A study of various morphologic variables and troponin I in pericardial fluid as possible discriminators of sudden cardiac death

Pathologists frequently examine victims of sudden cardiac death. In some cases, a firm diagnosis of cardiac-related death can be made based on conclusive gross and histologic findings. In many other cases, we find evidence supportive of, but not diagnostic of, cardiac death (e.g., atherosclerotic coronary artery disease, cardiomegaly, myocardial scarring). A final cohort consists of cases of sudden death with minimal to mild cardiac disease, no other significant pathology, and negative toxicologic studies. This prospective study compared 38 cardiac-related deaths with 52 control cases with respect to concentrations of pericardial cardiac troponin I (cTnI), heart weight, evidence of old and/or recent myocardial injury, and presence of significant coronary artery disease. The influence of documented chest trauma and/or perimortem cardiopulmonary resuscitation (CPR) on levels of cTnI was also analyzed. Even though median cTnI levels were significantly higher in cardiac deaths than in controls (p = .003), cTnI was not found to be a significant predictor of cardiac deaths, as determined by discriminant analysis (p = .52). Heart weight >500 g, evidence of old and recent myocardial injury, and significant coronary artery disease were seen statistically more often in cardiac deaths than in controls (p < or = .005 in each case), and median age was significantly higher in cardiac deaths than in controls (p = .001). Based on a stepwise logistic regression model, significant coronary artery disease, old and recent myocardial injury, and heart weight >500 g were found to contribute significantly to the prediction of cardiac death. Finally, neither chest injury nor CPR significantly affected concentrations of cTnI in pericardial fluid. These data confirm that the presence of acute and remote myocardial injury, significant coronary artery disease, and cardiomegaly (heart weight >500 g) strongly supports the diagnosis of a cardiac-related death. In contrast to a recently published report, we do not find that elevated concentrations of cTnI in pericardial fluid are strong indicators of cardiac-related deaths using our methodology.     

Mast cell tryptase and hemolysis after trauma

BACKGROUND: We have previously found increased mast cell tryptase in accidental deaths due to trauma, indicating that mast cell degranulation had occurred. The present study was designed to confirm the previous observation and to determine if tryptase release after trauma is acute or delayed. Furthermore, the importance of hemolysis and direct trauma to the mast cells was investigated. MATERIALS AND METHODS: Mast cell tryptase was measured in post-mortem blood from the femoral vein in 27 cases of death from trauma and in 27 control cases by means of a commercially available immunoassay. The trauma cases were further classified into groups with single versus multiple trauma, and groups with short survival time (i.e. death at the scene of the accident) versus longer survival time (death in hospital). In five multi-trauma deaths, blood was sampled locally from the sites of crush injury. RESULTS: The mean value of tryptase in femoral vein blood was 35.6+/-34.6 microg/l in the entire trauma group and 14.7+/-6.5 microg/l in the controls (P<0.005). In bloody liquid sampled from crush injuries, tryptase was substantially elevated in all cases, with a mean of 227+/-146 microg/l. In cases with short survival time, tryptase was significantly higher than in those who died after several hours or days in hospital (P<0.001). No statistically significant difference was seen between multi- and single-trauma cases. A correlation between hemolysis in the samples and elevated tryptase was found only in the trauma cases (P<0.05), but experimentally induced hemolysis in vitro was not found to influence the measurements. CONCLUSION: Mast cell tryptase becomes elevated in trauma deaths and this seems to be ascribable either to direct mechanical injury to tissue mast cells and/or to cell lysis. In patients initially surviving severe injuries, the effects of massive release of histamine and other mast cell mediators might be of importance for treatment strategies and prognosis.     

Detection of apoptosis in ischemic heart. Usefulness in the diagnosis of early myocardial injury

Myocardial samples of hearts with histologic findings of acute myocardial infarction (group A), sudden coronary deaths without histologic changes (group B), and chronic ischemic heart disease (group C) were analyzed to investigate the appearance of apoptosis in acute and chronic ischemic cardiac disorders. This analysis involved the morphologic detection of DNA strand breaks in myocyte nuclei by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay and the biochemical determination of DNA laddering in the myocardium using archival formalin-fixed, paraffin-embedded tissue sections of human myocardium. The authors demonstrated that apoptosis of myocardial cells could occur after ischemic myocardial cell injury. In all documented cases of acute myocardial infarction (group A), the infarcted area included extensive presence of both apoptosis and necrosis. In the tissue bordering on and away from the obviously infarcted areas, positive nuclei were intermingled with nonstained normal myocytes. The number of positive nuclei decreased with the distance from the infarction foci. In group B, myocardial samples showed focal or diffuse nuclear positivity of varying degrees for apoptosis, confirming the presence of myocardial ischemic cell death, whereas the histologic diagnosis remained inconclusive. This finding suggests that apoptosis could be used as a marker for acute ischemic injury. In group C, stained nuclei were dispersed with intermingled normal cardiomyocytes.     

