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Finite element analysis of transmural stress in left ventricular aneurysm
Vol. 203, No. 3S, September 2006
CONCLUSIONS: Patients undergoing VATS lobectomy for clinical stage I NSCLC, despite more comorbidities, had fewer postoperative complications. The approaches have equivalent operative time, blood loss, length of stay, and survival. Compared to OT, VATS lobectomy for clinical stage I NSCLC appears to be a less morbid operation.
Deficiency of TNFR1 protects myocardium through STAT3, SOCS3, and IL-6, but not p38 MAPK or IL-1 beta Meijing Wang MD, MS, Paul Crisostomo MD, Keith Lillemoe MD, Daniel Meldrum MD Indiana University Medical Center, Indianapolis, IN INTRODUCTION: Suppressor of cytokine signaling (SOCS) proteins are major inhibitors of cytokine signaling via the JAK/STAT pathway. TNF plays an important role in the development of heart failure. There is a direct correlation between myocardial function and myocardial TNF levels in humans. However, it is unknown whether TNF mediates myocardial inflammation via STAT3/SOCS3 signaling in the heart, and if so, whether this effect is through the type 1 55-kDa TNF receptor (TNFR1). We hypothesized that TNFR1 deficiency protects myocardial function and decreases myocardial IL-6 production via the STAT3/SOCS3 pathway in response to TNF. METHODS: Isolated male mouse hearts (n⫽4/group) from wild type (WT), TNFR1 knockout (TNFR1KO) were subjected to direct TNF infusion (500 pg/ml/min x 30 min) and LVDP, ⫹dP/dT, ⫺dP/dT were continuously recorded. Heart tissue was performed for active forms of STAT3, p38, SOCS3 (Western blot) and IL-6, IL1beta (ELISA). p⬍0.05⫽statistically significant. RESULTS: TNFR1KO had significantly better myocardial function (LVDP: 37.9⫹/⫺4.4 vs. WT 20.6⫹/⫺3.2mmHg; ⫹dP/dt: 1176.4⫹/⫺159.1 vs. WT 589.1⫹/⫺85.6 mmHg/s; ⫺dP/dt: ⫺877.2⫹/⫺115.4 vs. WT ⫺448.6⫹/⫺61.8mmHg/s) and greater expression of SOCS3 after TNF(% of SOCS3/GAPDH: 45⫹/ ⫺4.5% vs. WT 22⫹/⫺6.5%). TNFR1 deficiency decreased STAT3 activation (% p-STAT3/STAT3: 29⫹/⫺6.4% vs. WT 45⫹/ ⫺8.8%). IL-6 decreased in TNFR1KO (150.2⫹/⫺3.65 pg/mg protein) vs. WT (211.4⫹/⫺26.08). TNFR1 deficiency did not change expression of p38 and IL-1 beta following TNF infusion. CONCLUSIONS: Deficiency of TNFR1 protects myocardium through STAT3, SOCS3, and IL-6, but not p38 MAPK or IL-1 beta.
Regional systolic and remodeling strain differences during cardiac remodeling Ahmet Kilic MD, G Kwame Yankey MD, Tim Nolan MS, Tieluo Li MD, Jennifer Nash MS, Guangming Cheng MD, Zhongjun Wu PhD, Bartley Griffith MD University of Maryland, Baltimore, MD INTRODUCTION: The purpose of this study is to investigate differences in systolic and remodeling strains in the infarct, adjacent and remote regions of the left ventricular (LV) myocardium in an ovine postinfarction model.
