Effect of Short-term Cardiovascular Conditioning and Low-Fat Diet on Myocardial Blood Flow and Flow Reserve
Background Cardiovascular conditioning reduces resting myocardial oxygen demand by lowering systolic blood pressure and heart rate. Lower myocardial oxygen demand at rest would be expected to be associated with a decrease in resting myocardial blood flow and, consequently, an increase in myocardial flow reserve as the ratio of hyperemic to resting blood flow. However, the effect of controlled exercise together with a low-lipid diet on myocardial blood flow and flow reserve has not been examined in humans.
Methods and Results Myocardial blood flow at rest and after dipyridamole-induced hyperemia (0.56 mg/kg IV) was quantified with [13N]ammonia and positron emission tomography in 13 volunteers before and upon completion of a 6-week program of cardiovascular conditioning and a low-fat diet. Exercise capacity and serum lipid profiles were also assessed at the start and finish of the program. Eight normal volunteers of similar age not participating in the conditioning program served as a control group. Cardiovascular conditioning lowered the resting rate-pressure product (8859±2128 versus 7450±1496, P<.001), serum cholesterol (217±36 versus 181±26 mg/dL), LDL cholesterol (140±32 versus 114±24 mg/dL), and triglycerides (145±53 versus 116±33 mg/dL, all P<.05). Exercise tolerance (metabolic equivalent of the task, METs) improved significantly from 10.0±3.0 to 14.4±3.6 (P<.01). Resting blood flow decreased (0.78±0.18 versus 0.69±0.14 mL · g−1 · min−1, P<.05), whereas hyperemic blood flow increased (2.06±0.35 versus 2.25±0.40 mL · g−1 · min−1, P<.05), resulting in an improved myocardial flow reserve (2.82±1.07 versus 3.39±0.91, P<.05). Overall, the myocardial flow reserve was significantly related to exercise performance (METs). In the control group, no changes in resting rate-pressure product, serum cholesterol levels, exercise performance, resting or hyperemic myocardial blood flow, or flow reserve were observed.
Conclusions Short-term cardiovascular conditioning together with a low-fat diet results in an improved myocardial flow reserve by lowering resting blood flow and increasing coronary vasodilatory capacity. These changes are associated with an improved exercise capacity and may offer a protective effect in patients with coronary artery disease.
The myocardial flow reserve declines with age primarily because of an age-dependent, progressive increase in resting cardiac work and, consequently, in myocardial blood flow at rest. This increase in resting cardiac work might be ascribed to a more sedentary lifestyle in the older population. Hyperemic blood flows tend to be lower in older volunteers, although no statistically significant reduction has been demonstrated.1 Cardiovascular conditioning together with a low-fat diet is known to lower resting heart rates and blood pressure.2 3 4 Therefore, we hypothesized that cardiovascular conditioning together with a low-fat diet might augment the myocardial flow reserve, primarily by decreasing cardiac work and, in turn, myocardial blood flow at rest. The net effect of these lifestyle modifications on myocardial blood flow at rest and during pharmacological stress remains unknown but can now be quantified noninvasively with positron emission tomography (PET) using [13N]ammonia as a tracer of blood flow.5 6 7
The aim of the present study was to measure the response of myocardial blood flow and flow reserve to cardiovascular conditioning together with a low-fat diet and to relate this response in blood flow to changes in (1) hemodynamics, (2) serum lipids, and (3) exercise performance.
The study group consisted of 13 volunteers (11 men, 2 women; mean age, 57±7 years). All were enrolled in the Pritikin Longevity Center outpatient program.8 Four subjects had a history of coronary artery disease as evidenced by prior coronary artery bypass surgery (n=2) or myocardial infarction (n=2). Four of the subjects had a history of systolic hypertension in excess of 150 mm Hg. The serum cholesterol levels exceeded 200 mg/dL in 9 of the 13 participants (69%). The majority of participants were therefore at increased risk for or had documented coronary artery disease.9 None of the participants had been on any lipid-lowering, cardiac, or antihypertensive medication before or during the study period.