Sudden cardiac death due to giant cell inflammatory processes

Granulomatous inflammation of the myocardium may occur in a number of systemic disease processes including those with infectious etiologies such as fungal, mycobacterial and parasitic infections, as well as hypersensitivity reactions, and rarely autoimmune disorders. In many of these disorders, giant cells are components of the inflammatory infiltrate. Systemic granulomatous processes of unknown pathogenesis, most notably sarcoidosis, may also be associated with involvement of the myocardium. Occasionally, these disorders are associated with sudden death due to pathologic involvement of the heart. In contrast, giant cell myocarditis, also known as idiopathic myocarditis, a rare, frequently fulminant and fatal disorder of unknown etiology, is isolated to the heart and lacks systemic involvement. This disorder is most commonly diagnosed at autopsy. We present two cases in which sudden death resulted from a giant cell inflammatory process affecting the myocardium. Both individuals lacked antemortem diagnoses and collapsed at their respective places of employment. These cases compare and contrast the clinical and pathologic issues involved in the differential diagnoses of the subgroup of sudden cardiac deaths resulting from giant cell inflammatory processes that affect the myocardium, as well as the value of histologic examination and immunohistochemical studies.     

Tongue bite injuries--a diagnostic criterium for death in epileptic seizure?

Bite marks of the tongue are often associated with epileptic seizures, although information about the real frequency of bite marks of the tongue is hard to find. This is also true for their presence in deaths of epileptics or in deaths in general. The purpose of this investigation was to analyze the frequency of bite marks of the tongue in deaths of epileptics in comparison to a control group. Further points of interest were the spectrum of the causes of death recorded, toxicological data as well as the presence and localization of external head injuries. The study group consisted of 105 individuals with a known history of epilepsy, the control group of 107 individuals with sudden cardiac death. Autopsy reports were analyzed retrospectively. In the first group bite marks of the tongue were seen in 21% (in the subgroup "observed death during seizure" even in 64%) and were thus significantly more frequent than in the control group (2%). In 35 cases of the study material an unnatural manner of death was found (trauma, especially craniocerebral trauma, drowning, asphyxia, intoxication) and in 70 cases a natural death was assumed. However, in 41 of these the exact cause of death was not ascertainable. According to the SUDEP criteria (Ficker 2000, Nilsson 1999) 29 of these cases could be categorized as possible or probable SUDEP (sudden unexpected death in epilepsy) with 17 showing bite marks of the tongue. The fact that half of the remaining 12 cases showed bite marks of the tongue suggests at least for these cases that death occurred during the seizure. Head injuries were reported in 41% of the epilepsy group--in the subgroup "observed death during seizure" in 73%. Our investigation did not produce evidence for a higher frequency of bite marks of the tongue in cases in which resuscitation had been attempted. In our experience the presence of fresh bite marks of the tongue--according to histological findings--is a useful signs for the assignment of death to an epileptic seizure and especially for death during acute convulsion.     

Ecstasy (MDMA) deaths in New York City: a case series and review of the literature

MDMA ("ecstasy") has gained renewed popularity as a drug of abuse. To access the epidemiology and causes of death of MDMA-positive fatalities, all deaths investigated by the OCME that tested positive for MDMA (22 deaths) between January 1997 and June 2000 were reviewed. There were three deaths in each 1997 and 1998, eleven in 1999, and five in the first part of 2000. Of these 22 deaths, 13 were due to acute drug intoxications, 7 due to mechanical injury (blunt trauma, gunshot wounds), and 2 due to a combination of natural disease and acute drug intoxication. Evidence of recent opiate and/or cocaine use was found in 7 of the acute intoxication deaths and in none of the traumatic or combination natural/intoxication deaths. The race of all decedents was White between the ages of 17-41 years, and 18 of 22 were men.     

