Key result
Pretreatment with morphine significantly reduced left ventricular-developed pressure (52.8 vs 102.5 mmHg) and enhanced doxorubicin-induced cardiotoxicity in isolated rat hearts.
Why the study?
Does morphine pretreatment reduce doxorubicin-induced cardiotoxicity in a rat model?
Does morphine pretreatment reduce doxorubicin-induced cardiotoxicity in a rat model?
Absolute Event Rate: 52.8% vs 102.5%
p-value: p=<0.05
Pretreatment with morphine exerts a cardiodepressive effect and enhances doxorubicin-induced cardiotoxicity in a rat model, an effect that is abolished by naloxone.
May caution opioid co-administration in anthracycline models; leaves open clinical translation and challenges cardioprotection assumptions.
Interventions to reduce the cardiotoxicity of doxorubicin are clinically relevant. Pharmacological preconditioning mimicking ischemic preconditioning has been demonstrated with morphine and represents an acceptable clinical intervention. The purpose of this study was to examine if pretreatment in vivo with morphine could reduce doxorubicin-induced cardiotoxicity ex vivo in a rat model. Wistar rats were divided into six groups and pretreated with an intraperitoneal (i.p.) injection of 3 or 10 mg/kg morphine, 1 mg/kg naloxone and saline, 1 mg/kg naloxone and 3 mg/kg morphine or saline, 60 min before excision of the heart. Biochemical indices such as troponin T (TnT) and hydrogen peroxide (H2O2) in effluate were measured together with physiological parameters in Langendorff hearts before and after doxorubicin infusion (2 mg/mL 0.05 mL/min for 45 min). Myocardial content of doxorubicin was measured at the end of infusion. Pretreatment with morphine, irrespective of dosage, produced a significant loss in left ventricular-developed pressure and an increase of TnT and H2O2 in effluate before doxorubicin infusion (p < 0.05). Morphine also produced a significant increase in left ventricular end-diastolic pressure and an increase of TnT and H2O2 in effluate (p < 0.05) at the end of doxorubicin infusion. Naloxone, a non-selective opioid receptor antagonist, abolished the effects of morphine both before and after doxorubicin infusion. Morphine, irrespective of dosage, increased myocardial content of doxorubicin compared to pretreatment with saline (p < 0.05). Pretreatment with morphine is associated with a cardiodepressive effect and enhances cardiotoxicity of doxorubicin measured by increased myocardial accumulation of doxorubicin and physiological and biochemical indices. The negative effects observed in our rat model are abolished by naloxone.
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Hole et al. (2014) studied Doxorubicin-induced cardiotoxicity (n=36). Morphine vs. Saline was evaluated on Left ventricular-developed pressure (LVDP) at the end of doxorubicin infusion (p=<0.05). Pretreatment with morphine significantly reduced left ventricular-developed pressure (52.8 vs 102.5 mmHg) and enhanced doxorubicin-induced cardiotoxicity in isolated rat hearts.