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John M Canty - One of the best experts on this subject based on the ideXlab platform.

  • 1 Reductions in Mitochondrial Oxygen Consumption and Preservation of High Energy Phosphate Levels Following Simulated Ischemia in Chronic
    2016
    Co-Authors: Hibernating Myocardium, John M Canty, James A Fallavollita, Gen Suzuki, Rebeccah F. Young
    Abstract:

    We performed the present study to determine whether Hibernating Myocardium is chronically protected from ischemia. Myocardial tissue was rapidly excised from Hibernating LAD regions (∆WT 2.8±0.2 vs. 5.4±0.3 mm in remote Myocardium) and high-energy phosphates were quantified by HPLC during simulated ischemia in vitro (37°C). At baseline, ATP (20.1±1.0 vs. 26.7±2.1 μmol/g dry weight, p<0.05), ADP (8.1±0.4 vs. 10.3±0.8 μmol/g, p<0.05) and total adenine nucleotides (31.2±1.3 vs. 40.1±2.9 μmol/g, p<0.05) were depressed vs. normal Myocardium while total creatine, CP and ATP/ADP ratios were unchanged. During simulated ischemia, there was a marked attenuation of ATP depletion (5.6±0.9 vs. 13.7±1.7 μmol/g at 20-minutes in control, p<0.05) and mitochondrial respiration (State 3 145±13 vs. 187±11 ng atoms O2/mg protein/min, p< 0.05) while lactate accumulation was unaffected. These in vitro changes were accompanied by protection of the Hibernating heart from acute stunning during demand-induced ischemia. Thus, despite contractile dysfunction at rest, Hibernating Myocardium is ischemia tolerant with reduced mitochondrial respiration and slowing of ATP depletion during simulated ischemia which may maintain myocyte viability. Key words- energy metabolism; mitochondrial respiration; stunned Myocardium; hibernatin

  • Reproducible Ion-Current-Based Approach for 24-Plex Comparison of the Tissue Proteomes of Hibernating versus Normal Myocardium in Swine Models
    2016
    Co-Authors: Xiaotao Duan, James A Fallavollita, John M Canty
    Abstract:

    ABSTRACT: Hibernating Myocardium is an adaptive response to repetitive myocardial ischemia that is clinically common, but the mechanism of adaptation is poorly understood. Here we compared the proteomes of Hibernating versus normal Myocardium in a porcine model with 24 biological replicates. Using the ion-current-based proteomic strategy optimized in this study to expand upon previous proteomic work, we identified differentially expressed proteins in new molecular pathways of cardiovascular interest. The methodological strategy includes efficient extraction with detergent cocktail; precipitation/digestion procedure with high, quantitative peptide recovery; reproducible nano-LC/MS analysis on a long, heated column packed with small particles; and quantification based on ion-current peak areas. Under the optimized conditions, high efficiency and reproducibility were achieved for each step, which enabled a reliable comparison of 24 the myocardial samples. To achieve confident discovery of differentially regulated proteins in Hibernating Myocardium, we used highly stringent criteria to define “quantifiabl

  • Global Intracoronary Infusion of Allogeneic Cardiosphere-Derived Cells Improves Ventricular Function and Stimulates Endogenous Myocyte Regeneration throughout the Heart in Swine with
    2016
    Co-Authors: Hibernating Myocardium, Gen Suzuki, Rebeccah F. Young, Brian R. Weil, Merced M. Leiker, Thomas R. Cimato, A E. Ribbeck, John M Canty
    Abstract:

    Background: Cardiosphere-derived cells (CDCs) improve ventricular function and reduce fibrotic volume when administered via an infarct-related artery using the ‘‘stop-flow’ ’ technique. Unfortunately, myocyte loss and dysfunction occur globally in many patients with ischemic and non-ischemic cardiomyopathy, necessitating an approach to distribute CDCs throughout the entire heart. We therefore determined whether global intracoronary infusion of CDCs under continuous flow improves contractile function and stimulates new myocyte formation. Methods and Results: Swine with Hibernating Myocardium from a chronic LAD occlusion were studied 3-months after instrumentation (n = 25). CDCs isolated from myocardial biopsies were infused into each major coronary artery (,336106 icCDCs). Global icCDC infusion was safe and while,3 % of injected CDCs were retained, they did not affect ventricular function or myocyte proliferation in normal animals. In contrast, four-weeks after icCDCs were administered to animals with Hibernating Myocardium, %LADWT increased from 2366 to 5165 % (p,0.01). In diseased hearts, myocyte proliferation (phospho-histone-H3) increased in Hibernating and remote regions with a concomitant increase in myocyte nuclear density. These effects were accompanied by reductions in myocyte diameter consistent with new myocyte formation. Only rare myocytes arose from sex-mismatched donor CDCs. Conclusions: Global icCDC infusion under continuous flow is feasible and improves contractile function, regresses myocyt

