Tissue alkaline phosphatase activity and expression in an experimental infant swine model of cardiopulmonary bypass with deep hypothermic circulatory arrest

Abstract

Background: Infant cardiac surgery with cardiopulmonary bypass results in decreased circulating alkaline phosphatase that is associated with poor postoperative outcomes. Bovine intestinal alkaline phosphatase infusion represents a novel therapy for post-cardiac surgery organ injury. However, the effects of cardiopulmonary bypass and bovine-intestinal alkaline phosphatase infusion on tissue-level alkaline phosphatase activity/expression are unknown. Methods: Infant pigs (n = 20) underwent cardiopulmonary bypass with deep hypothermic circulatory arrest followed by four hours of intensive care. Seven control animals underwent mechanical ventilation only. Cardiopulmonary bypass/deep hypothermic circulatory arrest animals were given escalating doses of bovine intestinal alkaline phosphatase infusion (0-25 U/kg/hr.; n = 5/dose). Kidney, liver, ileum, jejunum, colon, heart and lung were collected for measurement of tissue alkaline phosphatase activity and mRNA. Results: Tissue alkaline phosphatase activity varied significantly across organs with the highest levels found in the kidney and small intestine. Cardiopulmonary bypass with deep hypothermic circulatory arrest resulted in decreased kidney alkaline phosphatase activity and increased lung alkaline phosphatase activity, with no significant changes in the other organs. Alkaline phosphatase mRNA expression was increased in both the lung and the ileum. The highest dose of bovine intestinal alkaline phosphatase resulted in increased kidney and liver tissue alkaline phosphatase activity. Conclusions: Changes in alkaline phosphatase activity after cardiopulmonary bypass with deep hypothermic circulatory arrest and bovine intestinal alkaline phosphatase delivery are tissue specific. Kidneys, lung, and ileal alkaline phosphatase appear most affected by cardiopulmonary bypass with deep hypothermic circulatory arrest and further research is warranted to determine the mechanism and biologic importance of these changes.

Ethanol Leaf Extract of Synsepalum dulcificum Schumach. & Thonn. (Sapotaceae) Induces Distortions in Renal, Hepatic and Reproductive Indices in Sprague-Dawley Rats

“…In this study, AST and ALP were significantly increased compared to control. This suggests a pertubatory effect of the extract on hepatocytes cytoskeleton and predictive osteotoxic (Ahmad et al, 2002;Giannini et al, 2005;Davidson et al, 2019;Khailova et al, 2020). Bilirubin is the product of haemoglobin catabolism.…”

“…Increase in AST is secondary to hepatic insult which may be as a result of disruption to hepatocytes membrane architecture elicited by toxicants (Olson et al, 2000). ALP is used as a biomarker for plasma membrane integrity of tissues (Khailova et al, 2020). Serum ALP is an osteogenic marker (Wu et al, 2017) and is elevated as a consequence of bone disease (Sarac and Saygili, 2014).…”

Dietary 25 Hydroxyvitamin D3 Improved Serum Concentration Level and Alkaline Phosphatase Activity during Lactation but Had Meager Impact on Post-Farrowing Reproductive Performance in Sows

“…The need for phosphorus (P) is the most probable driving factor for increased ALP activity during lactation. At the jejunum of the small intestine, dietary P is absorbed into the bloodstream and transported to organs where it mediates various metabolic functions, including those of fetal and mammary gland development during gestation and lactation, thereby contributing significantly to the total P level in the circulation [11]. In a P replete state, unbound P can be readily absorbed into the circulation; this process drives the activity of ALP [36].…”

“…This enzyme is highly expressed in growing animals due to an increase in the activity of osteoblasts. However, hepatic cells also play a role in augmenting the enzyme levels in mature animals [11]. The activity of ALP is required to metabolize inorganic phosphates, reduce pyrophosphates (which are known inhibitors of mineralization), and increase phosphate localization in osteons [12].…”

Hemodinâmica pulmonar em pacientes pediátricos com defeitos septais cardíacos congênitos e hipertensão pulmonar: o papel da síndrome de Down e da resposta inflamatória sistêmica

“…No contexto pediátrico, os efeitos da circulação extracorpórea sobre o tecido pulmonar têm sido amplamente estudados tanto no cenário clínico como em modelos experimentais (152,153). Estudos têm sido desenvolvidos no sentido de identificar mecanismos moleculares envolvidos na lesão pulmonar.…”