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[Effects of morphine of different concentrations on myocardial action potential]
Abstract:
The effects of morphine at different concentrations on myocardial action potential were studied in isolated right ventricular papillary muscles of the guinea pig. It was observed that morphine at low concentrations (0.2-1.6 mumol/L) shortened the action potential duration (ADP) and effective refractory period (ERP) in a concentration dependent manner. These effects could be abolished by naloxone (1 mumol/L), phentolamine, tetraethylammonium (TEA) and cesium chloride (Cs+), but not by verapamil. On the other hand, morphine at high concentrations (15-120 mumol/L) prolonged ADP and ERP in a concentration dependent manner. The effects were unaffected by low dose of naloxone (1.2 mumol/L) but were abolished by high dose of naloxone (10 mumol/L), phentolamine, TEA, Cs+ and verapamil. These results suggest that morphine at low and high concentrations might stimulate different subtypes of opioid receptors. The effects of morphine in low concentrations are associated with the activation of potassium channel, whereas the effects of morphine at high concentrations are associated with the activation of potassium channel, calcium channel or calcium activated potassium channel. The action of opioid receptor was closely related to alpha adrenoreceptors.
Insights
Morphine affects heart muscle differently based on concentration. Low doses shorten action potential duration and refractory period, while high doses prolong them, suggesting distinct opioid receptor actions.
Area of Science:
- Cardiology
- Pharmacology
- Electrophysiology
Context:
- Morphine, an opioid analgesic, has known effects on the central nervous system.
- Its direct impact on cardiac electrophysiology, particularly at varying concentrations, requires detailed investigation.
- Understanding these effects is crucial for managing potential cardiac side effects of opioid use.
Purpose:
- To investigate the concentration-dependent effects of morphine on myocardial action potential duration (ADP) and effective refractory period (ERP) in guinea pig ventricular papillary muscles.
- To elucidate the specific ion channels and receptor subtypes involved in morphine's cardiac actions.
- To differentiate the mechanisms underlying low-dose versus high-dose morphine effects on cardiac electrophysiology.
Summary:
- Low concentrations (0.2-1.6 mumol/L) of morphine shortened ADP and ERP, effects reversible by naloxone, phentolamine, tetraethylammonium (TEA), and cesium chloride (Cs+), but not verapamil.
- High concentrations (15-120 mumol/L) of morphine prolonged ADP and ERP, with effects abolished by high-dose naloxone, phentolamine, TEA, Cs+, and verapamil.
- These findings suggest morphine stimulates different opioid receptor subtypes at low and high concentrations, involving potassium and calcium channels, and alpha-adrenoreceptors.
Impact:
- Reveals distinct concentration-dependent mechanisms of morphine on cardiac electrophysiology.
- Highlights the potential involvement of multiple ion channels (potassium, calcium) and receptor subtypes in morphine's cardiac effects.
- Provides a basis for understanding and potentially mitigating opioid-induced cardiotoxicity.