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Biomedical subjects

M A Davis

Publications and source records attributed to M A Davis.

At least 235 records · Page 13Linked to original sources
PubMed1977

"Reverse coronary steal" induced by coronary vasoconstriction following coronary artery occlusion in dogs.

The phenomenon of "coronary steal," i.e., the shunting of blood from ischemic to normally perfused areas of myocardium, has been described as an effect of the administration of several vasodilating agents. This study was performed to ascertain whether the reverse situation can be induced, i.e., whether vasoconstriction of the vessels supplying the nonischemic zone could increase the collateral flow to the ischemic area. In 16 open chest dogs, 15 and 30 min after occlusion of the left anterior descending coronary artery, epicardial electrograms were recorded and regional myocardial blood flow (RMBF) was measured with radiolabeled microspheres. Methoxamine was infused intravenously between 17 and 30 min, the mean arterial pressure being kept constant. The results indicate that while the coronary arterial flow to the normal myocardium fell from 90.6 +/- 4.3 to 77.7 +/- 3.2 ml/min/100 g (P less than 0.01), the collateral blood flow to the ischemic area increased from 21.4 +/- 3.5 to 41.0 +/- 4.2 ml/min/100 g (P less than 0.01), and thereby reduced acute myocardial ischemic injury. This favorable redistribution of blood flow might be considered a "reverse coronary steal."

Animals↗
PubMed1977

The effects of hyaluronidase on coronary blood flow following coronary artery occlusion in the dog.

In an attempt to determine the mechanism by which hyaluronidase reduces myocardial injury following coronary artery occlusion, myocardial blood flow was studied in 20 open-chest dogs with occlusion of the left anterior descending coronary artery. Ten dogs served as controls, and 10 received hyaluronidase (500 NF units/kg) intravenously 20 minutes after occlusion. At 15 minutes and at 6 hours after occlusion, regional myocardial blood flow in the epicardial and endocardial halves of both ischemic and nonischemic zones were determined with radiolabeled microspheres. Mean arterial pressure, heart rate, and cardiac output were similar in the untreated and treated dogs through the 6 hours of the experiment. Moreover, regional blood flow to nonischemic myocardium (areas without epicardial S-T segment elevation 15 minutes after occlusion) was similar in the two groups 15 minutes and 6 hours after occlusion. Fifteen minutes after occlusion, the flow to the ischemic myocardium subjacent to sites with S-T segment elevation exceeding 2 mV) in the untreated group was: transmural, 28.1 +/- 2.2 (mean +/- SE) ml/min per 100 g; endocardial, 20.7 +/- 1.8; and epicardial, 38.5 +/- 3.1. The endocardial-epicardial flow ratio was 0.56 +/- 0.04. Six hours after occlusion, the untreated group demonstrated a further decrease in blood flow to the ischemic myocardium: transmural, 15.2 +/- 1.4 ml/min per 100 g; endocardial, 6.8 +/- 1.1; and epicardial, 24.3 +/- 1.9. The endocardial-epicardial flow ratio fell to 0.28 +/- 0.04. In contrast, the hyaluronidase-treated dogs showed no further reduction in blood flow to ischemic myocardium 6 hours after occlusion: transmural, 30.3 +/- 3.1 ml/min per 100 g; endocardial, 21.3 +/- 2.5; and epicardial, 38.8 +/- 3.8. These regional myocardial flows were significantly higher than those of the untreated dogs 6 hours after occlusion. Thus, salvage of damaged myocardium by hyaluronidase might be explained by its beneficial effect on collateral blood flow to the ischemic tissue, though this effect on collateral flow could be the consequence rather than the cause of this salvage.

Animals↗
PubMed1977

Myocardial infarct imaging agents. III. Synthesis and evaluation of [203Hg] hydroxymercuriphthaleins.

Four Hg-203-mercurated phthaleins were prepared, purified, and compared with [203Hg] mercuric nitrate, [3H] phenolphthalein [203Hg] hydroxymercurifluorescein and Tc-99m-pyrophosphate in a rat model of myocardial necrosis to determine their specificities for damaged myocardium. The ratios of damaged myocardium to normal myocardium, and to blood, for the [203Hg] hydroxymercuriphthaleins (20.7-34.1 and 12.1-20.1, respectively) were somewhat lower than those reported previously for [203Hg] hydroxymercurifluorescein, but were higher than those found with [203Hg] mercuric nitrate, [3H] phenolphthalein, and Tc-99m pyrophosphate. Both the hydroxymercuri- functional group and the phthalein moiety are required for selectivity. The removal of the oxygen bridge present in fluorescein, and the replacement of carboxylic acid by sulfonic acid, had no significant effects on the sequestration process in damaged tissue.

