Biomedical subjects

F M Bengel

Publications and source records attributed to F M Bengel.

At least 19 recordsLinked to original sources

PubMed2003

Myocardial perfusion and coronary flow reserve assessed by positron emission tomography in patients after Fontan-like operations.

Ventricular dysfunction in patients after Fontan-like operations (FLOs) is a serious complication that might contribute to poor long-term results. Ischemic heart disease will have debilitating consequences on a Fontan heart. Ten patients (15.8 +/- 5.01 years) after FLO had transesophageal echocardiography and cardiac catheterization 9.3 +/- 4.2 years after surgery. Myocardial perfusion was assessed by NH3-positron emission tomography (rest/adenosine) and compared with that of 10 healthy adults (26.1 +/- 6.3 years). Ventricular function was normal in 4 and reduced in 6 patients; end systolic and end diastolic meridional wall stress was significantly elevated in the FLO group. Coronary angiography revealed no stenosis of the coronaries. Compared to normals, myocardial blood flow (MBF) at rest was higher in the FLO group (0.99 +/- 0.25 vs 0.77 +/- 0.17 ml/g/min, p <0.05), whereas MBF after vasodilatation (2.12 +/- 0.78 vs 3.10 +/- 0.85 ml/g/min, p <0.05) and coronary flow reserve (CFR) was reduced (2.5 +/- 0.88 vs 4.1 +/- 1.01, p <0.05), especially in those with impaired ventricular function. Coronary vascular resistance after vasodilatation was elevated in the FLO group (38.2 +/- 17.4 vs 24.5 +/- 8.3 mmHg/ml/g/min, p <0.05). Altered MBF, increased meridional wall stress, and impaired CFR are common findings in FLO. Attenuated CFR and reduced ventricular function are significantly correlated and may be risk factors for the long-term outcome.

Adolescent↗

PubMed2003

Cardiac autonomic dysinnervation and myocardial blood flow in long-term Type 1 diabetic patients.

AIMS: The aim of the study was to assess scintigraphically the relationship between myocardial blood flow response and sympathetic dysinnervation in long-term Type 1 diabetic patients. Effects of the iron chelator deferoxamine on myocardial blood flow were studied and they were investigated according to the presence of cardiac sympathetic dysfunction. METHODS: Myocardial blood flow (MBF) was assessed with N-13 ammonia positron emission tomography in 13 long-term Type 1 diabetic patients and 13 control subjects at rest and in response to sympathetic stimulation (cold pressor test (CPT)). In diabetic patients, the study was repeated after preinfusion with deferoxamine. Furthermore, 123I metaiodobenzylguanidine (MIBG) scintigraphy was applied to assess regional cardiac sympathetic dysinnervation (uptake score 1 = normal, homogeneous uptake em leader 6 = no uptake). RESULTS: In diabetic patients, MBF increased in response to CPT from 78 +/- 18 ml/100 g/min to 84 +/- 26 ml/100 g (8%, P < 0.001). Control subjects demonstrated an increase from 63 +/- 17 ml/100 g to 84 +/- 26 ml/100 g (33%, P < 0.001), respectively. Resting MBF was higher in diabetic patients than in control subjects (P < 0.001). In diabetic patients, increase in MBF in response to CPT was significant in regions with a MIBG uptake score of 3 did not exhibit a significant increase in MBF in response to CPT. After administration of deferoxamine, the increase in MBF in response to CPT was 23% and the magnitude of increase was related to the MIBG uptake score (r = 0.40, P < 0.0001). CONCLUSIONS: Myocardial blood flow response to sympathetic stimulation is significantly impaired in long-term Type 1 diabetes. After preinfusion with deferoxamine the impairment is partially reversed and a relationship between myocardial blood flow and the extent of cardiac sympathetic dysfunction is observed.

3-Iodobenzylguanidine↗

PubMed2003

Alterations of myocardial presynaptic sympathetic innervation in patients with multi-vessel coronary artery disease but without history of myocardial infarction.