Cardiothoracic Surgery
S21
METHODS: Sixteen sonomicrometry transducers were placed into the LV free wall to assess regional contractile function by systolic strain and structural alteration by remodeling strain. All animals underwent daily hemodynamic and strain measurements. RESULTS: Systolic function of the remote zone was preserved with strain of ⫺21.2 ⫾3.8, ⫺22.2 ⫾ 1.6, ⫺26.0 ⫾ 0.2, ⫺28.6 ⫾ 3.2 and ⫺27.6 ⫾ 1.2 (%) at pre-, post-, 2 weeks, 6 weeks and 8 weeks postinfarction. The adjacent zone showed progressive dysfunction with strain of ⫺18.6 ⫾ 6.9, ⫺15.4 ⫾ 4.3, ⫺10.3 ⫾ 9.6, ⫺7.8 ⫾ 13.9, ⫺7.7 ⫾ 10.2. The infarct zone became non-contractile immediately postinfarction with strain of ⫺14.0 ⫾ 1.5, ⫺6.6 ⫾ 11.8, 3.1 ⫾ 1.5, 2.1 ⫾1.2, 1.4 ⫾ 0.8. Using pre-infarction end diastolic geometry as reference, the remote zone had a progressive increase in remodeling areal strain of 7.2 ⫾ 2.3, 1.5 ⫾ 3.4, 7.5 ⫾ 3.5 and 16.0 ⫾ 6.9; the adjacent zone had values of 2.0 ⫾ 1.3, 12.3 ⫾ 3.9, 29.6 ⫾ 6.7 and 33.4 ⫾ 9.8; and the infarct zone with 6.0 ⫾ 4.5, 13.0 ⫾ 5.6, 21.5 ⫾ 6.7, 60.1 ⫾ 8.7. CONCLUSIONS: Regional function strain and geometrical structural analysis can be used to illustrate the dynamics and progression of cardiac remodeling.
Finite element analysis of transmural stress in left ventricular aneurysm Amod P Tendulkar MD, Joseph Walker PhD, Julius Guccione PhD, Mark Ratcliffe MD University of California, San Francisco, Oakland, CA INTRODUCTION: Normally, there is a transmural variation in stress that is related to myofiber orientation. Finite element analysis (FEA) is a computational tool used to calculate stress. In REA, infinitesimal deformation method (IDM) uses stiff linear material properties and does not account for myofiber orientation whereas finite deformation method (FDM) uses non-linear physiologic material properties based on myofiber orientation to compute stress. We hypothesized that FDM will demonstrate better transmural variation in stress than IDM. METHODS: A FE mesh was created from MRI of sheep hearts (n⫽3) with left ventricular aneurysm (LVA). Aneurysm, border-zone and remote regions were identified. Validated material properties were used for FDM. Stiff,isotropic material properties were used for IDM. Endocardial surface was pressurized to 78.7mmHg. End systolic stresses (circumferential(CS) and longitudinal(LS)) were calculated for every element and then grouped by region and transmural location. ANOVA and post-hoc analysis with p⬍0.05 was determined significant. RESULTS: Transmural variation was observed in CS calculated by FDM in the endocardium versus midwall and epicardium (p⬍0.0001) in aneurysm and remote regions. Only remote region had transmural variation in calculated CS for IDM (p⬍0.01). LS was different in endocardium versus epicardium in aneurysm and remote regions and endocardium versus midwall in aneurysm region (p⬍0.0001) for FDM. IDM demonstrated a difference between midwall and epicardium in remote only (p⬍0.04). Finally, the two methods were also different (p⬍0.03).
S22
Cardiothoracic Surgery
J Am Coll Surg
Table. Transmural stress Aneurysm Circumferential Stress Endocardium Midwall Epicardium
IDM
FDM
Endocardium Midwall Epicardium
IDM
FDM
Remote IDM
FDM
29.7⫾4.5 39.9⫾7.4 26.2⫾1.1 37.8⫾4.5 18.9⫾1 30.3⫾2 31.4⫾3.7 33.1⫾5.4 22.5⫾1.6 31.4⫾2.6 14.6⫾1.2 24.5⫾2 31.3⫾3 30.8⫾3.7 20.2⫾1.7 35.2⫾2.5 13.9⫾1.4 22.7⫾2.5 Aneurysm
Longitudinal Stress
Border-zone
IDM
FDM
Border-zone IDM
FDM
Remote IDM
FDM
28.5⫾2.3 40.3⫾9.9 13.5⫾1.5 3.4⫾2 5.57⫾0.5 ⫺5.5⫾1 29.2⫾1.7 33.4⫾6.7 12.7⫾1.4 4.3⫾1 5.0⫾0.7 ⫺2.2⫾0.9 28.5⫾1.8 31.6⫾4.4 12.0⫾2.1 5.9⫾0.1 8.45⫾0.9 1.1⫾0.7
CONCLUSIONS: IDM failed to demonstrate transmural stress variation when compared to the gold standard FDM. Therefore, FDM should be the method of choice to predict stress in patients with LVA.
