Increased Stiffness Is the Major Early Abnormality in a Pig Model of Severe Aortic Stenosis and Predisposes to Congestive Heart Failure in the Absence of Systolic Dysfunction
Background It remains unclear whether abnormal systolic function and relaxation are essential for developing heart failure in pathophysiology of severe aortic stenosis. Methods and Results Yorkshire pigs underwent surgical banding of the ascending aorta. The animals were followed for up to 5 months...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2015-05-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://doi.org/10.1161/JAHA.115.001925 |
| _version_ | 1828388444413362176 |
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| author | Kiyotake Ishikawa Jaume Aguero Jae Gyun Oh Nadjib Hammoudi Lauren A. Fish Lauren Leonardson Belén Picatoste Carlos G. Santos‐Gallego Kenneth M. Fish Roger J. Hajjar |
| author_facet | Kiyotake Ishikawa Jaume Aguero Jae Gyun Oh Nadjib Hammoudi Lauren A. Fish Lauren Leonardson Belén Picatoste Carlos G. Santos‐Gallego Kenneth M. Fish Roger J. Hajjar |
| author_sort | Kiyotake Ishikawa |
| collection | DOAJ |
| description | Background It remains unclear whether abnormal systolic function and relaxation are essential for developing heart failure in pathophysiology of severe aortic stenosis. Methods and Results Yorkshire pigs underwent surgical banding of the ascending aorta. The animals were followed for up to 5 months after surgery, and cardiac function was assessed comprehensively by invasive pressure–volume measurements, 3‐dimensional echocardiography, echocardiographic speckle‐tracking strain, and postmortem molecular and histological analyses. Pigs with aortic banding (n=6) exhibited significant left ventricular hypertrophy with increased stiffness compared with the control pigs (n=7) (end‐diastolic pressure–volume relationship β: 0.053±0.017 versus 0.028±0.009 mm Hg/mL, P=0.007); however, all other parameters corresponding to systolic function, including ejection fraction, end‐systolic pressure–volume relationship, preload recruitable stroke work, echocardiographic circumferential strain, and longitudinal strain, were not impaired in pigs with aortic banding. Relaxation parameters were also similar between groups. Sarcoplasmic reticulum calcium (Ca2+) ATPase protein levels in the left ventricle were similar. There were significant increases in 3‐dimensional echocardiographic left atrial volumes, suggesting the usefulness of these indexes to detect increased stiffness. Right atrial pacing with a heart rate of 120 beats per minute induced increased end‐diastolic pressure in pigs with aortic banding in contrast to decreased end‐diastolic pressure in the control pigs. Histological evaluation revealed that increased stiffness was accompanied by cardiomyocyte hypertrophy and increased perimysial and perivascular fibrosis. Conclusion Increased stiffness is the major early pathological process that predisposes to congestive heart failure without abnormalities in systolic function and relaxation in a clinically relevant animal model of aortic stenosis. |
| first_indexed | 2024-12-10T06:13:19Z |
| format | Article |
| id | doaj.art-2ef996fdb3d04ea6b3c9a60bf212ae01 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-12-10T06:13:19Z |
| publishDate | 2015-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-2ef996fdb3d04ea6b3c9a60bf212ae012022-12-22T01:59:30ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802015-05-0145n/an/a10.1161/JAHA.115.001925Increased Stiffness Is the Major Early Abnormality in a Pig Model of Severe Aortic Stenosis and Predisposes to Congestive Heart Failure in the Absence of Systolic DysfunctionKiyotake Ishikawa0Jaume Aguero1Jae Gyun Oh2Nadjib Hammoudi3Lauren A. Fish4Lauren Leonardson5Belén Picatoste6Carlos G. Santos‐Gallego7Kenneth M. Fish8Roger J. Hajjar9Cardiovascular Research Center Icahn School of Medicine at Mount Sinai New York NYCardiovascular Research Center Icahn School of Medicine at Mount Sinai New York NYCardiovascular Research Center Icahn School of Medicine at Mount Sinai New York NYCardiovascular Research Center Icahn School of Medicine at Mount Sinai New York NYCardiovascular Research Center Icahn School of Medicine at Mount Sinai New York NYCardiovascular Research