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

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.