcts with employment of lead shot alone as emboli to occlude branches of the pulmonary artery. They, therefore, concluded that no factor except embolism is necessary to produce infarction. Clinical observation long ago revealed that pulmonary infarction following an embolus occurred usually in patients who had concomitant pulmonary

EXPERIMENTAL PULMONARY INFARCTION: Abnormal Pulmonary Circulation as a Prerequisite for Pulmonary Infarction Following an Embolus

ACUTE toxicity of mercurial diuretics has been noted frequently, but no extensive investigation of substances to counteract this toxicity has been reported. 1 There are two apparently distinct immediate reactions in human beings—a nonfatal hypersensitivity 2 and a fatal cardiac reaction. Experiments in animals 1a and observations in human beings 1c have determined that death is caused by ventricular fibrillation. Ascorbic acid has been used to detoxify chemotherapeutic heavy metals, especially arsenic. 3 It is an effective physiologic reducing agent. Certain animals, including dogs, can synthesize ascorbic acid and are therefore suitable experimental animals. We have extended the investigation of the mechanism of immediate death in dogs from mercurial diuretics for the three commonly employed ones, mercurophylline injection, mersalyl and theophylline and mercuhydrin. We have also studied the possible detoxifying effect of ascorbic acid on these preparations. The addition of another substance to a mercurial diuretic in an effort to

Mercurial diuretics; a comparison of acute cardiac toxicity in animals and the effect of ascorbic acid on detoxification in their intravenous administration.

RRECENT advances in the surgical alteration 1 and correction of certain congenital defects of the heart and the great vessels make it imperative that more exact diagnoses of such lesions be made. Intravenous catheterization of the heart has been found to be a most useful aid in ascertaining the condition when such congenital abnormalities are suspected. Forssmann, 2 in 1929, first introduced the method by catheterizing his own heart. In 1941, Cournand and Ranges 3 emphasized its applicability to the study of certain physiologic changes that occur in various types of heart disease. Blood samples may be obtained from various parts of the venous system, from the right side of the heart and from the pulmonary artery and its branches for estimation of the oxygen content. At the same sites, the blood pressure may be determined with a Hamilton manometer 4 or similar apparatus. Other investigators 5 have used this method to

Don W. Chapman

Papers

EXPERIMENTAL PULMONARY INFARCTION: Abnormal Pulmonary Circulation as a Prerequisite for Pulmonary Infarction Following an Embolus

Mercurial diuretics; a comparison of acute cardiac toxicity in animals and the effect of ascorbic acid on detoxification in their intravenous administration.

INTRAVENOUS CATHETERIZATION OF THE HEART IN SUSPECTED CONGENITAL HEART DISEASE: Report of Seventy-Two Cases

The use of oral mercuhydrin combined with ascorbic acid in cardiac decompensation.

Intravenous catheterization of the heart in the diagnosis of congenital heart disease