Toward the bioremediation of dioxin-polluted soil: structural and functional analyses of in situ microbial populations by quinone profiling and culture-dependent methods.

In order to obtain basic information toward the bioremediation of dioxin-polluted soil, microbial communities in farmland soils polluted with high concentrations of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) were studied by quinone profiling as well as conventional microbiological methods. The concentration of PCDD/Fs in the polluted soils ranged from 36 to 4,980 pg toxicity equivalent quality (TEQ) g(-1) dry weight of soil. There was an inverse relationship between the levels of PCDD/Fs and microbial biomass as measured by direct cell counting and quinone profiling. The most abundant quinone type detected was either MK-6 or Q-10. In addition, MK-8, MK-8(H2), and MK-9(H8) were detected in significant amounts. Numerical analysis of quinone profiles showed that the heavily polluted soils (> or = 1,430 pg TEQ g(-1)) contained different community structures from lightly polluted soils (< or = 56 pg TEQ g(-1)). Cultivation of the microbial populations in the heavily polluted soils with dibenzofuran or 2-chlorodibenzofuran resulted in enrichment of Q-10-containing bacteria. When the heavily polluted soil was incubated in static bottles with autoclaved compost as an organic nutrient additive, the concentrations of PCDD/Fs in the soil were decreased by 22% after 3 months of incubation. These results indicate that dioxin pollution exerted a significant effect on microbial populations in soil in terms of quantity, quality, and activity. The in situ microbial populations in the dioxin-polluted soil were suggested to have a potential for the transformation of PCDD/Fs and oxidative degradation of the lower chlorinated ones thus produced.

QRST integral analysis of body surface electrocardiographic mapping for assessing exercise-induced changes in the spatial distribution of local repolarization properties in patients with coronary artery disease and in patients with previous anterior infarction.

We studied resting, postexercise, difference (postexercise - rest) QRST isointegral maps, and the correlation coefficient between resting and postexercise maps. Study I Fifteen controls and 48 patients without previous myocardial infarction were studied. In coronary syndrome X group (n = 14), no patients showed an abnormally negative area on the postexercise map. In coronary ST depression group (n = 26), 12 patients (46%) showed an abnormally negative area on the postexercise map, and the correlation coefficient was low. Although all control, syndrome X, and coronary ST depression patients showed the global-downward type of difference map, coronary ST elevation patients (n = 8) showed the right-downward and left-upward type, right-upward and left-downward type, or reversed saddle type. Coronary ST depression is related to a globally marked decrease in local repolarization forces. Coronary ST elevation is associated with multidirectional changes in local repolarization forces. Study II Fifty-one patients with previous anterior infarction (29 with residual ischemia and 22 without) were studied. The incidence of the global-positive type of maps was increased and that of the saddle-type map was decreased from rest to postexercise in both groups. The global-upward type or right-downward and left-upward type of difference map was observed in both groups, but the reversed saddle type, right-upward and left-downward type, or global-downward type was observed in the residual ischemia group (34%, 24%, and 14%, respectively). Residual ischemia causes multidirectional changes or a global decrease in local repolarization forces. In both studies, multidirectional changes in local repolarization forces may be related to the vulnerability to ventricular arrhythmias.

Sympathetic nervous response relative to the adenosine triphosphate supply-demand imbalance during exercise is augmented in patients with heart failure.

