Myocardial blood flow and its transit time, oxygen utilization, and efficiency of highly endurance-trained human heart.

Highly endurance-trained athlete's heart represents the most extreme form of cardiac adaptation to physical stress, but its circulatory alterations remain obscure. In the present study, myocardial blood flow (MBF), blood mean transit time (MTT), oxygen extraction fraction (OEF) and consumption (MVO2), and efficiency of cardiac work were quantified in highly trained male endurance athletes and control subjects at rest and during supine cycling exercise using [(15)O]-labeled radiotracers and positron emission tomography. Heart rate and MBF were lower in athletes both at rest and during exercise. OEF increased in response to exercise in both groups, but was higher in athletes (70 ± 21 vs. 63 ± 11 % at rest and 86 ± 13 vs. 73 ± 10 % during exercise). MTT was longer and vascular resistance higher in athletes both at rest and during exercise, but arterial content of 2,3-diphosphoglycerate (oxygen affinity) was unchanged. MVO2 per gram of myocardium trended (p = 0.08) lower in athletes both at rest and during exercise, while myocardial efficiency of work and MVO2 per beat were not different between groups. Arterial levels of free fatty acids were ~twofold higher in athletes likely leading to higher myocardial fatty acid oxidation and hence oxygen cost, which may have blunted the bradycardia-induced decrease in MVO2. Finally, the observed group differences in MBF, OEF, MTT and vascular resistance remained significant also after they were controlled for differences in MVO2. In conclusion, in highly endurance-trained human heart, increased myocardial blood transition time enables higher oxygen extraction levels with a lower myocardial blood flow and higher vascular resistance. These physiological adaptations to exercise training occur independently of the level of oxygen consumption and together with training-induced bradycardia may serve as mechanisms to increase functional reserve of the human heart.

Circulating N-terminal brain natriuretic peptide and cardiac function in response to acute systemic hypoxia in healthy humans.

BACKGROUND: As it remains unclear whether hypoxia of cardiomyocytes could trigger the release of brain natriuretic peptide (BNP) in humans, we investigated whether breathing normobaric hypoxic gas mixture increases the circulating NT-proBNP in healthy male subjects. METHODS: Ten healthy young men (age 29 ± 5 yrs, BMI 24.7 ± 2.8 kg/m2) breathed normobaric hypoxic gas mixture (11% O2/89% N2) for one hour. Venous blood samples were obtained immediately before, during, and 2 and 24 hours after hypoxic exposure. Cardiac function and flow velocity profile in the middle left anterior descending coronary artery (LAD) were measured by Doppler echocardiography. RESULTS: Arterial oxygen saturation decreased steadily from baseline value of 99 ± 1% after the initiation hypoxia challenge and reached steady-state level of 73 ± 6% within 20-30 minutes. Cardiac output increased from 6.0 ± 1.2 to 8.1 ± 1.6 L/min and ejection fraction from 67 ± 4% to 75 ± 6% (both p < 0.001). Peak diastolic flow velocity in the LAD increased from 0.16 ± 0.04 to 0.28 ± 0.07 m/s, while its diameter remained unchanged. In the whole study group, NT-proBNP was similar to baseline (60 ± 32 pmol/ml) at all time points. However, at 24 h, concentration of NT-proBNP was higher (34 ± 18%) in five subjects and lower (17 ± 17%), p = 0.002 between the groups) in five subjects than at baseline. CONCLUSION: In conclusion, there is no consistent increase in circulating NT-proBNP in response to breathing severely hypoxic normobaric gas mixture in healthy humans, a possible reason being that the oxygen flux to cardiac myocytes does not decrease because of increased coronary blood flow. However, the divergent individual responses as well as responses in different cardiac diseases warrant further investigations.

Myocardial blood flow and adenosine A2A receptor density in endurance athletes and untrained men.

