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Biomedical subjects

F R Cobb

Publications and source records attributed to F R Cobb.

At least 55 records · Page 3Linked to original sources

Effects of atrial natriuretic peptide on proximal epicardial coronary arteries and coronary blood flow in conscious dogs.

The effects of atrial natriuretic peptide (ANP) on proximal epicardial coronary artery dimensions and coronary blood flow were examined in 7 awake dogs chronically instrumented with miniature coronary dimension crystals and Doppler flow probes on the circumflex coronary artery. ANP (10, 50, and 150 micrograms) was infused as a bolus via the left atrial catheter. Aortic pressure, left ventricular end-diastolic pressure, heart rate, and dP/dt did not change significantly with any dose of ANP. ANP caused transient (1-5 minutes) dose-related increases in coronary blood flow; maximum increases were 28.1 +/- 6.9%, 40.2 +/- 6.2%, and 73.9 +/- 12.5% with the 10-, 50-, and 150-micrograms doses, respectively. ANP also induced prolonged (average 70.2 +/- 28.6 minutes with 150-micrograms dose) dose-related increases in coronary diameter; maximum increases were 3.1 +/- 1.0%, 3.9 +/- 1.5%, and 5.7 +/- 1.3% with the 10-, 50-, and 150-micrograms doses, respectively. The increase in diameter was not attenuated when the transient increase in blood flow was prevented by partial occlusion with a pneumatic snare. Combined autonomic blockade with propranolol (1 mg/kg), phentolamine (1 mg/kg), and atropine (0.06 mg/kg) attenuated the relative increase in coronary flow but did not alter the increases in epicardial coronary diameter produced by ANP. These data demonstrate that bolus injection of ANP effects preferential, sustained, dose-dependent, flow-independent increases in epicardial coronary dimensions and relatively brief dose-dependent increases in coronary blood flow. The vasodilator effects of ANP on epicardial vessels are direct and are not mediated via the autonomic nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Vasoactive effects of serotonin on proximal coronary arteries in awake dogs.

This study evaluates the vasoactive effects and mechanisms of action of serotonin on epicardial arteries in awake dogs chronically instrumented with miniature piezoelectric dimension crystals on the proximal circumflex coronary artery. Serotonin (2-16 micrograms) infused as a bolus in the left atrium effected a dose-related biphasic response, which was characterized by an initial increase in vessel dimension with a peak response at 45-75 seconds, followed by a delayed and more sustained vasoconstriction, with a maximum response at 2-8 minutes. The magnitude of the initial vasodilation was generally greater than the delayed vasoconstriction. The initial vasodilation remained unchanged after selective S2 blockade with ketanserin (0.3 mg/kg) and was only minimally but insignificantly attenuated when flow was held constant but was reduced after S1 and S2 blockade with methysergide (0.25 mg/kg). Selective S2 blockade with ketanserin (0.3 mg/kg) attenuated the delayed vasoconstriction in most but not all dogs; the effect of ketanserin was, however, not significant when the entire group was considered. Selective endothelial denudation effectively eliminated the initial vasodilation response to serotonin and significantly augmented the delayed vasoconstriction when the dogs were studied 1-2 days after denudation. The data indicate that in the awake dog, serotonin effects a biphasic vasomotor response characterized by an initial vasodilation that is mediated primarily through a direct endothelium-dependent S1 mechanism followed by a delayed vasoconstriction that is probably mediated via a direct S2 effect on the vascular smooth muscle and is attenuated by the normal endothelium.

Animals↗

Physiologic basis for the age-related decline in aerobic work capacity.

