Biomedical subjects

F R Cobb

Publications and source records attributed to F R Cobb.

At least 19 recordsLinked to original sources

PubMed1993

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.

Animals↗

PubMed1993

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.

Acetylcholine↗

PubMed1992

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.

Chronic Disease↗

PubMed1991

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)

Adult↗

PubMed1991

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.

Aged↗

PubMed1991

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)

Aged↗

PubMed1991

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.

Affect↗

PubMed1991

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.

Aged↗

PubMed1991

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.

Aged↗

PubMed1991

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.

3-Hydroxyacyl CoA Dehydrogenases↗

PubMed1991

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.

Acetylcholine↗

PubMed1991

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)

Angina Pectoris↗

PubMed1990

Nitric oxide modulates epicardial coronary basal vasomotor tone in awake dogs.

This study evaluates the role of endogenous nitric oxide in the modulation of basal coronary vasomotor tone by studying the effects of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide formation from L-arginine, on resting epicardial coronary diameter and coronary flow. L-NMMA (5 mg/kg) was infused in seven awake dogs chronically instrumented with coronary dimension crystals for measurement of epicardial coronary diameter, and Doppler flow probes for quantitation of phasic coronary flow (vasomotion of distal regulatory resistance coronary vessels). Epicardial coronary diameter decreased 5.5% from 3.47 +/- 0.17 to 3.28 +/- 0.15 mm (mean +/- SE). The diameter change was gradual, reaching a maximum at 13 +/- 2 min after infusion, and persistent, lasting greater than 90 min. Phasic coronary flow did not change. Mean aortic pressure significantly increased from 99 +/- 3 to 111 +/- 3 mmHg and heart rate decreased from 56 +/- 4 to 46 +/- 3 beats/min. Left ventricular end-diastolic pressure and contractility were not significantly altered. L-Arginine (66 mg/kg) but not D-arginine reversed all hemodynamic parameters. These data support an important role of nitric oxide in modulating basal epicardial coronary vasomotor tone and systemic vascular resistance.

Animals↗

PubMed1990

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.

Acetylcholine↗

PubMed1990

Skeletal muscle biochemistry and histology in ambulatory patients with long-term heart failure.

Recent studies in patients with long-term heart failure have suggested that intrinsic abnormalities in skeletal muscle can contribute to the development of early lactic acidosis and fatigue during exercise. The present study provides an analysis of substrate and enzyme content, fiber typing, and capillarization in skeletal muscle biopsy samples obtained at rest from the vastus lateralis in 11 patients with long-term heart failure (left ventricular ejection fraction, 21 +/- 8%) and nine normal subjects. Patients demonstrated a reduced peak exercise oxygen consumption (13.0 +/- 3.3 ml/kg/min) when compared with normals (30.2 +/- 8.6 ml/kg/min, p less than 0.001) and had an accelerated rise in blood lactate levels during exercise. In mixed fiber skeletal muscle, total phosphorylase and glycolytic enzyme activities were not different in the two groups, whereas mitochondrial enzymes involved in terminal oxidation were decreased in patients as compared with normal subjects as indicated by reductions in succinate dehydrogenase (51 +/- 15 vs. 81 +/- 17 microM/g protein/min, p less than 0.001) and citrate synthetase (26 +/- 7 vs. 43 +/- 20 microM/g protein/min, p less than 0.05). 3-Hydroxyacyl-CoA-dehydrogenase, an important enzyme mediating beta-oxidation of fatty acids, was also reduced in patients as compared with normals (18 +/- 7 vs. 27 +/- 10 microM/g protein/min, p less than 0.05). There was no difference in high-energy phosphagens or lactate concentration of mixed muscle in the two groups, whereas glycogen content was decreased in patients (262 +/- 29 vs. 298 +/- 35 microM glucosyl units/kg dry wt, p = 0.01). Patients demonstrated a reduced percentage of slow twitch type I fibers (36 +/- 7% vs. 52 +/- 22%, p less than 0.05) and had a higher percentage of type IIb fast twitch fibers (24 +/- 9% vs. 11 +/- 12%, p = 0.02), which were smaller than the type IIb fibers seen in normal subjects (p less than 0.05). In patients, the number of capillaries per fiber was decreased for type I and type IIa fibers (both, p less than 0.03), but the ratio of capillaries to cross-sectional fiber area was not different for the two groups. These data demonstrate major alterations in skeletal muscle histology and biochemistry in patients with long-term heart failure, including fiber atrophy, a decrease in percentage of composition of type I fibers, and an increase in type IIb fibers accompanied by a decrease in oxidative enzyme capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

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.

Cardiac Catheterization↗

PubMed1990

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)

Adrenergic beta-Antagonists↗

PubMed1990

The anaerobic threshold in chronic heart failure. Relation to blood lactate, ventilatory basis, reproducibility, and response to exercise training.

In patients with chronic heart failure (CHF), the anaerobic threshold by gas exchange (ATge) represents a potentially useful parameter for assessing functional disability and the response to therapeutic interventions designed to improve exercise tolerance. We measured the ventilatory, hemodynamic, and metabolic responses to maximal bicycle exercise in 64 patients with CHF and 38 age-matched normal subjects. The ratio of ventilation to carbon dioxide production (VE/VCO2) was increased during exercise in patients as compared with normal subjects although VE was closely related to VCO2 in both individual normal subjects and patients (all, r greater than 0.92, p less than 0.01). Increased VE/VCO2 in patients was unrelated to increased pulmonary vascular pressures but was closely linked to increases in the pulmonary dead space to tidal volume ratio (Vd/Vt). Despite hemodynamic abnormalities in patients, PaCO2 was regulated at normal levels during exercise. In a second study, we determined the ATge in 18 patients with CHF and 18 normal subjects by the ventilatory equivalents method. The ATge could be identified from unaveraged breath-by-breath data as the initial increase in VE/VO2 without an increase in the VE/VCO2 in 15 of 18 patients and in 16 of 18 normal subjects. The ATge demonstrated good day-to-day reproducibility (r = 0.91, p less than 0.001, SEE = 1.74 ml/kg/min) and low interobserver variability and was associated with comparable increases in arterial lactate in the two groups above the resting value, 0.9 +/- 0.4 mM/l in patients and 0.8 +/- 0.5 mM/l in normal subjects. To examine the effects of a chronic intervention on the ATge, 12 patients with CHF underwent exercise training for 4-6 months. Training resulted in a 23% improvement in peak VO2 and a decrease in blood lactate accumulation during submaximal exercise. This was associated with decreased VE and VCO2 during submaximal exercise, an increased VO2 at which the ATge occurred from 10.1 +/- 1.2 ml/kg/min to 12.1 +/- 2.6 ml/kg/min (p less than 0.01) and an increase in exercise duration during a symptom-limited, constant work-rate protocol (938 +/- 110 seconds vs. 1,421 +/- 691 seconds, p less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Anaerobic Threshold↗