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312
S152
Abstracts
311 WITHDRAWN 312 PARACRINE EFFECTS OF TRANSPLANTED BONE MARROW CELLS AND SKELETAL MYOBLASTS ON RECIPIENT CARDIOMYOCYTE FUNCTION IN A RAT MODEL OF HEART FAILURE J. Lee,1 S. Fukushima,1 M.A. Stagg,1 G.K. Soppa,1 S.J. Youssef,1 M.H. Yacoub,1 K. Suzuki,1 C.M. Terracciano,1 1National Heart & Lung Institute, Imperial College London, Harefield, Middlesex, United Kingdom Cell transplantation has been proposed as a therapy for heart failure. However, low numbers of surviving transplanted cells cannot explain the functional myocardial improvement directly, and the cellular mechanisms responsible remain unknown. We hypothesise that transplanted cells exert paracrine effects that improve Ca regulation in recipient ventricular myocytes. Heart failure (HF) was induced in Sprague-Dawley rats by left coronary artery ligation. After 3 weeks left ventricular ejection fraction (EF), monitored by echocardiography, decreased in HF compared with sham-operated (SHAM) rats (34.9⫾4% [44] vs 79.5⫾2.1% [16]; Mean⫾SEM –). Bone marrow cells (BM) or skeletal myoblasts (SK), both from GFP-expressing rats, were injected into the heart by intramuscular or retrograde route. After 5 weeks both cell types improved EF (BM from 34.1⫾1.7% to 43.2⫾3% [13] p⫽0.007; SK from 36.9⫾1.5% to 44.5⫾2.6% [17] p⫽0.009) whereas there was no difference after PBS injection only. Isolated ventricular myocytes were GFP-negative. Ca transient amplitude, measured using indo-1, was decreased in HF (0.079⫾0.003 [60] p⬍0.001 vs SHAM (0.103⫾0.004 [56])). After SK transplantation, but not BM, indo-1 transient amplitude increased (SK: 0.104⫾0.003 [111] p⬍0.001; BM: 0.081⫾0.004 [42]). Indo-1 time-topeak (TTP) was delayed in HF, but transplantation of either cell type abolished this delay (TTP, ms: SHAM 39.5⫾0.66 [56], HF 43.4⫾0.89 [60], BM 37.0⫾ 0.13 [42] (p⬍0.001 vs HF), SK 36.8⫾0.62 [111] (p⬍0.001 vs HF)). L-type calcium-current density was increased in SK compared with HF but was unchanged in BM (SHAM -3.24⫾0.19 pA/pF, HF -2.86⫾0.15 pA/pF, BM -3.22⫾0.18 pA/pF, SK -3.7⫾0.22 pA/pF (p⬍0.05 vs HF)). We conclude that BM and SK transplantation affects Ca regulation in recipient cardiomyocytes and this can be responsible for the improvement in heart function. The mechanisms involved, possibly paracrine, require further investigation. 313 QUANTIFICATION OF LEFT VENTRICULAR MECHANICAL DYSSYNCHRONY BY CONDUCTANCE CATHETER IN THE FAILING HEART: EFFECT OF BIVENTRICULAR PACING ´ s,2 B. Merkely,2 S. Hagl,1 1Cardiac Surgery, G. Szabo ´ ,1 P. Soo University of Heidelberg, Heidelberg, Germany; 2Cardiovascular Surgery, Semmelweis University, Budapest, Hungary Mechanical dyssynchrony is important codeterminant of cardiac dysfunction in heart failure. We evaluated new indexes to quantify temporal and spatial aspects of mechanical dyssynchrony derived from on-line segmental conductance catheter signals. To test the feasibility and usefulness of our approach, we determined cardiac function and left ventricular (LV) dyssynchrony in normal (n⫽6) and failing canine hearts (rapid pacing: 180 min-1, 12 weeks, n⫽7) before and after biventricular pacing. Segmental signals were defined as dyssynchronous at each time point if its change were opposite to the simultaneous change in the total LV volume. Overall dyssynchrony was calculated as the mean of the segmental dyssynchronies during systole (DYSsys) and diastole (DYSdias). Ineffective blood shifting
The Journal of Heart and Lung Transplantation February 2006
within the LV (IBF) was calculated as the sum of the absolute volume changes of all segments and subtracting the total absolute total volume change and expressed as percent fraction of total effective flow. Mechanical dispersion (DISP) was assessed by segmental lag times. LV contractility was described by the slope of the endsystolic pressure-volume relationships (Ees). Pacing induced heart failure led to significantly reduced Ees. Indexes of LV dyssynchrony were increased in the heart failure group. Biventricular pacing improved Ees by reduction of mechanical dyssynchrony (Table 1). Pacing induced heart failure in canines leads to reduced LV contractility and significant LV mechanical dyssynchrony which can be improved by biventricular pacing. The proposed indexes provide additional, new and quantitative information on temporal and spatial aspects of mechanical dyssynchrony and may refine diagnosis of cardiac dysfunction and evaluation of interventions. Table 1 Ees DYSsys DYSdias DISP IBF
Control
Heart Failure
Biventricular pacing
6.9 ⫾ 1.0 9⫾8 3⫾2 18 ⫾ 7 11 ⫾ 4
2.3 ⫾ 0.3ⴱ 39 ⫾ 7ⴱ 41 ⫾ 7ⴱ 70 ⫾ 15ⴱ 66 ⫾ 12ⴱ ⴱp ⬍ 0.05 vs control
