Biomedical subjects

Emanuele Barbato

Publications and source records attributed to Emanuele Barbato.

15 recordsLinked to original sources

PubMed2006

Assessment of renal flow and flow reserve in humans.

OBJECTIVES: The purpose of this work was to establish the normal range of maximal renal hyperemic response in humans and to identify the ideal renal vasodilatory stimuli. BACKGROUND: Stenotic renovascular atherosclerosis is increasingly treated by percutaneous transluminal renal intervention but with an unpredictable outcome. This may be due to hemodynamically non-significant stenosis or the presence of irreversible damage to the glomerular circulation. We propose that the renovascular hyperemic response may help identify appropriate patients. METHODS: In 28 normotensive patients, quantitative angiographic measurements of the renal artery were obtained, and renal artery pressure and flow velocity were continuously recorded after various hyperemic agents. RESULTS: In a first group of 11 patients, a significant increase in renal artery average peak velocity (APV) was observed after intrarenal (IR) bolus injection of 600 microg isosorbide dinitrate (41 +/- 19%), 30 mg papaverine (50 +/- 34%), 50 microg dopamine (94 +/- 54%), 0.8 microg x kg(-1) fenoldopam (80 +/- 25%), and during IR infusion of 1 microg x kg(-1) x min(-1) fenoldopam (86 +/- 28%). A second group of 17 patients received intravenous infusion of dopamine (3, 5, 10, 20, 30, and 40 microg x kg(-1) x min(-1)). The 3 and 5 microg x kg(-1) x min(-1) of dopamine modestly reduced renal resistance index (RI) (-13 +/- 15% and -25 +/- 20%, respectively). At higher dosages, no further decline in RI was observed. No significant change in vessel diameter was observed before and after the administration of the pharmacological stimuli suggesting that changes in APV corresponded with changes in absolute renal blood flow. CONCLUSIONS: The normal renal flow reserve averages approximately 2 in humans with normal renal function. An IR bolus injection of 50 microg x kg(-1) of dopamine is the most convenient means to elicit maximal renal hyperemia.

Adult↗

PubMed2005

Effect of phentolamine on the hyperemic response to adenosine in patients with microvascular disease.

For accurate measurement of the fractional flow reserve (FFR) of the myocardium, the presence of maximum hyperemia is of paramount importance. It has been suggested that the hyperemic effect of the conventionally used hyperemic stimulus, adenosine, could be submaximal in patients who have microvascular dysfunction and that adding alpha-blocking agents could augment the hyperemic response in these patients. We studied the effect of the nonselective alpha-blocking agent phentolamine, which was administered in addition to adenosine after achieving hyperemia, in patients who had microvascular disease and those who did not. Thirty patients who were referred for percutaneous coronary intervention were selected. Of these 30 patients, 15 had strong indications for microvascular disease and 15 did not. FFR was measured using intracoronary adenosine, intravenous adenosine, and intracoronary papaverine before and after intracoronary administration of the nonselective alpha blocker phentolamine. In patients who did not have microvascular disease, no differences in hyperemic response to adenosine were noted, whether or not alpha blockade was given before adenosine administration; FFR levels before and after phentolamine were 0.76 and 0.75, respectively, using intracoronary adenosine (p = 0.10) and 0.75 and 0.74, respectively, using intravenous adenosine (p = 0.20). In contrast, in patients who had microvascular disease, some increase in hyperemic response was observed after administration of phentolamine; FFR levels decreased from 0.74 to 0.70 using intracoronary adenosine (p = 0.003) and from 0.75 to 0.72 using intravenous adenosine (p = 0.04). Although statistically significant, the observed further decrease in microvascular resistance after addition of phentolamine was small and did not affect clinical decision making in any patient. In conclusion, when measuring FFR, routinely adding an alpha-blocking agent to adenosine does not affect clinical decision making.

Adenosine↗

PubMed2005

Elevated myocardial and lymphocyte GRK2 expression and activity in human heart failure.

