Denervation supersensitivity of refractoriness in noninfarcted areas apical to transmural myocardial infarction

J. J. Kammerling, F. J. Green, A. M. Watanabe, H. Inoue, M. J. Barber, D. P. Henry, D. P. Zipes

Research output: Contribution to journalArticle

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Abstract

Denervation supersensitivity was demonstrated in anesthetized dogs 5 to 10 days after transmural myocardial infarction produced by latex embolization of a diagnoal branch of the left anterior descending coronary artery. Sympathetic efferent denervation in noninfarcted myocardium apical to the infarction was demonstrated by a 90% depletion of myocardial norepinephrine content in the apical (45 ± 15 pg norepinephrine/g tissue) vs basal (437 ± 76 pg/g tissue) regions and by the lack of effective refractory period (ERP) shortening during bilateral ansae subclaviae stimulation in 34% of sites apical to the infarction. Supersensitivity in the area apical to the infarction was manifested by an exaggerated shortening of the ERP during both norepinephrine and isoproterenol infusions, with an upward and leftward shift in the dose-response curves in the apical vs basal regions (p <.001). The cellular mechanism for denervation supersensitivity did not involve detectable changes in the β-adrenergic receptor adenylate cyclase system. There was no difference in the density of β-adrenergic receptors ([125I]-cyanopindolol) in the apical (268.6 ± 22.7 fmol/mg protein) vs the basal (253.5 ± 24.8 fmol/mg protein) regions. Adenylate cyclase activity stimulated by guanosine triphosphate plus isoproterenol was slightly greater in the apical (58.7 ± 17.4%) than in the basal (49.6 ± 10.9%) region, but this difference did not reach statistical significance (p = .068). Muscarinic modulation of β-receptor coupling (oxotremorine attenuation of guanosine triphosphate plus isoproterenol-stimulated adenylate cyclase activity) also was not significantly different at the apical (31.6 ± 17.5% inhibition) and basal (21.4 ± 20.9% inhibition) sites. These data show that a transmural myocardial infarction produces denervation supersensitivity in areas apical to the infarction, but in this preparation no differences in the total number or a redistribution of β-adrenergic receptors or adenylate cyclase activity were detected.

Original languageEnglish (US)
Pages (from-to)383-393
Number of pages11
JournalCirculation
Volume76
Issue number2
StatePublished - 1987
Externally publishedYes

Fingerprint

Denervation
Adenylyl Cyclases
Infarction
Myocardial Infarction
Isoproterenol
Adrenergic Receptors
Norepinephrine
Guanosine Triphosphate
Oxotremorine
Sympathectomy
Latex
Muscarinic Receptors
Coronary Vessels
Myocardium
Proteins
Dogs

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Kammerling, J. J., Green, F. J., Watanabe, A. M., Inoue, H., Barber, M. J., Henry, D. P., & Zipes, D. P. (1987). Denervation supersensitivity of refractoriness in noninfarcted areas apical to transmural myocardial infarction. Circulation, 76(2), 383-393.

Denervation supersensitivity of refractoriness in noninfarcted areas apical to transmural myocardial infarction. / Kammerling, J. J.; Green, F. J.; Watanabe, A. M.; Inoue, H.; Barber, M. J.; Henry, D. P.; Zipes, D. P.

In: Circulation, Vol. 76, No. 2, 1987, p. 383-393.

Research output: Contribution to journalArticle

Kammerling, JJ, Green, FJ, Watanabe, AM, Inoue, H, Barber, MJ, Henry, DP & Zipes, DP 1987, 'Denervation supersensitivity of refractoriness in noninfarcted areas apical to transmural myocardial infarction', Circulation, vol. 76, no. 2, pp. 383-393.
Kammerling JJ, Green FJ, Watanabe AM, Inoue H, Barber MJ, Henry DP et al. Denervation supersensitivity of refractoriness in noninfarcted areas apical to transmural myocardial infarction. Circulation. 1987;76(2):383-393.
Kammerling, J. J. ; Green, F. J. ; Watanabe, A. M. ; Inoue, H. ; Barber, M. J. ; Henry, D. P. ; Zipes, D. P. / Denervation supersensitivity of refractoriness in noninfarcted areas apical to transmural myocardial infarction. In: Circulation. 1987 ; Vol. 76, No. 2. pp. 383-393.
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abstract = "Denervation supersensitivity was demonstrated in anesthetized dogs 5 to 10 days after transmural myocardial infarction produced by latex embolization of a diagnoal branch of the left anterior descending coronary artery. Sympathetic efferent denervation in noninfarcted myocardium apical to the infarction was demonstrated by a 90{\%} depletion of myocardial norepinephrine content in the apical (45 ± 15 pg norepinephrine/g tissue) vs basal (437 ± 76 pg/g tissue) regions and by the lack of effective refractory period (ERP) shortening during bilateral ansae subclaviae stimulation in 34{\%} of sites apical to the infarction. Supersensitivity in the area apical to the infarction was manifested by an exaggerated shortening of the ERP during both norepinephrine and isoproterenol infusions, with an upward and leftward shift in the dose-response curves in the apical vs basal regions (p <.001). The cellular mechanism for denervation supersensitivity did not involve detectable changes in the β-adrenergic receptor adenylate cyclase system. There was no difference in the density of β-adrenergic receptors ([125I]-cyanopindolol) in the apical (268.6 ± 22.7 fmol/mg protein) vs the basal (253.5 ± 24.8 fmol/mg protein) regions. Adenylate cyclase activity stimulated by guanosine triphosphate plus isoproterenol was slightly greater in the apical (58.7 ± 17.4{\%}) than in the basal (49.6 ± 10.9{\%}) region, but this difference did not reach statistical significance (p = .068). Muscarinic modulation of β-receptor coupling (oxotremorine attenuation of guanosine triphosphate plus isoproterenol-stimulated adenylate cyclase activity) also was not significantly different at the apical (31.6 ± 17.5{\%} inhibition) and basal (21.4 ± 20.9{\%} inhibition) sites. These data show that a transmural myocardial infarction produces denervation supersensitivity in areas apical to the infarction, but in this preparation no differences in the total number or a redistribution of β-adrenergic receptors or adenylate cyclase activity were detected.",
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AU - Green, F. J.

