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Pilot proteomic profile of differentially regulated proteins in right atrial appendage before and after cardiac surgery using cardioplegia and cardiopulmonary bypass.

ABSTRACT: Although highly protective, cardiac surgery using cardioplegia and cardiopulmonary bypass (CP/CPB) subjects myocardium to hypothermic reversible ischemic injury that can impair cardiac function which results in a greatly enhanced risk of mortality. Acute changes in myocardial contractile activity are likely regulated via protein modifications. We performed the following study to determine changes in the protein profile of human myocardium following CP/CPB.Right atrial appendage was collected from 8 male patients pre and post-CP/CPB. Atrial tissue lysates were subjected to 2-dimensional electrophoresis, total protein staining, gel averaging, and quantitative densitometry. Ten prominent spots regulated in response to CP/CPB were identified using mass spectrometry. Two hundred twenty-five and 256 protein spots were reliably detected in 2D-gels from pre- and post-CP/CPB patients, respectively. Five unique (ie, not detected post-CP/CPB) and 17 significantly increased spots were detected pre-CP/CPB. Thirty-four unique and 25 significantly increased spots were detected in the post-CP/CPB group. Identified proteins that changed after CP/CPB included: MLC-2a, ATP-synthase delta chain and Enoyl-CoenzymeA hydratase, glutathione-s-transferase omega, alpha-1-acid-glycoprotein, and phosphatidylethanolamine-binding protein.Cardiac surgery results in multiple consistent changes in the human myocardial protein profile. CP/CPB modifies specific cytoskeletal, metabolic, and inflammatory proteins potentially involved in deleterious effects of CP/CPB.

SUBMITTER: Clements RT

PROVIDER: S-EPMC2629397 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Pilot proteomic profile of differentially regulated proteins in right atrial appendage before and after cardiac surgery using cardioplegia and cardiopulmonary bypass.

Clements Richard T RT Smejkal Gary G Sodha Neel R NR Ivanov Alexander R AR Asara John M JM Feng Jun J Lazarev Alexander A Gautam Shiva S Senthilnathan Venkatachalam V Khabbaz Kamal R KR Bianchi Cesario C Sellke Frank W FW

Circulation 20080901 14 Suppl

<h4>Background</h4>Although highly protective, cardiac surgery using cardioplegia and cardiopulmonary bypass (CP/CPB) subjects myocardium to hypothermic reversible ischemic injury that can impair cardiac function which results in a greatly enhanced risk of mortality. Acute changes in myocardial contractile activity are likely regulated via protein modifications. We performed the following study to determine changes in the protein profile of human myocardium following CP/CPB.<h4>Methods and resul ...[more]

PMID: 18824761

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Project description:BACKGROUND:The urinary proteome of patients undergoing cardiopulmonary bypass (CPB) may provide important insights into systemic and renal changes associated with the procedure. Such information may ultimately provide a basis to differentiate changes or properties associated with the development of acute kidney injury. While mass spectrometry (MS) analysis offers the potential for in-depth compositional analysis it is often limited in coverage and relative quantitation capacity. The aim of this study was to develop a process flow for the preparation and comparison of the intraoperative urinary proteome. METHODS:Urines were collected from patients at the start of CPB and 1-h into CPB. Pooled samples (n = 5) from each time point were processed using a modified Filter Assisted Sample Preparation protocol. The resulting peptides were analyzed by 2D-LC-MS/MS and by 1D-LC-MS/MS SWATH (Sequential Window acquisition of All Theoretical fragment ion spectra). RESULTS:The 2D-LC-MS/MS analysis identified 1324 proteins in the two pools, of which 744 were quantifiable. The SWATH approach provided quantitation for 730 proteins, 552 of which overlapped with the common population from the 2D-IDA results. Intensity correlation filtering between the two methods gave 475 proteins for biological interpretation. Proteins displaying greater than threefold changes (>log2 1.59) at 1-hour CPB relative to the initiation of CPB (26 down-regulated and 22 up-regulated) were selected for further analysis. Up-regulated proteins were enriched in GO terms related to humoral immune response, predominantly innate immunity (C4b, lactotransferrin, protein S100-A8, cathelicidin, myeloperoxidase) and extracellular matrix reorganization (e.g. MMP-9). CONCLUSIONS:This study describes a scheme for processing urine from patients undergoing CPB for mass spectrometry-based analysis. The introduction of SWATH into the workflow offers a sample and instrument sparing approach to obtaining consistent in-depth sample analysis. The design of the methodology is such that it can be readily applied to large numbers of clinical samples with the potential for automation. The results also suggest that activation of the innate immune responses occur during cardiac bypass surgery.

Project description:Potassium-based depolarizing St Thomas' Hospital cardioplegic solution No 2 administered as intermittent, oxygenated blood is considered as a gold standard for myocardial protection during cardiac surgery. However, the alternative concept of polarizing arrest may have beneficial protective effects. We hypothesize that polarized arrest with esmolol/adenosine/magnesium (St Thomas' Hospital Polarizing cardioplegic solution) in cold, intermittent oxygenated blood offers comparable myocardial protection in a clinically relevant animal model.Twenty anaesthetized young pigs, 42 ± 2 (standard deviation) kg on standardized tepid cardiopulmonary bypass (CPB) were randomized (10 per group) to depolarizing or polarizing cardiac arrest for 60 min with cardioplegia administered in the aortic root every 20 min as freshly mixed cold, intermittent, oxygenated blood. Global and local baseline and postoperative cardiac function 60, 120 and 180 min after myocardial reperfusion was evaluated with pressure-conductance catheter and strain by Tissue Doppler Imaging. Regional tissue blood flow, cleaved caspase-3 activity, GRK2 phosphorylation and mitochondrial function and ultrastructure were evaluated in myocardial tissue samples.Left ventricular function and general haemodynamics did not differ between groups before CPB. Cardiac asystole was obtained and maintained during aortic cross-clamping. Compared with baseline, heart rate was increased and left ventricular end-systolic and end-diastolic pressures decreased in both groups after weaning. Cardiac index, systolic pressure and radial peak systolic strain did not differ between groups. Contractility, evaluated as dP/dtmax, gradually increased from 120 to 180 min after declamping in animals with polarizing cardioplegia and was significantly higher, 1871 ± 160 (standard error) mmHg/s, compared with standard potassium-based cardioplegic arrest, 1351 ± 70 mmHg/s, after 180 min of reperfusion (P = 0.008). Radial peak ejection strain rate increased and the load-independent variable preload recruitable stroke work was increased with polarizing cardioplegia after 180 min, 64 ± 3 vs 54 ± 2 mmHg (P = 0.018), indicating better preserved left ventricular contractility with polarizing cardioplegia. Phosphorylation of GRK2 in myocardial tissue did not differ between groups. Fractional cytoplasmic volume in myocytes was reduced in hearts arrested with polarizing cardioplegia, indicating reduction of cytoplasmic oedema.Polarizing oxygenated blood cardioplegia with esmolol/adenosine/magnesium offers comparable myocardial protection and improves contractility compared with the standard potassium-based depolarizing blood cardioplegia.

Dataset Information

Pilot proteomic profile of differentially regulated proteins in right atrial appendage before and after cardiac surgery using cardioplegia and cardiopulmonary bypass.

Publications

Pilot proteomic profile of differentially regulated proteins in right atrial appendage before and after cardiac surgery using cardioplegia and cardiopulmonary bypass.

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