Endothelial function in patients with chest pain and normal coronary arteries.
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Chest Pain↗
Biomedical subjects
P G Camici
Publications and source records attributed to P G Camici.
The value of quantitative myocardial perfusion imaging with positron emission tomography in coronary artery disease.
Positron Emission Tomography (PET) is the only available technique that permits quantification of regional myocardial perfusion in humans. To this end, tracer kinetic models and appropriate tracers such as 13N-Ammonia and 15O labeled water are required. Quantification is possible because accurate radioactivity quantities can be measured externally, both for the vascular and myocardial compartments. Normal value for baseline and maximal perfusion after pharmacologically induced vasodilatation of the resistance microcirculatory vessels are age-dependent. The functional hemodynamic significance of epicardial stenoses can be estimated from the progressive reduction in coronary perfusion reserve, which decreases progressively when stenosis severity reaches 40% in diameter. The effect of revascularization procedures such as CABG and PTCA can be objectively measured. In addition, there is increasing evidence from PET studies that resistive vessel dysfunction (probably through endothelial factors) contributes to the reduced perfusion reserve in patients with epicardial coronary artery disease. Therefore quantification of myocardial perfusion with PET appears an ideally suited endpoint for primary and secondary prevention trials.
Coronary Artery Bypass↗
Biodistribution and metabolism of [N-methyl-11C]m-hydroxyephedrine in the rat.
Biodistribution and metabolism of [N-methyl-11C]m-hydroxyephedrine ([11C]mHED), an analogue of noradrenaline, were assessed in rats. Pretreatment with desipramine, an uptake blocker, reduced uptake of radioactivity in myocardium but not in lung, liver, kidney, and muscle. Brain uptake was negligible. HPLC showed six radioactive metabolites in plasma and liver but none in myocardium. Co-injection of unlabelled mHED or metaraminol with [11C]mHED demonstrated no difference between the in vivo binding potentials for mHED and metaraminol in myocardium.
Animals↗
Calculation of single detector efficiencies and extension of the normalization sinogram in PET.
A fast iterative method is presented for calculating single detector efficiencies for positron emission tomographs. These efficiencies can be used to extend the normalization scan to areas outside that covered by the normalization source. The root mean square (rms) error of the calculated single detector efficiencies decreases exponentially with the number of iterations. Thirty iterations per normalization image are sufficient and take about 1 s on a SUN Classic. The geometry factors are composed of factors which only depend on the distance from the centre of the field-of-view (FOV) and of factors which show a more complex pattern over the normalization sinogram. The geometry factors are specific to each scanner. On the ECAT 931 scanner the complex part of the geometry factors showed a diamond shaped pattern (caused by the varying sensitivity of single detectors in a detector block with varying angle of incidence) and S-shaped curves (representing attenuation caused by supporting rods for the ring source). The coefficient of variation of the diamond-shaped pattern was 4% for detectors farthest from the centre of the FOV. Extensions of the normalization scan may, therefore, contain a relative rms error of about 4% if the applied geometry factors only take the distance from the centre of the FOV into account.
Biophysical Phenomena↗
Microcirculation: what is the role of calcium antagonists?
This review article discusses some of the potentially beneficial effects of calcium antagonists on the coronary microcirculation. These include their vasodilating action on coronary resistance vessels as well as their effects on extravascular resistance (i.e. intramyocardial pressure). Examples are presented of how the non-invasive measurement of myocardial blood flow and flow reserve by means of positron emission tomography can contribute to the understanding of the effects of drug treatment on the coronary microcirculation. The action of calcium antagonists on the coronary microcirculation may help explain the efficacy of these drugs against ischaemia and ischaemia-reperfusion damage.
Animals↗
Coronary vasodilator reserve in primary and secondary left ventricular hypertrophy. A study with positron emission tomography.
