CLINICAL STUDIES
Early impairment of coronary flow reserve in young men with borderline hypertension
Hanna Laine, MDa,
Olli T. Raitakari, MDa,
Harri Niinikoski, MDa,
Olli-Pekka Pitkänen, MDa,
Hidehiro Iida, DSca*,
Jorma Viikari, MDa,
Pirjo Nuutila, MDa and
Juhani Knuuti, MDa
a Departments of Medicine, Clinical Physiology, Cardiorespiratory Research Unit and Nuclear Medicine, Turku Positron Emission Tomography Centre, Turku University, Turku, Finland
* Research Institute for Brain and Blood Vessels, Akita, Japan
Manuscript received October 6, 1997;
revised manuscript received March 25, 1998,
accepted April 9, 1998.
Address for correspondence: Dr. Hanna Laine, Department of Medicine, University of Turku, FIN-20520 Turku, Finland
hannal{at}pet.tyks.fi
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Abstract
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Objectives. The purpose of this study was to investigate whether functional abnormalities in coronary vasomotion are present in young healthy asymptomatic men fulfilling the World Health Organization (WHO) criteria for borderline hypertension.
Background. Previous studies have reported reduced coronary flow reserve in middle-aged subjects with sustained hypertension and hypertension-induced microvascular heart disease or left ventricular hypertrophy.
Methods. Myocardial blood flow was measured at baseline and during dipyridamole-induced hyperemia by means of positron emission tomography and oxygen-15–labeled water in asymptomatic young men with borderline hypertension (group 1: n = 16, mean ± SD age 37 ± 4 years, 24-h ambulatory blood pressure 135 ± 10/81 ± 9 mm Hg) and matched healthy control subjects (group 2: n = 19, age 35 ± 3 years, 24-h ambulatory blood pressure 119 ± 8/69 ± 8 mm Hg, p < 0.001). Left ventricular (LV) mass, dimensions and function were measured by echocardiography.
Results. LV mass, dimensions and diastolic function were similar in the study groups. Baseline myocardial blood flow was similar (0.83 ± 0.21 vs. 0.80 ± 0.22 ml/g per min, group 1 vs. group 2, respectively, p = NS), and a significant increase in flow was detected after dipyridamole infusion (0.56 mg/kg body weight in 4 min intravenously) in both groups. However, the flow response to dipyridamole was significantly lower in group 1, leading to lower hyperemic flow in group 1 than in group 2 (2.85 ± 1.20 vs. 3.80 ± 1.44 ml/g per min, respectively). Consequently, the coronary flow response was lower in hypertensive than in normotensive men (3.46 ± 1.23 vs. 4.99 ± 2.5 ml/g per min, group 1 vs. group 2, respectively, p < 0.05).
Conclusions. These results demonstrate reduced coronary reactivity present in young asymptomatic men with borderline hypertension and no signs of hypertension-induced angina or left ventricular hypertrophy. Because baseline basal myocardial blood flow was unchanged, the reduction in coronary flow reserve depends on an impaired maximal vasodilator capacity.
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Abbreviations and Acronyms
| | ECG | = electrocardiogram, electrocardiographic | | [15O]CO | = oxygen-15–labeled carbon monoxide | | HDL | = high density lipoprotein | | [15O]H2O | = oxygen-15–labeled water | | LDL | = low density lipoprotein | | LV | = left ventricular | | LVM | = left ventricular mass | | PET | = positron emission tomography (tomographic) | | ROI | = region of interest | | WHO | = World Health Organization |
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Reduced coronary flow reserve has been suggested to be one of the earliest abnormalities associated with coronary artery disease (1). Previous studies have reported reduced coronary flow reserve in hypertensive subjects with (2–4) or without left ventricular (LV) hypertrophy (3–10). However, all these studies were limited to hypertensive patients with symptoms suggestive of coronary artery disease because coronary flow reserve measurements in these earlier studies required invasive coronary catherization. Recently, a less invasive transesophageal echocardiographic method was applied (11), and reduced coronary reserve was also reported in asymptomatic, previously treated hypertensive subjects without LV hypertrophy. However, in that study only 6 of the 33 studied middle-aged hypertensive subjects (mean age 58 years) did not have LV hypertrophy or symptoms of angina. Thus, although previous studies have demonstrated abnormal coronary flow responses in middle-aged subjects with sustained hypertension or with hypertension-induced microvascular angina, it is unknown whether abnormalities in functional coronary reactivity are present in young asymptomatic subjects with borderline hypertension. If this is the case, it would suggest active recognization and intervention of borderline hypertension because antihypertensive treatment has been shown to improve impaired coronary flow reserve (5,9,12,13) and to reduce symptoms of microvascular angina in patients with essential hypertension (9).
