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Black Bean Extract Inhibits Cardiac Fibrosis and Restores Cardiac Function in an Acute Non-Ischemic Cardiomyopathy Mouse Model
The 13th Annual Scientific Meeting
HFSA
S19
Finally E´ S-L peak difference correlated with E´ S-L time delay (r 5 -0.23, p 5 0.03). Correlation between E´ S-L peak difference and LR was significant even after controlling for LV ejection fraction. Conclusion: Left ventricular diastolic asynergy is affected by longitudinal cardiac rotation. Normalization of diastolic asynergy may be an important target for patients undergoing cardiac resynchronization therapy.
050 Black Bean Extract Inhibits Cardiac Fibrosis and Restores Cardiac Function in an Acute Non-Ischemic Cardiomyopathy Mouse Model Keith A. Youker1, Ahmad Khalil1, Carlos Orrego1, Jose Flores-Arredondo2, Sergio Serrano2, Jorge Moreno2, Guillermo Torre-Amione1; 1Cardiology, The Methodist DeBakey Heart & Vascular, The Methodist Hospital, Houston, TX; 2Cardiology, Instituto Tecnolo´gico y de Estudios Superiores de Monterre, Monterrey, Nuevo Leon, Mexico These data show that ZF cardiac function can be modulated by agents known to affect cardiac performance in humans and other mammals, positioning ZF in the spectrum of translational models for studying cardiac contractility and heart failure. However, our data also reveal a developmental sensitivity to inotropy modulating drugs: manipulation of contractility with ISO does not occur before 72 hpf in ZF hearts in vivo. Further studies are necessary to identify whether the onset of ISO sensitivity results from changing adrenergic receptor expression.
049 Impact of Longitudinal Cardiac Rotation on Left Ventricular Diastolic Asynergy Chirapa Puntawangkoon, David Verhaert, Bruce Wilkoff, Richard A. Grimm, James D. Thomas, Zoran B. Popovic; Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH Introduction: Diastolic asynergy, defined by heterogeneity of the timing and amplitude of segmental early diastolic tissue velocities, is often noted but poorly understood. Hypothesis: Left ventricular (LV) longitudinal rotation (LR), a ‘‘rocking’’ motion of the heart often seen in cardiac resynchronization therapy candidates, is associated with amplitude and time measures of diastolic asynergy. Methods: We studied consecutive 98 patients aged 64 6 13 years that were referred for cardiac resynchronization therapy. LR was assessed in apical 4-chamber view by speckletracking technique. Peak early (E´) myocardial velocity and time to peak velocity of basal septal and lateral LV wall were analyzed from color tissue Doppler data and used to calculate E´ septo-lateral (S-L) peak difference and E´ S-L time delay as measures of diastolic asynergy. Results: Of 98 cases, 77% were male, mean QRS was 162 6 27ms, 53% had evidence of significant coronary arteriosclerosis (CAD), while LV ejection fraction was 26 6 10%. Average LR was -2.3 6 3.7 degree (minus sign indicates systolic clockwise rotation in the apical 4-chamber view), E´ S-L time delay was 13 6 62 msec, and E´ S-L peak difference was -1.1 6 2.5 cm/ sec. LR was higher in non-CAD patients compared to CAD patients (-4.45 6 3.26 vs -0.4 6 3.02, p! 0.001). LR had inverse correlation with lateral E´ (p!0.001 and r5 -0.4), but no significant correlation with septal E´ (p50.57). LR correlated with E´ (S-L) peak difference (r 5-0.51, p!0.001) and showed a trend for correlation with E´ S-L time delay (r 5 -0.19, p 5 0.09).
Introduction: Black Bean (BB) extracts, high in anti-oxidants and flavinoids, have reduced liver fibrosis in a rat model. Our objective was to determine the effect of BB extracts on cardiac fibrosis and resulting functional changes in the heart. Methods: Murine cardiac derived fibroblast were stimulated with 10% fetal calf serum (FCS) with/without inclusion of black bean extract (BB) followed by realtime PCR. C57BL6 mice which receive L-NAME (an inhibitor of nitric oxide) and NaCl in their drinking water and continous infusion of Angiotensin II for four weeks via an osmotic pump. BB extract was incorporated into the standard oral diet. All experiments were performed on 5 mice in each group and repeated 3 times in series. Real-time PCR, echocardiography, immunohistochemistry, H&E and picro-sirius red staining techniques were employed to evaluate the effects. Results: Studies on murine cardiac fibroblast showed that BB extract decreased FCS induced increases in collagen 1 and TGF-b expression. Next, oral suplementation with BB extract in mice treated to induce acute heart failure, prevented the gain in body weight observed in HF mice as well as prevented the upregulation of cardiac expression of BNP and ET-1, TGF-b. Furthermore, the reduction in ejection fraction seen in HF mice (EF532%) was not observed in the group of mice treated with BB extract (EF566%). Finally, histological analysis of myocardium showed a reduction in interestitial fibrosis in BB treated mice compared to HF mice (tissue area stained, 35% vs 15%). Figure shows the change in ejection fraction (A) and fibrosis (B) in control, HF and BB treated mice. Conclusions: In an acute non-ischemic cardiomyopathy mouse model, the oral administration of BB extract prevents the development of cardiac fibrosis as well as the deterioration of cardiac function. The mechanisms of action are not known but we suggest that at least in part, may be mediated by specific effects on cardiac fibroblast function.
