scholarly journals Plasma prohepcidin as a negative acute phase reactant after large cardiac surgery with a deep hypothermic circulatory arrest

2009 ◽  
pp. 827-833
Author(s):  
P Maruna ◽  
J Lindner ◽  
J Kunštýř ◽  
K Kubzová ◽  
J Hubáček

Hepcidin is a key regulator of iron metabolism and a mediator of anemia in inflammation. Recent in vitro studies recognized prohepcidin as a type II acute phase protein regulating via interleukin-6. The aim of the present study was to investigate the time course of plasma prohepcidin after a large cardiac surgery in relation to IL-6 and other inflammatory parameters. Patients with chronic thromboembolic hypertension (n=22, males/females 14/8, age 51.9±10.2 years) underwent pulmonary endarterectomy using cardiopulmonary bypass and deep hypothermic circulatory arrest were included into study. Arterial concentrations of prohepcidin, IL-1β, IL-6, IL-8, tumor necrosis factor-α, and C-reactive protein were measured before/after sternotomy, after circulatory arrest, after separation from bypass, and then 12, 18, 24, 36, 48 h and 72 h after the separation from bypass. Hemodynamic parameters, hematocrit and markers of iron metabolism were followed up. Pulmonary endarterectomy induced a 48 % fall in plasma prohepcidin; minimal concentrations were detected after separation from cardiopulmonary bypass. Prohepcidin decline correlated with an extracorporeal circulation time (p<0.01), while elevated IL-6 levels were inversely associated with duration of prohepcidin decline. Postoperative prohepcidin did not correlate with markers of iron metabolism or hemoglobin concentrations within a 72-h period after separation from CPB. Prohepcidin showed itself as a negative acute phase reactant during systemic inflammatory response syndrome associated with a cardiac surgery. Results indicate that the evolution of prohepcidin in postoperative period implies the antagonism of stimulatory effect of IL-6 and contraregulatory factors inhibiting prohepcidin synthesis or increasing prohepcidin clearance.

2011 ◽  
pp. 493-502 ◽  
Author(s):  
P. MARUNA ◽  
M. VOKURKA ◽  
J. LINDNER

Hepcidin, a recently discovered antimicrobial peptide synthesized in the liver, was identified to be the key mediator of iron metabolism and distribution. Despite our knowledge of hepcidin increased in recent years, there are only limited data on hepcidin regulation during systemic inflammatory response in human subjects. In a prospective study, the time course of plasma hepcidin was analyzed in relations to six inflammatory parameters – plasma cytokines and acute-phase proteins in patients undergoing uncomplicated pulmonary endarterectomy. Twenty-four patients (males, aged 52.6±10.2 years, treated with pulmonary endarterectomy in a deep hypothermic circulatory arrest) were enrolled into study. Hepcidin, interleukin (IL)-6, IL-8, tumor necrosis factor-α, C-reactive protein, α1-antitrypsin and ceruloplasmin arterial concentrations were measured before surgery and repeatedly within 120 h post-operatively. Hemodynamic parameters, hematocrit and markers of iron metabolism were followed up. In a postoperative period, hepcidin increased from preoperative level 8.9 ng/ml (6.2-10.7) (median and interquartile range) to maximum 16.4 ng/ml (14.1-18.7) measured 72 h after the end of surgery. Maximum post-operative concentrations of hepcidin correlated positively with maximum IL-6 levels. Both hepcidin and IL-6 maximum concentrations correlated positively with extracorporeal circulation time. In conclusions, the study demonstrated that plasma hepcidin is a positive acute-phase reactant in relation to an uncomplicated large cardiac surgery. Hepcidin increase was related to IL-6 concentrations and to the duration of surgical procedure. Our clinical findings are in conformity with recent experimental studies defining hepcidin as a type II acute-phase protein.


2020 ◽  
Author(s):  
Ludmila Khailova ◽  
Justin Robison ◽  
James Jaggers ◽  
Richard Ing ◽  
Scott Lawson ◽  
...  

Abstract Background: Infant cardiac surgery with cardiopulmonary bypass results in decreased circulating alkaline phosphatase that is associated with poor post-operative 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 (0-25U/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.


Perfusion ◽  
2020 ◽  
Vol 36 (1) ◽  
pp. 87-96
Author(s):  
Dennis Veerhoek ◽  
Laurentius JM van Barneveld ◽  
Renard G Haumann ◽  
Suzanne K Kamminga ◽  
Alexander BA Vonk ◽  
...  