In patients with myocardial infarction, left ventricular sympathetic denervation exceeds the size of the scar tissue. However, little is known about the regional innervation in patients with coronary artery disease (CAD) but no myocardial infarction. Using positron emission tomography (PET) with N-ammonia and C-hydroxyephedrine (HED), resting perfusion and presynaptic sympathetic innervation were studied in eight patients (seven males, one female; 58+/-9 years) with multi-vessel CAD and no history of myocardial infarction. Using polar map analysis of the PET data, the results were regionally compared with normal databases. The mean HED retention was 8.0%+/-2.0% x min(-1). Myocardial resting perfusion was normal in 23 of 24 vascular territories. Despite normal resting perfusion, significantly reduced HED retention, indicating dysinnervation, was found in 14 of 23 (61%) vascular territories (six of eight patients). Of the dysinnervated territories, 11 (79%) showed angiographically severe stenosis (>or=90% of native vessel/coronary artery bypass graft), eight (57%) showed ischaemia (myocardial perfusion scintigraphy/stress-electrocardiogram) and 12 (86%) had been revascularized. Of the nine segments with normal innervation, two (22%) revealed severe stenosis, two (22%) showed ischaemia and seven (78%) had been revascularized. It can be concluded that, in patients with advanced CAD and normal left ventricular function, dysinnervation can occur in the absence of myocardial infarction. This is consistent with the hypothesis that sympathetic neurones are more susceptible than myocytes to ischaemic damage.

Aged↗

PubMed2003

Impaired myocardial blood flow and coronary flow reserve of the anatomical right systemic ventricle in patients with congenitally corrected transposition of the great arteries.

OBJECTIVES: To investigate myocardial blood flow of the morphological right systemic ventricle in unoperated patients with congenitally corrected transposition of the great arteries (CCTGA) by positron emission tomography (PET). DESIGN: Prospective cross sectional clinical study. SETTING: Tertiary referral centre for paediatric cardiology. PATIENTS: 15 patients with CCTGA were investigated by PET with nitrogen-13 ammonia at rest and during adenosine vasodilatation. A subgroup of seven patients had isolated CCTGA (group A, mean (SD) age 30.3 (11.9) years) and the remaining eight patients had complex CCTGA associated with subpulmonary stenosis; four of this second group also had ventricular septal defect (group B, mean (SD) age 30.6 (16.4) years). Eleven healthy adults (mean (SD) age 26.2 (5.1) years) served as the control group. RESULTS: Resting myocardial blood flow was not different between both groups of patients with CCTGA and the controls. Hyperaemic blood flows were significantly lower in both groups of CCTGA than in the control group (mean (SD) 195 (21) ml/100g/min in group A, 201 (27) ml/100g/min in group B, 309 (74) ml/100g/min in the control group; p < 0.001). Thus, coronary flow reserve was significantly lower in both groups of CCTGA than in the control group (mean (SD) 2.5 (0.28) in group A, 2.6 (0.48) in group B, and 4.0 (0.73) in the control group; p < 0.001). CONCLUSION: Blood flow measurements suggest that coronary reserve is decreased in the absence of ischaemic symptoms in patients with CCTGA. The global impairment of stress flow dynamics may indicate altered global vasoreactivity, and quantitative changes in microcirculation suggest that their role in the pathogenesis of systemic right ventricular dysfunction is important.

Adenosine↗

PubMed2001

Effect of sympathetic reinnervation on cardiac performance after heart transplantation.