AIMS: The G protein-coupled receptor kinase-2 (GRK2 or beta-ARK1) regulates beta-adrenergic receptors (beta-ARs) in the heart, and its cardiac expression is elevated in human heart failure (HF). We sought to determine whether myocardial levels and activity of GRK2 could be monitored using white blood cells, which have been used to study cardiac beta-ARs. Moreover, we were interested in determining whether GRK2 levels in myocardium and lymphocytes may be associated with beta-AR dysfunction and HF severity. METHODS AND RESULTS: In myocardial biopsies from explanted failing human hearts, GRK activity was inversely correlated with beta-AR-mediated cAMP production (R(2)=-0.215, P<0.05, n=24). Multiple regression analysis confirmed that GRK activity participates with beta-AR density to regulate catecholamine-sensitive cAMP responses. Importantly, there was a direct correlation between myocardial and lymphocytes GRK2 activity (R(2)=0.5686, P<0.05, n=10). Lymphocyte GRK activity was assessed in HF patients with various ejection fractions (EFs) (n=33), and kinase activity was significantly higher in patients with lower EFs and was higher with increasing NYHA class (P<0.001). CONCLUSION: Myocardial GRK2 expression and activity are mirrored by lymphocyte levels of this kinase, and its elevation in HF is associated with the loss of beta-AR responsiveness and appears to increase with disease severity. Therefore, lymphocytes may provide a surrogate for monitoring cardiac GRK2 in human HF.

Aged↗

PubMed2005

Pressure-derived measurement of coronary flow reserve.

OBJECTIVES: We aimed to validate the technique of measuring the coronary flow reserve (CFR) with coronary pressure measurements against an established thermodilution technique. BACKGROUND: The CFR has traditionally required measurement of coronary blood flow velocity with the Doppler wire and, more recently, using a thermodilution technique with the coronary pressure wire. However, recent work has suggested that the CFR may be derived from pressure measurements alone (the ratio of the square root of the pressure drop across an epicardial stenosis during hyperemia to that value at rest). This depends on the assumption that friction losses across a coronary stenosis are negligible. METHODS: We compared pressure-derived CFR values with those obtained by the thermodilution technique using the intracoronary pressure wire in 38 stenoses in 34 patients with significant coronary stenoses undergoing percutaneous intervention. We also compared these two techniques of measuring CFR in 25 stenoses (6 vessels) artificially created by inflating small balloons within a stented coronary artery after percutaneous intervention. RESULTS: There is a close linear relationship between pressure-derived and thermodilution CFR in native (r(2) = 0.52; p < 0.001) and artificial stenoses (r(2) = 0.54; p < 0.05), although the pressure-derived technique appears to systematically underestimate CFR values in both situations. This applies to native and artificial stenoses. CONCLUSIONS: Coronary flow reserve cannot be measured merely with pressure alone, and it cannot be safely assumed that friction losses are negligible across a native coronary stenosis. These data suggest that friction loss is an important determinant of the pressure gradient along an atherosclerotic coronary artery.

Aged↗

PubMed2005

Role of beta2 adrenergic receptors in human atherosclerotic coronary arteries.