The nonrandomized and nonconcurrent control group consisted of 8 normal volunteers (mean age, 53±10 years; 6 men, 2 women) who did not undergo any cardiovascular conditioning program. None had known coronary artery disease, 1 had mild systolic hypertension, 3 had a history of elevated serum cholesterol levels, and none was on any medication. All participants refrained from intake of caffeine-containing food or beverages for at least 24 hours before the PET study. Each signed an informed consent form approved by the UCLA Human Subject Protection Committee.
All participants of the study group underwent a 6-week program consisting of daily aerobic exercise, the Pritikin low-fat/low-cholesterol diet, and relaxation techniques.2 This program is subsequently referred to as “cardiovascular conditioning.” Exercise, primarily walking, was performed to achieve 70% of the maximal heart rate achieved on the stress test for at least 30 to 45 minutes. Participants attended the center 3 days per week, where they had a prepared meal, an exercise session, and a lecture on how to follow the diet as well as the relation between diet and exercise and diseases common in our society. The Pritikin eating plan consists of less than 10% of calories from fat, 10% to 15% from protein, and 75% to 80% from carbohydrates (vegetables, fruits, legumes, and whole grains). The diet contained 3 to 4 g of NaCl and less than 100 mg of cholesterol per day.8
Measurements Before and After Cardiovascular Conditioning
As part of screening before cardiovascular conditioning, all participants underwent a thorough history and physical examination and rest and stress ECG. Two-dimensional echocardiography at rest was performed before the initial PET study in each participant and analyzed visually by an independent observer for the presence of resting wall motion abnormalities.
Exercise Stress Testing
Heart rate and blood pressure were measured. In addition, exercise capacity before and after cardiovascular conditioning was assessed in each participant of the study and the control group using a Bruce treadmill protocol. Exercise capacity was expressed as metabolic equivalents of oxygen consumption (or metabolic equivalents of the task, METs).10
Serum Lipid Profiles
Serum lipids (total and HDL cholesterol and triglycerides) were measured with an Olympus autoanalyzer using enzymatic methods. LDL cholesterol was calculated according to the methods of Friedwald et al.11
Measurement of Myocardial Blood Flow
Myocardial blood flow at rest and during dipyridamole-induced hyperemia (0.56 mg/kg IV) was quantified in all study participants with intravenous [13N]ammonia and PET at 2 to 3 days before and 2 to 4 days after completion of the 6-week cardiovascular conditioning program (average time interval, 46±5 days). In the control group, resting and hyperemic blood flows were quantified twice within 44±7 days (NS versus study group). Throughout each flow measurement, the ECG was monitored continuously while heart rate and arterial blood pressure (cuff measurements) were obtained at 1-minute intervals.
The methods used for the quantification of myocardial blood flow at rest and during dipyridamole-induced hyperemia have been described in detail previously.1 In brief, after intravenous injection of [13N]ammonia (10 to 15 mCi), serial transaxial images were acquired with whole-body PET (model 931/8, CTI-Siemens). The transaxially acquired images were then reoriented into six short-axis images of the left ventricle, assembled into polar maps of myocardial blood flow, and compared with a reference database of normals.12
In the healthy participants, three 90-degree regions of interest were placed in the three territories of the major coronary arteries. In the 4 participants with coronary artery disease, only segments with normal wall motion and homogeneous [13N]ammonia distribution on both the resting and hyperemic polar maps were analyzed. The two (in the 4 patients with coronary artery disease) or three (in the 9 healthy subjects) regions of interest were copied to the serially acquired images to derive myocardial tissue time-activity curves,1 which were corrected for partial volume effect by assuming a uniform left ventricular wall thickness of 1 cm13 for activity spillover from the left ventricular blood pool to the left ventricular myocardium13 and for physical decay of [13N]ammonia activity.
The arterial input function was derived from a small region of interest in the center of the left ventricular blood pool and copied to the serially acquired images.14 The first 120 seconds of the decay-corrected myocardial and blood pool time activity data were then fitted with a previously validated two-compartment model for [13N]ammonia.6 The sectorial values of blood flow were averaged, and one mean flow value for blood flow was obtained in each patient.
