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.

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.

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 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.

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 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.

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.

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.

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.

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.

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.

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.

Myocardial perfusion after marathon running.

We investigated the effects of acute prolonged exercise (marathon running) on cardiac function and myocardial perfusion. Cardiac dimensions and function were measured in seven endurance-trained men using echocardiography before and repeatedly after marathon (42.2 km) running (at 10 min, 150 min, and 20 h). Myocardial perfusion and perfusion resistance were measured using positron emission tomography and 15O-H2O before and 85-115 min after running. Echocardiographic indices showed only mild and clinically non-significant changes in cardiac function after running. Rate-pressure-corrected basal myocardial perfusion (0.89+/-0.13 vs. 1.20+/-0.32 mL min(-1) g(-1), P=0.04) was increased after running. Also, adenosine-stimulated perfusion tended to be higher (3.67+/-0.81 vs. 4.47+/-0.52 mL min(-1) g(-1), P=0.12) and perfusion resistance during adenosine stimulation was significantly lower after running (26+/-6 vs. 18+/-3 mmHg min g mL(-1), P=0.03). Plasma free fatty acid (FFA) concentration was significantly increased after running. These results show that marathon running does not cause marked changes in cardiac function in healthy men. Basal perfusion was increased after exercise, probably reflecting changes in fuel preferences to increased use of FFAs. Strenuous exercise also seems to enhance coronary reactivity, which could thereby serve as a protective mechanism to vascular events after exercise.

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.

Myocardial perfusion reserve and oxidative metabolism contribute to exercise capacity in patients with dilated cardiomyopathy.

BACKGROUND: Exercise intolerance is a hallmark symptom in patients with heart failure; however, myocardial factors contributing to the limited exercise capacity are not fully characterized. METHODS: Twenty patients with stable heart failure resulting from idiopathic dilated cardiomyopathy (DCM) and 13 controls were studied. Myocardial perfusion, biventricular oxidative metabolism, and insulin-stimulated glucose uptake were measured using positron emission tomography and [(15)O]H(2)O, [(11)C]acetate, and [(18)F]FDG. RESULTS: Hyperemic perfusion and perfusion reserve were significantly lower in the DCM patients compared with the healthy subjects. There was no difference in left ventricular oxidative metabolism between the 2 groups; however, the patients had a 19% higher right ventricular oxidative metabolism (P=.005). Consequently, the ratio of right to left ventricular oxidative metabolism was also higher (31%) in the patients. There was a strong inverse association between decreased exercise capacity and the ratio of right to left ventricular oxidative metabolism (r=-.68, P<.01) and a positive association with myocardial perfusion reserve (r=.62, P<.01) in the patient group. These 2 parameters along with resting left ventricular work explained 57% of the variability in peak exercise capacity. CONCLUSIONS: Impaired perfusion reserve and an exaggerated imbalance in right to left ventricular oxidative metabolism appear to significantly contribute to the impaired exercise capacity in these DCM patients.

C-peptide improves adenosine-induced myocardial vasodilation in type 1 diabetes patients.

Patients with type 1 (insulin-dependent) diabetes show reduced skeletal muscle blood flow and coronary vasodilatory function despite intensive insulin therapy and good metabolic control. Administration of proinsulin C-peptide increases skeletal muscle blood flow in these patients, but a possible influence of C-peptide on myocardial vasodilatory function in type 1 diabetes has not been investigated. Ten otherwise healthy young male type 1 diabetic patients (Hb A1c 6.6%, range 5.7-7.9%) were studied on two consecutive days during normoinsulinemia and euglycemia in a double-blind, randomized, crossover design, receiving intravenous infusion of C-peptide (5 pmol.kg-1.min-1) for 120 min on one day and saline infusion on the other day. Myocardial blood flow (MBF) was measured at rest and during adenosine administration (140 microg.kg-1.min-1) both before and during the C-peptide or saline infusions by use of positron emission tomography and [15O]H2O administration. Basal MBF was not significantly different in the patients compared with an age-matched control group, but adenosine-induced myocardial vasodilation was 30% lower (P < 0.05) in the patients. During C-peptide administration, adenosine-stimulated MBF increased on average 35% more than during saline infusion (P < 0.02) and reached values similar to those for the healthy controls. Moreover, as evaluated from transthoracal echocardiographic measurements, C-peptide infusion resulted in significant increases in both left ventricular ejection fraction (+5%, P < 0.05) and stroke volume (+7%, P < 0.05). It is concluded that short-term C-peptide infusion in physiological amounts increases the hyperemic MBF and left-ventricular function in type 1 diabetic patients.

Exercise training improves insulin-stimulated myocardial glucose uptake in patients with dilated cardiomyopathy.

BACKGROUND: The effects of exercise training on myocardial substrate utilization have not previously been studied in patients with idiopathic dilated cardiomyopathy and mild heart failure. METHODS AND RESULTS: Myocardial glucose uptake was studied in 15 clinically stable patients with dilated cardiomyopathy (New York Heart Association class I-II, ejection fraction 34% +/- 8%) with the use of 2-[fluorine 18]fluoro-2-deoxy-d-glucose ([F-18]FDG) and positron emission tomography under euglycemic hyperinsulinemia. Eight of these patients participated in a 5-month endurance and strength training program, whereas seven patients served as nontrained subjects. Left ventricular function was assessed by 2-dimensional echocardiography before and after the intervention. After the training period, insulin-stimulated myocardial fractional [F-18]FDG uptake and glucose uptake rates were significantly increased in the anterior, lateral, and septal walls (P <.01) in the trained subjects but remained unchanged in the nontrained subjects. In the trained patients, whole-body insulin-stimulated glucose uptake was enhanced and serum free fatty acid levels were suppressed during hyperinsulinemia compared with the baseline study (P <.05). No changes were observed in the nontrained group. CONCLUSIONS: These results indicate that exercise training in patients with dilated cardiomyopathy improves insulin-stimulated myocardial glucose uptake. This improvement in glucose uptake may be indicative of a switch in myocardial preference to a more energy-efficient substrate.

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.