  • Reproducible Ion-Current-Based Approach for 24-Plex Comparison of the Tissue Proteomes of Hibernating versus Normal Myocardium in Swine Models
    2015
    Co-Authors: Rebeccah Young, James A Fallavollita, Brian J. Page, Xiaomeng Shen, Nazneen Tata, Xiaotao Duan, John M Canty
    Abstract:

    Hibernating Myocardium is an adaptive response to repetitive myocardial ischemia that is clinically common, but the mechanism of adaptation is poorly understood. Here we compared the proteomes of Hibernating versus normal Myocardium in a porcine model with 24 biological replicates. Using the ion-current-based proteomic strategy optimized in this study to expand upon previous proteomic work, we identified differentially expressed proteins in new molecular pathways of cardiovascular interest. The methodological strategy includes efficient extraction with detergent cocktail; precipitation/digestion procedure with high, quantitative peptide recovery; reproducible nano-LC/MS analysis on a long, heated column packed with small particles; and quantification based on ion-current peak areas. Under the optimized conditions, high efficiency and reproducibility were achieved for each step, which enabled a reliable comparison of 24 the myocardial samples. To achieve confident discovery of differentially regulated proteins in Hibernating Myocardium, we used highly stringent criteria to define “quantifiable proteins”. These included the filtering criteria of low peptide FDR and S/N > 10 for peptide ion currents, and each protein was quantified independently from ≥2 distinct peptides. For a broad methodological validation, the quantitative results were compared with a parallel, well-validated 2D-DIGE analysis of the same model. Excellent agreement between the two orthogonal methods was observed (R = 0.74), and the ion-current-based method quantified almost one order of magnitude more proteins. In Hibernating Myocardium, 225 significantly altered proteins were discovered with a low false-discovery rate (∼3%). These proteins are involved in biological processes including metabolism, apoptosis, stress response, contraction, cytoskeleton, transcription, and translation. This provides compelling evidence that Hibernating Myocardium adapts to chronic ischemia. The major metabolic mechanisms include a down-regulation of mitochondrial respiration and an increase in glycolysis. Meanwhile, cardioprotective and cytoskeletal proteins are increased, while cardiomyocyte contractile proteins are reduced. These intrinsic adaptations to regional ischemia maintain long-term cardiomyocyte viability at the expense of contractile function

  • abstract 334 intracoronary allogeneic mesenchymal stem cells and cardiosphere derived cells exert comparable effects on myocyte and capillary proliferation without promoting functional arteriogenesis in swine with chronic myocardial ischemia
    Arteriosclerosis Thrombosis and Vascular Biology, 2014
    Co-Authors: Brian R. Weil, James A Fallavollita, Gen Suzuki, Merced M. Leiker, Beth A Palka, John M Canty
    Abstract:

    Objective: Allogeneic icMSCs and icCDCs each improve function of Hibernating Myocardium but the underlying mechanisms remain unclear. We performed the present study to assess the effects of icMSCs and icCDCs on myocardial perfusion and remodeling of the coronary microcirculation in a large animal model of chronic regional ischemia. Methods: Cyclosporine-treated swine (200 mg/day) with Hibernating Myocardium from a chronic LAD stenosis received ~35 x 106 icMSCs, ~35 x 106 icCDCs, or vehicle. Regional function (echocardiography), adenosine-vasodilated perfusion (microspheres) and vascular remodeling were assessed 1-month after treatment. Results: Baseline LAD wall thickening (%WT) was reduced in all animals ( LAD 38 ± 2% vs. 83 ± 5% in remote, p<0.01) but not different between treatment groups. Coronary flow during vasodilation was also critically reduced at baseline (LAD 2.4 ± 0.3 ml/min/g vs. 4.6 ± 0.3 ml/min/g in remote, p<0.01). Intracoronary stem cell infusion improved LAD %WT but did not alter vasodilated perfusion (Table). Although capillary density increased in relative proportion to the increase in myocyte number, there were no significant changes in arteriolar density following cell therapy. Conclusion: These data demonstrate that the functional improvement afforded by allogeneic icMSCs and icCDCs is accompanied by concomitant capillary angiogenesis and myocyte regeneration in Hibernating Myocardium. However, myocardial perfusion deficits persist due to an inability of either cell type to promote functional arteriogenesis, indicating that cell therapy-mediated functional benefits occur independently of changes in coronary blood flow. ![][1] [1]: /embed/graphic-1.gif

James A Fallavollita - One of the best experts on this subject based on the ideXlab platform.

