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PubMed1980

Na+ and Ca2+ ingestion: plasma volume-electrolyte distribution at rest and exercise.

Plasma volume (PV), protein, and electrolyte shifts were measured in two groups of five men in the supine position during rest, exercise (40-47% VO2max), and recovery in cool (Ta = 26.5 degrees C) and hot (Ta = 39.4 degrees C) environments. They drank 16-17 ml/kg hypertonic (1.5%) NaCl, isotonic (0.9%) NaCl, or hypertonic (1.5%) calcium gluconate solutions during the preexercise rest period. Hyper-Na consumption retarded the rise in PV (hypervolemia) at rest in the cool but not in the heat. Ingestion of iso-Na and hyper-Na resulted in twofold greater hypervolemia at rest in the heat. During exercise and recovery, PV was highest with hyper-Na in the heat. Hyper-Ca prevented the normal hypervolemic response at rest in both environments. The normal hypervolemic responses during exercise were not influenced by any drink composition. The results suggest hypertonic drinks may be better for maintaining PV levels during exercise in heat; but calcium must be used with care.

Adult↗
PubMed1981

Hypoxia effects on plasma volume shifts at rest, work, and recovery in supine posture.

The purpose of this study was to determine the effects acute exposure to hypoxia (less than 1.5 h; gas mixture 12.6% O2-87.4% N2) has on plasma volume (PV) shifts during rest and exercise. Nine unacclimatized males performed identical protocols in the supine posture in both normoxic (N) and hypoxic (H) conditions. The protocol was rest 60 min, submaximal exercise (PWC 140, work rate eliciting a heart rate of 140 beats/min) for 30 min, immediately followed by maximal exercise, and 10 min of passive recovery. There were slight but significant losses of 2.7 and 1.4% PV at rest in H and N conditions, respectively. At the same relative intensity of submaximal exercise (work loads reduced by 22% in H conditions), PV losses were nearly identical (N = 11.2%, H = 11.8%). There was a further PV efflux subsequent to maximal exercise (N = 7.9%, H = 5.2%). The maximum PV efflux, from the beginning of rest to the end of maximal exercise, was 20% for both conditions. Total plasma protein (PP) content was unchanged during rest or exercise for either N or H conditions. After 10 min of recovery, restitution of PV was 10% below preexercise values for both N and H conditions. We conclude that acute hypoxic exposure does not influence the loss of VP or PP during submaximal or maximal exercise.

Adult↗
PubMed1982

An automated, indirect assessment of cardiac output during rest and exercise.

The present study describes a modification of the equilibration CO2-rebreathing technique for determining cardiac output (Q), utilizing the Beckman Metabolic Measurement Cart (MMC) to provide partial automation of the procedures described by Jones et al. (Clinical Exercise Testing. Philadelphia, PA: Saunders, 1975). Q was determined in six normal healthy males to establish the reliability of the technique at rest, and during exercise at power outputs of 49 and 98 W, or 300 and 600 kpm/min. An additional 11 patients, who were symptomatic for coronary artery disease and scheduled for right and left heart catheterization, were used in validating these procedures against Q determined by the thermodilution method. The automated CO2-rebreathing procedure was found to be reliable at rest and during exercise, and demonstrated a direct linear relationship with VO2 (r = 0.90). Also, this procedure correlated (r = 0.87) with the thermodilution method during supine rest, and both methods were quite consistent between trials within the same subject. It was concluded that the CO2-rebreathing procedure used in this study, as interfaced with the Beckman MMC, provides reasonable estimates of Q, both in patients during supine rest, and in normal healthy subjects at rest and during low to moderate levels of exercise.

Adult↗
PubMed1982

Superficial shell insulation in resting and exercising men in cold water.

