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Biomedical subjects

Paolo G Camici

Publications and source records attributed to Paolo G Camici.

52 records · Page 3Linked to original sources
PubMed2002

Myocardial beta-adrenoceptor density one month after acute myocardial infarction predicts left ventricular volumes at six months.

OBJECTIVE: To investigate whether myocardial beta-adrenoceptor (beta-AR) downregulation precedes and predicts left ventricular (LV) dilation after acute myocardial infarction (AMI), we measured beta-AR density within four weeks of AMI and correlated it with serial measurements of LV volumes. BACKGROUND: Patients who develop heart failure following AMI have an increased sympathetic drive to the heart within the first four weeks after infarction. METHODS: We prospectively studied 61 patients in whom AMI was the first presentation of coronary artery disease (CAD) and with no signs of heart failure. The LV volumes were measured one, three, and six months after AMI by echocardiography. Beta-AR density was measured using positron emission tomography with S-[(11)C]CGP 12177. Seventeen matched healthy volunteers served as controls. RESULTS: Whole heart beta-AR density was lower in patients than in controls (6.25 +/- 0.98 pmol/g vs. 8.32 +/- 2.14 pmol/g, p < 0.0001). In patients, beta-AR density was inversely correlated with end-systolic and end-diastolic volumes six months after AMI. Patients whose LV was dilated at six months had a lower beta-AR density in noninfarcted myocardium than patients without dilation (6.15 pmol/g vs. 6.98 pmol/g, p = 0.008). In addition, beta-AR density in noninfarcted myocardium was higher when the infarct-related artery was patent (6.87 +/- 1.14 pmol/g vs. 5.76 +/- 0.86 pmol/g occluded, p < 0.01). CONCLUSIONS: Myocardial beta-AR density is reduced after AMI in the absence of heart failure, and the reduction predicts later LV dilation. These data are suggestive of an enhanced sympathetic drive to the heart, having an important etiologic role in LV remodeling after AMI.

Aged↗
PubMed2002

Accuracy of PET in predicting functional recovery after revascularisation in patients with chronic ischaemic dysfunction: head-to-head comparison between blood flow, glucose utilisation and water-perfusable tissue fraction.

Accurate prediction of improvement in left ventricular ejection fraction (LVEF) after revascularisation is critical in the therapeutic decision-making process in patients with chronic ischaemic dysfunction. Positron emission tomography (PET) allows non-invasive evaluation of myocardial blood flow (MBF), metabolic rate of glucose (MRG, absolute and relative) and the water-perfusable tissue fraction (PTF). Each of these indices has been proposed for the prediction of functional recovery. Their relative merits, however, are unknown, because a direct head-to-head comparison of their predictive accuracy in the same patients has not been performed. In this study, MBF, MRG (absolute and relative) and PTF were evaluated in 34 patients with severe ischaemic LV dysfunction (LVEF 32%+/-9%). MBF and PTF were determined by oxygen-15 labelled water PET, and MRG (absolute and relative) was determined by fluorine-18 fluorodeoxyglucose (FDG) PET during hyperinsulinaemic euglycaemic clamp. LVEF was measured by radionuclide ventriculography before and 4-6 months after surgery. Sensitivities of MBF, PTF, absolute MRG and relative MRG in predicting improvement in LVEF were 80%, 80%, 90% and 100%, respectively. Their specificities were 54%, 67%, 71% and 71%, respectively. The lowest specificity was obtained for MBF, an intermediate specificity was obtained for PTF and the highest specificities were obtained with FDG PET using absolute and relative MRG. It is concluded that metabolic imaging is superior to perfusion-based indexes for assessment of the potential for functional recovery after revascularisation.

Adult↗
PubMed2002

Absolute blood flow and oxygen consumption in stunned myocardium in patients with coronary artery disease.

