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Biomedical subjects

J A Madden

Publications and source records attributed to J A Madden.

At least 55 records · Page 3Linked to original sources
PubMed1985

Hypoxia-induced activation in small isolated pulmonary arteries from the cat.

Effects of hypoxia on force development and membrane potential were studied in isolated small (less than 300 microns diam) and large (greater than 500 microns diam) pulmonary arteries from cats. There was a consistent and reproducible hypoxic constrictor response in small pulmonary arteries that began at PO2 values between 350 and 300 Torr and reached a maximum at PO2 between 50 and 30 Torr. In the small artery smooth muscle cell the membrane potential, which was -51 +/- 1.4 mV at a PO2 of 400 Torr, was depolarized to -37 +/- 2 mV at a PO2 of 50 Torr. In contrast, larger arteries did not exhibit significant hypoxic constriction or depolarization upon exposure to low PO2. Constriction in small arteries was not blocked by phentolamine. Treatment with a low dose of indomethacin (10(-9) M) augmented the response; however, a larger dose of indomethacin (10(-3) M) blocked the constriction to hypoxia but not to 30 mM KCl. Depolarization during hypoxia was not blocked by ouabain. Results of this study suggest that the hypoxic response of these isolated small pulmonary vessels may be like that seen in the intact lung. Furthermore, these data suggest that hypoxic vasoconstriction may be mediated by electrical events occurring at the pulmonary arterial muscle cell membrane either directly or via mediators released from the vessel wall.

Animals↗
PubMed1985

Hypoxic induction of Ca2+-dependent action potentials in small pulmonary arteries of the cat.

Small pulmonary arteries (less than 300 micron) from cats were mounted in myographs to record mechanical and electrical responses to hypoxia. When these preparations were exposed to a PO2 of 30-50 Torr after equilibration at 300 Torr they consistently developed active force, which increased or decreased in amplitude as [Ca2+] was raised or lowered, respectively, and was blocked on addition of verapamil. Intracellular electrical recording with glass microelectrodes demonstrated membrane depolarization and action potential generation when PO2 was lowered. Steady-state voltage vs. applied current curves obtained before and during hypoxia showed a significant reduction in input resistance. The relationship between membrane potential and extracellular K+ was not different during hypoxia compared with control, suggesting that there were not marked changes in K+ permeability under this condition. In the presence of verapamil to block Ca2+ inward current the hypoxia-induced action potentials were abolished concomitant with partial membrane repolarization. The results of these studies suggest that in certain isolated pulmonary arteries hypoxia induces contraction by a mechanism involving an increased Ca2+ conductance. These data suggest that the sensor involved in hypoxic pulmonary vasoconstriction may lie within the vessel wall and somehow mediates changes in smooth muscle ionic conductances.

Action Potentials↗
PubMed1985

A membrane electrical mechanism for hypoxic vasoconstriction of small pulmonary arteries from cat.

Using specially fabricated muscle myographs, we examined electrical and mechanical responses to reduction of PO2 in small (less than 300 micron) pulmonary arteries excised from cat lungs. Upon lowering PO2 from 400 to 50 mm Hg, these preparations consistently developed contractile responses concomitant with membrane depolarization and action potential generation. The largest changes in electromechanical responses to reduction of PO2 occurred between 150 and 50 mm Hg. These data strongly suggest that hypoxic activation of small pulmonary arteries is mediated by direct effects of reduced PO2 on muscle cell membrane ionic conductance systems.

Animals↗
PubMed1984

Cellular mechanisms of opiate receptor stimulation in cat middle cerebral artery.

To determine some of the cellular mechanisms of opiate receptor stimulation in cat middle cerebral arterial muscle, intracellular electrical measurements and force development were monitored before and after addition of morphine. Addition of morphine resulted in a dose-dependent hyperpolarization of the muscle cells in the middle cerebral artery with a concomitant relaxation, indicating a high degree of electromechanical coupling in this preparation. The curve relating membrane potential vs. morphine was shifted to the right and downward by naloxone, demonstrating competitive inhibition at receptor sites. When middle cerebral arteries were studied from animals which had been injected with morphine prior to sacrifice, a significant hyperpolarization of the membrane was recorded when studied in an organ bath. This hyperpolarization was abolished if the animal had been pretreated with naloxone prior to morphine injection, suggesting that morphine may act in vivo as we have observed it to act in vitro. Morphine-induced hyperpolarization could be blocked in the organ bath when potassium conductance (gk) was inhibited. Similarly, the reduction in the slope of the voltage/current curve induced by morphine was blocked by agents which reduced gk. These data suggest the presence of opiate receptors on cat cerebral artery and suggest that morphine relaxes these vessels through a mechanism involving increased gk. These findings suggest a role for opiate-mediated systems in cerebral vascular control.