Murine carotid aneurysms develop without down regulation of Nogo-B expression: A novel model for human thoracic aneurysms Stephen P Maloney MD, Alexander Yakimov MD, Akihito Muto MD, PhD, Paul Tang MD, Jose Pimiento MD, Fabio Kudo MD, PhD, Tormod Westvik MD, Stanley Dudrick MD, William Sessa PhD, George Tellides MD, PhD, Alan Dardik MD, PhD Yale University School of Medicine, Waterbury, CT INTRODUCTION: Although abdominal aortic aneurysms are associated with smooth muscle cell (SMC) apoptosis, ascending thoracic aneurysms are associated with preserved SMC density. Decreased expression of Nogo-B has recently been described as a marker of vascular injury. To determine whether proximal thoracic aneurysms are associated with injury, we examined the expression of Nogo-B in human specimens and a mouse model. METHODS: Normal and aneurysmal human ascending thoracic aortic surgical specimens (n⫽24) were analyzed for Nogo-B mRNA expression using quantitative PCR. Aneurysms were induced in adult (3 mo) C57Bl/6 mice by periadventitial application of CaCl2 (0.5M) to the right carotid artery. Vessel diameter was measured using a calibrated grid and compared to the contralateral carotid artery; aneurysmal and control specimens were analyzed for Nogo-B using qPCR. RESULTS: Human aortic aneurysms had preserved SMC density and Nogo-B expression compared to nonaneurysmal aortae (aneurysms, 0.256 ⫾ 0.08 vs. control, 0.152 ⫾ 0.02; p⫽0.2). Murine carotid aneurysms were 26% larger at 5 weeks (525 ⫾ 8 `ım, vs. 389 ⫾ 11 `ım; n⫽7; p⬍.0001, ANOVA). Murine aneurysms had increased expression of both Nogo-AB (14 ⫾ 1 vs. 9 ⫾ 3; p⫽0.003) and Nogo-B (46 ⫾ 18 vs. 18 ⫾ 4; p⫽0.02) compared to control arteries. CONCLUSIONS: Preserved Nogo-B expression in human thoracic aneurysms suggests that proximal aortic aneurysms develop without vessel injury. Murine carotid aneurysms similarly have increased
Nogo-B expression, also suggesting aneurysmal formation without injury. Murine carotid aneurysms may be a novel model for human thoracic aneurysm development.
Survival of human marrow stem cells (MSCs) implanted into acutely infarcted rat myocardium: A xenotransplant model Rony Atoui MD, Juan Francisco Asenjo MD, Minh Duong BSc, Ray Chiu MD, PhD, Dominique Shum-Tim MD McGill University Health Center, Montreal, QC, Canada INTRODUCTION: Cellular transplantation is a promising approach for myocardial regeneration therapy. Recently we have demonstrated the unique immune tolerance of MSCs obtained from mice and pigs. In order to confirm these findings in human cells, which currently remain controversial, purified clonal human MSCs characterized with specific CD markers, were used as donor cells in a xenogeneic transplant model. METHODS: Myocardial infarctions were created in Lewis rats by proximal left coronary ligation. The animals were randomized into 3 groups. In group I (n⫽20), lac-Z labeled human MSC (3⫻106 cells) were implanted around the infarcted area. In group II (n⫽10), isogenic rat MSC were used instead and in group III (n⫽10), culture medium was used. No immunosuppression was given at any time. Immunohistochemical staining was done on specimens taken serially to assess for the presence of -galactosidase activity in the recipient hearts. RESULTS: In group I and II, engrafted MSC were detected within the rat myocardium beyond at least 4 weeks after cell transplantation without immunosuppression. No extensive cellular infiltrates were noted. Furthermore, some of these cells started to differentiate into a mature cardiomyocytic phenotype. CONCLUSIONS: Human MSC implanted into immunologically mismatched ischemic myocardium were tolerated, with persistent engraftment of these cells. This study confirms the unique immune tolerance of human MSCs, indicating the feasibility of using these cells as “universal donor cells” with fascinating economic and clinical implications whereby xenogeneic or allogeneic MSC could be expanded, cryopreserved and available on the shelf, ready for implantation into patients following myocardial infarction.
Cardiopulmonary bypass with cardioplegic arrest activates protein kinase C in the human myocardium Neel R Sodha MD, Richard Clements PhD, Jun Feng MD, PhD, Munir Boodhwani MD, Basel Ramlawi MD, Shigetoshi Mieno MD, PhD, Cesario Bianchi MD, PhD, Frank W Sellke MD Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA INTRODUCTION: The Protein Kinase C family consists of 12 isoforms, of which six have been found in human myocardium (alpha,
CONCLUSIONS: Patients undergoing VATS lobectomy for clinical stage I NSCLC, despite more comorbidities, had fewer postoperative complications. The approaches have equivalent operative time, blood loss, length of stay, and survival. Compared to OT, VATS lobectomy for clinical stage I NSCLC appears to be a less morbid operation.
