Functional and structural alterations with 24-hour myocardial hibernation and recovery after reperfusion: A pig model of myocardial hibernation

C. Chen, L. Chen, J. T. Fallon, L. Ma, L. Li, L. Bow, D. Knibbs, R. McKay, Linda Gillam, D. D. Waters

Research output: Contribution to journalArticle

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Abstract

Background: Short-term myocardial hibernation of 3 hours resulting from a moderate resting coronary flow reduction has been reproduced in pigs. This study was designed to determine whether any structural changes accompany short-term hibernation caused by a moderate flow reduction maintained for 24 hours and whether any such structural alterations are reversible after reperfusion. Methods and Results: A severe left anterior descending coronary artery (LAD) stenosis was created with a reduction of resting flow to ≃60% of baseline and maintained for 24 hours. Regional coronary flow was measured by a flowmeter; wall thickening was determined by echocardiography, and local metabolic changes were measured. Of 17 pigs, 11 completed the study protocol of 24 hours. The LAD flow was reduced from 0.91±0.11 to 0.52±0.13 mL · min-1 · g-1, a 43% mean decrease, at 15 minutes after the LAD stenosis and was maintained at 0.56±0.11 mL · min-1 · g-1 at 24 hours. The reduction of regional coronary flow initially produced acute myocardial ischemia, as evidenced by reduced regional wall thickening (from 37.2±6.9% at baseline to 11.5±6.8%), regional lactate production (-0.34±0.28 μmol · g-1 · min-1), and a decrease in regional coronary venous pH (from 7.41±0.035 at baseline to 7.30±0.030). At 24 hours, the reductions in coronary flow and wall thickening were maintained relatively constant and the rate-pressure product was relatively unchanged, but lactate production ceased and regional H+ concentration normalized, with a tendency toward a further reduction in regional oxygen consumption, from 3.10±0.90 mL · min-1 · 100 g-1 at 15 minutes after stenosis to 2.52±0.95 mL · min-1 · 100 g- 1 at 24 hours (P=.06), indicating metabolic adaptation of the hypoperfused regions. Of 11 pigs, 6 were free of myocardial infarction; 3 had patchy necrosis involving 4%, 5%, and 6% of the area at risk; and 2 other pigs had a few scattered myocytes with necrosis, detected only by light and electron microscopy. Ultrastructural changes consisted of a partial loss of myofibrils and an increase in mitochondria and glycogen deposition. Regional wall thickening recovered 1 week after reperfusion in most pigs, and the ultrastructural changes reverted to normal. Conclusions: In this pig model, moderately ischemic myocardium undergoes metabolic and structural adaptations but preserves the capacity to recover both functionally and ultrastructurally after reperfusion.

Original languageEnglish (US)
Pages (from-to)507-516
Number of pages10
JournalCirculation
Volume94
Issue number3
DOIs
StatePublished - Jan 1 1996
Externally publishedYes

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Myocardial Stunning
Reperfusion
Swine
Lactic Acid
Pathologic Constriction
Necrosis
Hibernation
Flowmeters
Myofibrils
Coronary Stenosis
Glycogen
Oxygen Consumption
Muscle Cells
Myocardial Ischemia
Echocardiography
Myocardium
Electron Microscopy
Mitochondria
Myocardial Infarction
Light

