Paul J. Rogers

Catecholamine metabolic pathways and exercise training. Plasma and urine catecholamines, metabolic enzymes, and chromogranin-A.

BackgroundBecause acute exercise increases systemic catecholamines, we sought to determine whether exercise training would alter daily or exercise-related catecholamine release and inactivation. Methods and ResultsIn 24-hour urine collections, catecholamines and metabolites provided indexes of overall oxidative deamination, sulfation, and O-methylation. Plasma catecholamines, the sulfoconjugates of each, and chromogranin-A were determined at rest and during exercise in 10 well-trained male subjects and nine minimally trained male subjects (maximal oxygen uptake 55.2 and 42.5 ml/kg/min, respectively), and levels of activities of catechol-Omethyltransferase (COMT), monamine oxidase B (MAO-B), and thermolabile phenolsulfotransferase (TL-PST) were also determined. Plasma-free catecholamines showed minimal differences between the two groups at submaximal exercise (4 minutes) but large differences at maximal exercise, reflecting the different exercise levels attained. Inactivation of plasma catecholamines by sulfation across rest and exercise tended to be greater in the well-trained group, with small increases in both plasma sulfoconjugated dopamine and sulfoconjugated norepinephrine. In the well-trained group, urinary metabolites demonstrated trends toward increased dopamine release (p < 0.07) and small increases in the daily release of epinephrine and its sulfoconjugated metabolites. Indexes of deamination, sulfoconjugation, and 0-methylation, with the exception of a reduced deamination of dopamine and the activities of COMT, MAO-B, and TL-PST were not different in the two groups. ConclusionsDespite considerable differences in the exercise activities per week between well-trained and minimally trained individuals, there were minimal differences in the release and metabolism of catecholamines at rest or during exercise.

The influence of gating on measurements of myocardium at risk and infarct size during acute myocardial infarction by tomographic technetium 99m-labeled sestamibi imaging

BackgroundSerial perfusion imaging with 99mTc-labeled sestamibi has been useful in the assessment of myocardial salvage from reperfusion therapy during acute myocardial infarction. Studies in animal models have shown that discernible perfusion defects can be created by left ventricular asynergy from partial volume effects in the setting of homogenous perfusion tracer distribution. The purpose of this study was to examine the influence of gating on serial perfusion images during acute myocardial infarction to determine the magnitude of potential partial volume effects.Methods and Results99mTc-labeled sestamibi was injected into 18 patients during acute myocardial infarction and 29 patients 5 to 8 days after myocardial infarction. Tomographic imaging was acquired in gated format (16 frames per R-R cycle of the electrocardiogram) for each set of images. All frames were summed to produce ungated images. Tomographic images were quantified on three different thresholds to define the perfusion defect: 50%, 60%, and 70% of maximal counts. Severity of perfusion defects was calculated as the lowest ratio of minimum/maximum counts on five short-axis slices. Regional wall motion was assessed subjectively on the gated images by cine-loop display. Radionuclide ventriculography was performed at 6 weeks. There was a close correlation between perfusion defect size on ungated images and end-diastolic and end-systolic images independent of the quantitative threshold used (r=0.90 to 0.93; p<0.0001 for all correlations). Gated images provided consistently significantly greater estimates of perfusion defect size and severity by a small increment (3% to 9% of the left ventricle; p<0.05 for all comparisons) independently of the quantitative threshold used or the time of imaging (acute or late). Ungated images provided slightly better correlations with left ventricular ejection fraction at 6 weeks independently of the quantitative threshold used and despite significant wall motion abnormalities present on both the acute and final studies.ConclusionsThe differences between perfusion defect size for gated and ungated images were highly significant as a group, but the magnitude of difference was small and not clinically relevant. The larger estimates provided by end-diastolic gated images are opposite the difference expected if partial volume effects were significantly influencing perfusion defect size. Partial volume effects appear to have minimal impact on clinical tomographic imaging during acute myocardial infarction for the quantification of myocardium at risk and infarct size.