Mean values are given with standard deviations. Changes in serum lipid levels, hemodynamic and blood flow data, and exercise performance (METs) from baseline to follow-up were compared using the Student’s t test for paired data. Correlations were sought using least-squares regression analysis. Probability values less than .05 were considered significant.
Each of the 4 volunteers with known coronary artery disease in the study group exhibited a resting wall motion abnormality in one myocardial segment. These segments were excluded from further quantitative tomographic analysis. In the 9 remaining participants, wall motion was normal by echocardiography. No echocardiographic studies were performed in the control group.
Hemodynamic Findings and Exercise Capacity
The hemodynamic measurements obtained in the study group and in the control group at baseline and at follow-up are listed in Table 1⇓. In the study group, resting systolic blood pressure (P<.05), mean aortic blood pressure (P<.05), and heart rate (P<.05) decreased, whereas diastolic blood pressure remained unchanged from the baseline to the follow-up study. The rate-pressure product decreased from 8859±2128 to 7450±1496 mm Hg/min (P<.001). Similar decreases for systolic blood pressure were observed during intravenous dipyridamole. However, heart rate and diastolic blood pressure during dipyridamole remained unchanged from baseline to follow-up. Exercise capacity, expressed as metabolic equivalents of whole-body oxygen consumption (METs), improved from 10±3 to 14±3.6 at follow-up (P<.01). However, this improvement might be explained by a “learning effect” rather than by the conditioning program.
In contrast, no significant changes in rate-pressure product at rest (7905±1271 versus 8113±1849), mean aortic blood pressure during dipyridamole (82±7 versus 86±8 mm Hg), or exercise capacity (11.4±1.0 versus 11.5±0.8 METs) were observed in the control group (also see Table 1⇑).
Serum Lipid Profiles
The serum lipid profiles before and upon completion of the diet and cardiovascular conditioning program are listed in Table 2⇓. Total cholesterol, triglycerides, and LDL cholesterol were lower after cardiovascular conditioning (P<.05), whereas HDL cholesterol remained unchanged. In contrast, no changes in total cholesterol (197±17 versus 203±16 mg/dL), triglycerides (148±61 versus 138±37 mg/dL), and LDL cholesterol (119±17 versus 127±17 mg/dL) or HDL cholesterol (39±9 versus 41±10 mg/dL) were observed in the control group.
Semiquantitative Image Analysis
Polar map analysis of the myocardial [13N]ammonia uptake at rest and during hyperemia revealed regional myocardial blood flow defects in 4 of the 13 participants of the study group. The flow defects corresponded in location to the wall motion abnormalities as noted on two-dimensional echocardiography. Pharmacological vasodilation in the 4 patients with coronary artery disease did not alter the extent or the severity of the flow defects, nor did it induce new flow defects. Semiquantitative analysis of the polar maps further indicated that these flow defects on the rest and hyperemic images remained unchanged after cardiovascular conditioning. The remaining 9 subjects (69.3%) had normal wall motion at rest and homogeneous [13N]ammonia activity distributions in both pairs of rest and hyperemic [13N]ammonia blood flow studies as compared with a database of normal. Furthermore, no perfusion abnormalities were observed on any of the [13N]ammonia blood flow studies in the 8 participants of the control group.
Myocardial Blood Flow
The individual blood flow measurements obtained in the participants of the conditioning program are listed in Table 1⇑. Resting blood flow averaged 0.78±0.18 mL · g−1 · min−1 at baseline and declined to 0.69±0.14 mL · g−1 · min−1 after completion of the Pritikin program (P<.05). This decline in resting myocardial blood flow paralleled the reduction in the resting rate-pressure product. Overall, myocardial blood flow correlated significantly with the rate-pressure product (r=.84; SEE, 0.0001; P<.0001; Fig 1⇓). In contrast, no changes in resting blood flow were observed in the control group (0.71±0.13 versus 0.79±0.14 mL · g−1 · min−1).