Deficiency of TNFR1 protects myocardium through STAT3, SOCS3, and IL-6, but not p38 MAPK or IL-1 beta Meijing Wang MD, MS, Paul Crisostomo MD, Keith Lillemoe MD, Daniel Meldrum MD Indiana University Medical Center, Indianapolis, IN INTRODUCTION: Suppressor of cytokine signaling (SOCS) proteins are major inhibitors of cytokine signaling via the JAK/STAT pathway. TNF plays an important role in the development of heart failure. There is a direct correlation between myocardial function and myocardial TNF levels in humans. However, it is unknown whether TNF mediates myocardial inflammation via STAT3/SOCS3 signaling in the heart, and if so, whether this effect is through the type 1 55-kDa TNF receptor (TNFR1). We hypothesized that TNFR1 deficiency protects myocardial function and decreases myocardial IL-6 production via the STAT3/SOCS3 pathway in response to TNF. METHODS: Isolated male mouse hearts (n⫽4/group) from wild type (WT), TNFR1 knockout (TNFR1KO) were subjected to direct TNF infusion (500 pg/ml/min x 30 min) and LVDP, ⫹dP/dT, ⫺dP/dT were continuously recorded. Heart tissue was performed for active forms of STAT3, p38, SOCS3 (Western blot) and IL-6, IL1beta (ELISA). p⬍0.05⫽statistically significant. RESULTS: TNFR1KO had significantly better myocardial function (LVDP: 37.9⫹/⫺4.4 vs. WT 20.6⫹/⫺3.2mmHg; ⫹dP/dt: 1176.4⫹/⫺159.1 vs. WT 589.1⫹/⫺85.6 mmHg/s; ⫺dP/dt: ⫺877.2⫹/⫺115.4 vs. WT ⫺448.6⫹/⫺61.8mmHg/s) and greater expression of SOCS3 after TNF(% of SOCS3/GAPDH: 45⫹/ ⫺4.5% vs. WT 22⫹/⫺6.5%). TNFR1 deficiency decreased STAT3 activation (% p-STAT3/STAT3: 29⫹/⫺6.4% vs. WT 45⫹/ ⫺8.8%). IL-6 decreased in TNFR1KO (150.2⫹/⫺3.65 pg/mg protein) vs. WT (211.4⫹/⫺26.08). TNFR1 deficiency did not change expression of p38 and IL-1 beta following TNF infusion. CONCLUSIONS: Deficiency of TNFR1 protects myocardium through STAT3, SOCS3, and IL-6, but not p38 MAPK or IL-1 beta.
Regional systolic and remodeling strain differences during cardiac remodeling Ahmet Kilic MD, G Kwame Yankey MD, Tim Nolan MS, Tieluo Li MD, Jennifer Nash MS, Guangming Cheng MD, Zhongjun Wu PhD, Bartley Griffith MD University of Maryland, Baltimore, MD INTRODUCTION: The purpose of this study is to investigate differences in systolic and remodeling strains in the infarct, adjacent and remote regions of the left ventricular (LV) myocardium in an ovine postinfarction model.
