Comparison of [18F]FDG-PET, [99mTc]-HMPAO-SPECT, and [123I]-iomazenil-SPECT in localising the epileptogenic cortex.

OBJECTIVES: Firstly, to compare the findings of interictal 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and of single photon emission computed tomography (SPECT) using 99mTc-hexamethyl propylene-amine-oxime (HMPAO) and 123I-iomazenil in localising the epileptogenic cortex in patients who were candidates for epilepsy surgery, but in whom clinical findings, video EEG monitoring (V-EEG), MRI, and neuropsychological evaluations did not give any definite localisation of the seizure onset. Secondly, to assess the ability of these functional methods to help in the decision about the epilepsy surgery. METHODS: Eighteen epileptic patients were studied with FDG-PET and iomazenil-SPECT. HMPAO-SPECT was performed in 11 of these 18 patients. Two references for localisation was used--ictal subdural EEG recordings (S-EEG) and the operated region. RESULTS: Fifteen of 18 patients had localising findings in S-EEG. FDG-PET findings were in accordance with the references in 13 patients and iomazenil-SPECT in nine patients. HMPAO-SPECT visualised the focus less accurately than the two other methods. In three patients S-EEG showed independent bitemporal seizure onset. In these patients FDG-PET showed no lateralisation. However, iomazenil-SPECT showed temporal lobe lateralisation in two of them. CONCLUSION: FDG-PET seemed to localise the epileptogenic cortex more accurately than interictal iomazenil-SPECT in patients with complicated focal epilepsy.

Coronary flow reserve is impaired in young men with familial hypercholesterolemia.

OBJECTIVES: We sought to investigate whether functional abnormalities in coronary vasomotion exist in young adults by studying 15 men (age 31 +/- 8 years [mean +/- SD]) with familial hypercholesterolemia (FH) and a matched group of 20 healthy control subjects. BACKGROUND: Precursors of morphologic coronary artery disease are known to be present in adolescents and young adults with a high risk factor profile. METHODS: Myocardial blood flow was measured at the basal state and during dipyridamole-induced hyperemia using positron emission tomography and oxygen-15-labeled water. RESULTS: Serum total and low density lipoprotein cholesterol concentrations were higher in the patients than in the control subjects (mean +/- SD): 7.7 +/- 1.9 versus 5.3 +/- 1.5 mmol/liter (298 +/- 73 vs. 205 +/- 58 mg/dl) and 6.1 +/- 1.8 versus 3.5 +/- 1.4 mmol/liter (236 +/- 70 vs. 135 +/- 54 mg/dl), respectively (both p < 0.001). The baseline myocardial blood flow was similar in the patients and control subjects: 0.92 +/- 0.24 versus 0.83 +/- 0.13 ml/g per min, respectively (p = 0.21). A significant increase in flow was observed in both groups after dipyridamole infusion, but the flow at maximal vasodilation was 29% lower in the patients: 3.19 +/- 1.59 versus 4.49 +/- 1.27 ml/g per min (p = 0.011). Consequently, coronary flow reserve (the ratio of hyperemia flow to basal flow) was 35% lower in the patients than in the control subjects: 3.5 +/- 1.6 versus 5.4 +/- 1.5 (p = 0.0008). Total coronary resistance during hyperemia was higher in the patients than in the control subjects: 36 +/- 25 versus 21 +/- 10 mm Hg/min per g per ml (p = 0.045). Coronary flow reserve was inversely associated with serum total cholesterol concentration: r = -0.43 (p = 0.009). CONCLUSIONS: Coronary flow reserve is reduced in young men with FH, and, consequently, coronary resistance during hyperemia is increased. The results demonstrate very early impairment of coronary vasomotion in hypercholesterolemic patients.

Glucose uptake in the chronically dysfunctional but viable myocardium.