Animals↗
PubMed1984

Sodium kinetics and membrane potential in aorta of magnesium-deficient rats.

In light of the important role of magnesium (Mg) in vascular smooth muscle function, this study was undertaken to examine effects of dietary Mg deficiency on membrane potential (Em), sodium (Na) efflux and distribution, and total ion content in rat aorta. Rats were fed either Mg-sufficient or Mg-deficient diets for 30 days. The aortic arch was removed and a segment incubated in 22Na to monitor kinetics of Na efflux. Another segment was used for measurement of Em under control conditions and during ouabain suffusion. Total tissue water and ion content were also determined. Results of this work indicate that, in aorta from Mg-deficient rats, Em was less polarized and Na accumulated intracellularly. Although the Em in Mg-deficient aorta was not affected by ouabain, which suggested Na-K pump inhibition, Na efflux was greater in Mg-deficient aorta, suggesting increased passive permeability changes to Na as the mechanism responsible for these changes.

Animals↗
PubMed1983

Some effects of aldosterone on sodium kinetics and distribution in porcine arterial wall.

Transport rate constants for Na+ exchanges and relative Na+ compartment distribution in isolated pig carotid wall were determined with the aid of 22Na+ as tracer that was continuously washed out. A three-compartment model consisting of 1) extracellular, 2) intracellular, and 3) subcellular spaces was found to represent adequately the kinetics of 22Na+. It was found that d-aldosterone (0.85 X 10(-6) M) added to the incubating medium for 3 h causes significant changes in two transport rate constants and in the distribution of sodium within different compartments. Total tissue water, nonradioactive sodium (tracee), and potassium are not altered by aldosterone; however, when amounts of Na+ tracee are calculated for each compartment, aldosterone significantly reduces the amount of Na+ in compartment 2. Overall, the results indicate that aldosterone induces a translocation of Na+ into the extracellular space at the expense of the intracellular space. The findings are interpreted in the light of recent reports on the role of altered function of the Na+-K+ pump under aldosterone influence or arterial hypertension.

Aldosterone↗
PubMed1983

Effects of dietary magnesium deficiency on thallium-20 1 kinetics and distribution in rat myocardium: concise communication.

Kinetics and distribution of TI-201 were studied in myocardium of rats with chronic dietary induced Mg deficiency. Rats were fed the Mg-deficient diet for 30 days and were then injected intravenously with 0.2 mCi of TI-201. Comparable control animals were fed a standard laboratory diet. One-half hour after injection, rats were killed and a segment of myocardium was washed with nonradioactive Krebs solution in a special chamber. Radioactivity in the tissue was recorded continuously for 1 hr. A three-compartment model (extracellular, main intracellular, and subcellular) was found to describe adequately the kinetics of TI-201. In myocardium of Mg-deficient animals, significant changes in values of transport rate constants and compartment sizes for TI-201 indicated a moderate decrease in extracellular compartment and a threefold enlargement in subcellular compartment (presumably mitochondrial) at the expense of the main intracellular compartment, which underwent a marked reduction. Bulk TI-201 uptake in myocardium of Mg-deficient rats was unchanged. The findings are interpreted as being consistent with mitochondrial alterations reported in Mg-deficient animals. Clinical implications are discussed.

Animals↗
PubMed1982

Diffusional and compartmental models for tracer washout records of Na in dog carotid.

This paper re-examines studies of Na kinetics in canine carotid arterial wall previously reported by three groups of investigators. The similarities and differences in experimental and analytical approaches for Na arterial wall washout therein are reviewed. Major conclusions are: (1) A three-compartment model in series is adequate for all short and long (after subtracting the small slow exponential) records. (2) Values for the diffusion coefficient, however, varied markedly among the different groups. (3) A continuous sampling method as opposed to an intermittent one measures better the kinetics of a rapidly exchanging ion as Na+. (4) Models based on individual washout records are better than those based on ensemble averaging. Characterization of sets of results in terms of mean values for comparing parameters provides significant potential for distinguishing quantitative features between control and treated sets despite inadequacies in data sampling or model specifications.

Animals↗
PubMed1982

Myocardial K kinetics in rats on Mg-deficient diet.