To determine the physiologic mechanisms of the decline in aerobic work performance with age, a cross-sectional study was performed. Twenty-four sedentary male volunteers, aged 20 to 50 years, underwent right-sided cardiac catheterization, arterial cannulation, radionuclide angiography and expired gas analysis for detailed evaluation of central and peripheral cardiovascular function during submaximal and maximal exercise. Habitual physical activity level varied but was well matched across the age range. Over the 3-decade age range studied, there was no detectable change in cardiovascular function at rest. When peak exercise variables were examined, an age-related 25% decrease in O2 consumption was noted (r = -0.43, p = 0.04); this was associated with a 25% decrease in peak cardiac index (r = -0.54, p = 0.01) and a 20% decrease in peak heart rate (r = -0.63, p = 0.002). In addition, there was an age-related increase in calculated systemic and pulmonary vascular resistances and an increase in left ventricular ejection time. No age relation was seen for exercise stroke volume index, end-diastolic volume index, end-systolic volume index, pulmonary artery wedge pressure, ejection fraction or arteriovenous O2 difference. These results indicate that the age-related decline in aerobic work performance among men aged 20 to 50 years results primarily from a reduced exercise heart rate in older subjects rather than from a reduction in stroke volume or peripheral O2 utilization.

Adult↗

Comparison of nifedipine alone with propranolol alone for stable angina pectoris including hemodynamics at rest and during exercise.

The effects of nifedipine (60 to 90 mg/day) and propranolol (240 mg/day) on symptoms, angina threshold and cardiac function were compared in a placebo-controlled, double-blind, crossover study. Five-week treatment periods with nifedipine and propranolol were compared with 2 weeks of placebo treatment in 21 men with chronic stable angina pectoris, 13 of whom had symptoms both at rest and on exertion. Compared with placebo, New York Heart Association functional class improved in patients equally with nifedipine (p = 0.001) and propranolol (p = 0.006). Frequency of chest pain decreased with nifedipine (p = 0.001) and propranolol (p = 0.01), and nitroglycerin consumption similarly decreased with both treatments. Nifedipine significantly delayed the onset of chest pain (p = 0.01) and 1 mm of ST-segment depression (p = 0.002) during bicycle exercise; smaller increases with propranolol were not statistically significant. A preferential clinical response to nifedipine (9 patients) or propranolol (6 patients) was unrelated to the presence or absence of pain at rest or to any baseline hemodynamic finding. Nifedipine and propranolol were equally effective in relieving exertional ischemia as shown by improvements in ejection fraction at identical workloads, from 0.48 +/- 0.11 to 0.58 +/- 0.12 (p less than 0.001) and 0.56 +/- 0.14 (p less than 0.001), respectively. Exercise wall motion, assessed by a semiquantitative wall motion score, also improved with both drugs. Propranolol treatment decreased exercise cardiac output by 14% (p = 0.01) through its effect on heart rate. In contrast, nifedipine treatment had no effect on cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Tachycardia-induced cardiomyopathy: a reversible form of left ventricular dysfunction.

Eight patients, aged 5 to 57 years, with uncontrolled symptomatic tachycardia for 2.5 to 41 years (mean 15) and significant left ventricular (LV) dysfunction in the absence of any other apparent underlying cardiac disease underwent evaluation. Incessant tachycardia was present for 0.5 to 6.0 years (mean 2.1) in 7 patients. One patient had an ectopic atrial tachycardia and 7 patients had an accessory atrioventricular pathway that participated in reciprocating tachycardia. Six patients underwent surgery; the ectopic focus was ablated in 1 patient and an accessory pathway was divided in 5 patients. One patient underwent open ablation of the His bundle and 1 patient underwent closed-chest ablation of the atrioventricular conduction system. Myocardial biopsy specimens were obtained from 5 patients, none of which yielded a specific diagnosis. Pretreatment radionuclide angiography demonstrated a mean ejection fraction (EF) of 19 +/- 9% (range 10 to 35%). Following tachycardia control a marked improvement in LV function was noted in 6 of 8 patients at rest and in 1 additional patient during exercise. The EF increased to 33 +/- 17% (range 16 to 56%) an average of 8 days after treatment and to 45 +/- 15% (range 22 to 67%) at late follow-up 3.5 +/- 40 months (mean 17) later (p less than 0.005). Seven patients remain asymptomatic 11 to 40 months (mean 22) after the corrective procedure and have resumed normal activities. These findings suggest that chronic uncontrolled tachycardia may result in significant LV dysfunction, which is reversible in some cases after control of the arrhythmia.