OBJECTIVE: Increase in plasma hypoxanthine (HX) (purine nucleotide degradation product from working muscle) reflects insufficiency of adenosine triphosphate (ATP) supply during exercise, and the exercise-induced increase in plasma norepinephrine (NE) can be an index of sympathetic nerve activity. The aim of this study was to investigate the relationship between plasma NE and plasma HX during exercise in patients with heart failure (HF) according to its severity. METHODS: Blood lactate, plasma HX, and plasma NE were measured at rest and after symptom-limited cardiopulmonary exercise test in 54 patients with HF (New York Heart Association [NYHA] classes I:18, II:20, III:16) and 19 normal subjects. RESULTS: Peak work rate and peak oxygen uptake decreased as the NYHA functional class increased. Blood lactate and plasma HX levels at rest were comparable, but peak blood lactate (normal, NYHA I, II, III: 6.4+/-0.3, 5.6+/-0.4, 5.3+/-0.3, 3.5+/-0.2 mmol/L) and peak plasma HX (3.6+/-0.4, 3.0+/-0.5, 2.4+/-0.3, 1.4+/-0.1 micromol/L) were progressively smaller as HF worsened. Resting plasma NE (137+/-15, 180+/-29, 201+/-21, 318+/-55 pg/mL) was significantly higher in NYHA class III HF, but peak plasma NE (2,235+/-356, 2,021+/-326, 2,188+/-292, 2,210+/-316 pg/mL) was not different among groups. The ratio of the exercise increments in plasma NE to the increments in plasma HX during exercise (deltaplasma NE/deltaplasma HX: 666+/-96, 1,083+/-229, 1,252+/-222, 2,260+/-351) increased according to the severity of HF. CONCLUSION: These data suggest that plasma levels of HX after maximal exercise are smaller as HF worsened, and sympathetic responsiveness to the imbalance of ATP supply-demand during exercise is augmented according to the severity of HF.

Effects of a new angiotensin-converting enzyme inhibitor, alacepril, on changes in neurohormonal factors and arterial baroreflex sensitivity in patients with congestive heart failure.

OBJECTIVE: Patients with heart failure have abnormal neurohormonal regulation during orthostatic stress, and abnormal arterial baroreflex function. This study investigated the effects of alacepril, a new angiotensin-converting enzyme inhibitor with sulfhydryls, on changes in neurohormonal factors during tilt and on the arterial baroreflex control of heart rate. METHODS: Plasma concentrations of noradrenaline, adrenaline, renin activity, angiotensin II, and atrial natriuretic peptide were measured at supine rest and after 30 degrees head-up tilt with measurements of central venous pressure and cardiac dimensions in seven patients with congestive heart failure (65 years, ejection fraction = 34%). Arterial baroreflex control of heart rate was assessed by phenylephrine bolus. The arterial baroreflex test was re-examined 3 h after oral alacepril (37.5 mg). The tilt and arterial baroreflex tests were repeated 12 weeks after alacepril treatment (50 mg x day(-1)). RESULTS: Heart rate, blood pressure, and neurohormonal factors did not differ before and after chronic alacepril, except for a trend toward an increase in renin activity (2.0 vs 4.9 ng x ml(-1) x h(-1)). Head-up tilt decreased central venous pressure (-2.5 mmHg) with a decrease in cardiac dimensions in the pre-alacepril phase. These changes were accompanied by increases in noradrenaline, adrenaline, and angiotensin II and a decrease in atrial natriuretic peptide. After chronic alacepril, the increase in noradrenaline during head-up tilt tended to be smaller (84 vs 30 pg x ml(-1)), with similar changes in central venous pressure (-3.4 mmHg) and cardiac dimensions. Both acute (3.6 vs 4.8 ms mmHg(-1)) and chronic (3.6 vs 6.7 ms mmHg(-1)) alacepril treatment was associated with a trend towards an increase in the arterial baroreflex control of heart rate. CONCLUSION: These results suggest that treatment with alacepril may cause a reduction of sympathetic activation during orthostatic stress and may enhance arterial baroreflex function in patients with mild to moderate heart failure.

Effects of spironolactone on exercise capacity and neurohormonal factors in patients with heart failure treated with loop diuretics and angiotensin-converting enzyme inhibitor.