BACKGROUND: Adrenergic regulation of coronary vasomotion is balanced between alpha1-adrenergic-mediated (alpha1-AR) constriction and beta2-adrenergic-mediated (beta2-AR) relaxation. This study aimed at assessing the role of beta2-ARs in normal, mildly atherosclerotic, and stenotic human coronary arteries. METHODS AND RESULTS: During intracoronary (IC) infusion of increasing doses of the beta2-AR agonist salbutamol (0.15, 0.3, and 0.6 mug/min) and the endothelial vasodilator acetylcholine (1, 3, and 10 microg/min), we measured (1) changes in lumen diameter (LD) by quantitative coronary angiography in 34 normal, 55 mildly atherosclerotic, and 42 stenotic coronary artery segments and (2) changes in average peak velocity (APV) and coronary blood flow (CBF) with the use of Doppler flow wire in 11 normal, 10 mildly atherosclerotic, and 11 stenotic coronary arteries. In 6 of 11 stenotic coronary arteries, the protocol was repeated after an IC bolus (12 microg/kg) of the alpha-adrenergic blocker phentolamine. In 6 of 11 normal coronary arteries, the protocol was repeated after an IC infusion (60 micromol/min) of N(G)-monomethyl-L-arginine (L-NMMA), a nitric oxide inhibitor. Neither salbutamol IC infusion nor acetylcholine significantly changed heart rate or blood pressure, whereas L-NMMA slightly increased blood pressure. In normal coronary arteries, salbutamol increased LD (LD max %: 11+/-2, P<0.05), APV (APV max %: 53+/-17, P<0.05), and CBF (CBF max %: 57+/-17, P<0.05), whereas L-NMMA caused a blunted APV (APV max %: 27+/-6, P<0.05) and CBF (CBF max %: 29+/-6, P<0.05) response to salbutamol. In mildly atherosclerotic coronary arteries, the salbutamol increase in LD (LD max %: 10+/-2, P<0.05), APV (APV max %: 33+/-12, P<0.05), and CBF (CBF max %: 37+/-12, P<0.05) was preserved. In stenotic coronary arteries, salbutamol induced a paradoxical reduction in LD (LD max %: -6+/-2, P<0.05), APV (APV max %: -15+/-9, P<0.05), and CBF (CBF max %: -15+/-6, P<0.05), which was no longer observed after phentolamine. Acetylcholine increased LD (LD max %: 14+/-3, P<0.05), APV (APV max %: 61+/-20, P<0.05), and CBF (CBF max %: 67+/-19, P<0.05) in normal coronary arteries. In mildly atherosclerotic coronary arteries, acetylcholine induced a significant reduction in LD (LD max %: -15+/-2, P<0.05) and no changes in APV (APV max %: -6+/-13, P=NS) and CBF (CBF max %: -10+/-13, P=NS). In stenotic coronary arteries, acetylcholine significantly reduced LD (LD max %: -15+/-3, P<0.05), APV (APV max %: -15+/-9, P<0.05), and CBF (CBF max %: -15+/-6, P<0.05). CONCLUSIONS: In severely atherosclerotic coronary arteries, beta2-adrenergic vasodilatation is impaired, and this might contribute to alter the vasomotor balance, further precipitating myocardial ischemia during sympathetic activation.

Acetylcholine↗

PubMed2005

[Current concepts of the physiopathology of coronary beta-adrenergic receptors, and their clinical applications].

Beta-adrenergic vasodilation plays a key role in the regulation of coronary blood flow, in particular during sympathetic nervous system activation. Beta1-adrenergic receptors are mostly represented in epicardial coronary vessel, while beta2 receptors are located in microvasculature. Coronary atherosclerosis is associated with a significant impairment of beta-adrenergic receptor response. This might contribute to precipitate myocardial ischemia.

Adrenergic beta-Agonists↗

PubMed2005

Functional assessment of coronary atherosclerosis in the catheterization laboratory: the key role of fractional flow reserve.

Patients with suspected coronary artery disease often undergo coronary angiography without prior non-invasive functional stress testing, mainly because of logistic reasons, shortcomings of the non-invasive tests, and a more widespread confidence in invasive techniques. The availability in the catheterization laboratory of the pressure-derived fractional flow reserve (FFR) has provided the interventional cardiologist with the ideal tool for appropriate decision-making based on the functional significance of the coronary stenosis detected at the angiogram. In fact, FFR allows a more refined and individualized understanding of the true severity of coronary artery disease, and, therefore, a more appropriate selection of the epicardial lesions to be treated, especially in patients with dubious lesions and complex disease. A clinical decision-making based on coronary pressure measurement results in a more effective strategy than placing stents on a "trial and error" basis. This is particularly true in case of drug-eluting stents where an approach based on an indiscriminate multi-stenting will annihilate the benefits of these new stents and be unacceptably expensive. In addition, many angiographically mild stenoses happen to be hemodynamically significant and, therefore, deserve revascularization, especially in the drug-eluting stent era.

Catheterization↗

PubMed2005

Stenting and abciximab in primary angioplasty: a review of current status.

Improvement of stent deployment techniques and advances in antiplatelet therapy have shown that stenting in the setting of ST-elevation myocardial infarction (STEMI) is safe and effective. Randomized trials have found that as compared to balloon angioplasty, coronary stenting does not reduce mortality and reinfarction, despite the reduction in target vessel revascularization. Furthermore, these benefits seem to be reduced when applied to unselected patients with STEMI. Direct stenting represents an attractive strategy with potential benefits in terms of myocardial perfusion. Future randomized trials are needed to evaluate if this strategy is associated with a significant impact on outcome, and to provide cost-benefit analysis of an unrestricted use of drug-eluting stent in this high-risk subset of patients. Data from randomized trials have shown that the additional use of abciximab reduces mortality in primary angioplasty. Since the feasibility of long-distance transportation has been shown in several randomized trials, early pharmacological pretreatment may confer further advantages by early recanalization and shorter ischemic time, particularly in high-risk patients. Further large randomized trials are needed to clarify the potential role of small molecules in primary angioplasty for STEMI.

