Blood-pressure-waveform monitoring without interruptions due to changes in arterial compliance: The use of the vibrational and volume-clamp methods.

The arterial-blood-pressure (ABP) waveform can be monitored by the volume-clamp method. The photoplethysmography (PPG) signal is measured and clamped at maximum arterial compliance (PPGcmax) by controlling the external pressure (EP) with a cuff. PPGcmax is determined by the volume-oscillometric method though ABP measurement is regularly interrupted. To overcome this drawback, the vibrational method superimposes high-frequency vibrations on EP and measures the PPG response to estimate the "vibrational" compliance (Cv) and the PPGcmax. This method, though, has never been validated or implemented simultaneously with the volume-clamp method because the control has always been unstable. We implemented a custom-made device with a novel control system, monitoring stability and adapting the gain at high frequencies, plus lower-amplitude EP vibrations. We compared, in eleven volunteers, the EP at PPGcmax determined by the volume-oscillometric and the vibrational methods. Both exhibited a good linear correlation (r2 >0.92) and Bland-Altman agreement (95% confidence interval <15 mmHg). Moreover, in three volunteers, the vibrational and volume-clamp methods were implemented together while experimentally changing the ABP and/or Cv without manifesting control-system instability. Cv measured with the vibrational method could be used by the volume-clamp method to measure the ABP waveform without any interruptions due to changes in arterial compliance.

Aceptabilidad y conocimientos sobre la vacunación contra el virus del papiloma humano (VPH) en médicos ginecólogos de la Argentina

OBJETIVO: Evaluar entre los ginecólogos argentinos la aceptabilidad y prescripción de la vacuna contra el virus del papiloma humano (VPH), los conocimientos sobre sus características y uso, y las nociones médico-biológicas sobre infección por VPH y cáncer cervicouterino. MATERIAL Y MÉTODOS: Entre noviembre de 2009 y marzo de 2010 se encuestaron a 686 ginecólogos vía internet. RESULTADOS: Más de 80% de los encuestados prescribe la vacuna, conoce sus características y administración, y considera la necesidad de continuar con el tamizaje cervical en mujeres vacunadas. El 37% posee un conocimiento global de la relación entre vacuna y detección/tratamiento de la patología cervical. De los encuestados, 25% subestima la magnitud de la infección, ≈30% no reconoce el rol etiológico del VPH en la enfermedad, y ≈40% posee un conocimiento global del manejo de la infección. CONCLUSIONES: La aceptabilidad de la vacuna contra el VPH es alta. Debe reforzarse la capacitación de los profesionales sobre vacunación y patología cervical, así como las nociones médico-biológicas sobre infección por VPH y cáncer cervicouterino.

OBJECTIVE: To evaluate HPV vaccine acceptability and prescription; knowledge about HPV vaccine; and knowledge about HPV infection and cervical cancer among Argentinean gynecologists. MATERIALS AND METHODS: Between November 2009 and March 2010 we carried out an internet survey of 686 gynecologists. RESULTS: More than 80% of gynecologists prescribed HPV vaccine, knew characteristics of HPV vaccines, and knew that women will still need regular cervical cancer screening after HPV vaccination; 37% had global knowledge about relationship between vaccine, detection and treatment of cervical cancer; 25% underestimated the epidemiological extent of HPV infections, ≈30% was not aware of the causative relationship between HPV infection and cervical cancer and ≈40% had global knowledge about management of HPV infection. CONCLUSIONS: HPV vaccine acceptability is high. Physicians need to be fully informed on HPV vaccination and cervical cancer as well as HPV infection management.

[HPV vaccine acceptability and knowledge among gynecologists in Argentina]. / Aceptabilidad y conocimientos sobre la vacunación contra el virus del papiloma humano (VPH) en médicos ginecólogos de la Argentina.

OBJECTIVE: To evaluate HPV vaccine acceptability and prescription; knowledge about HPV vaccine; and knowledge about HPV infection and cervical cancer among Argentinean gynecologists. MATERIALS AND METHODS: Between November 2009 and March 2010 we carried out an internet survey of 686 gynecologists. RESULTS: More than 80% of gynecologists prescribed HPV vaccine, knew characteristics of HPV vaccines, and knew that women will still need regular cervical cancer screening after HPV vaccination; 37% had global knowledge about relationship between vaccine, detection and treatment of cervical cancer; 25% underestimated the epidemiological extent of HPV infections, ≈30% was not aware of the causative relationship between HPV infection and cervical cancer and ≈40% had global knowledge about management of HPV infection. CONCLUSIONS: HPV vaccine acceptability is high. Physicians need to be fully informed on HPV vaccination and cervical cancer as well as HPV infection management.

