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Biomedical subjects

M J Frey

Publications and source records attributed to M J Frey.

At least 37 records · Page 2Linked to original sources
PubMed1989

Sympathetic vasoconstriction during exercise in ambulatory patients with left ventricular failure.

In patients with heart failure, exercise is thought to increase sympathetic vasoconstrictor tone. To investigate the extent of this sympathetic activation, we studied the effect of maximal exercise on nonexercising vascular beds in 35 patients with left ventricular failure (ejection fraction, 21 +/- 8%; peak exercise oxygen uptake (VO2), 12.3 +/- 3.5 ml/min/kg). In 28 patients, cardiac output and leg blood flow were measured during maximal upright bicycle exercise. Total flow to nonexercising tissue was then calculated as cardiac output--(2 x leg flow). In seven patients and six normal subjects, forearm blood flow was measured during supine bicycle exercise before and after alpha-adrenergic blockade with intravenous phentolamine. Maximal upright exercise increased the vascular resistance of nonexercising tissue from 34 +/- 16 units at upright rest to 45 +/- 25 units (p less than 0.02) but did not affect total flow to nonexercising tissue (rest, 2.9 +/- 1.0; maximal exercise, 2.8 +/- 1.4 l/min; p = NS). Supine exercise had no significant effect on forearm blood flow or vascular resistance in the normal subjects. In the patients with heart failure, supine exercise increased forearm vascular resistance from 45 +/- 17 to 58 +/- 25 mm Hg/ml/min/100 ml (p less than 0.02), again with no change in tissue flow (rest, 2.4 +/- 0.1; maximal exercise, 2.4 +/- 0.9 ml/min/100 ml; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Output↗
PubMed1989

Mechanisms of downregulation of beta-adrenergic receptors: perspective on the role of beta-adrenergic receptors in congestive heart failure.

The impaired inotropic responsiveness of myocardial tissue to catecholamines in congestive heart failure has been ascribed to downregulation of beta-adrenergic receptors. It has been reported recently that resistance to catecholamines is related to a defect in the guanine nucleotide binding protein that couples the beta-adrenergic receptor to adenylate cyclase. Studies of beta-adrenergic receptors were carried out using three different experimental protocols: (a) the interactions of the atypical agonists pindolol and celiprolol with beta-adrenergic receptors from C6 glioma cells (40% beta 1, 60% beta 2) were compared with those of the full agonist isoproterenol; (b) the ability of pindolol, celiprolol, and isoproterenol to induce downregulation and sequestration of beta-adrenergic receptors in wild-type S49 lymphoma cells was compared with the responses observed with a mutant line of S49 cells (cyc-, which lack Gs activity); and (c) the differential response of patients with heart failure and age-matched control subjects to exercise-induced changes in the density of beta-adrenergic receptors and isoproterenol-stimulated adenylate cyclase activity on circulating lymphocytes was investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

Down-Regulation↗
PubMed1989

Assessment of anatomy and cardiac function by Doppler echocardiography.

In this article, we have reviewed the impact of the new technique of Doppler ultrasound upon the assessment of aortic stenosis, aortic regurgitation, and diastolic left ventricular function. It is a powerful new technique that greatly extends our ability to understand the pathophysiology of these conditions. However, its use must be tempered with an appreciation of the limitations of the new technique and knowledge of the circumstances in which it may yield erroneous results.

Aortic Valve↗
PubMed1988

Effect on peripheral arterioles of chronic fluid and sodium retention in heart failure.

To determine whether chronic fluid and sodium retention in heart failure adversely affects peripheral arteriolar behavior, systemic vascular resistance and skeletal muscle vasodilation were compared in eight control dogs and nine dogs with chronic fluid and sodium retention (ascites = 2.3 +/- 2.3 liters) induced by rapid ventricular pacing for 2 months. At rest, both groups exhibited comparable systemic vascular resistance (control 45 +/- 14 versus heart failure 40 +/- 7 U) and femoral bed vascular resistance (control 18.7 +/- 6.9 versus heart failure 19.0 +/- 7.2 x 10(2) U) (both p = NS). Femoral bed resistance also decreased similarly in both groups during treadmill exercise (resistance at peak exercise: control 4.7 +/- 3.0 versus heart failure 4.9 +/- 0.9 x 10(2) U [p = NS]). In isolated gracilis muscle, vascular resistance was also comparable in both groups at rest (control 7.3 +/- 3.3 versus heart failure 10.2 +/- 3.6 x 10(3) U/100 g), at peak exercise (control 1.6 +/- 0.5 versus heart failure 1.8 +/- 0.9 x 10(3) U/100 g) and after maximal vasodilation with papaverine (control 0.7 +/- 0.3 versus heart failure 0.9 +/- 0.3 x 10(3) U/100 g) (all p = NS). These data suggest that chronic fluid and sodium retention in heart failure does not alter peripheral arteriolar behavior.