From measurements of subcutaneous fat temperature (Tsf) at known depths below the surface, skin surface temperature (Tsk), and direct skin heat flux (H), the superficial shell isulation (Iss) of the thigh (fat + skin) was calculated as Iss (degrees C.m2.w-1) = (Tsf - Tsk)/H in nine male subjects immersed head out in a well-stirred water bath. Also, at critical water temperature (CWT = 28-33 degrees C), eight of the subjects rested for 3 h, enabling overall maximal tissue insulation (It,max) to be calculated as It,max (degrees C.m2.W-1) = (Tre - Tw)/(0.92 M +/- delta S), where Tre is rectal temperature, Tw is water temperature, M is metabolic rate, and s is loss or gain of body heat. Five subjects performed up to 2 h of mild leg cycling, preceded and followed by 60 min of rest, and both thigh Iss and overall It were measured during exercise. Iss increased from minimal values in Tw greater than 33 degrees C to maximal values (Iss,max) at CWT or below. Iss,max was linearly related to tissue thickness (d) in millimeters of fat plus skin, Iss,max (degrees C.m2.W-1) = 0.0048d-0.0052; r = 0.95, n = 37, and was not influenced by leg exercise up to a metabolic rate of 150 W.m-2 in CWT despite large increases in Tsf and H and large decreases in overall It. The slope of Iss,max vs. depth, 0.0048 degrees C.m2.W-1.mm-1, is almost identical to thermal resistivity of fat in vitro, suggesting that the superficial shell is unperfused in CWT at rest or during mild exercise. When maximal superficial shell insulation (It,ss,max) for the whole body was calculated with allowance for differing fat thicknesses and surface areas of body regions, it could account for only 10-15% of overall It,max at rest and 35-40% of overall It in mild exercise. We suggest that the poorly perfused muscle shell plays a more important role as a defense against cooling at CWT than does the superficial shell (fat + skin), particularly at rest.

Adipose Tissue↗
PubMed1983

Effect of triiodothyronine on body temperature at rest and during exercise in dogs.

To determine the effect of the thyroid hormones on body temperature at rest and during exercise, five mongrel dogs were trained to run on a treadmill and then treated with exogenous triiodothyronine (T3) (1 mg/kg) to elevate circulating T3 levels or propylthiouracil (PTU) (200 mg/day for 14 days) to lower endogenous T3 levels. When compared with levels in euthyroid controls at rest and during exercise, rectal temperature (Tre) was increased (P less than or equal to 0.01 and P less than or equal to 0.02, rest and exercise, respectively) in T3-treated dogs and decreased (P less than 0.05 and P less than 0.01) in the PTU-treated dogs. Although the rise in Tre from rest to exercise in the PTU trial was slightly less than that of the control runs (1.23 vs 1.44 degrees C, respectively; P = 0.05), it was similar to the rise in Tre observed in the T3 experiments (1.37 degrees C). Because T3 treatment resulted in an elevation in exercise oxygen consumption (VO2), untreated dogs were run at elevated work loads such that their VO2 matched that recorded when pretreated with T3. Exercise Tre in these experiments was lower (P less than 0.02) than after T3 treatment, even though the exercise metabolic rates were equivalent. It was concluded that 1) although T3 alters body temperature, the magnitude of the rise in Tre during exercise is not dependent on T3 concentration and 2) the effects of T3 on body temperature at rest and during exercise are mediated through mechanisms other than alterations in metabolic rate.

Animals↗
PubMed1983

Effect of a 42.2-km footrace and subsequent rest or exercise on muscle glycogen and enzymes.

The purpose of this study was to determine the effect of running a marathon and subsequent rest or exercise during a 7-day recovery period on muscle glycogen, glycogen synthase, hexokinase, and the activity of hexose monophosphate pathway enzymes. Ten well-trained runners were randomly assigned to either a postmarathon rest or exercise group. The rest group (n = 5) performed no physical activity, whereas the exercise group ran at their highest tolerable volitional intensity for 20-45 min during the recovery period. Muscle biopsies were obtained from the gastrocnemius before and after the marathon and 1, 3, 5, and 7 days after the marathon. Muscle glycogen was supercompensated before the marathon (196 mmol glucosyl units kg wet tissue wt-1, mmol X kg-1) and was reduced to 25 mmol X kg-1 after the marathon. Seven days later it was 141 and 109 mmol X kg-1 in the rest and exercise groups, respectively. Measurement of glycogen synthase activity ratio indicated an active enzyme only immediately postmarathon, whereas measurement of glycogen synthase fractional velocity and relative velocity indicated an active enzyme immediately postmarathon and 1 day postmarathon. Hexokinase activity was significantly elevated immediately after the marathon and remained elevated through 5 days postmarathon. The activities of the hexose monophosphate pathway enzymes declined steadily during the experimental period and were significantly reduced 5 and 7 days postmarathon. Low-intensity exercise during the recovery week did not significantly differentiate the exercise group from the rest group.

Adult↗
PubMed1984

Effect of a 42.2-km footrace and subsequent rest or exercise on muscular strength and work capacity.