OBJECTIVES: In patients with coronary artery disease (CAD), we sought to demonstrate normal myocardial blood flow (MBF) and myocardial oxygen consumption (MMRO(2)) to post-ischemic myocardium that exhibited reversible dysfunction and the relation between the severity of the dysfunction and the preceding ischemia. BACKGROUND: In animal models of stunning, MBF and MMRO(2) are normal or near normal, and the severity of stunning is related to the degree of the preceding ischemia. METHODS: Myocardial blood flow and MMRO(2) were measured using positron emission tomography and oxygen 15-labelled water (H(2)(15)O) and oxygen 15-labelled oxygen ((15)O(2)), respectively, in 14 patients with CAD and normal left ventricular (LV) function. Global ejection fraction and regional LV systolic function (SF) were measured using quantitative echocardiography during and after dobutamine-induced ischemia. RESULTS: Ejection fraction and SF were reduced 30 min after dobutamine (both: p < 0.01) but recovered by 120 min. Myocardial blood flow (ml/min per g) to regions with reversible LV dysfunction was normal at baseline and during dysfunction (0.88 [0.82 to 0.99] and 1.09 [0.75 to 1.37], respectively, p = NS) as was MMRO(2) (ml/min per 100 g) (16.64 [10.16 to 16.18] and 11.68 [8.43 to 15.30] respectively, p = NS). Left ventricular dysfunction was related to stenosis severity and peak MBF. Regions were divided into those subtended by a stenosis of <50%, 50% to 80% and >80% luminal diameter. Systolic function 30 min after dobutamine was 93.9% (83.4% to 104.4%) (p = NS), 85.4% (80.0% to 90.9%) and 67.4% (56.2% to 78.7%) (both: p < 0.001), respectively. Peak MBF was 2.0 (1.71 to 2.31), 1.75 (1.65 to 1.85) (p = 0.01 compared with <50%) and 1.47 (1.33 to 1.60) (p = 0.03 compared with 50% to 80% and p = 0.002 compared with <50%), respectively. CONCLUSIONS: In patients with CAD, dobutamine produces prolonged, but reversible, LV dysfunction when MBF is normal, confirming stunning. This stunning is related to the severity of the coronary stenosis and the reduction in peak MBF. Myocardial oxygen consumption to stunned myocardium is normal.

Adrenergic beta-Agonists↗
PubMed2002

Mechanisms of coronary microcirculatory dysfunction in patients with aortic stenosis and angiographically normal coronary arteries.

BACKGROUND: Development of left ventricular hypertrophy in aortic stenosis (AS) is accompanied by coronary microcirculatory dysfunction, demonstrated by an impaired coronary vasodilator reserve (CVR). However, evidence for regional abnormalities in myocardial blood flow (MBF) and the potential mechanisms is limited. The aims of this study were to quantitatively demonstrate differences in subendocardial and subepicardial microcirculation and to investigate the relative contribution of myocyte hypertrophy, hemodynamic load, severity of AS, and coronary perfusion to impairment in microcirculatory function. METHODS AND RESULTS: Twenty patients with isolated moderate to severe AS were studied using echocardiography to assess severity of AS, cardiovascular magnetic resonance to measure left ventricular mass (LVM), and PET to quantify resting and hyperemic (dipyridamole 0.56 mg/kg) MBF and CVR in both the subendocardium and subepicardium. In the patients with most severe AS (n=15), the subendocardial to subepicardial MBF ratio decreased from 1.14+/-7 at rest to 0.92+/-7 during hyperemia (P<0.005), and subendocardial CVR (1.43+/-3) was lower than subepicardial CVR (1.78+/-35; P=0.01). Resting total LV blood flow was linearly related to LVM, whereas CVR was not. Increase of total LV blood flow during hyperemia (mean value, 89.6+/-6%; range, 17% to 233%) was linearly related to aortic valve area. The decrease in CVR was related to severity of AS, increase in hemodynamic load, and reduction in diastolic perfusion time, particularly in the subendocardium. CONCLUSIONS: CVR was more severely impaired in the subendocardium in patients with LVH attributable to severe AS. Severity of impairment was related to aortic valve area, hemodynamic load imposed, and diastolic perfusion rather than to LVM.

Adult↗
PubMed2002

Assessment of infarct size by positron emission tomography and [18F]2-fluoro-2-deoxy-D-glucose: a new absolute threshold technique.

Along with hibernating myocardium, infarct size is a critical term in the progression of left ventricular remodelling and congestive heart failure. Both infarcted and hibernating myocardium determine changes in remote non-ischaemic tissue. This study was designed to test the accuracy of a new technique to quantify infarct size using positron emission tomography (PET) with [18F]2-fluoro-2-deoxy-D-glucose (FDG). Studies were carried out in (a) nine pigs with acute myocardial infarction (two sham-operated), produced by a 90-min occlusion of the circumflex coronary artery followed by a 4-h reperfusion, and (b) humans (six patients with ischaemic cardiomyopathy awaiting cardiac transplantation and five normal volunteers). In both animals and patients, myocardial FDG uptake was measured by PET during hyperinsulinaemic-euglycaemic clamp. Infarct size was quantified by an absolute threshold of tracer uptake obtained from the parametric (voxel-by-voxel) image of the metabolic rate of FDG. PET infarct size estimates were compared with independent ex vivo planimetric measurements of the explanted swine and patient hearts (at transplantation) after staining with triphenyltetrazolium chloride. There was good agreement between the planimetric and PET infarct size estimates both in pigs (n=9; r=0.96, v=0.94x+0.64, SEE=0.10, P<0.0001) and in humans (n=11; r=0.94, y=0.72x+2.93, SEE=0.09, P<0.0001). This study demonstrates the feasibility and accuracy of this PET method in estimating infarct size both in a model of reperfused acute myocardial infarction and in chronic ischaemic cardiomyopathy, although larger studies are needed to confirm these findings.