BACKGROUND: Late after cardiac transplantation, limited reinnervation of the transplanted heart may occur, but little is known about the effect of reinnervation on cardiac function and exercise performance. METHODS: We quantified the extent of myocardial reinnervation noninvasively in 29 cardiac-transplant recipients, using positron-emission tomography and the catecholamine analogue [11C]hydroxyephedrine. Global and regional ventricular function at rest and during standardized exercise testing were measured with the use of radionuclide angiography, and the results were compared with those in 10 healthy controls. RESULTS: Sympathetic reinnervation, mainly in the anteroseptal wall, was present in 16 of the 29 transplant recipients. At rest, hemodynamic differences were not observed between the patients with reinnervation and those with denervation. However, the latter group had a shorter mean (+/-SD) exercise time (6.1+/-1.5, minutes vs. 8.2+/-1.2 in the group with reinnervation; P<0.01) and a lower peak heart rate (121+/-13 vs. 143+/-15 beats per minute, P<0.01). The contractile response to exercise was significantly enchanced in transplant recipients with reinnervation and similar to that of normal controls. In a multivariate analysis, hydroxyephedrine retention was the only independent determinant of the exercise-induced increase in the ejection fraction. CONCLUSIONS: In heart-transplant recipients, the restoration of sympathetic innervation is associated with improved responses of the heart rate and contractile function to exercise. These results support the functional importance of reinnervation in transplanted hearts.

Carbon Radioisotopes↗

PubMed2001

Myocardial blood flow and flow reserve after coronary reimplantation in patients after arterial switch and ross operation.

BACKGROUND: Coronary reimplantation is used in therapy for congenital heart disease, such as in the arterial switch (ASO) and Ross operations. The adequacy of myocardial perfusion may remain a matter of concern. The aim of the present study was to stratify the effect of coronary reimplantation on myocardial perfusion and to highlight the clinical relevance of any attenuation in myocardial perfusion. METHODS AND RESULTS: A total of 21 children with transposition of the great arteries at a mean interval of 11.2+/-2.9 years after ASO and 9 adolescents at a mean interval of 4.2+/-2.1 years after the Ross procedure were investigated. All patients were asymptomatic and had a normal exercise capacity. On stress echocardiography, 2 of the ASO patients had dyskinetic areas within the left ventricular myocardium, and 5 had adenosine-induced perfusion defects on positron emission tomography. No coronary obstruction was detected on coronary angiography in any patient, but a common finding was right coronary dominance and a small caliber of the distal part of the left anterior descending artery. Coronary flow reserve (CFR) was significantly reduced in all patients after ASO when compared with 10 normal healthy volunteers (age, 25.6+/-5.3 years). CFR was normal in the 9 patients who had the Ross operation (age, 19.2+/-7.6 years); exercise-induced perfusion defects were not detected in the Ross patients. CONCLUSIONS: Children after ASO are asymptomatic, without clinical signs of coronary dysfunction. In contrast to patients who had the Ross operation, stress-induced perfusion defects and an attenuated CFR were documented. The prognostic implications of these findings and the clinical consequences are unclear; nevertheless, close clinical follow-up of ASO patients is mandatory.

Adolescent↗

PubMed2001

Myocardial efficiency and sympathetic reinnervation after orthotopic heart transplantation: a noninvasive study with positron emission tomography.

BACKGROUND: The lack of cardiac catecholamine uptake and storage caused by sympathetic denervation may influence performance of the transplanted heart. Reinnervation, occurring late after transplantation, may partially resolve these effects. In this study, oxidative metabolism and its relation to cardiac work were compared in allografts and normal and failing hearts, and the effects of sympathetic reinnervation were evaluated. METHODS AND RESULTS: Twenty-seven nonrejecting, symptom-free transplant recipients, 11 healthy control subjects, and 10 patients with severe dilated cardiomyopathy underwent PET with (11)C acetate for assessment of oxidative metabolism by the clearance constant k(mono) and radionuclide angiography or MRI for measurement of ventricular function, geometry, and work. Efficiency was estimated noninvasively by a work-metabolic index [WMI=(stroke volumexheart ratexsystolic pressure)/k(mono)]. In 14 of 27 transplants, presence of regional reinnervation was identified with PET and the catecholamine analogue (11)C hydroxyephedrine (extent, 24+/-14% of left ventricle). The WMI was comparable in normal subjects and reinnervated and denervated transplants (6.2+/-2.3 versus 4.9+/-2.0 versus 4.9+/-1.2. 10(6) mm Hg. mL; P=NS) and significantly lower in cardiomyopathy patients (3.0+/-1.3. 10(6) mm Hg. mL; P<0.001). For normal subjects and transplant recipients, the WMI was significantly correlated with afterload (peripheral vascular resistance; r=-0.65, P<0.01), preload (end-diastolic volume; r=0.78, P<0.01), and stroke volume (r=0.81, P<0.01) but not with hydroxyephedrine retention (transplants only; r=0.09, P=NS). CONCLUSIONS: After transplantation, cardiac efficiency is improved compared with failing hearts and comparable to normal hearts. Differences between denervated and reinnervated allografts were not surveyed. Additionally, the dependency on loading conditions and contractility was preserved, suggesting that normal regulatory interactions for efficiency are intact and that sympathetic tone does not play a role under resting conditions.