Previous human studies have shown divergent results concerning the effects of exercise training on myocardial blood flow (MBF) at rest or during adenosine-induced hyperaemia in humans. We studied whether these responses are related to alterations in adenosine A2A receptor (A2AR) density in the left-ventricular (LV) myocardium, size and work output of the athlete's heart, or to fitness level. MBF at baseline and during intravenous adenosine infusion, and A2AR density at baseline were measured using positron emission tomography, and by a novel A(2A)R tracer in 10 healthy male endurance athletes (ET) and 10 healthy untrained (UT) men. Structural LV parameters were measured with echocardiography. LV mass index was 71% higher in ET than UT (193 +/- 18 g m(-2) versus 114 +/- 13 g m(-2), respectively). MBF per gram of tissue was significantly lower in the ET than UT at baseline, but this was only partly explained by reduced LV work load since MBF corrected for LV work was higher in ET than UT, as well as total MBF. The MBF during adenosine-induced hyperaemia was reduced in ET compared to UT, and the fitter the athlete was, the lower was adenosine-induced MBF. A2AR density was not different between the groups and was not coupled to resting or adenosine-mediated MBF. The novel findings of the present study show that the adaptations in the heart of highly trained endurance athletes lead to relative myocardial 'overperfusion' at rest. On the other hand hyperaemic perfusion is reduced, but is not explained by A2AR density.

Insulin improves myocardial blood flow in patients with type 2 diabetes and coronary artery disease.

Insulin infusion improves myocardial blood flow (MBF) in healthy subjects. Until now, the effect of insulin on myocardial perfusion in type 2 diabetic subjects with coronary artery disease (CAD) has been unknown. We studied the effects of insulin on MBF in ischemic regions evaluated by single-photon emission-computed tomography and coronary angiography and in nonischemic regions in 43 subjects (ages 63 +/- 7 years) with type 2 diabetes (HbA(1c) 7.1 +/- 0.9%). MBF was measured at fasting and during a euglycemic-hyperinsulinemic clamp at rest (n = 43) and during adenosine-induced (140 mug . kg(-1) . min(-1) for 7 min) hyperemia (n = 26) using positron emission tomography and (15)O-labeled water. MBF was significantly attenuated in ischemic regions as compared with in nonischemic regions (P < 0.0001) and was increased by insulin as compared with in the fasting state (P < 0.0001). At rest, insulin infusion increased MBF by 13% in ischemic regions (P = 0.043) and 22% in nonischemic regions (P = 0.003). During adenosine infusion, insulin enhanced MBF by 20% (P = 0.018) in ischemic regions and 18% (P = 0.045) in nonischemic regions. In conclusion, insulin infusion improved MBF similarly in ischemic and nonischemic regions in type 2 diabetic subjects with CAD. Consequently, in addition to its metabolic effects, insulin infusion may improve endothelial function and thus increase the threshold for ischemia and partly contribute to the beneficial effects found in clinical trials in these subjects.

Rosiglitazone improves myocardial glucose uptake in patients with type 2 diabetes and coronary artery disease: a 16-week randomized, double-blind, placebo-controlled study.

Rosiglitazone therapy improves insulin sensitivity and glucose uptake in patients with uncomplicated type 2 diabetes. In coronary artery disease (CAD), glucose is an important source of energy and preserved myocardial glucose uptake is essential for the viability of jeopardized myocardium. The aim was to test whether rosiglitazone changes myocardial metabolism in type 2 diabetic patients with CAD. We studied 54 patients (38 men and 16 women) with type 2 diabetes (HbA(1c) 7.2 + 0.9%) and CAD. Myocardial glucose uptake was measured with [(18)F]fluoro-2-deoxy-d-glucose positron emission tomography in ischemic (evaluated by single-photon emission tomography and coronary angiography) and nonischemic regions during euglycemic-hyperinsulinemic clamp before and after a 16-week intervention period with rosiglitazone (n = 27) or placebo (n = 27). Rosiglitazone significantly improved glycemic control (P < 0.0001) and whole-body insulin sensitivity (P < 0.0001). Rosiglitazone increased myocardial glucose uptake from 20.6 +/- 11.8 to 25.5 +/- 12.4 micromol . 100 g(-1) . min(-1) (P = 0.038 vs. baseline, P = 0.023 vs. placebo) in ischemic regions and from 21.7 +/- 12.1 to 28.0 +/- 12.7 micromol . 100 g(-1) . min(-1) (P = 0.014 vs. baseline, P = 0.003 vs. placebo) in nonischemic regions. The increase in myocardial glucose uptake was partly explained by the suppression of free fatty acid levels during clamp. Rosiglitazone therapy significantly increased insulin sensitivity and improved myocardial glucose uptake in type 2 diabetic patients with CAD. These results suggest that rosiglitazone therapy may facilitate myocardial glucose storage and utilization in these patients.