For clinical risk stratification studies, a safe technique with minimal invasiviness, allowing detection of early abnormalities and a direct comparison with a healthy control group, is needed. Use of positron emission tomography (PET) and oxygen-15–labeled water ([15O]H2O) is currently the most accurate nonivasive approach available for measuring myocardial perfusion (14). Additionally, a marked correlation has been demonstrated (15) between myocardial perfusion reserve and the degree of angiographically documented coronary artery disease using PET, [15O]H2O and dipyridamole as a coronary vasodilatatory agent. Using nonivasive PET imaging, our group has recently reported alterations in functional vascular reactivity in young men with familial hypercholesterolemia (16) and found the number of conventional coronary artery risk variables to be related to coronary flow reserve (17). In the present study PET, [15O]H2O and dipyridamole were used to quantitate coronary reactivity in healthy young men selected from participants of an epidemiologic study. Two subject groups were selected on the basis of blood pressure values—one fulfilling World Health Organization (WHO) criteria for borderline hypertension and one with normal blood pressure values.
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Methods
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Subjects.
The study subjects were recruited from families participating in the Special Turku Coronary Risk Factor Intervention Project (STRIP) baby project (18) that sought to study the effects of dietary intervention on coronary risk factors in young children. We used data that had been previously obtained from the children’s fathers. Young (<40 years old), lean (body mass index <28 kg/m2), nonsmoking and nondiabetic men were included. Subjects had no medication. Two groups of subjects were selected on the basis of earlier blood pressure measurements taken on three previous occasions  1 year apart. Group 1 included men with blood pressure values classified by WHO as borderline hypertension (systolic blood pressure 140 to 160 mm Hg or diastolic blood pressure 90 to 95 mm Hg, or both) (19). Group 2 included men with normal blood pressure (<140/85 mm Hg) for all measurements. The two study groups were matched for age, body mass index and serum cholesterol concentration. Family history of coronary heart disease was comparable between the groups (two subjects had a positive family history of early coronary heart disease in group 1 and one subject in group 2). Family history was considered to be positive if documented coronary artery disease was present in at least one of the subject’s first-degree relatives <50 years old (male relatives) or <60 years old (female relatives). The study protocol was successfully carried out in 16 men from group 1 and 19 men from group 2.
Study design.
Study subjects were instructed to avoid all caffeine-containing drinks and foods for 12 h before the PET studies. Myocardial perfusion was measured twice—once at rest and once after administration of dipyridamole. Heart rate and the electrocardiogram (ECG) were monitored continuously during the studies. Blood pressure was monitored with an automatic oscillometric blood pressure monitor (OMRON HEM-705C, Omron Healthcare, Hamburg, Germany) during the PET study. The study protocol was accepted by the ethics committee of Turku University Central Hospital. Each subject provided written informed consent.
Production of oxygen-15–labeled carbon monoxide and [15O]H2O.
For production of oxygen-15 a low-energy deuteron accelerator (Cyclone 3) was used (Ion Beam Application, Louvain-la-Neuve, Belgium). Oxygen-15–labeled carbon monoxide ([15O]CO) was produced using conventional methods (20). [15O]H2O was produced using dialysis techniques in a continuously working water module (21). Production for CO and water were 2.5 and 1.7 GBq/min, respectively. Sterility and pyrogenity tests for water and chromatographic analysis for gases were performed to verify the purity of the products.
Image acquisition, processing and corrections.
