Mitochondrial DNA is Elevated in the Circulation After OPCAB, CABG and TRAUMA

None/Trivial

Mild

2012 ANZSCTS Annual Scientific Meeting

Moderate

Mod-Sev

Severe

OPEN CMR

84.6%

15.4%

0%

0%

0%

Echo

92.3%

7.7%

0%

0%

0%

TAVI CMR

15%

35%

20%

20%

10%

Echo

35%

35%

20%

5%

0%

Discussion: When compared to CMR based quantitative analysis, TTE consistently underestimated the degree of paravalvular aortic regurgitation. This underestimation may in part explain the recent findings of the PARTNER trial, which has demonstrated ‘mild’ paravalvular leak to be a predictor of long-term mortality as TTE assessed mild may in fact be quantitatively higher. http://dx.doi.org/10.1016/j.hlc.2013.03.032 2012 Poster Presentation/Panel 7

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also trauma patients had higher mtDNA than CABG and OPCAB patients at each time point that did not reach statistical significance. The ratio of mitochondrial to nucelar DNA was significantly elevated after trauma than CABG or OPCAB (day 5 CABG 1.187 vs. day 5 OPCAB 1.158 vs. day 5 trauma 1.239, p < 0.01). Conclusion: Mitochondrial DNA is elevated in the plasma after CABG, OPCAB and trauma. The greater increase in mtDNA after trauma may explain the increased incidence of SIRS that occurs after severe trauma compared with either CABG or OPCAB. Further work is required to determine whether mtDNA can predict the risk of SIRS in the post-operative recovery. http://dx.doi.org/10.1016/j.hlc.2013.03.033 2012 Poster Presentation/Panel 8 Off-Pump Coronary Artery Bypass Surgery Induces Prolonged Alterations to Host Neutrophil Physiology

Mitochondrial DNA is Elevated in the Circulation After OPCAB, CABG and TRAUMA

J.J.B. Edelman 1,2,3,4,∗ , Y.L. Fung 1,2,3,4 , G.J. 1,2,3,4 1,2,3,4 Pennings , P.G. Bannon , L. Kritharides 1,2,3,4 , J.F. Fraser 1,2,3,4 , M.P. Vallely 1,2,3,4

J.J.B. Edelman ∗ , M.B. Kirschner, A. White, Z. Balogh, P.G. Bannon, L. Kritharides, J.F. Fraser, G. Reid, M.P. Vallely

2 Royal

The Baird Institute, Asbestos Diseases Research Institute, Department of Trauma, John Hunter Hospital, ANZAC Research Institute, Critical Care Research Group, Australia Introduction: The release of mitochondrial DNA (mtDNA) into the circulation has recently been proposed as the mechanistic link between severe trauma and systemic inflammatory response syndrome (SIRS). A similar relationship could be responsible for inflammatory response observed in CABG/OPCAB patients. Methods: Blood was drawn from 36 patients undergoing CABG or OPCAB pre-operatively, and on day 1, 3 and 5 post-operatively; and from 13 patients on days 1, 3 and 5 after severe traumatic injury. These were compared to 12 healthy controls. Following isolation of genomic DNA, quantitative PCR (qPCR) was use to measure levels of the mitochondrial genes COX3, cytochrome B and NADH, as well as level of nuclear ␤-globin. Data was expressed as the inverse of the threshold for detection (1/Cq). Levels of mtDNA after traumatic injury were compared with those of healthy controls. Results: Healthy controls and patients with traumatic injury were significantly younger than those undergoing surgical revascularisation and had fewer co-morbidities. However, there was no significant difference in baseline mtDNA levels between patients undergoing CABG or OPCAB and healthy controls. Compared with preoperative baseline, there was a significant increase in the levels of mtDNA in both CABG and OPCAB that persisted until post-operative day 5 (CABG: pre-operative 0.033 vs. day 5 0.044, p < 0.001; OPCAB pre-operative 0.031 vs. day 5 0.043, p < 0.001). Patients after trauma had significantly higher mtDNA levels than healthy controls (healthy controls 0.032 vs. day 1 0.045, day 5 0.048 p < 0.0001);

1 The

Baird Institute, Sydney, Australia Prince Alfred Hospital, Sydney, Australia 3 ANZAC Research Institute, Sydney, Australia 4 Critical Care Research Group, Brisbane, Australia Introducion: Persistent alteration to host polymorphonuclear cell (PMN) physiology has been demonstrated after cardiac surgery performed with cardiopulmonary bypass. However, to date PMN physiology and function beyond the first 24 h has not been investigated after cardiac surgery performed without cardiopulmonary bypass (OPCAB). Methods: Blood samples of 15 patients were collected pre-operatively, and on days 1, 3 and 5 after OPCAB. Expression of CD11b, CD18, CBRM 1/5 and CD62L were assessed by flow cytometry under resting conditions and after stimulation with formyl methionyl-leucylphenylalanine (fMLP), and respiratory burst activity was also measured. Results: Under resting conditions, PMN CD11b, CBRM1/5 and CD62L expression were minimally altered by surgery at the measured time points. Compared with the response of pre-operative PMNs, PMNs assayed on days 3 and 5 after OPCAB demonstrated a significantly blunted increase in the expression of CD11b and CBRM1/5 after fMLP stimulation (CD11b: pre-operative +160%, day 3 +119%, day 5. 75%; p < 0.001), significantly diminished shedding of CD62L (pre-operative −88% vs. day 3 −79% vs. day 5 −81%, p < 0.05) in response to platelet activating factor (PAF) and fMLP, and diminished superoxide production after stimulation on day 3 (pre-operative +641% vs. day 3 +363%). Conclusion: The alteration of PMN function after OPCAB implies that cardiac surgical trauma, rather than cardiopulmonary bypass, directly modulates host PMN physiology. The prolonged alteration in neutrophil

ABSTRACTS

Heart, Lung and Circulation 2013;22:455–489