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Chen, C. ; Chen, L. ; Fallon, J. T. ; Ma, L. ; Li, L. ; Bow, L. ; Knibbs, D. ; McKay, R. ; Gillam, Linda ; Waters, D. D. / Functional and structural alterations with 24-hour myocardial hibernation and recovery after reperfusion : A pig model of myocardial hibernation. In: Circulation. 1996 ; Vol. 94, No. 3. pp. 507-516.
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title = "Functional and structural alterations with 24-hour myocardial hibernation and recovery after reperfusion: A pig model of myocardial hibernation",
abstract = "Background: Short-term myocardial hibernation of 3 hours resulting from a moderate resting coronary flow reduction has been reproduced in pigs. This study was designed to determine whether any structural changes accompany short-term hibernation caused by a moderate flow reduction maintained for 24 hours and whether any such structural alterations are reversible after reperfusion. Methods and Results: A severe left anterior descending coronary artery (LAD) stenosis was created with a reduction of resting flow to ≃60{\%} of baseline and maintained for 24 hours. Regional coronary flow was measured by a flowmeter; wall thickening was determined by echocardiography, and local metabolic changes were measured. Of 17 pigs, 11 completed the study protocol of 24 hours. The LAD flow was reduced from 0.91±0.11 to 0.52±0.13 mL · min-1 · g-1, a 43{\%} mean decrease, at 15 minutes after the LAD stenosis and was maintained at 0.56±0.11 mL · min-1 · g-1 at 24 hours. The reduction of regional coronary flow initially produced acute myocardial ischemia, as evidenced by reduced regional wall thickening (from 37.2±6.9{\%} at baseline to 11.5±6.8{\%}), regional lactate production (-0.34±0.28 μmol · g-1 · min-1), and a decrease in regional coronary venous pH (from 7.41±0.035 at baseline to 7.30±0.030). At 24 hours, the reductions in coronary flow and wall thickening were maintained relatively constant and the rate-pressure product was relatively unchanged, but lactate production ceased and regional H+ concentration normalized, with a tendency toward a further reduction in regional oxygen consumption, from 3.10±0.90 mL · min-1 · 100 g-1 at 15 minutes after stenosis to 2.52±0.95 mL · min-1 · 100 g- 1 at 24 hours (P=.06), indicating metabolic adaptation of the hypoperfused regions. Of 11 pigs, 6 were free of myocardial infarction; 3 had patchy necrosis involving 4{\%}, 5{\%}, and 6{\%} of the area at risk; and 2 other pigs had a few scattered myocytes with necrosis, detected only by light and electron microscopy. Ultrastructural changes consisted of a partial loss of myofibrils and an increase in mitochondria and glycogen deposition. Regional wall thickening recovered 1 week after reperfusion in most pigs, and the ultrastructural changes reverted to normal. Conclusions: In this pig model, moderately ischemic myocardium undergoes metabolic and structural adaptations but preserves the capacity to recover both functionally and ultrastructurally after reperfusion.",
author = "C. Chen and L. Chen and Fallon, {J. T.} and L. Ma and L. Li and L. Bow and D. Knibbs and R. McKay and Linda Gillam and Waters, {D. D.}",
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Functional and structural alterations with 24-hour myocardial hibernation and recovery after reperfusion : A pig model of myocardial hibernation. / Chen, C.; Chen, L.; Fallon, J. T.; Ma, L.; Li, L.; Bow, L.; Knibbs, D.; McKay, R.; Gillam, Linda; Waters, D. D.

In: Circulation, Vol. 94, No. 3, 01.01.1996, p. 507-516.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Functional and structural alterations with 24-hour myocardial hibernation and recovery after reperfusion

T2 - A pig model of myocardial hibernation

AU - Chen, C.

AU - Chen, L.

AU - Fallon, J. T.

AU - Ma, L.

AU - Li, L.

AU - Bow, L.

AU - Knibbs, D.

AU - McKay, R.

AU - Gillam, Linda

AU - Waters, D. D.

