engleski

The pentadecapeptide BPC 157 prevents and reverses cardiac arrythmias and sphincter pressure failure caused by hyperkalemia

Background. Prolonged severe hyperkalemia induces suppression of the electrical activity of the heart which can lead to the cardiac arrest and sustained pressure failure in gastrointestinal sphincters [(LES) lower esophageal and (PS) pyloric sphincter] in rats. We assessed the effect of the gastric pentadecapeptide BPC 157 upon the effect of hyperkalemia on cardiac action and sphincter's pressure. Materials and methods. Wistar rats received KCl solution (9mEq/kg) i.p. ECG was continuously recorded. We assessed sphincter's pressure (as described J Pharmacol Sci, 2003, 2006, 2007, values were expressed as percentage of normal value) and K, Na, Ca serum values at 5, 10, 25, 30 min after the administration of KCl solution. Pentadecapeptide BPC 157 (10 μg/kg, i.p.) was given 30 min before KCl solution (pretreatment) either 5 min after (postreatment) KCl solution. Results. Severe hyperkalemia (K=12.5±2.2mmol/l) caused sphincter's pressure failure (LES pressure was at 5min 47% of normal value, at 10min 62%, at 25min 75%, at 30min 87%, PS pressure was at 5min 76% of normal velue, at 10min 66%, at 25min 56%, at 30min 50%) and progressing arrhythmias in control group. ECG recorded peaked T waves (at 5min), widening of the QRS-complex (0.05±0.002sec vrs 0.025±0.001sec in healty animals) with absence of P waves (at 10min), significant bradycardia (200±20/min versus 320±30/min in healthy animals) with asystolic pauses (0.6±0.025sec) (at 25min) and progression to cardic arrest (at 30min) in control group. At BPC 157 pretreated animals the sustained hyperkalemia persisted. On ECG regular sinus rhythm were recorded all the time with only peaked T waves. Sphincter's pressure were recovered at all time intervals approaching to the normal pressure values [LES 117%, PS 143% (at 5min), LES 110%, PS 133% (at 10min), LES 105%, PS 116% (at 25min), LES 100%, PS 96% (at 30min)]. BPC 157 at posttreated animals have not reversed sustained hyperkalemia, but amelioration of the arrhythmias occurred [peaked T waves (at 10min), widening of the QRS complex (0.05±0.002sec) (at 25min), regular sinus rhythm with slightly wide QRS complex (0.03±0.05sec vrs 0.025±0.001sec in healty animals) (at 30min)] as well the recovery of the sphincter's pressure failure [LES 95%, PS 90% (at 10min), LES 100%, PS 92% (at 25min), LES 110%, PS 95% (at 30min)]. Conclusion. Hyperkalemia causes arrhythmias and sphincter's pressure disturbances. Along with hyperkalemia, prominent sphincter's pressure fall precedes more severe arrhythmias. BPC 157 medication both prevented and reversed sphincter's pressure failure and arrhythmias, without reversal of hyperkalemia. There is ongoing reasrch on effect of pentadecapeptide BPC 157 on hyprekalemia in cell culture (HEK-293 cells) in witch preliminary results suggest that this peptide activate Na/K ATPase and through that way modulate efect of hyperkalemia on cell membrane potential. This could be potentional mechanisam which can explain results of this study.

BPC 157; hyperkalemia; cardiac arrythmias; rats

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