Aged↗

PubMed2001

Global and regional functional measurements with gated FDG PET in comparison with left ventriculography.

The purpose of this study was to validate the measurement of global and regional left ventricular cardiac function with ECG-gated fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) by comparison with the corresponding indices from X-ray left ventriculography (LVG). Twenty-six patients (23 men, 3 women, mean age 60.4 years) underwent LVG and ECG-gated (eight frames/cycle) FDG-PET within an interval of 10.2+/-6.8 days. A volumetric sampling approach was used to obtain both global (EF: ejection fraction) and regional [%WT: relative regional count increase from end-diastolic (ED) to end-systolic (ES) phase] functional parameters. The gated PET parameters were compared with the corresponding findings of LVG in seven myocardial segments. EF(gated PET) and EF(LVG) did not differ significantly (30%+/-10% vs 32%+/-10%, P=NS). The two EF values correlated significantly, showing no significant systematic measurement bias [EF(gated PET) = 2.61+0.86 x EF(LVG), R=0.84, P<0.0001]. Inter- and intra-observer reproducibility for EF were R=0.95, P<0.0001 and R=0.92, P<0.0001, respectively. Regional function was evaluated with LVG in 144 myocardial segments comprising 35 normokinetic, 70 hypokinetic and 39 a/dyskinetic segments. Visual analysis of LVG and gated PET correlated significantly (P<0.001), with an overall concordance ratio of 58% (83/144, kappa=0.35). Gated PET overestimated the regional function in 27% (39/144) and underestimated it in 15% (22/144). %WT showed significant differences between each pair of groups (a/dyskinesis, 13.2%+/-9.3%; hypokinesis, 17.1%+/-8.8%; normokinesis, 21.8%+/-10.9%). Inter- and intra-observer reproducibility was significant for %WT (R=0.77, P<0.0001 and R=0.79, P<0.0001, respectively). In conclusion, gated FDG PET permits assessment of global left ventricular cardiac function. In addition, assessment of regional function is feasible using the visual or the quantitative parameters.

Aged↗

PubMed2001

How heterogeneous is the cardiac autonomic innervation?

The rich autonomic innervation of the heart plays an important role in modifying cardiovascular function. Recently developed in vivo scintigraphic imaging techniques allow for visualization of the autonomic innervation of the heart. Studies using the modalities have shown heterogeneity of sympathetic innervation in various kinds of pathological conditions as well as normal human heart. The inferioposterior region shows typically less sympathetic innervation than the anterior region. In addition, neuropathic processes appear to commence in inferior-apical regions extending towards the base of the heart. Arrhythmogeneity has been related to the heterogeneous innervation of the heart and heterogeneous uptake of radiolabeled catecholamine analogues, such as I-123 metaiodobenzylguanidine, can be found in patients with arrhythmia. In dilated cardiomyopathy, reduced uptake indicates a poor prognosis which allows risk stratification for patients with heart failure. Heterogeneity of the reinnervation process following heart transplantation has also been investigated. Evidence was found of reinnervation primarily in the basal anterioseptal region and to a lesser degree in the inferioposterior and apical regions. Tracer approaches are uniquely suited to identify regionally altered innervation and provide tools for linking information on cardiac autonomic innervation with other clinical aspects.

Arrhythmias, Cardiac↗

PubMed2001

Relationship between altered sympathetic innervation, oxidative metabolism and contractile function in the cardiomyopathic human heart; a non-invasive study using positron emission tomography.

