(Hypertension. 2000;36:343.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
Coronary Vasodilator Capacity and Epicardial Vessel Remodeling in Physiological and Hypertensive Hypertrophy
From the Institute of Clinical Physiology, CNR (M.K., G.B.), and Department of Internal Medicine (F.G., F.F., C.G., C.P.), University of Pisa, and Clinica Medica Generale, Ospedale Maggiore, University of Milan (L.G.), Italy.
Correspondence to Carlo Palombo, MD, Institute of Clinical Physiology, CNR, via Savi 8, 56 126 Pisa, Italy. E-mail palombo{at}po.ifc.pi.cnr.it
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Abstract—The aim of this study was to compare resting coronary flow velocity, determinants of myocardial oxygen demand, and coronary vasodilator capacity in subjects with physiological, exercise-induced, and hypertensive left ventricular hypertrophy. Sixteen healthy sedentary men, 16 endurance athletes, and 16 hypertensive subjects (mean±SEM for left ventricular mass index: 94.9±5.5, 184.6±8.4, 154.4±9.5 g/m2, respectively) were studied by transesophageal and transthoracic Doppler echocardiography. Coronary flow velocity in left anterior descending artery and cross-sectional area of left main artery were assessed at rest and during dipyridamole-induced vasodilation. Myocardial oxygen demand was estimated through rate-pressure product, left ventricular wall stress, and inotropic function. Coronary flow reserve and minimum coronary resistance were comparable to those of sedentary men in athletes (mean±SEM: 3.23±0.16 versus 3.60±0.18 and 0.96±0.06 versus 1.04±0.04 mm Hg · s · cm-1), while in hypertensive subjects they were decreased and increased, respectively (mean±SEM: 2.31±0.08 and 1.21±0.10 mm Hg · s · cm-1; P<0.05 for both). Resting flow velocity was directly related to rate-pressure product in sedentary men and athletes and also to wall stress in athletes, while these correlations were absent in hypertensives. Dilation of left main artery after dipyridamole was significantly higher in athletes than in sedentary men and hypertensive subjects (mean±SEM for area change: 32.9±3.7% versus 12.8±2.5% and 6.4±3.3%; P<0.05 and 0.01). These data indicate that vasodilator capacity of coronary microcirculation is not impaired in athletes with physiological hypertrophy, in contrast to hypertensive patients. The relationship between resting flow velocity and determinants of oxygen demand is preserved in physiological hypertrophy but missing in hypertensive hypertrophy. Furthermore, the vasodilator capacity of coronary macrocirculation is also enhanced in exercise-trained subjects.
Key Words: hypertrophy, left ventricular • circulation • exercise • aging
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Left ventricular hypertrophy (LVH) represents an adaptive mechanism by which the heart normalizes wall stress and preserves left ventricular (LV) function. Both systemic hypertension and chronic exercise training may induce LVH. While hypertensive LVH represents a risk factor for cardiovascular morbidity and mortality1 and is associated with an impairment in coronary vasodilator capacity,2 3 chronic exercise training is supposed to improve cardiovascular capacity and to reduce morbidity and mortality.4 5 Experimental studies suggest an exercise-induced protective adaptation in coronary circulation, which may include both structural changes6 7 and changes in vasomotor responses.8 9 10 It was demonstrated that in normotensive animals, such as rat,11 12 dog,13 and swine,7 chronic exercise training results in an improvement of coronary vasodilator reserve. By contrast, studies comparing coronary vasodilator capacity in hypertensive patients with LVH and physically trained subjects with similar age and LV mass are not available.