  • Spatial heterogeneity in fasting and insulinstimulated 18F-2-deoxyglucose uptake in pigs with Hibernating Myocardium. Circulation 2000
    2016
    Co-Authors: James A Fallavollita
    Abstract:

    Background—Previous studies of Hibernating Myocardium in the fasting state have shown regionally increased 18F-2-deoxyglucose (FDG) uptake with a marked transmural gradient. We hypothesized that this adaptation to chronic ischemia might be associated with altered maximal FDG uptake. Methods and Results—Pigs were instrumented with a 1.5-mm proximal left anterior descending artery (LAD) stenosis. Studies were conducted 10664 days later on anesthetized animals with complete LAD occlusion and anteroapical dysfunction. In fasting animals (n59), FDG uptake in dysfunctional LAD regions was 2-fold higher than in normally perfused Myocardium (7.961.2 versus 4.060.5mmol z min21 z 100 g21, P,0.05), with a pronounced transmural gradient (endocardial/epicardial ratio 2.5660.19 versus 1.2560.03, P,0.05). Euglycemic, hyperinsulinemic clamp (insulin clamp, n58) produced a 5- to 9-fold increase in FDG uptake, but there was no longer a regional difference in accumulation (LAD, 37.864.2 versus normal, 36.465.1 mmol z min21 z 100 g21, P5NS) and the transmural distribution was uniform. FDG uptake in the fasting state varied inversely with coronary flow during vasodilation. In contrast, during insulin clamp there was no relation between FDG uptake and vasodilated flow, resulting in a reduced spatial heterogeneity in individual samples (relative dispersion5SD/mean; fasting, 5265 % versus insulin, 2462%, P,0.05). Conclusions—In the fasting state, FDG uptake in pigs with Hibernating Myocardium was heterogeneous and was increased in dysfunctional regions with a marked transmural gradient and high spatial heterogeneity. In contrast

  • 1 Reductions in Mitochondrial Oxygen Consumption and Preservation of High Energy Phosphate Levels Following Simulated Ischemia in Chronic
    2016
    Co-Authors: Hibernating Myocardium, John M Canty, James A Fallavollita, Gen Suzuki, Rebeccah F. Young
    Abstract:

    We performed the present study to determine whether Hibernating Myocardium is chronically protected from ischemia. Myocardial tissue was rapidly excised from Hibernating LAD regions (∆WT 2.8±0.2 vs. 5.4±0.3 mm in remote Myocardium) and high-energy phosphates were quantified by HPLC during simulated ischemia in vitro (37°C). At baseline, ATP (20.1±1.0 vs. 26.7±2.1 μmol/g dry weight, p<0.05), ADP (8.1±0.4 vs. 10.3±0.8 μmol/g, p<0.05) and total adenine nucleotides (31.2±1.3 vs. 40.1±2.9 μmol/g, p<0.05) were depressed vs. normal Myocardium while total creatine, CP and ATP/ADP ratios were unchanged. During simulated ischemia, there was a marked attenuation of ATP depletion (5.6±0.9 vs. 13.7±1.7 μmol/g at 20-minutes in control, p<0.05) and mitochondrial respiration (State 3 145±13 vs. 187±11 ng atoms O2/mg protein/min, p< 0.05) while lactate accumulation was unaffected. These in vitro changes were accompanied by protection of the Hibernating heart from acute stunning during demand-induced ischemia. Thus, despite contractile dysfunction at rest, Hibernating Myocardium is ischemia tolerant with reduced mitochondrial respiration and slowing of ATP depletion during simulated ischemia which may maintain myocyte viability. Key words- energy metabolism; mitochondrial respiration; stunned Myocardium; hibernatin