1. Treatment with spironolactone is reported to be useful when combined with loop diuretics and an angiotensin-converting enzyme (ACE) inhibitor in severe congestive heart failure (CHF). However, the effects of the addition of spironolactone on exercise capacity and neurohormonal variables have not been demonstrated. This study determined the effects of additive spironolactone on exercise capacity and neurohormonal factors in patients with mild CHF. 2. Oxygen uptake (VO2), plasma norepinephrine (NE), renin activity (PRA), angiotensin II (AII), aldosterone (ALD), and atrial natriuretic peptide (ANP) were measured at rest and after peak exercise in nine patients with CHF (six idiopathic and three ischemic cardiomyopathy; New York Heart Association (NYHA) classes II and III) who were already taking furosemide (mean 29 +/- 5 mg/day) and enalapril (mean 4.7 +/- 0.8 mg/day). Studies were repeated after 16 weeks of treatment with additive single daily dose of 25 mg of spironolactone. In four of nine patients, the exercise test was repeated after a 4-weeks washout of spironolactone. 3. Treatment with spironolactone caused natriuresis, decreased cardiothoracic ratio in chest X-ray (before vs. after treatment: 53.7 +/- 1.2 vs. 50.7 +/- 1.4%, P < 0.01), and improved NYHA functional class. Peak VO2 (17.1 +/- 1.6 vs. 17.5 +/- 2.2 ml/min/kg, NS) and heart rate and blood pressure responses to exercise were not altered. Resting NE (215 +/- 41 vs. 492 +/- 85 pg/ml, P < 0.01) and resting PRA (8.2 +/- 2.3 vs. 16.2 +/- 4.1 ng/ml/hr, P < 0.01) as well as peak NE (1618 +/- 313 vs. 2712 +/- 374 pg/ml, P < 0.01) and peak PRA (12.8 +/- 3.2 vs. 28.1 +/- 11.8 ng/ml/hr, P = 0.17) were augmented after additive spironolactone. ALD and AII were insignificantly increased, and ANP was insignificantly decreased at peak exercise after spironolactone treatment. Spironolactone washout was associated with a trend of the neurohormones to return toward pretreatment values. 4. In conclusion, chronic additive treatment with spironolactone was associated with neurohormonal activation both at rest and during exercise without changing the exercise capacity of patients with mild CHF who were already on loop diuretics and ACE inhibitor therapy.

Augmented exercise plasma noradrenaline with impaired chronotropic responsiveness in patients with hypertrophic cardiomyopathy.

1. There is controversy regarding plasma catecholamine levels in patients with hypertrophic cardiomyopathy (HCM) and few data exist on serial plasma catecholamine measurements during exercise. The present study determined whether cardiovascular and plasma catecholamine responses to exercise were altered in patients with HCM. 2. Plasma noradrenaline (NA) and adrenaline were measured at rest, at the end of each stage during exercise and immediately and 5 min after submaximal treadmill exercise in 15 patients with non-obstructive HCM (13 males, two females; mean (+/- SEM) age 54 +/- 3 years) and in 15 age- and sex-matched controls. The ratio of the increment in heart rate (HR) divided by the increment in plasma NA during exercise (delta HR/delta NA) was used as an index of chronotropic sympathetic responsiveness to exercise. 3. Exercise duration was shorter (11.2 +/- 0.6 vs 8.7 +/- 0.6 min for control vs HCM, respectively; P < 0.01) and diastolic blood pressure was significantly higher at stages I and II of modified Bruce protocol HCM. 4. Resting plasma NA levels (149 +/- 17 vs 167 +/- 28 pg/mL for control vs HCM, respectively; NS) were not different, but plasma NA levels at stages I and II were significantly higher in HCM than in controls (243 +/- 26 vs 399 +/- 69 pg/mL (P < 0.05) and 308 +/- 30 vs 548 +/- 110 pg/mL (P < 0.05), respectively). 5. Peak plasma NA levels were not significantly higher in HCM than in controls (578 +/- 59 vs 918 +/- 184 pg/mL, respectively; NS). 6. The ratio delta HR/delta NA was significantly lower in HCM compared with control at stages I and II (0.49 +/- 0.10 vs 0.21 +/- 0.05 (P < 0.05) and 0.38 +/- 0.06 vs 0.20 +/- 0.05 (P < 0.05), respectively). There were no differences in plasma adrenaline responses during exercise between the two groups. 7. Patients with HCM had augmented plasma NA levels during submaximal exercise with a higher diastolic blood pressure response. Chronotropic sympathetic responsiveness was impaired during the early stages of exercise in patients with HCM.

Responses of plasma catecholamines, renin-angiotensin-aldosterone system, and atrial natriuretic peptide to exercise in patients with essential hypertension.