BACKGROUND: The regulation of glucose uptake in the dysfunctional but viable myocardium has not been studied previously in humans. METHODS AND RESULTS: Seven patients with an occluded major coronary artery but no previous infarction were studied twice with 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography, once in the fasting state and once during hyperinsulinemic euglycemic clamping. Myocardial blood flow was measured with [(15)O]H2O. The myocardial region beyond an occluded artery that showed stable wall-motion abnormality represented chronically dysfunctional but viable tissue. Six of the patients were later revascularized, and wall-motion recovery was detected in the corresponding regions, which confirmed viability. A slightly reduced myocardial blood flow was detected in the dysfunctional than in the remote myocardial regions (0.81 +/- 0.27 versus 1.02 +/- 0.23 mL x g(-1) x min(-1),P=.036). In the fasting state, glucose uptake was slightly increased in the dysfunctional regions compared with normal myocardium (15 +/- 10 versus 11 +/- 10 micromol/100 g per minute, P=.038). During insulin clamping, a striking increase in glucose uptake by insulin was obtained in both the dysfunctional and the normal regions (72 +/- 22 and 79 +/- 21 micromol/100 g per minute, respectively; P<.001, fasting versus clamping). CONCLUSIONS: Contrary to previous suggestions, glucose uptake can be increased strikingly by insulin in chronically dysfunctional but viable myocardium. This demonstrates that insulin control over glucose uptake is preserved in the dysfunctional myocardium and provides a rational basis for metabolic intervention.

Insulin increases blood volume in human skeletal muscle: studies using [15O]CO and positron emission tomography.

High insulin concentrations increase blood flow in the leg, but it is unknown whether this effect is associated with a change in muscle blood volume. In the present study, we used positron emission tomography combined with inhalation of [15O]carbon monoxide to quantitate the effect of insulin on skeletal muscle blood volume in humans. The reproducibility of the method was determined from two consecutive measurements performed in the basal state in five normal subjects. The coefficient of variation of the repeated measurements was 3.0 +/- 1.8%. In 14 normal subjects [age 35 +/- 3 yr, body mass index 24.9 +/- 1.3 (SE) kg/m2], skeletal muscle blood volume was determined in the femoral region in the basal state and during euglycemic hyperinsulinemia (serum insulin 3,200 +/- 190 pmol/l). The mean muscle blood volume was 3.3 +/- 0.1 ml/0.1 kg muscle in the basal state. Insulin increased muscle blood volume by 9 +/- 2% to 3.6 +/- 0.2 ml/0.1 kg muscle (P < 0.01). The rate of whole body glucose uptake was 53 +/- 6 mumol.kg-1.min-1 and correlated with muscle blood volume during insulin stimulation (r = 0.65, P < 0.02). We conclude that high insulin concentrations exert a true vasodilatory effect in human skeletal muscle.

The effect of insulin and FFA on myocardial glucose uptake.

In addition to direct stimulation of glucose uptake and metabolism in cardiac myocytes, insulin inhibits lipolysis and, thereby, reduces serum free fatty acid (FFA) concentrations. This, in turn, has been suggested to enhance myocardial glucose utilization. To study the mechanism of insulin action on myocardial glucose uptake (MGU) in vivo, five patients with stable coronary artery disease were studied with positron emission tomography (PET) and [18F]FDG. All patients underwent two PET studies after a 12-h fast, once during low serum FFA but high insulin concentrations (during insulin clamp), and once during low serum FFA and low insulin concentrations (in the fasting state after two oral doses of 250 mg of an antilipolytic drug, acipimox). The MGU in the normal myocardium was measured using dynamic PET imaging. Plasma glucose concentrations were comparable during the insulin clamp and after administration of acipimox (5.0 +/- 0.4 v 5.2 +/- 0.3 mmol/l, n.s.). Serum insulin concentrations were high during clamp but remained in low fasting concentrations after acipimox (74 +/- 9 mU/l v 6 +/- 5 mU/l, P = 0.0001). Serum FFA concentrations were similar during both approaches (230 +/- 110 v 200 +/- 40 mumol/l, respectively, n.s.). No difference in cardiac work load was detected between the approaches. The calculated MGU values in normal myocardium were similar during both approaches (57 +/- 23 mumol/min/100 g v 61 +/- 14 mumol/min/100 g, respectively, n.s.). The MGU values correlated inversely to serum FFA concentration (r = -0.87, P = 0.001) and directly to myocardial work load (r = 0.73, P = 0.016) but not to serum insulin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhancement of myocardial [fluorine-18]fluorodeoxyglucose uptake by a nicotinic acid derivative.