Patients were positioned supine in an 15-slice ECAT 931/08-12 tomograph (Siemens/CTI) with a measured axial resolution of 6.7 and 6.5 mm in-plane. To correct for photon attenuation a transmission scan was performed for 20 min, before the emission scan, with a removable ring source containing germanium-68. After the transmission scan, the subjects’ nostrils were closed, and they inhaled [15O]CO for 2 min through a three-way inhalation flap-valve (0.14% CO mixed with room air). After the inhalation, 2 min were allowed for CO to combine with hemoglobin in red blood cells before a static scan for 4 min was started. During the scan period, three blood samples were drawn at 2-min intervals, and blood radioactivity was measured immediately with a well counter (Bicron 3MW3/3). A 10-min period was allowed for [15O]CO radioactive decay before the flow measurements.
Flow was measured at baseline and 2 min after the end of intravenous administration of dipyridamole (0.56 mg/kg body weight over 4 min). [15O]H2O was injected intravenously over 2 min, and dynamic scanning was started for 6 min (6 x 5 s, 6 x 15 s, 8 x 30 s). All data were corrected for deadtime, decay and photon attenuation and were reconstructed into a 128 x 128 matrix. The final in-plane resolution in the reconstructed and Hann-filtered (0.3 cycles/s) images was 9.5 mm (full-width half-maximum).
Calculation of regional blood flow.
Regions of interest (ROIs) were drawn in the lateral, anterior and septal walls of the left ventricle in four representative transaxial slices in each study. The ROIs outlined in the baseline images were copied to the images obtained after dipyridamole administration. Values of regional myocardial blood flow (in ml/g tissue per min) were calculated according to the previously published method using the single-compartment model (22,23).
The arterial input function was obtained from the LV time–activity curve by means of a previously validated method (24), in which corrections were made for the limited recovery of the LV ROI and the spillover from the myocardial signals. No regional differences were found in myocardial perfusion. Therefore, to enhance accuracy and statistic significance of the flow measurements, the average blood flow of global myocardium was calculated and used in further analysis. Coronary flow reserve was defined as the ratio of myocardial blood flow after dipyridamole to baseline flow.
Echocardiographic examination.
All echocardiographic recordings and analyses were performed by the same investigator (O.T.R.) using a commercially available ultrasound scanner (Acuson 128XP/10). The study subjects rested >15 min before they were examined in the left lateral decubitus position. After echocardiographic study, blood pressure was measured. Standard echocardiographic views of the left ventricle were obtained, and cardiac dimensions were measured. The following variables were used for echocardiographic measurements of the left ventricle; LV end-diastolic diameter (LVDd); LV end-systolic diameter (LVDs); LV posterior wall thickness in diastole (LVPWd); LV posterior wall thickness in systole (LVPWs). Left ventricular mass (LVM) was calculated as follows:  where IVSd = interventricular septal thickness during diastole (25). LVM index (LVMI) was expressed as LVM per body surface area (g/m2). LV systolic function was assessed by calculating the percent fractional shortening of the left ventricle as  and LV ejection fraction (percent) as (LV diastolic volume – LV systolic volume)/LV diastolic volume. LV meridional peak systolic wall stress (PSWS) (103 dynes/cm2) was calculated by the following formula:  (26). From the mitral flow velocity tracings, the early (E) and late (A) mitral flow peak velocities were measured. LV diastolic function was assessed by calculating the mitral Doppler peak early diastolic blood flow velocity (E) to peak late diastolic flow velocity (A) ratio (E/A ratio).
Ambulatory blood pressure measurements.
Ambulatory blood pressure was monitored using an auscultatory method (Novacor Diasys). The recorder was installed by an experienced technician. The accuracy and reproductibility of this device have been previously reported to be excellent (27). The device was installed in the left arm in the morning, and blood pressure was verified against a mercury sphygmomanometer in the supine, sitting and standing positions both when installing and taking off the automatic device. The ambulatory blood pressure reading was aimed at within a 5-mm Hg limit from the simultaneous auscultatory reading. Ambulatory blood pressure was recorded at 20-min intervals during the daytime and at 60-min intervals during the night.
Analytic procedures.