The present study was designed to compare coronary function, including resting coronary flow and its determinants, vasodilator capacity of conductive and resistive coronary vessels, and remodeling of epicardial vessels in highly trained subjects with physiological LVH, hypertensive subjects with a similar degree of LVH, and healthy sedentary men with normal LV mass. In addition, the effect of aging on coronary vasodilator capacity was compared between hypertensive and exercise-trained subjects.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Study Population
The study population consisted of 48 subjects, all men: 16 healthy, untrained volunteers (aged 18 to 62 years), 16 endurance athletes (marathon runners and triathletes) with mild to moderate LVH (aged 20 to 79 years), and 16 hypertensive subjects with mild to moderate LVH (aged 41 to 68 years). The mean duration of exercise conditioning in athletes was 28±15 years. LVH in hypertensive subjects and athletes was defined as LV mass index value of 117 g/m2.14 Coronary artery disease, valvular or primary myocardial heart disease, diabetes, and dyslipidemia were ruled out. None of the controls and athletes was receiving any therapy at the time of the study; in hypertensive patients, calcium antagonists were discontinued at least 72 hours before the study, and all other medications had been stopped for at least 1 week. The study was approved by the internal ethics committee, and all participants provided informed consent according to the Declaration of Helsinki.
Study Protocol
The proximal part of the left anterior descending artery (LAD)
was visualized from the upper esophagus by a
transesophageal approach, according to a previously
described procedure.15 Blood flow was detected by color
and spectral Doppler, and basal coronary flow velocity
recording was acquired (SONOS 2500, Hewlett-Packard Co).
Digitized "zoomed" 2-dimensional images of the left main
coronary artery (LMA) were stored for diameter measurement.
To assess LV wall stress and inotropic function, the probe was briefly advanced to the stomach, and transgastric short-axis view of the left ventricle at the level of papillary muscle was acquired (in both 2-dimensional and M-mode images). Subsequently, the probe was withdrawn to the upper esophagus, and the Doppler signal from LAD was obtained again. Basal coronary flow velocity was remeasured, and high-dose infusion of dipyridamole (0.84 mg/kg for 9 minutes) was started through an indwelling 18-gauge cannula in an antecubital vein. The Doppler signal from the LAD was recorded continuously during dipyridamole infusion and for 8 minutes afterward. Flow velocity was measured by pulsed Doppler; when the velocity exceeded the Doppler limit, continuous-wave Doppler was used. The LMA diameter was remeasured at the maximal flow response. At the end of the study, aminophylline 80 mg was injected in bolus to antagonize the effects of dipyridamole.
Throughout the study, 3-lead ECG and blood pressure (Finapres; Ohmeda) were continuously monitored, and 12-lead ECG was recorded every 2 minutes.
Echocardiographic Indices
LV mass, peak systolic wall stress (PSWS) (pascals),
end-systolic wall stress (ESWS) (pascals), and midwall
fractional shortening (MFS) (%) were calculated according to the
corresponding formulas.16 17 18 The measurements necessary
for calculations were obtained from M-mode images of the left ventricle
in transthoracic parasternal (for LV mass) or
transesophageal transgastric (for PSWS, ESWS, and MFS)
view. Triple product (TP) (mm Hg · bpm · g) was
calculated by multiplying rate-pressure product (RPP) by LV
mass.
Coronary Blood Flow Velocity Measurement
The average of instantaneous spectral peak velocities during
cardiac cycle (APV) (cm/s) was measured rather than peak
diastolic velocity because it better corresponds to volume
flow rate.19 The reproducibility of these measurements was
proven in previous studies.15 20 The mean of 5
beats was used for statistical analysis.
The maximal coronary vasodilator response to
dipyridamole was assessed as both coronary flow
reserve (CFR) and minimum coronary vascular resistance (MCR)
(mm Hg · s ·
cm-1) and calculated
according to the corresponding formulas.15 Furthermore,
the ratio of resting coronary vascular resistance (CVR)
to MCR (ie, resistance ratio [RR]) and the percent change from
resting CVR to MCR (
CVR) (%) were calculated. The accuracy of
transesophageal echocardiography
(TEE) Doppler for the assessment of coronary vasodilator
capacity was preliminarily validated against
intracoronary Doppler (Flow-wire, Cardiometrics) in
a different group of 10 hypertensive patients undergoing
coronary angiography for chest pain. The time interval between
TEE and intracoronary Doppler study did not exceed 1
week.
In all study groups, correlations of resting APV with age, LV mass, resting RPP, TP, PSWS, ESWS, and MFS as well as correlation of APV after high-dose dipyridamole with age and LV mass were investigated by means of regression analysis.