Abciximab↗

PubMed2004

Tissue doppler imaging predicts recovery of left ventricular function after recanalization of an occluded coronary artery.

OBJECTIVES: We tested the hypothesis that the tissue Doppler imaging (TDI)-derived positive preejection velocity (+VIC) can predict the recovery of contractile function after revascularization in patients with a recent myocardial infarction. BACKGROUND: In experimental studies, the presence and extent of TDI-derived +VIC correlated with the extent of viable myocardium. METHODS: Forty-three patients with a large myocardial infarction and an occluded left anterior descending (n = 38) or dominant right coronary (n = 5) artery were selected. The median duration of occlusion was 24 h. Longitudinal myocardial velocities were recorded at rest by pulsed-wave TDI echocardiography 6 +/- 2 h after revascularization. Functional recovery was defined as an increase in segmental chordal shortening > or =10% at three-month follow-up left ventricular angiogram as compared with baseline. RESULTS: A good quality TDI signal was obtained in 309 of 324 analyzed segments (95.4%). Severe dysfunction was present in 198 segments of which 126 (64%) showed recovery at three-month follow-up. Sampling of all dysfunctional segments lasted 11 +/- 4 min per patient. Sensitivity, specificity, and accuracy of the +VIC to predict segmental recovery were 91%, 71%, and 84%, respectively. The percentage of segments that were dysfunctional at angiography but showed a +VIC correlated with improvement of both global left ventricular ejection fraction (r = 0.60, p = 0.001) and wall motion score index (r = -0.78, p < 0.0001) at follow-up. CONCLUSIONS: Assessment of +VIC by pulsed-wave TDI is a simple and accurate method that predicts recovery of contractile function after revascularization in patients with a recent myocardial infarction.

Angioplasty, Balloon, Coronary↗

PubMed2004

Validation of coronary flow reserve measurements by thermodilution in clinical practice.

BACKGROUND: Coronary flow reserve (CFR) and fractional flow reserve (FFR) provide complementary information on the coronary circulation. Using a pressure wire, it is possible to calculate CFR by thermodilution (CFR(thermo)), so that FFR and CFR can be measured with a single guide wire. The present multicentric study was performed to compare the feasibility of CFR(thermo)obtained with an improved algorithm and a standardized injection technique and its agreement with Doppler-derived CFR (CFR(Doppler)). METHODS AND RESULTS: In 86 patients with coronary artery disease recruited during 1 week in eight centres FFR, CFR(thermo)and CFR(Doppler)were measured. FFR could be obtained in all patients (100%). An optimal CFR(Doppler)could be obtained in 69% of the patients. CFR(thermo)could be obtained in 97% of the patients. A significant correlation was found between CFR(Doppler)and CFR(thermo)(r=0.79, P<0.0001) but CFR(thermo)tended to be higher than CFR(Doppler). CONCLUSIONS: In a setting close to 'real world' practice, this multicentric study confirms the feasibility and reliability of thermodilution-derived CFR. In addition, the safety and the swiftness of assessing FFR and CFR with one single guide wire makes the latter a unique clinical tool for the evaluation of the coronary circulation.

Coronary Circulation↗

PubMed2004

Alpha-adrenergic receptor blockade and hyperaemic response in patients with intermediate coronary stenoses.

