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Tommaso Gori

Publications and source records attributed to Tommaso Gori.

At least 19 recordsLinked to original sources
PubMed2006

Effectiveness and safety of sirolimus stent implantation for coronary in-stent restenosis: the TRUE (Tuscany Registry of Sirolimus for Unselected In-Stent Restenosis) Registry.

OBJECTIVES: This study sought to evaluate the effectiveness and safety of the sirolimus-eluting stent in the treatment of in-stent restenosis (ISR) in consecutive unselected patients undergoing coronary intervention in a real-world scenario. BACKGROUND: Restenosis after bare metal stenting is characterized by a high rate of re-restenosis once treated with repeated percutaneous coronary intervention. METHODS: The study was designed as a prospective two-center registry. We enrolled 244 patients with ISR in a native coronary artery or saphenous vein graft who had clinical indication for repeat intervention. RESULTS: Sirolimus stent implantation was successful in all lesions. At 9-month follow-up, death occurred in 4 (1.6%) patients, myocardial infarction in 4 (1.6%), and ischemia-driven target lesion revascularization (TLR) in 12 (4.9%), for a cumulative event-free survival of 227 (93%). Although 9-month follow-up angiography was planned in all patients, only 150 (62%) patients completed it, and restenosis was present in 13 (8.7%) patients. Diabetes and non-ST-segment elevation acute coronary syndrome at presentation were the only independent predictors of freedom from ischemia-driven TLR and major adverse cardiac events. CONCLUSIONS: Sirolimus stent implantation for the treatment of ISR is effective and safe. In diabetic patients and in those with acute coronary syndrome, the higher rate of recurrence requires further evaluation.

Aged↗
PubMed2006

Postconditioning fails to prevent radial artery endothelial dysfunction induced by ischemia and reperfusion: evidence from a human in vivo study.

Animal studies have shown that, as compared with unrestricted reperfusion, exposure to brief periods of controlled ischemia (postconditioning) at the end of a prolonged ischemia reduces the extent of tissue damage. We set out to test whether postconditioning can prevent endothelial dysfunction induced by ischemia and reperfusion in a human in vivo model. Ten healthy young non-smoking volunteers were enrolled in this cross-over, controlled, investigator-blinded study. Subjects were exposed to 15 min of forearm ischemia followed by either unrestricted reperfusion or postconditioning (3 periods of 20 s of ischemia separated by 10 s of reperfusion). Endothelium-dependent flow-mediated dilation (FMD) was measured at the level of the radial artery before and after ischemia (with or without postconditioning). Forearm ischemia blunted FMD in both study visits (unrestricted reperfusion visit: before ischemia, 7.7% +/- 1.3%; after ischemia, 2.5% +/- 1.4%; and postconditioning visit: before, 7.3% +/- 1.2%; after, 2.6 +/- 1.6%; P < 0.05 for both, P = not significant (NS) between visits). In contrast with data from animal studies, postconditioning (20 s ischemia-- 10 s reperfusion repeated 3 times) does not limit post-ischemic endothelial dysfunction in this human in vivo model. Further human studies are necessary to evaluate other reperfusion protocols in an attempt to limit post-ischemic tissue damage.

Adult↗
PubMed2006

Ischemia and reperfusion: the endothelial perspective. A radical view.

Ischemia and reperfusion (IR) injury causes a variety of changes in tissue homeostasis that lead to necrosis and/or programmed cell death. Due to its strategic location at the luminal surface of vessels, the vascular endothelium is particularly sensitive to IR. In particular, endothelial biosynthetic activities (and their protective effects) appear to be impaired by the oxidative burst induced by a sudden increase in oxygen free radical species upon reperfusion. Importantly, this endothelial damage can be easily assessed in vivo in humans by measuring endothelium-dependent vasorelaxation. Paradoxically, recent studies have emphasized the central role of free radicals (including oxygen free radicals and nitric oxide) also in a protective process, denominated ischemic preconditioning, i.e. a condition whereby a given stimulus can increase the tolerance of a tissue to IR damage. We discuss the role of the endothelium in determining the mechanism of IR injury, and on the other side, the effect of IR injury on endothelial function. In particular, we focus on the role of reactive free radicals in endothelial IR injury and in the development of ischemic preconditioning.