Immunohistochemical investigation of ubiquitin and myoglobin in the kidney in medicolegal autopsy cases

We examined the immunohistochemical distributions of ubiquitin (Ub) and myoglobin (Mb) in human kidney tissues to assist the pathological assessment of death due to trauma. Medicolegal autopsy cases at our institute (n=138: 0-96 years of age, 105 males and 33 females) were examined. Causes of death were blunt injury (n=31), sharp injury (n=15), poisoning (n=11), drowning (n=10), fire fatalities (n=25), hypothermia (n=7), asphyxiation (n=14), hyperthermia (n=3), and natural diseases (n=22) for controls. Immunostaining of Ub and Mb was performed on the formalin-fixed paraffin-embedded kidney tissue sections. Quantitative analyses by estimating the proportion of Ub- and Mb-positive cells (%positivity) of renal tubule epithelial cells showed that the positivities for Ub and Mb were higher in subjects who died due to fire, blunt injury, sharp injury and fatal hypothermia than in other groups. The Ub-positivity correlated with the severity of airway thermal injury in fire deaths, survival time in blunt injury, and serum markers for renal failure in deaths due to sharp injury. Concomitant increases in the tubular Mb- and Ub-positivities were characteristic to deaths from injury and hypothermia. These findings suggest that Ub may serve as a sensitive indicator of the fatal influence of traumas.     

Asplenia as a cause of sudden unexpected death in childhood

Sudden unexpected death in childhood is rare. The commonest causes of such deaths are a result of fulminating infections of the respiratory or nervous systems. Other causes include unsuspected congenital abnormalities of the heart, acute metabolic disorders, and rarities such as internal hemorrhages and pulmonary thrombosis. Recognition of children with congenital asplenia who are otherwise normal but have an increased susceptibility to overwhelming sepsis is extremely difficult. We reviewed 1763 autopsy files from our institution over 5 years (1990-1995), of which 293 were classified as pediatric cases. The vast majority of the cases were stillbirths and deaths within the first year of life as a result of complex congenital anomalies. Four cases of asplenia were identified in our entire series, 3 of which were of the congenital syndromal variety and 1 of which was a case of isolated sporadic congenital asplenia. All 4 cases of asplenia were analyzed in detail with respect to autopsy findings and cause of death. Severe complex cardiac malformations were present in the congenital syndromal asplenia patients; these other malformations contributed significantly to their death. In this report, we discuss in detail the autopsy findings in a previously healthy 4-year-old girl who presented with a brief 8-hour history of being unwell and died within 4 hours of admission into the hospital. She had sporadic, isolated congenital asplenia complicated by high-grade type 6B pneumococcemia and acute bilateral adrenal hemorrhage (Waterhouse-Friderichsen syndrome). Previously healthy children who clinically deteriorate very rapidly should have a blood smear done as part of their clinical workup. The detection of Howell-Jolly bodies on a peripheral blood smear can be an indicator of asplenia, and this diagnosis can be confirmed by medical imaging of the abdomen. Such steps may aid in the aggressive management of isolated congenital asplenia and thereby avert untimely death.     

Efficacy of cerebro-spinal fluid biochemistry in the diagnosis of brain insult.

Postmortem biochemical indices may provide a useful adjunct to morphological studies in the identification of antemortem brain insult. We studied 34 routine medico-legal cases categorising them into one of four diagnostic groups. There were 11 cases of head trauma, 7 of 'hypoxia' (3 hangings and 4 carbon monoxide or drug poisonings), 7 sudden cardiac deaths and 9 miscellaneous cases. Survival time and postmortem interval was known for each case. The degree of cranio-cerebral trauma was graded. Cerebro-spinal fluid (CSF) and vitreous humour were analysed for calcium, glucose, total proteins, aldolase, aspartate transaminase (AST), alanine transaminase (ALT), gamma glutamyltransferase (GGT), lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase BB isoenzyme (CK-BB). CK-BB was also measured in superior vena cava serum. In CSF there was a significant correlation between the severity of cranio-cerebral trauma and levels of aldolase, CK-BB, AST, ALT and total proteins. CSF CK-BB, median units/l (range), for the groupings of head trauma, hypoxia, sudden cardiac death and miscellaneous were respectively 823 (2-3431); 96 (2-187); 4 (2-25); 5 (1-69). Corresponding serum CK-BB levels were 240 (28-322); 390 (26-411); 180 (20-482); 79 (18-530).     