AIMS: To identify functional and metabolic correlates of impaired presynaptic sympathetic innervation in the cardiomyopathic human heart using non-invasive correlative imaging. METHODS AND RESULTS: In 10 patients with idiopathic dilated cardiomyopathy, presynaptic catecholamine uptake sites were quantified by positron emission tomography with C-11 hydroxyephedrine. Oxidative metabolism was measured using C-11 acetate. Global and regional function was assessed by tomographic radionuclide angiography. Left ventricular ejection fraction in patients was 19%+/-10%. Myocardial hydroxyephedrine retention was abnormally low in 58%+/-38% of the left ventricles. Globally and regionally, hydroxyephedrine retention was significantly correlated with ventricular function (r=0.67, P=0.03 with left ventricular ejection fraction; r=0.31, P<0.01 with regional endocardial shortening). Multivariate analysis confirmed hydroxyephedrine retention as the closest independent determinant of left ventricular ejection fraction. Oxidative metabolism was determined by rate pressure product as a measure of workload (r=0.78, P<0.01) and peripheral vascular resistance as a measure of afterload (r=-0.61, P=0.06), but did not correlate with hydroxyephedrine retention (r=0.08 for global, r=0.04 for regional parameters). CONCLUSION: Alterations of presynaptic sympathetic innervation in dilated cardiomyopathy are associated with impaired contractile function, suggesting a common pathogenetic pathway. Overall oxidative metabolism, however, was not directly correlated with these findings. Normal regulatory mechanisms for oxidative metabolism were operational.

Cardiomyopathy, Dilated↗

PubMed2001

Reappearance of cardiac presynaptic sympathetic nerve terminals in the transplanted heart: correlation between PET using (11)C-hydroxyephedrine and invasively measured norepinephrine release.

UNLABELLED: Previously, sympathetic reinnervation of the transplanted heart has been described using invasive catheterization techniques and noninvasive radionuclide imaging techniques. However, little is known about the agreement between these 2 methods. Thus, correlation between (11)C-hydroxyephedrine (HED) PET and invasively measured norepinephrine (NE) release was investigated in transplant recipients in this study. METHODS: Using PET and the catecholamine analog HED, 17 patients were studied between 2 mo and 13.6 y after transplantation. Based on results in completely denervated hearts, areas with HED retention >7%/min were defined as reinnervated. Additionally, transcardiac NE release induced by intravenous tyramine (55 microg/kg) was measured by coronary sinus and aortic catheterization within 1 wk of the PET study. NE levels between coronary sinus and aortic root, DeltaNE(CS-AO), were calculated at baseline and after tyramine administration. Differences of more than 3 SD of baseline (>163 pg/mL) were interpreted as reinnervation. RESULTS: HED retention indicated reinnervation in 10 patients. Maximal HED retention ranged from 4.3%/min to 16.4%/min. DeltaNE(CS-AO) 1 min after tyramine administration ranged between -10 pg/mL and 1157 pg/mL, and 8 patients were above the reinnervation threshold. Fisher's exact test demonstrated good agreement between results of PET and DeltaNE(CS-AO) measurements (P = 0.002). Maximal HED retention was also significantly correlated with NE release (r = 0.69; P = 0.001). CONCLUSION: Results of invasively measured NE release and noninvasive (11)C-HED PET are well correlated. This study further supports the usefulness of PET as a noninvasive approach for detection of reappearance of catecholamine uptake sites after heart transplantation.

Adrenergic Fibers↗

PubMed2000

Uptake of radiolabeled 2'-fluoro-2'-deoxy-5-iodo-1-beta-D-arabinofuranosyluracil in cardiac cells after adenoviral transfer of the herpesvirus thymidine kinase gene: the cellular basis for cardiac gene imaging.