Endothelium, Vascular↗
PubMed2006

The effect of ischemia and reperfusion on microvascular function: a human in vivo comparative study with conduit arteries.

Although microvascular dysfunction is of critical importance in the pathophysiology of myocardial ischemic syndromes, no study has investigated whether there are differences in the sensitivity to ischemia and reperfusion injury between microvessels and conduit arteries. Ten healthy young nonsmoking male volunteers (age range 24-45) were enrolled. Parameters measured included radial (conduit) artery (endothelium-dependent) flow-mediated dilation, microvascular cutaneous reactive hyperemia (using laser Doppler) and acetylcholine-induced microvascular vasodilation (laser Doppler iontophoresis). Data were acquired before and after ischemic injury (15 minutes of ischemia of the brachial artery followed by 15 minutes reperfusion) and analyzed in a randomized, blinded fashion. Conduit artery FMD was significantly blunted after ischemia (before: 7.5 +/- 1.1%; after: 2.9 +/- 1.0%, P < 0.05). Conversely, ischemia had no effect on microvascular reactive hyperemia (P = ns) and acetylcholine-induced vasodilation (P = ns). Using a human in vivo model, we demonstrate that microvessels are more resistant to ischemic injury as compared to conduit arteries.

Acetylcholine↗
PubMed2006

Correlation analysis between different parameters of conduit artery and microvascular vasodilation.

Impaired endothelial responsiveness to specific vasodilator stimuli has been used as a surrogate marker of cardiovascular risk. Multiple methods allow testing endothelial responses in both microvessels and conduit arteries, but it is still unclear whether there is a relationship in endothelial function between these two different vascular beds. Twenty-five healthy young non smoking male volunteers (age range 24-45) were enrolled. Radial (conduit) artery (endothelium-dependent) flow-mediated dilation (FMD), microvascular cutaneous reactive hyperemia (using laser Doppler) and acetylcholine-induced microvascular vasodilation (laser Doppler iontophoresis) were measured. Data were analyzed in a randomized fashion in order to test the existence of a correlation among these measures of endothelium (in)dependent vasodilation. Conduit artery FMD showed a negative correlation with resting radial artery diameter (R=0.44, P<0.05). There was a correlation between peak responsiveness to acetylcholine and peak reactive hyperemia (R=0.41, P<0.05). Conversely, absolutely no correlation was shown between FMD and measures of microvascular vasomotion, including reactive hyperemia (P=ns) and acetylcholine-induced vasodilation (P=ns). Using three different human in vivo models, we test conduit artery and microvascular endothelial vasodilation. While microvascular flow reserve measurements induced by endothelium-dependent and independent stimuli appear to be linearly correlated, we show no correlation in endothelium-dependent vasomotion between the micro- and macrocirculation.

Adult↗
PubMed2005

A "fat" cough.

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Cardiac Surgical Procedures↗
PubMed2005

Sildenafil prevents endothelial dysfunction induced by ischemia and reperfusion via opening of adenosine triphosphate-sensitive potassium channels: a human in vivo study.

BACKGROUND: Animal studies have demonstrated that administration of sildenafil can limit myocardial damage induced by prolonged ischemia, an effect that appears to be mediated by opening of adenosine triphosphate-sensitive potassium (K(ATP)) channels. No study has investigated whether sildenafil can also prevent the impairment in endothelium-dependent vasodilatation induced by ischemia-reperfusion (IR) in humans. METHODS AND RESULTS: In a double-blind, placebo-controlled, crossover design, 10 healthy male volunteers (25 to 45 years old) were randomized to oral sildenafil (50 mg) or placebo. Two hours later, endothelium-dependent, flow-mediated dilatation (FMD) of the radial artery was measured before and after IR (15 minutes of ischemia at the level of the brachial artery followed by 15 minutes of reperfusion). Seven days later, subjects received the other treatment (ie, placebo or sildenafil) and underwent the same protocol. Pre-IR radial artery diameter and FMD, as well as baseline radial artery diameter after IR, were similar between visits (P=NS). After placebo administration, IR significantly blunted FMD (before IR: 7.9+/-1.1%; after IR: 1.2+/-0.7%, P<0.01). Importantly, sildenafil limited this impairment in endothelium-dependent vasodilatation (before IR: 7.0+/-0.9%; after IR: 6.2+/-1.1%, P=NS; P<0.01 compared with placebo). In a separate protocol, this protective effect was completely prevented by previous administration of the sulfonylurea glibenclamide (glyburide, 5 mg), a blocker of K(ATP) channels (n=7; FMD before IR: 10.3+/-1.5%; after IR: 1.3+/-1.4%, P<0.05). CONCLUSIONS: In humans, oral sildenafil induces potent protection against IR-induced endothelial dysfunction through opening of K(ATP) channels. Further studies are needed to test the potential clinical implications of this finding.

