Indices of apoptosis activation after blood cardioplegia and cardiopulmonary bypass

Basel Ramlawi, Jun Feng, Shigetoshi Mieno, Csaba Szabo, Zsuzsanna Zsengeller, Richard Clements, Neel Sodha, Munir Boodhwani, Cesario Bianchi, Frank W. Sellke

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

BACKGROUND - Cardioplegic arrest (CA) using cold blood cardioplegia (CBC) has been reported to reduce ischemia-reperfusion (IR)-induced myocardial injury via apoptosis. We studied key apoptotic mediators via the caspase-dependent and intrinsic pathways as well as poly(ADP)-ribosylating protein (PARP) activity in myocardial and peripheral tissues after CA and cardiopulmonary bypass (CBP). METHODS AND RESULTS - Right atrial (RA) and skeletal muscle(SM) was harvested from cardiac surgical patients with similar baseline characteristics (N =6) before and after CPB and CBC. Total and modified caspase-3, Bcl-2, Bad, apoptosis-inducing factor (AIF), and PARP were quantified by immunoblotting. Terminal caspase-3 activity was assessed and immunohistochemistry was performed for PARP and AIF. TUNEL staining was used for identification of apoptotic cells. Microarray gene expression analysis was performed using Affymetrix U95 GeneChip. In RA tissue, CA with CBC significantly increased phosphorylation of Bcl-2 (Ser), Bad (Ser) (2.63±0.4 and 1.77±0.3-fold respectively; P<0.05), and cleavage of the downstream caspase 3 (1.45±0.1-fold; P<0.05). There was no significant change in total protein levels. Also, there was an increase in mature AIF (57 kDa) levels (1.22±0.01-fold; P<0.05) and a trend toward nuclear translocation on histological staining. Caspase 3 activity was increased 1.5±0.14-fold (P<0.05). The number of apoptotic cells in atrial tissue increased after compared with before CPB/CA using TUNEL staining (1.55±0.66 versus 0.325±0.05%, respectively; P=0.03). In contrast, SM samples did not show any of the changes observed in RA tissue after CPB. CONCLUSION - Despite optimal current surgical myocardial protection, we found that CA with CBC induced both programmed cell death and survival signaling in myocardial tissue.

Original languageEnglish (US)
JournalCirculation
Volume114
Issue numberSUPPL. 1
DOIs
StatePublished - Jul 2006
Externally publishedYes

Fingerprint

Induced Heart Arrest
Cardiopulmonary Bypass
Apoptosis Inducing Factor
Caspase 3
Apoptosis
In Situ Nick-End Labeling
Staining and Labeling
Skeletal Muscle
Myocardial Reperfusion Injury
Caspases
Immunoblotting
Cell Survival
Cell Death
Ischemia
Cell Count
Immunohistochemistry
Phosphorylation
Gene Expression
poly(ADP)-ribosylated proteins
Proteins

Keywords

  • Apoptosis
  • Blood cardioplegia
  • Extracorporeal circulation
  • Ischemia reperfusion
  • Myocardial protection
  • Signal transduction

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Ramlawi, B., Feng, J., Mieno, S., Szabo, C., Zsengeller, Z., Clements, R., ... Sellke, F. W. (2006). Indices of apoptosis activation after blood cardioplegia and cardiopulmonary bypass. Circulation, 114(SUPPL. 1). https://doi.org/10.1161/CIRCULATIONAHA.105.000828

Indices of apoptosis activation after blood cardioplegia and cardiopulmonary bypass. / Ramlawi, Basel; Feng, Jun; Mieno, Shigetoshi; Szabo, Csaba; Zsengeller, Zsuzsanna; Clements, Richard; Sodha, Neel; Boodhwani, Munir; Bianchi, Cesario; Sellke, Frank W.

In: Circulation, Vol. 114, No. SUPPL. 1, 07.2006.