HFSA
S19
Finally E´ S-L peak difference correlated with E´ S-L time delay (r 5 -0.23, p 5 0.03). Correlation between E´ S-L peak difference and LR was significant even after controlling for LV ejection fraction. Conclusion: Left ventricular diastolic asynergy is affected by longitudinal cardiac rotation. Normalization of diastolic asynergy may be an important target for patients undergoing cardiac resynchronization therapy.
050 Black Bean Extract Inhibits Cardiac Fibrosis and Restores Cardiac Function in an Acute Non-Ischemic Cardiomyopathy Mouse Model Keith A. Youker1, Ahmad Khalil1, Carlos Orrego1, Jose Flores-Arredondo2, Sergio Serrano2, Jorge Moreno2, Guillermo Torre-Amione1; 1Cardiology, The Methodist DeBakey Heart & Vascular, The Methodist Hospital, Houston, TX; 2Cardiology, Instituto Tecnolo´gico y de Estudios Superiores de Monterre, Monterrey, Nuevo Leon, Mexico These data show that ZF cardiac function can be modulated by agents known to affect cardiac performance in humans and other mammals, positioning ZF in the spectrum of translational models for studying cardiac contractility and heart failure. However, our data also reveal a developmental sensitivity to inotropy modulating drugs: manipulation of contractility with ISO does not occur before 72 hpf in ZF hearts in vivo. Further studies are necessary to identify whether the onset of ISO sensitivity results from changing adrenergic receptor expression.
049 Impact of Longitudinal Cardiac Rotation on Left Ventricular Diastolic Asynergy Chirapa Puntawangkoon, David Verhaert, Bruce Wilkoff, Richard A. Grimm, James D. Thomas, Zoran B. Popovic; Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH Introduction: Diastolic asynergy, defined by heterogeneity of the timing and amplitude of segmental early diastolic tissue velocities, is often noted but poorly understood. Hypothesis: Left ventricular (LV) longitudinal rotation (LR), a ‘‘rocking’’ motion of the heart often seen in cardiac resynchronization therapy candidates, is associated with amplitude and time measures of diastolic asynergy. Methods: We studied consecutive 98 patients aged 64 6 13 years that were referred for cardiac resynchronization therapy. LR was assessed in apical 4-chamber view by speckletracking technique. Peak early (E´) myocardial velocity and time to peak velocity of basal septal and lateral LV wall were analyzed from color tissue Doppler data and used to calculate E´ septo-lateral (S-L) peak difference and E´ S-L time delay as measures of diastolic asynergy. Results: Of 98 cases, 77% were male, mean QRS was 162 6 27ms, 53% had evidence of significant coronary arteriosclerosis (CAD), while LV ejection fraction was 26 6 10%. Average LR was -2.3 6 3.7 degree (minus sign indicates systolic clockwise rotation in the apical 4-chamber view), E´ S-L time delay was 13 6 62 msec, and E´ S-L peak difference was -1.1 6 2.5 cm/ sec. LR was higher in non-CAD patients compared to CAD patients (-4.45 6 3.26 vs -0.4 6 3.02, p! 0.001). LR had inverse correlation with lateral E´ (p!0.001 and r5 -0.4), but no significant correlation with septal E´ (p50.57). LR correlated with E´ (S-L) peak difference (r 5-0.51, p!0.001) and showed a trend for correlation with E´ S-L time delay (r 5 -0.19, p 5 0.09).
Introduction: Black Bean (BB) extracts, high in anti-oxidants and flavinoids, have reduced liver fibrosis in a rat model. Our objective was to determine the effect of BB extracts on cardiac fibrosis and resulting functional changes in the heart. Methods: Murine cardiac derived fibroblast were stimulated with 10% fetal calf serum (FCS) with/without inclusion of black bean extract (BB) followed by realtime PCR. C57BL6 mice which receive L-NAME (an inhibitor of nitric oxide) and NaCl in their drinking water and continous infusion of Angiotensin II for four weeks via an osmotic pump. BB extract was incorporated into the standard oral diet. All experiments were performed on 5 mice in each group and repeated 3 times in series. Real-time PCR, echocardiography, immunohistochemistry, H&E and picro-sirius red staining techniques were employed to evaluate the effects. Results: Studies on murine cardiac fibroblast showed that BB extract decreased FCS induced increases in collagen 1 and TGF-b expression. Next, oral suplementation with BB extract in mice treated to induce acute heart failure, prevented the gain in body weight observed in HF mice as well as prevented the upregulation of cardiac expression of BNP and ET-1, TGF-b. Furthermore, the reduction in ejection fraction seen in HF mice (EF532%) was not observed in the group of mice treated with BB extract (EF566%). Finally, histological analysis of myocardium showed a reduction in interestitial fibrosis in BB treated mice compared to HF mice (tissue area stained, 35% vs 15%). Figure shows the change in ejection fraction (A) and fibrosis (B) in control, HF and BB treated mice. Conclusions: In an acute non-ischemic cardiomyopathy mouse model, the oral administration of BB extract prevents the development of cardiac fibrosis as well as the deterioration of cardiac function. The mechanisms of action are not known but we suggest that at least in part, may be mediated by specific effects on cardiac fibroblast function.