Kinetics and distribution of K were studied in myocardiuum of chronic Mg-deficient rats. The experimental design was as follows. Rats were fed either Mg-deficient or control diet for 30 days. They were then injected with 0.2 mCi of K-43. One half hour after injection they were killed and a segment of myocardium was washed with nonradioactive Krebs solution in a special chamber. Radioactivity remaining in the tissue was recorded continuously for 1 hour. A three-compartment model (extracellular, main intracellular, and subcellular) was used; transport rate constants (kij) and relative compartment sizes (qj) were determined. In myocardium of Mg-deficient rats the kij's and q's indicated greatly reduced intracellular accumulation of K but a large accumulation of K within the subcellular compartment probably mitochondrial. There was also some enlargement of the extracellular compartment. The extracellular to overall intracellular ratio for K increased 46% in Mg-deficient myocardium. The hypothesis that dietary Mg deficiency affects Na-K pump function is discussed.

Animals↗
PubMed1982

Myocardial kinetics and organ distribution of thallium-201 in two different age groups of rats.

Effects of aging were investigated on kinetics and distribution of 201 thallium (201TI) in isolated myocardial tissue and other organs of rats after injection in vivo of this radionuclide. Older rats showed a trend toward lesser organ uptake, but this was statistically significant only in kidneys, fat, and fur. Experimental outflow curves for 201TI from isolated myocardial wall segments revealed a sustained higher level of 201TI in the older rats throughout the outflow. Further analysis of the washout kinetics with a three-compartment model (extracellular, intracellular, and subcellular) showed a significant reduction of extracellular compartment and increase of subcellular compartment in older rats. The extracellular to overall intracellular ratio also decreased significantly in the older rats. The changes found for 201TI in extracellular and subcellular myocardial compartments in older rats at rest are also similar to those seen in myocardium of young rats after exercise. It is concluded that, although aging has effects on distribution of 201TI in myocardium, such effects are not likely to impair the quality of myocardial scintigraphy in older patient

Age Factors↗
PubMed1981

Rapid radiometric method for determining drug susceptibility of Mycobacterium avium-intracellulare.

A rapid radiometric method for susceptibility testing of Mycobacterium avium-intracellulare to eight chemotherapeutic agents was compared with a conventional method. Results were available within 72 h by radiometric testing in contrast to 21 days by the conventional method. The radiometric and conventional methods agreed to 61% of the tests, but growth inhibition of greater than or equal to 50% was detectable only by radiometric testing in an additional 36.5% of the tests. In only 2.5% of the tests was the radiometric method unable to detect complete inhibition shown by the conventional method. Quantifiable increases in inhibition with increasing concentration of isoniazid were more frequently detectable by the radiometric method than by conventional testing. The radiometric method is a simple, rapid, and quantitative test for drug susceptibility of mycobacteria and warrants further investigation.

Carbon Radioisotopes↗
PubMed1981

Effects of exercise on kinetics and distribution of K-43 and Tl-201 in isolated myocardium: concise communication.

Kinetics and distribution of K-43 and Tl-201 were studied in isolated myocardial tissue from rats to assess the effects of exercise. The experimental design was as follows. Rats in some groups were forced to swim for 2 hr; immediately after swimming, they were injected with 0.2 mCi of 43KCl or 201TlCl; at 0.5 or 3 hr after injection they were killed and a myocardial segment was obtained and subjected to washouts with nonradioactive Krebs fluid in a special chamber. The radioactivity remaining in the tissue was recorded continuously for 1 hr. In control groups ("rested") the exercise was omitted. Altogether there were four groups of ten animals each for both K-43 and Tl-201. A three-compartment model (extracellular, main intracellular, and subcellular) was used; transport rate constants and relative compartment sizes were determined. The most striking finding was the unchangeability of K-43 parameters with regard to experimental condition (rest compared with exercise) and sampling time (0.5 compared with 3 hr after radionuclide injection). On the other hand, Tl-201 parameters were modified by exercise and sampling time. Notable differences between K-43 and Tl-201 kinetics were found. The hypothesis that alterations at the cellular level may affect regional myocardial distribution of a radionuclide is discussed.

Animals↗
PubMed1981

Differences between 201Tl and 43K tissue distribution in rested and exercises rats.

