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Heroin Addiction and Related Clinical Problems: 2021, 23, N4 (pages: 15 - 23)

Effect of methadone and treadmill exercise on myocardial infarction in morphine withdrawn rats

Alizadeh M., Miladi-Gorji H., Sameni H., Bandegi A., Ebadatipour E., and Zahedi-Khorasani M.

Summary: Background: The effects of Methadone Maintenance Treatment (MMT) on myocardial infarction (MI) are still controversial. Given that exercise is known to be cardio-protective, the effects of mild treadmill exercise on isoproterenol-induced MI in morphine-withdrawal rats receiving MMT was investigated in the present study. Methods: Male Wistar rats (n=112) were divided into the following subgroups: saline, MMT, morphine-dependent, morphine withdrawal/MMT; each of these groups was, in its turn, subdivided into sedentary, and exercise with or without MI. Morphine dependency was induced by issuing morphine prescriptions for 14 consecutive days. Then rats received MMT or saline, and were forced to run every day on a treadmill for 30 days consecutively. At that point MI was induced by isoproterenol injection, and haemodynamic, biochemical and histological parameters were measured. Results: MMT significantly increased maximum dp/dt (p< 0.001), arterial blood pressure (p< 0.05), and heart rate (p< 0.01), while it decreased left ventricular end-diastolic pressure (p< 0.01) in non-MI rats. But it increased cardiac troponin I (p< 0.001), malondialdehyde (p< 0.01) and lowered superoxide dismutase (p< 0.01), glutathione peroxidase (p< 0.01) and damaged histological factors (inflammation, oedemas, congestion and haemorrhage). Exercise modulated most of the haemodynamic, biochemical and histological factors in the saline and MMT groups. Isoproterenol significantly damaged haemodynamic, biochemical and histological factors in the saline and MMT groups (for all of these factors, p< 0.01), but it had no significant effects on morphine-dependent or morphine-withdrawal/MMT rats. These effects were, however, improved by exercise. Conclusions: The findings of the present study revealed that MMT has risky effects on the heart in morphine-naive rats – effects that were, however, attenuated by mild treadmill exercise. So these study results go to show that physical activity and cardiovascular monitoring are likely to have beneficial effects on methadone consumers.