  • Reproducible Ion-Current-Based Approach for 24-Plex Comparison of the Tissue Proteomes of Hibernating versus Normal Myocardium in Swine Models
    2016
    Co-Authors: Xiaotao Duan, James A Fallavollita, John M Canty
    Abstract:

    ABSTRACT: Hibernating Myocardium is an adaptive response to repetitive myocardial ischemia that is clinically common, but the mechanism of adaptation is poorly understood. Here we compared the proteomes of Hibernating versus normal Myocardium in a porcine model with 24 biological replicates. Using the ion-current-based proteomic strategy optimized in this study to expand upon previous proteomic work, we identified differentially expressed proteins in new molecular pathways of cardiovascular interest. The methodological strategy includes efficient extraction with detergent cocktail; precipitation/digestion procedure with high, quantitative peptide recovery; reproducible nano-LC/MS analysis on a long, heated column packed with small particles; and quantification based on ion-current peak areas. Under the optimized conditions, high efficiency and reproducibility were achieved for each step, which enabled a reliable comparison of 24 the myocardial samples. To achieve confident discovery of differentially regulated proteins in Hibernating Myocardium, we used highly stringent criteria to define “quantifiabl

  • Reproducible Ion-Current-Based Approach for 24-Plex Comparison of the Tissue Proteomes of Hibernating versus Normal Myocardium in Swine Models
    2015
    Co-Authors: Rebeccah Young, James A Fallavollita, Brian J. Page, Xiaomeng Shen, Nazneen Tata, Xiaotao Duan, John M Canty
    Abstract:

    Hibernating Myocardium is an adaptive response to repetitive myocardial ischemia that is clinically common, but the mechanism of adaptation is poorly understood. Here we compared the proteomes of Hibernating versus normal Myocardium in a porcine model with 24 biological replicates. Using the ion-current-based proteomic strategy optimized in this study to expand upon previous proteomic work, we identified differentially expressed proteins in new molecular pathways of cardiovascular interest. The methodological strategy includes efficient extraction with detergent cocktail; precipitation/digestion procedure with high, quantitative peptide recovery; reproducible nano-LC/MS analysis on a long, heated column packed with small particles; and quantification based on ion-current peak areas. Under the optimized conditions, high efficiency and reproducibility were achieved for each step, which enabled a reliable comparison of 24 the myocardial samples. To achieve confident discovery of differentially regulated proteins in Hibernating Myocardium, we used highly stringent criteria to define “quantifiable proteins”. These included the filtering criteria of low peptide FDR and S/N > 10 for peptide ion currents, and each protein was quantified independently from ≥2 distinct peptides. For a broad methodological validation, the quantitative results were compared with a parallel, well-validated 2D-DIGE analysis of the same model. Excellent agreement between the two orthogonal methods was observed (R = 0.74), and the ion-current-based method quantified almost one order of magnitude more proteins. In Hibernating Myocardium, 225 significantly altered proteins were discovered with a low false-discovery rate (∼3%). These proteins are involved in biological processes including metabolism, apoptosis, stress response, contraction, cytoskeleton, transcription, and translation. This provides compelling evidence that Hibernating Myocardium adapts to chronic ischemia. The major metabolic mechanisms include a down-regulation of mitochondrial respiration and an increase in glycolysis. Meanwhile, cardioprotective and cytoskeletal proteins are increased, while cardiomyocyte contractile proteins are reduced. These intrinsic adaptations to regional ischemia maintain long-term cardiomyocyte viability at the expense of contractile function

  • abstract 334 intracoronary allogeneic mesenchymal stem cells and cardiosphere derived cells exert comparable effects on myocyte and capillary proliferation without promoting functional arteriogenesis in swine with chronic myocardial ischemia
    Arteriosclerosis Thrombosis and Vascular Biology, 2014
    Co-Authors: Brian R. Weil, James A Fallavollita, Gen Suzuki, Merced M. Leiker, Beth A Palka, John M Canty
    Abstract:

    Objective: Allogeneic icMSCs and icCDCs each improve function of Hibernating Myocardium but the underlying mechanisms remain unclear. We performed the present study to assess the effects of icMSCs and icCDCs on myocardial perfusion and remodeling of the coronary microcirculation in a large animal model of chronic regional ischemia. Methods: Cyclosporine-treated swine (200 mg/day) with Hibernating Myocardium from a chronic LAD stenosis received ~35 x 106 icMSCs, ~35 x 106 icCDCs, or vehicle. Regional function (echocardiography), adenosine-vasodilated perfusion (microspheres) and vascular remodeling were assessed 1-month after treatment. Results: Baseline LAD wall thickening (%WT) was reduced in all animals ( LAD 38 ± 2% vs. 83 ± 5% in remote, p<0.01) but not different between treatment groups. Coronary flow during vasodilation was also critically reduced at baseline (LAD 2.4 ± 0.3 ml/min/g vs. 4.6 ± 0.3 ml/min/g in remote, p<0.01). Intracoronary stem cell infusion improved LAD %WT but did not alter vasodilated perfusion (Table). Although capillary density increased in relative proportion to the increase in myocyte number, there were no significant changes in arteriolar density following cell therapy. Conclusion: These data demonstrate that the functional improvement afforded by allogeneic icMSCs and icCDCs is accompanied by concomitant capillary angiogenesis and myocyte regeneration in Hibernating Myocardium. However, myocardial perfusion deficits persist due to an inability of either cell type to promote functional arteriogenesis, indicating that cell therapy-mediated functional benefits occur independently of changes in coronary blood flow. ![][1] [1]: /embed/graphic-1.gif

William L Winters - One of the best experts on this subject based on the ideXlab platform.

  • identification of Hibernating Myocardium with quantitative intravenous myocardial contrast echocardiography comparison with dobutamine echocardiography and thallium 201 scintigraphy
    Circulation, 2003
    Co-Authors: Sarah Shimoni, Mario S Verani, Miguel A Quinones, Nikolaos G Frangogiannis, Constadina J Aggeli, Kesavan Shan, Rafael Espada, George V Letsou, Gerald M Lawrie, William L Winters
    Abstract:

    Background— There are currently no data on the accuracy of intravenous myocardial contrast echocardiography (MCE) in detecting myocardial hibernation in man and its comparative accuracy to dobutamine echocardiography (DE) or thallium 201 (Tl201) scintigraphy. Methods and Results— Twenty patients with coronary artery disease and ventricular dysfunction underwent MCE 1 to 5 days before bypass surgery and repeat echocardiography at 3 to 4 months. Patients also underwent DE (n=18) and rest-redistribution Tl201 tomography (n=16) before revascularization. MCE was performed using continuous Optison infusion (12 to 16 cc/h) with intermittent pulse inversion harmonics and incremental triggering (1:1 to 1:8). Myocardial contrast intensity (MCI) replenishment curves were constructed to derive quantitative MCE indices of blood velocity and flow. Recovery of function occurred in 38% of dysfunctional segments. MCE parameters of perfusion in Hibernating Myocardium were similar to segments with normal function and higher...

  • identification of Hibernating Myocardium with quantitative intravenous myocardial contrast echocardiography comparison with dobutamine echocardiography and thallium 201 scintigraphy
    Circulation, 2003
    Co-Authors: Sarah Shimoni, Mario S Verani, Miguel A Quinones, Nikolaos G Frangogiannis, Constadina J Aggeli, Kesavan Shan, Rafael Espada, George V Letsou, Gerald M Lawrie, William L Winters
    Abstract:

    BACKGROUND: There are currently no data on the accuracy of intravenous myocardial contrast echocardiography (MCE) in detecting myocardial hibernation in man and its comparative accuracy to dobutamine echocardiography (DE) or thallium 201 (Tl(201)) scintigraphy. METHODS AND RESULTS: Twenty patients with coronary artery disease and ventricular dysfunction underwent MCE 1 to 5 days before bypass surgery and repeat echocardiography at 3 to 4 months. Patients also underwent DE (n=18) and rest-redistribution Tl(201) tomography (n=16) before revascularization. MCE was performed using continuous Optison infusion (12 to 16 cc/h) with intermittent pulse inversion harmonics and incremental triggering (1:1 to 1:8). Myocardial contrast intensity (MCI) replenishment curves were constructed to derive quantitative MCE indices of blood velocity and flow. Recovery of function occurred in 38% of dysfunctional segments. MCE parameters of perfusion in Hibernating Myocardium were similar to segments with normal function and higher than dysfunctional Myocardium without recovery of function (P or =60% (P 1.5 dB/s for recovery of function was 90% and was similar to Tl(201) scintigraphy (92%) and any contractile reserve (80%); specificity was higher than for Tl(201) and DE (63%, 45%, and 54%, respectively; P<0.05). CONCLUSIONS: MCE with intravenous contrast identifies myocardial hibernation in humans. Prediction of viable Myocardium with MCE is best using quantification of myocardial blood flow and provides improved accuracy compared with DE and Tl(201) scintigraphy.