Center Icahn School of Medicine at Mount Sinai New York NYCardiovascular Research Center Icahn School of Medicine at Mount Sinai New York NYCardiovascular Research Center Icahn School of Medicine at Mount Sinai New York NYCardiovascular Research Center Icahn School of Medicine at Mount Sinai New York NYCardiovascular Research Center Icahn School of Medicine at Mount Sinai New York NYBackground It remains unclear whether abnormal systolic function and relaxation are essential for developing heart failure in pathophysiology of severe aortic stenosis. Methods and Results Yorkshire pigs underwent surgical banding of the ascending aorta. The animals were followed for up to 5 months after surgery, and cardiac function was assessed comprehensively by invasive pressure–volume measurements, 3‐dimensional echocardiography, echocardiographic speckle‐tracking strain, and postmortem molecular and histological analyses. Pigs with aortic banding (n=6) exhibited significant left ventricular hypertrophy with increased stiffness compared with the control pigs (n=7) (end‐diastolic pressure–volume relationship β: 0.053±0.017 versus 0.028±0.009 mm Hg/mL, P=0.007); however, all other parameters corresponding to systolic function, including ejection fraction, end‐systolic pressure–volume relationship, preload recruitable stroke work, echocardiographic circumferential strain, and longitudinal strain, were not impaired in pigs with aortic banding. Relaxation parameters were also similar between groups. Sarcoplasmic reticulum calcium (Ca2+) ATPase protein levels in the left ventricle were similar. There were significant increases in 3‐dimensional echocardiographic left atrial volumes, suggesting the usefulness of these indexes to detect increased stiffness. Right atrial pacing with a heart rate of 120 beats per minute induced increased end‐diastolic pressure in pigs with aortic banding in contrast to decreased end‐diastolic pressure in the control pigs. Histological evaluation revealed that increased stiffness was accompanied by cardiomyocyte hypertrophy and increased perimysial and perivascular fibrosis. Conclusion Increased stiffness is the major early pathological process that predisposes to congestive heart failure without abnormalities in systolic function and relaxation in a clinically relevant animal model of aortic stenosis.https://doi.org/10.1161/JAHA.115.001925diastolic dysfunctionfibrosishypertrophystiffnesssystolic dysfunction |
| spellingShingle | Kiyotake Ishikawa Jaume Aguero Jae Gyun Oh Nadjib Hammoudi Lauren A. Fish Lauren Leonardson Belén Picatoste Carlos G. Santos‐Gallego Kenneth M. Fish Roger J. Hajjar Increased Stiffness Is the Major Early Abnormality in a Pig Model of Severe Aortic Stenosis and Predisposes to Congestive Heart Failure in the Absence of Systolic Dysfunction Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease diastolic dysfunction fibrosis hypertrophy stiffness systolic dysfunction |
| title | Increased Stiffness Is the Major Early Abnormality in a Pig Model of Severe Aortic Stenosis and Predisposes to Congestive Heart Failure in the Absence of Systolic Dysfunction |
| title_full | Increased Stiffness Is the Major Early Abnormality in a Pig Model of Severe Aortic Stenosis and Predisposes to Congestive Heart Failure in the Absence of Systolic Dysfunction |
| title_fullStr | Increased Stiffness Is the Major Early Abnormality in a Pig Model of Severe Aortic Stenosis and Predisposes to Congestive Heart Failure in the Absence of Systolic Dysfunction |
| title_full_unstemmed | Increased Stiffness Is the Major Early Abnormality in a Pig Model of Severe Aortic Stenosis and Predisposes to Congestive Heart Failure in the Absence of Systolic Dysfunction |
| title_short | Increased Stiffness Is the Major Early Abnormality in a Pig Model of Severe Aortic Stenosis and Predisposes to Congestive Heart Failure in the Absence of Systolic Dysfunction |
| title_sort | increased stiffness is the major early abnormality in a pig model of severe aortic stenosis and predisposes to congestive heart failure in the absence of systolic dysfunction |
| topic | diastolic dysfunction fibrosis hypertrophy stiffness systolic dysfunction |
| url | https://doi.org/10.1161/JAHA.115.001925 |
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