BACKGROUND: Maximal hyperaemia is paramount in the diagnosis of patients with coronary artery disease. However in these patients, enhanced alpha-adrenergic microvascular vasoconstriction may preclude adenosine to induce maximal hyperaemia. AIM: To assess the presence and the clinical relevance of residual microvascular resistance after administration of adenosine. METHODS AND RESULTS: Fractional flow reserve (FFR, calculated by coronary pressure measurements during adenosine-induced hyperaemia) was assessed in 85 patients with an intermediate coronary stenosis (mean diameter stenosis of 50+/-1%) and normal left ventricular function which were divided into the following three groups: (a) 33 patients before and after IC bolus of phentolamine, an alpha1-, alpha2-adrenergic blocker; (b) 32 patients before and after IC bolus of urapidil, a selective alpha1-adrenergic blocker; (c) 20 patients before and after IC bolus of saline. Since minimal luminal diameter remained unchanged before and after phentolamine (1.46+/-0.06 vs. 1.47+/-0.06 mm, ns), urapidil (1.46+/-0.06 vs. 1.39+/-0.08, ns), and saline (1.56+/-0.08 vs. 1.55+/-0.08, ns), changes in FFR reflects changes in microvascular resistance. Overall, phentolamine and urapidil induced a slight but significant decrease in FFR (phentolamine: 0.79+/-0.02 vs. 0.77+/-0.02, p<0.05; urapidil: 0.78+/-0.02 vs. 0.75+/-0.02, p<0.05). However, only 6 patients showed a change in FFR from > or = 0.75 to <0.75 and no patients showed a change in FFR from > or = 0.80 to <0.75 that could have influenced clinical decision making. Saline did not induce any change in FFR. Phentolamine and urapidil induced only transient and negligible haemodynamic changes in heart rate and blood pressure. CONCLUSIONS: The administration of alpha-adrenergic blockers in addition to adenosine unmasks a small, yet clinically irrelevant, degree of residual microvascular tone. The consequential changes in FFR values do not significantly affect clinical decision making.

Adrenergic alpha-Antagonists↗

PubMed2003

Effects of intravenous dobutamine on coronary vasomotion in humans.

OBJECTIVES: We sought to investigate the vascular mechanisms of dobutamine-induced myocardial ischemia. BACKGROUND: Dobutamine stress is often used as a surrogate for exercise. The effects of dobutamine on the epicardial arteries are incompletely understood and possibly different from those of physical exercise. METHODS: Intravenous (IV) dobutamine (40 microg/kg per min) was administered in 19 patients with normal, 23 patients with mildly atherosclerotic, and 12 patients with stenotic coronary arteries. In another two groups of patients with stenotic arteries, IV dobutamine was preceded by 1) an intracoronary (IC) bolus of the alpha-adrenergic blocker phentolamine (12 microg/kg, n = 12); and 2) an IC infusion of the nitric oxide substrate L-arginine (150 micromol/l per min for 20 min, n = 11). Intravenous saline instead of dobutamine was infused into eight patients with normal arteries. After dobutamine (or saline), an IC bolus of isosorbide dinitrate (ISDN, 0.2 mg) was given. Coronary vasomotion was evaluated by quantitative coronary angiography on angiograms obtained after each dose of dobutamine, saline, phentolamine, L-arginine, and ISDN. RESULTS: Dobutamine increased the rate-pressure product and heart rate similarly in all patients except those who received saline. Dobutamine induced vasodilation in normal (change in luminal diameter [DeltaLD] vs. baseline: 19 +/- 2%) and in mildly atherosclerotic arteries (DeltaLD: 8 +/- 2%, p < 0.05 vs. normal). In stenotic arteries, dobutamine did not induce significant vasomotion (DeltaLD: -3 +/- 3%); the latter was improved by L-arginine (DeltaLD: 10 +/- 3%, p < 0.05 vs. stenotic arteries) and fully restored by phentolamine (DeltaLD: 19 +/- 3%, p < 0.05 vs. stenotic arteries). CONCLUSIONS: Endothelial dysfunction and enhanced alpha-adrenergic tone contribute to the loss of dobutamine-induced vasodilation in coronary atherosclerosis. In contrast to physical exercise, dobutamine does not induce "paradoxical vasoconstriction" of atherosclerotic coronary arteries.

Adrenergic beta-Agonists↗

PubMed2003

Intracoronary and intravenous adenosine 5'-triphosphate, adenosine, papaverine, and contrast medium to assess fractional flow reserve in humans.