OBJECTIVES: Coronary vasodilator reserve is reduced in hypertrophic cardiomyopathy and secondary left ventricular hypertrophy despite angiographically normal coronaries. The aim of the present study was to assess whether quantitative differences exist between these conditions. METHODS: Using positron emission tomography with H2(15)O, myocardial blood flow was measured at baseline and following intravenous dipyridamole (0.56 mg.kg-1) in 12 hypertrophic cardiomyopathy patients (age 34 (11) years, mean (SD), all male), 16 secondary left ventricular hypertrophy patients (age 58 (20) years, P < 0.01 vs hypertrophic cardiomyopathy; 10 female) and 40 normal controls (age 54 (20), 13 female). In view of the known decline of post-dipyridamole myocardial blood flow with age, myocardial blood flow was compared between the patient groups and appropriately matched subsets of the total control group. RESULTS: Baseline myocardial blood flow in the hypertrophic cardiomyopathy patients was 0.82 (0.23) ml.min-1.g-1 vs 0.94 (0.14) ml.min-1.g-1 in its matched control group, P = ns. For the secondary left ventricular hypertrophy patient group, baseline myocardial blood flow was 1.17 (0.40) ml.min-1.g-1 vs 1.06 (0.28) ml.min-1.g-1 for the secondary left ventricular hypertrophy matched control group, P = ns. Following dipyridamole, myocardial blood flow was 1.64 (0.44) ml.min-1.g.-1 in hypertrophic cardiomyopathy patients vs 3.50 (0.95) ml.min-1.g-1 for the hypertrophic cardiomyopathy matched control group, P = 0.0001. For the left ventricular hypertrophy patients, post-dipyridamole myocardial blood flow was 2.27 (0.60) ml.min-1.g-1 vs 2.94 (1.29) ml.min-1.g-1 for the left ventricular hypertrophy controls, P = 0.06. Coronary vasodilator reserve (dipyridamole-myocardial blood flow/baseline-myocardial blood flow) was 2.05 (0.61) for hypertrophic cardiomyopathy patients vs 3.81 (0.98) for the hypertrophic cardiomyopathy controls (P = 0.0001, patients vs controls) and 2.06 (0.62) for left ventricular hypertrophy patients vs 2.90 (1.38) for the left ventricular hypertrophy controls, P < 0.03 patients vs controls. After correction of baseline myocardial blood flow for baseline heart rate x systolic pressure product, coronary vasodilator reserve for the hypertrophic cardiomyopathy patients was 2.06 (1.06) vs 4.34 (1.54) for the hypertrophic cardiomyopathy controls. P = 0.0002 and in the secondary left ventricular hypertrophy patients, the values were 2.13 (0.64) vs 2.89 (1.42) in the secondary left ventricular hypertrophy controls, P < 0.05. CONCLUSION: In both hypertrophic cardiomyopathy and secondary left ventricular hypertrophy, the computed coronary vasodilator reserve is impaired, even after correction for baseline cardiac work. However, the extent of the reduction is greater in the hypertrophic cardiomyopathy patients. In the blunting of vasodilator reserve of secondary left ventricular hypertrophy, the patients' greater hyperaemic response is partly offset by the higher baseline myocardial blood flow.
Adult↗
Cardiac and skeletal muscle insulin resistance in patients with coronary heart disease. A study with positron emission tomography.
Patients with coronary artery disease or heart failure have been shown to be insulin resistant. Whether in these patients heart muscle participates in the insulin resistance, and whether reduced blood flow is a mechanism for such resistance is not known. We measured heart and skeletal muscle blood flow and glucose uptake during euglycemic hyperinsulinemia (insulin clamp) in 15 male patients with angiographically proven coronary artery disease and chronic regional wall motion abnormalities. Six age- and weight-matched healthy subjects served as controls. Regional glucose uptake was measured by positron emission tomography using [18F]2-fluoro-2-deoxy-D-glucose (FDG), blood flow was measured by the H2(15)O method. Myocardial glucose utilization was measured in regions with normal perfusion and wall motion as assessed by radionuclide ventriculography. Whole-body glucose uptake was 37+/-4 micromol x min(-1) x kg(-1) in controls and 14+/-2 mciromol x min(-1) x kg(-1) in patients (P = 0.001). Myocardial blood flow (1.09+/-0.06 vs. 0.97+/-0.04 ml x min(-1) x g(-1), controls vs. patients) and skeletal muscle (arm) blood flow (0.046+/-0.012 vs. 0.043+/-0.006 ml x min(-1) x g(-1)) were similar in the two groups (P = NS for both). In contrast, in patients both myocardial (0.38+/-0.03 vs. 0.70+/-0.03 micromol x min(-1) x g(-1), P = 0.0005) and muscle glucose uptake (0.026+/-0.004 vs. 0.056+/-0.006 micromol x min(-1) x g(-1), P = 0.005) were markedly reduced in comparison with controls. In the whole dataset, a direct relationship existed between insulin-stimulated glucose uptake in heart and skeletal muscle. Patients with a history of myocardial infarction and a low ejection fraction are insulin resistant. This insulin resistance affects both the myocardium and skeletal muscle and is independent of blood flow.