Two-Dimensional Speckle-Tracking during Dobutamine Stress Echocardiography in the Detection of Myocardial Ischemia in Patients with Suspected Coronary Artery Disease.

BACKGROUND: Two-dimensional speckle-tracking applied to dobutamine stress echocardiography (DSE) may aid in the detection of coronary artery disease (CAD). The aim of this study was to determine the value of strain, strain rate, and postsystolic strain index (PSI) measured by speckle-tracking during DSE in the evaluation of the presence, extent, and severity of myocardial ischemia. METHODS: Fifty patients 63 ± 7 years of age with intermediate probability of CAD were prospectively recruited. All patients underwent DSE, quantitative positron emission tomographic perfusion imaging, and invasive angiography. Regional peak systolic longitudinal strain, strain rate, and PSI were measured at rest, at a dobutamine dose of 20 µg/kg/min, at peak stress, and at early recovery (1 min after stress). Obstructive CAD was defined as >75% stenosis or 40% to 75% stenosis combined with either fractional flow reserve < 0.80 or abnormal findings on myocardial perfusion positron emission tomography. RESULTS: Obstructive CAD was detected in 22 patients and in 36 of 150 coronary arteries. Strain analyses showed the highest reproducibility at rest, at a dobutamine dose of 20 µg/kg/min, and at early recovery. Increased PSI and reduced strain during early recovery were the strongest predictors of obstructive CAD and were associated with the extent, localization, and depth of myocardial ischemia by positron emission tomography. On vessel-based analysis, strain, PSI, and visual analysis of wall motion provided comparable diagnostic accuracy, whereas the combination of strain or PSI with visual analysis provided incremental value over visual analysis alone. CONCLUSIONS: Assessment of systolic or postsystolic strain by speckle-tracking echocardiography during early recovery after DSE can help in the detection of hemodynamically significant coronary stenosis compared with visual wall motion analysis alone.

Dose-dependent vasodilating effects of insulin on adenosine-stimulated myocardial blood flow.

In the peripheral vasculature, insulin induces time- and dose-dependent vasodilation. We have recently demonstrated that insulin potentiates adenosine-stimulated myocardial blood flow. However, it is unknown whether insulin's effects on the coronary vasculature are dose dependent. In this study, we quantitated myocardial blood flow and adenosine-stimulated coronary flow (140 microg.kg(-1).min(-1) for 5 min) in 10 healthy men (age, 32 +/- 6 years; BMI, 24.1 +/- 1.8 kg/m(2)) using positron emission tomography and (15)O-labeled water. Hyperemic myocardial blood flow was measured in the basal state, during euglycemic physiological hyperinsulinemia (serum insulin approximately 65 mU/l) and during supraphysiological hyperinsulinemia (serum insulin approximately 460 mU/l). Basal myocardial blood flow was 0.84 +/- 0.17 ml.g(-1).min(-1). Physiological hyperinsulinemia increased the adenosine-stimulated flow by 20% (from 3.92 +/- 1.17 to 4.72 +/- 0.96 ml.g(- 1).min(-1); P < 0.05). Supraphysiological hyperinsulinemia further enhanced the adenosine-stimulated flow by 19% (to 5.61 +/- 1.03 ml.g(-1).min(-1); P < 0.05). These effects were not explained by changes in systemic hemodynamics, since coronary resistance decreased during each insulin infusion (P < 0.05). In addition, hyperemic myocardial blood flow responses during insulin stimulation were positively correlated with whole-body glucose uptake. The results demonstrate that insulin is able to enhance hyperemic myocardial blood flow in a dose-dependent manner in healthy subjects. These effects might contribute to the known beneficial dose-dependent effects of insulin on myocardial ischemia.

Exercise training improves biventricular oxidative metabolism and left ventricular efficiency in patients with dilated cardiomyopathy.