Animals↗
PubMed2002

Immunocytochemical evidence for inducible nitric oxide synthase and cyclooxygenase-2 expression with nitrotyrosine formation in human hibernating myocardium.

BACKGROUND: Myocardial hibernation may result from repetitive episodes of transient ischaemia leading to prolonged dysfunction. Inducible nitric oxide synthase (iNOS) expression has been demonstrated in animals following brief, non-lethal ischaemia-reperfusion injury. We therefore, hypothesised that in human hibernating myocardium: 1). iNOS would be present; 2). the reaction of nitric oxide and superoxide would form the strong oxidant peroxynitrite; 3) that this process would be accompanied by the expression of cyclooxygenase-2 (Cox-2) which interacts with NOS and whose products could further affect myocardial function. METHOD AND RESULTS: In sixteen patients with coronary artery disease (CAD), left ventricular biopsies were obtained from chronically dysfunctional segments subtended by a stenotic artery (> 75 %) and shown to be viable by (18)F-fluorodeoxyglucose positron emission tomography. Comparison was made with myocardial biopsies (n = 8) from normally contracting myocardium in patients undergoing coronary surgery, from unused transplant donors and at post-mortem. Regional wall motion score improved in all patients 6 months post-revascularisation (from 2.7 +/- 0.7 to 1.5 +/- 0.5; p < 0.001), confirming hibernation. Immunocytochemistry localized reactivity to iNOS, Cox-2 and nitrotyrosine (a marker of peroxynitrite formation) to cardiomyocytes from hibernating segments. No difference in reactivity to endothelial NOS was seen between hibernating and control cardiomyocytes. CONCLUSION: Cox-2 and iNOS are co-expressed in hibernating myocardium with nitrotyrosine suggesting nitric oxide production and peroxynitrite formation. We propose that this is secondary to ischaemia-reperfusion and that the products of these enzymes may have consequences for myocardial contractile function and survival.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

Low frequency spectral component of heart rate variability and myocardial beta-adrenoceptor density after acute myocardial infarction.

OBJECTIVE: The low frequency spectral component (LF; 0.04-0.15 Hz) of heart rate variability (HRV) is considered to be an index of sympathetic modulation of sinus node activity under physiological conditions, although the relationship is less clearly defined in non-physiological conditions. Several cardiovascular diseases are characterized by an absent or blunted 24-h pattern of the LF spectral component. The aim of the present study was to investigate the relationship between chronically increased neural sympathetic efferent drive to the heart, quantified in terms of downregulation of myocardial beta-receptors, and the 24-h power of the LF spectral component in patients after acute myocardial infarction. METHODS: In 24 patients, HRV was analyzed for a 24-h period, one month after an uncomplicated Q wave myocardial infarction. The following time domain measures and spectral components were calculated: mean RR, SDNN, SDANN, RMSSD, SDNN index, pNN50, and very low frequency (VLF), low frequency (LF) and high frequency (HF) spectral components. The density of beta-adrenoceptors was measured in vivo by positron emission tomography (PET) with 11-CGP-12177. RESULTS: Post-AMI patients had normal plasma levels of adrenaline and noradrenaline (respectively 1.48 +/- 0.18 and 0.28 +/- 0.03 IU/L) but reduced myocardial beta-adrenoceptor density (6.86 +/- 0.24 pmol/g). Patients had similar heart rates but lower values of SDNN and SDANN compared with control subjects. The absolute and normalized power of the spectral components were similar in the two groups, but the usual day-night oscillation was blunted in patients. Moreover, the day-night change in the power of the LF spectral component was positively related (r = 0.51; p < 0.001) to the myocardial beta-adrenoceptor density. CONCLUSIONS: The loss of the day-night oscillation of the LF spectral component appears to be a significant marker of sustained sympathetic over-activity in post-AMI patients.

Acute Disease↗
PubMed2002

Regional myocardial blood flow and glucose utilization during fasting and physiological hyperinsulinemia in humans.