Introduction: Pulmonary endarterectomy requires cardiopulmonary bypass and deep hypothermic circulatory arrest, which may prolong the activated clotting time. We investigated whether activated clotting time–guided anticoagulation under these circumstances suppresses hemostatic activation. Methods: Individual heparin sensitivity was determined by the heparin dose–response test, and anticoagulation was monitored by the activated clotting time and heparin concentration. Perioperative hemostasis was evaluated by thromboelastometry, platelet aggregation, and several plasma coagulation markers. Results: Eighteen patients were included in this study. During cooling, tube-based activated clotting time increased from 719 (95% confidence interval = 566-872 seconds) to 1,273 (95% confidence interval = 1,136-1,410 seconds; p < 0.01) and the cartridge-based activated clotting time increased from 693 (95% confidence interval = 590-796 seconds) to 883 (95% confidence interval = 806-960 seconds; p < 0.01), while thrombin–antithrombin showed an eightfold increase. The heparin concentration showed a slightly declining trend during cardiopulmonary bypass. After protamine administration (protamine-to-heparin bolus ratio of 0.82 (0.71-0.90)), more than half of the patients showed an intrinsically activated coagulation test and intrinsically activated coagulation test without heparin effect clotting time >240 seconds. Platelet aggregation through activation of the P2Y12 (adenosine diphosphate test) and thrombin receptor (thrombin receptor activating peptide-6 test) decreased (both −33%) and PF4 levels almost doubled (from 48 (95% confidence interval = 42-53 ng/mL) to 77 (95% confidence interval = 71-82 ng/mL); p < 0.01) between weaning from cardiopulmonary bypass and 3 minutes after protamine administration. Conclusion: This study shows a wide variation in individual heparin sensitivity in patients undergoing pulmonary endarterectomy with deep hypothermic circulatory arrest. Although activated clotting time–guided anticoagulation management may underestimate the level of anticoagulation and consequently result in a less profound inhibition of hemostatic activation, this study lacked power to detect adverse outcomes.


2004 ◽  
Vol 51 (3) ◽  
pp. 117-119
Author(s):  
Dusko Nezic ◽  
S. Borovic ◽  
Milan Cirkovic ◽  
Ljiljana Lausevic-Vuk ◽  
A. Kenkovski ◽  
...  

Two cases with catastrophic hemorrhage in redo cardiac surgery are described. In the first one tearing of right ventricle with uncontrolled bleeding occurred during sternal reentry. In the second one, tearing of the right atria occurred while the patient was on cardiopulmonary bypass. In both cases we were able to control bleeding using Foley catheter, which enabled us to proceed to deep hypothermic circulatory arrest to repair heart chambers (due to dense adhesions it was impossible to m?nage it in any other way). We have found this combined technique to be extremely useful tool to control catastrophic hemorrhage during redo cardiac surgery.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jesse A. Davidson ◽  
Ludmila Khailova ◽  
Amy Treece ◽  
Justin Robison ◽  
Danielle E. Soranno ◽  
...  

Abstract Acute kidney injury (AKI) is associated with prolonged hospitalization and mortality following infant cardiac surgery, but therapeutic options are limited. Alkaline phosphatase (AP) infusion reduced AKI in phase 2 sepsis trials but has not been evaluated for cardiac surgery-induced AKI. We developed a porcine model of infant cardiopulmonary bypass (CPB) with deep hypothermic circulatory arrest (DHCA) to investigate post-CPB/DHCA AKI, measure serum/renal tissue AP activity with escalating doses of AP infusion, and provide preliminary assessment of AP infusion for prevention of AKI. Infant pigs underwent CPB with DHCA followed by survival for 4 h. Groups were treated with escalating doses of bovine intestinal AP (1, 5, or 25U/kg/hr). Anesthesia controls were mechanically ventilated for 7 h without CPB. CPB/DHCA animals demonstrated histologic and biomarker evidence of AKI as well as decreased serum and renal tissue AP compared to anesthesia controls. Only high dose AP infusion significantly increased serum or renal tissue AP activity. Preliminary efficacy evaluation demonstrated a trend towards decreased AKI in the high dose AP group. The results of this dose-finding study indicate that AP infusion at the dose of 25U/kg/hr corrects serum and tissue AP deficiency and may prevent AKI in this piglet model of infant CPB/DHCA.


2020 ◽  
Author(s):  
Ludmila Khailova ◽  
Justin Robison ◽  
James Jaggers ◽  
Richard Ing ◽  
Scott Lawson ◽  
...  

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 (0-25U/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.


Perfusion ◽  
2008 ◽  
Vol 23 (4) ◽  
pp. 243-245 ◽  
Author(s):  
J Molnar ◽  
S Colah ◽  
M Larobina ◽  
SR Large ◽  
JE Arrowsmith ◽  
...  

As a consequence of the rising global prevalence and magnitude of obesity, a greater proportion of patients presenting for cardiac surgery is morbidly obese. Being overweight (body mass index; BMI 25-29.9 kg/m2) or obese (BMI 30-35 kg/m2) appears to confer some survival benefit following cardiac surgery. By contrast, morbid obesity (BMI >40 kg/m2) is associated with an increased likelihood of postoperative complications and prolonged intensive care unit and hospital length of stay. The physical difficulties encountered when managing this group of patients is exemplified by those undergoing complex, multiple procedures requiring prolonged cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). We present the successful management of a massively obese 19-year-old male (BMI 45 kg/m2) with Marfan’s syndrome who required aortic root and arch replacement under DHCA. The selection of extracorporeal circuit components to accommodate a large circulating volume and permit high CPB flow rates (>9 l/min) is discussed.


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