BACKGROUND: Gene therapy is a promising approach for the treatment of cardiac diseases. Coexpression of therapeutic genes with a suitable marker gene would allow for the noninvasive imaging of successful gene transfer and expression via radiolabeled marker substrates. In the present study, such an approach was first applied to cardiac tissue. METHODS AND RESULTS: The combination of the herpesvirus thymidine kinase reporter gene (HSV1-tk) and radiolabeled 2'-fluoro-2'-deoxy-5-iodo-1-beta-D-arabinofuranosyluracil (FIAU) was evaluated. H9c2 rat cardiomyoblasts were infected in vitro with a replication-defective HSV1-tk-containing adenovirus and a negative control virus. The intracellular uptake of [(14)C]FIAU increased with increasing multiplicity of infection and with time after infection. Uptake in negative controls remained <15% of positive controls. Additionally, vectors were applied intramyocardially in Wistar rats. The marker substrate [(125)I]FIAU was injected intravenously 3 days later, and animals were killed after 24 hours. Autoradiographically, regional transgene expression was clearly identified in animals receiving the adenovirus containing HSV1-tk (3. 4+/-2.2-fold increase of radioactivity at vector administration site compared with remote myocardium), whereas nonspecific uptake in negative controls was low (<10% of positive controls). CONCLUSIONS: Using an adenoviral vector, HSV1-tk can be successfully expressed in cardiac cells in vitro and in vivo, yielding high uptake of radiolabeled FIAU. The results suggest that imaging transgene expression in the heart is feasible and may be used to monitor gene therapy noninvasively.

Adenoviridae↗

PubMed2000

Extent of cardiac sympathetic neuronal damage is determined by the area of ischemia in patients with acute coronary syndromes.

BACKGROUND: Prior studies have demonstrated that acute ischemic injury causes sympathetic neuronal damage exceeding the area of necrosis. The aim of this study was to test the hypothesis that sympathetic neuronal damage measured by (123)I-metaiodobenzylguanidine (MIBG) imaging would be determined by the area of ischemia as reflected by area at risk in patients undergoing reperfusion therapy for acute coronary syndromes. METHODS AND RESULTS: In 12 patients, the myocardium at risk was assessed by (99m)Tc-sestamibi SPECT before reperfusion, and infarct size was measured by follow-up (99m)Tc-sestamibi SPECT 1 week later. All patients also underwent (123)I-MIBG SPECT within a mean of 11 days after onset. The SPECT image analysis was based on a semiquantitative polar map approach. Defect size on the (123)I-MIBG or (99m)Tc-sestamibi SPECT was measured for the left ventricle (LV) with the use of a threshold of -2.5 SD from the mean value of a normal database and was expressed as %LV. The (123)I-MIBG defect size (47+/-18%LV) was larger than the infarct size (27+/-23%LV, P<0. 001) but was similar to the risk area (49+/-18%LV, P=NS). Furthermore, the (123)I-MIBG defect size was closely correlated with the risk area (r=0.905, P<0.001). CONCLUSIONS: Sympathetic neuronal damage measured by (123)I-MIBG SPECT is larger than infarct size and is closely related to risk area, suggesting high sensitivity of neuronal structures to ischemia compared with myocardial cells.

Adult↗

PubMed2000

[Nuclear medicine studies of the heart].

Nuclear imaging methods provide noninvasive indexes of myocardial function, perfusion, and metabolism and are well accepted in clinical cardiology. Advances in prevention and treatment of cardiac disease have resulted in decreasing cardiovascular mortality in industrialized nations. The improvement in therapeutic options has increased the demand for diagnostic tests that might guide clinical decision making. Information beyond the pure anatomic characterization of coronary stenoses is required. Nuclear imaging can be used for early detection and monitoring of the severity and extent of disease. The prognostic potential of such functional testing is being increasingly appreciated and used to guide therapy, thereby resulting in improvement of the quality and cost-effectiveness of the workup of patients with cardiovascular disease. Extensive clinical validation has resulted in growing acceptance of these techniques. Furthermore, ongoing improvement of imaging techniques and development of new radiopharmaceuticals will pave the way for disease-specific, molecular-targeted cardiac imaging in the future.

Cardiomyopathies↗

PubMed2000

Non-invasive assessment of the effect of cardiac sympathetic innervation on metabolism of the human heart.

