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CD45RA- Progenitors in the Failing Human Heart
S14 Journal of Cardiac Failure Vol. 15 No. 6S Suppl. 2009 although severe isolated TR can cause a hemodyamic pattern of complete equalization of all diastolic pressures, the pulmonary artery systolic pressures tends to be higher(O50) whereas in constrictive pericarditis, in the absence of preexisting pulmonary HTN, a normal or only slightly increased pulmonary artery systolic pressure is seen.
034 Identification of Lin-CD34D/CD38-/CD90D/CD45RA- Progenitors in the Failing Human Heart Asangi R. Kumarapeli1, Gwenn Danet-Desnoyers1, Andrew D. Bantly2, Jonni S. Moore2, Kenneth B. Margulies1; 1Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA; 2Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA Background: Heart failure is a major cause of death and disability in the USA with only cardiac transplantation offering definitive but limited therapeutic outcomes. Hence, strategies for cardiac regeneration have been the focus of many research endeavors. Our lab has been trying to identify the inherent myogenic potential of the failing heart. Recently, we were able to show that the failing myocardium consisted of abundant CD117þ cells that differentiated into immature cardiomyocytes in co-culture systems. This study tries to identify the presence of other progenitor cells in the non-myocyte small cell fraction of the adult human hearts. Method: Cells were isolated from the left ventricular free wall of non-failing and failing enrolled. All subjects underwent administration of gadolinium contrast, at a dose of 0.1 mmol/kg, ten min prior to application of cross clamp across the aorta. The explanted hearts were imaged with a 1.5 T CMR scanner using a high resolution T1 weighted 3D volume data set. The explanted hearts were sectioned into 5-8 short axis slices using a commercial rotating meat slicer. All slices were stained with triphenyltetrazolium chloride (TTC) and photographed. Experienced observers separately analyzed matched slices from the DE-CMR data sets and the histopathologic sections. The DE-CMR slices were planimetered to quantify the extent of enhanced and nonenhanced myocardium on each slice. The histopathologic sections were planimetered to calculate the extent of myocardium exhibiting TTC uptake. Results: Three subjects with differing etiologies of heart failure were enrolled: ischemic, nonischemic left heart failure from cardiac amyloidosis, and nonischemic right heart failure from primary pulmonary hypertension. The mean age was 57.3 6 3.5 years, duration of heart failure 15 6 9 months; 1 man and 2 women; mean LVEF 41 6 12%. There was a strong relationship between the extent of nonenhanced myocardium on DE-CMR and extent of TTC uptake on histopathology (r5-.99; p!0.001) as shown in the figure. Conclusion: There is a strong correlation between findings on DE-CMR and histopathology in human failing hearts. This relationship exists for both ischemic and nonischemic etiologies for heart failure.
036 hearts via collagenase perfusion. After serial filtration (smallest 30mm) to obtain the mononuclear cells, a panel of fluorescent markers containing CD34, CD38, CD90, CD45RA and a Lineage cocktail was used to phenotype these cells by flow cytometry. Sternal bone marrow, when available from the heart donors was also analyzed with the same marker panel. Results: We were able to identify a distinct population of CD90þ/CD45RA- cells among the Lin- CD34þ/CD38- cardiac mononuclear cells. As shown in the figure, failing hearts showed nearly a 2 fold increase in Lin-CD34þ/CD38-/CD90þ/CD45RA- cells compared to non-failing hearts. This population was also identifiable in the bone marrow with no clear distinction between the failing and non-failing patients. Interestingly, hearts contained a higher Lin-CD34þ/CD38- fraction compared to bone marrow where the CD34þ/ CD38þ fraction was proportionately higher. Conclusion: A Lin- CD34þ/CD38-/ CD90þ/CD45RA- progenitor cell subpopulation with in vivo hematopoietic properties has recently been identified in the human cord blood. We were able to identify a similar population in the human hearts and bone marrow. The finding of an abundance of this progenitor cell subpopulation in the failing hearts highlights the need to clarify its functional capacity.