Evaluation of Coronary Artery Caliber
LMA diameter was measured basally and during maximal flow
response in 2-dimensional images. Measurements were provided by bow
compasses from digitized "zoomed" diastolic images at 3
different segments of LMA, and the mean value was used to
calculate LMA area. The mean of 5 cardiac cycles was used for
statistical analysis. Correlations of LMA area at baseline and
after dipyridamole with age and LV mass were
investigated by means of regression analysis. The accuracy of
TEE for the measurement of epicardial vessel diameter was preliminarily
validated against quantitative coronary angiography in a
different group of 20 subjects with normal coronary arteries
undergoing diagnostic coronary angiography for
chest pain.
Data Analysis
Data in the tables are expressed as mean±1 SEM. ANOVA
was used when appropriate. To assess statistical significance between
groups, Scheffé’s F test was applied, with a value of
P<0.05 considered significant. Regression analysis
was performed with simple linear and multiple stepwise models.
Statistical analysis was performed by commonly available
software (StatView SE+ Graphics, Abacus Concepts Inc). The agreement
between TEE Doppler, intracoronary Doppler, and
quantitative coronary angiography, respectively, was assessed
according to the Bland-Altman approach.21
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Validation of the TEE approach for measurement of CFR and LMA diameter against intracoronary Doppler and quantitative coronary angiography, respectively, is presented in Figure 1.
|
Age and Echocardiographic Measurements
Mean age was comparable between hypertensive subjects and athletes
and was slightly lower in healthy sedentary men (Table 1). Elderly subjects were defined
as those aged 
65 years.22 LV mass and mass index were
higher in athletes than in hypertensive subjects (P<0.05
for LV mass index) because of slightly higher LV diastolic
diameter. MFS was reduced in hypertensive subjects (P<0.05
versus sedentary men). No differences between groups were observed for
PSWS and ESWS.
|
Systemic Hemodynamics
Systolic, diastolic, and mean blood pressure
measured simultaneously with coronary flow
velocity, both at rest and after high-dose
dipyridamole, were higher in the hypertensive group
(Table 2). Heart rate was lower in
athletes than in hypertensive subjects. Resting RPP was higher in
hypertensive subjects than in either sedentary men or athletes
(P<0.01 versus both).
|
Coronary Blood Flow Velocity Responses
Resting APV of LAD flow was significantly higher in hypertensive
subjects than in controls (P<0.05) and athletes
(P<0.01) (Table 3). After
administration of dipyridamole, no differences were
observed between groups. Thus, in hypertensive subjects MCR was higher
and CFR, RR, and CVR were lower than in controls and athletes.
|
Resting APV was directly related to resting RPP and TP in sedentary men and athletes (Figure 2) but not in hypertensive subjects; in athletes only, it was also related to PSWS (y=7.0+0.16x; r=0.52, P<0.05) and ESWS (y=3.0+0.41x; r=0.65, P<0.01). In stepwise multiple regression analysis, only RPP entered the regression against resting APV in sedentary men and athletes. Both resting and peak APV during dipyridamole were not related to LV mass or age in any group.
|
).
Response of Coronary Artery Caliber to
Dipyridamole
The diameter of the LMA could be measured in 34 subjects (71%)
(12 controls, 9 hypertensive subjects, and 13 athletes). LMA
cross-sectional area at baseline and after administration of
dipyridamole in the 3 groups is represented
in Figure 3. In athletes, basal LMA area
was slightly increased compared with sedentary men and significantly
increased compared with hypertensive subjects (P<0.05).
Athletes also had significantly enhanced dilation of LMA either as
absolute values or percent increase (Table 3). In hypertensive
subjects, an inverse relation was observed between age and LMA area
(y=25.3-0.27x; r=-0.73,
P<0.05). No relationship between LMA area and LV mass was
observed in any group.
|
Effect of Aging on Coronary Flow Velocity at Rest and
Coronary Vasodilator Capacity
The effect of aging on coronary circulation was not
evaluated in healthy sedentary men since none of them reached the age
of 65 years (Table 4). In hypertensive
subjects, resting APV was comparable between subjects older and younger
than 65 years, despite significant differences in blood pressure and LV
wall stress. APV after administration of dipyridamole
was lower in older hypertensive subjects, even if measured under higher
perfusion pressure, thus resulting in higher MCR and lower CFR, RR, and
CVR.
|
By contrast, older athletes demonstrated higher resting APV, mean blood
pressure, RPP, and LV wall stress than younger ones. APV and mean blood
pressure after administration of dipyridamole were
slightly higher in older athletes. Thus, CFR was significantly lower in
older athletes, but MCR, RR, and CVR were comparable in older and
younger athletes.
