Studies of a targeted risk reduction intervention through defined exercise (STRRIDE).

PURPOSE: The Studies of a Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE) trial is a randomized controlled clinical trial designed to study the effects of exercise training regimens differing in dose (kcal.wk-1) and/or intensity (relative to peak VO2) on established cardiovascular risk factors and to investigate the peripheral biologic mechanisms through which chronic physical activity alters carbohydrate and lipid metabolism to result in improvements in these parameters of cardiovascular risk in humans. METHODS: We will recruit 384 subjects and randomly assign them to one of three exercise training regimens or to a sedentary control group. The recruiting goal is to attain a subject population that is 50% female and 30% ethnic minority. The overall strategy is to use graded exercise training regimens in moderately overweight subjects with impairments in insulin action and mild to moderate lipid abnormalities to investigate whether there are dose or intensity effects and whether adaptations in skeletal muscle (fiber type, metabolic capacity, and/or capillary surface area) account for improvements in insulin action and parameters of lipoprotein metabolism. We will study these variables before and after exercise training, and over the course of a 2-wk detraining period. The study sample size is chosen to power the study to examine differences in responses between subjects of different gender and ethnicity to exercise training with respect to the least sensitive parameter-skeletal muscle capillary density. RESULTS: The driving hypothesis is that improvements in cardiovascular risk parameters derived from habitual exercise are primarily mediated through adaptations occurring in skeletal muscle. CONCLUSION: Identification that amount and intensity of exercise matter for achieving general and specific health benefits and a better understanding of the peripheral mechanisms mediating the responses in carbohydrate and lipid metabolism to chronic physical activity will lead to better informed recommendations for those undertaking an exercise program to improve cardiovascular risk.

Kissing stents in the aortic bifurcation.

BACKGROUND: We report the first series of simultaneously delivered stents used to treat stenosis of the aortic bifurcation. Surgical treatment of aortoiliac occlusive disease carries up to a 3% mortality rate. Percutaneous balloon techniques to treat aortic bifurcation stenosis, although safer, are still associated with up to a 9% incidence of dissection, thrombosis, or significant residual stenosis. Kissing stent insertion should decrease the incidence of these complications. METHODS: Twenty patients underwent kissing stent insertion. Suitable candidates included patients with symptoms of lower limb ischemia and significant atherosclerotic lesions in both ostial common iliac arteries (n = 15) or with extremely complex single ostial iliac stenoses (n = 5). Palmaz stents were delivered simultaneously to both limbs of the aortic bifurcation. RESULTS: Kissing stent insertion was successfully performed in all 20 patients without acute complications. Mean percent stenosis decreased from 46.2%+/-24.8% to -6.8%+/-13.3% (P = .0001) in the right iliac artery, 42.3%+/-22.8% to -1.6% +/-18.1% (P = .0001) in the left iliac artery, and 19.1%+/-16.6% to 2.3%+/-16.4% (P= .0008) in the distal aorta. Intermittent claudication symptoms were improved in 18 (95%) of 19 patients with 12 (63%) of 19 patients becoming totally asymptomatic. The strongest predictor of clinical outcome after kissing stent insertion was the preprocedural extent of femoropopliteal disease: 8 (89%) of 9 patients with femoropopliteal narrowing <75% bilaterally became completely asymptomatic at follow-up compared with only 3 (30%) of 10 patients with more severe stenoses (P = .02). CONCLUSIONS: We have demonstrated in 20 patients that stenoses of the aortic bifurcation can be treated effectively with kissing stents with few serious adverse events.

Quantification of myocardial perfusion by MRI after coronary occlusion.

The objectives of this study were to define the relationship between the first order constant of Gd-DTPA transfer (K1) and the myocardial blood flow (MBF) at rest and to compare it with an equivalent relationship obtained for positron emission tomography (PET). In a canine model of permanent coronary occlusion (n = 4), myocardial and blood time concentration curves obtained by 13N-ammonia PET and Gd-DTPA-enhanced MRI were fitted by a one-compartment model to determine K1. A linear relationship was observed between MRI-derived K1 and MBF measured by microspheres (K1 = 0.88 x flow -0.015, R = 0.95), which compares favorably with the equivalent relationship derived from PET (K1 = 0.74 x flow +0.16, R = 0.88). The results of this preliminary study suggest that, at rest and distal to a permanently occluded coronary artery, myocardial perfusion quantification by MRI is possible and can challenge PET.

