Biomedical subjects

C G Rhodes

Publications and source records attributed to C G Rhodes.

81 records · Page 5Linked to original sources

PubMedDate not supplied

Effect of long-term beta2-agonist dosing on human cardiac beta-adrenoceptor expression in vivo: comparison with changes in lung and mononuclear leukocyte beta-receptors.

BACKGROUND: Tachyphylaxis to the cardiac effects of beta-adrenoceptor stimulation after long-term beta2-agonist administration is well recognized, but the influence on global cardiac beta-adrenoceptor density has not been previously investigated in vivo. Positron emission tomography (PET) has made possible the noninvasive quantification of regional receptor density. This study assesses the effect of long-term beta2-agonist dosing on cardiac beta-adrenoceptors. METHODS AND RESULTS: Beta-adrenoceptors in the hearts of 29 healthy male subjects aged 35 +/- 8 years were imaged and quantified in vivo by means of PET and compared with the receptor density in the same subjects' lung tissue. Mononuclear leukocyte (MNL) beta-receptor density was determined in vitro by means of a radioligand binding assay. Beta-receptor density was 8.41 +/- 2.03 pmol/gm tissue in heart, 10.81 +/- 1.91 pmol/gm tissue in lung, and 38.0 +/- 17.5 fmol/mg protein on MNLs. There was a weak relationship between cardiac and pulmonary beta-receptor densities (r = 0.45, p < 0.02) but not between cardiac and MNL receptor density. In seven subjects, the measurements were repeated after 2 weeks of albuterol treatment (4 mg orally twice daily and 200 microg inhaled four times daily in the first week, with doubling of the dose during the second week). After the albuterol treatment, beta-receptor density fell on average by 19% (p < 0.05) in the heart compared with 22% (p < 0.05) in the lung and 42% (p < 0.05) in MNLs. Correlations were found between the percentage changes in receptor density in heart and lung (r = 0.98, p < 0.001) and in heart and MNLs (r = 0.99, p < 0.002). CONCLUSIONS: Two weeks of high-dose albuterol results in equivalent downregulation of beta-receptors in vivo, both in the lung and in the heart.

Adrenergic beta-2 Receptor Agonists↗

PubMedDate not supplied

Influence of intravascular activity on the determination of blood flow and oxygen extraction in normal and ulcerated legs using the 15O steady-state technique and positron emission tomography.

An analysis using the 15O steady-state inhalation technique has been carried out into the effects of correction for intravascular activity on the determination of blood flow and oxygen extraction ratio (OER) in the legs of patients affected by ulceration. Transaxial images of the distribution of activity in a plane passing through the ulcer were obtained during steady-state inhalation of C15O2 and 15O2, respectively, using a single slice positron emission tomographic scanner. From these, the basic tracer model equations were solved to obtain blood flow and oxygen extraction with and without additional correction for the presence of intravascular activity. The latter was obtained from a scan following the inhalation of a tracer quantity of 11CO, which labels the red blood cell pool. Mean blood flow and OER in ulcerated regions were 0.087 ml/ml/min and 0.33, respectively. With correction for blood volume, assumed to be all venous, the mean OER decreased to 0.12. In the "mirror" region of normal legs mean blood flow was 0.011 ml/ml/min with uncorrected and corrected OER values of 0.87 and 0.75, respectively. The effect of assuming a nonzero arterial volume increases as flow and OER decrease but is uncertain due to the unknown arterial fraction. Correction for intravascular 15O is essential and generally the assumption that all blood volume is venous is adequate.

Humans↗

PubMedDate not supplied

Physical aspects of cardiac scanning with a block detector positron tomograph.

Physical aspects relating to cardiac scanning are described for an eight ring (15 plane) positron tomograph consisting of BGO block detectors (CTI/Siemens 931-08/12). Performance parameters were derived from a cylindrical heart phantom having a "myocardial" wall of thickness varying from 3 mm to 27 mm. This phantom was inserted into a chest phantom consisting of simulated chest wall, lungs, and arms. Recovery coefficients for myocardial thicknesses of 10 mm and 15 mm were 0.75 and 0.9, respectively. Division by the transmission minus "blood pool" (extravascular density) image was found to give a variation of corrected myocardial counts within +/- 5% when transmission data were smoothed. The on-line dead time correction algorithm was found to be accurate to within 5% up to 20 mCi (740 MBq) in the axial field of view (FOV) (10.8 cm) in the central chamber of the heart phantom. However, the correction factor at this rate is approximately 3, which would imply poor use of administered dose. Counts in the image due to scatter are approximately 2% in the (cold) central cavity of the heart phantom relative to counts/pixel in the active myocardium. The presence of phantom arms in the FOV was found to have only a small effect on mean pixel counts and noise in the heart phantom image, as did movement of the arms within a reasonable range.

Calibration↗

PubMedDate not supplied

Myocardial presynaptic and postsynaptic autonomic dysfunction in hypertrophic cardiomyopathy.

Although hypertrophic cardiomyopathy (HCM) is genetically determined, several other factors, including autonomic dysfunction, may play a role in the phenotypic expression. A recent study using positron emission tomography with [11C]CGP 12177 ([11C]CGP) demonstrated that beta-adrenoceptor (betaAR) density is reduced in HCM and is correlated with disease progression. This present study tested the hypothesis that this downregulation is associated with reduced catecholamine reuptake (uptake 1) by myocardial sympathetic nerve terminals leading to increased local norepinephrine concentration. Myocardial presynaptic catecholamine reuptake was assessed by measuring the volume of distribution (Vd) of the catecholamine analogue [11C]hydroxyephedrine ([11C]HED) in 9 unrelated HCM patients aged 45+/-15 years. The maximum number of binding sites (Bmax) for myocardial betaAR density was measured in 13 unrelated HCM patients aged 40+/-12 years using the nonselective beta blocker [11C]CGP. Six patients were studied with both [11C]HED and [11C]CGP. Comparison was made with two groups of healthy control subjects for each ligand ([11C]HED, n=10, aged 35+/-8 years; [11C]CGP, n=19, aged 44+/-16 years). Myocardial Vd of [11C]HED (33.4+/-4.3 mL/g tissue) and betaAR density (7.3+/-2.6 pmol/g tissue) were significantly reduced in HCM patients compared with control subjects (71.0+/-18.8 mL/g tissue, P<.001, and 10.2+/-2.9 pmol/g tissue, P=.008, respectively). These results are consistent with our hypothesis that myocardial betaAR downregulation in HCM is associated with an impaired uptake-1 mechanism and hence increased local catecholamine levels.

Adult↗

PubMedDate not supplied