An electrocardiographic, molecular and biochemical approach to explore the cardioprotective effect of vasopressin and milrinone against phosphide toxicity in rats

The present study was conducted to identify the protective effect of vasopressin (AVP) and milrinone
on cardiovascular function, mitochondrial complex activities, cellular ATP reserve, oxidative stress, and
apoptosis in rats poisoned by aluminum phosphide (AlP). Rats were divided into five groups (n = 12)
including control, AlP (12.5 mg/kg), AlP + AVP (2.0 Units/kg), AlP + milrinone (0.25 mg/kg) and
AlP + AVP + milrinone. After treatment, the animals were connected to an electronic cardiovascular
monitoring device to monitor electrocardiographic (ECG) parameter. Finally, oxidative stress biomarkers,
mitochondrial complex activities, ADP/ATP ratio and apoptosis were evaluated on the heart tissues. Results
indicated that AlP administration induced ECG abnormalities along with a decline in blood pressure and
heart rate. AVP and milrinone significantly ameliorated these changes in all treated groups. Considerable
protective effects on oxidative stress biomarkers, complex IV activity, ADP/ATP ratio and caspase-3 and
-9 activities in treated groups were also found. These findings were supported by flow cytometry assay
of cardiomyocytes. In conclusion, administration of AVP and milrinone, not only improve cardiovascular
functions in AlP poisoned rats in the short time, but after a long time can also restore mitochondrial
function and ATP level and reduce the oxidative damage, which prevent cardiomyocytes from entering
the apoptotic phase.