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Pathogenic role of cardiac mast cell activation/degranulation,TNF-alpha, and cell death in acute drug-related fatalities.

Perskvist N, Söderberg C, van Hage M, Edston E - Vasc Health Risk Manag (2007)

Bottom Line: In the myocardium of overdose victims, MC-infiltration and degranulation were significantly increased as well as production of myocytic TNF-alpha compared with the SND cases.Mast cells are recruited and activated in the heart of drug-associated deaths and the myocytes are the main source of TNF-alpha with the ability of different production patterns.The high degree of MC degranulation and the elevated levels of tryptase together with the pathological changes in heart of drug-related victims resemble that of the anaphylactic deaths as demonstrated in our previous study.

View Article: PubMed Central - PubMed

Affiliation: National Board of Forensic Medicine, Department of Forensic Medicine, Linköping, Sweden. nasrin.perskvist@imv.liu.se

ABSTRACT

Background: Intravenous injection of narcotic stimulants affects many cellular functions relevant for the pathophysiological mechanisms of heart failure. There is considerable evidence that mast cells (MCs), TNF-alpha, and cell death play crucial roles in the pathogenesis and progression of cardiac arrest. In this study, we examined and compared the participation of MCs, TNF-alpha, apoptosis and necrosis in the heart of drug-related fatalities and the victims of sudden death due to the cardiac failure or aortic dissection.

Methods and results: Serum level of postmortem tryptase was determined in all study subjects that consisted of 50 autopsy cases: 30 drug overdose fatalities which were further divided into two groups with high and low level of tryptase, and 20 cases of sudden natural death (SND). The distribution profile of cardiac infiltrated-MCs and production patterns of TNF and C9 (necrotic marker) were investigated immunohistochemically. In situ-detection of apoptosis with TUNEL was applied to the heart sections. The level of tryptase was elevated (>45 microg/L) in the drug fatalities but remained below the cut-off value in SND. In the myocardium of overdose victims, MC-infiltration and degranulation were significantly increased as well as production of myocytic TNF-alpha compared with the SND cases. The expressions profile of myocytic TNF varied between the groups. Apoptotic myocytes were seen more frequently in the SND group while necrosis was more evident in the heart of drug-related fatalities.

Conclusion: Mast cells are recruited and activated in the heart of drug-associated deaths and the myocytes are the main source of TNF-alpha with the ability of different production patterns. The high degree of MC degranulation and the elevated levels of tryptase together with the pathological changes in heart of drug-related victims resemble that of the anaphylactic deaths as demonstrated in our previous study.

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(a) Dual immunostaining of anti-tryptase and -chymase in the same mast cell located within the interior wall of right ventricle. The insert: Cardiac mast cell staining only with anti-tryptase, MCT. (b) Mast cell degranulation in the heart section of a drug victim. Original magnification × 400, in A and × 200 in b.
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fig1: (a) Dual immunostaining of anti-tryptase and -chymase in the same mast cell located within the interior wall of right ventricle. The insert: Cardiac mast cell staining only with anti-tryptase, MCT. (b) Mast cell degranulation in the heart section of a drug victim. Original magnification × 400, in A and × 200 in b.

Mentions: In pulmonary and cardiac tissues, two populations of MCs were apparent: one resembled typical connective tissue type MCs that stained with both anti-tryptase and chymase (MCTC), and the other was atypical or mucosal MC that reacted only to anti-tryptase antibody. This population was seen in appreciable amounts in the lung but a minor number was found also in heart tissue. Due to a negligible quantity of tissue MCC, this subset was excluded from statistical analysis. Significantly higher amounts of infiltrated MCs were observed in the HLT and LLT-cardiac sections than the other groups (p < 0.015 Kruskal-Wallis test, Table 4). The number of MCTC predominated among the cardiac MCs. Moreover, we observed that in 10 cases of 13 (77%) and 4 cases of 17 (23.5%) in HLT- and LLT-heart sections, respectively, more than 60% (on average) of the infiltrated MCs were degranulated (Figure 1b), while none of SND-heart sections showed this phenomenon (Table 5). In lung sections of drug deaths with high levels of femoral tryptase (HLT), there were higher numbers of infiltrated MC-subsets at the site of bronchial smooth muscle (p < 0.05) and parenchymal tissues compared with the other two groups (Table 4). No significant differences were seen between the amount of infiltrated MCs in SND cases and drug deaths with low tryptase levels (LLT) (Table 4). Figure 1a, showing the infiltrated MC-subsets in the heart sections, illustrates the differences in immunostaining between these cells.