Venous blood samples were taken after 12 h of overnight fasting during the same week as the PET study. Plasma glucose was determined by the glucose oxidase method (28). Serum insulin was measured by a radioimmunoassay kit (Pharmacia, Uppsala, Sweden). All lipid determinations were done in the laboratory of Turku University Hospital. Serum total cholesterol, high density lipoprotein (HDL) cholesterol and triglyceride concentrations were measured using standard enzymatic methods (Boehringer Mannheim GmbH, Mannheim, Germany) with a fully automated analyzer (Hitachi 704, Hitachi Ltd., Tokyo, Japan). HDL cholesterol was measured after polyethyleneglycol (molecular weight 6,000, final concentration 10%) precipitation (29). The low density lipoprotein (LDL) cholesterol concentration was calculated by using the Friedewald formula (30).
Statistical methods.
Results are expressed as mean value ± SD. The difference in flow values between the groups and the response to dipyridamole and the interaction of these two variables were statistically tested using analysis of variance of repeated measures (31). Associations between risk and flow variables were studied by calculating the Pearson correlation coefficients. A p value <0.05 was considered statistically significant. All statistical tests were performed with the SAS statistical analysis system (SAS Institute).
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Results
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Study subjects.
The characteristics of the subjects are shown in Table 1. Blood pressures were higher in group 1 when measured as office blood pressures before the PET study or as 24-h ambulatory blood pressure (Table 1). There were no differences in serum cholesterol, HDL cholesterol, LDL cholesterol, insulin or plasma glucose concentrations between the study groups (Table 1). The group 1 serum triglyceride concentration was slightly higher than that in group 2 (2.0 ± 1.0 vs. 1.3 ± 0.8 mmol/liter, group 1 vs. group 2, respectively, p < 0.05).
LVM and LV dimensions and early diastolic filling patterns were similar in the study groups (Table 2). LV ejection fraction and fractional shortening were normal in both groups but were significantly higher in group 1 (Table 2). LV wall stress was higher in group 1 (205 ± 36 x 103 dynes/cm2) than in group 2 (183 ± 6 x 103 dynes/cm2, p < 0.05).
Hemodynamic measurements during PET.
Blood pressure and rate–pressure product were higher in subjects with mild hypertension both basally and during vasodilation (Table 3). No difference in heart rate was detected (Table 3). Dipyridamole administration induced a significant increase in heart rate and rate–pressure product in both groups, and the response to dipyridamole was similar in both groups (Table 3).
Myocardial blood flow, coronary flow reserve and vascular resistance.
Basal myocardial blood flow was similar in both study groups (0.83 ± 0.21 vs. 0.81 ± 0.21 ml/g per min, group 1 vs. group 2, respectively, p = NS). Dipyridamole infusion increased flow significantly in both groups (p < 0.001): in group 1 by 2.02 ± 0.93 ml/g per min (p < 0.001) and in group 2 by 3.01 ± 1.22 ml/g per min (p < 0.001) (Fig. 1), but the effect of dipyridamole was different between the groups (interaction between the study groups and the response to dipyridamole, p < 0.05). During maximal vasodilation, myocardial blood flow was lower in group 1 than in group 2 (2.85 ± 1.20 vs. 3.80 ± 1.44 ml/g per min, group 1 vs. group 2, respectively, p < 0.05). Subsequently, coronary flow reserve was significantly lower in borderline than in normotensive subjects (3.46 ± 1.23 vs. 4.99 ± 2.50, respectively, p < 0.05) (Fig. 2). Coronary flow reserve correlated inversely with systolic and diastolic 24-h ambulatory blood pressure values (coronary flow reserve vs. 24-h systolic blood pressure: r = –0.35, p < 0.05; coronary flow reserve vs. 24-h diastolic blood pressure: r = –0.35, p < 0.05) and with systolic and diastolic daytime ambulatory blood pressure values in the pooled data (coronary flow reserve vs. daytime systolic blood pressure: r = –0.36, p < 0.05; coronary flow reserve vs. daytime diastolic blood pressure: r = –0.36, p < 0.05). When the groups were analyzed separately, no correlation was found between coronary flow reserve and blood pressure values in group 1. However, in group 2, significant inverse correlations were found between coronary flow reserve and systolic 24-h ambulatory blood pressure (r = –0.48, p < 0.05) and systolic daytime ambulatory blood pressure (r = –0.51, p < 0.05). No significant associations were found between flow variables and serum lipoprotein levels.