Altered expression of myosin heavy chain in human skeletal muscle in chronic heart failure.

To explore further alterations in skeletal muscle in chronic heart failure (CHF), we examined myosin heavy chain (MHC) isoforms from biopsies of the vastus lateralis in nine male patients with class II-III (CHF) (left ventricular ejection fraction (LVEF) 26 +/- 11%, peak oxygen consumption (peak VO2) 12.6 +/- 2 mL.kg-1.min-1) and nine age-matched sedentary normal males (NL). The relative content of MHC isoforms I, IIa, and IIx was determined by gel electrophoresis as follows: The normal sedentary group (NL) had a higher percent of MHC type I when compared with the patients (NL 48.4 +/- 7% vs CHF patients 24 +/- 21.6%, P < 0.05, no difference between MCH IIa (NL 45.1 +/- 10.5% vs CHF 56.0 +/- 12.5%), and CHF patients had a higher relative content of MHC type IIx than did the normal group (NL 6.5 +/- 9.6% vs CHF 20.0 +/- 12.9%, P < 0.05. Three of nine patients had no detectable MHC type I. In patients relative expression of MHC type I (%) was related to peak VO2 (r = 0.70, P < 0.05). Our results indicate that major alterations in MHC isoform expression are present in skeletal muscle in CHF. These alterations parallel previously reported changes in fiber typing that may affect contractile function i skeletal muscle and possibly exercise performance. The absence of MHC type I in some CHF patients suggests that skeletal muscle changes in this disorder are not solely a result of deconditioning, buy may reflect a specific skeletal muscle myopathy in this disorder.

Hydralazine and isosorbide dinitrate combination improves exercise tolerance in heart failure. Results from V-HeFT I and V-HeFT II. The V-HeFT VA Cooperative Studies Group.

BACKGROUND: To better define the effects of long-term vasodilator therapy on exercise performance in chronic congestive heart failure, we compared placebo with prazosin and with the combination of hydralazine and isosorbide dinitrate (Hyd-Iso) in 642 men over a 5-year period in V-HeFT I. METHODS AND RESULTS: Patients were randomized (double-blind) to 20 mg of prazosin daily or 300 mg of hydralazine plus 160 mg daily of isosorbide dinitrate or placebo. We compared enalapril (20 mg daily), a converting enzyme inhibitor, with Hyd-Iso in 804 men over another 5-year period in V-HeFT II: Background therapy in both trials consisted of digitalis and diuretics. Serial bicycle ergometric exercise was performed with gas exchange measurements during progressive incremental work rates to a symptom-limited peak end point. Gas exchange anaerobic threshold (ATge) measurement was performed in the second trial. In V-HeFT I, an increase in peak VO2 with Hyd-Iso compared with placebo approached significance at 2 months (p < 0.16) and was significant (p < 0.04) at 1 year. In V-HeFT II, Hyd-Iso significantly increased peak VO2 compared with enalapril (p < 0.01 at 3 months, p < 0.02 at 6 months and 2 years). The changes in ATge measurements were not statistically different between the two treatment groups in V-HeFT II: CONCLUSIONS: Combination therapy with Hyd-Iso was more effective in increasing peak VO2 than placebo, prazosin, or enalapril in patients with mild-to-moderate congestive heart failure. Long-term data were confounded by mortality and other events, which may have led to an underestimate of the benefits of Hyd-Iso over placebo and an underestimate of the long-term benefits of enalapril on exercise performance. Therefore, short-term improvement in exercise performance is a suitable therapeutic end point, but long-term studies should more appropriately assess mortality.

Heterogeneous effects of nitroglycerin on the conductance and resistance coronary arterial vasculature.