Adult↗
Myocardial beta-adrenoceptor density and plasma catecholamines in syndrome X.
Recent research has cast doubt on the ischemic hypothesis of etiology of syndrome X (anginal pain, ischemic-like changes in the stress electrocardiogram, but normal coronary arteriogram). Abnormalities of pain perception have been shown and abnormal sympathetic nervous system activation has also been implicated. The aim of this study was to test the hypothesis that downregulation of myocardial beta adrenoceptors is demonstrable in patients with syndrome X. Such downregulation would be consistent with raised myocardial catecholamine concentrations. We performed positron emission tomography with (11)C-CGP-12177 to measure beta-adrenoceptor density. Plasma catecholamines were sampled simultaneously and assayed using high-performance liquid chromatography. Twenty syndrome X patients (11 female, age 57 +/- 9 SD years, range 33 to 69) and 18 matched controls (9 women, age 50 +/- 13 years, range 25 to 65; p = NS vs patients) were studied. Myocardial beta-adrenoceptor density did not differ between syndrome X patients and controls: 8.0 (1.9) pmol/g for patients versus 8.3 (2.1) pmol/g for controls; p = 0.62. No differences were found between patients and controls for plasma norepinephrine (2.82 [1.07] and 2.76 [1.18] nM, respectively; p = 0.89) or for epinephrine (0.29 [0.14] and 0.30 [0.20] nM, respectively; p = 0.84). In patients with syndrome X, beta-adrenoceptor density is normal and, by inference, myocardial catecholamines would also be normal. This weakens the case for a generalized enhancement of sympathetic activation in this disorder, although increased sympathetic reactivity during actual episodes of chest pain remains a possibility.
Adrenergic beta-Antagonists↗
Silent ischemia as a central problem: regional brain activation compared in silent and painful myocardial ischemia.
OBJECTIVE: To test whether the silence of painless myocardial ischemia is caused by abnormal handling by the central nervous system of afferent messages from the heart. DESIGN: Nonrandomized study. SETTING: A tertiary referral center (postgraduate medical school). PATIENTS: 2 matched groups of nondiabetic patients with coronary artery disease. Group A consisted of nine patients with reproducible stress-induced angina; group B consisted of nine patients with reproducible stress-induced myocardial ischemia but no angina. INTERVENTIONS: Intravenous placebo infusion and low-dose (5 and 10 micrograms/ kg per minute) and high-dose (20 to 35 micrograms/kg per minute) dobutamine infusions. MEASUREMENTS: Positron emission tomography was used to measure regional cerebral blood flow changes as an index of neuronal activation during painful and silent myocardial ischemia induced by intravenous dobutamine. RESULTS: Regional cerebral blood flow changes during myocardial ischemia were compared with those during baseline conditions and during placebo infusion. During myocardial ischemia, regional cerebral blood flow increased bilaterally in the thalami and prefrontal, basal frontal, and ventral cingulate corticles in patients in group A. Both thalami were activated in group B, but cortical activation was limited to the right frontal region. A formal comparison of groups A and B showed significant differences (P < 0.01) in activation of the basal frontal cortex, ventral cingulate cortex, and left temporal pole. In both groups, thalamic regional cerebral blood flow remained increased after the symptoms and signs of ischemia had ceased. CONCLUSIONS: Bilateral activation of the thalamus can be shown in both angina and silent ischemia; thus, peripheral nerve dysfunction cannot completely explain silent ischemia. Frontal cortical activation appears to be necessary for the sensation of pain. Abnormal central processing of afferent pain messages from the heart may play a determining role in silent myocardial ischemia.