Research output: Contribution to journalArticle

Ramlawi, B, Feng, J, Mieno, S, Szabo, C, Zsengeller, Z, Clements, R, Sodha, N, Boodhwani, M, Bianchi, C & Sellke, FW 2006, 'Indices of apoptosis activation after blood cardioplegia and cardiopulmonary bypass', Circulation, vol. 114, no. SUPPL. 1. https://doi.org/10.1161/CIRCULATIONAHA.105.000828
Ramlawi B, Feng J, Mieno S, Szabo C, Zsengeller Z, Clements R et al. Indices of apoptosis activation after blood cardioplegia and cardiopulmonary bypass. Circulation. 2006 Jul;114(SUPPL. 1). https://doi.org/10.1161/CIRCULATIONAHA.105.000828
Ramlawi, Basel ; Feng, Jun ; Mieno, Shigetoshi ; Szabo, Csaba ; Zsengeller, Zsuzsanna ; Clements, Richard ; Sodha, Neel ; Boodhwani, Munir ; Bianchi, Cesario ; Sellke, Frank W. / Indices of apoptosis activation after blood cardioplegia and cardiopulmonary bypass. In: Circulation. 2006 ; Vol. 114, No. SUPPL. 1.
@article{55ba7b459788430982e7e217be2bd426,
title = "Indices of apoptosis activation after blood cardioplegia and cardiopulmonary bypass",
abstract = "BACKGROUND - Cardioplegic arrest (CA) using cold blood cardioplegia (CBC) has been reported to reduce ischemia-reperfusion (IR)-induced myocardial injury via apoptosis. We studied key apoptotic mediators via the caspase-dependent and intrinsic pathways as well as poly(ADP)-ribosylating protein (PARP) activity in myocardial and peripheral tissues after CA and cardiopulmonary bypass (CBP). METHODS AND RESULTS - Right atrial (RA) and skeletal muscle(SM) was harvested from cardiac surgical patients with similar baseline characteristics (N =6) before and after CPB and CBC. Total and modified caspase-3, Bcl-2, Bad, apoptosis-inducing factor (AIF), and PARP were quantified by immunoblotting. Terminal caspase-3 activity was assessed and immunohistochemistry was performed for PARP and AIF. TUNEL staining was used for identification of apoptotic cells. Microarray gene expression analysis was performed using Affymetrix U95 GeneChip. In RA tissue, CA with CBC significantly increased phosphorylation of Bcl-2 (Ser), Bad (Ser) (2.63±0.4 and 1.77±0.3-fold respectively; P<0.05), and cleavage of the downstream caspase 3 (1.45±0.1-fold; P<0.05). There was no significant change in total protein levels. Also, there was an increase in mature AIF (57 kDa) levels (1.22±0.01-fold; P<0.05) and a trend toward nuclear translocation on histological staining. Caspase 3 activity was increased 1.5±0.14-fold (P<0.05). The number of apoptotic cells in atrial tissue increased after compared with before CPB/CA using TUNEL staining (1.55±0.66 versus 0.325±0.05{\%}, respectively; P=0.03). In contrast, SM samples did not show any of the changes observed in RA tissue after CPB. CONCLUSION - Despite optimal current surgical myocardial protection, we found that CA with CBC induced both programmed cell death and survival signaling in myocardial tissue.",
keywords = "Apoptosis, Blood cardioplegia, Extracorporeal circulation, Ischemia reperfusion, Myocardial protection, Signal transduction",
author = "Basel Ramlawi and Jun Feng and Shigetoshi Mieno and Csaba Szabo and Zsuzsanna Zsengeller and Richard Clements and Neel Sodha and Munir Boodhwani and Cesario Bianchi and Sellke, {Frank W.}",
year = "2006",
month = "7",
doi = "10.1161/CIRCULATIONAHA.105.000828",
language = "English (US)",
volume = "114",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "SUPPL. 1",

}

TY - JOUR

T1 - Indices of apoptosis activation after blood cardioplegia and cardiopulmonary bypass

AU - Ramlawi, Basel

AU - Feng, Jun

AU - Mieno, Shigetoshi

AU - Szabo, Csaba

AU - Zsengeller, Zsuzsanna

AU - Clements, Richard

AU - Sodha, Neel

AU - Boodhwani, Munir

AU - Bianchi, Cesario

AU - Sellke, Frank W.