PY - 1996/1/1

Y1 - 1996/1/1

N2 - Background: Short-term myocardial hibernation of 3 hours resulting from a moderate resting coronary flow reduction has been reproduced in pigs. This study was designed to determine whether any structural changes accompany short-term hibernation caused by a moderate flow reduction maintained for 24 hours and whether any such structural alterations are reversible after reperfusion. Methods and Results: A severe left anterior descending coronary artery (LAD) stenosis was created with a reduction of resting flow to ≃60% of baseline and maintained for 24 hours. Regional coronary flow was measured by a flowmeter; wall thickening was determined by echocardiography, and local metabolic changes were measured. Of 17 pigs, 11 completed the study protocol of 24 hours. The LAD flow was reduced from 0.91±0.11 to 0.52±0.13 mL · min-1 · g-1, a 43% mean decrease, at 15 minutes after the LAD stenosis and was maintained at 0.56±0.11 mL · min-1 · g-1 at 24 hours. The reduction of regional coronary flow initially produced acute myocardial ischemia, as evidenced by reduced regional wall thickening (from 37.2±6.9% at baseline to 11.5±6.8%), regional lactate production (-0.34±0.28 μmol · g-1 · min-1), and a decrease in regional coronary venous pH (from 7.41±0.035 at baseline to 7.30±0.030). At 24 hours, the reductions in coronary flow and wall thickening were maintained relatively constant and the rate-pressure product was relatively unchanged, but lactate production ceased and regional H+ concentration normalized, with a tendency toward a further reduction in regional oxygen consumption, from 3.10±0.90 mL · min-1 · 100 g-1 at 15 minutes after stenosis to 2.52±0.95 mL · min-1 · 100 g- 1 at 24 hours (P=.06), indicating metabolic adaptation of the hypoperfused regions. Of 11 pigs, 6 were free of myocardial infarction; 3 had patchy necrosis involving 4%, 5%, and 6% of the area at risk; and 2 other pigs had a few scattered myocytes with necrosis, detected only by light and electron microscopy. Ultrastructural changes consisted of a partial loss of myofibrils and an increase in mitochondria and glycogen deposition. Regional wall thickening recovered 1 week after reperfusion in most pigs, and the ultrastructural changes reverted to normal. Conclusions: In this pig model, moderately ischemic myocardium undergoes metabolic and structural adaptations but preserves the capacity to recover both functionally and ultrastructurally after reperfusion.

AB - Background: Short-term myocardial hibernation of 3 hours resulting from a moderate resting coronary flow reduction has been reproduced in pigs. This study was designed to determine whether any structural changes accompany short-term hibernation caused by a moderate flow reduction maintained for 24 hours and whether any such structural alterations are reversible after reperfusion. Methods and Results: A severe left anterior descending coronary artery (LAD) stenosis was created with a reduction of resting flow to ≃60% of baseline and maintained for 24 hours. Regional coronary flow was measured by a flowmeter; wall thickening was determined by echocardiography, and local metabolic changes were measured. Of 17 pigs, 11 completed the study protocol of 24 hours. The LAD flow was reduced from 0.91±0.11 to 0.52±0.13 mL · min-1 · g-1, a 43% mean decrease, at 15 minutes after the LAD stenosis and was maintained at 0.56±0.11 mL · min-1 · g-1 at 24 hours. The reduction of regional coronary flow initially produced acute myocardial ischemia, as evidenced by reduced regional wall thickening (from 37.2±6.9% at baseline to 11.5±6.8%), regional lactate production (-0.34±0.28 μmol · g-1 · min-1), and a decrease in regional coronary venous pH (from 7.41±0.035 at baseline to 7.30±0.030). At 24 hours, the reductions in coronary flow and wall thickening were maintained relatively constant and the rate-pressure product was relatively unchanged, but lactate production ceased and regional H+ concentration normalized, with a tendency toward a further reduction in regional oxygen consumption, from 3.10±0.90 mL · min-1 · 100 g-1 at 15 minutes after stenosis to 2.52±0.95 mL · min-1 · 100 g- 1 at 24 hours (P=.06), indicating metabolic adaptation of the hypoperfused regions. Of 11 pigs, 6 were free of myocardial infarction; 3 had patchy necrosis involving 4%, 5%, and 6% of the area at risk; and 2 other pigs had a few scattered myocytes with necrosis, detected only by light and electron microscopy. Ultrastructural changes consisted of a partial loss of myofibrils and an increase in mitochondria and glycogen deposition. Regional wall thickening recovered 1 week after reperfusion in most pigs, and the ultrastructural changes reverted to normal. Conclusions: In this pig model, moderately ischemic myocardium undergoes metabolic and structural adaptations but preserves the capacity to recover both functionally and ultrastructurally after reperfusion.

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