Ventricular muscarinic receptor remodeling in patients with and without primary ventricular fibrillation. An imaging study.

BACKGROUND: Vagal innervation modulates the electrical stability of the left ventricle (LV) during ischemia. Thus, abnormal parasympathetic activity in myocardial infarction (MI) patients with primary ventricular fibrillation (FV) can account for their arrhythmic disorders. We evaluated LV muscarinic receptor density (B (max)) after MI in patients with (FV(G), n = 11) or without (nFV(G), n = 12) primary FV. METHODS AND RESULTS: The B (max) was measured by positron emission tomography and the specific antagonist [(11)C]methylquinuclidinyl benzilate ([(11)C]MQNB) in 23 patients 39 ± 19 days post-MI, and 10 volunteers. Myocardial damage was quantified by delayed contrast-enhanced magnetic resonance imaging. Three short-axis slices per subject were analyzed and six time-activity curves per slice were fitted to a 3-compartment ligand-receptor model. The B (max) in remote regions of the 23 patients (67 ± 36 pmol/mL · tissue; n = 139) was higher than in normal regions of volunteers (33 ± 16 pmol/mL · tissue; n = 171; P = .01). Receptor density in remote regions was similarly upregulated in nFV(G) (69 ± 31 pmol/mL · tissue, n = 73) and FV(G) (66 ± 40 pmol/mL · tissue, n = 66; P = .72). In damaged regions, the B (max) was reduced in both patient groups (44 pmol/mL · tissue). CONCLUSIONS: Chronically infarcted patients with or without primary FV share similar patterns of ventricular muscarinic receptor remodeling, characterized by receptor upregulation, in remote non-damaged territories.

Heart rate reduction with ivabradine increases ischaemia-induced ventricular fibrillation threshold: role of myocyte structure and myocardial perfusion.

AIMS: We showed previously that ivabradine (IVA), a selective inhibitor of the cardiac pacemaker I(f) current, achieved protection against ischaemia-induced ventricular fibrillation (VF) in pigs by increasing the VF threshold (VFT). This was correlated to the heart rate reduction (HRR), the limitation of monophasic action potential shortening and the reduction of the hypoxic area. This study investigated myocyte ultrastructure and regional myocardial blood flow (RMBF), potentially involved in these cardioprotective effects of IVA. METHODS AND RESULTS: Myocardial ischaemia was induced in pigs by total 1-min occlusion of the left anterior descending coronary artery following i.v. administration of saline (n=6) or IVA (0.25 mg/kg, n=6). Electrophysiological and haemodynamic parameters, the hypoxic area and the presence of myocyte ultrastructural lesions were evaluated. The RMBF was assessed using positron emission tomography following ischaemia/reperfusion in IVA (0.25 mg/kg, i.v., n=6) or vagal stimulation (n=4) groups. Compared with saline, IVA induced a 32% HRR (p<0.01), a 2.9-fold increase in the VFT (p<0.001) and a reduction of the hypoxic area without any change in left ventricular dP/dt(max). IVA preserved cardiomyocyte morphology, particularly mitochondrial ultrastructure. Compared with baseline, RMBF during reperfusion was increased in the hypoxic area following IVA administration (+218% vs. +97%, p<0.05) or vagal stimulation (+195% vs. +127%, p<0.05). This increase was sharply reduced by atrial pacing in IVA-group. CONCLUSION: IVA exerts a cardioprotection from ischaemia-induced VF by increasing RMBF and preserving cardiomyocyte and mitochondrial ultrastructure, which opens new perspectives regarding potential targets that would be involved in the anti-ischaemic effects of IVA.

Muscarinic receptor upregulation in patients with myocardial infarction: a new paradigm.