Adult↗
PubMed2005

Folic Acid does not limit endothelial dysfunction induced by ischemia and reperfusion: a human study.

Nitric oxide synthase (NOS) uncoupling is a condition of increased production of superoxide anion associated with a decreased production of nitric oxide (NO) by this enzyme. Folic acid can prevent and/or reverse NOS uncoupling in the setting of diabetes, smoking, hypercholesterolemia, and nitrate tolerance. Whereas animal studies showed a protective effect of folic acid in ischemia and reperfusion (IR) injury, no study tested whether folic acid administration limits IR-induced endothelial dysfunction in humans. In a double-blind, parallel study, 20 healthy young male volunteers were randomized to receive folic acid, 10 mg/d for 7 days, or matching placebo. At the end of the treatment period, endothelium-dependent, flow-mediated dilation (FMD) of the radial artery was measured before and after IR injury (15 minutes of ischemia at the level of the brachial artery followed by 15 minutes of reperfusion). There was no difference at baseline between groups in any variable. In the placebo group, IR significantly blunted FMD (before IR, 6.7+/-1.0%; after IR, 1.5+/-1.3%, P<0.01). A similar effect was observed in the folic acid group (before IR, 6.3+/-1.1%; after IR, 2.1+/-1.0%, P=ns compared with placebo). As opposed to animal studies, high-dose folic acid does not protect the vascular endothelium from IR injury in humans.

Blood Flow Velocity↗
PubMed2005

The role of reactive free radicals in ischemic preconditioning--clinical and evolutionary implications.

Ischemic preconditioning is a condition of reduced sensitivity to ischemic damage. This protective state can be induced by exposure to periods of brief, sublethal, ischemia prior to a protracted ischemic event, but, more interestingly, also by administration of specific drugs. Recent studies have emphasized the central role of free radicals (including superoxide anion and nitric oxide) in this process. In line with these observations, studies have demonstrated that also drugs such as organic nitrates, which are able to release nitric oxide (but also the highly oxidant superoxide anion) can induce preconditioning. Starting from our observations made in human experimental models regarding the effects of chronic therapy with organic nitrates, we criticize the hypothesis whereby nitrates might be used to induce a state similar to preconditioning upon chronic exposure. As well, we propose a theory for the evolutionary meaning of ischemic preconditioning based on the hypothesis that, while protective over short periods of time, continuous exposure to oxidant free radicals might be associated with a loss of this protective effect and, in certain cases, with an increased oxidative damage.

Biological Evolution↗
PubMed2005

Current perspectives. Therapy with organic nitrates: newer ideas, more controversies.

Because of their potent hemodynamic effects, organic nitrates have been introduced in the cardiovascular pharmacopoeia since more than a century in the treatment of coronary artery disease and congestive heart failure. Today, nitroglycerin is the most commonly prescribed generic drug in Italy. While their hemodynamic effects and some of their side effects (e.g. nitrate tolerance, the rebound phenomenon) are at least in part known, little is known regarding other effects of nitrates, for instance their antiaggregant, preconditioning-mimetic, and antiatherosclerotic properties. These effects might have tremendous importance in the treatment of cardiovascular patients. At the same time, the effects of nitrate-derived oxygen free radical species require further investigation. This review provides an update on recent findings in this field.

Cardiovascular Diseases↗
PubMed2005

Outcome of percutaneous hybrid coronary revascularization: bare metal stents jeopardize the benefit of sirolimus-eluting stents in the real world.