OBJECTIVES: The aim of this study was to determine the effect of exercise training on myocardial oxidative metabolism and efficiency in patients with idiopathic dilated cardiomyopathy (DCM) and mild heart failure (HF). BACKGROUND: Exercise training is known to improve exercise tolerance and quality of life in patients with chronic HF. However, little is known about how exercise training may influence myocardial energetics. METHODS: Twenty clinically stable patients with DCM (New York Heart Association classes I through III) were prospectively separated into a training group (five-month training program; n = 9) and a non-trained control group (n = 11). Oxidative metabolism in both the right and left ventricles (RV and LV) was measured using [(11)C]acetate and positron emission tomography. Myocardial work power was measured using echocardiography. Myocardial efficiency for forward work was calculated as myocardial work power per mass/LV oxidative metabolism. RESULTS: Significant improvements were noted in exercise capacity (VO(2)) and ejection fraction in the training group, whereas no changes were observed in the non-trained group. Exercise training reduced both RV and LV oxidative metabolism and elicited a significant increase in LV forward work efficiency, although no significant changes were observed in the non-trained group. CONCLUSIONS: Exercise training improves exercise tolerance and LV function. This is accompanied by a decrease in biventricular oxidative metabolism and enhanced forward work efficiency. Therefore, exercise training elicits an energetically favorable improvement in myocardial function and exercise tolerance in patients with DCM.

Increased lipoprotein(a) is associated with reduced myocardial vasoreactivity in young healthy men.

OBJECTIVES AND BACKGROUND: We examined the association between lipoprotein(a) and myocardial vasoreactivity in healthy men. METHODS: Thirty non-smoking healthy men (age 34+/-6 years) were studied: 9 had increased lipoprotein(a) (>200 mg/L) concentrations (lipoprotein(a) 317 (range 218-550) mg/L) and 21 had normal lipoprotein(a) (<200 mg/L) concentrations (lipoprotein(a) 57 (range 13-156) mg/L). The myocardial blood flow measurements were performed basally and during adenosine infusion (140 microg/kg/min) with or without simultaneous physiological hyperinsulinemia (insulin infusion at a rate of 1 mU/kg/min) using positron emission tomography and [(15)O]H(2)O. RESULTS: Basal myocardial blood flow was similar between the subjects with increased and normal lipoprotein(a) (0.76+/-0.20 and 0.79+/-0.20 mLg(-1) min(-1), NS). Adenosine-stimulated flow tended to be reduced in subjects with increased lipoprotein(a) (3.1+/-0.7 mLg(-1) min(-1) versus 3.7+/-1.1 mLg(-1) min(-1), respectively, p=0.1). During physiological hyperinsulinemia adenosine-stimulated flow was further enhanced in both groups but significantly blunted in subjects with increased lipoprotein(a) (3.7+/-0.8 mLg(-1) min(-1) versus 4.8+/-1.4 mLg(-1) min(-1), respectively, p=0.03). This difference remained significant after simultaneous controlling for BMI, HbA1c, LDL-cholesterol, HDL-cholesterol and blood pressure (p=0.04). CONCLUSIONS: Already young healthy men with lipoprotein(a) concentrations greater than 200mg/L are characterized by impaired myocardial vasoreactivity.

Effect of spinal cord stimulation on myocardial perfusion reserve in patients with refractory angina pectoris.