3.7 ⫾ 0.2† 12 ⫾ 7† 13 ⫾ 6† 27 ⫾ 7† 23 ⫾ 7† †p ⬍ 0.05 vs heart failure
314 POST-TRANSPLANT EMPLOYMENT AND ITS RELATIONSHIP TO PHYSICAL STATUS W. Paris,1 I. Nizami,2 C. Hille,2 R. Cross,2 D. Nelson,2 C. Elkins,2 P. Kanaly,2 J. Chaffin,2 1School of Social Work, Southern Illinois University, Carbondale, IL; 2Nazih Zuhdi Transplantation Institute, Integris Baptist Medical Center, Oklahoma City, OK Post-transplant (TX) employment has long been considered an indication of functional benefit to the recipient and social benefit to the community. There are studies which suggest that ⬎50% of those which are physically able remain unemployed and continue to draw disability post-TX. The purpose of the present study is to explore this issue by use of the American Medical Association Guide to Physical Impairment (AMGPI) which allows the physician to categorize the patient’s physical ability based on objective scales specific to heart TX (i.e., medication reactions, stamina, chronic pain, etc. . .). Participants were 43 randomly selected TX recipients from a Mid-Western US multi-organ transplant program. Using the AMGPI categories for physical comparison found that 90% (18/20) of those that were employed and viewed themselves as physically able had ⬍15% physical impairment. For those unemployed recipients that continued to perceive themselves as physically unable to work found that 83% (15/18) had between 15–29% physical impairment. A Spearman’s correlation found the differences were inversely significant at p⬍0.01. When employment status and perception of employment ability were compared on the basis of mean EF and 6 minute walk results there were no significant differences found. The results suggest that when physical and employment status are compared by traditional means there is no indication of physical limitations sufficient to justify continued perception of inability to work. However, use of criteria which takes into account medical issues specifically related to heart TX recipients suggests that they do continue to suffer physical impairment which may support their contention of continued physical inability to work. These findings clearly conflict with the earlier reports and indicate the need for additional analysis of the AMGPI to help determine the physical limitations specific to continued perception of inability to work post-TX.
Abstracts
311 WITHDRAWN 312 PARACRINE EFFECTS OF TRANSPLANTED BONE MARROW CELLS AND SKELETAL MYOBLASTS ON RECIPIENT CARDIOMYOCYTE FUNCTION IN A RAT MODEL OF HEART FAILURE J. Lee,1 S. Fukushima,1 M.A. Stagg,1 G.K. Soppa,1 S.J. Youssef,1 M.H. Yacoub,1 K. Suzuki,1 C.M. Terracciano,1 1National Heart & Lung Institute, Imperial College London, Harefield, Middlesex, United Kingdom Cell transplantation has been proposed as a therapy for heart failure. However, low numbers of surviving transplanted cells cannot explain the functional myocardial improvement directly, and the cellular mechanisms responsible remain unknown. We hypothesise that transplanted cells exert paracrine effects that improve Ca regulation in recipient ventricular myocytes. Heart failure (HF) was induced in Sprague-Dawley rats by left coronary artery ligation. After 3 weeks left ventricular ejection fraction (EF), monitored by echocardiography, decreased in HF compared with sham-operated (SHAM) rats (34.9⫾4% [44] vs 79.5⫾2.1% [16]; Mean⫾SEM –). Bone marrow cells (BM) or skeletal myoblasts (SK), both from GFP-expressing rats, were injected into the heart by intramuscular or retrograde route. After 5 weeks both cell types improved EF (BM from 34.1⫾1.7% to 43.2⫾3% [13] p⫽0.007; SK from 36.9⫾1.5% to 44.5⫾2.6% [17] p⫽0.009) whereas there was no difference after PBS injection only. Isolated ventricular myocytes were GFP-negative. Ca transient amplitude, measured using indo-1, was decreased in HF (0.079⫾0.003 [60] p⬍0.001 vs SHAM (0.103⫾0.004 [56])). After SK transplantation, but not BM, indo-1 transient amplitude increased (SK: 0.104⫾0.003 [111] p⬍0.001; BM: 0.081⫾0.004 [42]). Indo-1 time-topeak (TTP) was delayed in HF, but transplantation of either cell type abolished this delay (TTP, ms: SHAM 39.5⫾0.66 [56], HF 43.4⫾0.89 [60], BM 37.0⫾ 0.13 [42] (p⬍0.001 vs HF), SK 36.8⫾0.62 [111] (p⬍0.001 vs HF)). L-type calcium-current density was increased in SK compared with HF but was unchanged in BM (SHAM -3.24⫾0.19 pA/pF, HF -2.86⫾0.15 pA/pF, BM -3.22⫾0.18 pA/pF, SK -3.7⫾0.22 pA/pF (p⬍0.05 vs HF)). We conclude that BM and SK transplantation affects Ca regulation in recipient cardiomyocytes and this can be responsible for the improvement in heart function. The mechanisms involved, possibly paracrine, require further investigation. 