UNLABELLED: Recently, the euglycemic hyperinsulinemic clamp technique was shown to give excellent image quality during metabolic steady-state conditions. Acipimox is a new potent nicotinic acid derivative that rapidly reduces serum free fatty acid (FFA) levels by inhibiting lipolysis in peripheral tissue. METHODS: To compare the effects of acipimox administration and insulin clamp on [18F]fluorodeoxyglucose ([18F]FDG) uptake and myocardial glucose utilization, five nondiabetic and seven type II diabetic patients who had had previous myocardial infarctions were studied twice: once during a clamp study and once after the administration of acipimox (2 x 250 mg orally). All patients also underwent resting SPECT perfusion imaging prior to PET scans. RESULTS: The patients tolerated acipimox well. Although fasting plasma glucose levels were higher in diabetic patients (9.2 +/- 3.4 versus 5.5 +/- 0.3 mM, p = 0.03), they were decreased both during clamping and after acipimox; during imaging, no significant differences between the groups and approaches were detected. By visual analysis, the image quality and myocardial [18F]FDG uptake patterns were similar during clamping and after acipimox. Compared with the relative [18F]FDG uptake values obtained during clamping, acipimox yielded similar results in normal, mismatch and scar segments (r = 0.88, p = 0.0001). Similar rMGU values were also obtained during both approaches. CONCLUSION: Thus, PET imaging with [18F]FDG after the administration of acipimox is a simple and feasible method for clinical viability studies both in nondiabetic and diabetic patients. It results in excellent image quality and gives rMGU levels similar to the insulin clamp technique.

Myocardial viability: fluorine-18-deoxyglucose positron emission tomography in prediction of wall motion recovery after revascularization.

To assess the value of positron emission tomography (PET) imaging with fluorine-18-deoxyglucose ([18F]FDG) in predicting cardiac wall motion recovery after revascularization, 48 consecutive patients with previous myocardial infarction were studied. The normalized [18F]FDG uptake at rest was assessed semiquantitatively and compared to perfusion at rest as studied by SPECT imaging. Wall motion was analyzed with echocardiography before and after revascularization. Wall motion recovery occurred in 27 (30%) of the revascularized 90 dysfunctional segments. Preserved [18F]FDG uptake (mean +/- 2 SD) was commonly found in dysfunctional segments, but only 54% of these segments recovered after revascularization. Subnormal [18F]FDG uptake identified accurately the segments with no potential to recover (predictive value 100%). By using an optimized threshold value for normalized [18F]FDG uptake, the sensitivity of 85% and specificity of 84% to predict functional recovery were reached simultaneously. However, in the segments with moderately or severely reduced perfusion at rest, the diagnostic accuracy of [18F]FDG uptake for viability was 100%. The results of this study show that the presence of viable tissue indicated by preserved [18F]FDG uptake does not inevitably imply functional recovery after revascularization. However, acceptable diagnostic accuracy for viability might be reached by [18F]FDG alone, providing that appropriate uptake limits are used. The combined evaluation of [18F]FDG uptake and perfusion enables precise assessment of myocardial viability.

The value of quantitative analysis of glucose utilization in detection of myocardial viability by PET.

To study whether absolute quantitation of regional myocardial glucose utilization (rMGU) enhances detection of myocardial viability, 70 nondiabetic patients with prior myocardial infarction and angiographically confirmed coronary artery disease were studied with [18F]FDG PET after oral glucose loading. Forty-eight patients were also revascularized and underwent echocardiography after revascularization to detect wall motion recovery. The rMGU was calculated in eight myocardial segments in each patient and the results were compared to normalized (relative) [18F]FDG uptake values. In normal segments (n = 225), rMGU was 56 +/- 18 mumole/min/100 g (mean +/- s.d.) and relative [18F]FDG uptake 97% +/- 12%. The interindividual variation of rMGU in normal myocardium was greater than the intraindividual variation (s.d. 31% versus 11%). The respective values for relative [18F]FDG uptake were 9% and 10%. Both rMGU and [18F]FDG uptake were significantly reduced in segments with scarring observed visually during bypass surgery (29 +/- 19 mumole/min/100 g and 45% +/- 22%, n = 26). The rMGU and [18F]FDG uptake were higher in segments that recovered after revascularization (53 +/- 17 mumole/min/100/g and 110% +/- 21%, n = 27) than in those that did not (37 +/- 20 mumole/min/100 g and 65% +/- 24%, n = 63). However, due to larger variability of rMGU values, normalized [18F]FDG uptake was superior to rMGU in separating normal and scar segments as well as in predicting wall motion recovery. We conclude that rMGU variability is notable and is caused mainly by variations between patients. Interindividual variation is reduced by normalization, which results in more accurate assessment of myocardial viability. Thus, static imaging and semiquantitative analysis are sufficient for the clinical assessment of myocardial viability.

