Copper Chelation Represses the Vascular Response to Injury

The induction of an acute inflammatory response followed by the release of polypeptide cytokines and growth factors from peripheral blood monocytes has been implicated in mediating the response to vascular injury. Because the Cu2+-binding proteins IL-1alpha and fibroblast growth factor 1 are exported into the extracellular compartment in a stress-dependent manner by using intracellular Cu2+ to facilitate the formation of S100A13 heterotetrameric complexes and these signal peptideless polypeptides have been implicated as regulators of vascular injury in vivo, we examined the ability of Cu2+ chelation to repress neointimal thickening in response to injury. We observed that the oral administration of the Cu2+ chelator tetrathiomolybdate was able to reduce neointimal thickening after balloon injury in the rat. Interestingly, although immunohistochemical analysis of control neointimal sections exhibited prominent staining for MAC1, IL-1alpha, S100A13, and the acidic phospholipid phosphatidylserine, similar sections obtained from tetrathiomolybdate-treated animals did not. Further, adenoviral gene transfer of the IL-1 receptor antagonist during vascular injury also significantly reduced the area of neointimal thickening. Our data suggest that intracellular copper may be involved in mediating the response to injury in vivo by its ability to regulate the stress-induced release of IL-1alpha by using the nonclassical export mechanism employed by human peripheral blood mononuclear cells in vitro

Value of the Electrocardiogram in Localizing the Occlusion Site in the Left Anterior Descending Coronary Artery in Acute Anterior Myocardial Infarction

OBJECTIVES The study assessed the value of the electrocardiogram (ECG) as predictor of the left anterior descending coronary artery (LAD) occlusion site in relation to the first septal perforator (S1) and/or the first diagonal branch (D1) in patients with acute anterior myocardial infarction (AMI). BACKGROUND In anterior AMI, determination of the exact site of LAD occlusion is important because the more proximal the occlusion the less favorable the prognosis

In vitro evaluation of the influence of pulsatile intraventricular pumping on ventricular pressure patterns

The Pulsatile catheter (PUCA) pump consists of a single port membrane pump connected to an indwelling valved catheter. This so-called transarterial blood pump was originally designed to be introduced through a superficial artery into the left ventricular cavity to pump blood from the left ventricle into the ascending aorta. By introducing the catheter directly into the thoracic aorta or the pulmonary artery, the possibility is created of applying large-diameter catheter PUCA pumps as left, right, or biventricular assist devices (LVAD, RVAD, or BIVAD) without damaging any of the structures of the heart. The pump performance of an 8 mm PUCA pump prototype (internal diameter catheter, 8 mm; catheter length, 40 cm; stroke volume, 80 ml) was studied in a mock circulation to investigate the influence of pulsatile intraventricular pumping on ventricular pressure patterns. The pumping mode of the PUCA pump was changed from approximately 1:1 ([n + 1]:n) to 1:2 ([1/2n + 1]:n) and 1:3 ([1/3n + 1]:n) in relation to the frequency of a ventricle-simulating membrane pump. Apart from the pumping mode, timing of the PUCA pump driving system (ejection phase) seems to be crucial in obtaining optimal unloading of the ventricle.</p

Autoperfusion balloon catheter for complicated coronary angioplasty: prospective study with retrospective controls

Prolonged angioplasty balloon inflation with an autoperfusion balloon for failed conventional coronary angioplasty, was compared with emergency surgery for this condition. Restenosis was assessed 6 weeks after successful intervention with the autoperfusion balloon. Forty consecutive patients with persistent acute occlusion and/or severe intimal dissection during conventional angioplasty, were treated with the autoperfusion balloon. They were candidates for emergency surgery if it failed. Total inflation time was significantly longer (p <0.001) with the autoperfusion balloon (27.5; 10-180 min) than with the standard balloon (10; 1-20 min) (median; range). The number of inflations was significantly lower (p <0.001) with the autoperfusion balloon (2; 1-5 times) than with the standard balloon (5; 2-14 times) (median; range). Two patients died, one before surgery could be performed. The autoperfusion balloon was successful in 26 patients (65%). After 6 weeks, 16 (62%) were asymptomatic without anti-anginal medication, 24 underwent repeat angiography, 10 (42%) had restenosis, 7 (27%) underwent elective bypass surgery. Emergency surgery remained necessary in 13 patients (33%), 9 received arterial grafts. In 31 retrospective controls, who had undergone immediate surgery for the same indication, only venous grafts could be used. Thus, prolonged autoperfusion balloon inflation was successful in 65% of the cases of failed, conventional angioplasty. The angiographic restenosis rate after 6 weeks was 42%. If emergency surgery remained necessary, the autoperfusion balloon facilitated the use of arterial bypass grafts