Afferent Pathways↗
Pathophysiology of chronic left ventricular dysfunction. New insights from the measurement of absolute myocardial blood flow and glucose utilization.
BACKGROUND: Chronically dysfunctional myocardium may improve after coronary revascularization. This condition was thought to be due to a chronically reduced myocardial blood flow (MBF). Recently, however, it has been shown that in patients without previous infarction but with chronic left ventricular dysfunction, baseline MBF was normal. METHODS AND RESULTS: To study the pathophysiology of chronic left ventricular dysfunction in patients with previous infarction, regional MBF (milliliter per minute per gram of water-perfusable tissue) and glucose utilization (MRG; micromoles per minute per gram) during hyperinsulinemic euglycemic clamp were measured with positron emission tomography in 30 patients before bypass. At baseline, 133 myocardial segments were normal, and 107 were dysfunctional. After revascularization, 59 of 107 segments improved, while 48 of 107 were unchanged. MBF was 0.92 +/- 0.25 mL.min-1.g-1 in normal segments, 0.87 +/- 0.31 mL.min-1.g-1 in improved segments (P = NS versus normal), and 0.82 +/- 0.40 mL.min-1.g-1 in unchanged segments (P < .05 versus normal). In 90% of the dysfunctional segments, MBF was > 0.42 mL.min-1.g-1, a cutoff value corresponding to the mean MBF minus 2 SD in normal segments. The MRG was 0.71 +/- 0.14 mumol.min-1.g-1 in 9 age-matched normal subjects, 0.45 +/- 0.19 mumol.min-1.g-1 (P < .01) in normal segments, 0.44 +/- 0.14 mumol.min-1.g-1 in improved segments (P = NS versus normal), and 0.34 +/- 0.17 mumol.min-1.g-1 in unchanged segments (P < .01 versus normal and improved). CONCLUSIONS: The results suggest that resting MBF measured with 15O-labeled water in chronically dysfunctional segments is not reduced and that the myocardium of these patients is less sensitive to insulin than that of normal subjects.
Adult↗
Non-invasive measurement of left ventricular volumes and function by gated positron emission tomography.
To date cardiac positron emission tomography (PET) studies have focussed on the measurement of myocardial blood flow, metabolism and receptors while left ventricular (LV) function and dimensions have been derived from other modalities. The main drawback of this approach is the difficulty of data co-registration, which limits clinical interpretation. The aim of this study was to evaluate whether it is possible to measure absolute cardiac volumes, and consequently LV function parameters such as ejection fraction, and wall motion with gated PET. Nineteen patients underwent a PET scan and planar radionuclide ventriculography (MUGA) within 9+/-9 days. A 9-min scan (16 gates/cardiac cycle) was acquired after inhalation of 3 MBq/ml of oxygen-15 labelled carbon monoxide at the rate of 500 ml/min over 4 min using a multislice PET camera. Noise reduction was performed on the gated image to enhance the definition of the ventricles before reslicing to the short-axis view. A threshold value was used to detect the edge of the LV at each gate. LV volumes at each gate were estimated by summing the volume of voxels within the LV boundary. PET measurements of LV volumes were as follows: LV end-diastolic volume ranged from 72 to 233 ml and LV end-systolic volume ranged from 24 to 203 ml. Phantom experiments supported the validity of this approach for estimating volumes. LV ejection fraction measured with MUGA was 38.4%+/-16.3% (range 15%-71%) and that measured with PET was 39.6%+/-17.7% (range 9%-72%) (P=NS). The LV ejection fraction measurements were highly correlated (r2=0.824). These results indicate that: (1) absolute end-diastolic and end-systolic volumes can be quantified using gated PET and (2) LV ejection fraction can be accurately measured by gated PET simultaneously with the other physiological PET parameters.
Coronary Disease↗
Insulin sensitivity in cardiological syndrome X.