This study assessed the effects of nitroglycerin (NTG) on epicardial conductance and blood flow regulatory vessels over a wide dose range (10(-10) to 10(-6) mol NTG) in chronically instrumented awake mongrel dogs. NTG bolus injection caused dose-dependent dilation of both conductance and blood flow regulatory vessels. The dose-response curves for blood flow were shifted markedly to the right of the response of conductance vessels so that the proximal vessels had reached 50% of their maximum vasodilation before significant increases in blood flow. The calculated doses for half-maximal vasodilation were 2.8 x 10(-8) and 7.8 x 10(-7) mol for conductance and blood flow, respectively, indicating an approximately 39 times greater sensitivity of the proximal vessels to NTG. NTG had a striking dose-dependent effect on the duration of vasodilation of conductance vessels but did not have a dose-dependent duration effect on coronary blood flow. Although acetylcholine demonstrated a dose-dependent response effect on the conductance vessels similar to NTG, the conductance and resistance vessels demonstrated the same sensitivity to acetylcholine, supporting the view that differences in the mechanics of vasodilation of the two vessel segments did not account for the differential sensitivities to NTG.

Recovery of myocardial function after repetitive episodes of reversible ischemia.

The question of whether recovery of regional myocardial function after repetitive, reversible ischemia differs from recovery after a single episode of myocardial ischemia remains controversial. Therefore, eight conscious dogs were instrumented with ultrasonic dimension transducers and left ventricular micromanometers. Each animal underwent (in random sequence, 72 h apart) a single 15-min left anterior descending coronary arterial (LAD) occlusion and two 15-min LAD occlusions separated by 1 h of reperfusion. The preload recruitable work area (PRWA; the area beneath the regional stroke work vs. end-diastolic length relationship) quantified regional myocardial performance. Repetitive ischemia significantly delayed recovery of PRWA over the first 24 h (P < 0.05). Although postischemic myocardial creep resolved rapidly after single occlusion, double occlusion prevented recovery of creep during the first 4 h of reperfusion. The recovery time course of PRWA paralleled the resolution of myocardial creep, suggesting that creep contributed significantly to delayed functional recovery and that myocardial "stunning" after repetitive ischemia may result in part from interaction between postischemic diastolic properties and systolic dysfunction.

Central hemodynamic response to exercise in patients with chronic heart failure.

Although the pathophysiology of exercise intolerance in patients with chronic heart failure (CHF) is not fully understood, it appears that the cardiac output response plays an important role in limiting exercise in this disorder. Although previous studies have demonstrated that peak VO2 is not related to left ventricular (LV) ejection fraction, studies have consistently identified peak exercise cardiac output as an important predictor of peak VO2. It is likely that a reduced cardiac output to work rate relationship in CHF causes hypoperfusion of both working skeletal muscle and visceral organs, which leads to early anaerobic metabolism and fatigue. Several factors may influence the cardiac output response in patients with severe systolic LV dysfunction, including heart rate, diastolic LV function, and the mitral regurgitation fraction. Although stroke volume increases through use of the Frank-Starling mechanism in many patients with severe systolic LV dysfunction, some patients with this disorder may not increase stroke volume during exercise due to diastolic LV dysfunction or pericardial constraint. The finding that this latter group has more severe exercise intolerance suggests that diastolic dysfunction may further decrease peak VO2 in this disorder. Variations in the mitral regurgitation fraction also have been found to have an important effect on exercise stroke volume in some patients with CHF. Therefore, the finding that LV ejection fraction at rest or during exercise is not related to peak VO2 in patients with systolic LV dysfunction does not necessarily indicate that central hemodynamics do not play a role in exercise intolerance. Rather, it is likely that variability in the LV ejection fraction with exercise, which does not take variable increases in LV end-diastolic volume or mitral regurgitation into account, plays only a modest role in determining the stroke volume and cardiac output response to exercise in patients with severe systolic dysfunction.

Long-term effects of exercise on psychological functioning in older men and women.