Neurohormonal responses to exercise have not been studied fully in patients with essential hypertension (HT). This study determined if neurohormonal responses to exercise are altered between three subgroups of HT categorized by basal plasma renin activity (PRA). Plasma norepinephrine, epinephrine, atrial natriuretic peptide (ANP), PRA, angiotensin II (AII), and aldosterone were measured at rest and after submaximal treadmill exercise in 39 patients with essential HT (WHO classes I-II) and 13 controls. Patients with HT were divided into three subgroups based on the PRA level [low-renin (< 0.5) HT (n = 14), normal-renin (0.5-2.0) HT (n = 13), and high-renin (> 2.0) HT (n = 12)]. Patients with HT had higher blood pressure during exercise compared to controls, but blood pressure responses were similar among low-, normal-, and high-renin HT. Neurohormonal factors were comparable between all hypertensives and controls, except for higher plasma AII at rest in patients with HT. When neurohormones were compared among three subgroups of HT, plasma norepinephrine and epinephrine responses were similar. Patients with high-renin HT had higher PRA and AII, and lower ANP levels at rest and after exercise. In all hypertensives, negative correlations were observed between resting PRA and resting ANP (r = -0.41, p < 0.01), as well as peak PRA and peak ANP (r = -0.33, p < 0.05). Thus, neurohormonal responses to exercise varied with similar cardiac responses among subgroups of essential HT stratified according to renin levels. Patients with high-renin HT had augmented renin-angiotensin system activity with a decrease in ANP levels both at rest and after exercise. A reciprocal relationship between renin-angiotensin system activity and ANP was observed both at rest and after exercise in HT.

Responses of catecholamines, renin-angiotensin system, and atrial natriuretic peptide to exercise in untrained men and women.

1. Plasma norepinephrine (NE), epinephrine (E), renin activity (PRA), angiotensin II (ATII), aldosterone (ALD), and atrial natriuretic peptide (ANP) were measured in 20 male and 15 female subjects during submaximal treadmill test. 2. Exercise duration was not different between the two groups (male vs. female: 13.4 +/- 0.8 min vs. 11.6 +/- 0.7 min, ns). Female subjects had higher heart rate during exercise, while systolic blood pressure at peak exercise was higher in male subjects. 3. Plasma NE, E, ANP, and ATII responses were comparable between male and female subjects, but PRA both at rest and during exercise and ALD at rest were significantly higher in male subjects. 4. Cardiac responses to submaximal exercise were different between male and female subjects, but neurohormonal responses were comparable between the two groups except for the high PRA at rest and during exercise and high plasma ALD at rest in male subjects.

Effects of enalapril on the exercise capacity and neurohumoral factors during exercise in patients with chronic heart failure.

The effects of enalapril on exercise capacity and neurohumoral factors during exercise were evaluated in 10 patients with heart failure. Echocardiograms and exercise testing with expired gas analysis were performed before and after enalapril. Blood samples were obtained before and after exercise. Both ejection fraction and percent fractional shortening increased with enalapril (p < 0.05). The anaerobic threshold and peak VO2 did not change with enalapril. Epinephrine and norepinephrine levels at peak exercise decreased with enalapril (p < 0.1). Plasma renin both at rest and at peak exercise increased with enalapril (p < 0.1). Angiotensin II was lower after enalapril both at rest and at peak exercise (p < 0.1 and p < 0.05, respectively). Aldosterone was lower after enalapril both at rest and at peak exercise (p < 0.05). Atrial natriuretic peptide (ANP) was lower after enalapril both at rest and at peak exercise. There was no significant correlations between peak VO2 and changes in neurohumoral factors before and after enalapril during exercise. In conclusion, neurohumoral changes with enalapril occurred during exercise even if exercise capacity did not improve. Moreover, the improvement of cardiac function at rest and neurohumoral factors with enalapril did not lead to a change of exercise capacity.

Augmented response in plasma atrial natriuretic peptide to dynamic exercise in patients with congestive heart failure.