OBJECTIVES: To test whether cardiological syndrome X is an insulin-resistant state. SETTING, DESIGN AND SUBJECTS: The coronary care unit of a referral centre for angina pectoris in Pisa, Italy. A case-control study, involving 10 patients with unequivocal (angiographycally proven) cardiological syndrome X, but normal glucose tolerance, blood pressure and lipid levels, and 13 matched healthy subjects. MAIN OUTCOME MEASURES: Insulin sensitivity and pattern of substrate oxidation (assessed by the euglycaemic insulin clamp technique in combination with indirect calorimetry). RESULTS: Fasting plasma glucose and insulin levels were 5.05 +/- 0.11 versus 4.88 +/- 0.11 mmol l-1 and 68 +/- 10 versus 56 +/- 6 pmol l-1, respectively (controls versus patients, ns). During the insulin clamp, glucose disposal rate was nearly identical in patients and controls (25.9 +/- 1.8 and 27.2 +/- 1.8 mumol kg-1 min-1, respectively. P = 0.88). Non-oxidative glucose disposal accounted for similar proportions of total glucose uptake (59 versus 53%, patients versus controls, ns). Resting energy expenditure (13.7 +/- 0.6 versus 13.8 +/- 0.8 cal kg-1 min-1, ns) and insulin-induced thermogenesis were similar in the two groups. Fasting plasma NEFA concentrations (0.64 +/- 0.09 and 0.64 +/- 0.06 mmol l-1, patients and controls, ns) fell in a similar time-course and to virtually identical nadirs (0.13 +/- 0.02 and 0.14 +/- 0.02 mmol l-1) after insulin infusion. Fasting plasma potassium was similar in patients and controls (3.99 +/- 0.10 and 4.16 +/- 0.04 mmol l-1, ns), and insulin induced equivalent hypokalaemia (-14 versus -19%). CONCLUSIONS: None of the in vivo actions of insulin were impaired in patients with 'pure' syndrome X when compared to matched controls. Therefore, we conclude that cardiological syndrome X is not an insulin resistant state per se, and that any decrease in insulin sensitivity found in this condition is likely to be secondary.
Blood Glucose↗
The impact of myocardial blood flow quantitation with PET on the understanding of cardiac diseases.
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Adult↗
Myocardial beta adrenoceptor density in primary and secondary left ventricular hypertrophy.
OBJECTIVES: Myocardial beta-adrenoceptor density has been found to be reduced in hypertrophic cardiomyopathy, even when systolic function is preserved. Our purpose in the current study was to investigate whether beta-adrenoceptor down-regulation was unique to hypertrophic cardiomyopathy, or is also present in secondary myocardial hypertrophy. METHODS: Myocardial beta-adrenoceptor density was measured in 11 patients with hypertrophic cardiomyopathy, eight patients with left ventricular hypertrophy secondary to arterial hypertension or aortic valve disease and 18 normal control subjects, using positron emission tomography with 11C-CGP-12177 as the myocardial beta-adrenoceptor ligand. RESULTS: Reflecting the natural incidence of the conditions, the age of the hypertrophic cardiomyopathy patients was 37 (10) [mean (SD), range 20-51] years and that of the secondary hypertrophy patients 64 (18), [range 26-80] years; P < 0.01. The controls' ages were 50 (13), [range 21-65] years; however, since beta-adrenoceptor density is known to be influenced by age, the controls' data was split into groups matched to the hypertrophic cardiomyopathy and secondary hypertrophy patient sets. For the hypertrophic cardiomyopathy patients, mean left ventricular beta-adrenoceptor was 7.70 (1.86) pmol.g-1 compared to 10.17 (2.44) pmol.g-1 for a matched set of 15 controls; P < 0.01. In secondary left ventricular hypertrophy, beta-adrenoceptor was 6.35 (1.70) pmol.g-1 compared to 9.16 (2.00) pmol.g-1 for a matched set of 10 controls; P < 0.01. Plasma noradrenaline was 5.5 (2.2) nmol.l-1 in hypertrophic cardiomyopathy and 2.5 (1.0) nmol.l-1 for the matched controls; P < 0.01. The results for adrenaline were 2.2 (1.1) vs 0.4 (0.3) nmol.l-1 respectively; P < 0.001. For the secondary hypertrophy patients, the corresponding figures were 2.5 (1.2) vs 2.5 (1.0) nmol.l-1 for noradrenaline for patients and controls respectively (P = ns); and for adrenaline 0.2 (0.1) and 0.3 (0.2) nmol.l-1 respectively, P = ns. On multiple regression analysis, no relationships could be demonstrated amongst plasma catecholamines, beta-adrenoceptor, myocardial blood flow and echocardiographic E/A ratio and fractional shortening. CONCLUSION: Myocardial beta-adrenoceptor density appears to be comparably decreased in both primary and secondary left ventricular hypertrophy in the presence of preserved left ventricular systolic function.