Cardiothoracic Surgery
S21
METHODS: Sixteen sonomicrometry transducers were placed into the LV free wall to assess regional contractile function by systolic strain and structural alteration by remodeling strain. All animals underwent daily hemodynamic and strain measurements. RESULTS: Systolic function of the remote zone was preserved with strain of ⫺21.2 ⫾3.8, ⫺22.2 ⫾ 1.6, ⫺26.0 ⫾ 0.2, ⫺28.6 ⫾ 3.2 and ⫺27.6 ⫾ 1.2 (%) at pre-, post-, 2 weeks, 6 weeks and 8 weeks postinfarction. The adjacent zone showed progressive dysfunction with strain of ⫺18.6 ⫾ 6.9, ⫺15.4 ⫾ 4.3, ⫺10.3 ⫾ 9.6, ⫺7.8 ⫾ 13.9, ⫺7.7 ⫾ 10.2. The infarct zone became non-contractile immediately postinfarction with strain of ⫺14.0 ⫾ 1.5, ⫺6.6 ⫾ 11.8, 3.1 ⫾ 1.5, 2.1 ⫾1.2, 1.4 ⫾ 0.8. Using pre-infarction end diastolic geometry as reference, the remote zone had a progressive increase in remodeling areal strain of 7.2 ⫾ 2.3, 1.5 ⫾ 3.4, 7.5 ⫾ 3.5 and 16.0 ⫾ 6.9; the adjacent zone had values of 2.0 ⫾ 1.3, 12.3 ⫾ 3.9, 29.6 ⫾ 6.7 and 33.4 ⫾ 9.8; and the infarct zone with 6.0 ⫾ 4.5, 13.0 ⫾ 5.6, 21.5 ⫾ 6.7, 60.1 ⫾ 8.7. CONCLUSIONS: Regional function strain and geometrical structural analysis can be used to illustrate the dynamics and progression of cardiac remodeling.
Finite element analysis of transmural stress in left ventricular aneurysm Amod P Tendulkar MD, Joseph Walker PhD, Julius Guccione PhD, Mark Ratcliffe MD University of California, San Francisco, Oakland, CA INTRODUCTION: Normally, there is a transmural variation in stress that is related to myofiber orientation. Finite element analysis (FEA) is a computational tool used to calculate stress. In REA, infinitesimal deformation method (IDM) uses stiff linear material properties and does not account for myofiber orientation whereas finite deformation method (FDM) uses non-linear physiologic material properties based on myofiber orientation to compute stress. We hypothesized that FDM will demonstrate better transmural variation in stress than IDM. METHODS: A FE mesh was created from MRI of sheep hearts (n⫽3) with left ventricular aneurysm (LVA). Aneurysm, border-zone and remote regions were identified. Validated material properties were used for FDM. Stiff,isotropic material properties were used for IDM. Endocardial surface was pressurized to 78.7mmHg. End systolic stresses (circumferential(CS) and longitudinal(LS)) were calculated for every element and then grouped by region and transmural location. ANOVA and post-hoc analysis with p⬍0.05 was determined significant. RESULTS: Transmural variation was observed in CS calculated by FDM in the endocardium versus midwall and epicardium (p⬍0.0001) in aneurysm and remote regions. Only remote region had transmural variation in calculated CS for IDM (p⬍0.01). LS was different in endocardium versus epicardium in aneurysm and remote regions and endocardium versus midwall in aneurysm region (p⬍0.0001) for FDM. IDM demonstrated a difference between midwall and epicardium in remote only (p⬍0.04). Finally, the two methods were also different (p⬍0.03).
S22
Cardiothoracic Surgery
J Am Coll Surg
Table. Transmural stress Aneurysm Circumferential Stress Endocardium Midwall Epicardium
IDM
FDM
Endocardium Midwall Epicardium
IDM
FDM
Remote IDM
FDM
29.7⫾4.5 39.9⫾7.4 26.2⫾1.1 37.8⫾4.5 18.9⫾1 30.3⫾2 31.4⫾3.7 33.1⫾5.4 22.5⫾1.6 31.4⫾2.6 14.6⫾1.2 24.5⫾2 31.3⫾3 30.8⫾3.7 20.2⫾1.7 35.2⫾2.5 13.9⫾1.4 22.7⫾2.5 Aneurysm
Longitudinal Stress
Border-zone
IDM
FDM
Border-zone IDM
FDM
Remote IDM
FDM
28.5⫾2.3 40.3⫾9.9 13.5⫾1.5 3.4⫾2 5.57⫾0.5 ⫺5.5⫾1 29.2⫾1.7 33.4⫾6.7 12.7⫾1.4 4.3⫾1 5.0⫾0.7 ⫺2.2⫾0.9 28.5⫾1.8 31.6⫾4.4 12.0⫾2.1 5.9⫾0.1 8.45⫾0.9 1.1⫾0.7
CONCLUSIONS: IDM failed to demonstrate transmural stress variation when compared to the gold standard FDM. Therefore, FDM should be the method of choice to predict stress in patients with LVA.