PY - 2006/7

Y1 - 2006/7

N2 - BACKGROUND - Cardioplegic arrest (CA) using cold blood cardioplegia (CBC) has been reported to reduce ischemia-reperfusion (IR)-induced myocardial injury via apoptosis. We studied key apoptotic mediators via the caspase-dependent and intrinsic pathways as well as poly(ADP)-ribosylating protein (PARP) activity in myocardial and peripheral tissues after CA and cardiopulmonary bypass (CBP). METHODS AND RESULTS - Right atrial (RA) and skeletal muscle(SM) was harvested from cardiac surgical patients with similar baseline characteristics (N =6) before and after CPB and CBC. Total and modified caspase-3, Bcl-2, Bad, apoptosis-inducing factor (AIF), and PARP were quantified by immunoblotting. Terminal caspase-3 activity was assessed and immunohistochemistry was performed for PARP and AIF. TUNEL staining was used for identification of apoptotic cells. Microarray gene expression analysis was performed using Affymetrix U95 GeneChip. In RA tissue, CA with CBC significantly increased phosphorylation of Bcl-2 (Ser), Bad (Ser) (2.63±0.4 and 1.77±0.3-fold respectively; P<0.05), and cleavage of the downstream caspase 3 (1.45±0.1-fold; P<0.05). There was no significant change in total protein levels. Also, there was an increase in mature AIF (57 kDa) levels (1.22±0.01-fold; P<0.05) and a trend toward nuclear translocation on histological staining. Caspase 3 activity was increased 1.5±0.14-fold (P<0.05). The number of apoptotic cells in atrial tissue increased after compared with before CPB/CA using TUNEL staining (1.55±0.66 versus 0.325±0.05%, respectively; P=0.03). In contrast, SM samples did not show any of the changes observed in RA tissue after CPB. CONCLUSION - Despite optimal current surgical myocardial protection, we found that CA with CBC induced both programmed cell death and survival signaling in myocardial tissue.

AB - BACKGROUND - Cardioplegic arrest (CA) using cold blood cardioplegia (CBC) has been reported to reduce ischemia-reperfusion (IR)-induced myocardial injury via apoptosis. We studied key apoptotic mediators via the caspase-dependent and intrinsic pathways as well as poly(ADP)-ribosylating protein (PARP) activity in myocardial and peripheral tissues after CA and cardiopulmonary bypass (CBP). METHODS AND RESULTS - Right atrial (RA) and skeletal muscle(SM) was harvested from cardiac surgical patients with similar baseline characteristics (N =6) before and after CPB and CBC. Total and modified caspase-3, Bcl-2, Bad, apoptosis-inducing factor (AIF), and PARP were quantified by immunoblotting. Terminal caspase-3 activity was assessed and immunohistochemistry was performed for PARP and AIF. TUNEL staining was used for identification of apoptotic cells. Microarray gene expression analysis was performed using Affymetrix U95 GeneChip. In RA tissue, CA with CBC significantly increased phosphorylation of Bcl-2 (Ser), Bad (Ser) (2.63±0.4 and 1.77±0.3-fold respectively; P<0.05), and cleavage of the downstream caspase 3 (1.45±0.1-fold; P<0.05). There was no significant change in total protein levels. Also, there was an increase in mature AIF (57 kDa) levels (1.22±0.01-fold; P<0.05) and a trend toward nuclear translocation on histological staining. Caspase 3 activity was increased 1.5±0.14-fold (P<0.05). The number of apoptotic cells in atrial tissue increased after compared with before CPB/CA using TUNEL staining (1.55±0.66 versus 0.325±0.05%, respectively; P=0.03). In contrast, SM samples did not show any of the changes observed in RA tissue after CPB. CONCLUSION - Despite optimal current surgical myocardial protection, we found that CA with CBC induced both programmed cell death and survival signaling in myocardial tissue.

KW - Apoptosis

KW - Blood cardioplegia

KW - Extracorporeal circulation

KW - Ischemia reperfusion

KW - Myocardial protection

KW - Signal transduction

UR - http://www.scopus.com/inward/record.url?scp=33747202779&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33747202779&partnerID=8YFLogxK

U2 - 10.1161/CIRCULATIONAHA.105.000828

DO - 10.1161/CIRCULATIONAHA.105.000828

M3 - Article

C2 - 16820582

AN - SCOPUS:33747202779

VL - 114

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - SUPPL. 1

ER -