The role of cardiac sympathetic nerves in the regulation of myocardial metabolism is not well defined. Owing to the presence of incomplete reinnervation, heart transplant recipients provide a unique model to study the effects of efferent sympathetic innervation. Using this model, we sought to determine the influence of cardiac sympathetic signals on substrate utilisation and overall oxidative metabolism. In 21 transplant recipients, positron emission tomography was applied to determine sympathetic innervation with the noradrenaline analogue carbon11 hydroxyephedrine, oxidative metabolism with carbon11 acetate (n=14), and glucose utilisation with fluorine-18 fluorodeoxyglucose (n=7). The reinnervated area comprised 22% +/- 20% of the left ventricle. Oxidative metabolism was similar in denervated and reinnervated myocardium [0.06 +/- 0.01 vs 0.06 +/- 0.01/min for k(mono)], while glucose uptake was significantly higher in denervated myocardium (6.9 +/- 6.6 vs 6.0 +/- 6.2 micromol/min/100 g; P=0.03). Reinnervation mainly occurred in the territory of the left anterior descending artery, where retention of 11C-hydroxyephedrine (6.8 +/- 2.7%/min) was higher compared with territories of the left circumflex (4.1 +/- 1.7%/min; P<0.01) and right coronary (3.8 +/- 1.1%/min; P<0.01) arteries. Oxidative metabolism was similar in all three territories, but compared with the reinnervated territory of the left anterior descending artery (53% +/- 16% of maximum), relative FDG uptake was higher in territories of the left circumflex (76% +/- 6%, P<0.01) and right coronary (67% +/- 10%, P<0.05) arteries. Similar degrees of regional heterogeneity were not observed in normals. Thus, while overall energy production through oxidative metabolism remains unaffected, cardiac utilisation of glucose in the fasting state is increased in the absence of catecholamine uptake sites. Innervated myocardium, however, may preferentially utilise free fatty acids, suggesting a role for sympathetic tone in substrate utilisation.

Aged↗

PubMed2000

Non-invasive estimation of myocardial efficiency using positron emission tomography and carbon-11 acetate--comparison between the normal and failing human heart.

The clearance kinetics of carbon-11 acetate, assessed by positron emission tomography (PET), can be combined with measurements of ventricular function for non-invasive estimation of myocardial oxygen consumption and efficiency. In the present study, this approach was applied to gain further insights into alterations in the failing heart by comparison with results obtained in normals. We studied ten patients with idiopathic dilated cardiomyopathy (DCM) and 11 healthy normals by dynamic PET with 11C-acetate and either tomographic radionuclide ventriculography or cine magnetic resonance imaging. A "stroke work index" (SWI) was calculated by: SWI = systolic blood pressure x stroke volume/body surface area. To estimate myocardial efficiency, a "work-metabolic index" (WMI) was then obtained as follows: WMI = SWI x heart rate/k(mono), where k(mono) is the washout constant for 11C-acetate derived from monoexponential fitting. In DCM patients, left ventricular ejection fraction was 19%+/-10% and end-diastolic volume was 92+/-28 ml/m2 (vs 64%+/-7% and 55+/-8 ml/m2 in normals, P<0.001). Myocardial oxidative metabolism, reflected by k(mono), was significantly lower compared with that in normals (0.040+/-0.011/min vs 0.060+/-0.015/min; P<0.003). The SWI (1674+/-761 vs 4736+/-895 mmHg x ml/m2; P<0.001) and the WMI as an estimate of efficiency (2.98+/-1.30 vs 6.20+/-2.25 x 10(6) mmHg x ml/m2; P<0.001) were lower in DCM patients, too. Overall, the WMI correlated positively with ejection parameters (r=0.73, P<0.001 for ejection fraction; r=0.93, P<0.001 for stroke volume), and inversely with systemic vascular resistance (r=-0.77; P<0.001). There was a weak positive correlation between WMI and end-diastolic volume in normals (r=0.45; P=0.17), while in DCM patients, a non-significant negative correlation coefficient (r=-0.21; P=0.57) was obtained. In conclusion non-invasive estimates of oxygen consumption and efficiency in the failing heart were reduced compared with those in normals. Estimates of efficiency increased with increasing contractile performance, and decreased with increasing ventricular afterload. In contrast to normals, the failing heart was not able to respond with an increase in efficiency to increasing ventricular volume. The present data support the usefulness of the WMI for non-invasive characterization of cardiac efficiency and may serve as a background for improved evaluation of medical therapy for heart failure.