Adolescent↗

Value and limitation of biplane rest and exercise radionuclide angiography for assessing individual bypass grafts: a prospective study.

This prospective study evaluated the ability of serial biplane rest and exercise radionuclide angiography to predict the status of individual coronary bypass grafts in 20 patients 2 to 6 months after surgery. The preoperative coronary angiogram was used to assign vessels to 10 regions of distribution on the radionuclide angiogram. Predictions of graft adequacy for individual vessels were based on a detailed assessment of rest and exercise wall motion in their regions of supply. Of 59 grafts, 38 were judged adequate (patent with less than 75% stenosis) and 21 inadequate by postoperative catheterization. Radionuclide prediction of graft status was possible for 32 of the 59 grafts, including 19 of 24 left anterior descending, 7 of 19 circumflex and 6 of 16 right coronary artery grafts. The status of the remaining 27 grafts could not be assessed because of normal wall motion in their region of supply both pre- and postoperatively (22 vessels) or because a region of supply was not represented on the biplane radionuclide angiogram (5 vessels). Of the 32 predictions made, 25 (78%) were correct, including 13 (93%) of 14 predictions of graft adequacy and 12 (67%) of 18 predictions of graft inadequacy. The single incorrect prediction of graft adequacy resulted from improved exercise wall motion in a region supplied by a graft judged as having a 75% anastomotic stenosis. Most incorrect predictions of graft inadequacy were due to new septal or other rest wall motion abnormalities postoperatively. The comparison of pre- and postoperative studies was essential to maintain the predictive ability of the test. Thus, a detailed analysis of regional wall motion by rest and exercise radionuclide angiography can be used to predict the status of individual coronary artery bypass grafts. Reliable predictions can be made for most successful anterior descending grafts, and may permit cardiac catheterization to be deferred in certain cases. However, the method is limited by the need to perform preoperative exercise studies, by the low number of right and circumflex coronary artery grafts that can be evaluated and by the poor specificity of predictions of graft failure.

Adult↗

Regulation of stroke volume during submaximal and maximal upright exercise in normal man.

To characterize the hemodynamic factors that regulate stroke volume during upright exercise in normal man, 24 asymptomatic male volunteers were evaluated by simultaneous right heart catheterization, radionuclide angiography, and expired gas analysis during staged upright bicycle exercise to exhaustion. From rest to peak exercise, oxygen consumption increased from 0.33 to 2.55 liters/min (7.7-fold), cardiac index increased from 3.0 to 9.7 liters/min per m2 (3.2-fold), and arteriovenous oxygen difference increased from 5.8 to 14.1 vol% (2.5-fold). The increase in cardiac index resulted from an increase in heart rate from 73 to 167 beats/min (2.5-fold), and an increase in left ventricular stroke volume index from 41 to 58 ml/m2 (1.4-fold). During low levels of exercise, there was a linear increase in cardiac index due to an increase in both heart rate and stroke volume index; stroke volume index increased as a result of an increase in left ventricular filling pressure and end-diastolic volume index and, to a much smaller extent, a decrease in end-systolic volume index. During high levels of exercise, further increases in cardiac index resulted entirely from an increase in heart rate, since stroke volume index increased no further. Left ventricular end-diastolic volume index decreased despite a linear increase in pulmonary artery wedge pressure; stroke volume index was maintained by a further decrease in end-systolic volume index. The degree to which stroke volume index increased during exercise in individuals correlated with the change in end-diastolic volume index (r = 0.66) but not with the change in end-systolic volume index (r = 0.07). Thus, the mechanism by which left ventricular stroke volume increases during upright exercise in man is dependent upon the changing relationship between heart rate, left ventricular filling, and left ventricular contractility. At low levels of exertion, an increase in left ventricular filling pressure and end-diastolic volume are important determinants of the stroke volume response through the Starling mechanism. At high levels of exertion, the exercise tachycardia is accompanied by a decrease in end-diastolic volume despite a progressive increase in filling pressure, so that stroke volume must be maintained by a decrease in end-systolic volume.