Animals↗
PubMed1977

Radiopharmaceuticals for acutely damaged myocardium. II: Synthesis and evaluation of [203Hg] hydroxymercurifluoresceins.

Six [203Hg] hydroxymercurifluoresceins were prepared by two methods and compared with [3H] fluorescein, [131I] rose bengal, and [203Hg] mercuric nitrate, in a rat model for myocardial necrosis, to determine their specificities for damaged myocardium (DM). The nonhalogenated [203Hg] hydroxymercurifluorescein had the highest ratios of the series for DM/normal heart (51.5+/-13.5) and DM/blood (22.1+/-8.1). Halide substituents at the 2' or 4' positions of the fluorescein moiety decreased the tissue selectivity, and bis-hydroxymercuration had no significant effect. The six tracers studied had greater absolute uptake and better target-to-nontarget ratios than [3H] fluorescein, [131I] rose bengal, or [203Hg] mercuric nitrate, indicating a cooperative effect between the fluorescein and hydroxymercuri-moieties in the overall sequestration process in damaged tissues.

Animals↗
PubMed1976

Bone scanning: radionuclidic reaction mechanisms.

One of the major successes of nuclear medicine in recent years has been the clinical utility of the 99mTc-labeled bone-imaging agents. This article is concerned with the evidence available for the mechanisms by which these and other such radiopharmaceuticals localize at sites in the skeleton.

Animals↗
PubMed1976

Comparison of 99mTc-labeled phosphate and phosphonate agents for skeletal imaging.

The use of 99mTc-labeled phosphate and phosphonate compounds in place of 18F, 85Sr, and 87Sr for bone scintigraphy has become commonplace throughout the world in a relatively short time. The labeling of polyphosphate with 99mTc 4 years ago, followed rapidly by the introduction of 99mTc-labeled pyrophosphate for skeletal imaging, must therefore be regarded as a major contribution to the practice of diagnostic nuclear medicine. The markedly reduced patient radiation exposure and concomitant increase in photon detection efficiency derived from the more favorable physical decay characteristics of 99mTc led to increased sensitivity and resolution and in turn to improved diagnostic efficacy. The subsequent clinical use of the phosphonate complex 99mTc-HEDP represented a further modification of the same basic approach. Current clinical trials with 99mTc-labeled methylene diphosphonic acid (MDP), which appears to demonstrate enhanced biologic properties for scintigraphy of the osseous structures, is the latest example in this series of refinements. This article compares the technetium-labeled agents already in clinical use and, using animal data, contrasts them with several new multifunctional phosphonates and the novel inorganic compound sodium imidodiphosphate (IDP). In addition, an attempt is made to clarify the conflicting evidence in the nuclear medicine literature regarding the relationship between polyphosphate chain length and skeletal uptake.

Animals↗
PubMed1976

Comparison between the effects of nitroprusside and nitroglycerin on ischemic injury during acute myocardial infarction.

This clinical and experimental investigation was designed to delineate and compare the relative effects of sodium nitroprusside (NP) and nitroglycerin (TNG) on electrocardiographic ischemic injury following acute myocardial infarction in patients and following coronary artery occlusion in dogs. Accordingly, in ten patients with anterior acute myocardial infarction and ST-segment elevation stable for 60 min, the effects of NP (average 95 mug/min i.v.) and TNG (average 0.48 mg sublingually) were studied. The hemodynamic actions of NP and TNG were directionally similar. However, NP increased average ST-segment elevation (ST) by 2.0 +/- 0.2 mm, while TNG reduced ST by 1.4 +/- 0.4 mm. In order to clarify this disparity, coronary artery occlusions were carried out in 14 open-chest dogs. During control, NP and TNG time periods, epicardial electrograms were recorded and regional myocardial blood flow (RMBF) determined by the microsphere technique. Nitropruside increased ST-segment elevation from 4.6 +/- 0.6 to 5.7 +/- 0.6 mV (P less than 0.05) and reduced RMBF from 35 +/- 3 to 27 +/- 2 ml/min/100 g (P less than 0.01) in the ischemic zones. In contrast, TNG reduced ST-segment elevation from 4.9 +/- 0.7 to 3.0 +/- 0.7 mV (P less than 0.05), while increasing RMBF TO 43 +/0 4 ml/min/100 G (P less than 0.05) and the endo/epicardial ratio from 0.57 +/- 0.06 to 0.69 +/- 0.07 (P less than 0.01). Although TNG and NP exhibit similar hemodynamic effects, TNG reduced electrocardiographic ischemic injury, at least in part, by increasing perfusion of the ischemic areas and redistributing it favorably, while NP increased electrocardiographic ischemic injury, at least in part, by reducing perfusion. Therefore, TNG seems preferable to NP for reducing preload and afterload in patients during the early phase of acute myocardial infarction.