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
To the best of our knowledge, this is the first study comparing the features of coronary circulation in men with physiological, exercise-induced LVH and in hypertensive patients of similar age and LV mass. Detailed information on coronary vasodilator capacity in exercise-induced LVH was obtained in various animal models.6 7 8 11 12 13 However, studies in endurance athletes thus far provided data on morphology and function of LV myocardium23 24 and size and dilating capacity of large coronary arteries,24 25 while vasodilator capacity of coronary microcirculation was studied only in small series of young athletes without a control group of hypertensive patients with comparable LVH.26 27 In this study, we took advantage of an integrated echocardiographic approach that allowed us to assess, in a noninvasive manner, resting coronary flow velocity together with the main determinants of myocardial oxygen demand,16 17 18 as well as the response of coronary flow velocity and epicardial vessel diameter to intravenous infusion of a vasodilator agent.15 20
The main findings of the study are as follows: (1) in hypertensive LVH, the correlation between resting coronary flow velocity and determinants of myocardial oxygen demand is missing, while this relationship is preserved in physiological LVH; (2) maximal coronary vasodilation at the microcirculatory level is preserved in athletes with physiological LVH, while it is impaired in hypertensive LVH; (3) exercise training accompanied by physiological LVH is associated with a favorable remodeling and enhanced vasodilator capacity of the epicardial vessels; and (4) the effect of aging on coronary microcirculation is different between hypertensive subjects with LVH and athletes with physiological LVH.
Altogether, these results suggest that hypertensive disease, but not LVH per se, modifies the simple relationship between resting flow velocity and determinants of resting myocardial oxygen demand and that, as previously reported in exercising pigs,6 adaptive changes at the microvascular level parallel exercise-induced but not hypertensive LVH. In regard to conduit vessels, exercise training induces a favorable remodeling because of frequent high-flow stimuli caused by a substantial increase in myocardial oxygen demand during exercise load,24 25 while chronic pressure increment results in hypertensive vascular remodeling with thickening of the medial layer and normal or slightly decreased luminal diameter,28 with luminal narrowing progressively increasing with age. The enhanced dilating response of LMA to dipyridamole observed in athletes, 3-fold compared with sedentary controls and 5-fold compared with hypertensive patients, can be partially endothelium mediated29 30 and partially dependent on increased sensitivity of coronary smooth muscle to endothelium-independent vasodilator.25 31 Mechanisms underlying the age-dependent decrease of CFR are different between athletes and hypertensive subjects: in older athletes the reduction in CFR is primarily due to an increase in basal blood pressure, cardiac work, and flow velocity and not to a reduced vasodilator capacity. A similar pattern of age-related change in CFR was described for a normal population.32 In contrast, the further reduction in CFR observed in older hypertensive subjects was the result of a decreased hyperemic flow velocity and increased MCR, suggesting a role of aging in enhancing the impairment of coronary vasodilator capacity in arterial hypertension. Progressive increase in myocardial fibrosis with aging has been proposed as a possible mechanism limiting CFR in experimental models of hypertension.33
Study Limitations
TEE Doppler allows measurement of coronary flow
velocity in LAD and vessel caliber at the LMA level. Consequently,
volumetric flow cannot be assessed by this approach, and
microcirculatory function must be evaluated through the flow velocity
response to an arteriolar vasodilator. Actually, Wangler et
al34 and Marcus et al35 demonstrated that
changes in coronary blood flow velocity are closely correlated
with changes in microsphere-measured myocardial perfusion, thus
representing a good index of CFR, and we validated our TEE
Doppler flow velocity measurements against those by
intracoronary Doppler guidewire. The LMA diameter in this
study was measured not to extrapolate volumetric flow but as an optimal
window to assess remodeling and vasodilator capacity of epicardial
coronary artery. Measurement of LMA diameter by the TEE
approach shows relatively lower feasibility than Doppler
recording of coronary flow; however, our validation of
TEE against quantitative coronary angiography shows good
accuracy of the measurement, when feasible, in keeping with the
findings of Hildick-Smith and Shapiro36 using
transthoracic echocardiography.