Regional Right Ventricular Wall Stress and Thickness in Pulmonary Hypertension Chirag A. Chauhan1, Derek R. Wisnieski4, Christopher R. Deible2, Michael A. Mathier3, Joan Lacomis2, Sanjeev G. Shroff4, Michael R. Pinsky5, Marc A. Simon3; 1Department of Internal Medicine, University of Pittsburgh, Pittsburgh, PA; 2Department of Radiology; 3 Cardiovascular Institute; 4Department of Bioengineering; 5Department of Critical Care Medicine Background: Right ventricular (RV) dysfunction in pulmonary hypertension (PH), characterized by chamber dilation and hypertrophy, is theorized to result from increased wall stress (s). We characterized regional RV s from ECG-gated multislice computed tomography (MSCT) using ellipsoidal modeling in PH patients with compensated (PH-C) and decompensated (PH-D) RV function. Methods: A total of 18
Table 1. Patient data in end-systole Normal
PH-C
5
6
N
035 Histologic Correlates of Delayed Enhancement CMR in Ischemic and Nonischemic Heart Failure Omar M. Cheema, Keith Youker, Ankit A. Patel, Ahmad Khalil, Jerry D. Estep, Carlos M. Orrego, Guillermo A. Torre, Dipan J. Shah; Cardiology, Methodist DeBakey Heart & Vascular Center, Houston, TX
Infudibulum Free Wall Inferior Wall
RVP h s h s h s
(mm Hg) (mm) (kPa) (mm) (kPa) (mm) (kPa)
29.4 5.4 11.7 4.5 20.3 4.4 14.3
6 6 6 6 6 6 6
2.3 0.6 4.0 1.0 6.4 1.3 4.6
58 5.5 30.3 5.8 40.0 4.4 33.2
6 6 6 6 6 6 6
PH-D 7
23.3 0.8 9.1* 2.4 22.8* 1.1 14.0*
91.1 8.2 44.3 8.6 55.7 7.4 40.8
6 6 6 6 6 6 6
19.1 2.7* 17.3* 3.3* 22.9* 1.3* 9.3*
Mean values6SD are shown. *P!0.05 compared with Normal. N, subjects; RVP, right ventricular pressure.
Introduction: Delayed enhancement cardiovascular magnetic resonance (DE-CMR) has emerged as a powerful diagnostic tool for the assessment of viable and nonviable myocardium. Prior studies have demonstrated a strong relationship between DECMR and histopathology in animal models of ischemic injury. There is limited data validating DE-CMR findings in human hearts in the setting of heart failure. We hypothesized that there would be a strong relationship between DE-CMR and histopathology in human failing hearts in both ischemic and nonischemic heart failure. Methods: Subjects undergoing heart transplantation for end stage heart failure were
patients (age 51 6 11, 8 males, mean pulmonary artery pressure [MPAP] range 13-79 mmHg) underwent right heart catheterization and ECG-gated MSCT of the chest. Patients were divided into 3 groups: Normal (MPAP#25 mmHg), PH-C (MPAPO25 mmHg and right atrial pressure [RAP]!10 mmHg) and PH-D (MPAPO25 mmHg and RAP$10 mmHg). CT images were analyzed in both short axis
034 Identification of Lin-CD34D/CD38-/CD90D/CD45RA- Progenitors in the Failing Human Heart Asangi R. Kumarapeli1, Gwenn Danet-Desnoyers1, Andrew D. Bantly2, Jonni S. Moore2, Kenneth B. Margulies1; 1Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA; 2Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA Background: Heart failure is a major cause of death and disability in the USA with only cardiac transplantation offering definitive but limited therapeutic outcomes. Hence, strategies for cardiac regeneration have been the focus of many research endeavors. Our lab has been trying to identify the inherent myogenic potential of the failing heart. Recently, we were able to show that the failing myocardium consisted of abundant CD117þ cells that differentiated into immature cardiomyocytes in co-culture systems. This study tries to identify the presence of other progenitor cells in the non-myocyte small cell fraction of the adult human hearts. Method: Cells were isolated from the left ventricular free wall of non-failing and failing enrolled. All subjects underwent administration of gadolinium contrast, at a dose of 0.1 mmol/kg, ten min prior to application of cross clamp across the aorta. The explanted hearts were imaged with a 1.5 T CMR scanner using a high resolution T1 weighted 3D volume data set. The explanted hearts were sectioned into 5-8 short axis slices using a commercial rotating meat slicer. All slices were stained with triphenyltetrazolium chloride (TTC) and photographed. Experienced observers separately analyzed matched slices from the DE-CMR data sets and the histopathologic sections. The DE-CMR slices were planimetered to quantify the extent of enhanced and nonenhanced myocardium on each slice. The histopathologic sections were planimetered to calculate the extent of myocardium exhibiting TTC uptake. Results: Three subjects with differing etiologies of heart failure were enrolled: ischemic, nonischemic left heart failure from cardiac amyloidosis, and nonischemic right heart failure from primary pulmonary hypertension. The mean age was 57.3 6 3.5 years, duration of heart failure 15 6 9 months; 1 man and 2 women; mean LVEF 41 6 12%. There was a strong relationship between the extent of nonenhanced myocardium on DE-CMR and extent of TTC uptake on histopathology (r5-.99; p!0.001) as shown in the figure. Conclusion: There is a strong correlation between findings on DE-CMR and histopathology in human failing hearts. This relationship exists for both ischemic and nonischemic etiologies for heart failure.