The purpose of this study was to determine the psychological, behavioral, and cognitive changes associated with up to 14 months of aerobic exercise training. For the first 4 months of the study, 101 older (greater than 60 years) men and women were randomly assigned to one of three conditions: Aerobic exercise, Yoga, or a Waiting List control group. Before and following the intervention, all subjects completed a comprehensive assessment battery, including measures of mood and cognitive functioning. A semi-crossover design was employed such that, following completion of the second assessment, all subjects completed 4 months of aerobic exercise and underwent a third assessment. Subjects were given the option of participating in 6 additional months of supervised aerobic exercise (14 months total), and all subjects, regardless of their exercise status, completed a fourth assessment. Results indicated that subjects experienced a 10-15% improvement in aerobic capacity. In general, there were relatively few improvements in cognitive performance associated with aerobic exercise, although subjects who maintained their exercise participation for 14 months experienced improvements in some psychiatric symptoms. However, the healthy subjects in this study were functioning at a relatively high level to begin with, and exercise training may produce greater improvements among elderly with concomitant physical or emotional impairments.

Effects of exercise training on bone density in older men and women.

OBJECTIVES: To determine the effects of up to 14 months of aerobic exercise on measures of bone density in older adults. DESIGN: Randomized controlled trial with subjects assigned to either an aerobic exercise condition, non-aerobic yoga, or a wait list non-exercise control group for 4 months. Aerobic fitness and bone density were evaluated in all subjects at baseline (Time 1) and after 4 months (Time 2). A semi-crossover design was utilized with all subjects completing 4 months of aerobic exercise, followed by another evaluation (Time 3). All subjects were then given the option of 6 additional months of aerobic exercise, after which they had a fourth evaluation (Time 4). SETTING: An outpatient exercise rehabilitation facility at a large, major medical center. SUBJECTS: One-hundred-one healthy men (n = 50) and women (n = 51) over age 60 (Mean age = 67.0), recruited from the community. INTERVENTION: The exercise program included stretching, cycle ergometry, and walking three times per week for 60 minutes throughout the course of the study. OUTCOME MEASURES: Aerobic fitness (VO2max) as assessed by cycle ergometry, and bone density (bone mineral content) measured by single photon absorptiometry. RESULTS: Subjects achieved a 10%-15% increase in VO2max after 4 months of exercise training, and 1%-6% further improvement with additional training. Aerobic fitness was associated with significant increases in bone density in men, but not women, who maintained aerobic exercise for 14 months.

Altered skeletal muscle metabolic response to exercise in chronic heart failure. Relation to skeletal muscle aerobic enzyme activity.

BACKGROUND: Exertional fatigue, which frequently limits exercise in patients with chronic heart failure, is associated with early anaerobic metabolism in skeletal muscle. The present study was designed to examine the skeletal muscle metabolic response to exercise in this disorder and determine the relation of reduced muscle blood flow and skeletal muscle biochemistry and histology to the early onset of anaerobic metabolism in patients. METHODS AND RESULTS: We evaluated leg blood flow, blood lactate, and skeletal muscle metabolic responses (by vastus lateralis biopsies) during upright bicycle exercise in 11 patients with chronic heart failure (ejection fraction 21 +/- 8%) and nine normal subjects. In patients compared to normal subjects, peak exercise oxygen consumption was decreased (13.0 +/- 3.3 ml/kg/min versus 30.2 +/- 8.6 ml/kg/min, p less than 0.01), whereas peak respiratory exchange ratio and femoral venous oxygen content were not different (both p greater than 0.25), indicating comparable exercise end points. At rest in patients versus normals, there was a reduction in the activity of hexokinase (p = 0.08), citrate synthetase (p less than 0.02), succinate dehydrogenase (p = 0.0007), and 3-hydroxyacyl CoA dehydrogenase (p = 0.04). In patients, leg blood flow was decreased at rest, submaximal, and maximal exercise when compared to normal subjects (all p less than 0.05), and blood lactate accumulation was accelerated. In patients, during submaximal exercise blood lactate levels were not closely related to leg blood flow but were inversely related to rest citrate synthetase activity in skeletal muscle (r = -0.74, p less than 0.05). At peak exercise there were no intergroup differences in skeletal muscle glycolytic intermediates, adenosine nucleotides, or glycogen, whereas in patients compared to normal subjects less lactate accumulation and phosphocreatine depletion were noted (both p less than 0.05), suggesting that factors other than the magnitude of phosphocreatine depletion or lactate accumulation may influence skeletal muscle fatigue in this disorder. CONCLUSIONS: The results of the present study suggest that in patients with chronic heart failure reduced aerobic activity in skeletal muscle plays an important role in mediating the early onset of anaerobic metabolism during exercise. Our findings are consistent with the concept that reduced aerobic enzyme activity in skeletal muscle is, in part, responsible for determining exercise tolerance and possibly the response to chronic intervention in patients with chronic heart failure.

