An experimental model of chronic myocardial hibernation

James D. St. Louis, G. Chad Hughes, Alan P. Kypson, Timothy R DeGrado, Carolyn L. Donovan, R. Edward Coleman, Bangliang Yin, Charles Steenbergen, Kevin P. Landolfo, James E. Lowe

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Background. Hibernating myocardium describes persistently impaired ventricular function at rest caused by reduced coronary blood flow. However, a realistic animal model reproducing this chronic ischemic state does not exist. The purpose of this study was to explore whether chronic low-flow hibernation could be produced in swine. Methods. Miniswine underwent 90% stenosis of the left circumflex coronary artery. Positron emission tomography and dobutamine stress echocardiography were performed 3 and 30 days (n = 6) or 14 days (n = 4) after occlusion to evaluate myocardial blood flow and viability. Triphenyl tetrazolium chloride assessed percent infarction. Electron microscopy was used to identify cellular changes characteristic of hibernating myocardium. Results. Positron emission tomography (13N-labeled- ammonia) 3 days after occlusion demonstrated a significant reduction in myocardial blood flow in the left circumflex distribution. This reduced flow was accompanied by increased glucose use (18F-fluorodeoxyglucose), which is consistent with hibernating myocardium. Thirty days after occlusion, positron emission tomography demonstrated persistent low flow with increased glucose use in the left circumflex distribution. Dobutamine stress echocardiography 3 days after occlusion demonstrated severe hypocontractility at rest in the left circumflex region. Regional wall motion improved with low-dose dobutamine followed by deterioration at higher doses (biphasic response), findings consistent with hibernating myocardium. The results of dobutamine stress echocardiography were unchanged 30 days after occlusion. Triphenyl tetrazolium chloride staining (n = 6) revealed a mean of 8% ± 2% infarction of the area-at-risk localized to the endocardial surface. Electron microscopy (n = 4) 14 days after occlusion demonstrated loss of contractile elements and large areas of glycogen accumulation within viable cardiomyocytes, also characteristic of hibernating myocardium. Conclusions. Chronic low-flow myocardial hibernation can be reproduced in an animal model after partial coronary occlusion. This model may prove useful in the study of the mechanisms underlying hibernating myocardium and the use of therapies designed to improve blood flow to the heart. (C) 2000 by The Society of Thoracic Surgeons.

Original languageEnglish (US)
Pages (from-to)1351-1357
Number of pages7
JournalAnnals of Thoracic Surgery
Volume69
Issue number5
DOIs
StatePublished - May 2000
Externally publishedYes

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Myocardial Stunning
Myocardium
Theoretical Models
Stress Echocardiography
Positron-Emission Tomography
Infarction
Chlorides
Electron Microscopy
Animal Models
Glucose
Hibernation
Dobutamine
Ventricular Function
Coronary Occlusion
Fluorodeoxyglucose F18
Glycogen
Ammonia
Cardiac Myocytes
Coronary Vessels
Pathologic Constriction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

St. Louis, J. D., Chad Hughes, G., Kypson, A. P., DeGrado, T. R., Donovan, C. L., Edward Coleman, R., ... Lowe, J. E. (2000). An experimental model of chronic myocardial hibernation. Annals of Thoracic Surgery, 69(5), 1351-1357. https://doi.org/10.1016/S0003-4975(00)01130-9

An experimental model of chronic myocardial hibernation. / St. Louis, James D.; Chad Hughes, G.; Kypson, Alan P.; DeGrado, Timothy R; Donovan, Carolyn L.; Edward Coleman, R.; Yin, Bangliang; Steenbergen, Charles; Landolfo, Kevin P.; Lowe, James E.

In: Annals of Thoracic Surgery, Vol. 69, No. 5, 05.2000, p. 1351-1357.

Research output: Contribution to journalArticle

St. Louis, JD, Chad Hughes, G, Kypson, AP, DeGrado, TR, Donovan, CL, Edward Coleman, R, Yin, B, Steenbergen, C, Landolfo, KP & Lowe, JE 2000, 'An experimental model of chronic myocardial hibernation', Annals of Thoracic Surgery, vol. 69, no. 5, pp. 1351-1357. https://doi.org/10.1016/S0003-4975(00)01130-9
St. Louis JD, Chad Hughes G, Kypson AP, DeGrado TR, Donovan CL, Edward Coleman R et al. An experimental model of chronic myocardial hibernation. Annals of Thoracic Surgery. 2000 May;69(5):1351-1357. https://doi.org/10.1016/S0003-4975(00)01130-9
St. Louis, James D. ; Chad Hughes, G. ; Kypson, Alan P. ; DeGrado, Timothy R ; Donovan, Carolyn L. ; Edward Coleman, R. ; Yin, Bangliang ; Steenbergen, Charles ; Landolfo, Kevin P. ; Lowe, James E. / An experimental model of chronic myocardial hibernation. In: Annals of Thoracic Surgery. 2000 ; Vol. 69, No. 5. pp. 1351-1357.
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abstract = "Background. Hibernating myocardium describes persistently impaired ventricular function at rest caused by reduced coronary blood flow. However, a realistic animal model reproducing this chronic ischemic state does not exist. The purpose of this study was to explore whether chronic low-flow hibernation could be produced in swine. Methods. Miniswine underwent 90{\%} stenosis of the left circumflex coronary artery. Positron emission tomography and dobutamine stress echocardiography were performed 3 and 30 days (n = 6) or 14 days (n = 4) after occlusion to evaluate myocardial blood flow and viability. Triphenyl tetrazolium chloride assessed percent infarction. Electron microscopy was used to identify cellular changes characteristic of hibernating myocardium. Results. Positron emission tomography (13N-labeled- ammonia) 3 days after occlusion demonstrated a significant reduction in myocardial blood flow in the left circumflex distribution. This reduced flow was accompanied by increased glucose use (18F-fluorodeoxyglucose), which is consistent with hibernating myocardium. Thirty days after occlusion, positron emission tomography demonstrated persistent low flow with increased glucose use in the left circumflex distribution. Dobutamine stress echocardiography 3 days after occlusion demonstrated severe hypocontractility at rest in the left circumflex region. Regional wall motion improved with low-dose dobutamine followed by deterioration at higher doses (biphasic response), findings consistent with hibernating myocardium. The results of dobutamine stress echocardiography were unchanged 30 days after occlusion. Triphenyl tetrazolium chloride staining (n = 6) revealed a mean of 8{\%} ± 2{\%} infarction of the area-at-risk localized to the endocardial surface. Electron microscopy (n = 4) 14 days after occlusion demonstrated loss of contractile elements and large areas of glycogen accumulation within viable cardiomyocytes, also characteristic of hibernating myocardium. Conclusions. Chronic low-flow myocardial hibernation can be reproduced in an animal model after partial coronary occlusion. This model may prove useful in the study of the mechanisms underlying hibernating myocardium and the use of therapies designed to improve blood flow to the heart. (C) 2000 by The Society of Thoracic Surgeons.",
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T1 - An experimental model of chronic myocardial hibernation