This study 1) quantitates the effect of a 42.2-km footrace (marathon) on leg extensor strength (maximal peak torque, MPT) and work capacity (WC, measured during a leg extensor fatigue test), and 2) describes the effect of either a rest or exercise regimen for 1 wk after the marathon on the recovery of MPT and WC. Ten trained male runners performed personal records in a marathon and were then randomly assigned to either a rest or exercise-recovery group. The rest group did not train, whereas the exercise group ran 20-45 min/day at their selected intensity of exercise [50-60% maximal O2 consumption (Vo2max)] during the recovery week. MPT was measured at 1.1, 3.2, and 5.3 rad X s-1. The total work generated during a 50-contraction active extension-passive flexion fatigue test conducted at 3.2 rad X s-1 was defined as WC. Reports of perceived soreness of the quadriceps were obtained before each strength-testing session. These measurements were obtained before the marathon and 15-20 min and 1, 3, 5, and 7 days postmarathon. A significant reduction in MPT and WC resulted and continued 1 day postmarathon. MPT of both groups improved through day 5 postmarathon at 1.1 and 3.2 rad X s-1. MPT of the rest group improved through day 7 postmarathon but remained less than premarathon MPT. Recovery of MPT was impaired in the exercise group through days 5-7 postmarathon after 40-45 min exercise at 60% Vo2max. WC was recovered 3 days postmarathon in the rest group but was still impaired 7 days postmarathon in the exercise group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Cardiac cycle length variability in ponies at rest and during exercise.

We evaluated cardiac cycle length variability in ponies at rest and during strenuous exercise with and without premedication with atropine. In the absence of premedication, cardiac cycle length at rest was 1,112 +/- 53 ms, the individual cardiac cycle length standard deviation (SDCL) was 75 +/- 23 ms, and the individual cycle length coefficient of variation (CVCL) was 6.32 +/- 1.62. Exercise significantly decreased (P < 0.05) all three indexes (290 +/- 9 ms, 5 +/- 1 ms, and 1.65 +/- 0.20, respectively). Atropine premedication significantly reduced resting cardiac cycle length (685 +/- 46 ms), SDCL (10 +/- 2 ms), and CVCL (1.45 +/- 0.19) compared with nonpremedicated values. Cardiac cycle length was significantly decreased by exercise after atropine premedication, but no statistically significant changes occurred in SDCL or CVCL. Thus, although considerable cardiac cycle length variability exists in nonpremedicated ponies at rest, it is nearly completely abolished by strenuous exercise. The absence of significant differences between the indexes of variability during exercise without premedication, at rest after atropine, and during exercise after atropine indicates that cardiac cycle length variability in the pony is mediated primarily through activity of the parasympathetic system.

Animals↗
PubMed1994

Increased dependence on blood glucose in smokers during rest and sustained exercise.

To evaluate the hypothesis that smoking increases the dependence on blood glucose as a fuel, seven male smokers [28.7 +/- 1.7 (SE) yr. 77.7 +/- 4.3 kg] and seven nonsmokers (NS; 29.1 +/- 0.9 yr, 78.7 +/- 5.3 kg) were studied in the postabsorptive condition. NS received a primed continuous infusion of [6,6-2H]glucose and [1-13C]glucose during 90 min of rest and 60 min of exercise at 49.7 +/- 0.8% of peak O2 consumption on one occasion; chronic smokers continued their overnight abstinence from smoking (CS) for one trial but, on another occasion, acutely smoked (AS) two cigarettes immediately before resting measurements and another cigarette before exercise. Plasma glucose levels were similar among all groups at all times during the trials; however, the glucose rates of appearance (Ra) at rest in CS (1.96 +/- 0.14 mg.kg-1 x min-1) and AS (2.02 +/- 0.14) were higher than in NS (1.41 +/- 0.15, P < 0.05). With exercise, the glucose Ra values rose in all groups above resting values but were significantly greater in CS (4.76 +/- 0.50) and AS (4.71 +/- 0.53) than in NS (3.31 +/- 0.16). Glucose oxidation during exercise was elevated in smokers (2.31 +/- 0.37 mg.kg-1 x min-1 in CS and 2.18 +/- 0.34 in AS) compared with NS (1.09 +/- 0.18, P < 0.05). Nicotine levels correlated with the glucose Ra in AS (r = 0.93, P < 0.01). In conclusion, the results indicate that long-term smoking, independent of acute smoking, increases the dependence on blood glucose as a fuel during rest and sustained submaximal exercise.

Adult↗
PubMed1995

Regional pulmonary blood flow during rest, tilt, and exercise in unanesthetized dogs.