AU - Watanabe, A. M.

AU - Inoue, H.

AU - Barber, M. J.

AU - Henry, D. P.

AU - Zipes, D. P.

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N2 - Denervation supersensitivity was demonstrated in anesthetized dogs 5 to 10 days after transmural myocardial infarction produced by latex embolization of a diagnoal branch of the left anterior descending coronary artery. Sympathetic efferent denervation in noninfarcted myocardium apical to the infarction was demonstrated by a 90% depletion of myocardial norepinephrine content in the apical (45 ± 15 pg norepinephrine/g tissue) vs basal (437 ± 76 pg/g tissue) regions and by the lack of effective refractory period (ERP) shortening during bilateral ansae subclaviae stimulation in 34% of sites apical to the infarction. Supersensitivity in the area apical to the infarction was manifested by an exaggerated shortening of the ERP during both norepinephrine and isoproterenol infusions, with an upward and leftward shift in the dose-response curves in the apical vs basal regions (p <.001). The cellular mechanism for denervation supersensitivity did not involve detectable changes in the β-adrenergic receptor adenylate cyclase system. There was no difference in the density of β-adrenergic receptors ([125I]-cyanopindolol) in the apical (268.6 ± 22.7 fmol/mg protein) vs the basal (253.5 ± 24.8 fmol/mg protein) regions. Adenylate cyclase activity stimulated by guanosine triphosphate plus isoproterenol was slightly greater in the apical (58.7 ± 17.4%) than in the basal (49.6 ± 10.9%) region, but this difference did not reach statistical significance (p = .068). Muscarinic modulation of β-receptor coupling (oxotremorine attenuation of guanosine triphosphate plus isoproterenol-stimulated adenylate cyclase activity) also was not significantly different at the apical (31.6 ± 17.5% inhibition) and basal (21.4 ± 20.9% inhibition) sites. These data show that a transmural myocardial infarction produces denervation supersensitivity in areas apical to the infarction, but in this preparation no differences in the total number or a redistribution of β-adrenergic receptors or adenylate cyclase activity were detected.

AB - Denervation supersensitivity was demonstrated in anesthetized dogs 5 to 10 days after transmural myocardial infarction produced by latex embolization of a diagnoal branch of the left anterior descending coronary artery. Sympathetic efferent denervation in noninfarcted myocardium apical to the infarction was demonstrated by a 90% depletion of myocardial norepinephrine content in the apical (45 ± 15 pg norepinephrine/g tissue) vs basal (437 ± 76 pg/g tissue) regions and by the lack of effective refractory period (ERP) shortening during bilateral ansae subclaviae stimulation in 34% of sites apical to the infarction. Supersensitivity in the area apical to the infarction was manifested by an exaggerated shortening of the ERP during both norepinephrine and isoproterenol infusions, with an upward and leftward shift in the dose-response curves in the apical vs basal regions (p <.001). The cellular mechanism for denervation supersensitivity did not involve detectable changes in the β-adrenergic receptor adenylate cyclase system. There was no difference in the density of β-adrenergic receptors ([125I]-cyanopindolol) in the apical (268.6 ± 22.7 fmol/mg protein) vs the basal (253.5 ± 24.8 fmol/mg protein) regions. Adenylate cyclase activity stimulated by guanosine triphosphate plus isoproterenol was slightly greater in the apical (58.7 ± 17.4%) than in the basal (49.6 ± 10.9%) region, but this difference did not reach statistical significance (p = .068). Muscarinic modulation of β-receptor coupling (oxotremorine attenuation of guanosine triphosphate plus isoproterenol-stimulated adenylate cyclase activity) also was not significantly different at the apical (31.6 ± 17.5% inhibition) and basal (21.4 ± 20.9% inhibition) sites. These data show that a transmural myocardial infarction produces denervation supersensitivity in areas apical to the infarction, but in this preparation no differences in the total number or a redistribution of β-adrenergic receptors or adenylate cyclase activity were detected.

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