Adult↗

Value of radionuclide angiography for predicting specific cardiac events after acute myocardial infarction.

The value of rest and exercise radionuclide angiography (RNA) for predicting specific events including death, recurrent acute myocardial infarction (AMI), coronary care unit readmission for unstable chest pain, and medically refractory angina after AMI was studied in 106 consecutive survivors of AMI. Analysis of the RNA variables using the Cox proportional hazards regression model yielded significant associations of the time to death with ejection fraction at rest and during exercise (X2 = 11.1 and 14.0, respectively). Both variables added significant prognostic information to the clinical assessment (X2 = 4.3 and 5.7, respectively). The change in ejection fraction from rest to exercise predicted the time to coronary artery bypass grafting for medically refractory angina before (X2 = 21.0) and after (X2 = 13.2) adjustment for the clinical descriptors, but did not predict death or other non-fatal events. Significant correlations were found between RNA variables and a variety of clinical descriptors previously reported to have prognostic significance. Clinical and RNA variables that are measures of left ventricular function were predictive of subsequent mortality, whereas those that reflect residual potentially ischemic myocardium were predictive of subsequent nonfatal ischemic events. Rest and exercise RNA after AMI provides significant prognostic information regarding specific events during follow-up independent of that provided by clinical assessment.

Adult↗

Effects of reestablishing blood flow on extent of myocardial infarction in conscious dogs.

The effects of permanent circumflex coronary artery occlusion (PO) compared with reestablishing blood flow (OR) at 2 and 6 h after occlusion on the final extent of histological infarction (HI) was assessed in chronically instrumented awake dogs. The relationships between the extent of left ventricular ischemia measured by microsphere techniques and HI in the PO group were used as models to predict the expected infarction in the 2- and 6-h OR groups. Mean HI (+/-SD) in the PO and 6- and 2-h OR groups was 21 +/- 13, 19 +/- 10, and 13 +/- 12% of left ventricular weight, respectively; values were not significantly different. The extent of HI in samples grouped according to epicardial and endocardial layers and ischemic blood flow ranges (0-15, 16-30, 31-50, 51-75% of control region blood flow) was reduced in the 2-h but not 6-h OR group. Analysis of individual animals using total ischemic region blood flow to epicardial and endocardial layers demonstrated that OR at 2 h but not 6 h reduced infarction in most animals but not in certain animals with the largest ischemic regions.

Animals↗

Left ventricular ejection fraction after acute coronary occlusion in conscious dogs: relation to the extent and site of myocardial infarction.

The change in left ventricular radionuclide ejection fraction after acute occlusion of the left anterior descending (LAD) or circumflex (LC) coronary artery was compared with the ultimate histologic extent of myocardial infarction in conscious dogs. The acute change in ejection fraction correlated with size of infarction in 14 dogs with occlusions of the LAD coronary artery (r = .89, y = 1.12x + 14.2) and in 27 dogs with occlusions of the LC coronary artery (r = .71, y = 0.73x + 7.9); the slope of the regression equation was greater (p less than .05) for those with LAD than for those with LC occlusions. Multivariate analysis revealed no independent contribution of left ventricular weight, the subendocardial extent of infarction, or change in heart rate to the acute change in ejection fraction. These data indicate that the decrease in ejection fraction after coronary occlusion is determined primarily by the size of the ischemic area, which also determines size of infarction. In dogs instrumented over a long term, infarcts in the LAD myocardial distribution result in greater decreases in ejection fraction than infarcts of comparable size in the LC distribution.

Animals↗

Animal models for protecting ischemic myocardium: results of the NHLBI Cooperative Study. Comparison of unconscious and conscious dog models.