Dipyridamole-induced hyperemic blood flow increased from 2.06±0.35 mL · g−1 · min−1 at baseline to 2.25±0.40 mL · g−1 · min−1 (P<.01) at follow-up (Table 1⇑). No significant correlations between hyperemic blood flow and the rate-pressure product or the mean aortic blood pressure were found. Furthermore, the magnitude of hyperemic blood flows did not correlate with serum cholesterol or LDL cholesterol levels. However, changes in hyperemic blood flow from baseline to follow-up tended to correlate with changes in serum cholesterol levels (P=.07) but not with LDL cholesterol. Overall, hyperemic blood flow was correlated with exercise performance (METs; r=.5; SEE, 1.84; P<.05). No significant changes in hyperemic blood flow were observed in the control group (2.10±0.23 versus 2.08±0.36 mL · g−1 · min−1).
Myocardial Blood Flow Reserve
In the study group, the lower resting blood flow after cardiovascular conditioning together with higher hyperemic flow resulted in a significant increase in myocardial flow reserve (2.82±1.07 versus 3.39±0.91; P<.01; Table 1⇑). Myocardial flow reserve before and after the conditioning program correlated, as expected, with resting blood flow (r=−.77; SEE, 1.04; P<.01 and r=.71; SEE, 1.45; P<.01), resting rate-pressure product (r=.73; SEE, 0.0001; P<.01 and r=.62; SEE, 0.0001; P<.05; Fig 2⇓), and hyperemic blood flow (r=.61; SEE, 0.64; P<.05 and r=.58; SEE, 0.54; P<.05).
Changes in myocardial flow reserve were associated with changes in resting blood flow (r=.82; SEE, 0.33; P<.001), hyperemic blood flow (r=.71; SEE, 0.49; P<.01) and resting rate-pressure product (r=.57; SEE, 0.97; P<.05; Fig 3⇓), and changes of total serum cholesterol (r=.58; SEE, 0.85; P<.05; Fig 4⇓). Changes in LDL cholesterol tended to correlate with changes in myocardial flow reserve, yet this correlation failed to attain statistical significance (r=.50, P=.076). Myocardial flow reserve was directly correlated with exercise capacity (r=.58; P<.01; SEE, 1.04; Fig 5⇓).
In the control group, there were no significant changes in myocardial flow reserve from baseline to follow-up (3.05±0.61 versus 2.72±0.80 mL · g−1 · min−1).
Coronary Vascular Resistance
During maximal coronary vasodilation, hyperemic blood flows depend on coronary driving pressure, among other factors. To relate the coronary driving pressure to hyperemic blood flows, an index of the coronary vascular resistance was established as the ratio of the mean aortic blood pressure (mm Hg) over myocardial blood flow (mL · g−1 · min−1). Resting coronary resistance remained unchanged from baseline to follow-up (138±32 versus 146±28 mm Hg · mL−1 · g−1 · min−1). In contrast, coronary vascular resistance during dipyridamole-induced hyperemia (“minimal coronary resistance”) decreased from 52±11 to 45±10 mm Hg · mL−1 · g−1 · min−1 (P<.01).
No statistically significant correlations were found between minimal coronary vascular resistance or its changes and serum cholesterol or LDL cholesterol levels or their changes. However, minimal coronary vascular resistance correlated with exercise performance (METs; r=.58; SEE, 1.84; P<.05).
In the control group, minimal coronary vascular resistance remained unchanged between the initial study and the follow-up study (41±6 versus 42±6 mm Hg ·mL−1 · g−1 · min−1).
The findings of this study indicate that cardiovascular conditioning consisting of regular, controlled physical exercise, low-fat diet, and relaxation techniques enhances myocardial flow reserve. This increase results largely from a reduction in resting cardiac work and consequently, resting myocardial blood flow. An unexpected finding of this study was that cardiovascular conditioning also resulted in higher hyperemic blood flow, which contributed to the observed increase in myocardial flow reserve. This improvement in flow reserve was correlated significantly with an improvement in exercise capacity. The absence of significant alterations in blood flow and flow reserve in a control group supports the notion that the changes in myocardial blood flow and vasodilator capacity can in fact be attributed to cardiovascular conditioning.
