A B S T R A C T This study was performed to elucidate the localization at the cellular level of technetium-99m phosphorus (991'Tc-P) radiopharmaceuticals in acute myocardial infarcts and the mechanisms responsible for 99mTc-P uptake in acute myocardial infarcts and other tissues. In 20 dogs with proximal left anterior descending coronary arterial ligation for 1-3 days, elevated calcium levels were measured at all sites of increased 99mTc-P uptake (acute myocardial infarcts, necrotic thoracotomy muscle, lactating breast, and normal bone); however, a consistent linear relationship between 99mTc-P and calcium levels was not observed. A strong correlation (r = 0.95 and 0.99, n = 2 dogs) was demonstrated between levels of 3H-diphosphonate and 99mTc-P in infarcted myocardium. Auito studies revealed major localization of both 99mTc-P and calcium in the soluble supernate and membranedebris fractions of infarcted myocardium and less than 2% of total 99mTc-P and calcium in the mitochondrial fractions; however, electron microscopic examination showed that mitochondria with calcific deposits were not preserved in the mitochondrial fractions. In vitro studies evaluating the role of serum protein binding on tissue uptake of 99mTc-P agents demonstrated that, in spite of significant complexing with serum proteins, serum 99mTc-P activity retained the ability to adsorb to calcium hydroxyapatite and amorphous calciumni phosphate. In vivo stuidies showed that concentration of human seirum albtumin (labeled with iodine-131) in infarcted myocardiutim reached a maximuiim of only 3.8 times normal after a circulation time of 96 h, whereas 99mTc-P uiptake was at least 10 times normal after a circulation time as short as 1 h. It is concluded that: (a) 99mTc-P uptake in acutely infarcted myocardium, and possibly other types of soft tissue damage, is limited to necrotic and severely injured cells; (b) concentration of 99mTc-P results from selective adsorption of 99mTc-P with various forms of tissue calcium stores, including amorphous calcium phosphate, crystalline hydroxyapatite, and calcium complexed with myofibrils and other macromolecules, possibly supplemented by calcium-independent complexing with organic macromolecules; and (c) lack of a linear relationship between 99mTc-P and tissuie calcitum levels mainly results from local differences in composition and physicochemical properties of tissuie calcium stores and from local variations in levels of blood flow f'or delivery of 99mTc-P agents.

A B S T R A C T Experimental myocardial ischemia pro

In the present study, we tested the hypotheses that 1) different species have different myocardial adrenergic receptor numbers and 2) selected "slow-channel" calcium antagonists compete with alpha-adrenergic antagonists for binding to varying degrees in different species. The data obtained in the present study demonstrate that there is a markedly decreased number of alpha 1-adrenergic and increased number of beta-adrenergic receptors in canine compared with rabbit and rat myocardium. The differences in adrenergic receptor numbers exist without major differences in alpha 1-adrenergic receptor affinity in the species studied. There was no significant difference in left ventricular or plasma catecholamine content between the rat and dog. Selected slow-channel calcium antagonists compete for alpha 1-adrenergic receptor binding in rabbit, rat, and canine myocardium. However, only in rabbit myocardium does verapamil antagonize alpha 1-adrenergic receptor binding at moderate concentrations, whereas verapamil in canine and rat myocardium and 1) 600 in all three species antagonize alpha 1-adrenergic receptor binding only at relatively high concentrations. Nifedipine, a dihydropyridine-type slow-channel calcium antagonist, had no effect on prazosin binding to rat, rabbit, and dog myocardial membranes.

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