Murine carotid aneurysms develop without down regulation of Nogo-B expression: A novel model for human thoracic aneurysms Stephen P Maloney MD, Alexander Yakimov MD, Akihito Muto MD, PhD, Paul Tang MD, Jose Pimiento MD, Fabio Kudo MD, PhD, Tormod Westvik MD, Stanley Dudrick MD, William Sessa PhD, George Tellides MD, PhD, Alan Dardik MD, PhD Yale University School of Medicine, Waterbury, CT INTRODUCTION: Although abdominal aortic aneurysms are associated with smooth muscle cell (SMC) apoptosis, ascending thoracic aneurysms are associated with preserved SMC density. Decreased expression of Nogo-B has recently been described as a marker of vascular injury. To determine whether proximal thoracic aneurysms are associated with injury, we examined the expression of Nogo-B in human specimens and a mouse model. METHODS: Normal and aneurysmal human ascending thoracic aortic surgical specimens (n⫽24) were analyzed for Nogo-B mRNA expression using quantitative PCR. Aneurysms were induced in adult (3 mo) C57Bl/6 mice by periadventitial application of CaCl2 (0.5M) to the right carotid artery. Vessel diameter was measured using a calibrated grid and compared to the contralateral carotid artery; aneurysmal and control specimens were analyzed for Nogo-B using qPCR. RESULTS: Human aortic aneurysms had preserved SMC density and Nogo-B expression compared to nonaneurysmal aortae (aneurysms, 0.256 ⫾ 0.08 vs. control, 0.152 ⫾ 0.02; p⫽0.2). Murine carotid aneurysms were 26% larger at 5 weeks (525 ⫾ 8 `ım, vs. 389 ⫾ 11 `ım; n⫽7; p⬍.0001, ANOVA). Murine aneurysms had increased expression of both Nogo-AB (14 ⫾ 1 vs. 9 ⫾ 3; p⫽0.003) and Nogo-B (46 ⫾ 18 vs. 18 ⫾ 4; p⫽0.02) compared to control arteries. CONCLUSIONS: Preserved Nogo-B expression in human thoracic aneurysms suggests that proximal aortic aneurysms develop without vessel injury. Murine carotid aneurysms similarly have increased
Nogo-B expression, also suggesting aneurysmal formation without injury. Murine carotid aneurysms may be a novel model for human thoracic aneurysm development.
Survival of human marrow stem cells (MSCs) implanted into acutely infarcted rat myocardium: A xenotransplant model Rony Atoui MD, Juan Francisco Asenjo MD, Minh Duong BSc, Ray Chiu MD, PhD, Dominique Shum-Tim MD McGill University Health Center, Montreal, QC, Canada INTRODUCTION: Cellular transplantation is a promising approach for myocardial regeneration therapy. Recently we have demonstrated the unique immune tolerance of MSCs obtained from mice and pigs. In order to confirm these findings in human cells, which currently remain controversial, purified clonal human MSCs characterized with specific CD markers, were used as donor cells in a xenogeneic transplant model. METHODS: Myocardial infarctions were created in Lewis rats by proximal left coronary ligation. The animals were randomized into 3 groups. In group I (n⫽20), lac-Z labeled human MSC (3⫻106 cells) were implanted around the infarcted area. In group II (n⫽10), isogenic rat MSC were used instead and in group III (n⫽10), culture medium was used. No immunosuppression was given at any time. Immunohistochemical staining was done on specimens taken serially to assess for the presence of -galactosidase activity in the recipient hearts. RESULTS: In group I and II, engrafted MSC were detected within the rat myocardium beyond at least 4 weeks after cell transplantation without immunosuppression. No extensive cellular infiltrates were noted. Furthermore, some of these cells started to differentiate into a mature cardiomyocytic phenotype. CONCLUSIONS: Human MSC implanted into immunologically mismatched ischemic myocardium were tolerated, with persistent engraftment of these cells. This study confirms the unique immune tolerance of human MSCs, indicating the feasibility of using these cells as “universal donor cells” with fascinating economic and clinical implications whereby xenogeneic or allogeneic MSC could be expanded, cryopreserved and available on the shelf, ready for implantation into patients following myocardial infarction.
Cardiopulmonary bypass with cardioplegic arrest activates protein kinase C in the human myocardium Neel R Sodha MD, Richard Clements PhD, Jun Feng MD, PhD, Munir Boodhwani MD, Basel Ramlawi MD, Shigetoshi Mieno MD, PhD, Cesario Bianchi MD, PhD, Frank W Sellke MD Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA INTRODUCTION: The Protein Kinase C family consists of 12 isoforms, of which six have been found in human myocardium (alpha,