We investigated the effect of insulin on total and regional myocardial blood flow (MBF) and glucose uptake (MGU) in healthy subjects (50 +/- 5 yr) by means of positron emission tomography (PET) with oxygen-15-labeled water (H(2)(15)O) and fluorine-18 labeled fluorodeoxyglucose ((18)FDG) before and during physiological hyperinsulinemia (40 mU.min(-1).m(-2)). Twelve male subjects were included in the study. During hyperinsulinemia, MBF increased from 0.91 +/- 0.28 to 1.01 +/- 0.31 ml.min(-1).g(-1) (n = 7 patients, P = 0.05; n = 112 regions, P < 0.005). Intersubject variability ranged from -3.0 to +41%. MGU increased from 0.11 +/- 0.08 (n = 5) to 0.56 +/- 0.08 micromol.min(-1).g(-1) (P < 0.0001, n = 7). MBF and insulin-mediated MGU were higher in the septum and anterior and lateral wall along short-axis regions of the heart. During hyperinsulinemia, MBF was also higher in the apex and midventricle compared with the base. MBF and MGU were positively correlated before (r = 0.66, P < 0.0001) and during hyperinsulinemia (r = 0.24, P < 0.05). These results provide evidence that insulin stimulates MBF in normal human hearts and appears to involve mainly those regions of the heart where insulin-mediated MGU is higher. Furthermore, regional distribution of insulin-stimulated MBF and MGU does not appear to be uniform across the left ventricular wall of healthy subjects.

Coronary Circulation↗
PubMed2002

Effect of repeated episodes of reversible myocardial ischemia on myocardial blood flow and function in humans.

Nine patients with coronary artery disease and normal left ventricular (LV) function underwent two episodes of dobutamine-induced ischemia to determine whether repeated episodes of ischemia lead to cumulative stunning. Positron emission tomography (PET) and oxygen 15-labeled H(2)O was used to assess myocardial blood flow (MBF) at baseline, peak stress, and after stress for each ischemic episode. Quantitative echocardiographic assessment of global ejection fraction (EF) and regional systolic function (SF) was performed at rest and regular intervals after dobutamine. SF was assessed for regions subtended by a coronary artery with a >70% diameter stenosis. Both EF and SF were more severely impaired 45 min after the second episode of stress compared with 45 min after the first (both P < 0.01), despite no difference in duration of the two dobutamine infusions or MBF at peak stress (1.72 vs. 1.69). After both episodes of ischemia, when LV function was impaired but subsequently recovered, MBF (1.15 +/- 0.39 and 1.20 +/- 0.43, respectively) was no different to baseline MBF (1.02 +/- 0.35), confirming that repeated episodes of dobutamine-induced ischemia lead to cumulative myocardial stunning.

Aged↗
PubMed2002

Independent association of type 2 diabetes and coronary artery disease with myocardial insulin resistance.

Clustering of classical cardiovascular risk factors is insufficient to account for the excess coronary artery disease (CAD) of patients with diabetes, and chronic hyperglycemia and insulin resistance (IR) are obvious culprits. Whole-body and skeletal muscle IR is characteristic of patients with type 2 diabetes, but whether it extends to the normally contracting cardiac muscle is controversial. We investigated whether type 2 diabetes is associated with myocardial IR independent of CAD in a case-control series (n = 55) of male nondiabetic and diabetic (type 2 and type 1) patients with or without angiographically documented CAD. Baseline blood flow ((15)O-water) and insulin-stimulated glucose uptake ((18)F-fluoro-deoxyglucose) during euglycemic (5.6 mmol/l), physiological hyperinsulinemia (40 mU x min(-1) x m(-2) insulin clamp) were measured by positron emission tomography in skeletal muscle and normally contracting myocardium. Skeletal muscle glucose uptake was reduced in association with both CAD and type 2 diabetes. In regions with normal baseline perfusion, insulin-mediated myocardial glucose uptake was reduced in non-CAD type 2 diabetic (0.36 +/- 0.14 micro mol x min(-1). g(-1)) and nondiabetic CAD patients (0.44 +/- 0.15 micro mol x min(- 1) x g(-1)) in comparison with healthy control subjects (0.61 +/- 0.08) or with non-CAD type 1 diabetic patients (0.80 +/- 0.13; P < 0.001 for both CAD and diabetes). Neither basal skeletal muscle nor basal myocardial blood flow differed across groups; both skeletal muscle and myocardial IR were directly related to whole-body IR. We conclude that type 2 diabetes is specifically associated with myocardial IR that is independent of and nonadditive with angiographic CAD and proportional to skeletal muscle and whole-body IR.