We assessed the heterogeneity of regional pulmonary blood flow (PBFr), using radioactive microspheres in five unanesthetized dogs standing at rest (Rest), standing at a 45 degrees upward tilt (Tilt), and during moderate treadmill exercise (Exer). The excised lungs were cut into 1-cm3 pieces along transverse, horizontal, and longitudinal planes. Mean PBFr increased from 23.3 ml.min-1.g-1 at Rest to 57.4 ml.min-1.g-1 during Exer, but the relative dispersions were not statistically different between states (47.3-51.9%). A small but significant gravity-dependent gradient in PBFr of < or = 4.7%/cm (r2 < or = 0.118) as well as a PBFr decreasing radial gradient from the lung midpoint of < or = 7.2%/cm (r2 < or = 0.108) were present in all states. PBFr at Rest was highly correlated with those at Tilt (r2 = 0.773) and Exer (r2 = 0.888), and a variable PBFr gradient of < or = 2.5%/cm from base to apex was observed. Fractal dimensions calculated using relative dispersion as a function of aggregated sample size were not significantly different between states and were 1.132 (r2 = 0.987) at Rest, 1.121 (r2 = 0.973) at Tilt, and 1.149 (r2 = 0.986) during Exer. Thus, gravity and centripetal gradients consistently accounted for a maximal difference of only about twofold in PBFr and < 11% of overall PBFr heterogeneity in 1-cm3 samples. Recursive anatomic branching of pulmonary arteries and local mechanical factors apparently account for most of the blood flow heterogeneity in small pieces of lung.

Animals↗
PubMed1999

Effect of furosemide on pulmonary blood flow distribution in resting and exercising horses.

We determined the spatial distribution of pulmonary blood flow (PBF) with 15-micron fluorescent-labeled microspheres during rest and exercise in five Thoroughbred horses before and 4 h after furosemide administration (0.5 mg/kg iv). The primary finding of this study was that PBF redistribution occurred from rest to exercise, both with and without furosemide. However, there was less blood flow to the dorsal portion of the lung during exercise postfurosemide compared with prefurosemide. Furosemide did alter the resting perfusion distribution by increasing the flow to the ventral regions of the lung; however, that increase in flow was abated with exercise. Other findings included 1) unchanged gas exchange and cardiac output during rest and exercise after vs. before furosemide, 2) a decrease in pulmonary arterial pressure after furosemide, 3) an increase in the slope of the relationship of PBF vs. vertical height up the lung during exercise, both with and without furosemide, and 4) a decrease in blood flow to the dorsal region of the lung at rest after furosemide. Pulmonary perfusion variability within the lung may be a function of the anatomy of the pulmonary vessels that results in a predominantly fixed spatial pattern of flow distribution.

Animals↗
PubMed2002

Glutamate ingestion and its effects at rest and during exercise in humans.

Glutamate is central to several transamination reactions that affect the production of ammonia, alanine, glutamine, as well as TCA cycle intermediates during exercise. To further study glutamate metabolism, we administered 150 mg/kg body wt of monosodium glutamate (MSG) and placebo to seven male subjects who then either rested or exercised (15-min cycling at approximately 85% maximal oxygen consumption). MSG ingestion resulted in elevated plasma glutamate, aspartate, and taurine, both at rest and during exercise (P < 0.05), whereas most other amino acids were unchanged. Neither plasma alanine nor ammonia was altered at rest. During exercise and after glutamate ingestion, alanine was increased (P < 0.05) and ammonia was attenuated (P < 0.05). Glutamine was also elevated after glutamate ingestion during rest and exercise trials. MSG administration also resulted in elevated insulin levels (P < 0.05), which were parallel to the trend in C-peptide levels. Thus MSG can successfully elevate plasma glutamate, both at rest and during exercise. The plasma amino acid responses suggest that increased glutamate availability during exercise alters its distribution in transamination reactions within active muscle, which results in elevated alanine and decreased ammonia levels.

Administration, Oral↗
PubMed2003

Diurnal variation of aldosterone and plasma renin activity: timing relation to melatonin and cortisol and consistency after prolonged bed rest.