Conclusions
In contrast to findings in hypertensive patients with LVH,
exercise-induced, physiological LVH in athletes of
comparable age is associated with enhanced vasodilator capacity of
coronary conductance vessels and preserved vasodilator capacity
at the resistance artery level. In addition, the relationships between
resting flow velocity and determinants of myocardial oxygen demand are
preserved in exercise-induced but not in hypertensive LVH. These data
indicate that LVH per se does not necessarily imply an impairment in
flow-function coupling and coronary vasodilator capacity.
Furthermore, the effect of aging on arteriolar vasodilator capacity
seems to be different in hypertensive and
physiological LVH.
|
Acknowledgments |
|---|
We thank Elena Barberini for editorial assistance.
Received November 3, 1999; first decision January 6, 2000; accepted April 6, 2000.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
- Sullivan JM, Zwaag RW, El-Zeky F, Ramanathan KB, Mirvid DM. Left ventricular hypertrophy: effect on survival. J Am Coll Cardiol. 1993;22:508–513.[Abstract]
-
Schwartzkopff B, Motz W, Frenzel H, Vogt M, Knauer S,
Strauer BE. Structural and functional alterations of the
intramyocardial coronary arterioles in patients with
arterial hypertension. Circulation. 1993;88:993–1003.
[Abstract/Free Full Text] -
Parodi O, Neglia D, Palombo C, Sambuceti G, Giorgetti
A, Marabotti C, Gallopin M, Simonetti I, LíAbbate A.
Comparative effects of enalapril and verapamil on
myocardial blood flow in systemic hypertension. Circulation. 1997;96:864–873.
[Abstract/Free Full Text] - Eichner ER. Exercise and heart disease. Am J Med. 1983;75:1008–1023.[Medline] [Order article via Infotrieve]
-
Ehsani AA, Ogawa T, Miller TR, Spina RJ, Jilka SM.
Exercise training improves left ventricular
systolic function in older men. Circulation. 1991;83:96–103.
[Abstract/Free Full Text] -
Breisch EA, White FC, Nimmo LE, McKirkan MD, Bloor CM.
Exercise-induced cardiac hypertrophy: a correlation of
blood flow and microvasculature. J Appl Physiol. 1986;60:1259–1267.
[Abstract/Free Full Text] -
Laughlin MH, Overholser KA, Bhatte MJ. Exercise
training increases coronary transport reserve in miniature
swine. J Appl Physiol.. 1989;67:1140–1149.
[Abstract/Free Full Text] - Parker JL, Oltman CL, Muller JM, Myers PR, Adams RH, Laughlin MH. Effect of exercise training on regulation of tone in coronary arteries and arterioles. Med Sci Sports Exerc. 1994;26:1252–1261.[Medline] [Order article via Infotrieve]
-
Muller JM, Myers PR, Laughlin MH. Vasodilator
responses of coronary resistance arteries of exercise-trained
pig. Circulation. 1994;89:2308–2314.
[Abstract/Free Full Text] -
Berdeux A, Ghaleh B, Dubois-Randé JL, Vigué
B, Drieu La Rochelle C, Hittinger L, Giudicelli JF. Role of vascular
endothelium in exercise-induced dilation of large
epicardial coronary arteries in conscious dogs.
Circulation. 1994;89:2799–2808.
[Abstract/Free Full Text] -
Wicker P, Abdul-Samad M, Rakusan K, Tarazi RC, Healy B.
Effects of chronic exercise on the coronary circulation in
conscious rats with renovascular hypertension. Hypertension. 1987;10:74–81.