Neurohormonal activation is present and neurohormonal responses to dynamic exercise are altered in patients with congestive heart failure (CHF). The aim of this study was to determine if the responses of atrial natriuretic peptide (ANP) normalized for peak oxygen consumption (peak VO2) to exercise are augmented in patients with CHF. Ventilatory and ANP responses were assessed in 28 patients with CHF (NYHA classes II: 16, III: 12), 17 patients in NYHA class I, and 14 normal subjects during symptom-limited cardiopulmonary exercise testing. Plasma ANP was measured at rest and immediately after peak exercise. The increase in ANP was divided by peak VO2 and this ratio [ANP-Exercise Ratio: (peak ANP-rest ANP)/peak VO2] was compared among the 3 groups. Peak VO2 (Normal, NYHA I, CHF: 29.9 +/- 1.7, 24.0 +/- 1.3, 17.4 +/- 0.8 ml/min per kg), anaerobic threshold and peak work rate were lower in patients with CHF. The resting ANP level was significantly higher in patients with CHF (Normal, NYHA I, CHF: 35.4 +/- 4.6, 42.9 +/- 5.8, 80.8 +/- 12.9 pg/ml). The ANP level increased during exercise in all 3 groups, and patients with CHF had a significantly higher ANP level than normal subjects and NYHA class I patients (Normal, NYHA I, CHF: 65.3 +/- 10.7, 75.9 +/- 14.4, 141.6 +/- 20.1 pg/ml). The ANP-Exercise Ratio in patients with CHF was significantly higher than those in normal subjects and NYHA class I patients (Normal, NYHA I, CHF: 0.96 +/- 0.26, 1.32 +/- 0.38, 3.59 +/- 0.72). These data suggest that patients with CHF but not those in NYHA class I have an augmented ANP response, as reflected by both absolute ANP levels and by the exercise ratio, which was normalized by the peak exercise level.

Catecholamines, renin-angiotensin-aldosterone system, and atrial natriuretic peptide at rest and during submaximal exercise in patients with congestive heart failure.

The aim of this study was to determine the responses of plasma catecholamines, renin-angiotensin-aldosterone (RAA) activity, and plasma atrial natriuretic peptide (ANP) to exercise in patients with congestive heart failure (CHF). Cardiac and neurohormonal responses were assessed during submaximal treadmill exercise testing in 23 patients with CHF (New York Heart Association classes I-III) and 13 control subjects (without CHF). Plasma norepinephrine, epinephrine, renin activity (PRA), angiotensin II (ATII), aldosterone, and ANP were measured at rest and immediately after exercise. Exercise duration was shorter in patients with CHF (control, 10.4 +/- 0.9 minute; CHF, 6.2 +/- 0.7 minute; P < 0.01). Heart rate and blood pressure responses were similar except for the smaller peak heart rate (control, 145 +/- 5 beats per minute; CHF, 129 +/- 4 beats per minute; P < 0.05) and higher systolic blood pressure at recovery stage (control, 122 +/- 4 mm Hg; CHF, 142 +/- 4 mm Hg; P < 0.01) in patients with CHF. At rest, plasma norepinephrine levels were insignificantly higher in patients with CHF (control, 110 +/- 10 pg/mL; CHF, 170 +/- 26 pg/mL; P = 0.09), and ANP levels (control, 40 +/- 5 pg/mL; CHF, 94 +/- 17 pg/mL; P < 0.05) and PRA levels (control, 0.77 +/- 0.11 ng/mL/hr; CHF, 4.33 +/- 1.25 ng/mL/hr; P < 0.05) were significantly higher. There were no differences in peak norepinephrine, epinephrine, or ANP between the two groups. Angiotensin II and aldosterone levels were similar between the two groups, although, in patients with CHF, there was a trend toward higher levels of ATII while at rest (control, 12.4 +/- 1.4 pg/mL; CHF, 20.3 +/- 3.3 pg/mL; P = 0.08) and at peak (control, 20.5 +/- 1.8 pg/mL; CHF, 41.0 +/- 9.4 pg/mL; P = 0.10). Peak values of PRA, ATII, and aldosterone positively correlated with respective resting values of PRA (r = 0.88 ng/mL/hr, P < 0.01), ATII (r = 0.63 pg/mL, P < 0.01), and aldosterone (r = 0.99, P < 0.01). Peak norepinephrine and peak ANP also positively correlated with respective resting values of norepinephrine (r = 0.58 pg/mL, P < 0.05) and ANP (r = 0.94, P < 0.01). Analysis of these results showed that patients with CHF had significantly higher levels of PRA and ANP at rest, and a trend toward augmentation in RAA system activity during exercise with less exercise workload. Basal level of neurohormones seemed to be an important determinant for the degree of exercise-induced neurohormonal activation in patients with CHF.