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Figure 1 Myocardial blood flow at baseline and during dipyridamole-induced hyperemia. The myocardial blood flow response to dipyridamole was significantly lower in group 1 than in group 2 (p < 0.05). Triangles = individual flow values of the study subjects.
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Discussion
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Abnormal coronary flow reserve has been previously reported in middle-aged hypertensive patients with hypertension-induced microvascular angina (3–9) or with hypertension-induced LV hypertrophy (2–4). Recently, coronary flow reserve has also been reported (11) to be reduced in a small group of asymptomatic previously treated hypertensive subjects without LV hypertrophy. However, in that study only 6 of the 33 previously treated middle-aged hypertensive subjects (mean age 58 years) were asymptomatic and had a normal LVM. Thus, to our knowledge, the present study is the first to show that a significant reduction in coronary reactivity is present in young asymptomatic men with borderline hypertension and normal LVM.
Dipyridamole as a vasoactive agent.
We used dipyridamole as a vasoactive agent to test coronary vascular function. Dipyridamole increases interstitial adenosine concentration in vascular smooth muscle cells and leads to relaxation of coronary resistance vessels (32), and thus the increment in coronary blood flow induced by dipyridamole has been suggested to be primarily endothelium independent. However, increased shear stress associated with increased flow is found to induce release of vasodilating substances from endothelial cells (33) and to elicit more prominent vasodilation in the vessels with preserved endothelial function. Indeed, in several studies (34–36) endothelium-dependent coronary vasodilation has been found to be associated with flow responses induced by adenosine or dipyridamole. Therefore, the coronary flow response as assessed by intravenous dipyridamole infusion, most likely reflects the combined effect of vascular smooth muscle relaxation and endothelial-mediated vasodilatory function and can be used as an integrating measure of coronary reactivity (1,15,37).
Factors that may impair coronary flow reserve in essential hypertension.
In the present study reduced coronary flow reserve was observed in young asymptomatic men with borderline hypertension, although basal myocardial blood flow and LVM and function were normal. These findings raise the possibility that reduced endothelial vasodilation or vascular smooth muscle cell relaxation, or both, is present in borderline hypertension because the present findings are not explained by changes in basal blood flow or by hypertensive heart disease. In experimental animal models of hypertension, reduced release of endothelium-derived nitric oxide or hyperpolarizing factor (38), augmented release of endothelium-derived constricting factors (39) and inactivation of endothelium-derived relaxing factors (40) have been reported. These previous experimental findings have been supported by a recent report of reduced basal nitric oxide synthesis in hypertensive subjects (41), suggesting that endothelial dysfunction is coupled with diminished basal nitric oxide production in essential hypertension.
The reduced coronary vasodilator reserve in patients with sustained hypertension has been suggested to be due to a combination of impaired endothelium-dependent vasodilation and structural abnormalities (11). Abnormal endothelium-dependent coronary vasodilation in response to intracoronary infusion of acetylcholine has been demonstrated in hypertensive subjects with angina but angiographically normal coronary arteries (7,8). A recent study (9) suggested that the diminished endothelium-dependent dilation of resistance coronary arteries in hypertensive subjects is related to a generalized endothelial abnormality, but that diminished endothelium-dependent dilation of large epicardial coronary arteries is related to a selective abnormality in the muscarinic receptors of the endothelium. Structural abnormalities, such as alterations of intramyocardial arteries (42,43), increased perivascular fibrosis and increased myocardial fibrosis (41), have been suggested to explain part of the reduced coronary dilatory capacity in hypertensive subjects with microvascular angina. In addition to these structural changes, extravascular compression of hypertrophied myocardium and inadequate angiogenesis (44) may also explain reduced coronary reactivity in patients with essential hypertension and LV hypertrophy.
Vascular reactivity and cardiovascular risk status.
The subjects of the present study were all nonsmokers and nondiabetic. Age, body mass index, serum total cholesterol, HDL cholesterol, LDL cholesterol, insulin and plasma glucose concentrations and family history of coronary heart disease were comparable between the study groups. Serum triglyceride concentrations were slightly higher in hypertensive than in control subjects. However, in accordance with previous studies (1,17), no association was found between triglyceride concentration and flow reserve in the present study. Thus, it is unlikely that the slightly higher triglyceride concentrations in the hypertensive subjects would have acted as a confounding factor. LV systolic function was normal in both study groups but was higher in the borderline hypertensive than in the control subjects. This finding is similar to previous studies (45–48) reporting enhanced LV systolic performance in some subjects with primary hypertension.