[Abstract/Free Full Text] -
Buttrick PM, Levine HA, Schaible TF, Ciambrone G,
Scheuer J. Early increases in coronary vascular reserve in
exercised rats are independent of cardiac hypertrophy.
J Appl Physiol. 1985;59:1861–1865.
[Abstract/Free Full Text] -
Laughlin MH, Diana JN, Tipton CM. Effects of exercise
training on coronary reactive hyperemia and blood flow
in the dog. J Appl Physiol. 1978;45:604–610.
[Abstract/Free Full Text] - De Simone G, Devereux RB, Daniels SR, Koren MJ, Meyer RA, Laragh JH. Effect of growth on variability of left ventricular mass: assessment of allometric signals in adults and children and their capacity to predict cardiovascular risk. J Am Coll Cardiol. 1995;25:1056–1062.[Abstract]
-
Kozàkovà M, Palombo C, Pratali L, Pittella
G, Galetta F, L’Abbate A. Mechanism of coronary flow reserve
impairment in human hypertension: an integrated approach by
transthoracic and transesophageal
echocardiography. Hypertension. 1997;29:551–559.
[Abstract/Free Full Text] -
Devereux RB, Reichek N.
Echocardiographic determination of left
ventricular mass in man: anatomic validation of the method.
Circulation. 1977;55:613–618.
[Abstract/Free Full Text] -
Reichek N, Wilson J, St. John Sutton M, Plappert TA,
Goldberg S, Hirshfeld JW. Noninvasive determination of left
ventricular end-systolic stress: validation of the
method and initial application. Circulation. 1982;65:99–108.
[Free Full Text] - deSimone G, Devereux RB, Roman MJ, Ganau A, Saba PS, Alderman MH, Laragh JH. Assessment of left ventricular function by the midwall fractional shortening/end-systolic stress relation in humans. J Am Coll Cardiol. 1994;23:1444–1451.[Abstract]
-
Doucette JW, Corl PD, Payne HM, Flynn AE, Goto M, Nassi
M, Segal J. Validation of Doppler guide wire for intravascular
measurement of coronary artery flow velocity.
Circulation. 1992;85:1899–1991.
[Abstract/Free Full Text] -
Kozàkovà M, Palombo C, Pratali L, Bigalli
G, Marzilli M, Distante A, L’Abbate A. Assessment of coronary
reserve by transesophageal Doppler
echocardiography: head-to-head comparison between
different modalities of dipyridamole and
adenosine administration. Eur Heart J.. 1997;18:514–523.
[Abstract/Free Full Text] - Bland MJ, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet. 1986;1:307–309.[Medline] [Order article via Infotrieve]
- Pearson AC, Gudipati CV, Labovitz AJ. Effect of aging on left ventricular structure and function. Am Heart J. 1991;121:871–875.[Medline] [Order article via Infotrieve]
- Douglas SP, O’Tool ML, Hiller WD, Reichek N. Left ventricular structure and function by echocardiography in ultraendurance athletes. Am J Cardiol. 1986;58:805–809.[Medline] [Order article via Infotrieve]
- Pelliccia A, Sparato A, Granata J, Biffi A, Caselli G, Alabiso A. Coronary arteries in physiological hypertrophy: echocardiographic evidence of increased proximal size in elite athletes. Int J Sports Med. 1990;11:120–126.[Medline] [Order article via Infotrieve]
-
Haskell WL, Sims M, Bortz WM, St. Goar FG, Alderman EL.
Coronary artery size and dilating capacity in ultradistance
runners. Circulation. 1993;87:1076–1082.
[Abstract/Free Full Text] - Radvan J, Choudhury L, Sheridan DJ, Camici PG. Comparison of coronary vasodilator reserve in elite rowing athletes versus hypertrophic cardiomyopathy. Am J Cardiol. 1997;80:1621–1623.[Medline] [Order article via Infotrieve]
- Toraa M, Pouillard F, Merlet P, Friemel F. Cardiac hypertrophy and coronary reserve in endurance athletes. Can J Appl Physiol. 1999;24:87–95.[Medline] [Order article via Infotrieve]
- Agabiti-Rosei E, Rizzoni D, Castellano M, Porteri E, Zulli R, Muiesan ML, Bettoni G, Salvetti M, Muiesan P, Giulini SM. Media:lumen ratio in human small resistance arteries is related to forearm minimal vascular resistance. J Hypertens. 1995;13:341–347.[Medline] [Order article via Infotrieve]
-
Wang J, Wolin MS, Hintze TH. Chronic exercise enhances
endothelium-mediated dilation of epicardial
coronary artery in conscious dogs. Circ Res. 1993;73:829–838.