Exercise radionuclide angiocardiography predicts cardiac death in patients with coronary artery disease.

The purpose of this investigation was to document the relative importance of three clinical and three radionuclide variables for prediction of cardiac death in a consecutive group of patients evaluated for coronary artery disease. During a 6 1/2-year period, beginning in January 1978, 2,042 consecutive patients underwent radionuclide angiocardiography, with a clinical diagnosis of coronary artery disease, at Duke University Medical Center. A subgroup of 318 patients who underwent surgical myocardial revascularization near the time of initial study were excluded from later analysis. Clinical follow-up information was complete in a group of 1,663 patients who did not undergo interventional therapy. The 141 cardiac deaths in these 1,663 patients were the study end point. Cox proportional hazards models analyzed the prognostic information contained in three clinical variables (pain type, age, and sex) and three radionuclide angiocardiogram variables (exercise ejection fraction, resting end-diastolic volume, and change in heart rate with exercise). One-variable models confirmed the prognostic importance of each of these six variables. A multivariable model in which all six variables were used showed clinical variables to contain only 5% and the radionuclide variables 95% of the prognostic information. The exercise ejection fraction was the single most important variable, which alone contained 85% of the total information in the model. Curves relating probability of no cardiac death to the exercise ejection fraction identified a value of 0.50 as an inflection point. Patients with exercise ejection fractions below 0.50 demonstrate a probability of cardiac death that increases as the ejection fraction decreases.(ABSTRACT TRUNCATED AT 250 WORDS)

Dynamic regulation of leg vasomotor tone in patients with chronic heart failure.

We examined the central hemodynamic (n = 5) and leg blood flow (n = 9) responses to one- and two-leg bicycle exercise in nine ambulatory patients with chronic heart failure due to left ventricular systolic dysfunction (ejection fraction 17 +/- 9%). During peak one- vs. two-leg exercise, leg blood flow (thermodilution) tended to be higher (1.99 +/- 0.91 vs. 1.67 +/- 0.91 l/min, P = 0.07), whereas femoral arteriovenous oxygen difference was lower (13.6 +/- 3.1 vs. 15.0 +/- 2.9 ml/dl, P less than 0.01). Comparison of data from exercise stages matched for single-leg work rate during one- vs. two-leg exercise demonstrated that cardiac output was similar while both oxygen consumption and central arteriovenous oxygen differences were lower, indicating relative improvement in the cardiac output response at a given single-leg work rate during one-leg exercise. This was accompanied by higher leg blood flow (1.56 +/- 0.76 vs. 1.83 +/- 0.72 l/min, P = 0.02) and a tendency for leg vascular resistance to be lower (92 +/- 54 vs. 80 +/- 48 Torr.l-1.min, P = 0.08) without any change in blood lactate. These data indicate that, in patients with chronic heart failure, leg vasomotor tone is dynamically regulated, independent of skeletal muscle metabolism, and is not determined solely by intrinsic abnormalities in skeletal muscle vasodilator capacity. Our results suggest that relative improvements in central cardiac function may lead to a reflex release of skeletal muscle vasoconstrictor tone in this disorder.