036 hearts via collagenase perfusion. After serial filtration (smallest 30mm) to obtain the mononuclear cells, a panel of fluorescent markers containing CD34, CD38, CD90, CD45RA and a Lineage cocktail was used to phenotype these cells by flow cytometry. Sternal bone marrow, when available from the heart donors was also analyzed with the same marker panel. Results: We were able to identify a distinct population of CD90þ/CD45RA- cells among the Lin- CD34þ/CD38- cardiac mononuclear cells. As shown in the figure, failing hearts showed nearly a 2 fold increase in Lin-CD34þ/CD38-/CD90þ/CD45RA- cells compared to non-failing hearts. This population was also identifiable in the bone marrow with no clear distinction between the failing and non-failing patients. Interestingly, hearts contained a higher Lin-CD34þ/CD38- fraction compared to bone marrow where the CD34þ/ CD38þ fraction was proportionately higher. Conclusion: A Lin- CD34þ/CD38-/ CD90þ/CD45RA- progenitor cell subpopulation with in vivo hematopoietic properties has recently been identified in the human cord blood. We were able to identify a similar population in the human hearts and bone marrow. The finding of an abundance of this progenitor cell subpopulation in the failing hearts highlights the need to clarify its functional capacity.
Regional Right Ventricular Wall Stress and Thickness in Pulmonary Hypertension Chirag A. Chauhan1, Derek R. Wisnieski4, Christopher R. Deible2, Michael A. Mathier3, Joan Lacomis2, Sanjeev G. Shroff4, Michael R. Pinsky5, Marc A. Simon3; 1Department of Internal Medicine, University of Pittsburgh, Pittsburgh, PA; 2Department of Radiology; 3 Cardiovascular Institute; 4Department of Bioengineering; 5Department of Critical Care Medicine Background: Right ventricular (RV) dysfunction in pulmonary hypertension (PH), characterized by chamber dilation and hypertrophy, is theorized to result from increased wall stress (s). We characterized regional RV s from ECG-gated multislice computed tomography (MSCT) using ellipsoidal modeling in PH patients with compensated (PH-C) and decompensated (PH-D) RV function. Methods: A total of 18
Table 1. Patient data in end-systole Normal
PH-C
5
6
N
035 Histologic Correlates of Delayed Enhancement CMR in Ischemic and Nonischemic Heart Failure Omar M. Cheema, Keith Youker, Ankit A. Patel, Ahmad Khalil, Jerry D. Estep, Carlos M. Orrego, Guillermo A. Torre, Dipan J. Shah; Cardiology, Methodist DeBakey Heart & Vascular Center, Houston, TX
Infudibulum Free Wall Inferior Wall
RVP h s h s h s
(mm Hg) (mm) (kPa) (mm) (kPa) (mm) (kPa)
29.4 5.4 11.7 4.5 20.3 4.4 14.3
6 6 6 6 6 6 6
2.3 0.6 4.0 1.0 6.4 1.3 4.6
58 5.5 30.3 5.8 40.0 4.4 33.2
6 6 6 6 6 6 6
PH-D 7
23.3 0.8 9.1* 2.4 22.8* 1.1 14.0*
91.1 8.2 44.3 8.6 55.7 7.4 40.8
6 6 6 6 6 6 6
19.1 2.7* 17.3* 3.3* 22.9* 1.3* 9.3*
Mean values6SD are shown. *P!0.05 compared with Normal. N, subjects; RVP, right ventricular pressure.
Introduction: Delayed enhancement cardiovascular magnetic resonance (DE-CMR) has emerged as a powerful diagnostic tool for the assessment of viable and nonviable myocardium. Prior studies have demonstrated a strong relationship between DECMR and histopathology in animal models of ischemic injury. There is limited data validating DE-CMR findings in human hearts in the setting of heart failure. We hypothesized that there would be a strong relationship between DE-CMR and histopathology in human failing hearts in both ischemic and nonischemic heart failure. Methods: Subjects undergoing heart transplantation for end stage heart failure were
patients (age 51 6 11, 8 males, mean pulmonary artery pressure [MPAP] range 13-79 mmHg) underwent right heart catheterization and ECG-gated MSCT of the chest. Patients were divided into 3 groups: Normal (MPAP#25 mmHg), PH-C (MPAPO25 mmHg and right atrial pressure [RAP]!10 mmHg) and PH-D (MPAPO25 mmHg and RAP$10 mmHg). CT images were analyzed in both short axis