Adult↗
PubMed2002

Measurement of ventricular volumes and function: a comparison of gated PET and cardiovascular magnetic resonance.

UNLABELLED: The aim of this study was to compare cardiac volume and function assessment using PET with the reference technique of cardiovascular magnetic resonance (CMR). METHODS: Left ventricular (LV) and right ventricular (RV) end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and ejection fractions (EF) were measured in 9 patients using both CMR and PET with inhaled C(15)O. RESULTS: Correlation between the techniques was generally reasonable (r values ranged from 0.63 to 0.99). Best agreement was seen for ESV (LV and RV). With PET, there was a tendency to underestimate LV EF and EDV, and RV EDV and SV. Agreement was worst for LV SV. Percentage difference between CMR and PET measurements ranged from -2% to 15%; Bland-Altman limits of agreement ranged from 24% to 75%. CONCLUSION: Although small systematic differences exist, the agreement between PET and CMR suggests useful information regarding function, and volumes may be obtained from a standard PET protocol.

Algorithms↗
PubMed2002

Absolute quantification of myocardial blood flow with H(2)(15)O and 3-dimensional PET: an experimental validation.

UNLABELLED: The purpose of this study was to assess a 3-dimensional (3D)-only PET scanner (ECAT EXACT3D) for its use in the absolute quantification of myocardial blood flow (MBF) using H(2)(15)O. METHODS: Nine large white pigs were scanned with H(2)(15)O and C(15)O before and after partially occluding the circumflex (n = 4) or the left anterior descending (n = 5) coronary artery at rest and during hyperemia induced by intravenous dipyridamole. Radioactive microspheres labeled with either (57)Co or (46)Sc were injected during each of the H(2)(15)O scans, which allowed comparison between microsphere and PET measurements of regional MBF. PET analyses of 3D acquisition data were performed using filtered backprojection reconstruction and region-of-interest definition by factor and cluster analysis techniques and single-compartment model quantification. RESULTS: The Hanning filter applied in image reconstruction resulted in a left atrial blood volume recovery factor of 0.84 +/- 0.06. Differences between repeated measurements of recovery were small (mean, -0.8%; range, -6.6% to 3.6%). In 256 paired measurements of MBF ranging from 0.05 to 4.4 mL. g(- 1). min(-1), microsphere and PET measurements were fairly well correlated. The mean difference between the 2 methods was - 0.11 mL. g(-1). min(-1) and the limits of agreement (+2 SD) were -0.82 and 0.60 mL. g(-1). min(-1) (Bland-Altman plot). CONCLUSION: Dynamic measurements with H(2)(15)O using a 3D-only PET tomograph provide reliable and accurate measurements of absolute regional MBF over a wide flow range. The 3D acquisition technique can reduce the radiation dose to the subject while maintaining adequate counting statistics.

Animals↗
PubMedDate not supplied

Comparison of myocardial blood flow and coronary flow reserve during dobutamine and adenosine stress: Implications for pharmacologic stress testing in coronary artery disease.

BACKGROUND: Mechanistic differences between pharmacologic stressors may offer different clinical benefits. Therefore the effects of dobutamine and adenosine on absolute myocardial blood flow (MBF) and coronary flow reserve (CFR) were compared. METHODS AND RESULTS: We divided 36 patients (mean age, 61 +/- 8 years) with coronary artery disease into 2 groups based on stenosis severity as follows: greater than 50% but less than 75% (n = 16) and greater than 75% (n = 20). In addition, 18 normal volunteers (mean age, 46 +/- 7 years) served as control subjects. Groups of equal sizes received either dobutamine or adenosine. MBF at rest and peak MBF were measured by use of positron emission tomography in territories subtended by the stenosis (ischemic) and remote myocardium (remote), whereas left ventricular MBF was used in control subjects. CFR was calculated as peak MBF divided by MBF at rest. CFR was significantly greater with adenosine than with dobutamine stress in control subjects and remote CFR. Ischemic CFR was blunted to a similar degree with each stressor. Therefore adenosine achieved flow heterogeneity across all coronary stenosis severities greater than 50%. However, dobutamine achieved flow heterogeneity only in the presence of a severe coronary stenosis greater than 75% despite provoking a greater ischemic stimulus. CONCLUSION: Adenosine stress demonstrated a higher sensitivity and dobutamine demonstrated a higher specificity with quantitative perfusion imaging. Therefore adenosine is superior for diagnostic perfusion imaging, whereas dobutamine is better suited in combination with visual imaging and in the functional assessment of a known coronary stenosis.

Adenosine↗