Effects of inhibition of nitric oxide formation on basal vasomotion and endothelium-dependent responses of the coronary arteries in awake dogs.

The role of nitric oxide in basal vasomotor tone and stimulated endothelium-dependent dilations in the coronary arteries in chronically instrumented awake dogs was studied by examining the consequences of inhibiting endogenous nitric oxide formation with the specific inhibitor of nitric oxide formation, NG-monomethyl-L-arginine (L-NMMA). In four awake dogs, coronary dimension crystals were chronically implanted on the circumflex artery for the measurement of epicardial coronary diameter, and Doppler flow probes were implanted for quantitation of phasic coronary blood flow (vasomotion of distal regulatory resistance vessels). Basal epicardial coronary diameter, acetylcholine-stimulated endothelium-dependent dilation, and flow-induced endothelium-dependent dilation of the epicardial arteries and phasic blood flow were recorded before, and after 5, 15, 50, and 120 mg/kg of L-NMMA. L-NMMA induced a dose-related increase in basal epicardial coronary vasomotor tone. There was an accompanying increase in aortic pressure and a decrease in heart rate. At doses greater than or equal to 50 mg/kg, rest phasic coronary blood flow was also decreased. Left ventricular end-diastolic pressure and contractility were not significantly changed. In contrast, the flow-induced or acetylcholine-stimulated endothelium-dependent responses were attenuated only after infusion of the highest does of L-NMMA (120 mg/kg). The changes in the basal vasomotor tone and acetylcholine-stimulated endothelium-dependent responses returned towards the control states in the presence of L-arginine (660 mg/kg). These data support the view that nitric oxide plays a significant role in modulating basal vasomotion and endothelial-dependent dilation stimulated by acetylcholine or increase in blood flow in epicardial coronary arteries and also influence the regulation of coronary blood flow during physiologic conditions.

Stroke volume increases by similar mechanisms during upright exercise in normal men and women.

To define the effects of gender on stroke volume control during upright exercise in normal subjects, we examined central hemodynamics in 34 men and 27 women during staged bicycle ergometry. Central hemodynamics were assessed by right-sided cardiac catheterization and simultaneous radionuclide angiography. Left ventricular end-diastolic and end-systolic volumes were calculated from the stroke volume (by direct Fick) and the corresponding left ventricular ejection fraction. Men were larger than women (1.85 +/- 0.11 vs 1.65 +/- 0.13 m2, p less than 0.001) but groups were matched for age (39 +/- 12 vs 36 +/- 9 years, p = 0.27). Oxygen consumption at peak exercise was higher in men than in women (2.51 +/- 0.50 vs 1.74 +/- 0.30 liters/min, p less than 0.001) but was not different when adjusted for body weight (31.5 +/- 8.1 vs 28.4 +/- 6.4 ml/kg/min, p = 0.14), indicating similar levels of overall fitness in the 2 groups. At rest and during submaximal and maximal exercise, stroke volume and left ventricular end-diastolic and end-systolic volumes were higher in men than in women, but there were no intergroup differences in stroke volume index, left ventricular ejection fraction, and left ventricular end-diastolic or end-systolic volume indexes. Comparison of derived regression equations of cardiac index, stroke volume index and left ventricular end-diastolic and end-systolic volume indexes revealed no differences in the time course or magnitude of changes with respect to oxygen consumption, expressed as percentage of peak oxygen consumption, in the 2 groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise intolerance in patients with heart failure and preserved left ventricular systolic function: failure of the Frank-Starling mechanism.