Animals↗
PubMed1986

Corticosterone, free fatty acid and glucose responses of rats to footshock, fear, novel stimuli and instrumental reinforcement.

Rats were subjected to sessions of footshock, fear stimuli and instrumental reinforcement to assess responses of blood corticosterone, free fatty acids (FFA) and glucose. The corticosterone response to fearful situations exhibited a stimulus generalization decrement, thus demonstrating a contribution of Pavlovian classical conditioning to the activity of the hypothalamo-pituitary-adrenal system. Corticosterone levels were shown to decrease during operant sessions with large water reinforcements, while FFA and glucose levels were increasing, thus dissociating these stress measures. FFA responses to intermittent, intense footshock were found to be quadratic; blood levels of FFA increased within 10 min, decreased by 40 min, and then showed the increase with 80-min long sessions previously reported in the literature. This pattern of response was not influenced by prior food deprivation or different methods of sampling blood. Blood levels of FFA increased generally to novel/fearful situations and instrumental reinforcement sessions, which were stimulus situations less stressful than the footshock sessions. Glucose increases occurred to footshock and instrumental reinforcement sessions under some conditions, depending more than corticosterone and FFA on prior food deprivation and blood sampling method.

Animals↗
PubMed1984

Immunologic release of histamine from dog lung: comparison of in vivo and in vitro responses in the same animal.

The purpose of this study was to compare, for the first time, antigen-induced histamine release from the lung in the same natively allergic dogs both in vitro and in vivo. In six dogs, maximal antigen-induced histamine release from the lung correlated closely in vitro and in vivo (r = 0.94), although it varied widely between dogs (0% to 75.5% of total tissue histamine content); similarly, the antigen concentration to produce 50% of maximal histamine release varied sixfold between dogs (40 micrograms/ml to 250 micrograms/ml). In each of five other dogs, terbutaline sulfate administered intravenously caused a dose-dependent inhibition of antigen-induced histamine release from lung fragments in vitro: the maximal inhibition produced by 1 mg/kg was 60 +/- 4.5% (mean +/- SEM). In these same dogs, 10(-5)M terbutaline incubated with lung fragments in vitro caused inhibition of antigen-induced histamine release comparable to 1 mg/kg terbutaline in vivo. Increasing the dose of terbutaline in vitro produced maximal inhibition at 10(-4)M with no greater effect of the drug at 10(-3)M (71.4 +/- 3.8% inhibition). In both experimental situations propranolol caused a dose-dependent inhibition of beta-adrenergic modulation of Ascaris-induced release of histamine. This result supports the conclusion that terbutaline produced its effects by actions mediated by beta-adrenergic receptors on pulmonary mast cells. This experimental approach provides a suitable preparation in which to estimate the effective dose of agonists that modulate antigen-induced mast cell function in vivo.

Animals↗
PubMed1984

Radioenzymatic assay for measurement of tissue concentrations of histamine: adaptation to correct for adherence of histamine to mechanical homogenizers.

Because adherence of histamine to glass is well-known, we tested for its adherence to a mechanical homogenizer commonly used in the extraction of histamine from tissue samples. During 60 sec of homogenization, 15% to 17% of the histamine originally present in the samples "disappeared," and the reason for the disappearance was reversible binding of histamine to the homogenizer. Adding trace amounts of [14C]histamine to each sample before homogenization and measuring the disappearance of radioactivity during homogenization permitted correction for binding to the homogenizer. This technique for correction was validated by the measurement of endogenous concentrations of histamine in the tracheal posterior membranes of six dogs (range of mean concentrations: 0.63 to 1.51 ng/mg wet weight) followed by the measurement of known amounts of exogenous histamine added before homogenization to tracheal tissue samples from the same dogs. In the latter samples, 96 +/- 13% (mean +/- SEM) of the histamine added was measured by our technique. We conclude that binding of histamine to mechanical homogenizers may be an important cause of inaccuracy of the enzymatic assay for the measurement of histamine concentrations in tissue but that such binding may but that such binding may be easily corrected for.

Adhesiveness↗
PubMed1983

Effect of beta-adrenergic stimulation on experimental canine anaphylaxis in vivo.

We studied beta-adrenergic modulation of antigen-induced release of histamine and changes in lung function in natively allergic, anesthetized dogs. After thoracotomy and bilateral cervical vagotomy, samples of peripheral lung frozen in situ were obtained for measurement of adenosine cyclic 3',5'-monophosphate (cAMP) and histamine. In 11 dogs with beta-adrenergic blockade (propranolol), subsequent Ascaris suum antigen (intravenous) decreased lung tissue histamine 21.5% +/- 5.3% (mean +/- SE), with marked physiologic changes of anaphylaxis. In six other dogs, with no pharmacologic treatment before antigen, A. suum decreased lung tissue histamine only 11.5% +/- 1.9%. In six other dogs, terbutaline (1 mg/kg, i.v.) increased concentration of cAMP in peripheral lung, indicating stimulation of beta-adrenergic receptors, and inhibited response to A. suum. When a beta-adrenergic agonist was given 15 sec prior to A. suum, cAMP doubled and inhibition was incomplete. When a beta-agonist was given 150 sec prior to A. suum, cAMP increased fivefold and inhibition was complete.