BACKGROUND: Despite the major role attributed to myocardial vagal activity in left ventricular arrhythmogenesis in chronic myocardial infarction, the impact of infarction on left ventricular muscarinic receptor density remains unknown. METHODS AND RESULTS: Left ventricular muscarinic receptor density was measured in vivo by positron emission tomography using the specific antagonist [(11)C]methylquinuclidinyl benzilate ([(11)C]MQNB) in 11 patients 43+/-20 days after myocardial infarction and 9 healthy volunteers. The extent of myocardial damage was quantified by delayed contrast-enhanced MRI. Three short-axis slices from each subject were analyzed in matched positron emission tomography and MRI images. A 2-injection positron emission tomography protocol was used; [(11)C]MQNB time-activity curves were obtained in 6 regions per slice and fitted to a 3-compartment ligand-receptor model. Four classes of myocardial regions were considered: normal (in volunteers); remote, supplied by healthy or <70% diameter reduction arteries and without MRI signs of damage; potentially damaged, supplied by infarct-related or >70% diameter reduction arteries and without signs of damage; and damaged, with damage. The muscarinic receptor density in remote (67+/-30 pmol/mL tissue; n=86) and potentially damaged (71+/-30 pmol/mL tissue; n=42) regions of patients was higher than in normal regions of volunteers (32+/-17 pmol/mL tissue; n=156; P<0.001). The muscarinic receptor density in damaged regions (42+/-21 pmol/mL tissue; n=58) was reduced compared with remote and potentially damaged regions (P<0.001) but was not significantly different from normal regions in volunteers (P=0.093). CONCLUSIONS: Vagal control in patients with chronic myocardial infarction involves muscarinic receptor upregulation in remote nondamaged left ventricular regions. Our results suggest that the receptor density remains within normal values in myocardial regions containing damaged tissue.

Mechanisms leading to reversible mechanical dysfunction in severe CAD: alternatives to myocardial stunning.

Patients with severe chronic coronary artery disease (CAD) exhibit a highly altered myocardial pattern of perfusion, metabolism, and mechanical performance. In this context, the diagnosis of stunning remains elusive not only because of methodological and logistic considerations, but also because of the pathophysiological characteristics of the myocardium of these patients. In addition, a number of alternative pathophysiological mechanisms may act by mimicking the functional manifestations usually attributed to stunning. The present review describes three mechanisms that could theoretically lead to reversible mechanical dysfunction in these patients: myocardial wall stress, the tethering effect, and myocardial expression and release of auto- and paracrine agents. Attention is focused on the role of these mechanisms in scintigraphically "normal" regions (i.e., regions usually showing normal perfusion, glucose metabolism, and cellular integrity as assessed by nuclear imaging techniques), in which stunning is usually considered, but these mechanisms could also operate throughout the viable myocardium. We hypothesize that reversion of these three mechanisms could partially explain the unexpected functional benefit after reperfusion recently highlighted by high-spatial-resolution imaging techniques.

Importance of parametric mapping and deconvolution in analyzing magnetic resonance myocardial perfusion images.

AIM: : We sought to improve the clinical interpretation of first-pass myocardial magnetic resonance perfusion. Parametric analyses of the myocardial distribution of the contrast agent have been proposed. The objective of the present study was to compare the effectiveness of visual analysis and of a parametric approach in an animal model under acquisition conditions as close as possible to clinical reality. METHOD: : Experiments were conducted in vivo with various kinds of pharmacological stimulation in normal pigs and in pigs with stenosis of the left circumflex coronary artery. First-pass MR images and parametric maps were first assessed by medical experts. MR parameters, the myocardial signal intensity variation DeltaSI, ascending up-slope, and rMBF (blood flow calculated by fast discrete ARMA deconvolution) were then compared with blood flow measurements using radioactive microspheres. RESULTS AND CONCLUSIONS: : Interobserver agreement was 57% and 81% and accuracy 53% and 81%, for visual and for parametric map analysis, respectively. For deconvolution parameters, a linear relationship y = 371 + 1.27x, r = 0.78 was obtained between rMBF calculated by ARMA and the radioactive microsphere blood flow. Moreover, the fast and robust parametric mapping of rMBF by the discrete ARMA method allows MR evaluation of myocardial perfusion independently of hemodynamic conditions.

Tagged MRI and PET in severe CAD: discrepancy between preoperative inotropic reserve and intramyocardial functional outcome after revascularization.