AIMS: Epidural spinal cord stimulation (SCS) provides symptom relief in refractory angina pectoris, but its mechanism of action remains incompletely understood. We studied effects of short-term SCS therapy on myocardial ischaemia tolerance, myocardial perfusion reserve (MPR), and endothelium-mediated vasodilatation induced by cold pressor test (CPT) in patients with refractory angina pectoris. METHODS AND RESULTS: We prospectively recruited 18 patients with refractory angina pectoris and studied them after implantation of SCS device at baseline before starting the therapy and after 3 weeks of continuous SCS therapy. Myocardial ischaemia was evaluated by dobutamine stress echocardiography. Global and regional myocardial blood flow (MBF) were measured using positron emission tomography and (15)O-water at rest, during adenosine stress, and in response to CPT. Systemic haemodynamics were comparable before and after 3 weeks of SCS at rest, during adenosine stress and during CPT. Appearance of angina pectoris induced by dobutamine stress was delayed after SCS therapy. Global MPR increased (P = 0.02) from 1.7 ± 0.6 at baseline to 2.0 ± 0.6 after 3-week SCS therapy. This was associated with a significant reduction in global MBF at rest and increase in MBF induced by adenosine in the ischaemic regions. Global MBF response to CPT was improved after SCS (0.27 ± 0.20 vs. 0.40 ± 0.15, P = 0.03). CONCLUSION: Short-term SCS therapy improved myocardial ischaemia tolerance, absolute MPR, and endothelium-mediated vasomotor function in refractory angina pectoris, indicating that this therapy can alleviate myocardial perfusion abnormalities in advanced CAD.

Myocardial perfusion and perfusion reserve in endurance-trained men.

PURPOSE: This study was undertaken to determine whether endurance training is associated with changes in myocardial perfusion in humans. METHODS: Myocardial perfusion was measured in eleven trained and nine sedentary men at rest and during adenosine-stimulated hyperemia using positron emission tomography (PET). Left ventricular (LV) dimensions and mass were measured using echocardiography. Myocardial work per gram of tissue was calculated as (cardiac output. mean arterial blood pressure)/LV mass. RESULTS: LV mass was significantly higher and myocardial work per gram of tissue lower in the trained than in the untrained subjects. Basal (0.78 +/- 0.10 and 0.76 +/- 0.15 mL. min-1. g-1, P = NS) and adenosine-stimulated perfusion (3.46 +/- 0.91 and 3.14 +/- 0.70 mL. min-1. g-1, P = NS) were similar between trained and untrained men, respectively. Consequently, myocardial perfusion reserve was similar in both groups (4.4 +/- 1.2 and 4.1 +/- 0.7, P = NS). In addition, coronary resistance at baseline (115 +/- 17 vs 119 +/- 22, mm Hg. mL. min-1. g-1, P = NS) and during adenosine infusion (28 +/- 8 vs 30 +/- 8, mm Hg. mL. min-1. g-1, P = NS) were similar in both groups. Resting myocardial work correlated with resting myocardial perfusion in both groups, but the relationship between perfusion and work was different between the groups so that perfusion for a given myocardial work was significantly higher in trained subjects (0.56 +/- 0.04 and 0.34 +/- 0.05 mL. (mm Hg. L)-1, P < 0.001). CONCLUSIONS: These findings suggest that endurance trained subjects do not have different resting or adenosine-stimulated myocardial perfusion. However, the relationship between myocardial perfusion and work appears altered in the athletes.

Association between insulin resistance and reduced coronary vasoreactivity in healthy subjects.

BACKGROUND: Insulin resistance appears to be an important risk factor for coronary artery disease. OBJECTIVE: To examine the role of insulin resistance on coronary vasoreactivity in healthy subjects. PATIENTS AND METHODS: Myocardial blood flow was quantitated using positron emission tomography and oxygen-15-labelled water in 10 healthy, nonobese men. The perfusion measurements were performed basally and during adenosine infusion, which has been used as a measure of coronary vasoreactivity. After perfusion measurements were taken, whole-body glucose uptake was determined using the euglycemic hyperinsulinemic clamp technique. RESULTS: Basal myocardial blood flow was 0.89+/-0.21 mL.g(-1).min(-1); adenosine significantly increased the flow to 4.00+/-1.13 mL.g(-1).min(-1). Adenosine-stimulated myocardial blood flow was inversely associated with fasting serum insulin concentration (r=-0.69, P<0.05). Concordantly, hyperemic blood flow was associated with whole-body glucose uptake during euglycemic hyperinsulinemic conditions (r=0.64, P<0.05). Basal myocardial blood flow was not affected by insulin resistance. CONCLUSION: The results of the present study demonstrate the novel finding that insulin resistance is associated with reduced coronary vasoreactivity, even in healthy subjects.

The Sensitivity of Exercise Echocardiography Can Be Improved by Taking the Delayed Myocardial Contraction into Account.

