Bidirectional relationship between reduced blood pH and acute pancreatitis: A translational study of their noxious combination

Zoltan Rumbus, Emese Toth, Laszlo Poto, A. Vincze, G. Verès, L. Czakó, Emoke Olah, Katalin Marta, Alexandra Miko, Z. Rakonczay, Zsolt Balla, J. Kaszaki, Imre Foldesi, Jozsef Maleth, P. Hegyi, Andras Garami

Research output: Article

Abstract

Acute pancreatitis (AP) is often accompanied by alterations in the acid-base balance, but how blood pH influences the outcome of AP is largely unknown. We studied the association between blood pH and the outcome of AP with meta-analysis of clinical trials, and aimed to discover the causative relationship between blood pH and AP in animal models. PubMed, EMBASE, and Cochrane Controlled Trials Registry databases were searched from inception to January 2017. Human studies reporting systemic pH status and outcomes (mortality rate, severity scores, and length of hospital stay) of patient groups with AP were included in the analyses. We developed a new mouse model of chronic metabolic acidosis (MA) and induced mild or severe AP in the mice. Besides laboratory blood testing, the extent of pancreatic edema, necrosis, and leukocyte infiltration were assessed in tissue sections of the mice. Thirteen studies reported sufficient data in patient groups with AP (n = 2,311). Meta-analysis revealed markedly higher mortality, elevated severity scores, and longer hospital stay in AP patients with lower blood pH or base excess (P < 0.001 for all studied outcomes). Meta-regression analysis showed significant negative correlation between blood pH and mortality in severe AP. In our mouse model, preexisting MA deteriorated the pancreatic damage in mild and severe AP and, vice versa, severe AP further decreased the blood pH of mice with MA. In conclusion, MA worsens the outcome of AP, while severe AP augments the decrease of blood pH. The discovery of this vicious metabolic cycle opens up new therapeutic possibilities in AP.

Original languageEnglish
Article number1360
JournalFrontiers in Physiology
Volume9
Issue numberOCT
DOIs
Publication statusPublished - okt. 1 2018

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Pancreatitis
Acidosis
Meta-Analysis
Length of Stay
Mortality
Acid-Base Equilibrium
PubMed
Registries
Edema
Leukocytes
Necrosis
Animal Models
Regression Analysis
Clinical Trials
Databases

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Bidirectional relationship between reduced blood pH and acute pancreatitis : A translational study of their noxious combination. / Rumbus, Zoltan; Toth, Emese; Poto, Laszlo; Vincze, A.; Verès, G.; Czakó, L.; Olah, Emoke; Marta, Katalin; Miko, Alexandra; Rakonczay, Z.; Balla, Zsolt; Kaszaki, J.; Foldesi, Imre; Maleth, Jozsef; Hegyi, P.; Garami, Andras.

In: Frontiers in Physiology, Vol. 9, No. OCT, 1360, 01.10.2018.

Research output: Article

Rumbus, Zoltan ; Toth, Emese ; Poto, Laszlo ; Vincze, A. ; Verès, G. ; Czakó, L. ; Olah, Emoke ; Marta, Katalin ; Miko, Alexandra ; Rakonczay, Z. ; Balla, Zsolt ; Kaszaki, J. ; Foldesi, Imre ; Maleth, Jozsef ; Hegyi, P. ; Garami, Andras. / Bidirectional relationship between reduced blood pH and acute pancreatitis : A translational study of their noxious combination. In: Frontiers in Physiology. 2018 ; Vol. 9, No. OCT.
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AU - Rumbus, Zoltan

AU - Toth, Emese

AU - Poto, Laszlo

AU - Vincze, A.

AU - Verès, G.

AU - Czakó, L.

AU - Olah, Emoke

AU - Marta, Katalin

AU - Miko, Alexandra

AU - Rakonczay, Z.

AU - Balla, Zsolt

AU - Kaszaki, J.

AU - Foldesi, Imre

AU - Maleth, Jozsef

AU - Hegyi, P.

AU - Garami, Andras

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AB - Acute pancreatitis (AP) is often accompanied by alterations in the acid-base balance, but how blood pH influences the outcome of AP is largely unknown. We studied the association between blood pH and the outcome of AP with meta-analysis of clinical trials, and aimed to discover the causative relationship between blood pH and AP in animal models. PubMed, EMBASE, and Cochrane Controlled Trials Registry databases were searched from inception to January 2017. Human studies reporting systemic pH status and outcomes (mortality rate, severity scores, and length of hospital stay) of patient groups with AP were included in the analyses. We developed a new mouse model of chronic metabolic acidosis (MA) and induced mild or severe AP in the mice. Besides laboratory blood testing, the extent of pancreatic edema, necrosis, and leukocyte infiltration were assessed in tissue sections of the mice. Thirteen studies reported sufficient data in patient groups with AP (n = 2,311). Meta-analysis revealed markedly higher mortality, elevated severity scores, and longer hospital stay in AP patients with lower blood pH or base excess (P < 0.001 for all studied outcomes). Meta-regression analysis showed significant negative correlation between blood pH and mortality in severe AP. In our mouse model, preexisting MA deteriorated the pancreatic damage in mild and severe AP and, vice versa, severe AP further decreased the blood pH of mice with MA. In conclusion, MA worsens the outcome of AP, while severe AP augments the decrease of blood pH. The discovery of this vicious metabolic cycle opens up new therapeutic possibilities in AP.

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