[Abstract/Free Full Text] -
Lupi A, Buffon A, Finocchiaro ML, Conti E, Maseri A,
Crea F. Mechanisms of adenosine-induced epicardial
coronary artery dilatation. Eur Heart J. 1997;18:614–617.
[Abstract/Free Full Text] - Stewart JM, Xu X, Ochoa M, Hintze TH. Exercise reduces epicardial coronary artery wall stiffness: roles of cGMP and cAMP. Med Sci Sports Exerc. 1998;30:220–228.[Medline] [Order article via Infotrieve]
-
Czernin J, Muller P, Chan S, Brunken RC, Porenta G,
Krivokapich J, Chen K, Chan A, Phelps ME, Schelbert HR. Influence of
age and hemodynamics on myocardial blood flow and flow
reserve. Circulation. 1993;88:62–69.
[Abstract/Free Full Text] - Susic D, Nunez E, Hosoya K, Frohlich ED. Coronary hemodynamics in aging spontaneously hypertensive and normotensive Wistar-Kyoto rats. J Hypertens. 1998;16:231–237.[Medline] [Order article via Infotrieve]
- Wangler RD, Peters KG, Laughlin DE, Tomanek RJ, Marcus ML. A method for continuously assessing coronary blood flow velocity in rats. Am J Physiol. 1981;241:H816–H820.
-
Marcus M, Wright C, Doty D, Eastham C, Laughlin D,
Krumm P, Fastenow C, Brody M. Measurements of coronary velocity
and reactive hyperemia in coronary circulation in
humans. Circ Res. 1981;49:877–891.
[Free Full Text] - Hildick-Smith DJR, Shapiro LM. Transthoracic echocardiographic measurement of coronary artery diameter: validation against quantitative coronary angiography. J Am Soc Echocardiogr. 1998;11:893–897.[Medline] [Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  J. Varagic, E. D. Frohlich, D. Susic, J. Ahn, L. Matavelli, B. Lopez, and J. Diez AT1 receptor antagonism attenuates target organ effects of salt excess in SHRs without affecting pressure Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H853 - H858. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S H Poulsen, N H Andersen, L Heickendorff, and C E Mogensen Relation between plasma amino-terminal propeptide of procollagen type III and left ventricular longitudinal strain in essential hypertension Heart, May 1, 2005; 91(5): 624 - 629. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. de Simone Left Ventricular Geometry and Hypotension in End-Stage Renal Disease: A Mechanical Perspective J. Am. Soc. Nephrol., October 1, 2003; 14(10): 2421 - 2427. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kozakova, E. Ferrannini, and C. Palombo Relation Between Left Ventricular Midwall Function and Coronary Vasodilator Capacity in Arterial Hypertension Hypertension, October 1, 2003; 42(4): 528 - 533. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Malo, F. Desjardins, J.-F. Tanguay, J.-C. Tardif, M. Carrier, and L. P. Perrault Tetrahydrobiopterin and antioxidants reverse the coronary endothelial dysfunction associated with left ventricular hypertrophy in a porcine model Cardiovasc Res, August 1, 2003; 59(2): 501 - 511. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Xia, H. Y. Wen, M. E. Young, P. H. Guthrie, H. Taegtmeyer, and R. E. Kellems Mammalian Target of Rapamycin and Protein Kinase A Signaling Mediate the Cardiac Transcriptional Response to Glutamine J. Biol. Chem., April 4, 2003; 278(15): 13143 - 13150. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kozakova, G. de Simone, C. Morizzo, and C. Palombo Coronary Vasodilator Capacity and Hypertension-Induced Increase in Left Ventricular Mass Hypertension, February 1, 2003; 41(2): 224 - 229. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||