The purpose of this study was to test whether the systolic myocardial wall motion abnormalities at the early stages of ischemia are applicable to the diagnosis of coronary artery disease. Forty-four patients with suspected coronary artery disease were studied with the use of low-level exercise echocardiography. Exercise was stopped at the onset of first cardiac symptoms, and no patient exceeded 70% of the age-predicted maximal heart rate level. Forty patients had significant stenosis in at least one coronary artery on coronary angiography. Ten control subjects with a low probability of ischemic heart disease also were studied with exercise echocardiography. The first ischemic wall motion abnormality in systole, defined as delayed onset of the contraction (a regional delay of at least 100 milliseconds in a frame-by-frame analysis of echocardiograms) without any reduction in systolic movement, was regarded separately from hypokinesis (systolic wall motion excursion of less than 5 mm). When the delayed onset of the contraction also was taken into account, 37 of the 40 patients with coronary artery disease had an ischemic response after exercise. The sensitivity of the test thus was 93%. The reduction in systolic wall movement was detected in only 18 of these patients at the exercise level attained (70% or less of age-predicted maximal heart rate). There were two false-positive echocardiograms, but when the control group also was considered, the specificity of the test remained high at 86%. The sensitivity of exercise echocardiography can be increased by paying attention to the delayed onset of the systolic contraction, which occurs at the early stages of ischemia.

VO(2peak), myocardial hypertrophy, and myocardial blood flow in endurance-trained men.

INTRODUCTION: Endurance training induces cardiovascular and metabolic adaptations, leading to enhanced endurance capacity and exercise performance. Previous human studies have shown contradictory results in functional myocardial vascular adaptations to exercise training, and we hypothesized that this may be related to different degrees of hypertrophy in the trained heart. METHODS: We studied the interrelationships between peak aerobic power (V˙O2peak), myocardial blood flow (MBF) at rest and during adenosine-induced vasodilation, and parameters of myocardial hypertrophy in endurance-trained (ET, n = 31) and untrained (n = 17) subjects. MBF and myocardial hypertrophy were studied using positron emission tomography and echocardiography, respectively. RESULTS: Both V˙O2peak (P < 0.001) and left ventricular (LV) mass index (P < 0.001) were higher in the ET group. Basal MBF was similar between the groups. MBF during adenosine was significantly lower in the ET group (2.88 ± 1.01 vs 3.64 ± 1.11 mL·g·min, P < 0.05) but not when the difference in LV mass was taken into account. V˙O2peak correlated negatively with adenosine-stimulated MBF, but when LV mass was taken into account as a partial correlate, this correlation disappeared. CONCLUSIONS: The present results show that increased LV mass in ET subjects explains the reduced hyperemic myocardial perfusion in this subject population and suggests that excessive LV hypertrophy has negative effect on cardiac blood flow capacity.

The association between coronary flow reserve and development of coronary calcifications: a follow-up study for 11 years in healthy young men.

AIMS: We studied whether a reduced coronary flow reserve (CFR) in healthy young men independently predicts the presence of coronary artery disease as assessed by coronary artery calcification after 11 years of follow-up. METHODS AND RESULTS: Coronary microvascular dysfunction in early stages of coronary artery disease can be detected as a reduced CFR by positron emission tomography (PET). Seventy-seven healthy, lean, normotensive, non-smoking and non-diabetic men underwent 15-Oxygen ((15)O) water myocardial perfusion PET at rest and during vasodilator stress at the age of 35 ± 4 years at baseline. The subjects were followed-up for 11 ± 1 years and the coronary artery calcium score (CCS) was measured with computed tomography at the end of the follow-up. At the end of the follow-up, 30 (39%) individuals had CCS >0 (average 65 ± 93), but none had clinical symptoms or evidence of ischaemia in stress echocardiography. At baseline, the average CFR was comparable in individuals with CCS >0 and CCS = 0 (4.2 ± 1.4 vs. 4.0 ± 1.2, P = 0.4). Logistic regression analysis showed no associations between CFR, serum glucose, cholesterol levels, systolic blood pressure or body mass index at baseline and CCS at the end of the follow-up (P always >0.05). The presence of CCS (CCS >0) was associated with higher systolic and diastolic blood pressures at the end of the follow-up (137 ± 18 vs. 128 ± 11 mmHg, P = 0.04 and 86 ± 12 vs. 78 ± 11 mmHg, P = 0.01). CONCLUSIONS: Coronary reactivity to vasodilator-induced hyperaemia as assessed by perfusion PET was not predictive of the presence of coronary calcification after 11 years of follow-up in asymptomatic men with very low likelihood of coronary artery disease.