Pathogenic role of cardiac mast cell activation/degranulation,TNF-alpha, and cell death in acute drug-related fatalities.

Perskvist N, Söderberg C, van Hage M, Edston E - Vasc Health Risk Manag (2007)

(a) Dual immunostaining of anti-tryptase and -chymase in the same mast cell located within the interior wall of right ventricle. The insert: Cardiac mast cell staining only with anti-tryptase, MCT. (b) Mast cell degranulation in the heart section of a drug victim. Original magnification × 400, in A and × 200 in b.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2350147&req=5

fig1: (a) Dual immunostaining of anti-tryptase and -chymase in the same mast cell located within the interior wall of right ventricle. The insert: Cardiac mast cell staining only with anti-tryptase, MCT. (b) Mast cell degranulation in the heart section of a drug victim. Original magnification × 400, in A and × 200 in b.
Mentions: In pulmonary and cardiac tissues, two populations of MCs were apparent: one resembled typical connective tissue type MCs that stained with both anti-tryptase and chymase (MCTC), and the other was atypical or mucosal MC that reacted only to anti-tryptase antibody. This population was seen in appreciable amounts in the lung but a minor number was found also in heart tissue. Due to a negligible quantity of tissue MCC, this subset was excluded from statistical analysis. Significantly higher amounts of infiltrated MCs were observed in the HLT and LLT-cardiac sections than the other groups (p < 0.015 Kruskal-Wallis test, Table 4). The number of MCTC predominated among the cardiac MCs. Moreover, we observed that in 10 cases of 13 (77%) and 4 cases of 17 (23.5%) in HLT- and LLT-heart sections, respectively, more than 60% (on average) of the infiltrated MCs were degranulated (Figure 1b), while none of SND-heart sections showed this phenomenon (Table 5). In lung sections of drug deaths with high levels of femoral tryptase (HLT), there were higher numbers of infiltrated MC-subsets at the site of bronchial smooth muscle (p < 0.05) and parenchymal tissues compared with the other two groups (Table 4). No significant differences were seen between the amount of infiltrated MCs in SND cases and drug deaths with low tryptase levels (LLT) (Table 4). Figure 1a, showing the infiltrated MC-subsets in the heart sections, illustrates the differences in immunostaining between these cells.

Bottom Line: In the myocardium of overdose victims, MC-infiltration and degranulation were significantly increased as well as production of myocytic TNF-alpha compared with the SND cases.Mast cells are recruited and activated in the heart of drug-associated deaths and the myocytes are the main source of TNF-alpha with the ability of different production patterns.The high degree of MC degranulation and the elevated levels of tryptase together with the pathological changes in heart of drug-related victims resemble that of the anaphylactic deaths as demonstrated in our previous study.

View Article: PubMed Central - PubMed

Affiliation: National Board of Forensic Medicine, Department of Forensic Medicine, Linköping, Sweden. nasrin.perskvist@imv.liu.se

ABSTRACT

Background: Intravenous injection of narcotic stimulants affects many cellular functions relevant for the pathophysiological mechanisms of heart failure. There is considerable evidence that mast cells (MCs), TNF-alpha, and cell death play crucial roles in the pathogenesis and progression of cardiac arrest. In this study, we examined and compared the participation of MCs, TNF-alpha, apoptosis and necrosis in the heart of drug-related fatalities and the victims of sudden death due to the cardiac failure or aortic dissection.

Methods and results: Serum level of postmortem tryptase was determined in all study subjects that consisted of 50 autopsy cases: 30 drug overdose fatalities which were further divided into two groups with high and low level of tryptase, and 20 cases of sudden natural death (SND). The distribution profile of cardiac infiltrated-MCs and production patterns of TNF and C9 (necrotic marker) were investigated immunohistochemically. In situ-detection of apoptosis with TUNEL was applied to the heart sections. The level of tryptase was elevated (>45 microg/L) in the drug fatalities but remained below the cut-off value in SND. In the myocardium of overdose victims, MC-infiltration and degranulation were significantly increased as well as production of myocytic TNF-alpha compared with the SND cases. The expressions profile of myocytic TNF varied between the groups. Apoptotic myocytes were seen more frequently in the SND group while necrosis was more evident in the heart of drug-related fatalities.

Conclusion: Mast cells are recruited and activated in the heart of drug-associated deaths and the myocytes are the main source of TNF-alpha with the ability of different production patterns. The high degree of MC degranulation and the elevated levels of tryptase together with the pathological changes in heart of drug-related victims resemble that of the anaphylactic deaths as demonstrated in our previous study.

Show MeSH
Related in: MedlinePlus