Sarah Shimoni - One of the best experts on this subject based on the ideXlab platform.

  • identification of Hibernating Myocardium with quantitative intravenous myocardial contrast echocardiography comparison with dobutamine echocardiography and thallium 201 scintigraphy
    Circulation, 2003
    Co-Authors: Sarah Shimoni, Mario S Verani, Miguel A Quinones, Nikolaos G Frangogiannis, Constadina J Aggeli, Kesavan Shan, Rafael Espada, George V Letsou, Gerald M Lawrie, William L Winters
    Abstract:

    Background— There are currently no data on the accuracy of intravenous myocardial contrast echocardiography (MCE) in detecting myocardial hibernation in man and its comparative accuracy to dobutamine echocardiography (DE) or thallium 201 (Tl201) scintigraphy. Methods and Results— Twenty patients with coronary artery disease and ventricular dysfunction underwent MCE 1 to 5 days before bypass surgery and repeat echocardiography at 3 to 4 months. Patients also underwent DE (n=18) and rest-redistribution Tl201 tomography (n=16) before revascularization. MCE was performed using continuous Optison infusion (12 to 16 cc/h) with intermittent pulse inversion harmonics and incremental triggering (1:1 to 1:8). Myocardial contrast intensity (MCI) replenishment curves were constructed to derive quantitative MCE indices of blood velocity and flow. Recovery of function occurred in 38% of dysfunctional segments. MCE parameters of perfusion in Hibernating Myocardium were similar to segments with normal function and higher...

  • identification of Hibernating Myocardium with quantitative intravenous myocardial contrast echocardiography comparison with dobutamine echocardiography and thallium 201 scintigraphy
    Circulation, 2003
    Co-Authors: Sarah Shimoni, Mario S Verani, Miguel A Quinones, Nikolaos G Frangogiannis, Constadina J Aggeli, Kesavan Shan, Rafael Espada, George V Letsou, Gerald M Lawrie, William L Winters
    Abstract:

    BACKGROUND: There are currently no data on the accuracy of intravenous myocardial contrast echocardiography (MCE) in detecting myocardial hibernation in man and its comparative accuracy to dobutamine echocardiography (DE) or thallium 201 (Tl(201)) scintigraphy. METHODS AND RESULTS: Twenty patients with coronary artery disease and ventricular dysfunction underwent MCE 1 to 5 days before bypass surgery and repeat echocardiography at 3 to 4 months. Patients also underwent DE (n=18) and rest-redistribution Tl(201) tomography (n=16) before revascularization. MCE was performed using continuous Optison infusion (12 to 16 cc/h) with intermittent pulse inversion harmonics and incremental triggering (1:1 to 1:8). Myocardial contrast intensity (MCI) replenishment curves were constructed to derive quantitative MCE indices of blood velocity and flow. Recovery of function occurred in 38% of dysfunctional segments. MCE parameters of perfusion in Hibernating Myocardium were similar to segments with normal function and higher than dysfunctional Myocardium without recovery of function (P or =60% (P 1.5 dB/s for recovery of function was 90% and was similar to Tl(201) scintigraphy (92%) and any contractile reserve (80%); specificity was higher than for Tl(201) and DE (63%, 45%, and 54%, respectively; P<0.05). CONCLUSIONS: MCE with intravenous contrast identifies myocardial hibernation in humans. Prediction of viable Myocardium with MCE is best using quantification of myocardial blood flow and provides improved accuracy compared with DE and Tl(201) scintigraphy.

Nikolaos G Frangogiannis - One of the best experts on this subject based on the ideXlab platform.