The Animal Models for Protecting Ischemic Myocardium Study was undertaken for the purpose of developing reproducible animal models that could be used to assess interventions designed to limit infarct size. This paper describes the results obtained in an unconscious dog model and in a conscious dog model, developed in three participating laboratories. The unconscious dog model, involving reperfusion after 3 hours of ischemia in open-chest dogs, was intended to determine whether therapy followed by early reperfusion would limit infarct size more than reperfusion alone. The conscious dog model used chronically instrumented dogs and permanent coronary occlusion to better mimic myocardial infarction in man. In both models, the proximal circumflex artery was occluded, and the primary experimental endpoint was infarct size, as measured by histological techniques 3 days after the initial occlusion. Infarct size was analyzed in relation to baseline variables including the anatomic area at risk, collateral blood flow to the subepicardial zone of ischemia and hemodynamic determinants of myocardial metabolic demand. Most of the variation in infarct size in control dogs could be related to variation in the area at risk, collateral blood flow, and rate pressure product. Using multivariate analysis and groups of 15 dogs, an intervention that limited infarct size by 10-13% of the area at risk would have been detected 50% of the time. Larger treatment effects would be detected more readily, and smaller effects often would be missed, unless group sizes were larger. Two drugs, verapamil and ibuprofen, were evaluated in both models, with experimental group sizes averaging 13 and 20 dogs, in the unconscious and conscious models, respectively. Three of 15 verapamil-treated dogs in the unconscious model study had much smaller infarcts than expected from baseline parameters. With these exceptions, neither drug limited infarct size in either model.

Anesthesia↗

Assessment of regional left ventricular function using gated radionuclide angiography.

A simple method for the assessment of regional left ventricular (LV) function using gated radionuclide angiography is described. The method divides the LV region of interest in the left anterior oblique view into quadrants using a count-weighted center point and a transparent overlay. The regional ejection fraction (EF) was determined at rest and during upright bicycle exercise for each of 3 quadrants identified as posterior, septal and apical. The study group consisted of 50 patients with chest pain. Nine of these patients had normal coronary arteries and 41 had significant coronary artery disease (CAD). Regional EF measurements were highly reproducible at rest and exercise in all regions. Regional EF values at rest were compared with the subjective assessment of wall motion on the contrast ventriculogram and were significantly lower in regions with abnormal wall motion. Regional EF increased with exercise in all patients with normal coronary arteries. In patients with CAD and normal regional wall motion at rest, the regional exercise response was significantly more sensitive (p = 0.004) than global exercise response and marginally more sensitive (p = 0.06) than the subjective assessment of exercise wall motion on visual radionuclide images in the diagnosis of CAD. These results suggest that the measurement of regional LV function may be useful in the noninvasive diagnosis of CAD.

Adult↗

Relation between radionuclide angiographic regional ejection fraction and left ventricular regional ischemia in awake dogs.

Multigated equilibrium radionuclide angiography was used to quantitate global and regional ejection fraction (EF) in 26 awake dogs 10 minutes after distal and then proximal occlusion of the left anterior descending (LAD) or left circumflex (LC) coronary artery. Changes in global and regional EF were correlated with simultaneous measurements of the extent of acute left ventricular (LV) ischemia measured by radioisotope-labeled microspheres. The extent of ischemia, defined as the percentage of LV mass with greater than 25% reduction in blood flow from normal regional flow, was linearly related to the percent change in global EF after LAD (r = 0.84) and LC (r = 0.77) occlusions. The extent of ischemia also correlated with regional EF (r = 0.47 to 0.88 for LAD and r = 0.41 to 0.69 for LC occlusions). In 24 of 25 LAD occlusions and in all 20 LC occlusions that produced a measurable ischemic zone, the maximal percent change in regional EF exceeded the percent change in global EF. Two LAD occlusions and 2 LC occlusions reduced regional EF but not global EF. Thus, global and regional EF decreased in direct proportion to the extent of acute myocardial ischemia; regional ischemia produced greater changes in regional than in global EF.

Animals↗

Prognostic indicators from radionuclide angiography in medically treated patients with coronary artery disease.