Limitations of the study.
In the present study, only men with borderline hypertension were enrolled. Whether the same results can be extrapolated to female subjects of similar age and similar blood pressure values remains to be shown. We interpreted the present findings of reduced coronary reactivity to reflect reduced endothelial vasodilation or impaired vascular smooth muscle cell relaxation, or both, yet the exact mechanisms responsible for the hypertension-associated reduction in the ability of dipyridamole to induce coronary vasodilation remains to be determined. Although we studied healthy young asymptomatic subjects, coronary angiography or intracoronary ultrasound was not performed, and thus we cannot exclude that the presence of more advanced early-stage atherosclerosis might also explain the present finding of reduced coronary reactivity.
Conclusions.
The present study demonstrates reduced maximal coronary flow and flow reserve after dipyridamole administration in young asymptomatic men with borderline hypertension. Additionally, coronary flow reserve was related to ambulatory 24-h blood pressure values, supporting the concept that the presence of mildly elevated blood pressure is associated with an abnormal coronary flow response. Nevertheless, the prognostic value of these early changes in asymptomatic subjects remains to be defined by future studies.
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Acknowledgments
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We thank the staff of Turku PET Centre for excellent technical assistance.
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Footnotes
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The study was financially supported by grants from the Turku University Foundation and the Finnish Foundation for Cardiovascular Research, the Ida Montin Foundation and the Finnish Medical Foundation, Helsinki.
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N. Koivuviita, R. Tertti, M. Jarvisalo, M. Pietila, J. Hannukainen, J. Sundell, P. Nuutila, J. Knuuti, and K. Metsarinne
Increased basal myocardial perfusion in patients with chronic kidney disease without symptomatic coronary artery disease
Nephrol. Dial. Transplant.,
September 1, 2009;
24(9):
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[Abstract]
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M. J. Raher, H. Thibault, K. K. Poh, R. Liu, E. F. Halpern, G. Derumeaux, F. Ichinose, W. M. Zapol, K. D. Bloch, M. H. Picard, et al.
In Vivo Characterization of Murine Myocardial Perfusion With Myocardial Contrast Echocardiography: Validation and Application in Nitric Oxide Synthase 3 Deficient Mice
Circulation,
September 11, 2007;
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[Abstract]
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S. M. Vigano, M. Turiel, V. Martina, E. Meregalli, L. Tomasoni, G. De Blasio, L. Delfino, A. Edefonti, P. Grillo, M. Procaccio, et al.
Reduced coronary flow reserve in young adults with renal transplant
Nephrol. Dial. Transplant.,
August 1, 2007;
22(8):
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[Abstract]
[Full Text]
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A. Lerman, D. R. Holmes, J. Herrmann, and B. J. Gersh
Microcirculatory dysfunction in ST-elevation myocardial infarction: cause, consequence, or both?
Eur. Heart J.,
April 1, 2007;
28(7):
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[Abstract]
[Full Text]
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D. Erdogan, I. Yildirim, O. Ciftci, I. Ozer, M. Caliskan, H. Gullu, and H. Muderrisoglu
Effects of Normal Blood Pressure, Prehypertension, and Hypertension on Coronary Microvascular Function
Circulation,
February 6, 2007;
115(5):
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[Abstract]
[Full Text]
[PDF]
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T. O. Kiviniemi, A. Snapir, M. Saraste, J. O. Toikka, O. T. Raitakari, M. Ahotupa, J. J. Hartiala, M. Scheinin, and J. W. Koskenvuo
Determinants of coronary flow velocity reserve in healthy young men
Am J Physiol Heart Circ Physiol,
August 1, 2006;
291(2):
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[Abstract]
[Full Text]
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A. Indermuhle, R. Vogel, P. Meier, S. Wirth, R. Stoop, M. G. Mohaupt, and C. Seiler
The relative myocardial blood volume differentiates between hypertensive heart disease and athlete's heart in humans
Eur. Heart J.,
July 1, 2006;
27(13):
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[Abstract]
[Full Text]
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M. Rodriguez-Porcel, X.-Y. Zhu, A. R. Chade, B. Amores-Arriaga, N. M. Caplice, E. L. Ritman, A. Lerman, and L. O. Lerman
Functional and structural remodeling of the myocardial microvasculature in early experimental hypertension
Am J Physiol Heart Circ Physiol,
March 1, 2006;
290(3):
H978 - H984.