Acetates↗

PubMed2000

Effect of thyroid hormones on cardiac function, geometry, and oxidative metabolism assessed noninvasively by positron emission tomography and magnetic resonance imaging.

Thyroid hormones influence cardiac performance directly and indirectly via changes in peripheral circulation. Little, however, is known about the effect on myocardial oxidative metabolism and its relation to cardiac function and geometry. Patients with a history of thyroidectomy for thyroid cancer present a unique model to investigate the cardiac effects of hypothyroidism. Ten patients without heart disease were investigated in the hypothyroid state and again 4-6 weeks later under euthyroid conditions. Myocardial oxidative metabolism was measured by positron emission tomography with [11C]acetate and the clearance constant k(mono). Cine magnetic resonance imaging was applied to determine left ventricular geometry. A stroke work index (SWI = stroke volume x systolic blood pressure/ventricular mass) was calculated. Then, to estimate myocardial efficiency, a work metabolic index [WMI = SWI x heart rate/k(mono)] was obtained. Compared to hormone replacement, systemic vascular resistance and left ventricular mass were significantly higher in hypothyroidism. Ejection fraction and SWI were significantly lower. Despite an additional reduction of k(mono), the WMI was significantly lower, too. In summary, cardiac oxygen consumption is reduced in hypothyroidism. This reduction is associated with increased peripheral resistance and reduced contractility. Estimates of cardiac work are more severely suppressed than those of oxidative metabolism, suggesting decreased efficiency. These findings may provide an explanation for development or worsening of heart failure in hypothyroid patients with preexisting heart disease.

Acetates↗

PubMed2000

Coronary microvascular reactivity to sympathetic stimulation in patients with idiopathic dilated cardiomyopathy.

UNLABELLED: The objective of this study was to assess noninvasively the microvascular reactivity to sympathetic stimulation in patients with idiopathic dilated cardiomyopathy (IDC) and in healthy volunteers, who underwent cardiac catheterization for exclusion of coronary artery disease. METHODS: Myocardial flow was quantified with 13N-ammonia PET and tracer kinetic modeling at rest and in response to cold pressor testing (CPT). Ten healthy volunteers (8 men, 2 women; mean age +/- SD, 50.7 +/- 15 y) and 10 matched patients (8 men, 2 women; mean age, 52.5 +/- 14 y) with IDC (mean left ventricular ejection fraction, 0.30 +/- 0.12) were included in the study. RESULTS: Myocardial perfusion at rest was not significantly different between the groups. However, myocardial vascular resistance (MVR) was significantly lower in IDC patients at rest than in healthy volunteers. In response to CPT a significant decrease in MVR was found in healthy volunteers (1.9 +/- 0.4 to 1.5 +/- 0.4 mm Hg x 100 g/mL; 22% decrease) but not in IDC patients (1.5 +/- 0.4 to 1.4 +/- 0.3 mm Hg x 100 g/mL; 9% decrease). Consequently, the increase of the myocardial blood flow in response to CPT was significantly lower (P < 0.008) in IDC patients (56 +/- 17 to 66 +/- 18 mL/100g/min; 20% increase) compared with healthy volunteers (52 +/- 12 to 80 +/- 30 mL/100 g/min; 52% increase), whereas both showed comparable hemodynamic reactions. CONCLUSION: The data indicate that CPT in combination with 13N PET imaging is a valuable noninvasive tool for assessment of coronary microvascular reaction to sympathetic stimulation in IDC patients. Lower coronary vascular resistance was found in IDC patients at rest compared with healthy volunteers, suggesting possible exhaustion of sympathetically induced dilation of the coronary microvasculature in IDC patients at rest. This mechanism may explain the impaired flow response to cold in IDC patients in the present study.

Blood Pressure↗