BACKGROUND: In an effort to contain procedural costs while limiting the risk of in-stent restenosis, hybrid percutaneous revascularization (ie, stenting with at least one sirolimus-eluting stent [SES] and at least one bare metal stent [BMS] in the same patient) is felt to be a cost-effective alternative to exclusive SES use. OBJECTIVE: To describe the outcome of hybrid percutaneous revascularization for the treatment of patients with multiple coronary artery lesions. METHODS AND RESULTS: Fifty-six patients (42 men; mean age [+/- SEM] 64+/-2) underwent hybrid stenting (average of 1.2 SES/patient and 1.3 BMS/patient). SES were used to treat lesions at higher restenotic potential, including longer lesions, smaller target vessels and bifurcation lesions (mean stent length [+/- SEM] was 21.1+/-1.2 mm for SES and 16.0+/-0.6 mm for BMS; stent diameter mean [+/- SEM] was 2.9+/-0.0 mm for SES and 3.1+/-0.1 mm for BMS; bifurcation lesions were 43% for SES and 7% for BMS; all P<0.01). At nine months of clinical follow-up, no death or myocardial infarction was reported. Twenty-one patients underwent clinically driven repeat coronary angiography at a mean (+/- SEM) of 8+/-1 of months (range two to 12 months) follow-up. Target lesion revascularization procedures were recorded in six patients (11%) for nine lesions (6%). Of these lesions, seven were categorized after blinded analysis as due to in-BMS restenosis and two to in-SES restenosis (P=0.01); three patients (5.4%) underwent reangioplasty for de novo lesions. There was one case of acute in-SES thrombosis. SES showed significantly less neointimal hyperplasia (late lumen loss was 0.4+/-0.1 mm for SES and 1.3+/-0.1 mm for BMS; loss index was 0.15+/-0.05 for SES and 0.48+/-0.05 for BMS; all P<0.001). CONCLUSIONS: The use of SES resulted in less neointimal hyperplasia even when used to treat lesions at higher risk for restenosis based on angiographic characteristics. BMS implantation significantly limits this beneficial effect, compromising the outcome of hybrid percutaneous coronary revascularization.

Aged↗
PubMed2004

Continuous therapy with nitroglycerin impairs endothelium-dependent vasodilation but does not cause tolerance in conductance arteries: a human in vivo study.

We investigated in healthy humans whether continuous therapy with organic nitrates impairs conduit artery responses to nitroglycerin (GTN) as well as its effects on endothelium-dependent vasodilation. Sixteen young male volunteers were randomized to continuous treatment with either transdermal GTN (0.6 mg/h/24 hrs for 6 days) or no therapy. Endothelium-dependent (flow-mediated) dilatation (FMD) and endothelium-independent (GTN-mediated) dilatation (GMD) of the brachial artery were evaluated before randomization (session 1), after six days of transdermal GTN treatment (session 2), and three hours after withdrawal of transdermal GTN (session 3). In the GTN group, on session 1, 0.4 mg sublingual GTN increased resting brachial artery diameter from 0.40 +/- 0.03 to 0.45 +/- 0.03 cm (P < 0.01). At the time of session 2, this GTN-mediated vasodilation remained unchanged at baseline (0.47 +/- 0.04 cm), with no further significant dilatation in response to either stimulus. On session 3, three hours after patch removal, baseline brachial artery diameter and GMD returned to pretreatment values, but FMD remained blunted (session 1: 8.7 +/- 2.5; session 3: 4.1 +/- 1.7%, P < 0.05). There was no change in these variables in the control group. Our data demonstrate that continuous GTN therapy impairs endothelium-dependent vasodilation in conduit arteries yet does not induce nitrate tolerance.

Administration, Cutaneous↗
PubMed2003

Effect of folic acid on nitrate tolerance in healthy volunteers: differences between arterial and venous circulation.

This study investigated whether oral supplemental folic acid can prevent the development of nitrate tolerance and whether it has different effects on the arterial and venous systems. Twenty-four healthy male volunteers received either placebo or folic acid (10 mg/d) for 14 days. Additionally, all subjects underwent concurrent transdermal nitroglycerin therapy for 7 days. Venous occlusion forearm strain gauge plethysmography measured arterial and venous responses to sublingual nitroglycerin before and after treatment. Both arterial and venous responses were blunted in the placebo group after transdermal nitroglycerin. Folic acid prevented the development of nitrate tolerance in arteries but had no effect in veins.

Adult↗