Bupivacaine toxicity following accidental overdose still lacks therapeutic
solution. However, there are major arguments for testing
BPC 157 against
bupivacaine toxicity in vivo in rats, in particular, and then finally, in vitro. These are: the lack of any known
BPC 157 toxicity, a lifesaving effect via the mitigation of arrhythmias in rats underwent
hyperkalemia or digitalis toxicity, the elimination of
hyperkalemia and arrhythmias in rats underwent
succinylcholine toxicity and finally, the reduction of
potassium-induced depolarization in vitro (in HEK293 cells) in severe
hyperkalemia. Most importantly,
BPC 157 successfully prevents and counteracts
bupivacaine cardiotoxicity;
BPC 157 is effective even against the worst outcomes such as a severely prolonged QRS complex. Here, rats injected with
bupivacaine (100mg/kg IP) exhibited
bradycardia,
AV-block, ventricular ectopies,
ventricular tachycardia, T-wave elevation and
asystole. All of the fatalities had developed T-wave elevation, high-degree
AV-block, respiratory arrest and
asystole. These were largely counteracted by
BPC 157 administration (50µg/kg, 10µg/kg, 10ng/kg, or 10pg/kg IP) given 30min before or 1min after the
bupivacaine injection. When
BPC 157 was given 6min after
bupivacaine administration, and after the development of prolonged QRS intervals (20ms), the fatal outcome was markedly postponed. Additionally, the effect of
bupivacaine on cell membrane depolarization was explored by measuring membrane voltages (Vm) in HEK293 cells.
Bupivacaine (1mM) alone caused depolarization of the cells, while in combination with
BPC 157 (1µm), the
bupivacaine-induced depolarization was inhibited. Together, these findings suggest that the stable gastric pentadecapeptide
BPC 157 should be a potential
antidote for
bupivacaine cardiotoxicity.