Učinak pentadekapeptida BPC 157 na produljeni QT interval u štakora uzrokovan ponavljanim dozama antipsihotika i antiemetika [The influence of pentadecapeptide BPC 157 on prolonged QT interval in rats caused with repetitive doses of antipsyhotics and antiemetics]

Strinić, Dean (2015) Učinak pentadekapeptida BPC 157 na produljeni QT interval u štakora uzrokovan ponavljanim dozama antipsihotika i antiemetika [The influence of pentadecapeptide BPC 157 on prolonged QT interval in rats caused with repetitive doses of antipsyhotics and antiemetics]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Repetitive use of different neuroleptics and antiemetics can lead to prolonged QT interval. The aims of our research were to investigate whether the use of pentadecapeptide BPC 157 can prevent the occurence of prolonged QT interval and is this effect dose related. We used 150 Wistar rats in investigation and after the application of neuroleptics/antiemetics, in experimental group intraperitoneally was applied BPC 157 in doses of 10 mcg/kg and 10 ng/kg and in control group saline in dose of 5 mg/kg. The therapeutic effect of the BPC 157 was followed-up during one hour. The electrocardiogram was determined before and 30 minutes and one hour after the application of neuroleptics/antiemetics and BPC 157/saline with assessment of the heart rate, PQ, QRS and QT intervals. The same procedure was repeated every day during seven days. We have proven that applied neuroleptics/antiemetics significantly prolong QT interval, and domperidone has no such effect, because after its aplication, QT intervalremains unchanged. Furthemore, we have shown that the patological effect on the QT interval caused by neuroleptics and antiemetics, can be neutralize by using BPC 157at doses of 10 mg/kg or 10 ng/kg. This research should demonstrate new possibilities in using BPC 157 after repetitive doses of neuroleptics/antiemetics because there is still no adequate therapy for prolonged QT interval.

Abstract in Croatian

Cilj istraživanja je bio praćenje nastanka srčanih aritmija u štakora davanjem repetitivnih visokih doza neuroleptika/antiemetika, utvrditi mogućnost njihovog liječenja primjenom BPC 157 i uvidjeti da li je njegov terapijski učinak ovisan o primjenjenoj dozi. U istraživanju smo u 150 Wistar štakora davali BPC 157 u dozama od 10 mcg/kg i 10 ng/kg eksperimentalnoj skupini ili FO 5ml/kg kontrolnoj skupini intraperitonealno, i to odmah nakon primjene neuroleptika/antiemetika. Terapijski učinak BPC 157 promatrali smo kroz sat vremena. Elektrokardiogram smo pratili prije, pola sata i sat nakon primjene neuroleptika/antiemetika i BPC 157/fiziološke otopine te smo isti postupak ponavljali svakodnevno kroz 7 dana uz određivanje frekvencije srca, PQ, QRS i QT intervala. Dobijeni rezultati su ukazali da su štakori koji su dobijali neuroleptik/antiemetik i BPC 157 imali znatno kraći QT interval nego životinje iz kontrolne skupine (p<0,05). Dokazali smo da primjenjeni neuroleptici/antiemetici značajno produljuju QT interval, dok domperidon nema takav učinak, jer nakon njegove primjene duljina QT intervala ostaje gotovo nepromijenjena. Nadalje, dokazali smo da navedeni patološki učinak na QT interval, koji su izazvali neuroleptici i antiemetici neutraliziramo primjenom pentadekapepetida BPC 157 u dozama 10 mcg/kg i 10 ng/kg. Ovo istraživanje je trebalo rasvijetliti mogućnost djelovanja BPC 157 na prolongirani QT interval uzrokovan repetitivnim uzimanjem neuroleptika i antiemetika, jer do sada nemamo adekvatan terapijski odgovor prolongiranom QT intervalu.

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