Effect of EHDP on calcium accumulation and technetium-99m pyrophosphate uptake in experimental myocardial infarction

L. M. Buja, A. J. Tofe, R. W. Parkey, M. D. Francis, S. E. Lewis, P. V. Kulkarni, F. J. Bonte, J. T. Willerson

Research output: Contribution to journalArticle

Abstract

Ethane-l-hydroxy-1,1-diphosphonate (EHDP) inhibits bone mineral growth. This study was performed to test the hypohesis that EHDP would interfere with the process of calcium uptake and deposition in evolving myocardial infarction and thereby influence other parameters, including technetium-99m pyrophosphate (Tc-99m PYP) uptake and scintigraphic visualization of the infarcts. Permanent occlusion of the left anterior descending coronary artery (LAD) was produced in beagles. In seven dogs, serum EHDP was maintained at 10-15 μg/ml for 24 hours by continuous i.v. infusion, and seven control dogs were infused with saline. The Tc-99m PYP was injected 2 hours before sacrifice. EHDP-treated dogs showed a mild decrease (20%) in mean calcium content of infarcted myocardium (102.4±6.4 μg [±SEM] per gram wet weight [n=51] vs 126.7±9.5[n=49] [p<0.05]). These dogs showed a prominent decrease (37%) in mean Tc-99m PYP content of infarcted myocardium (18.2±1.4[% dose/gx10 -3] [n=46] vs 28.9±4.3 [n=46] [p<0.005]) and a marked decrease (65%) in infarct-to-normal ratio (6.1±0.9 [n=6] vs 15.9±3.7 [n=6] [p<0.05]). Positive relationships were demonstrated between myocardial Tc-99m PYP and calcium levels in the EHDP-treated dogs (r=0.69) and the control dogs (r=0.77). Infarct size and regional myocardial blood flow changes were similar in the EHDP-treated and control dogs. The average grade (0-4+) of the Tc-99m PYP myocardial scintigrams for infarcts greater than 3.5 g was 2.4±0.2 for control dogs and 1.1±0.4 for EHDP-treated dogs (p<0.05). Thus, EHDP infusion at the dose tested produced a mild decrease in calcium accumulation in canine infarcts; however, it produced a greater reduction in Tc-99m PYP uptake in the infarcts, probably by complexing with Tc-99m PYP binding sites and by dilution of Tc-99m PYP in circulating diphosphonate pool. These findings suggests that calcification inhibitors, and possibly other calcium-blocking agents, may alter the sensitivity of Tc-99m PYP myocardial scintigraphy, but the specific effects of each calcium antagonist must be evaluated.

Original languageEnglish (US)
Pages (from-to)1012-1017
Number of pages6
JournalCirculation
Volume64
Issue number5
StatePublished - 1981

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Ethane
Technetium
Diphosphonates
Myocardial Infarction
Dogs
Calcium
Myocardium
Calcium Pyrophosphate
diphosphoric acid
Myocardial Perfusion Imaging
Bone Development
Regional Blood Flow
Minerals
Canidae
Coronary Vessels
Binding Sites
Weights and Measures

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Buja, L. M., Tofe, A. J., Parkey, R. W., Francis, M. D., Lewis, S. E., Kulkarni, P. V., ... Willerson, J. T. (1981). Effect of EHDP on calcium accumulation and technetium-99m pyrophosphate uptake in experimental myocardial infarction. Circulation, 64(5), 1012-1017.

Effect of EHDP on calcium accumulation and technetium-99m pyrophosphate uptake in experimental myocardial infarction. / Buja, L. M.; Tofe, A. J.; Parkey, R. W.; Francis, M. D.; Lewis, S. E.; Kulkarni, P. V.; Bonte, F. J.; Willerson, J. T.

In: Circulation, Vol. 64, No. 5, 1981, p. 1012-1017.