Exercise-induced U-wave changes in patients with coronary artery disease--correlation with tomographic thallium-201 myocardial imaging.

We studied the relation between exercise-induced U-wave changes and the site of a reversible defect in tomographic 201Tl myocardial imaging. Coronary artery disease and control groups consisted of 116 and 42 patients, respectively. In the anteroapical-ischemia group (n = 37), the sensitivity of U-wave inversion in the anterior precordial leads for ischemia was 62% (23/37) and that of prominent U-waves without an increase in the height of the T-wave in the inferior limb leads was 57% (21/37). In this group, 18 patients (49%) met both criteria (18 [78%] of 23 patients with the former; 18 [86%] of 21 patients with the latter). In the posterior-ischemia group (n = 59), the sensitivity of prominent U-waves with a decrease in the height of the T-wave in the anterior precordial leads for ischemia was 63% (37/59) and that of U-wave inversion in the inferior limb leads was 20% (12/59). In this group, 12 patients (20%) met both criteria (12 [32%] of 37 patients with the former; all 12 patients with the latter). The specificity of U-wave criteria was 100%. In the anteroapical and posterior ischemia group (n = 20), the sensitivity of U-wave criteria for anteroapical and posterior ischemia was 85% (17/20) and 40% (8/20), respectively. In conclusion, U-wave criteria are not only specific but also sensitive for myocardial ischemia determined by 201Tl imaging.

Responses of plasma norepinephrine and renin-angiotensin-aldosterone system to dynamic exercise in patients with congestive heart failure.

BACKGROUND: Neurohormonal activation is present and neurohormonal responses to dynamic exercise are altered in congestive heart failure (CHF). Responses of plasma norepinephrine in various degrees of heart failure have been investigated, but the responses of the renin-angiotensin-aldosterone system have not been studied in relation to the severity of CHF. The aim of this study was to determine if the responses of the renin-angiotensin-aldosterone system to exercise are augmented according to the severity of CHF. METHODS AND RESULTS: Ventilatory and neurohormonal responses were assessed in 38 patients with CHF (New York Heart Association class: I, 13 patients; II, 14 patients; III, 11 patients) and 11 normal subjects during symptom-limited cardiopulmonary exercise testing. Plasma norepinephrine, renin activity, angiotensin II, and aldosterone were measured at rest and at peak exercise. The increments in neurohormones were divided by peak oxygen consumption, and these ratios (norepinephrine exercise ratio, plasma renin activity-exercise ratio, angiotensin II-exercise ratio, aldosterone-exercise ratio) were compared among groups. Peak oxygen consumption and anaerobic threshold decreased progressively with the severity of CHF. Neurohormonal profiles at rest showed that plasma norepinephrine levels were significantly higher, and the renin-angiotensin-aldosterone system was augmented only in patients with class III CHF. Neurohormones increased during exercise both in patients with CHF and in normal subjects, but patients with class III CHF had significantly higher plasma renin activity (10.11 +/- 2.32 ng/mL/h), angiotensin II (73.9 +/- 14.2 pg/mL), and aldosterone (265.2 +/- 61.1 pg/mL) than did normal subjects. Plasma renin activity-exercise ratio, angiotensin II-exercise ratio, and aldosterone-exercise ratio in patients with class III CHF were significantly higher compared to normal subjects. This augmentation of the renin-angiotensin-aldosterone system was not observed in class I or II patients. Peak plasma norepinephrine levels were not different among normal subjects and subgroups of CHF patients, but the norepinephrine-exercise ratio was significantly higher in classes II and III CHF compared to normal subjects. CONCLUSIONS: These data suggest that neurohormonal excitation during exercise increases along with the severity of CHF when normalized for peak exercise level.

Ammonia response to exercise in patients with congestive heart failure.

