We evaluated the use of a least-squares radionuclide separation technique to allow an increased number of myocardial blood flow measurements with radionuclide-labeled microspheres in dogs. Two sets of labeled microspheres were studied: a set of eight labeled with 125I, 153Gd, 57Co, 51Cr, 113Sn, 85Sr, 95Nb, and 46Sc; and a set of nine in which 125I and 46Sc were replaced with 114In, 54Mn, and 65Zn. For each microsphere label the nuclide activities determined by least-squares separation compared favorably with those actually added to in vitro samples containing a fixed amount of the other nuclides in the set. For the set of eight radionuclide-labeled microspheres, myocardial flow measurements made with the least-squares separation technique and the reference sample method were usually within 15% and almost all within 20% of direct measurements of coronary venous outflow in a right heart bypass preparation. Serial left atrial injections of 15-micron microspheres totaling 48 X 10(6) caused no significant changes in systemic hemodynamics, regional myocardial flows, or coronary pressure-flow relations, whether the coronary bed was autorelating or vasodilated with chromonar. We conclude that at least nine myocardial blood flow measurements can be made in dogs with acceptable accuracy and without evidence of dysfunction due to embolization of the coronary vascular bed. With appropriate validation, this method should be applicable to other organs and animal models as well.
We developed new nonradioactive microspheres and used more sensitive X-ray fluorescence spectrometers than used previously to measure regional blood flow in the heart and other organs. We demonstrated the chemical stability of eight kinds of heavy element-loaded microspheres and validated their use for regional blood flow measurement by comparing duplicate flows measured with radioactive and/or nonradioactive microspheres in both acute and chronic dog experiments. The wavelength-dispersive spectrometer (Philips PW 1480) has a higher sensitivity than the previously described X-ray fluorescent system and reduced the number of microspheres required for accurate measurement. The fine energy resolution of this system makes it possible to increase the numbers of different kinds of microspheres to be quantitated, but at present only eight kinds are available. We also used a synchrotron radiation-excited energy dispersive spectrometer. The monochromatic synchrotron radiation allowed us to obtain much higher signal-to-background ratios of X-ray fluorescence spectra than with the wavelength-dispersive system (50 dB more for Zr-loaded microspheres) and will enable analysis of fluorescent activity in smaller regions (< 20 mg) than the radioactive method does.
We determined the effects of time, type of anesthesia, and myocardial infarction on loss of radioactive microspheres averaging 9 or 15 micrometers diameter from left ventricular myocardium. The principle used to compute losses was comparison of the number of microspheres injected directly into coronary arteries to the numbers remaining in myocardium, appearing within 2-4 min in the coronary sinus, or trapped in the lungs. Losses of 9-micrometers microspheres within 2 min of injection were significantly greater for halothane (mean 6.3%) than nitrous oxide anesthesia (mean 3.3%), and in the next 2 h increased to 11.7 and 7.9%, respectively. Over 5 wk in conscious dogs losses were as high as 40 and 11% for 9 and 15 micrometers microspheres, respectively. Losses were not greater for infarcted than normal muscle, and negligible radioactivity appeared in paracardiac lymph nodes. Microspheres leaving the heart were almost all below 10.3 micrometers diameter, so that microspheres with diameters 10-14 (mean 12) micrometers might be the best size to use for myocardial studies.
We have previously shown that the incidence of patent ductus arteriosus (PDA) in premature infants whose mothers received prenatal glucocorticoid therapy was significantly lower than that of an untreated group. In addition, the incidence of respiratory distress syndrome was lower in the treated than in the untreated group. To determine whether glucocorticoids affect the ductus arteriosus itself, we studied the effects of a 48-h intravenous infusion of 1 mg/h hydrocortisone in prematurely born lambs (120-129 days, 0.84 gestation). Estimations of ductus patency were made on 1-h-old lambs by radioactive microsphere injections. We found that hydrocortisone infusions facilitate the closure of the ductus without altering the severity of respiratory distress in premature lambs. In the lamb, prostaglandin E2 (PGE2) inhibits the ability of the ductus to contract in response to O2. Because production of PGE2 has been shown to be inhibited by hydrocortisone in several isolated organ systems, we measured PGE2 plasma concentrations in treated and untreated animals. We found circulating PGE2 concentrations to be similar in the two groups; furthermore, release of PGE2 by isolated ductal rings in vitro was similar in treated and untreated animals. This contradicts the hypothesis that diminished PGE2 concentrations, either circulating or in the tissue, are the cause for ductus arteriosus closure in hydrocortisone-treated animals. However, hydrocortisone treatment decreases the sensitivity of the ductus arteriosus in vitro to the relaxing action of PGE2. These findings suggest that glucocorticoid treatment decreases the incidence of PDA in premature infants by affecting the interaction of PGE2 with ductal tissue.
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