Published: Journal of Analytical Toxicology, Volume 24, Number 2, March, pp.153-155

Redistribution of Methamphetamine in the Early Postmortem Period

To the Editor:

In a past issue of this journal, Barnhart et al. (1) reported details of the postmortem redistribution of methamphetamine. They compared the concentrations of amphetamine and methamphetamine in central blood (cardiac blood) with those in perpheral blood. In most of the cases they examined, the concentrations of amphetamine and methamphetamine in samples of central blood were much higher than in those of peripheral blood. Illustrating marked accumulation of amphetamine and methamphetamine in the myocardium in several cases, they ascribed the postmortem increases in the concentrations of these substances in cardiac blood to their diffusion from the myocardium. However, their data were not sufficient to determine the mechanism of the postmortem redistribution of methamphetamine because they failed to mention whether the central blood samples were taken from the left and right cardiac chambers separately or together. If methamphetamine in the myocardium is primarily responsible for the postmortem increase in the concentration of methamphetamine in cardiac blood, then the blood concentration of methamphetamine would be elevated in both the left and right cardiac chambers.

Recently, we attempted to determine the mechanism responsible for postmortem increases in the concentrations of basic drugs in cardiac blood during the early postmortem period by comparing toxicological data obtained from human autopsy cases with those obtained from animal experiments (2). In this study, we selected methamphetamine as one of the model drugs because its illegal use is currently one of the most serious social problems in Japan. Methamphetamine was isolated using liquid–liquid extraction and derivatized with trifluoroacetic anhydride; N-methylbenzylamine was selected as an internal standard. Identification and quantitation of methamphetamine were performed by GC–MS and GC, respectively.

Table I illustrates the concentrations of methamphetamine in the blood, lung, and myocardium of the three intravenous methamphetamine users. The postmortem intervals in Cases 1, 2, and 3 were estimated to be approximately 12 h, 9 h, and 2.5 days, respectively. None were trauma victims, and little indication of putrefication was observed. In Cases 1 and 2, blood in the cardiac chambers and pulmonary vessels was fluid, and the methamphetamine concentrations in blood from the cardiac chambers were 2.06 and 1.59 times higher, respectively, than those in blood from the right cardiac chambers. In Case 1, in which samples of femoral venous blood and pulmonary venous and arterial blood were also analyzed for methamphetamine, the concentration of methamphetamine in femoral venous blood was almost the same as that in blood from the right cardiac chambers, and the methamphetamine concentrations in pulmonary venous and arterial blood were a little higher than those in blood from the left and right cardiac chambers.

Based on these findings, we conducted an animal experiment. Rabbits were given 5 mg/kg methamphetamine hydrochloride intravenously and sacrificed 20 min later by intravenous injection of 1500 U sodium heparin and 2 mmol/kg potassium chloride. Immediately after death, thoracotomy was performed, and a small volume (approximately 0.2 mL) of blood was drawn from the left and right cardiac chambers by needle puncture. The rabbit carcasses were then left at room temperature in a supine position for 6 h, after or without ligation of the large vessels around the heart. Table II shows the results of the experiment. The concentrations of methamphetamine in samples of lung, myocardium, and pulmonary venous blood obtained 6 h postmortem were much higher than those in cardiac blood. Little difference in the concentration of methamphetamine was observed between the blood samples obtained from the left and right cardiac chambers of rabbits whose large vessels around the heart had been ligated for 6 h after death. However, in rabbit carcasses without such vessel ligation, the blood concentration of methamphetamine in the left, but not the right, cardiac chambers showed a tendency to be increased.

Our results indicate clearly that methamphetamine deposited in the lungs is redistributed rapidly into the pulmonary venous blood and then into the left cardiac chambers and that methamphetamine in the myocardium contributes little to the increase in its concentration in cardiac blood during the early postmortem period. As the lungs have the richest supply of blood vessels in the body, methamphetamine can be sequestered in the pulmonary tissues at high concentrations before death and diffuse into the thin-walled pulmonary veins more rapidly than into the thick-walled pulmonary arteries. Although cardiac blood samples are generally thought to be of qualitative value for postmortem drug testing, blood in the right cardiac chambers, as well as blood in the peripheral vessels, may be used for quantitative analysis, at least for amphetamines, during the early postmortem period.

References

1. F.E. Barnhart, J.R. Fogacci, and D.W. Reed. Methamphetamine—a study of postmortem redistribution. J. Anal. Toxicol. 23: 69–70 (1999).
2. F. Moriya and Y. Hashimoto. Redistribution of basic drugs into cardiac blood from surrounding tissues during early-stages postmortem. J. Forensic Sci. 44: 10–16 (1999).

The Author’s Reply:
The letter that we published in JAT (1) primarily focuses on the fact that postmortem redistribution does occur with methamphetamine. The exact mechanism was thought to be due to concentration in heart muscle, but it did not rule out other mechanisms. Hilberg et al. (2) and others have published on postmortem redistribution due to release from lung tissue. However, studies in this area all seem to use animal models.

In particular, Moriya and Hashimoto quantitated myocardial methamphetamine in only one case, Case 2, and it was 75% higher than the lung level. In human Cases 1 and 2, left-side heart blood concentrations were higher than right-side heart blood, and the case with the greater interval between death and sampling (Case 1) has the larger difference between left- and right-side samples. The rabbits studied received the same doses, but test values varied. The rabbits were intentionally sacrificed 20 min after injection; this does not replicate true-life experience. In addition, potassium is cardiotoxic, and because this could affect values, why not sacrifice animals with central nervous system trauma or in some manner other than administration of a cardiotoxic drug? The rabbits without ligated vessels showed increased methamphetamine levels in all samples as compared with ligated rabbits. This does not make logical sense. No peripheral samples were drawn from the rabbits, and peripheral samples are what our article addresses. The experiment parameters do not reflect the reality of methamphetamine overdoses. Not all victims die 20 min after taking the drug, and not all deaths are due to intravenous injections. If humans survive more than 20 min, perhaps the drug progressively accumulates in the myocardium and is flushed out of the lung vasculature. Are we discussing redistribution (movement) or postmortem release (unbinding)?

Finally, the central heart blood samples for our study were taken from the right atrium by incising the inferior vena cava as it enters the right atrium.

Frank E. Barnhart
San Diego Sheriff’s Crime Laboratory
5255 Mt. Etna Drive
San Diego, California 92117

References

1.  F.E. Barnhart, J.R. Fogacci, and D.W. Reed. Methamphetamine—a study of postmortem redistribution. J. Anal. Toxicol. 23: 69–70 (1999).
2. T. Hilberg, J. Morland, and A. Bjorneboe. Postmortem release of amitriptyline from the lungs; a mechanism of postmortem drug redistribution. Forensic Sci. Int. 64: 47–55 (1994).

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