OBJECTIVE: To assess energy depletion in skeletal muscle in patients with congestive heart failure by measuring blood purine metabolites during exercise and, at the same time, determine the implications of the ammonia response to exercise in these patients. SETTING: Tottori University Hospital, Yonago, Japan. PATIENTS: 49 heart failure patients (New York Heart Association (NYHA) grades I-III) and 16 normal subjects. MAIN OUTCOME MEASURES: Blood lactate, ammonia, and hypoxanthine levels were measured during exercise with expired gas analysis. RESULTS: In normal exercising subjects as well as in each heart failure subgroup, the ammonia threshold was significantly higher than both the lactate threshold [control: 21.8 (SD 5.3) v 17.4 (3.3) ml/kg/min; NYHA class I: 18.9 (3.8) v 15.5 (2.6); class II: 14.8 (2.5) v 12.7 (2.4); class III: 13.5 (2.6) v 11.8 (2.5)] and the ventilatory threshold (P < 0.01). The difference between the ammonia and lactate thresholds was noted in all normal subjects and in all heart failure patients. The ammonia threshold, however, was significantly lower in heart failure patients than in normal subjects and it decreased with increasing NYHA class (P < 0.01). Maximum ammonia levels were lower in the heart failure group and decreased further with higher NYHA classifications [control: 198 (52) mg/dl; NYHA class I: 170 (74); class II: 134 (58); class III: 72 (15); P < 0.01]. There were significant correlations between maximum ammonia values and maximum lactate, oxygen consumption, and hypoxanthine levels (r = 0.74, 0.48, and 0.87, respectively; P < 0.001). CONCLUSIONS: The ammonia threshold may reflect the onset of ATP depletion in exercising skeletal muscles, as opposed to the onset of anaerobic respiration. It seems therefore that energy depletion in skeletal muscles during exercise occurs after attaining the anaerobic threshold. Both aerobic and anaerobic capacities of skeletal muscle are reduced in patients with congestive heart failure.

Plasma concentrations and coronary vasodilation after sublingual and intracoronary administration of isosorbide dinitrate.

To investigate the relationship between plasma levels and coronary vasodilation after administration of isosorbide dinitrate (ISDN), the plasma concentration and diameters of six segments of the left coronary artery were measured before and after sublingual (SL) ISDN (5 mg) and left intracoronary (IC) administration of ISDN (3 mg) in 12 patients. After SL-ISDN, the systolic aortic pressure decreased with no significant concomitant changes in heart rate or diastolic aortic pressure. After IC-ISDN, all hemodynamic parameters showed significant changes, and these were greater after IC-ISDN than those after SL-ISDN. The individual mean vasodilation of six segments induced by SL- and IC-ISDN, were 23 +/- 9 and 35 +/- 11% (p < 0.01), respectively. Before SL-ISDN, ISDN was not detected in plasma. After SL- and IC-ISDN, however, the plasma values of the ISDN were 36.1 +/- 53.3 and 101.5 +/- 90.0 ng/ml (p < 0.01), respectively. Thus, both coronary vasodilative responses and plasma ISDN levels after IC-ISDN were significantly greater than those after SL-ISDN. However, neither the individual mean coronary vasodilation nor the hemodynamic changes correlated significantly with plasma ISDN levels. Consequently, with administration of the same dose, the coronary vasodilative response to ISDN did not correlate with plasma levels. Furthermore, IC-ISDN dilutes coronary arteries more effectively than SL-ISDN.

Exercise-induced ST-segment elevation--role of left ventricular wall motion abnormalities and coronary artery narrowing.

We studied the causes of exercise-induced ST-segment elevation. Group I consisted of 15 patients with anterior myocardial infarction in the absence of a coronary artery luminal narrowing of 75% or more. Group II consisted of 36 patients with predominantly exertional angina and a luminal narrowing of 90% or more in the left anterior descending coronary artery in the absence of previous myocardial infarction. In group I, exercise-induced ST-segment elevation occurred frequently during treadmill exercise (15/15, 100%). None of the patients showed 201Tl redistribution. The standard deviation of the phase in radionuclide ventriculography increased during bicycle exercise. Of group II patients, only those with 99% narrowing and poor collaterals showed exercise-induced ST-segment elevation (13/14, 93%), whereas none of those with complete occlusion or 99% narrowing and good collaterals, or 90% narrowing showed ST-segment elevation. In group II, patients with exercise-induced ST-segment elevation showed lower 201Tl uptake during exercise and washout in the territory of the diseased vessel than those without exercise-induced ST-segment elevation. In conclusion, wall motion abnormalities may cause exercise-induced ST-segment elevation independently of myocardial ischemia. In patients with predominantly exertional angina, exercise-induced ST-segment elevation may be a marker for 99% narrowing with poor collaterals and severe myocardial ischemia.

