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The combined effects of cocaine and amphetamine on primary postnatal rat heart cell cultures
1College of Pharmacy, University of Oklahoma Health Sciences Center, Department of Medicinal Chemistry and Pharmacodynamics, Oklahoma City 73190.
Insights
Perinatal exposure to cocaine and amphetamines harms infant heart cells. Even low doses of these drugs negatively impact myocardial cell structure and function, with higher doses causing cell death.
Area of Science:
- Cardiovascular Science
- Developmental Toxicology
- Cell Biology
Background:
- Perinatal exposure to cocaine (Coc) and amphetamines (Amph) is linked to adverse infant cardiovascular outcomes.
- Understanding the direct impact of these substances on developing heart cells is crucial.
Purpose of the Study:
- To investigate the dose- and time-dependent effects of Coc and Amph on postnatal rat myocardial cell cultures.
- To assess functional and morphological changes in cardiomyocytes exposed to these drugs.
Main Methods:
- Primary rat myocardial cell cultures were treated with varying doses of Coc and Amph.
- Evaluated parameters included contractile activity, cell morphology, lactate dehydrogenase (LDH) release, MTT formazan production, and neutral red (NR) retention.
Main Results:
- Highest drug doses abolished contractile activity.
- Lower doses of Coc and Amph reduced contractile area by 24 hours.
- Combined drug exposure significantly altered beating rates.
- Morphological alterations were observed across all treatment groups.
- LDH release indicated cell damage at higher drug concentrations.
Conclusions:
- Cocaine and amphetamines at doses ≥ 1 x 10(-5) M induce adverse effects on myocardial cell morphology and contractile function.
- These findings highlight the cardiotoxic potential of perinatal exposure to these substances.
Abstract:
Recent reports demonstrated that perinatal exposure to cocaine (Coc) and amphetamines (Amph) predisposed the infant to adverse cardiovascular consequences. Dose- and time-dependent effects of Coc and Amph on postnatal rat myocardial cell cultures are described. Contractile activity, morphology, lactate dehydrogenase (LDH) release, MTT formazan production, and neutral red (NR) retention were determined. No contractile activity was observed in cultures treated with the highest drug doses. After 24 h, the percentage of areas exhibiting contractile activity was decreased in cultures exposed to the lowest doses of both drugs. When Coc and Amph were combined, beating rates were significantly altered. Morphologic alterations were observed in all treatment groups. LDH release occurred in cultures exposed to the highest doses of both drugs. No significant differences were observed for MTT or NR. These data demonstrate that Coc and Amph doses > or = 1 x 10(-5) M induce adverse effects on morphology and contractile activity of postnatal myocardial cell cultures.