313 QUANTIFICATION OF LEFT VENTRICULAR MECHANICAL DYSSYNCHRONY BY CONDUCTANCE CATHETER IN THE FAILING HEART: EFFECT OF BIVENTRICULAR PACING ´ s,2 B. Merkely,2 S. Hagl,1 1Cardiac Surgery, G. Szabo ´ ,1 P. Soo University of Heidelberg, Heidelberg, Germany; 2Cardiovascular Surgery, Semmelweis University, Budapest, Hungary Mechanical dyssynchrony is important codeterminant of cardiac dysfunction in heart failure. We evaluated new indexes to quantify temporal and spatial aspects of mechanical dyssynchrony derived from on-line segmental conductance catheter signals. To test the feasibility and usefulness of our approach, we determined cardiac function and left ventricular (LV) dyssynchrony in normal (n⫽6) and failing canine hearts (rapid pacing: 180 min-1, 12 weeks, n⫽7) before and after biventricular pacing. Segmental signals were defined as dyssynchronous at each time point if its change were opposite to the simultaneous change in the total LV volume. Overall dyssynchrony was calculated as the mean of the segmental dyssynchronies during systole (DYSsys) and diastole (DYSdias). Ineffective blood shifting
The Journal of Heart and Lung Transplantation February 2006
within the LV (IBF) was calculated as the sum of the absolute volume changes of all segments and subtracting the total absolute total volume change and expressed as percent fraction of total effective flow. Mechanical dispersion (DISP) was assessed by segmental lag times. LV contractility was described by the slope of the endsystolic pressure-volume relationships (Ees). Pacing induced heart failure led to significantly reduced Ees. Indexes of LV dyssynchrony were increased in the heart failure group. Biventricular pacing improved Ees by reduction of mechanical dyssynchrony (Table 1). Pacing induced heart failure in canines leads to reduced LV contractility and significant LV mechanical dyssynchrony which can be improved by biventricular pacing. The proposed indexes provide additional, new and quantitative information on temporal and spatial aspects of mechanical dyssynchrony and may refine diagnosis of cardiac dysfunction and evaluation of interventions. Table 1 Ees DYSsys DYSdias DISP IBF
Control
Heart Failure
Biventricular pacing
6.9 ⫾ 1.0 9⫾8 3⫾2 18 ⫾ 7 11 ⫾ 4
2.3 ⫾ 0.3ⴱ 39 ⫾ 7ⴱ 41 ⫾ 7ⴱ 70 ⫾ 15ⴱ 66 ⫾ 12ⴱ ⴱp ⬍ 0.05 vs control
3.7 ⫾ 0.2† 12 ⫾ 7† 13 ⫾ 6† 27 ⫾ 7† 23 ⫾ 7† †p ⬍ 0.05 vs heart failure
314 POST-TRANSPLANT EMPLOYMENT AND ITS RELATIONSHIP TO PHYSICAL STATUS W. Paris,1 I. Nizami,2 C. Hille,2 R. Cross,2 D. Nelson,2 C. Elkins,2 P. Kanaly,2 J. Chaffin,2 1School of Social Work, Southern Illinois University, Carbondale, IL; 2Nazih Zuhdi Transplantation Institute, Integris Baptist Medical Center, Oklahoma City, OK Post-transplant (TX) employment has long been considered an indication of functional benefit to the recipient and social benefit to the community. There are studies which suggest that ⬎50% of those which are physically able remain unemployed and continue to draw disability post-TX. The purpose of the present study is to explore this issue by use of the American Medical Association Guide to Physical Impairment (AMGPI) which allows the physician to categorize the patient’s physical ability based on objective scales specific to heart TX (i.e., medication reactions, stamina, chronic pain, etc. . .). Participants were 43 randomly selected TX recipients from a Mid-Western US multi-organ transplant program. Using the AMGPI categories for physical comparison found that 90% (18/20) of those that were employed and viewed themselves as physically able had ⬍15% physical impairment. For those unemployed recipients that continued to perceive themselves as physically unable to work found that 83% (15/18) had between 15–29% physical impairment. A Spearman’s correlation found the differences were inversely significant at p⬍0.01. When employment status and perception of employment ability were compared on the basis of mean EF and 6 minute walk results there were no significant differences found. The results suggest that when physical and employment status are compared by traditional means there is no indication of physical limitations sufficient to justify continued perception of inability to work. However, use of criteria which takes into account medical issues specifically related to heart TX recipients suggests that they do continue to suffer physical impairment which may support their contention of continued physical inability to work. These findings clearly conflict with the earlier reports and indicate the need for additional analysis of the AMGPI to help determine the physical limitations specific to continued perception of inability to work post-TX.