Aminopeptidase and cathepsin A activity in vitreous humor in relation to causes of death

Brain autolysis happens rapidly, especially when environmental temperatures are high, and poses serious limitations for evaluating damage using morphologic methods. In the present study we have measured total proteins, cathepsin A and aminopeptidase activity in the vitreous humor in relation to cause of death and survival time. We have studied vitreous humor samples from 106 cadavers autopsied in the I.A.F. of Granada. The samples were classified according to causes of death as follows: myocardial infarction; hanging; other mechanical asphyxias; multiple trauma; craniocerebral trauma; other violent death; pulmonary functions; and other natural deaths. Total protein was measured by Lowry's method, and cathepsin A and aminopeptidase activity by the Bowen and Davison (1973) and Greenberg (1962) methods, respectively. Results are expressed in IU/l and in mIU/mg of protein. We found higher values of aminopeptidase and cathepsin A activity in groups with severe brain damage (craniocerebral trauma, multiple trauma, etc.) and lower values in groups of natural deaths. We believe, therefore, that aminopeptidase activity in vitreous humor may be a useful parameter for evaluating brain damage.     

Commotio cordis as a result of a fight: Report of a case considered to be imprudent homicide

Commotio cordis is a clinic-pathological syndrome related to sudden death in young people involved in sports activities. It has been described, mainly, in athletes without previous cardiac anomalies who received a minor blow to the chest which produces ventricular fibrillation and cardiac arrest in the absence of structural damage to the ribs, sternum, or heart. There are few reported cases of commotio cordis associated with violent, non-sports related actions, which are commonly considered to be imprudent homicides. We present the case of a 20-year-old man, who was kicked in the chest during a fight; he suddenly collapsed although advanced cardio-respiratory resuscitation started shortly. Autopsy showed no cardiac lesions concluding that death was due to commotio cordis (blunt trauma to the chest). Toxicological analysis determined the presence of 5.14 mg/L benzoylecgonine in blood. On the basis of medico-legal investigation, the official prosecution considered the death to be imprudent homicide and the aggressor was sentenced to 4 years in prison. We emphasize the importance of the knowledge of the death circumstances through the witnesses’ testimony, prior to beginning the autopsy, to confirm this important medico-legal diagnosis. Arrhythmogenic effects of cocaine and its contribution in the production of these deaths are also exposed.     

Congestion bleedings of the face and cardiopulmonary resuscitation--an attempt to evaluate their relationship

OBJECTIVES: Are any other factors besides the factor "cause of death" involved in the development of petechial hemorrhages (PET) of the head? The significance of the cause of death is well known, other factors have been rarely investigated in medical literature. Do they include cardiopulmonary resuscitation (CPR), as has been claimed in several forensic publications? MATERIALS AND METHODS: (a) 473 consecutive autopsy cases (without strangulation) evaluated by one examiner, which were appropriate for this investigation; (b) analysis of 181 cardiac deaths (investigated by all physicians of our institute). RESULTS: Petechiae were found in 13.3% of all cases and were clearly dependent on the cause of death, up to 20% were found in burn victims, intensive-care patients and cardiac fatalities. Petechiae were more frequently observed in the middle age groups (>20%) than in old persons (<10%). The number of PET cases increased with body mass but was lower in extremely obese persons, a greater number of cases with PET was also observed with increasing heart weight. PET were observed in 11% of the deaths without CPR compared to 19% with CPR. This difference was predominantly caused by the subgroup "acute coronary death", especially if victims younger than 60 years were considered, whereas in many other causes of death no difference in the prevalence of PET with or without CPR could be observed. CONCLUSION: Besides the cause of death, other factors (age, body mass and possibly even heart weight) influence the development of petechiae. The hypothesis that CPR alone produces PET is not confirmed by our experience.     

Immunohistochemical quantification of pulmonary mast-cells and post-mortem blood dosages of tryptase and eosinophil cationic protein in 48 heroin-related deaths

Recent studies suggest that many fatal heroin overdoses are caused by anaphylactoid reaction. In the present study we measured tryptase and eosinophil cationic protein in post-mortem blood of 48 deaths after heroin injection. We also investigated the presence and pulmonary distribution of mast-cells using specific immunohistochemical antibody for tryptase and morphometric evaluation in those cases of heroin-related deaths. The data were compared with 44 subjects who died following head trauma and to 32 cases of fatal anaphylactic shock. In the heroin-related death cases, the measurements of serum tryptase levels and eosinophil cationic protein dosages resulted in particularly elevated concentrations compared with the trauma cases. Nevertheless, the data that our study supplies by immunohistochemical techniques indicate that when mast-cells count in the lung was determined, no definite pattern was obtained between fatal heroin overdose cases and the control groups. Furthermore, the wide range of morphine concentrations found in post-mortem blood samples suggest that the term 'overdose' is relative and does not sufficiently characterize death associated with heroin addiction. Our study confirms that elevated concentrations of serum tryptase are associated with many heroin-related deaths. At this moment to attribute the cause of these deaths to 'heroin overdose' ignores the likely causal contribution of other possible systemic reactions to the mechanism of death.     