The purpose of this investigation was to determine which variables obtained when performing radionuclide angiography predict subsequent survival or total events (cardiovascular death or nonfatal myocardial infarction) in stable patients with symptomatic coronary artery disease (CAD). Univariable and multivariable analyses of 6 variables, including ejection fraction (EF) at rest and exercise, change in EF with exercise, development of ischemic chest pain or electrocardiographic changes, left ventricular (LV) wall motion abnormalities and exercise time were examined in 386 patients followed up to 4.5 years. Univariate analyses revealed that the exercise EF was the variable most closely associated with future events (p less than 0.01), followed by EF at rest, wall motion abnormalities and exercise time. Multivariable analyses revealed that once the exercise EF was known, no other radionuclide variables contributed independent information about the likelihood of future events. Multivariable analyses also revealed that the exercise EF describes much of the prognostic information of coronary anatomy. Our findings suggest that the radionuclide angiogram is useful in predicting future events in patients with stable CAD, although examination in conjunction with other clinical descriptors will be necessary to further quantify this contribution.

Cardiac Output↗

Mechanism and significance of a decrease in ejection fraction during exercise in patients with coronary artery disease and left ventricular dysfunction at rest.

The purpose of this study was to determine whether an exercise-induced decrease in ejection fraction in patients with coronary artery disease and left ventricular dysfunction at rest represents ischemia or the nonspecific response of a compromised left ventricle to exercise stress. Accordingly, radionuclide ejection fraction responses of 246 patients with coronary artery disease and an ejection fraction at rest of less than 0.50 were compared with those of a "nonischemic" control group of 48 patients with idiopathic dilated cardiomyopathy and a similar degree of ventricular dysfunction. The significance of the ejection fraction response in the group with coronary artery disease was further examined by relating it to the angiographic extent of coronary artery disease, severity of angina, incidence of chest pain and electrocardiographic ST segment depression during exercise and long-term prognosis. The ejection fraction decreased by greater than or equal to 0.01 and greater than or equal to 0.05 during exercise in 48 and 28%, respectively, of the patients with coronary artery disease compared with only 8 and 2%, respectively, of the patients with cardiomyopathy. When exercise was limited by fatigue at a submaximal heart rate, the ejection fraction decreased in 25% of the patients with coronary artery disease but in none of the patients with cardiomyopathy. Patients with coronary artery disease whose ejection fraction decreased during exercise had a significantly higher incidence of three vessel disease, exercise-induced chest pain or ST depression and late mortality than did patients whose ejection fraction did not decrease. These relations were confirmed equally in subgroups of patients with moderate (ejection fraction 0.30 to 0.49) and severe (ejection fraction less than 0.30) left ventricular dysfunction. Thus, in patients with coronary artery disease and left ventricular dysfunction at rest, a decrease in ejection fraction during exercise is more likely to indicate ischemia than a nonspecific left ventricular response to exercise stress. In the individual patient, a decrease of 0.05 or greater, or a decrease during submaximal exercise, appears to be highly specific for ischemia. A decrease in ejection fraction identifies a subgroup of patients with a high prevalence of multivessel coronary artery disease and a high risk of death during long-term follow-up on medical therapy.

Adult↗

Effects of physical conditioning on left ventricular ejection fraction in patients with coronary artery disease.

To address the hypothesis that physical conditioning may improve left ventricular function in patients with coronary artery disease, we performed first-pass radionuclide ventriculography in 53 patients at rest and during upright bicycle exercise before and after 6 to 12 months of exercise training. The peak bicycle workload achieved before the onset of fatigue, dyspnea, or angina increased by an average of 22% (p = .0001) after training, and mean heart rate at a workload equal to the pretraining maximum workload was decreased by 10 beats/min after training (p = .0002). Of 21 subjects with angina or exertional ST segment depression before training, 15 (71%) were able to exercise to the same workload without these manifestations of ischemia after training. Whereas neither mean resting left ventricular ejection fraction (LVEF) nor LVEF at peak exertion was significantly altered, mean LVEF at the pretraining maximum workload was increased from 0.50 to 0.54 (p = .002) after training. There was a significant correlation between the magnitude of training bradycardia and the increment in LVEF at the pretraining maximum workload (p = .009). We conclude that the relative bradycardia at comparable exercise workloads produced by exercise conditioning is associated with improvements in left ventricular performance as assessed by the LVEF. This observation is compatible with the hypothesis that training bradycardia in conditioned subjects with ischemic heart disease is associated with lower myocardial oxygen demand and lesser degrees of ischemia at comparable workloads. However, training effects on ventricular afterload or on ischemia contractile performance of the heart cannot be excluded.