Invasive cardiopulmonary exercise testing was performed in 7 patients who presented with congestive heart failure, normal left ventricular ejection fraction and no significant coronary or valvular heart disease and in 10 age-matched normal subjects. Compared with the normal subjects, patients demonstrates severe exercise intolerance with a 48% reduction in peak oxygen consumption (11.6 +/- 4.0 versus 22.7 +/- 6.1 ml/kg per min; p less than 0.001), primarily due to a 41% reduction in peak cardiac index (4.2 +/- 1.4 versus 7.1 +/- 1.1 liters/min per m2; p less than 0.001). In patients compared with normal subjects, peak left ventricular stroke volume index (34 +/- 9 versus 46 +/- 7 ml/min per m2; p less than 0.01) and end-diastolic volume index (56 +/- 14 versus 68 +/- 12 ml/min per m2; p less than 0.08) were reduced, whereas peak ejection fraction and end-systolic volume index were not different. In patients, the change in end-diastolic volume index during exercise correlated strongly with the change in stroke volume index (r = 0.97; p less than 0.0001) and cardiac index (r = 0.80; p less than 0.03). Pulmonary wedge pressure was markedly increased at peak exercise in patients compared with normal subjects (25.7 +/- 9.1 versus 7.1 +/- 4.4 mm Hg; p less than 0.0001). Patients demonstrated a shift of the left ventricular end-diastolic pressure-volume relation upward and to the left at rest. Increases in left ventricular filling pressure during exercise were not accompanied by increases in end-diastolic volume, indicating a limitation to left ventricular filling.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of exercise training on cardiorespiratory function in men and women older than 60 years of age.

This study reports the physiologic effects of up to 14 months of aerobic exercise in 101 older (greater than 60 years) men and women. After an extensive baseline physiologic assessment (Time 1), in which aerobic capacity and blood lipids were measured, subjects were randomized to an aerobic exercise condition (cycle ergometry, 3 times per week for 1 hour), nonaerobic yoga (2 times per week for 1 hour), or a waiting list nonexercise control group for 4 months, and then underwent a second (Time 2) assessment. At the completion of the second assessment, all remaining subjects completed 4 months of aerobic exercise and were reevaluated (Time 3). Subjects were given the option of participating in 6 additional months of supervised aerobic exercise, and all available subjects completed a fourth assessment (Time 4) 14 months after their initial baseline evaluation. Results indicated that subjects generally exhibited a 10 to 15% improvement in peak oxygen consumption after 4 months of aerobic exercise training, and a 1 to 6% improvement in aerobic power with additional aerobic exercise training. On the other hand, subjects, especially men, continued to have improvements in submaximal exercise performance (i.e., anaerobic threshold). In addition, aerobic exercise was associated with an improved lipid profile; subjects participating in aerobic exercise for up to 14 months exhibited increased levels of high-density lipoprotein cholesterol. Maintenance of regular aerobic exercise for an extended time interval is associated with greater cardiovascular benefits among older adults than has been reported previously.

Prognostic value of radionuclide angiography in medically treated patients with coronary artery disease. A comparison with clinical and catheterization variables.

To evaluate the usefulness of multiple measures from rest and exercise radionuclide angiography (RNA) in predicting cardiovascular death and cardiovascular events (death or nonfatal myocardial infarction) and to assess the prognostic usefulness of the RNA relative to clinical and catheterization data, we studied 571 stable patients with symptomatic coronary artery disease who had upright rest/exercise first-pass RNA within 3 months of catheterization and were medically treated. With a median follow-up of 5.4 years, 90 patients have died from cardiovascular causes, and 147 patients have either died or suffered a nonfatal myocardial infarction. Using the Cox regression model and a preselected group of RNA variables, the most important RNA predictor of mortality was exercise ejection fraction (chi 2 = 81, p less than 0.00001). Neither rest ejection fraction nor the change in ejection fraction from rest to exercise contributed additional predictive information. Two other RNA study variables, the change in heart rate from rest to exercise and rest end-diastolic volume index, did contribute additional prognostic information to the exercise ejection fraction (chi 2 = 23, p less than 0.0001). Compared with noninvasive clinical data (history, physical examination, electrocardiogram, and chest radiograph), RNA variables were considerably more predictive of mortality (chi 2 = 71 [clinical variables] versus chi 2 = 104 [RNA]). Remarkably, the strength of the relation of RNA variables with mortality was equivalent to that of the set of catheterization variables previously demonstrated in our large angiographic population to be prognostically important (chi 2 = 104 [RNA] versus chi 2 = 102 [catheterization variables]). The RNA contained 84% of the information provided by clinical and catheterization descriptors combined. Furthermore, the RNA contributed significant additional prognostic information to the clinical and catheterization data (chi 2 = 13.6, p = 0.0035). For cardiovascular events, the relative prognostic usefulness of the RNA was similar, although relations with this outcome were generally weaker. Descriptors from the rest/exercise RNA exhibit a powerful relation with long-term outcomes and can be useful in defining risk, even when clinical and catheterization data are available.