A comparison is made of relative organ-to-plasma uptake of 43K and 201Tl in rats at rest and after exercise (two hour swimming). Organs were obtained 0.5 or 3 hrs after radionuclide injection. Thus, there were four groups each for 43K and 201 Tl. For 201Tl the triad kidneys-heart-adrenals was very consistent throughout the four experimental situations in showing the highest uptake, whereas for 43K adrenals-heart-liver predominated at 0.5 hrs and thymus-liver at 3 hrs. The ratio 201Tl/43K in myocardium was always greater than unity in all four experimental situations. The heart-to-lung and heart-to-liver uptake ratios were lower in all cases for 43K vs. 201Tl. One of the most important findings was that exercise always determined an increase of these ratios for 201Tl, but it had an unfavorable effect on the 43K heart/lung ratio and no definite effect on the 43K heart/liver ratio. Our findings are analyzed in the light of previous publications. It is concluded that these two ions have biologically important different characteristics and that excessive and seemingly unjustified emphasis has been made on their physiological similarity.

Animals↗
PubMed1980

Organ-to-plasma uptake ratio of T1-201 in rats injected at rest or after strenuous exercise. An attempt to interpret the so-called redistribution of myocardial T1-201.

A comparison is made of relative organ-to-plasma T1-201 uptake in rats at rest and after exercise (2 h swimming). Organs were obtained 1/2 or 3 h after T1-201 injection. Under the four experimental conditions, the largest uptake was found in kidneys, heart and adrenal glands. The post-exercise to rest ratio of myocardial uptake is in agreement with clinical data reported in the literature. Two extensive tissues, skeletal muscle and fat, showed a remarkable increase of T1-201 uptake at 3 h as compared to 1/2 h in both rested and post-exercised animals. During the same time interval there was a temporal "washout" of T1-201 from heart (both at rest and after exercise) and kidney (after exercise only). The findings do not support the view of a delayed myocardial uptake phase of T1-201 during which T1-201 would be reintroduced into the blood from other body organs.

Animals↗
PubMed1979

Multiexponential and multicompartmental approaches for analysis of tracer washout data from animal.

A comparison is made between multiexponential and multicompartmental analyses of tracer washout data from biological tissues. Various analytical and computer methods are used to explore the relations between kinetic parameters of three-compartment models and parameters of three-exponential functions fitted to typical observed tracer washout records and also to examine relations between kinetic parameters of the same three-compartment models determined analytically and numerically. It is concluded that exponential factors and coefficients cannot always be equated respectively with conpartmental transport rate constants or compartment sizes. Sufficient analytical and computer methodologies exist so that selection of meaningful biological models should not be hampered by a lack of appropriate solution procedures.

Animals↗
PubMed1979

Computer-assisted liver-mass estimation from gamma-camera images.

We have devised a computer-assisted method for objective estimation of liver mass from the right lateral projection of radiocolloid images of the liver. Gamma-camera images were digitized, preprocessed, and stored in computer memory. The definition of liver for area measurement was adaptively determined by means of a Laplacian operator that measures change in radioactivity slope associated with the liver margin. Individual thresholds were calculated for each of 16 subregions. A liver-mass index was derived from a linear regression model correlating the area of the right lateral projection with liver weight at autopsy in 50 patients whose livers weighed between 0.8 to 3.0 Kg. The correlation coefficient found for this method was 0.83 using the equation: Liver Mass [kg] = Area [cm2]/275 [kg/cm2]--0.215 [kg]. Liver-mass estimates using an alternative computer-assisted method or representative manual methods adapted for gamma-camera images showed lower correlation with liver weight at autopsy.

Adult↗
PubMed1979

Partition of thallium-201 in isolated myocardial tissue of rats previously injected at rest or after exercise.

The kinetics and distribution of TI-201 in isolated myocardial tissue of rats injected i.v. with this radionuclide are compared at rest and after exercise (2 hr of forced swimming). At 1/2 and 3 hr after injection, a myocardial segment was obtained and subjected to continuous washout with the radioactivity remaining in the tissue recorded each 10 sec for 1 hr. Altogether there were four groups of ten animals each. A three-compartment model (extracellular, main intracellular, and subcellular) was found to describe adequately the kinetics of TI-201. In the groups studied 1/2 hr after TI-201 injection the most dramatic effect of exercise was a translocation of TI-201 into the subcellular compartment. The change was also present but less marked in samples from exercised rats obtained 3 hr after TI-201 injection, which suggests a transition to the resting stage. The findings suggest the possibility of structural subcellular differences in myocardial uptake for TI-201 in clinical images visualized after exercise and at rest.

Animals↗