Pulmonary blood flow and its distribution in highly trained endurance athletes and healthy control subjects.

Pulmonary blood flow (PBF) is an important determinant of endurance sports performance, yet studies investigating adaptations of the pulmonary circulation in athletes are scarce. In the present study, we investigated PBF, its distribution, and heterogeneity at baseline and during intravenous systemic adenosine infusion in 10 highly trained male endurance athletes and 10 untrained but fit healthy controls, using positron emission tomography and [(15)O]water at rest and during adenosine infusion at supine body posture. Our results indicate that PBF at rest and during adenosine stimulation was similar in both groups (213 ± 55 and 563 ± 138 ml·100 ml(-1)·min(-1) in athletes and 206 ± 83 and 473 ± 212 ml·100 ml(-1)·min(-1) in controls, respectively). Although the PBF response to adenosine was thus unchanged in athletes, overall PBF heterogeneity was reduced from rest to adenosine infusion (from 84 ± 18 to 70 ± 19%, P < 0.05), while remaining unchanged in healthy controls (77 ± 16 to 85 ± 33%, P = 0.4). Additionally, there was a marked gravitational influence on general PBF distribution so that clear dorsal dominance was observed both at rest and during adenosine infusion, but training status did not have an effect on this distribution. Regional blood flow heterogeneity was markedly lower in the high-perfusion dorsal areas, both at rest and during adenosine, in all subjects, but flow heterogeneity in dorsal area tended to further decrease in response to adenosine in athletes. In conclusion, reduced blood flow heterogeneity in response to adenosine in endurance athletes may be a reflection of capillary reserve, which is more extensively recruitable in athletes than in matched healthy control subjects.

Myocardial perfusion during exercise in endurance-trained and untrained humans.

Because of technical challenges very little is known about absolute myocardial perfusion in humans in vivo during physical exercise. In the present study we applied positron emission tomography (PET) in order to 1) investigate the effects of dynamic bicycle exercise on myocardial perfusion and 2) clarify the possible effects of endurance training on myocardial perfusion during exercise. Myocardial perfusion was measured in endurance-trained and healthy untrained subjects at rest and during absolutely the same (150 W) and relatively similar [70% maximal power output (W(max))] bicycle exercise intensities. On average, the absolute myocardial perfusion was 3.4-fold higher during 150 W (P < 0.001) and 4.9-fold higher during 70% W(max) (P < 0.001) than at rest. At 150 W myocardial perfusion was 46% lower in endurance-trained than in untrained subjects (1.67 +/- 0.45 vs. 3.00 +/- 0.75 ml x g(-1) x min(-1); P < 0.05), whereas during 70% W(max) perfusion was not significantly different between groups (P = not significant). When myocardial perfusion was normalized with rate-pressure product, the results were similar. Thus, according to the present results, myocardial perfusion increases in parallel with the increase in working intensity and in myocardial work rate. Endurance training seems to affect myocardial blood flow pattern during submaximal exercise and leads to more efficient myocardial pump function.

Positive family history of coronary artery disease is associated with reduced myocardial vasoreactivity in healthy men.