AU - St. Louis, James D.

AU - Chad Hughes, G.

AU - Kypson, Alan P.

AU - DeGrado, Timothy R

AU - Donovan, Carolyn L.

AU - Edward Coleman, R.

AU - Yin, Bangliang

AU - Steenbergen, Charles

AU - Landolfo, Kevin P.

AU - Lowe, James E.

PY - 2000/5

Y1 - 2000/5

N2 - Background. Hibernating myocardium describes persistently impaired ventricular function at rest caused by reduced coronary blood flow. However, a realistic animal model reproducing this chronic ischemic state does not exist. The purpose of this study was to explore whether chronic low-flow hibernation could be produced in swine. Methods. Miniswine underwent 90% stenosis of the left circumflex coronary artery. Positron emission tomography and dobutamine stress echocardiography were performed 3 and 30 days (n = 6) or 14 days (n = 4) after occlusion to evaluate myocardial blood flow and viability. Triphenyl tetrazolium chloride assessed percent infarction. Electron microscopy was used to identify cellular changes characteristic of hibernating myocardium. Results. Positron emission tomography (13N-labeled- ammonia) 3 days after occlusion demonstrated a significant reduction in myocardial blood flow in the left circumflex distribution. This reduced flow was accompanied by increased glucose use (18F-fluorodeoxyglucose), which is consistent with hibernating myocardium. Thirty days after occlusion, positron emission tomography demonstrated persistent low flow with increased glucose use in the left circumflex distribution. Dobutamine stress echocardiography 3 days after occlusion demonstrated severe hypocontractility at rest in the left circumflex region. Regional wall motion improved with low-dose dobutamine followed by deterioration at higher doses (biphasic response), findings consistent with hibernating myocardium. The results of dobutamine stress echocardiography were unchanged 30 days after occlusion. Triphenyl tetrazolium chloride staining (n = 6) revealed a mean of 8% ± 2% infarction of the area-at-risk localized to the endocardial surface. Electron microscopy (n = 4) 14 days after occlusion demonstrated loss of contractile elements and large areas of glycogen accumulation within viable cardiomyocytes, also characteristic of hibernating myocardium. Conclusions. Chronic low-flow myocardial hibernation can be reproduced in an animal model after partial coronary occlusion. This model may prove useful in the study of the mechanisms underlying hibernating myocardium and the use of therapies designed to improve blood flow to the heart. (C) 2000 by The Society of Thoracic Surgeons.

AB - Background. Hibernating myocardium describes persistently impaired ventricular function at rest caused by reduced coronary blood flow. However, a realistic animal model reproducing this chronic ischemic state does not exist. The purpose of this study was to explore whether chronic low-flow hibernation could be produced in swine. Methods. Miniswine underwent 90% stenosis of the left circumflex coronary artery. Positron emission tomography and dobutamine stress echocardiography were performed 3 and 30 days (n = 6) or 14 days (n = 4) after occlusion to evaluate myocardial blood flow and viability. Triphenyl tetrazolium chloride assessed percent infarction. Electron microscopy was used to identify cellular changes characteristic of hibernating myocardium. Results. Positron emission tomography (13N-labeled- ammonia) 3 days after occlusion demonstrated a significant reduction in myocardial blood flow in the left circumflex distribution. This reduced flow was accompanied by increased glucose use (18F-fluorodeoxyglucose), which is consistent with hibernating myocardium. Thirty days after occlusion, positron emission tomography demonstrated persistent low flow with increased glucose use in the left circumflex distribution. Dobutamine stress echocardiography 3 days after occlusion demonstrated severe hypocontractility at rest in the left circumflex region. Regional wall motion improved with low-dose dobutamine followed by deterioration at higher doses (biphasic response), findings consistent with hibernating myocardium. The results of dobutamine stress echocardiography were unchanged 30 days after occlusion. Triphenyl tetrazolium chloride staining (n = 6) revealed a mean of 8% ± 2% infarction of the area-at-risk localized to the endocardial surface. Electron microscopy (n = 4) 14 days after occlusion demonstrated loss of contractile elements and large areas of glycogen accumulation within viable cardiomyocytes, also characteristic of hibernating myocardium. Conclusions. Chronic low-flow myocardial hibernation can be reproduced in an animal model after partial coronary occlusion. This model may prove useful in the study of the mechanisms underlying hibernating myocardium and the use of therapies designed to improve blood flow to the heart. (C) 2000 by The Society of Thoracic Surgeons.

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