Preferential proximal coronary dilation by activators of guanylate cyclase in awake dogs.

The vasodilation effects of activators of guanylate cyclase, atrial natriuretic peptide (ANP), nitroglycerin (NTG), and acetylcholine (ACh), on the epicardial conductance arteries and the distal resistance coronary vessels were examined in chronically instrumented awake dogs and related serially to plasma guanosine 3',5'-cyclic monophosphate (cGMP) levels. Left atrial bolus injections of ANP (3 micrograms/kg; n = 7), NTG (13 micrograms/kg; n = 7), or ACh (0.13 micrograms/kg; n = 3) induced sustained increases in epicardial coronary dimension (ultrasonic crystals), 3.3, 5.7, and 6.7%, respectively, lasting greater than 40 min for ANP and NTG and greater than 3 min for ACh, and relatively brief increases in blood flow (resistance artery vasomotion) for each agent. Plasma samples withdrawn serially after injections of each agent demonstrated that only ANP increased cGMP level; the time course of ANP-induced epicardial vasodilation followed more closely the increase in cGMP than that of plasma ANP. These data demonstrated that these three activators of guanylate cyclase induced preferential sustained epicardial vasodilation and only brief distal coronary vasodilation with minor or no change in systemic hemodynamics. The prolonged increase in plasma cGMP after ANP injection suggested continuous cGMP production during ANP-induced proximal vasodilation. These data demonstrate a striking heterogeneity of vasomotor responses in the coronary arterial vasculature and suggest that cGMP-mediated vasodilation mechanisms are more predominant in proximal conductance arteries compared with distal resistance vessels.

Ischemia-induced epicardial vasoconstriction. A potential mechanism for distant myocardial ischemia.

This study evaluated the effects of transient coronary occlusion on the diameter of a nonischemic vessel or a nonischemic coronary segment proximal to the site of occlusion. Awake mongrel dogs chronically instrumented with dimension crystals, Doppler flow probes, and distal pneumatic occluders on the circumflex coronary arteries were subjected to transient 2-minute circumflex occlusions (n = 9) under constant heart rate (120 beats/min). Left ventricular end-diastolic pressure increased by 60% (from 10 +/- 1 to 16 +/- 2 mm Hg), and dP/dt decreased by 8% (from 2,048 +/- 130 to 1,885 +/- 110 mm Hg/sec); systemic hemodynamics were unaltered. Epicardial coronary diameter proximal to the site of occlusion decreased by 4.37% (from 3.62 +/- 0.25 to 3.46 +/- 0.29 mm, p less than 0.05). Constriction began 15-20 seconds after the onset of ischemia and progressed to maximum in 1-2 minutes. Combined alpha- and beta-receptor blockade (n = 8) with phentolamine (2 mg/kg) and propranolol (1 mg/kg) or cyclooxygenase inhibition (n = 5) with indomethacin (7.5 mg/kg) did not attenuate the ischemia-induced vasoconstriction response. Transient 2-minute occlusion of the left anterior descending coronary artery (n = 6) also elicited significant epicardial vasoconstriction in the circumflex coronary artery in the first minute (from 3.88 +/- 0.31 to 3.81 +/- 0.31 mm, p less than 0.05); the constriction was attenuated subsequently by an increase (25.5%) in circumflex flow. When left anterior descending occlusion was repeated (n = 6) with circumflex flow held constant, the ischemia-induced circumflex constriction was augmented; diameter decreased 3.7% (from 3.83 +/- 0.29 to 3.69 +/- 0.29 mm, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)