Adult↗
Does positron emission tomography contribute to the management of clinical cardiac problems?
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Cardiomyopathy, Hypertrophic↗
Myocardial beta adrenoceptors and left ventricular function in hypertrophic cardiomyopathy.
OBJECTIVE: To assess the relation between left ventricular function and myocardial beta adrenoceptor density. METHODS: 17 patients with hypertrophic cardiomyopathy, six with and 11 without heart failure, were studied. Left ventricular function was assessed by echocardiography, and myocardial beta adrenoceptors by positron emission tomography. Patient data were compared with those obtained in normal controls. RESULTS: Myocardial beta adrenoceptor density in the 17 patients was 7.00 (SD 1.90) pmol/g v 11.50 (2.18) pmol/g in normal controls (P < 0.01). beta Adrenoceptor density in the six patients with left ventricular failure was 5.61 (0.88) pmol/g v 7.71 (1.86) pmol/g in the 11 patients with normal ventricular function (P < 0.05), and there was a significant correlation (r = 0.52; P < 0.05) between left ventricular fractional shortening and myocardial beta adrenoceptor density. A positive correlation (r = 0.51; P < 0.05) was also found between myocardial beta adrenoceptor density and the E/A transmitral flow ratio, an index of left ventricular diastolic function. CONCLUSIONS: There is myocardial beta adrenoceptor downregulation in patients with hypertrophic cardiomyopathy with or without signs of heart failure.
Adult↗
Effect of alpha 1-adrenoceptor blockade on resting and hyperemic myocardial blood flow in normal humans.
In the present study we aimed to assess the effect of alpha 1-adrenoceptor blockade on resting and hyperemic myocardial blood flow in normal humans. Myocardial blood flow, at baseline and after dipyridamole, was measured with positron emission tomography and 15O-labeled water in 11 normal volunteers at control and during alpha 1-blockade with doxazosin. Baseline myocardial blood flow during alpha 1-blockade was not different from control, whereas coronary resistance was significantly lower (73.48 +/- 18.31 vs. 89.84 +/- 27.96 mmHg.min.ml-1.g-1; P < 0.05). After dipyridamole, myocardial blood flow during alpha 1-blockade was significantly higher (3.50 +/- 0.75 vs. 2.58 +/- 0.54 ml.min-1.g-1; P < 0.01) and coronary resistance lower (25.30 +/- 7.37 vs. 33.89 +/- 7.04 mmHg.min.ml-1.g-1; P < 0.01) compared with control. In conclusion, in normal humans, dipyridamole-induced increase in myocardial blood flow is limited by alpha 1-mediated coronary vasoconstriction.
Adrenergic alpha-Antagonists↗
Uptake of [N-methyl-11C]propionyl-L-carnitine (PLC) in human myocardium.
We studied the uptake of propionyl-L-carnitine from plasma by the myocardium in 10 human subjects using positron emission tomography. Propionyl-L-carnitine was labeled in the N-methyl position with carbon-11 (T1/2 = 20.4 min) and administered i.v. in trace amounts. The uptake of the radiolabel by the myocardium was then scanned over a period of 1 1/2 h. The activity-time course of the tracer in blood and plasma and the exchange of the label in plasma between propionyl carnitine, acetyl carnitine and free carnitine was followed during the scans. Myocardial blood flow was also measured in the same subjects. The results show an exchange of the tracer between the myocardium and plasma, and they show an apparently irreversible component of uptake, a result consistent with the incorporation of the label into relatively large intracellular carnitine pools.
Adult↗