Limitations of the Study
The cardiovascular conditioning program consisted of regular physical exercise combined with dietary and lifestyle changes. Therefore, it is difficult to determine which of these components accounted primarily for the improvement in flow reserve. The results offer no mechanistic explanations. Thus, it remains uncertain whether exercise, dietary changes, or both produced the increase in myocardial flow reserve. Yet, it seems likely that regular exercise was a main factor reducing cardiac work and thus blood flow at rest, as reported previously.2 3 4
As another limitation, myocardial blood flow and its changes were not quantified in dysfunctional myocardial segments of the 4 patients with coronary artery disease. The small sample size and the short duration of the program precluded a meaningful statistical analysis of the changes in dysfunctional myocardial regions. However, regression of coronary artery disease and thus, measurable changes in blood flow to ischemically compromised myocardium as described previously,15 would be expected to occur if the participants had continued cardiovascular conditioning for longer time periods. However, the semiquantitative findings on the polar maps of the [13N]ammonia uptake that indicated the presence of fixed flow defects and failed to identify new, hyperemia-induced flow abnormalities suggest that the flow defects together with the resting wall motion abnormalities primarily represented myocardial scarring.
The heterogeneity of the study population represents another potential limitation. The group consisted of apparently healthy volunteers and patients with hypertension, elevated serum cholesterol, or documented coronary artery disease. The most prominent changes in myocardial blood flow and flow reserve were, as expected, observed in patients with coronary artery disease and hypertension. The flow reserve in “normal” participants also tended to improve (from 3.33±1.22 to 3.67±1.02; see Table 1⇑). However, the addition of the 2 patients with hypertension to the subgroup of “healthy” participants resulted only in a tendency toward an improved flow reserve (P=.115).
The improvement in blood flow and flow reserve in the patients with coronary artery disease is not surprising. First, systolic blood pressure and rate-pressure product tended to be higher in patients than in the healthy participants. Thus, cardiovascular conditioning was likely to have a greater impact on resting cardiac work and hence, myocardial blood flow at rest. Second, the low-fat diet was more likely to affect the vasodilatory capacity in patients with more abnormal coronary vasomotion than in healthy subjects. This possibility is in agreement with recent findings that demonstrated reductions in extent and severity of perfusion abnormalities in patients with coronary artery disease by PET after aggressive lipid-lowering therapy.16 17 18 However, reductions in serum lipid levels might also account in part for the observed trend of an improved flow reserve in the apparently healthy volunteers.19 The more pronounced improvement in vasodilatory capacity in patients with coronary artery disease or hypertension suggests that this group might benefit most from cardiovascular conditioning and a low-fat diet.
The majority of participants were at an increased risk for coronary artery disease.9 Despite the high accuracy of PET for detection of coronary artery disease,20 21 coronary artery disease in the 9 asymptomatic subjects without clinical signs of coronary artery disease could have been ruled out with certainty only by coronary angiography. However, blood flow was quantified only in segments with normal resting wall motion and normal [13N]ammonia uptake at rest and during dipyridamole. Thus, it is unlikely that these myocardial territories were supplied by coronary arteries with significant disease. Moreover, each participant served as his or her own control. Myocardial blood flow was quantified in the same myocardial segments before and after cardiovascular conditioning. Therefore, even the presence of mild coronary artery disease would not invalidate the finding of an improved flow reserve after cardiovascular conditioning.
As another limitation, the age-matched control group was nonrandomized and none of the control subjects had documented coronary artery disease. However, 1 control subject had hypertension and 3 had elevated cholesterol levels. Thus, the control group and the participants in the conditioning program without coronary artery disease had similar demographic characteristics.