Usefulness of different myocardial sampling zones for the postmortem diagnosis of myocardial infarction

The diagnosis of myocardial infarction requires the use of a group of tests that are very efficient, quick and inexpensive. Another important consideration is the choice of myocardial sampling zones, especially in cases of differential diagnosis between a cardiac injury secondary to a trauma or violent asphyxia and others, secondary to myocardial infarction. The aim of this work was to choose, through discriminant analysis, the most useful zones of cardiac tissue for the quantification of free fatty acids and free carnitine and for the performance of the K/Na quotient, as biochemical parameters for the postmortem diagnosis of myocardial infarction. According to the discriminant analysis performed, seven zones of cardiac tissue are necessary to achieve a differential diagnosis among "myocardial infarction," "other natural deaths," and "violent deaths" with a 71.9% efficacy. Greater diagnostic efficacy was found (78.1%) for differentiating between "natural deaths" and "violent deaths."     

Differential accumulation of pulmonary and cardiac mast cell-subsets and eosinophils between fatal anaphylaxis and asthma death: a postmortem comparative study

The distribution profile of infiltrated mast cell-subpopulations and eosinophils in the lung and heart sections of the patients who died of severe allergic hyperresponsiveness, was investigated. Four study groups were designed comprising 9 cases who died in systemic anaphylaxis (Group I), 10 asthmatic individuals whose death were assigned to acute and severe bronchial asthma (Group II), 10 asthmatic cases who died from non-immunological diseases (Group III). Twenty consecutive autopsies of non-allergic subjects who died of unnatural causes (Group IV) served as control group in this study. Utilizing antibodies against human tryptase and chymase and a double immunohistochemical staining method, we distinguished successfully all three subsets of mast cells (MC), MC-TC (containing both tryptase and chymase), MC-T (containing only tryptase) and MC-C (containing only chymase) types, subdivided on the basis of the protease compositions of their secretory granules. In order to immunostaining eosinophils, we used antibody to major basic protein as a marker. We also measured postmortem blood tryptase, specific and total serum IgE. The intriguing finding of this study was the marked differences of cellular composition in the lung between fatal anaphylaxis and asthma death. Significant augmentation of MCs infiltrated in lung and heart sections of anaphylaxis patients and drastic infiltration of bronchial eosinophils in asthmatic death and consequent release of their related inflammatory mediators might explain the differential expression of the associated symptoms in these two groups. The anaphylactic deaths did show neither emphysema nor significant mucous bronchial secretions whereas all asthmatic deaths did. The degree of pulmonary congestion and edema was also more severe in anaphylaxis. This corresponded with the histological findings and the location and number of mast cell-subsets and eosinophils in the different compartments of the lungs. We have demonstrated that the third type of mast cell MC-C is only found in the lungs in anaphylactic deaths. The practical consequence of our study will be that it is now possible to confirm a suspicion of anaphylaxis death not only by measurements of serum mast cell tryptase, but also by immunohistochemical methods.     

Urine/blood ratios of ethanol in deaths attributed to acute alcohol poisoning and chronic alcoholism

The concentrations of ethanol were determined in femoral venous blood (BAC) and urine (UAC) and the UAC/BAC ratios were evaluated for a large case series of forensic autopsies in which the primary cause of death was either acute alcohol poisoning (N=628) or chronic alcoholism (N=647). In alcohol poisoning deaths both UAC and BAC were higher by about 2g/l compared with chronic alcoholism deaths. In acute alcohol poisoning deaths the minimum BAC was 0.74 g/l and the distribution of UAC/BAC ratios agreed well with the shape of a Gaussian curve with mean+/-standard deviation (S.D.) and median (2.5th and 97.5th centiles) of 1.18+/-0.182 and 1.18 (0.87 and 1.53), respectively. In alcoholism deaths, when the BAC was above 0.74 g/l (N=457) the mean+/-S.D. and median (2.5th and 97.5th centiles) UAC/BAC ratios were 1.30+/-0.29 and 1.26 (0.87 and 2.1), respectively. When the BAC was below 0.74 g/l (N=190), the mean and median UAC/BAC ratios were considerably higher, being 2.24 and 1.58, respectively. BAC and UAC were highly correlated in acute alcohol poisoning deaths (r=0.84, residual S.D.=0.47 g/l) and in chronic alcoholism deaths (r=0.95, residual S.D.=0.41 g/l). For both causes of death (N=1275), the correlation between BAC and UAC was r=0.95 and the residual S.D. was 0.46 g/l. The lower UAC/BAC ratio observed in acute alcohol poisoning deaths (mean and median 1.18:1) suggests that these individuals died before absorption and distribution of ethanol in all body fluids were complete. The higher UAC/BAC ratio in chronic alcoholism (median 1.30:1) is closer to the value expected for complete absorption and distribution of ethanol in all body fluids.     

