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Protamine and acute depletion of magnesium limit bone response to parathyroid hormone
K G Ragosta1, W H Bergstrom, D G Briggs
1Department of Pediatrics, State University of New York, Syracuse 13210, USA.
Insights
Protamine administration during cardiopulmonary bypass significantly lowers serum and ionized calcium levels in pediatric patients. This hypocalcemia is linked to protamine blocking parathyroid hormone receptors in bone.
Area of Science:
- Cardiovascular Surgery
- Pediatric Medicine
- Biochemistry
Background:
- Cardiopulmonary bypass (CPB) is a critical procedure in pediatric cardiac surgery.
- Maintaining calcium homeostasis is vital during CPB.
- Protamine is used to reverse heparin anticoagulation but can cause adverse effects.
Purpose of the Study:
- To investigate the effect of protamine on calcium homeostasis in pediatric patients undergoing CPB.
- To elucidate the mechanism behind protamine-induced hypocalcemia.
Main Methods:
- Studied nine pediatric patients undergoing CPB, measuring total and ionized calcium levels before and after protamine administration.
- Utilized a bone disk bioassay to assess bone response to parathyroid hormone (PTH) and protamine.
- Evaluated the role of magnesium in bone's response to PTH.
Main Results:
- Protamine administration led to a significant decrease in total serum calcium (8.44 to 7.49 mg/dL) and ionized calcium (1.39 to 1.31 mmol/L).
- Bone disks treated with protamine lost their responsiveness to PTH (E/C = 0.9, P = NS).
- Bone retained responsiveness to a PTH-induced messenger (E/C = 0.42, P < 0.001) and showed reversible loss of PTH response with magnesium depletion.
Conclusions:
- Protamine appears to block parathyroid hormone receptors, contributing to hypocalcemia during CPB.
- Magnesium depletion may also impair bone's response to PTH, potentially exacerbating hypocalcemia.
- These findings may explain persistent hypocalcemia in some pediatric patients post-CPB.
Abstract:
The effect of protamine on calcium homeostasis was studied in nine pediatric patients undergoing cardiopulmonary bypass. Total serum calcium decreased from 8.44 mg/dL to 7.49 mg/dL (P < 0.05) after protamine. Ionized calcium decreased from 1.39 to 1.31 mmol/L (P < 0.05). A bioassay determined the etiology of this response. Bone disks were placed in sera, protamine, parathyroid hormone, parathyroid hormone antibody, or magnesium-depleted solutions, then were incubated in solutions with known calcium content. The change in the media's calcium concentration reflects the bone's response to the initial stimulus. Calcium change is expressed as Experimental delta/Control delta (E/C). Normal bone responds to parathyroid hormone, E/C = 0.59 (P < 0.001). Protamine-treated bone loses this response, E/C = 0.9 (P = not significant [NS]). A parathyroid-hormone-induced osteoblast messenger was found. Protamine-treated bone continued to respond to this messenger, E/C = 0.42 (P < 0.001). Bone showed reversible loss of response to parathyroid hormone after incubation in magnesium-free solution, E/C = 0.93 (P = NS). With reincubation in magnesium, E/C = 0.69 (P < 0.01). Since protamine blocks parathyroid receptors, and magnesium depletion limits the bone's response to parathyroid hormone, this may explain the persistent hypocalcemia seen in some patients undergoing cardiopulmonary bypass.