Neurohumoral factor responses to mental (arithmetic) stress and dynamic exercise in normal subjects.

We examined the responses of plasma catecholamine and plasma renin activity (PRA) during mental (arithmetic) stress and dynamic exercise in 15 normal subjects. Compared to rest values, there was a significant increase in the plasma epinephrine concentration (E), but not in the plasma norepinephrine concentration (NE) or PRA during mental arithmetic. During dynamic exercise, there were significant increases in both NE and E and in PRA. The ratio of E to NE was significantly higher during mental arithmetic than during dynamic exercise. NE was significantly correlated with PRA at rest, during mental arithmetic and dynamic exercise. No significant correlations were observed between E and PRA. Dynamic exercise primarily induces a sympathetic nervous response, and mental (arithmetic) stress mainly induces an adrenal response. The renin-angiotensin-aldosterone system response may in part be regulated by sympathetic nervous activity during both mental (arithmetic) stress and dynamic exercise.

Nicorandil suppressed myocardial purine metabolism during exercise in patients with angina pectoris.

To elucidate the effect of Nicorandil on myocardial energy metabolism and myocardial sympathetic activity, we administered Nicorandil orally to eight patients with angina pectoris prior to exercise testing. Arterial and coronary sinus levels of lactate, ammonia, hypoxanthine (HX), adrenaline and noradrenaline were measured during exercise in order to determine the irrespective myocardial extraction ratios (MER). Compared to placebo, Nicorandil increased the time to development of significant ST depression (322 vs 390 s) while decreasing the maximum amplitude of ST depression (0.244 vs 0.216 mV). Heart rate, systolic blood pressure, and the rate pressure product during exercise were not significantly affected. The MER of lactate, measured during exercise, was significantly higher after Nicorandil than placebo (13.6 vs 27.9). Similarly, the MERs of ammonia and HX were significantly higher after Nicorandil (-46.0 vs 7.4% and -47.0 vs 9.9% respectively). Nicorandil, had no apparent effect on myocardial sympathetic activity as the MERs of adrenaline and noradrenaline were essentially unaffected. We conclude that Nicorandil decreased myocardial ischaemia and suppressed myocardial accelerated purine metabolism (a marker of cellular energy metabolism) during exercise in patients with angina pectoris. This effect appears not to be related to myocardial sympathetic activity.

Perfusion reserve of coronary collateral circulation and its significance in the development of exercise-induced ischemia in patients with multivessel disease.

To assess the perfusion reserve of coronary collateral circulation, we analyzed exercise-stress tomographic thallium-201 myocardial images in 12 patients who had total occlusion in the right coronary artery (RCA) or left circumflex coronary artery (LCX) with well-developed collateral circulation and 90% stenosis in the left anterior descending coronary artery (LAD). In 6 of the 12 patients, the collateral circulation was non-jeopardized (group A). In the remaining 6 patients, the collateral circulation was jeopardized (group B). All 6 of the patients in group A had an exercise-induced decrease in thallium uptake in the segments supplied by the occluded RCA or LCX with collateral circulation, and 3 (50%) of these 6 also showed a decrease in thallium uptake in the segments supplied by the LAD. All 6 of the patients in group B also had an exercise-induced decrease in thallium uptake in the segments supplied by the occluded RCA or LCX with collateral circulation, but none showed a decrease in thallium uptake in the segments supplied by the LAD. In conclusion, the perfusion reserve of collateral circulation is equal to or less than 90% stenosis and myocardial ischemia occurs first in the collateralized segments during exercise in patients with jeopardized collateral circulation.

Case report: a case of multiple coronary artery to left ventricular communications.

A 39-year-old man with anginal pain had multiple coronary artery to left ventricular communications. His electrocardiogram showed evidence of left ventricular hypertrophy, and an echocardiogram revealed a dilated left ventricle. A coronary angiogram revealed multiple coronary artery to left ventricular fistulae involving three major coronary arteries with no evidence of atherosclerotic lesions. Only 17 cases of such fistulous communications involving three major coronary arteries have been reported in the literature. It is suggested that the fistulous communications to the left ventricle was a cause of his angina pectoris, probably because of the coronary steal phenomenon.