In severe coronary artery disease (CAD), it has been shown that intramyocardial inotropic reserve as assessed with tagged magnetic resonance imaging (MRI) is uniformly distributed among positron emission tomography (PET) patterns reflecting normal or concomitant reductions in perfusion and glucose metabolism. This preliminary study aimed to delineate the relationship between preoperative values of intramyocardial inotropic reserve (in different PET patterns of perfusion and glucose uptake) and intramyocardial functional outcome after surgical revascularization in severe CAD. Twelve patients underwent preoperative tagged MRI (baseline, 10 microg.kg(-1).min(-1) of dobutamine), H2 15O/[18F]fluorodeoxyglucose PET imaging, and postoperative resting tagged MRI. Regional midmyocardial circumferential shortening (Ecc, in %) and PET patterns (normal, match viable, mismatch viable, and infarcted) were assessed in three tagged MRI/PET short-axis slices. Ecc at baseline ranged from 12 +/- 6 to 8 +/- 5 and 4 +/- 4% in normal, match-viable, and infarcted regions, respectively (P <0.05) and was 8 +/- 5% in mismatch-viable regions. Of the 429 regions studied, 187 showed preoperative inotropic reserve with dobutamine, but 238 showed postoperative functional improvement. Postoperative functional improvement was less common in infarcted regions (41 vs. approximately 60% in the other PET patterns), but the extent of improvement was similar among PET patterns (approximately 6%). Postoperative functional improvement occurred in 53% of all (normal, match viable, and mismatch viable) regions without inotropic reserve. In severe CAD, revascularization affords greater intramyocardial functional benefit than expected from the evaluation of intramyocardial inotropic reserve with low-dose dobutamine. Postoperative functional improvement in PET-viable regions without inotropic reserve suggests that factors other than regionally enhanced perfusion contribute to such functional improvement.

Dobutamine-tagged MRI for inotropic reserve assessment in severe CAD: relationship with PET findings.

The impact of blood flow reductions on the intramyocardial inotropic reserve has not yet been established in coronary artery disease (CAD). We therefore evaluated in severe CAD the relationship between positron emission tomography (PET) patterns of perfusion and glucose uptake and the corresponding tagged magnetic resonance imaging (tagged MRI) values of midmyocardial strains under low-dose dobutamine. Eighteen patients underwent tagged MRI (at rest, with dobutamine) and H2(15)O/18F-fluorodeoxyglucose PET. Regional midmyocardial circumferential shortening (Ecc) and PET patterns (normal, match viable, mismatch viable, and infarcted) were assessed in three tagged MRI/PET short-axis slices. Regional Ecc at rest correlated with both perfusion (r = 0.49) and glucose uptake (r = 0.58). The presence of the inotropic reserve was similar in normal, match viable, and infarcted (approximately 40% of regions vs. 52% in mismatch viable, P < 0.05), but the extent of the increase after dobutamine was lower in infarcted regions (P = 0.06). Within each PET pattern, regions were grouped according to their Ecc values at rest into three categories (high, intermediate, and low contractile performance). In mismatch viable (hibernation), the inotropic reserve was similar among the three categories, but in the other PET patterns the presence and extent of the inotropic reserve was higher in those regions with lowest Ecc (without significant differences in perfusion). In severe CAD, the presence of the inotropic reserve assessed by midmyocardial changes under dobutamine does not relate to resting perfusion. At a similar level of perfusion, the presence of the inotropic reserve is inversely related to contractile performance at rest, but our results suggest that it may not be true for hibernating myocardium.

Myocardial perfusion and glucose uptake coupling in CAD patients.