Left ventricular wall thickness was not measured in this study but was assumed to be 1 cm for purposes of correction for partial volume effects. Thus, left ventricular hypertrophy cannot be ruled out with certainty in hypertensive individuals although ECG signs were absent. The assumption of a uniform wall thickness of 1 cm for partial volume correction might have caused some errors in the flow measurements. However, left ventricular hypertrophy would have affected the baseline and follow-up blood flow measurements equally because significant changes in wall thickness were unlikely to have occurred during only 6 weeks of cardiovascular conditioning. Thus, while measured rather than estimated wall thickness might have yielded slightly different estimates of blood flow, possible errors resulting from assuming a fixed, uniform wall thickness would not have altered the observed directional changes in resting and hyperemic blood flows.
The current study demonstrates a significant 15% reduction in the resting rate-pressure product after cardiovascular conditioning. It might be argued that anxiety of the participants during the initial PET study accounted for the initially higher rate-pressure product. However, similar reductions in blood pressure and heart rate after cardiovascular conditioning have been reported previously.2 3 4 22 Moreover, no changes in resting rate-pressure product from baseline to follow-up were observed in the control group. Initial anxiety was therefore unlikely to explain the higher rate-pressure products during the flow measurements in the study group.
Effects of Cardiovascular Conditioning on Myocardial Flow Reserve
The myocardial flow reserves of 2.82±1.07 mL · g−1 · min−1 in the study group and 3.05±0.61 in the control group at baseline are similar to the 3.01±0.73 reported previously for healthy volunteers of similar age (57±7 and 53±10 years versus 64±9 years).1 Cardiovascular conditioning raised the myocardial blood flow reserve by 20% to 3.39±0.91 mL · g−1 · min−1, which is lower than the previously reported flow reserve of 4.08±0.9 in young volunteers (31±9 years) with similar rate-pressure products at rest (6895±1069 versus 7450±1496; P=NS) and low risk for coronary artery disease.1 The lower flow reserve in the current study group was caused by lower hyperemic blood flow, possibly because of the 4 patients with coronary artery disease and the higher likelihood of early coronary artery disease in the remaining participants.
Effects of Cardiovascular Conditioning on Myocardial Blood Flow at Rest
Regular exercise reduces blood pressure and heart rate at rest and during mental stress, possibly by reducing adrenergic activity. Accordingly, cardiac work and, in turn, myocardial oxygen consumption, decline at rest and possibly at any submaximal workload in patients with coronary artery disease and in healthy subjects.23 The lower myocardial oxygen demand would be expected to be associated with proportional reductions in myocardial blood flow.1 24 25 Consistent with these earlier observations, cardiovascular conditioning in this study reduced the resting rate-pressure product (as an index of myocardial oxygen consumption) by lowering systolic blood pressure and heart rate, whereas no such changes were observed in the control group. This was associated with a proportionate decline in resting blood flow in the study group, which in turn contributed to the improved flow reserve.
Effects of Cardiovascular Conditioning on Hyperemic Blood Flows
The observed increase in hyperemic blood flow and decrease in the minimal coronary resistance after cardiovascular conditioning were unexpected in the current study. In contrast, hyperemic blood flow remained unchanged in the control group. Possible explanations for this observation include (1) a reduction in extravascular compressive forces,26 (2) beneficial effects of lowered lipid levels on endothelium-dependent and endothelium-independent vasodilation,16 17 18 19 27 (3) lower blood viscosity caused by the reduction of serum lipid levels and as previously reported for this diet and exercise program,28 29 (4) capillary recruitment,30 or (5) an augmented, flow-mediated, endothelium-dependent dilatory response or even an enlargement of the conductance vessels.31 32 33
Hyperemic myocardial blood flow is modulated by extravascular compressive forces and thus might vary with changes in myocardial contractility.26 Exercise training increases myocardial contractility, which in turn can augment extravascular compressive forces and attenuate the hyperemic blood flow. Thus, reductions in extravascular compressive forces are unlikely to explain the increased hyperemic blood flow after cardiovascular conditioning.