OBJECTIVE: Positive family history as a risk factor for coronary artery disease seems to be most important in subjects who otherwise are at low risk. We examined the association between family history of coronary artery disease and myocardial vasoreactivity in healthy men. METHODS: 35 non-smoking healthy men (age 35+/-7 years) were studied: 16 had positive family history of coronary artery disease and 19 had negative family history. The myocardial blood flow measurements were performed basally and during adenosine infusion (140 mug/kg/min) with and without simultaneous physiological hyperinsulinemia (insulin infusion at a rate of 1 mU/kg/min) using positron emission tomography and O-15-water. RESULTS: Basal myocardial blood flow was similar between the subjects with positive and negative family history of coronary artery disease (0.79+/-0.19 and 0.79+/-0.21 mL g(-1) min(-1), NS). Adenosine stimulated flow was significantly reduced in subjects with positive family history (3.0+/-0.5 vs 4.0+/-1.2 mL g(-1) min(-1), respectively, p=0.003). During physiological hyperinsulinemia adenosine stimulated flow was further enhanced in both groups but significantly blunted in subjects with positive family history (3.7+/-0.9 vs 5.2+/-1.5 mL g(-1) min(-1), respectively, p=0.001). These differences remained significant after simultaneous controlling for age, BMI, HbA1c, LDL-cholesterol, HDL-cholesterol and blood pressure (p=0.002). CONCLUSIONS: Healthy non-smoking men with positive family history of coronary artery disease are characterized by impaired myocardial vasoreactivity.

Clinical practicality and predictive value of transoesophageal echocardiography in early cardioversion of atrial fibrillation.

AIMS: The objective of this study is to evaluate the feasibility of transoesophageal echocardiography (TOE)-guided cardioversion (CV) of atrial fibrillation (AF) in daily clinical practice. METHODS AND RESULTS: Transthoracic echocardiography and TOE were performed in 346 consecutive patients with AF lasting longer than 48 h or of unknown duration. If no intracavitary thrombus was found, CV was performed within 24 h of the TOE examination. Anticoagulation with subcutaneous low-molecular-weight heparin and warfarin was always started before CV. Warfarin was continued for at least 1 month after CV. The predictive value of several echocardiographic parameters including peak left atrial appendage emptying velocity (PLAAEV), left ventricular ejection fraction, left atrial diameter, and spontaneous echo contrast for the initial and long-term success of CV were evaluated. Transoesophageal echocardiography revealed no thrombus or other contraindications to CV in 274/346 (79%) patients. Early CV restored normal sinus rhythm or pacemaker rhythm in 90% (246/274) of the patients. One patient (0.3%) had a stroke within 30 days after CV. Peak left atrial appendage emptying velocity was significantly lower in patients with contraindications to early CV (P<0.001). However, neither PLAAEV nor any other echocardiographic parameter predicted the initial success of CV and the maintenance of sinus rhythm during long-term follow-up. CONCLUSION: Early TOE-guided CV with short-term anticoagulation is a safe and clinically effective alternative in treatment of AF lasting longer than 48 h or of unknown duration. The initial and long-term success of CV cannot be reliably predicted by echocardiographic parameters.

Blunted coronary vasoreactivity to insulin is an early alteration in hypertension.

Insulin resistance in the heart is not localized to the myocardium, but may also occur in blood vessels. We studied the effects of insulin on coronary vasodilation in hypertension. Coronary vascular resistance was quantitated in 11 nonsmoking men with untreated mild essential hypertension and 9 healthy normotensive men using positron emission tomography and (15)O-labeled water. The measurements were performed at baseline and during adenosine infusion (140 microg x kg(-1) x min(-1)) with or without simultaneous euglycemic physiological (serum insulin approximately 70 mU/l) and supraphysiological (serum insulin approximately 460 mU/l) hyperinsulinemia. Coronary resistance was significantly higher in hypertensive than normotensive subjects at baseline and during adenosine infusion. Physiological hyperinsulinemia decreased hyperemic coronary resistance significantly in both groups. Supraphysiological hyperinsulinemia further decreased the hyperemic coronary resistance in normotensive but not in hypertensive subjects, leading to higher hyperemic coronary resistance in hypertensive than normotensive subjects (27.2 +/- 8.7 vs. 19.2 +/- 4.9 mm Hg x min x g x ml(-1), p < 0.05). However, insulin-stimulated whole body glucose uptake values were similar between the groups during both insulin infusions. In conclusion, insulin-induced coronary vasodilation is blunted in young subjects with mild essential hypertension who are otherwise healthy. Coronary vascular resistance to insulin occurs although no change in peripheral glucose uptake can be detected. While we do not know whether the same results can be extrapolated to female or older subjects, these results indicate a novel defect in the regulation of coronary arteries in the early phase of hypertension.