Gene and Cell Therapy for Heart Failure

Cardiac gene and cell therapy have both entered clinical trials aimed at ameliorating ventricular dysfunction in patients with chronic congestive heart failure. The transduction of myocardial cells with viral constructs encoding a specific cardiomyocyte Ca2+ pump in the sarcoplasmic reticulum (SR), SRCa2+-ATPase has been shown to correct deficient Ca2+ handling in cardiomyocytes and improvements in contractility in preclinical studies, thus leading to the first clinical trial of gene therapy for heart failure. In cell therapy, it is not clear whether beneficial effects are cell-type specific and how improvements in contractility are brought about. Despite these uncertainties, a number of clinical trials are under way, supported by safety and efficacy data from trials of cell therapy in the setting of myocardial infarction. Safety concerns for gene therapy center on inflammatory and immune responses triggered by viral constructs, and for cell therapy with myoblast cells, the major concern is increased incidence of ventricular arrhythmia after cell transplantation. Principles and mechanisms of action of gene and cell therapy for heart failure are discussed, together with the potential influence of reactive oxygen species on the efficacy of these treatments and the status of myocardial-delivery techniques for viral constructs and cells. Antioxid. Redox Signal. 11, 2025–2042

Fractional flow reserve to determine the appropriateness of angioplasty in moderate coronary stenosis: a randomized trial

Background - PTCA of a coronary stenosis without documented ischemia at noninvasive stress testing is often performed, but its benefit is unproven. Coronary pressure-derived fractional flow reserve (FFR) is an invasive index of stenosis severity that is a reliable substitute for noninvasive stress testing. A value of 0.75 identifies stenoses with hemodynamic significance. Methods and Results - In 325 patients for whom PTCA was planned and who did not have documented ischemia, FFR of the stenosis was measured. If FFR was >0.75, patients were randomly assigned to deferral (deferral group; n=91) or performance (performance group; n=90) of PTCA. If FFR was <0.75, PTCA was performed as planned (reference group; n=144). Clinical follow-up was obtained at 1, 3, 6, 12, and 24 months. Event-free survival was similar between the deferral and performance groups (92% versus 89% at 12 months and 89% versus 83% at 24 months) but was significantly lower in the reference group (80% at 12 months and 78% at 24 months). In addition, the percentage of patients free from angina was similar between the deferral and performance groups (49% versus 50% at 12 months and 70% versus 51% at 24 months) but was significantly higher in the reference group (67% at 12 and 80% at 24 months). Conclusions - In patients with a coronary stenosis without evidence of ischemia, coronary pressure-derived FFR identifies those who will benefit from PTCA

Fractional flow reserve to determine the appropriateness of angioplasty in moderate coronary stenosis:a randomized trial

\u3cp\u3eBackground - PTCA of a coronary stenosis without documented ischemia at noninvasive stress testing is often performed, but its benefit is unproven. Coronary pressure-derived fractional flow reserve (FFR) is an invasive index of stenosis severity that is a reliable substitute for noninvasive stress testing. A value of 0.75 identifies stenoses with hemodynamic significance. Methods and Results - In 325 patients for whom PTCA was planned and who did not have documented ischemia, FFR of the stenosis was measured. If FFR was &gt;0.75, patients were randomly assigned to deferral (deferral group; n=91) or performance (performance group; n=90) of PTCA. If FFR was &lt;0.75, PTCA was performed as planned (reference group; n=144). Clinical follow-up was obtained at 1, 3, 6, 12, and 24 months. Event-free survival was similar between the deferral and performance groups (92% versus 89% at 12 months and 89% versus 83% at 24 months) but was significantly lower in the reference group (80% at 12 months and 78% at 24 months). In addition, the percentage of patients free from angina was similar between the deferral and performance groups (49% versus 50% at 12 months and 70% versus 51% at 24 months) but was significantly higher in the reference group (67% at 12 and 80% at 24 months). Conclusions - In patients with a coronary stenosis without evidence of ischemia, coronary pressure-derived FFR identifies those who will benefit from PTCA.\u3c/p\u3