[Abstract]
[Full Text]
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T. Pellegrino, G. Storto, P. P. Filardi, A. R. Sorrentino, A. Silvestro, M. Petretta, G. Brevetti, M. Chiariello, M. Salvatore, and A. Cuocolo
Relationship Between Brachial Artery Flow-Mediated Dilation and Coronary Flow Reserve in Patients with Peripheral Artery Disease
J. Nucl. Med.,
December 1, 2005;
46(12):
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[Abstract]
[Full Text]
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R. C. Brunken, J. K. Perloff, J. Czernin, R. Campisi, S. Purcell, P. D. Miner, J. S. Child, and H. R. Schelbert
Myocardial perfusion reserve in adults with cyanotic congenital heart disease
Am J Physiol Heart Circ Physiol,
November 1, 2005;
289(5):
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[Abstract]
[Full Text]
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M. L. E. Vicario, L. Cirillo, G. Storto, T. Pellegrino, N. Ragone, L. Fontanella, M. Petretta, D. Bonaduce, and A. Cuocolo
Influence of Risk Factors on Coronary Flow Reserve in Patients with 1-Vessel Coronary Artery Disease
J. Nucl. Med.,
September 1, 2005;
46(9):
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[Abstract]
[Full Text]
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N. H. Buus, M. Bottcher, C. G. Jorgensen, K. L. Christensen, K. Thygesen, T. T. Nielsen, and M. J. Mulvany
Myocardial Perfusion During Long-Term Angiotensin-Converting Enzyme Inhibition or {beta}-Blockade in Patients With Essential Hypertension
Hypertension,
October 1, 2004;
44(4):
465 - 470.
[Abstract]
[Full Text]
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J. Sundell, E. Engblom, J. Koistinen, A. Ylitalo, A. Naum, K. Q. Stolen, R. Kalliokoski, S. G. Nekolla, K. E. J. Airaksinen, J. J. Bax, et al.
The effects of cardiac resynchronization therapy on left ventricular function, myocardial energetics, and metabolic reserve in patients with dilated cardiomyopathy and heart failure
J. Am. Coll. Cardiol.,
March 17, 2004;
43(6):
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[Abstract]
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H Laine, J Sundell, P Nuutila, O T Raitakari, M Luotolahti, T Ronnemaa, T Elomaa, P Koskinen, and J Knuuti
Insulin induced increase in coronary flow reserve is abolished by dexamethasone in young men with uncomplicated type 1 diabetes
Heart,
March 1, 2004;
90(3):
270 - 276.
[Abstract]
[Full Text]
[PDF]
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E. Tadamura, M. Mamede, S. Kubo, H. Toyoda, M. Yamamuro, H. Iida, N. Tamaki, K. Nishimura, M. Komeda, and J. Konishi
The Effect of Nitroglycerin on Myocardial Blood Flow in Various Segments Characterized by Rest-Redistribution Thallium SPECT
J. Nucl. Med.,
May 1, 2003;
44(5):
745 - 751.