Pulmonary manifestations in lysinuric protein intolerance.

STUDY OBJECTIVES: To evaluate the pulmonary manifestations and the course of acute respiratory insufficiency associated with lysinuric protein intolerance (LPI). DESIGN: Retrospective review of clinical data and chest radiographs (total 225) obtained during the lifetime follow-up of 31 LPI patients. About half of the 25 patients without respiratory symptoms underwent high-resolution computed tomography (HRCT) of the lungs, radionuclide perfusion imaging, whole body plethysmography, and diffusing capacity measurements. PATIENTS: Thirty-one Finnish patients with LPI. RESULTS: During the follow-up period, four children with LPI died in respiratory insufficiency, 1 adult had an episode of respiratory insufficiency, and another had chronic symptoms, whereas 25 patients remained symptom-free. The radiologic findings in acute progressive respiratory insufficiency were uniform: at first, reticulonodular interstitial densities and, later on, progressive airspace disease. At autopsy, three patients showed pulmonary alveolar proteinosis and one had pulmonary hemorrhage and cholesterol granulomas. One adult had reversible respiratory insufficiency with signs of bronchiolitis obliterans, another adult had recurrent episodes of chest pain, dyspnea, and hypoxia. Of the symptom-free patients, one third (8 of 25) had signs suggestive of pulmonary fibrosis evidenced on chest radiographs and two thirds (8 of 14) had signs evidenced by HRCT films. Most symptom-free patients showed mild abnormalities either in perfusion imaging (9 of 12) or in function tests (8 of 12). CONCLUSION: In childhood, patients with LPI are highly predisposed to develop pulmonary hemorrhages and alveolar proteinosis. Interstitial lung densities may precede the acute phase. Most adult LPI patients show radiologic signs of interstitial lung disease but only a few show clinical impairment.

Accuracy of the Jamar dynamometer.

The purpose of the study was to check the calibrations of six Jamar dynamometers. Five handle positions were tested for each instrument, with the application of seven different external forces, from 5 kg to 60 kg. Between two testers the repeatability was also evaluated. Major differences in testing accuracies were not found according to different breadths of grip. The repeatability of testing accuracy among the two examiners was rather good, varying in average from only 1.2 kg to 1.4 kg per handle position. The error of absolute kilograms increased relating to heavier loads, but the percentage error decreased when the load increased. The accuracy of the older dynamometers was poorer than the accuracy of the newer ones. The normative values of hand grip related to different handle positions are reviewed.

Grip strength and hand position of the dynamometer in 204 Finnish adults.

A primary purpose of this study was to establish data on hand strength by Jamar dynamometer for normal Finnish adults aged 30 to 50 years. A second aim was to find out how five various breadths of grip affect the strength value. A sample of 103 male and 101 female adults, aged 19 to 62, from the southern part of Finland were tested using standardized positioning and instructions. Male and female subjects reached the highest grip strength using the third handle breadth of dynamometer, except females over 50 years. Female grip strength was 60% to 70% less than male grip strength. There was no significant difference in strength between dominant and non-dominant hands.

Euglycemic hyperinsulinemic clamp and oral glucose load in stimulating myocardial glucose utilization during positron emission tomography.

To enable assessment of myocardial viability, myocardial glucose utilization has commonly been stimulated by oral glucose loading. To compare the effects of glucose loading and insulin and glucose infusion (insulin clamp) on PET fluorodeoxyglucose ([18F]FDG) myocardial scan image quality and regional myocardial glucose utilization rate (rMGU), eight patients with angiographically documented coronary artery disease and previous myocardial Q-wave infarction were studied twice, once during insulin clamp and once 1 hr after oral glucose loading. The rMGU rates were derived by graphic Patlak analysis in 33 normal, 10 scar and 6 "hot spot" myocardial segments. Infusion of insulin and glucose gave stable plasma-glucose and serum-insulin levels during imaging. In contrast, glucose loading caused marked changes in plasma-glucose and insulin concentrations. The image quality was clearly superior and the fractional utilization rates of [18F]FDG were twice as high during insulin clamp than after glucose loading (p less than 0.0001). Due to the higher plasma-glucose levels after glucose loading, the calculated rMGU in normal, scar and hot spot myocardial segments was comparable between the two protocols. The insulin clamp technique makes it possible to adjust and maintain a metabolic steady state during the PET study. It does not alter [18F]FDG uptake patterns in different myocardial areas when compared to the standard glucose loading protocol, but this technique results in superior image quality and permits the use of smaller [18F] FDG patient doses.