Postmortem Serum Tryptase Levels with Special Regard to Acute Cardiac Deaths

An elevated serum tryptase concentration is considered a specific marker for systemic mast cell activation, a central feature of anaphylaxis. However, in some cases of acute cardiovascular death, high concentrations of serum tryptase are also observed. We compared the postmortem serum tryptase concentrations in 74 cases assigned to the following four groups: anaphylactic deaths (Group A, n = 20), acute cardiac deaths (Group ACD, n = 30), acute dissecting aneurysm ruptures (Group ADA, n = 10), and controls (Group C, n = 14). Additionally, the cutoff between Group A and the other groups was calculated using receiver‐operating characteristic (ROC) curve analysis. Tryptase concentrations were markedly elevated in Group A (p < 0.001), Group ACD (p = 0.015), and Group ADA (p = 0.005). The optimal cutoff was 43 ng/mL, the sensitivity was 90%, and the specificity was 98%. While elevated concentrations of tryptase were noted in practical autopsy cases, due attention should be paid to the differential diagnosis between anaphylactic and acute cardiovascular deaths.     

Death caused by cardioinhibitory reflex cardiac arrest--a systematic review of cases

Forensic pathologists often refer to the cardioinhibitory reflex cardiac arrest (CiRCA) following short neck trauma as a mechanism of death. We sought via a systematic review of the literature to identify circumstances under which carotid bifurcation stimulation could lead to death. Two independent reviewers selected case studies or reports from Medline, ISI Web of Knowledge, and Embase. Circumstances and contributory factors were extracted for each case. From the available data, authors independently assessed whether CiRCA was highly probable (no alternative explanation possible), probable (alternative explanation possible), or unlikely (alternative explanation highly probable). A narrative approach was used to define circumstances in which CiRCA remained possible. From the 48 published cases evoking CiRCA as a possible cause of death between 1881 and 2009, 28 were most likely to result of other mechanism of death (i.e., cerebral hypoxia due to carotid compression, mechanical asphyxia, myocardial infarction). CiRCA remained possible for 20 cases (including five based on anecdotal evidence only) with only one case with no alternative explanation other than CiRCA. Our findings support the presumption that reflex cardiac arrhythmia due to carotid bifurcation stimulation cannot provoke death alone. Actual state of knowledge suggests CiRCA might be contributory to death in the presence of drug abuse and/or cardiac pathology, often associated with physical and/or mental excitation.     

Immunohistochemical quantification of pulmonary mast-cells and post-mortem blood dosages of tryptase and eosinophil cationic protein in 48 heroin-related deaths

Recent studies suggest that many fatal heroin overdoses are caused by anaphylactoid reaction. In the present study we measured tryptase and eosinophil cationic protein in post-mortem blood of 48 deaths after heroin injection. We also investigated the presence and pulmonary distribution of mast-cells using specific immunohistochemical antibody for tryptase and morphometric evaluation in those cases of heroin-related deaths. The data were compared with 44 subjects who died following head trauma and to 32 cases of fatal anaphylactic shock. In the heroin-related death cases, the measurements of serum tryptase levels and eosinophil cationic protein dosages resulted in particularly elevated concentrations compared with the trauma cases. Nevertheless, the data that our study supplies by immunohistochemical techniques indicate that when mast-cells count in the lung was determined, no definite pattern was obtained between fatal heroin overdose cases and the control groups. Furthermore, the wide range of morphine concentrations found in post-mortem blood samples suggest that the term ‘overdose’ is relative and does not sufficiently characterize death associated with heroin addiction. Our study confirms that elevated concentrations of serum tryptase are associated with many heroin-related deaths. At this moment to attribute the cause of these deaths to ‘heroin overdose’ ignores the likely causal contribution of other possible systemic reactions to the mechanism of death.