Exposure to prolonged bed rest is known to induce changes in the renin-angiotensin-aldosterone system (RAAS) by way of posture, sodium and potassium balance, and stress, which may have serious consequences for patients. We focused on the diurnal variation of the RAAS by investigating changes in the levels of plasma renin activity (PRA) and aldosterone; for comparison to markers of the intrinsic pacemaker and to stress, we measured melatonin and cortisol. PRA, aldosterone, melatonin, and cortisol were measured hourly in 10 normal subjects with standardized sleep patterns, posture, and diet at baseline and after 11 days of prolonged bed rest conducted under a light-dark cycle. Circadian characteristics of hormone secretion patterns were estimated by multiple harmonic regression with excellent goodness-of-fit measures. Variability in the melatonin and cortisol patterns across subjects was minimal. Even for pulsatile hormones, this technique successfully estimated the acrophase, which was the salient feature. Baseline hormone peak times started with melatonin near the middle of the sleep period, followed by PRA, then aldosterone, and then cortisol around wake time. Prolonged bed rest did not induce significant changes in any timing characteristic of the secretion patterns. Baseline and prolonged bed rest peak times for melatonin and cortisol and amplitude characteristics for all hormones were highly correlated, indicating consistency within individuals. These data provide strong evidence that prolonged bed rest of 11 days' duration does not disrupt either the timing characteristics of the RAAS or the intrinsic pacemaker.

Adult↗
PubMed2003

Strength training counteracts motor performance losses during bed rest.

The purpose of the study was to determine the effect of bed rest with or without strength training on torque fluctuations and activation strategy of the muscles. Twelve young men participated in a 20-day bed rest study. Subjects were divided into a non-training group (BRCon) and a strength-training group (BRTr). The training comprised dynamic calf-raise and leg-press exercises. Before and after bed rest, subjects performed maximal contractions and steady submaximal isometric contractions of the ankle extensor muscles and of the knee extensor muscles (2.5-10% of maximal torque). Maximal torque decreased for both the ankle extensors (9%, P < 0.05) and knee extensors (16%, P < 0.05) in BRCon but not in BRTr. For the ankle extensors, the coefficient of variation (CV) for torque increased in both groups (P < 0.05), with a greater amount (P < 0.05) in BRCon (88%) compared with BRTr (41%). For the knee extensors, an increase in the CV for torque was observed only in BRCon (22%). The increase in the CV for torque in BRCon accompanied the greater changes in electromyogram amplitude of medial gastrocnemius (122%) and vastus lateralis (59%) compared with BRTr (P < 0.05). The results indicate that fluctuations in torque during submaximal contractions of the extensor muscles in the leg increase after bed rest and that strength training counteracted the decline in performance. The response varied across muscle groups. Alterations in muscle activation may lead to an increase in fluctuations in motor output after bed rest.

Adult↗
PubMed1982

Ejection fraction response to exercise in patients with chest pain, coronary artery disease and normal resting ventricular function.

We studied the ejection fraction (EF) response to upright exercise using first-pass radionuclide angiography (RNA) in 281 patients with chest pain, significant coronary artery disease and normal resting ventricular function. A wide range of resting function (heart rate and EF) and exercise function (heart rate, EF and peak work load) was measured in this population. The EF response to exercise (delta EF) varied widely, ranging from a decrease of 36% to an increase of 26%. Twenty-eight clinical, catheterization and RNA variables were examined to determine their relationship to delta EF. Considered individually, the variables showing the strongest relationship were resting pulse pressure, positive exercise ECG changes and adequate exercise. Multivariable analysis identified resting pulse pressure, adequate exercise, resting EF, the change in end-diastolic volume index with exercise, positive exercise ECG changes and, to a lesser degree, the number of diseased vessels as variables that were significant independent predictors of delta EF. These observations indicate that delta EF is a complex response that is influenced by many pathophysiologic variables in the presence of coronary artery disease. Several of these variables are not related to the extent of coronary artery disease.

Adult↗
PubMed1984

Beneficial effects of nifedipine on rest and exercise myocardial energetics in patients with congestive heart failure.

Rest and exercise systemic hemodynamic parameters, coronary blood flow, and myocardial energetics were assessed before and 15 min after the sublingual administration of 20 mg of nifedipine in 10 patients with idiopathic congestive cardiomyopathy. When compared with control, nifedipine increased rest and exercise cardiac index by 37% and 28%, respectively (p less than .001). Peripheral vasodilation was demonstrated with a drop in systemic arterial pressure, exercise pulmonary capillary wedge pressure, and systemic vascular resistance (p less than .05). The calcium-channel blocker did not alter myocardial oxygen consumption; however, coronary blood flow increased by 32% at rest (p less than .01) while coronary vascular resistance diminished both at rest and after exercise compared with control (p less than .05). Nifedipine elicited a decrease in the rest and exercise aortocoronary sinus oxygen difference while the coronary sinus oxygen saturation increased (p less than .01). In this group of patients with idiopathic congestive cardiomyopathy, nifedipine enhanced myocardial performance while increasing coronary blood flow and favorably altering the myocardial oxygen supply-demand balance.