Acute and long-term effects on myocardial ischemia of intermittent and continuous transdermal nitrate therapy in stable angina.

The aim of this study was to compare the efficacy and safety of continuous and intermittent transdermal nitrate therapy using ambulatory electrocardiographic (Holter) monitoring. Eighty-five patients with stable angina pectoris and positive exercise test results participated during their concomitant antiischemic medication in a randomized open trial lasting 12 weeks. After a 3-week run-in period with continuous therapy (10 mg/24 hours), patients were randomized to either continuous- or intermittent-therapy groups. In the intermittent-therapy group the patients removed their patch at night (the mean patch-off period was 10 hours). Forty-eight-hour Holter monitoring was performed in each patient after randomization, and again after 2 and 12 weeks. Eighteen patients withdrew, 9 in each group. A total of 11,194 hours of electrocardiography were recorded and 607 ischemic episodes were detected, of which 79% were asymptomatic and 95% appeared during daytime. The number of ischemic episodes per 48 hours with intermittent therapy was 3.1 +/- 0.7 (mean +/- SEM) after randomization, 1.8 +/- 0.4 at 2 weeks and 2.0 +/- 0.6 at 12 weeks. With continuous therapy the respective numbers were 3.8 +/- 1.1, 3.5 +/- 0.9 and 4.2 +/- 1.2. The differences were not statistically significant because a large number of patients (30%) had no ischemic episodes on Holter recording. However, when examining 47 patients with episodes during the study, the number of episodes was significantly reduced in the intermittent-therapy group (p less than 0.05 at 12 weeks). The changes in asymptomatic and symptomatic episodes were concordant. No changes and differences between the treatment groups were seen in nighttime episodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Carvedilol and atenolol once daily in the treatment of hypertension.

Fifty milligrams of carvedilol and 100 mg atenolol were administered in a random order once a day for 2 months to 43 patients with mild to moderate hypertension, in a double-blind crossover study. Blood pressure, heart rate and peripheral blood flow parameters (n = 11) were recorded 2 and 24 h after the drug administration. Supine blood pressure was the same 2 h after both carvedilol and atenolol administration, but carvedilol caused a greater decrease in standing systolic blood pressure 2 h after the administration (P less than 0.05). The heart rate decreased less with carvedilol (P less than 0.01). There was no difference in the effects exerted by the two therapies on systolic blood pressure and the heart rate 24 h after drug administration, but the diastolic blood pressure was higher in patients given carvedilol (92 versus 88 mmHg; P less than 0.05). Forearm blood flow, forearm vascular resistance and calf blood flow did not change significantly with either of the therapies. In conclusion, 50 mg carvedilol once a day is an effective antihypertensive therapy, though its duration of action did not reach that of 100 mg atenolol once a day. Peripheral vasodilation was similar with both therapies.

Postheparin plasma lipoprotein and hepatic lipase are determinants of hypo- and hyperalphalipoproteinemia.

To study the role of the two postheparin plasma lipolytic enzymes, lipoprotein lipase (LPL) and hepatic lipase (HL) in high density lipoprotein (HDL) metabolism at a population level, we determined serum lipoproteins, apoproteins A-I, A-II, B, and E, and postheparin plasma LPL and HL activities in 65 subjects with a mean HDL-cholesterol of 34 mg/dl and in 62 subjects with a mean HDL-cholesterol of 87 mg/dl. These two groups represented the highest and lowest 1.4 percentile of a random sample consisting 4,970 subjects. The variation in HDL level was due to a 4.1-fold difference in the HDL2 cholesterol (P less than 0.001) whereas the HDL3 cholesterol level was increased only by 32% (P less than 0.001) in the group with high HDL-cholesterol. Serum apoA-levels were 128 +/- 2.2 mg/dl and 210 +/- 2.8 mg/dl (mean +/- SEM) in hypo- and hyper-HDL cholesterolemia, respectively. Serum apoA-II concentration was elevated by 28% (P less than 0.001) in hyperalphalipoproteinemia. The apoA-I/A-II ratio was elevated only in women with high HDL-cholesterol but not in men, suggesting that elevation of apoA-I is involved in hyperalphalipoproteinemia in females, whereas both apoA proteins are elevated in men with high HDL cholesterol. Serum concentration of apoE and its phenotype distribution were similar in the two groups. The HL activity was reduced in the high HDL-cholesterol group (21.2 +/- 1.5 vs. 38.5 +/- 1.8 mumol/h/ml, P less than 0.001), whereas the LPL activity was elevated in the group with high HDL-cholesterol compared to subjects with low HDL-cholesterol (27.8 +/- 1.3 vs. 19.9 +/- 0.8 mumol/h/ml, P less than 0.001). The HL and LPL activities correlated in opposing ways with the HDL2 cholesterol (r = 0.57, P less than 0.001 and r = 0.51, P less than 0.001, respectively), and this appeared to be independent of the relative ponderosity by multiple correlation analysis. The results demonstrate major influence of both HL and LPL on serum HDL cholesterol concentration at a population level.