Serum triglyceride, total cholesterol, and LDL cholesterol levels declined with cardiovascular conditioning. Elevated serum LDL levels may attenuate endothelium-dependent vasodilation.34 In hypercholesterolemic nonhuman primates without macroscopic evidence of arteriosclerosis, endothelium-dependent vasodilation in response to intracoronary acetylcholine has been found to be impaired, whereas endothelium-independent vascular smooth muscle relaxation after intracoronary adenosine or sodium nitroprusside remained unaltered.35 However, one study in isolated rabbit arteries demonstrated an impairment of endothelium-independent vasodilation by nitroglycerin in the most severely diseased coronary arteries.27 Because segments with abnormal wall motion and blood flow were excluded from the current study, severe arteriosclerotic changes were unlikely to be present in the coronary territories analyzed. Reductions in serum cholesterol levels also might have contributed to the improved hyperemic blood flow via improved flow-mediated, endothelium-dependent vasodilation.33
Reductions in blood viscosity in response to cardiovascular conditioning, as for example due to lower cholesterol and triglyceride levels as reported previously,29 also might have affected beneficially the coronary vasodilatory capacity. However, blood viscosity and its changes were not measured in the current study.
Alternatively, cardiovascular conditioning might induce morphological changes of the coronary circulation. For instance, exercise training in rats has been found to increase the density of capillaries and thus, capillary recruitment,30 which could lead to a greater vasodilator capacity. However, the duration of cardiovascular conditioning required to produce increases in capillary density in humans remains unknown.
Increases in the diameter of the epicardial coronary arteries may serve as another possible explanation for the observed lower coronary resistance during pharmacological vasodilation. For example, short-term cardiovascular conditioning in dogs or a physically active lifestyle produced an increase in coronary artery diameter.32 36 Conversely, Langille and O’Donnel37 reported a 21% decrease in the diameter of rabbit carotid arteries after chronic reductions in blood flow.
More recently, Haskell et al31 observed a higher coronary vasodilating capacity in highly trained ultradistance runners compared with nontrained individuals. Nitroglycerin administration produced a 2.2-fold greater increase of the total coronary cross-sectional area in trained as compared with untrained individuals despite similar baseline coronary artery diameters. Also, the response of the brachial artery to pharmacological vasodilation is more pronounced in trained than in untrained individuals.38 The mechanisms underlying these changes remain unknown. Acute increases in blood flow might result in an augmented, flow-mediated, endothelium-dependent dilation of the large coronary arteries, which might be one important factor explaining the improved vasodilatory capacity after the conditioning program.33 However, it is also conceivable that frequent coronary flow increases due to daily exercise might induce structural modifications of the human coronary circulation.
Implications of the Study
The current study demonstrates that cardiovascular conditioning improves myocardial flow reserve. This improvement, observed in myocardium subtended by coronary arteries without apparent hemodynamically significant lesions, may have implications for patients with coronary artery disease. Cardiovascular conditioning in such patients may exert a protective effect on the coronary microcirculation by an increase in capillary density or by improved flow-mediated vasodilation and might thereby reduce the functional severity of coronary stenosis.
The Laboratory of Structural Biology and Molecular Medicine is operated for the US Department of Energy by the University of California under contract DE-FC03-87ER60615. This work was supported in part by the Director of the Office of Energy Research, Office of Health and Environmental Research, Washington, DC, by research grants HL-29845 and HL-33177, National Institutes of Health, Bethesda, Md, and by an Investigative Group Award by the Greater Los Angeles Affiliate of the American Heart Association, Los Angeles, Calif. We would like to thank Robert Pritikin, Director of the Pritikin Longevity Center, for recommending that his participants volunteer for our experiment. We thank Diane Martin for preparing figures and tables and Eileen Rosenfeld for skillful preparation of the manuscript. We want to thank Ron Sumida, Larry Pang, Francine Aguilar, Marc Hulgan, and Derjenn Liu for technical assistance.
- Received December 6, 1994.
- Accepted January 10, 1995.
- Copyright © 1995 by American Heart Association
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