[Abstract]
[Full Text]
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S. E. Langerak, H. W. Vliegen, J. W. Jukema, P. Kunz, A. H. Zwinderman, H. J. Lamb, E. E. van der Wall, and A. de Roos
Value of Magnetic Resonance Imaging for the Noninvasive Detection of Stenosis in Coronary Artery Bypass Grafts and Recipient Coronary Arteries
Circulation,
March 25, 2003;
107(11):
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[Abstract]
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H. Paiva, J. Laakso, H. Laine, R. Laaksonen, J. Knuuti, and O. T. Raitakari
Plasma asymmetric dimethylarginine and hyperemic myocardial blood flow in young subjects with borderline hypertension or familial hypercholesterolemia
J. Am. Coll. Cardiol.,
October 2, 2002;
40(7):
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[Abstract]
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S. Aronson, D. Boisvert, and W. Lapp
Isolated Systolic Hypertension Is Associated with Adverse Outcomes from Coronary Artery Bypass Grafting Surgery
Anesth. Analg.,
May 1, 2002;
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[Abstract]
[Full Text]
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J. Sundell, P. Nuutila, H. Laine, M. Luotolahti, K. Kalliokoski, O. Raitakari, and J. Knuuti
Dose-Dependent Vasodilating Effects of Insulin on Adenosine-Stimulated Myocardial Blood Flow
Diabetes,
April 1, 2002;
51(4):
1125 - 1130.
[Abstract]
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R. Scognamiglio, A. Avogaro, S. Vigili de Kreutzenberg, C. Negut, M. Palisi, E. Bagolin, and A. Tiengo
Effects of Treatment With Sulfonylurea Drugs or Insulin on Ischemia-Induced Myocardial Dysfunction in Type 2 Diabetes
Diabetes,
March 1, 2002;
51(3):
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[Abstract]
[Full Text]
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N. H. Buus, M. Bottcher, F. Hermansen, M. Sander, T. T. Nielsen, and M. J. Mulvany
Influence of Nitric Oxide Synthase and Adrenergic Inhibition on Adenosine-Induced Myocardial Hyperemia
Circulation,
November 6, 2001;
104(19):
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[Abstract]
[Full Text]
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J. W. Koskenvuo, J. J. Hartiala, J. Knuuti, H. Sakuma, J. O. Toikka, M. Komu, M. Saraste, and P. Niemi
Assessing Coronary Sinus Blood Flow in Patients with Coronary Artery Disease: A Comparison of Phase-Contrast MR Imaging with Positron Emission Tomography
Am. J. Roentgenol.,
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[Abstract]
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L. Schwartz and M. G. Bourassa
Evaluation of Patients With Chest Pain and Normal Coronary Angiograms
Arch Intern Med,
August 13, 2001;
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M Fujiwara, T Tamura, K Yoshida, K Nakagawa, M Nakao, M Yamanouchi, N Shikama, T Himi, and Y Masuda
Coronary flow reserve in angiographically normal coronary arteries with one-vessel coronary artery disease without traditional risk factors
Eur. Heart J.,
March 2, 2001;
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[Abstract]
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E. Tadamura, H. Iida, K. Matsumoto, M. Mamede, S. Kubo, H. Toyoda, T. Shiozaki, T. Mukai, Y. Magata, and J. Konishi
Comparison of myocardial blood flow during dobutamine-atropine infusion with that after dipyridamole administration in normal men
J. Am. Coll. Cardiol.,
January 1, 2001;
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H. Laine, P. Nuutila, M. Luotolahti, C. Meyer, T. Elomaa, P. Koskinen, T. Rönnemaa, and J. Knuuti
Insulin-Induced Increment of Coronary Flow Reserve Is Not Abolished by Dexamethasone in Healthy Young Men
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H. Laine, C. Katoh, M. Luotolahti, H. Yki-Jarvinen, I. Kantola, A. Jula, T. O. Takala, U. Ruotsalainen, H. Iida, M. Haaparanta, et al.
Myocardial Oxygen Consumption Is Unchanged but Efficiency Is Reduced in Patients With Essential Hypertension and Left Ventricular Hypertrophy
Circulation,
December 14, 1999;
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[Abstract]
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M. R. Ward and N. A. Herity
Percutaneous Transluminal Coronary Angioplasty Reverses Vasoconstriction of Stenotic Coronary Arteries in Hypertensive Patients
Circulation,
October 26, 1999;
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I. Yokoyama, S.-i. Momomura, T. Ohtake, K. Yonekura, W. Yang, N. Kobayakawa, T. Aoyagi, S. Sugiura, N. Yamada, K. Ohtomo, et al.
Improvement of Impaired Myocardial Vasodilatation Due to Diffuse Coronary Atherosclerosis in Hypercholesterolemics After Lipid-Lowering Therapy
Circulation,
July 13, 1999;
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[Abstract]
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Abstract
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