The antianginal efficacy and tolerability of controlled-release metoprolol once daily: a comparison with conventional metoprolol tablets twice daily.

In a randomized, double-blind, cross-over study treatment with a new controlled-release (CR) preparation of metoprolol, given once daily, was compared with treatment with conventional metoprolol tablets, given twice daily, in 115 patients with stable effort angina pectoris. The patients were treated with 100 mg/day or 200 mg/day, depending on their previous beta-blocker dose. Antianginal efficacy was estimated by counting the number of anginal attacks, by noting the consumption of nitroglycerin tablets, and by exercise tolerance testing. Adverse effects were recorded by a standardized questionnaire. When all patients were analysed together there were no differences in antianginal efficacy between the two treatment regimens. However, when the group taking 200 mg daily was analysed separately better exercise tolerance was found during metoprolol CR therapy, as measured by onset of chest pain and ST-segment change, compared with conventional metoprolol therapy. The two formulations were well tolerated. When given once daily in a total daily dose of 100 mg, the CR preparation induced less adverse effects than the conventional tablets, 50 mg twice daily. It was concluded that the new metoprolol CR preparation, given once daily, possesses the same antianginal efficacy as conventional metoprolol tablets, given twice daily, and may be better tolerated in patients susceptible to side-effects. The antianginal effect of metoprolol CR, 200 mg/day, may be greater over 24 h than that produced by conventional metoprolol tablets, 100 mg twice daily.

Anti-anginal efficacy of a controlled-release formulation of isosorbide-5-mononitrate once daily in angina patients on chronic beta-blockade.

The anti-anginal effect of a controlled-release (Durules) formulation of isosorbide-5-mononitrate (5-ISMN) 60 mg, Imdur, once daily was evaluated in a randomised double-blind, placebo-controlled, crossover study with a placebo run-in period. Each period lasted for 2 weeks. A total of 70 patients (58 men and 12 women) with stable exertional angina pectoris on beta-blockade, mean age 59 years (range 39-71), were included. Exercise testing was performed on a bicycle ergometer 3 hours after the dose at the end of each period. Anginal attacks and intake of sublingual nitroglycerin tablets were noted. Imdur in combination with a beta-blocker significantly increased the total exercise capacity, the time and total work until the onset of chest pain and at 1 mm ST-depression compared with beta-blockade alone. The attack rate and the nitroglycerin consumption were significantly decreased. Headache was the only significant side-effect. In conclusion, the addition of Imdur once daily to beta-blockade significantly increased the anti-anginal effect.

Exercise capacity and hemodynamics in persons aged 20 to 50 years with systemic hypertension treated with diltiazem and atenolol.

Hemodynamic responses and exercise capacity were studied during maximal exercise in 25 young hypertensive persons (mean age 40 years) taking placebo, diltiazem (mean 216 mg/day) and atenolol (mean 80 mg/day). The study was a crossover, double-blind, randomized trial, each medication period lasting 2 months. Sitting blood pressure (BP) was 160 +/- 19/109 +/- 8 mm Hg after run-in. Both drugs decreased BP significantly, diltiazem by 10/ 11 mm Hg and atenolol by 16/14 mm Hg (difference not significant between drugs). During exercise there were no differences among patients taking placebo, diltiazem and atenolol in peak workload and rating of perceived exertion. Atenolol significantly attenuated the increase in heart rate, BP and heart rate-BP product at each workload. Diastolic BP during exercise was significantly lower (6 to 10 mm Hg) during diltiazem therapy than during placebo at each workload. Thus, both diltiazem and atenolol decrease rest BP significantly without impairing exercise capacity.