Adult↗

Sex-related differences in the normal cardiac response to upright exercise.

In previous studies from this laboratory, we found that approximately 30% of women with chest pain and normal coronary arteries demonstrated either a decrease in or a failure to increase radionuclide ejection fraction during exercise. To examine the hypothesis that this apparent abnormality in left ventricular function represents a physiologic difference between men and women, we prospectively studied central and peripheral cardiovascular responses to exercise in 31 age-matched healthy volunteers (16 women and 15 men). A combination of quantitative radionuclide angiography and expired-gas analysis was used to measure ejection fraction and relative changes in end-diastolic counts, stroke counts, count output, and arteriovenous oxygen difference during symptom-limited upright bicycle exercise. Normal male and female volunteers demonstrated comparable baseline left ventricular function and similar aerobic capacity, as determined by weight-adjusted peak oxygen consumption (22.1 +/- 5.1 and 22.6 +/- 4.3 ml/kg/min, respectively). However, their cardiac responses to exercise were significantly different. Ejection fraction increased from 0.62 +/- 0.09 at rest to 0.77 +/- 0.07 during exercise in men (p less than .001), but was unchanged from 0.63 +/- 0.09 at rest to 0.64 +/- 0.10 during exercise in women. The ejection fraction increased by 5 points or more in 14 of 15 men, but in only seven of the 16 women. End-diastolic counts increased by 30% in women (p less than .001), but was unchanged in men. Because decreases in ejection fraction were matched by increases in end-diastolic counts, relative increases in stroke counts and count output were the same for men and women. These data demonstrate a basic difference between men and women with respect to the mechanism by which they achieve a normal response of stroke volume to exercise; these differences must be taken into account when measurements of cardiac function during exercise stress are used for diagnostic purposes.

Adult↗

Relationship between regional myocardial blood flow and thallium-201 distribution in the presence of coronary artery stenosis and dipyridamole-induced vasodilation.

This study assesses the relationship between the distribution of thallium-201 and myocardial blood flow during coronary vasodilation induced by intravenous dipyridamole in canine models of partial and complete coronary artery stenosis. 10 dogs were chronically instrumented with catheters in the left atrium and aorta and with a balloon occluder and electromagnetic flow probe on the proximal left circumflex coronary artery. Regional myocardial blood flow was measured during control conditions with radioisotope-labeled microspheres, and the phasic reactive hyperemic response to a 20-s transient occlusion was then recorded. Dipyridamole was then infused intravenously until phasic coronary blood flow increased to match peak hyperemic values. The left circumflex coronary artery was either partially occluded to reduce phasic blood flow to control values (group 1) or it was completely occluded (group 2), and thallium-201 and a second microsphere label were injected. 5 min later, the animals were sacrificed, the left ventricle was sectioned into 1-2-g samples, and thallium-201 activity and regional myocardial blood flow were measured. Curvilinear regression analyses between thallium-201 localization and myocardial blood flow during dipyridamole infusion demonstrated a slightly better fit to a second- as compared with a first-order model, indicating a slight roll-off of thallium activity as myocardial blood flow increases. During the dipyridamole infusion, the increases in phasic blood flow, the distributions of regional myocardial blood flow, and the relationships between thallium-201 localization and regional blood flow were comparable to values previously observed in exercising dogs with similar occlusions. These data provide basic validation that supports the use of intravenous dipyridamole and thallium-201 as an alternative to exercise stress and thallium-201 for evaluating the effects of coronary occlusive lesions on the distribution of regional myocardial blood flow.

Animals↗