Stable gastric pentadecapeptide BPC 157 and bupivacaine.
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.
Department of Anesthesiology and Resuscitation, County Hospital "Dr. Ivo Pedisic", Sisak, Croatia.
Gordana
G
Zivanovic-Posilovic
Department of Internal Medicine, County Hospital "Dr. Ivo Pedisic", Sisak, Croatia.
Diana
D
Balenovic
Department of Internal Medicine, County Hospital "Pozega", Pozega, Croatia.
Ivan
I
Barisic
Department of Internal Medicine, School of Medicine, University of Zagreb, Zagreb, Croatia.
Dean
D
Strinic
Department of Anesthesiology and Resuscitation, School of Medicine, University of Zagreb, Zagreb, Croatia.
Vasilije
V
Stambolija
Department of Internal Medicine, School of Medicine, University of Zagreb, Zagreb, Croatia.
Mario
M
Udovicic
Department of Anesthesiology and Resuscitation, School of Medicine, University of Zagreb, Zagreb, Croatia.
Sandra
S
Uzun
Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia.
Domagoj
D
Drmic
Laboratory of Molecular Neuropharmacology, Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia.
Josipa
J
Vlainic
Department of Internal Medicine, School of Medicine, University of Zagreb, Zagreb, Croatia.
Martina Lovric
ML
Bencic
Department of Physiology and Immunology, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Zagreb, Croatia.
Aleksandra
A
Sindic
Department of Pathology, School of Medicine, University of Zagreb, Zagreb, Croatia.
Sven
S
Seiwerth
Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia. Electronic address: sikiric@mef.hr.
Predrag
P
Sikiric
D000595:Amino Acid Sequence; D000818:Animals; D002045:Bupivacaine / Q000633:toxicity*; D004562:Electrocardiography / Q000187:drug effects; D057809:HEK293 Cells; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D010446:Peptide Fragments / Q000737:chemistry* / Q000494:pharmacology*; D055550:Protein Stability; D011506:Proteins / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects*
D007473:Ion Channels; D010446:Peptide Fragments; D011506:Proteins; C083833:BPC 157; D002045:Bupivacaine
BPC 157; Bupivacaine; Cardiotoxicity; HEK293 cell depolarization; Rats