Pulmonary edema in fatal heroin overdose: immunohistological investigations with IgE, collagen IV and laminin — no increase of defects of alveolar-capillary membranes

Abstract

Pulmonary edema complicating heroin overdosage is a well recognized entity and regarded as the major mechanism contributing to death in heroin addicts. It’s pathogenesis is unknown, several mechanisms are discussed: hypoxia-induced increase of pulmonary capillary permeability, depressed myocardial contractility, centrally induced respiratory depression, primary toxic effects on the alveolar capillaries and acute anaphylactic shock. The present study included opiate-related deaths (n=23) and a control group of sudden cardiovascular deaths (n=12) to verify the hypothesis, that defects of the alveolar capillary membranes and/or an acute anaphylactic reaction leads to pulmonary congestion, edema and hemorrhages. Lung specimens were obtained from these 35 autopsies of persons autopsied in the Institute of Forensic Medicine, University of Bonn, in 1997 and 1998. All specimens were examined with hematoxylin–eosin, prussian blue and investigated with immunohistological methods using primary antibodies against collagen IV, laminin and IgE. Defects of the basal laminae of the alveoli were found, demonstrated by laminin and collagen IV, and the number of IgE-positive cells was counted in both groups. There was an increased but not significant number of IgE-positive cells in the heroin-group and defects of the epithelial and endothelial basal laminae were found in both groups without significant differences.

Introduction

Heroin-induced pulmonary edema (‘heroin-lung’) was first described by Osler [1] in 1880. The clinical manifestation is characterized by pulmonary congestion, edema, hemorrhages and respiratory insufficiency. Although the cause for the increase in the permeability of alveolar capillary membranes remains obscure, several mechanisms have been suggested. Increased pulmonary capillary permeability in fatal drug addiction due to defects of the basement membrane is discussed as one reason for so called ‘heroin-lung’ [2]. One of the most discussed causes remains the profound hypoxemia that is found secondary to the heroin-induced hypoventilation and coma [3]. However, the same degree of hypoxemia was found in patients undergoing overdosage of barbiturates but without developing pulmonary edema, and when it does occur, it usually develops after several hours to days after hospitalization [4]. This suggests, that other factors may be important. To verify the hypothesis of primary toxic effects with defects/interruptions of the alveolar capillary membranes, antibodies against laminin and collagen IV as components of the normal basement membrane were used. To verify the hypothesis of acute anaphylactic reaction, the number of IgE-positive cells was counted. The normal basement membrane, as a blood–gas barrier (Fig. 1), can be separated into different zones ultrastructurally and immunohistochemically. The electron-lucent zone (lamina lucida) and the electron-dense zone (lamina densa) contain components such as collagen IV, laminin, nidogen, proteoglycans and fibronectin which help to bind epithelial cells to the basement membrane [5], [6], [7]. Type IV collagen is suggested to be responsible for much of the strength of the blood–gas barrier [8]. As a cause of pulmonary edema in cases of acute heroin fatalities, hypoxia-induced increase of pulmonary capillary permeability [9], depressed myocardial contractility [10], centrally induced respiratory depression, primary toxic effects on the alveolar capillaries that proved lethal [11] and acute anaphylactic shock [12] are discussed. In 1972 Katz et al. reported increased protein levels in heroin pulmonary edema in contrast to cardiac edema [13]. Also disturbances of lung functions are known in cases of pulmonary edema associated with heroin overdose [3], [14], [15].