Adrenergic beta-Agonists↗
PubMed1982

Characterization of tracheal mast cell reactions in vivo. Inhibition by a beta-adrenergic agonist.

In 12 anesthetized dogs, we tested the effects of pharmacologic beta-adrenergic stimulation on the severity of tracheal mast cell reactions in vivo (Am Rev Respir Dis 1979; 119:62). In control dogs, tracheal arterial injections of compound 48/80 produced arteriovenous differences in histamine concentrations across the trachea (35 +/- 15 ng/ml), but not the lung; this finding suggested selective degranulation of tracheal mast cells. Tracheal arteriovenous histamine differences correlated (r = 0.70) with tracheal contractions (12 +/- 4 g/cm) induced by compound 48/80 in these animals. In other dogs, injections of isoproterenol (10 micrograms/kg) before compound 48/80 prevented the development of both tracheal arteriovenous differences and contractions. We concluded that pharmacologic beta-adrenergic stimulation inhibited degranulation of tracheal mast cells. The preparation appears suitable for examining the effects of endogenous stimuli on the severity of mast cell reactions in the central airways of anesthetized dogs.

Adrenergic beta-Agonists↗
PubMed1980

Physiological and pharmacological properties of canine trachealis muscle in vivo.

In 23 dogs anesthetized with chloralose and urethan, we developed a preparation that premitted measurement of isometric tension in segments of the tracheal posterior membrane in situ. Length-tension studies showed an optimal length for contraction in each of 5 segments; in all 5 segments, length was optimal when resting tension was 22-35 g/cm. In 8 other segments, stimuli were delivered by systemic intravenous injections, by electrical stimulation of nerves, or by selective injections into the tracheal circulation; the time between delivery of repeated stimuli required for reproducible responses differed for each form of stimulation. Hypoxemia increased tension by 23.1 +/- 5.5 (SE) g/cm in 10 out of 10 other segments; these increases were the results of reflexes, not direct effects. Because the innervation and vascular supply of these segments were largely intact, we concluded that this preparation permits the study of neurohumoral mechanisms which modulate smooth muscle contraction in a prototypic central airway in vivo.

Acetylcholine↗
PubMed1980

Effect of intraventricular serotonin on the plasma cortisol response to restraint stress in unanesthetized sheep.

Serotonin infused into a lateral ventricle of unanesthetized sheep reduced the response of the hypothalamic-pituitary-adrenal axis to restraint stress. However, the attenuation of the adrenal response by serotonin was of only limited duration, suggesting that pharmacological manipulation of serotonin would not be effective in altering the adrenal response to stress.

Animals↗
PubMed1979

Experimental canine anaphylaxis: cyclic nucleotides, histamine, and lung function.

We studied the effects of Ascaris suum antigen (iv) in 32 natively allergic, anesthetized dogs. After thoracotomy, bilateral cervical vagotomy, and propranolol, samples of peripheral lung frozen in situ were obtained for measurement of cyclic nucleotides and histamine. Following Ascaris, lung histamine decreased 20.4 +/- 3.7% (mean +/- SE), cAMP increased 391 +/- 122%, and cGMP increased 110 +/- 20% with increased plasma histamine and physiological changes of anaphylaxis. No significant changes occurred in 10 control dogs. Release of histamine, reflecting immunological degranulation of mast cells, correlated closely with the physiological effects of anaphylaxis. beta-Adrenergic stimulation with isoproterenol prevented these physiological effects of anaphylaxis in three dogs studied. Furthermore, the level of cAMP induced in lung tissue by beta-adrenergic stimulation in these dogs correlated with the degree of inhibition of immunologically induced histamine release. These results illustrate the suitability of this experimental preparation to study the biochemical and physiological mechanisms of anaphylaxis in vivo.

Anaphylaxis↗
PubMed1978

Relationship of metal metabolism to vascular disease mortality rates in Texas.

The annual mortality rates for 1968 of six types of cardiovascular diseases among those persons over 45 years of age in 24 Texas communities were compared with respective community drinking water and urine metal levels of calcium, magnesium, potassium, lithium, strontium, and silicon. Numerous inverse correlations were found between mortality rates and the levels of various metals in both drinking water and urine. Positive correlations were also observed between several of the mortality rates and the ratio of the concentration of sodium to that of the other metals in both water and urine. Mean community urinary levels of lithium, magnesium, strontium, and silicon showed a direct correlation to the levels of exposure via the drinking water. The results of this study suggest that calcium, magnesium, lithium strontium, and silicon may protect against cardiovascular mortality; possibly, by competing with sodium and potassium for transport in the intestinal lumen, increasing excretion of sodium, or other mechanism.

Calcium↗