Neutrophils and platelets accumulate in the heart, lungs, and kidneys after cardiopulmonary bypass in neonatal pigs

Christensen, Vibeke Brix; Tønnesen, Else; Hjortdal, Vibeke E.; Chew, Michelle; Flø, Christian; Marqversen, J.; Hansen, Joachim Frølund; Andersen, Niels Trolle; Ravn, Hanne Berg

doi:10.1097/00003246-200203000-00029

Cited by 31 publications

(36 citation statements)

References 45 publications

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“…The 2-wk-old piglets used in this study are intended to be a model of the neonatal human heart, although, as with the human heart, the exact ultrastructural developmental stage is unknown. Nevertheless, similar porcine models have been used by other investigators to study neonatal myocardium (14,15). Overall, our results support the contention that the immature heart may be uniquely sensitive to the ischemia and reperfusion that occur with congenital heart surgery.…”

Section: Discussionsupporting

confidence: 86%

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Glucocorticoids Preserve Calpastatin and Troponin I during Cardiopulmonary Bypass in Immature Pigs

et al. 2003

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Degradation of troponin I (TnI) by calpain occurs with myocardial stunning in ischemia-reperfusion injury. Glucocorticoids attenuate myocardial ischemia-reperfusion injury, but their effect on TnI degradation is unknown. A piglet model was used to test the hypotheses that cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) are associated with TnI degradation and that TnI alterations could be prevented by glucocorticoid treatment. Piglets were cooled to 18°C, subjected to 2 h of circulatory arrest, rewarmed to 37°C, and allowed to recover for 2 h. Methylprednisolone was administered 6 h before surgery (3 0 mg/kg) and at initiation of CPB (30 mg/kg). The untreated group received saline. Left ventricular tissue was collected after recovery and analyzed by Western blot for TnI, calpain, and calpastatin (the natural inhibitor of calpain). CPB/ DHCA animals had 27.4 Ϯ 0.2% of total detected TnI present in degraded form. Glucocorticoid treatment significantly decreased the percentage of degraded TnI (12.0 Ϯ 0.1%, p Ͻ 0.05). Calpain I and calpain II increased after CPB/DHCA compared with non-CPB/DHCA controls (p Ͻ 0.05), with or without glucocorticoid treatment. Calpastatin significantly decreased in untreated CPB/DHCA animals compared with non-CPB/DHCA controls (p Ͻ 0.05), but levels were preserved by glucocorticoids. Glucocorticoids were associated with preservation of maximum rate of increase of left ventricular pressure at 95 Ϯ 10% of baseline, whereas maximum rate of increase of left ventricular pressure decreased to 62 Ϯ 12% of baseline without steroids. TnI degradation occurs after CPB/DHCA in neonatal pigs. Reduction in reperfusion injury by glucocorticoids may depend partly on preservation of calpastatin activity and intact TnI. Surgery for congenital heart disease often requires CPB and periods of myocardial ischemia. A period of total circulatory arrest may also be required, particularly for complex neonatal repairs. In the first 8 to 12 h after CPB there is a transient decrease in myocardial function consistent with reperfusion injury (1). Although the exact mechanisms of CPB-related myocardial injury remain unknown, there is substantial evidence that CPB can produce a systemic inflammatory response or free radical injury (2-4). The cysteine protease calpain exists in the myocardium in two isoforms, calpain I and calpain II. Recently, it has been suggested that activation of calpain during reperfusion of ischemic myocardium may be a key event in the process of myocardial stunning (5, 6). Calcium influx that occurs when ischemic myocardium is reperfused promotes dissociation of calpain from its inhibitor, calpastatin. Activated calpain then degrades the contractile regulatory protein TnI by cleavage at the C-terminus to form the fragment . Additional systematic degradation of the amino terminus can lead to subsequent smaller degradation products. Degradation products and covalent complexes of TnI have been observed in humans with ischemic heart disease (7,8).The use of glucocorticoids ...

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Section: Discussionsupporting

confidence: 86%

“…We therefore chose to examine CPB with DHCA in 2-wk-old piglets. Piglets of this age have routinely been used to mimic the neonatal human heart (14,15). This model was designed to simulate congenital heart surgery in the context of the immature myocardium.…”

mentioning

confidence: 99%

Glucocorticoids Preserve Calpastatin and Troponin I during Cardiopulmonary Bypass in Immature Pigs

et al. 2003

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“…It is well known that the lungs and kidneys are organs at high risk for postoperative dysfunction (1,4,13). The exact role of local cytokine production induced by the CPB procedure remains to be clarified, but the impaired oxygenation found in all CPB-pigs might be a consequence of the inflammatory state manifested as mRNA-cytokine production.…”

Section: Discussionmentioning

confidence: 99%

“…This postoperative temporary organ dysfunction is thought to be a consequence of the systemic inflammatory response elicited by cardiac surgery and CPB (4).…”

mentioning

confidence: 99%

Plasma cytokines do not reflect expression of pro‐ and anti‐inflammatory cytokine mRNA at organ level after cardiopulmonary bypass in neonatal pigs*

Christensen

Vestergaard²,

Chew

et al. 2003

Acta Anaesthesiol Scand

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“…4 The degree of injury resulting from leukocyteendothelial interaction correlates clinically with the post-operative impairment of major organs. 6 It is well known that CPB itself causes functional deterioration of the heart and lung. Such injury also occurs in the kidneys and the brain and is thought to reflect an exaggerated systemic inflammatory response by activation and accumulation of leukocytes.…”

Section: The Inflammatory Response To Cardiopulmonary Bypass (Complemmentioning

confidence: 99%

What is the Role of Leukocyte Depletion in Cardiac Surgery?

Lim

Anderson

Leong

et al. 2007

Heart, Lung and Circulation

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Neutrophils and platelets accumulate in the heart, lungs, and kidneys after cardiopulmonary bypass in neonatal pigs

Cited by 31 publications

References 45 publications

Glucocorticoids Preserve Calpastatin and Troponin I during Cardiopulmonary Bypass in Immature Pigs

Glucocorticoids Preserve Calpastatin and Troponin I during Cardiopulmonary Bypass in Immature Pigs

Plasma cytokines do not reflect expression of pro‐ and anti‐inflammatory cytokine mRNA at organ level after cardiopulmonary bypass in neonatal pigs*

What is the Role of Leukocyte Depletion in Cardiac Surgery?

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