PURPOSE: To evaluate coronary artery disease (CAD) patients regarding to their perfusion-glucose uptake relationship at rest for all myocardial regions and to determine whether this evaluation could typify patients with different positron emission tomography (PET)-pattern proportions and pathophysiological characteristics. METHODS: Rest/dipyridamole H(15)2O and 18FDG PET studies were performed in 23 patients with left ventricular dysfunction. Regional index (relative perfusion, %H(15)2O; relative glucose uptake, %18FDG) allowed to detect PERFUSION-metabolism mismatch (i.e. hibernation) and dipyridamole-induced reversible stress defects (RSD). RESULTS: The correlation (r) between %H(15)2O and % 18FDG at rest allowed definition of three groups: correlated (CORR; r > 0.7; n = 10), semicorrelated (SEMI; 0.5 < r < or = 0.7; n = 6) and uncorrelated (UNCO; r < or = 0.5; n = 7). In UNCO, 96% of regions had a %H(15)2O > or = 55% (p < 0.01 vs. 89 and 82% in SEMI and CORR) and 95% of regions had a %18FDG > or = 55% (p < 0.01 vs. 78 and 71% in SEMI and CORR). Mismatch proportions increased from CORR to SEMI and UNCO (11, 19 and 27%; p < 0.02) and proportion of regions with RSD was higher in UNCO and SEMI (25 and 24 vs. 6% in CORR; p < 0.01). Proportion of mismatch with RSD was at least three fold higher in UNCO (17/58) (p < 0.01 vs. 3/33 and 1/16 in SEMI and CORR). CONCLUSIONS: Analysis of perfusion and glucose uptake at rest allowed to typify three categories of CAD patients with different PET-patterns proportions, distinctive ranges of perfusion and glucose uptake and distinctive hyperemic response. Our results suggest that myocardial hibernation associated with defective hyperemic response is specific of patients with preserved perfusion and glucose uptake.

Cardiac retention of [11C]HED in genotyped long QT patients: a potential amplifier role for severity of the disease.

Although mutations in cardiac sodium and potassium channel genes are associated with congenital long QT syndrome (LQTS), a "modifier" role of the sympathetic nervous system was proposed to explain the distinct severity of the disease. We evaluated cardiac sympathetic innervation using [11C]hydroxyephedrine ([11C]HED) and positron emission tomography (PET) in genotyped LQTS patients. H215O and [11C]HED PET studies were performed in 11 patients (5 symptomatic) and 8 controls. Perfusion and [11C]HED images were depicted as 36-sector polar maps. Sectorial values of perfusion (H2O%), absolute (HEDRet) and relative retention (HED%Ret) of [11C]HED, and the ratio of HED%Ret to H2O% (HED%Ret/H2O%) were calculated. Normal databases were obtained from controls. Sectorial values below 2SD database values were defined as "outside sectors." Controls and patients showed similar sectorial perfusion. Sectorial HEDRet did not differ between groups, but means of HED%Ret were lower in three sectors for patients (P < 0.05). Three sectors from 3 controls had HED%Ret below 2SD, whereas 36 sectors in 9 patients were outside sectors (P < 0.01). In patients, average HED%Ret/H2O% was lower in 9 sectors (P < 0.05 vs. controls); 2 outside sectors were found in controls, but 43 outside sectors were found in patients (P < 0.01), 77% of them in the 5 symptomatic patients. Heterogeneous [11C]HED retention was localized in the septal, anterior, and lateral walls. Most LQTS patients showed a localized and decreased pattern of [11C]HED retention. The larger number of heterogeneous sectors in symptomatic patients suggests that sympathetic function could play an amplifier role for severity of the disease.

Factor analysis of medical image sequences improves evaluation of first-pass MR imaging acquisitions for myocardial perfusion.

RATIONALE AND OBJECTIVES: Factor analysis of medical image sequences (FAMIS) applied to gadolinium chelate-enhanced subsecond magnetic resonance (MR) imaging was evaluated as a postprocessing method for assessing myocardial perfusion in coronary artery disease (CAD). MATERIALS AND METHODS: To assess the accuracy of motion correction, five normal volunteers underwent MR imaging at rest. Thirteen patients with well-documented CAD and no myocardial infarction underwent MR imaging at rest and after dipyridamole administration. After motion correction, a single myocardial tissue factor (FAMISt) image was obtained with FAMIS for each raw MR imaging series acquisition. To evaluate how FAMIS could improve the analysis of these acquisitions, five readers visually assessed myocardial perfusion with FAMISt and raw MR images, and a multicase, multireader receiver operating characteristic analysis was performed. RESULTS: FAMISt images significantly improved detection of the perfusion defects when compared with raw MR images (P = .002). Areas under the receiver operating characteristic curves ranged from 0.84 to 0.93 with FAMISt images and from 0.48 to 0.85 with raw MR images. CONCLUSION: FAMIS applied to first-pass MR imaging series provided myocardial perfusion images that improve the objective assessment of myocardial perfusion in patients with CAD.