Adult↗
PubMed1985

Myocardial perfusion after aortocoronary bypass surgery: measurements at rest and after administration of isoproterenol.

This study examined quantitative regional myocardial perfusion (RMP) measured by the washout of 133Xe at rest and after an isoproterenol challenge in 50 patients (group I) studied 8 to 14 days after they underwent saphenous vein bypass grafting to the left coronary artery, and compared this with RMP measured in the native left coronary artery in 14 patients (group II) with significant coronary artery disease and in 12 normal subjects (group III). The double product of the heart rate and aortic systolic pressure was used as an indicator of demand. The statistical significance of group comparisons was analyzed with Dunn's multiple comparisons among means test. Analysis of the data showed no significant difference among the groups with respect to aortic systolic pressure. In subjects at rest, heart rate was lower in groups II and III than in group I, and double product was lower in group II than in group I. After isoproterenol, both heart rate and double product were lower in group II compared with groups I and III, but there was no significant difference between groups I and III with respect to heart rate or double product. Mean resting RMP in group II was lower than in group I; however, results of other group comparisons were insignificant for resting parameters. After isoproterenol, mean flow (ml/100 g/min) in group I was similar to flow in group III (130 +/- 24 vs 139 +/- 26). In contrast, the average flow response after isoproterenol was significantly less in group II when compared with that in group I (105 +/- 20 vs 130 +/- 24) and with that in group III (105 +/- 20 vs 139 +/- 26). Because of differences in levels of demand with isoproterenol, the change in flow was normalized to the percent increase in double product. These data showed results similar to those above, i.e., normalized RMP in patients with coronary artery disease was significantly lower than that in normal subjects (82 +/- 41 vs 119 +/- 57) and in revascularized patients (82 +/- 41 vs 105 +/- 54). However, there was no significant difference between normal subjects and patients who had undergone surgery. To further evaluate the relationship of flow response to demand parameters, we plotted RMP/double product vs resistance. The data revealed a significant correlation between these variables in all groups both in subjects at rest and after isoproterenol.(ABSTRACT TRUNCATED AT 400 WORDS)

Coronary Artery Bypass↗
PubMed1986

Efficacy and safety of medium- and high-dose diltiazem alone and in combination with digoxin for control of heart rate at rest and during exercise in patients with chronic atrial fibrillation.

We evaluated the efficacy and the safety of medium-(240 mn/day) and high-dose (360 mg/day) diltiazem alone and in combination with digoxin when used for control of heart rate in 12 patients with chronic atrial fibrillation. Medium-dose diltiazem was comparable to therapeutic dose of digoxin at rest (88 +/- 19 vs 86 +/- 12 beats/min) but superior during peak exercise (154 +/- 23 vs 170 +/- 20 beats/min; p less than .05). High-dose diltiazem resulted in better control of heart rate than digoxin both at rest (79 +/- 17 beats/min; p less than .05) and exercise (136 +/- 25 beats/min; p less than .05) but was associated with side effects in 75% of the patients. Combined therapy of digoxin and diltiazem enhanced the effect of digoxin alone and resulted in significantly better control of heart rate at rest (67 +/- beats/min with medium-dose and 65 +/- beats/min with high-dose diltiazem) and during peak exercise (132 +/- 32 and 121 +/- 24 beats/min, respectively). However, the difference in heart rate between these two doses was not significant. Reduction of heart rate combined with concomitant effect on blood pressure resulted in a significant fall in pressure-rate product at rest from 10,077 +/- 1708 mm Hg/min on digoxin alone to 7877 +/- 1818 mm Hg/min after the addition of medium-dose diltiazem (p less than .05) and during exercise form 25,670 +/- 3606 to 18,439 +/- 4115 mm Hg/min (p less than .05). Continued therapy with digoxin combined with diltiazem 240 mg/day for 21 +/- 8 days in nine patients showed persistent effect on heart rate and blood pressure without any toxic manifestations or change in serum digoxin (1.5 +/- 0.4 vs 1.3 +/- 0.4 ng/ml) or plasma diltiazem concentrations (204 +/- 72 vs 232 +/- 129 ng/ml). In conclusion, medium-dose diltiazem when combined with digoxin is an effective and safe regimen for the treatment of patients with chronic atrial fibrillation and enhances digoxin-mediated control of heart rate both at rest and during exercise.

Adult↗