BACKGROUND: Inducing both maximal and steady-state coronary hyperemia is of clinical importance to take full advantage of fractional flow reserve measurements. The present study compares different dosages and routes of administration of adenosine 5'-triphosphate (ATP), adenosine, contrast medium, and papaverine regarding their potential to achieve both maximal and steady-state hyperemia. METHODS AND RESULTS: In 21 patients with an isolated coronary stenosis, coronary vasodilation was induced successively by papaverine (20 mg intracoronary), adenosine (20 and 40 microg intracoronary), ATP (20 and 40 microg intracoronary), iohexol (6 mL intracoronary), adenosine or ATP through an antecubital vein (140 and 180 microg x kg(-1) x min(-1)), or adenosine or ATP through a femoral vein (140 and 180 microg x kg(-1) x min(-1)). Because vessel dimensions did not change, the ratio of distal coronary pressure (Pd) to aortic pressure (Pa) was used as an index of myocardial resistance. Pd/Pa was 0.77+/-0.21 at rest and decreased to 0.61+/-0.21 after papaverine. Pd/Pa decreased to a similar level with all other vasodilators, except with contrast medium (0.68+/-0.21; P<0.01 versus papaverine). Steady-state hyperemia could only be obtained by intracoronary papaverine and by intravenous ATP or adenosine. In another 23 patients, an intravenous infusion of ATP was varied from 0 to 280 microg x kg(-1) x min(-1). At doses >140 microg x kg(-1) x min(-1), there was neither a further decrease in Pd/Pa ratio nor a further increase in coronary flow velocities. CONCLUSIONS: Provided sufficient dosages are used, ATP, adenosine, and papaverine (but not contrast medium) induce maximal hyperemia and are therefore suitable to assess fractional flow reserve. Only intracoronary papaverine and intravenous ATP or adenosine induce steady-state hyperemia enabling a pressure pullback maneuver that is useful in assessing diffuse coronary atherosclerosis.

Adenosine↗

PubMed2003

Direct stenting.

Stents have ameliorated the outcome of percutaneous coronary interventions. Improved design, profile and flexibility of the currently available stents now permit to deliver the stent without pre-dilatation. In western European countries, stent implantation now occurs in up to 80% of all percutaneous revascularization procedures. In selected cases the safety and feasibility of direct stenting over conventional balloon-predilatation stenting has been demonstrated, in association with slightly superior outcome. This likely results from reduced vessel wall damage-dissections are sealed at the moment they are created-and distal embolization is reduced. In addition, a significant reduction in terms of costs and duration of procedures was demonstrated, while restenosis rate is not reduced with direct stenting.

Angioplasty, Balloon, Coronary↗

PubMed2002

Coronary thermodilution to assess flow reserve: validation in humans.

BACKGROUND: Guide wire-based simultaneous measurement of fractional flow reserve (FFR) and coronary flow reserve (CFR) is important to understand microvascular disease of the heart. The aim of this study was to investigate the feasibility of simultaneous measurement of FFR and CFR by one pressure-temperature sensor-tipped guide wire with the use of coronary thermodilution and to compare CFR by thermodilution (CFR(thermo)) with simultaneously measured Doppler CFR (CFR(Doppl)). METHODS AND RESULTS: In 103 coronary arteries in 50 patients, a pressure-temperature sensor-tipped 0.014-inch floppy guide wire and a 0.014-inch Doppler guide wire were introduced. Both normal vessels and a wide range of stenotic vessels were included. With 3 mL of saline at room temperature used as an indicator, by hand-injection, thermodilution curves in the coronary artery were obtained in triplicate, both at baseline and at intravenous adenosine-induced maximum hyperemia. After adequate curve-fitting, CFR(thermo) was calculated from the ratio of inverse mean transit times and compared with CFR(Doppl) calculated by velocities at hyperemia and baseline. Adequate sets of thermodilution curves and corresponding CFR(thermo) could be obtained in 87% of the arteries versus 91% for Doppler CFR and 100% for FFR. CFR(thermo) correlated fairly well to CFR(Doppl) (CFR(thermo)=0.84 CFR(Doppl)+0.17; r=0.80; P<0.001), although individual differences of >20% between both indexes were seen in a quarter of all arteries. CONCLUSIONS: This study shows the feasibility of simultaneous measurement of FFR (by coronary pressure) and CFR (by coronary thermodilution) in humans by one single guide wire in a practical and straightforward way and will facilitate assessment of microvascular disease.

Blood Flow Velocity↗