Research output: Contribution to journalArticle

Buja, LM, Tofe, AJ, Parkey, RW, Francis, MD, Lewis, SE, Kulkarni, PV, Bonte, FJ & Willerson, JT 1981, 'Effect of EHDP on calcium accumulation and technetium-99m pyrophosphate uptake in experimental myocardial infarction', Circulation, vol. 64, no. 5, pp. 1012-1017.
Buja LM, Tofe AJ, Parkey RW, Francis MD, Lewis SE, Kulkarni PV et al. Effect of EHDP on calcium accumulation and technetium-99m pyrophosphate uptake in experimental myocardial infarction. Circulation. 1981;64(5):1012-1017.
Buja, L. M. ; Tofe, A. J. ; Parkey, R. W. ; Francis, M. D. ; Lewis, S. E. ; Kulkarni, P. V. ; Bonte, F. J. ; Willerson, J. T. / Effect of EHDP on calcium accumulation and technetium-99m pyrophosphate uptake in experimental myocardial infarction. In: Circulation. 1981 ; Vol. 64, No. 5. pp. 1012-1017.
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abstract = "Ethane-l-hydroxy-1,1-diphosphonate (EHDP) inhibits bone mineral growth. This study was performed to test the hypohesis that EHDP would interfere with the process of calcium uptake and deposition in evolving myocardial infarction and thereby influence other parameters, including technetium-99m pyrophosphate (Tc-99m PYP) uptake and scintigraphic visualization of the infarcts. Permanent occlusion of the left anterior descending coronary artery (LAD) was produced in beagles. In seven dogs, serum EHDP was maintained at 10-15 μg/ml for 24 hours by continuous i.v. infusion, and seven control dogs were infused with saline. The Tc-99m PYP was injected 2 hours before sacrifice. EHDP-treated dogs showed a mild decrease (20{\%}) in mean calcium content of infarcted myocardium (102.4±6.4 μg [±SEM] per gram wet weight [n=51] vs 126.7±9.5[n=49] [p<0.05]). These dogs showed a prominent decrease (37{\%}) in mean Tc-99m PYP content of infarcted myocardium (18.2±1.4[{\%} dose/gx10 -3] [n=46] vs 28.9±4.3 [n=46] [p<0.005]) and a marked decrease (65{\%}) in infarct-to-normal ratio (6.1±0.9 [n=6] vs 15.9±3.7 [n=6] [p<0.05]). Positive relationships were demonstrated between myocardial Tc-99m PYP and calcium levels in the EHDP-treated dogs (r=0.69) and the control dogs (r=0.77). Infarct size and regional myocardial blood flow changes were similar in the EHDP-treated and control dogs. The average grade (0-4+) of the Tc-99m PYP myocardial scintigrams for infarcts greater than 3.5 g was 2.4±0.2 for control dogs and 1.1±0.4 for EHDP-treated dogs (p<0.05). Thus, EHDP infusion at the dose tested produced a mild decrease in calcium accumulation in canine infarcts; however, it produced a greater reduction in Tc-99m PYP uptake in the infarcts, probably by complexing with Tc-99m PYP binding sites and by dilution of Tc-99m PYP in circulating diphosphonate pool. These findings suggests that calcification inhibitors, and possibly other calcium-blocking agents, may alter the sensitivity of Tc-99m PYP myocardial scintigraphy, but the specific effects of each calcium antagonist must be evaluated.",
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AU - Tofe, A. J.

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AU - Francis, M. D.

AU - Lewis, S. E.

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N2 - Ethane-l-hydroxy-1,1-diphosphonate (EHDP) inhibits bone mineral growth. This study was performed to test the hypohesis that EHDP would interfere with the process of calcium uptake and deposition in evolving myocardial infarction and thereby influence other parameters, including technetium-99m pyrophosphate (Tc-99m PYP) uptake and scintigraphic visualization of the infarcts. Permanent occlusion of the left anterior descending coronary artery (LAD) was produced in beagles. In seven dogs, serum EHDP was maintained at 10-15 μg/ml for 24 hours by continuous i.v. infusion, and seven control dogs were infused with saline. The Tc-99m PYP was injected 2 hours before sacrifice. EHDP-treated dogs showed a mild decrease (20%) in mean calcium content of infarcted myocardium (102.4±6.4 μg [±SEM] per gram wet weight [n=51] vs 126.7±9.5[n=49] [p<0.05]). These dogs showed a prominent decrease (37%) in mean Tc-99m PYP content of infarcted myocardium (18.2±1.4[% dose/gx10 -3] [n=46] vs 28.9±4.3 [n=46] [p<0.005]) and a marked decrease (65%) in infarct-to-normal ratio (6.1±0.9 [n=6] vs 15.9±3.7 [n=6] [p<0.05]). Positive relationships were demonstrated between myocardial Tc-99m PYP and calcium levels in the EHDP-treated dogs (r=0.69) and the control dogs (r=0.77). Infarct size and regional myocardial blood flow changes were similar in the EHDP-treated and control dogs. The average grade (0-4+) of the Tc-99m PYP myocardial scintigrams for infarcts greater than 3.5 g was 2.4±0.2 for control dogs and 1.1±0.4 for EHDP-treated dogs (p<0.05). Thus, EHDP infusion at the dose tested produced a mild decrease in calcium accumulation in canine infarcts; however, it produced a greater reduction in Tc-99m PYP uptake in the infarcts, probably by complexing with Tc-99m PYP binding sites and by dilution of Tc-99m PYP in circulating diphosphonate pool. These findings suggests that calcification inhibitors, and possibly other calcium-blocking agents, may alter the sensitivity of Tc-99m PYP myocardial scintigraphy, but the specific effects of each calcium antagonist must be evaluated.

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