Epicardial coronary artery constriction with intravenous ethanol.

Although in vitro studies have demonstrated ethanol-induced coronary artery constriction, in vivo reports suggest an ethanol-related coronary dilator effect with increases in coronary blood flow. The principal difference in these studies is the demonstration of epicardial coronary constriction with ethanol, while dilation is described only in resistance vessels. Clinical studies have noted evidence of myocardial ischemia following ethanol ingestion in patients with coronary artery disease, suggesting ethanol-related constriction of diseased epicardial coronary arteries. This study hypothesized that intravenous ethanol would constrict canine epicardial coronary arteries while producing arteriolar resistance vessel dilatation. Ten closed-chest mongrel dogs weighing 24 +/- 1 kg (mean +/- SEM) were given 8 g of ethanol intravenously over 30 min. Left anterior descending and circumflex proximal artery diameters were measured by quantitative coronary angiography; myocardial flow was measured by Xenon washout, and myocardial flow distribution was measured with radioactive microspheres. Baseline proximal left anterior descending and circumflex artery areas were 6.3 +/- 0.5 and 5.8 +/- 0.4 mm2, respectively. Up to 30% left anterior descending and circumflex proximal artery narrowing was noted at 60 and 90 min following ethanol infusion. The constriction was reversed with nitroglycerin. There was a decrease in left anterior descending artery flow but no change in circumflex artery flow at 60 min. Blood ethanol level varied from 520 micrograms/ml initially to 205 micrograms/ml 90 min after the infusion terminated (intoxication = 1500 micrograms/ml). These data suggest that ethanol has significant vasoconstrictor action in vivo on epicardial coronary arteries.

Exercise training produces changes in free and conjugated catecholamines

In dogs the concentrations of conjugated dopamine in plasma have previously been shown to increase after exercise training. This study was done to determine whether conjugated norepinephrine and epinephrine also increase. Fifteen dogs were randomly divided into training (N = 8) or sedentary (N = 7) groups. All dogs were exercised acutely for 5 min at 4 mph with a 12% grade, following a 3-min warm-up, before and after either a 12-wk training or a 12-wk sedentary period. Free and conjugated catecholamines were determined in blood drawn at rest and during acute exercise using high-performance liquid chromatography (HPLC) with electrochemical detection. Before training, free norepinephrine, epinephrine, dopamine, and conjugated norepinephrine increased in plasma during acute exercise. Following the 12-wk training period, there were significant increases in free and conjugated dopamine and in conjugated norepinephrine in plasma taken at rest. There were no such increases in resting catecholamines after a 12-wk sedentary period. After either training or sedentary periods, dogs responded to acute exercise with an increase in free norepinephrine and a decrease in conjugated norepinephrine. Thus, after training both conjugated norepinephrine and dopamine, but not conjugated epinephrine, increased in plasma. The data suggest that sulfation of catecholamines increases as a result of exercise training.

Does exercise training alter myocardial creatine kinase Mb isoenzyme content

Skeletal muscle biopsies from highly trained endurance athletes have been shown to contain an increased percentage of the creatine kinase MB (CK-MB) isoenzyme, which has been attributed to continuous regeneration of the skeletal muscle fibers in response to exercise-induced injury. The purpose of this study was to determine whether myocardium undergoes a similar degenerative-regenerative process as a result of exercise training. Fifteen mongrel dogs underwent a 12-wk period of training (N = 8) or cage confinement (N = 7). The animals were then sacrificed, and samples of left and right ventricular myocardium were analyzed for total CK activity and CK-MB isoenzyme content. Percentages of CK-MB were slightly but insignificantly higher from both ventricles of exercise-trained as compared with cage-confined dogs: left ventricle, 4.6 +/- 0.6% vs 3.3 +/- 0.6%, respectively (P = 0.15); right ventricle, 4.0 +/- 0.4% vs 3.0 +/- 0.8%, respectively (P = 0.29). We conclude that chronic exercise training does not induce physiologically important degenerative changes in myocardium.