Acute Disease↗
PubMed1976

Evaluation of radiopharmaceuticals sequestered by acutely damaged myocardium.

Eighteen radiopharmaceuticals were screened in a small-animal model as potential infarct-localizing agents. Twelve of the 18 compounds were labeled with 99mTc, four with 203Hg, one with 131I, and one with either 203Hg or 125I. The model used heat-induced myocardial lesions in the rat. The absolute concentration within the lesion and also the activity ratios of injured myocardium to normal heart tissue, blood, and muscle were determined for all compounds. Among the 99mTc-labeled agents, two bone-seekers [pyrophosphate (PPi) and 1-hydroxyethylidine-1,1-diphosphonate (HEDP)] showed the most promise; these were followed by 99mTc-tetracycline analogs and 99mTc-glucoheptonaate. The tracer showing the most favorable concentration in the lesion and the best target-to-nontarget ratios was an iodinated derivatives of hydroxymercurifluorescein labeled with either 125I or 203Hg. Consideration of the structure of these compounds suggests that the presence of mercury or of a polycyclic aromatic structure, such as that found is tetracycline and fluorescein, was associated with localization in damaged myocardial tissue. Mercury bound to such an aromatic moiety may produce an additive or even a synergistic effect.

Animals↗
PubMed1976

Double-labeling of experimental acute myocardial infarcts with 113mIn- and 99mTc-EDTMP.

The feasibility of double-labeling of acute myocardial infarcts with 113mIn-EDTMP [ethylenediaminetetra(methylene phosphonic acid)] and 99mTc-EDTMP was evaluated. The in vitro distributions of these tracers in acute myocardial infarcts in dogs and their selectivities for infarcted versus noninfarcted myocardium were compared. Both tracers concentrated in acutely infarcted myocardium, and there was excellent correlation between their uptakes (r = 0.88). They also provided complete separation between infarcted and uninfarcted tissue, as checked by histology. Accordingly, these agents show promise for the multiple-labeling of acute myocardial infarcts in experiments to determine the natural course of myocardial infarction and the efficacy of therapy aimed at limiting infarct size. In addition, 113mIn-EDTMP may be useful for serial scintigraphy during the early phase of acute myocardial infarction when the damage may be, at least to some extent, reversible.

Animals↗
PubMed1975

Uptake of 99mTe-Sn-EHDP in beagles with advanced periodontal disease.

Bone seeking radiopharmaceuticals were used in conjunction with skeletal imaging techniques to study bone mineral metabolism in beagle jaws. In beagles with chronic destructive periodontal disease, the tooth-supporting bone exhibited an increased uptake of technetium-99m-tin-diphosphonate when compared to control dogs. Scan images of soft tissue and vascular pools in the diseased jaws were normal. When quantitative densitometric data derived from bone scan images were compared, it was found that values reflecting radionuclide uptake in dogs with chronic destructive periodontal disease were six times greater than corresponding values in control dogs.

Alveolar Process↗
PubMed1975

Radionuclide immunoglobulin lymphangiography: a case report.

Iodine-131-labeled immunospecific gamma globulin derived from immunization of rabbits with F antigen, a tumor associated antogen in Hodgkin's disease, has been utilized for intralymphatic infusion in a patient with known recurrent Hodgkin's disease inthe inguinofemoral and pelvic regions. Rectilinear scanning successfully delineatedthe tumor masses, and external monitoring showed retention of activity in the tumor sitesover an 8-day period.

Adult↗
PubMed1975

113mIn-labeled bone scanning agents.

Phosphonate analogs of EDTA and DTPA, in which the acetic acid has been replaced by methylene phosphonic acid (DTPMP and EDTMP) have been labeled with 113mIn and evaluated as skeletal imaging agents. Organ distribution in rats, blood clearances in dogs, and images obtained in rabbits are presented. 113mIn-DTPMP exhibits the desired characteristics to supplant 85Sr and other bone-seeking radiopharmaceuticals used in areas of the world where 99mTc is not routinely or regularly available.

Animals↗