  • development of murine ischemic cardiomyopathy is associated with a transient inflammatory reaction and depends on reactive oxygen species
    Proceedings of the National Academy of Sciences of the United States of America, 2003
    Co-Authors: Oliver Dewald, Nikolaos G Frangogiannis, Martin Zoerlein, Georg D Duerr, Christina Klemm, Pascal Knuefermann, George E Taffet, Lloyd H Michael, James D Crapo, A Welz
    Abstract:

    We examined the effects of daily repetitive brief (15 min) myocardial ischemia and reperfusion (I/R) in WT C57/BL6 and extracellular superoxide dismutase (EC-SOD)-overexpressing mice. In the absence of myocardial necrosis, I/R resulted in persistent fibrosis in ischemic areas of C57/BL6 mice associated with persistent global and segmental anterior wall dysfunction. The I/R protocol induced chemokines (peak 3 days) followed sequentially by infiltration of macrophages and myofibroblasts (5 days). Fibrosis peaked at 7 days and was stable at 28 days despite regression of the chemokine and cellular response. Discontinuation of I/R at 7 or 28 days led to regression of fibrosis and ventricular dysfunction. In contrast, the EC-SOD mice developed markedly less chemokine induction, cell response, and fibrosis, with no ventricular dysfunction. Reversible fibrosis and ventricular dysfunction are features of human Hibernating Myocardium. The reduction of the cellular and functional response in EC-SOD mice suggests a role for reactive O2 in the pathogenesis of ischemic cardiomyopathy.

  • identification of Hibernating Myocardium with quantitative intravenous myocardial contrast echocardiography comparison with dobutamine echocardiography and thallium 201 scintigraphy
    Circulation, 2003
    Co-Authors: Sarah Shimoni, Mario S Verani, Miguel A Quinones, Nikolaos G Frangogiannis, Constadina J Aggeli, Kesavan Shan, Rafael Espada, George V Letsou, Gerald M Lawrie, William L Winters
    Abstract:

    Background— There are currently no data on the accuracy of intravenous myocardial contrast echocardiography (MCE) in detecting myocardial hibernation in man and its comparative accuracy to dobutamine echocardiography (DE) or thallium 201 (Tl201) scintigraphy. Methods and Results— Twenty patients with coronary artery disease and ventricular dysfunction underwent MCE 1 to 5 days before bypass surgery and repeat echocardiography at 3 to 4 months. Patients also underwent DE (n=18) and rest-redistribution Tl201 tomography (n=16) before revascularization. MCE was performed using continuous Optison infusion (12 to 16 cc/h) with intermittent pulse inversion harmonics and incremental triggering (1:1 to 1:8). Myocardial contrast intensity (MCI) replenishment curves were constructed to derive quantitative MCE indices of blood velocity and flow. Recovery of function occurred in 38% of dysfunctional segments. MCE parameters of perfusion in Hibernating Myocardium were similar to segments with normal function and higher...

  • identification of Hibernating Myocardium with quantitative intravenous myocardial contrast echocardiography comparison with dobutamine echocardiography and thallium 201 scintigraphy
    Circulation, 2003
    Co-Authors: Sarah Shimoni, Mario S Verani, Miguel A Quinones, Nikolaos G Frangogiannis, Constadina J Aggeli, Kesavan Shan, Rafael Espada, George V Letsou, Gerald M Lawrie, William L Winters
    Abstract:

    BACKGROUND: There are currently no data on the accuracy of intravenous myocardial contrast echocardiography (MCE) in detecting myocardial hibernation in man and its comparative accuracy to dobutamine echocardiography (DE) or thallium 201 (Tl(201)) scintigraphy. METHODS AND RESULTS: Twenty patients with coronary artery disease and ventricular dysfunction underwent MCE 1 to 5 days before bypass surgery and repeat echocardiography at 3 to 4 months. Patients also underwent DE (n=18) and rest-redistribution Tl(201) tomography (n=16) before revascularization. MCE was performed using continuous Optison infusion (12 to 16 cc/h) with intermittent pulse inversion harmonics and incremental triggering (1:1 to 1:8). Myocardial contrast intensity (MCI) replenishment curves were constructed to derive quantitative MCE indices of blood velocity and flow. Recovery of function occurred in 38% of dysfunctional segments. MCE parameters of perfusion in Hibernating Myocardium were similar to segments with normal function and higher than dysfunctional Myocardium without recovery of function (P or =60% (P 1.5 dB/s for recovery of function was 90% and was similar to Tl(201) scintigraphy (92%) and any contractile reserve (80%); specificity was higher than for Tl(201) and DE (63%, 45%, and 54%, respectively; P<0.05). CONCLUSIONS: MCE with intravenous contrast identifies myocardial hibernation in humans. Prediction of viable Myocardium with MCE is best using quantification of myocardial blood flow and provides improved accuracy compared with DE and Tl(201) scintigraphy.