Publications

The effects of intravenous elgodipine, a new second-generation dihydropyridine calcium antagonist, on hemodynamics and coronary artery diameter were investigated in 15 patients undergoing cardiac catheterization for suspected coronary artery disease. Despite a significant decrease in systemic blood pressure, elgodipine infused at a rate of 1.5 μg/kg/min over a period of 10 minutes did not affect heart rate and left ventricular end-diastolic pressure. The contractile responses during isovolumic contraction showed a slight but significant increase in maximum velocity (56 ± 10 to 60 ± 10 seconds−1; p < 0.005), whereas the time constant of early relaxation was shortened from 49 ±11 to 44 ± 9 ms (p < 0.05). Coronary sinus and great cardiac vein flow increased significantly by 15 and 26%, respectively. As mean aortic pressure decreased, a significant decrease in coronary sinus (−27%) and great cardiac vein (−28%) resistance was observed, while the calculated myocardial oxygen consumption remained unchanged. In all, 69 coronary segments (including 13 stenotic segments) were analyzed quantitatively using computer-assisted quantitative coronary angiography. A significant increase in mean coronary artery diameter (2.27 ± 0.53 to 2.48 ± 0.53 mm; p < 0.000001), as well as in obstruction diameter, (1.08 ± 0.29 to 1.36 ± 0.32 mm; p < 0.02), was observed. The results demonstrate that elgodipine, in the route and dose described, induces significant vasodilatation of both coronary resistance and epicardial conductance vessels, without adverse effects on heart rate, myocardial oxygen demand and contractile indexes.

No abstract is provided for this article.

To assess the performance of the everolimus-eluting stent (EES) versus cobalt chromium bare-metal stent (BMS) in the setting of primary percutaneous coronary intervention for treatment of patients presenting with ST-segment elevation myocardial infarction (STEMI). The implantation of a drug-eluting stent in the setting of an acute myocardial infarction is still controversial. In several registries this clinical scenario has been associated with the development of stent thrombosis. The EES has demonstrated to reduce the stent thrombosis rate as compared to paclitaxel-eluting stent in randomised controlled trials, mainly performed in patients in stable clinical conditions. There are however few data regarding the effectiveness of EES in the context of STEMI.This is an investigator-driven, prospective, multicentre, multinational, randomised, single blind, two-arm, controlled trial (ClinicalTrials.gov number: NCT00828087). This trial, with an all comer design, randomises approximately 1,500 patients 1:1 to EES or BMS. Overall, any patient presenting with STEMI up to 48 hours who requires emergent percutaneous coronary intervention can be included. The primary endpoint is the patient-oriented combined endpoint of all-cause death, any myocardial infarction and any revascularisation at 1-year according to the Academic Research Consortium. Clinical follow-up will be scheduled at 30 days, six months, one year and yearly up to five years. No angiographic follow-up is mandated per protocol.This trial with broad inclusion and few exclusion criteria will shed light on the performance of the second generation EES in the complex scenario of STEMI.

No abstract is provided for this article.

1. The effects of an oral platelet activating factor (PAF) antagonist, BN52063, or matched placebo on inhaled PAF challenge were assessed in a double‐blind study in eight normal subjects. 2. PAF (24 micrograms) induced an immediate bronchoconstriction, with a maximum fall in flow at 30% of vital capacity from a partial flow volume manoeuvre (Vp30) of 47.1 +/‐ 7% (mean +/‐ s.e. mean) 5 min after inhalation following placebo treatment. Repeated PAF challenges at 15 min intervals resulted in tachyphylaxis of the bronchoconstrictor response. 3. Two hours after the ingestion of BN52063 (120 mg) the maximum bronchoconstriction induced by inhaled PAF was attenuated (35.9 +/‐ 9% fall at 5 min) with a significant reduction (P less than 0.05) in response after the first and second inhalations. 4. Inhaled PAF induced an immediate neutropenia (73.2 +/‐ 9% fall 5 min after inhalation) followed by a rebound neutrophilia, which were unaffected by pretreatment with BN52063. 5. Oral ingestion of a dose of BN52063 which is effective in reducing skin responses to PAF gave partial protection against the bronchoconstrictor effect of inhaled PAF in normal subjects.

Thin‐slice contiguous computed tomographic scanning was performed in four postmortem hearts with calcific aortic valve stenosis (mean weight: 583 ± 78 g; mean age: 65 ± 10 years) before, during, and after balloon valvuloplasty. Balloons of increasing diameter (15–19 mm single balloons, and 3 × 12‐mm trefoil‐shaped balloon) were positioned across the aortic valve and manually inflated to pressures of 3 to 4 atmospheres. During inflation of the 3 × 12‐mm balloon a larger residual orifice, potentially free for blood passage, was observed in the two cases with bicuspid valves and in one case with a fused tricuspid valve, while the reverse was noted in one case with a tricuspid valve without fusion. In most cases valvular orifice enlargement only occurred with larger diameter balloons. After valvuloplasty aortic valve area increased from 0.72 (range 0.20–0.95) cm 2 to 2.36 (range 0.95–3.14) cm 2 . The smallest orifice enlargement after dilatation occurred in case 1, where valvular calcified deposits had the largest volume and the highest computed tomographic attenuation value. In each patient macroscopic changes (fracture of nodular calcifications, commissural splitting, tearing of the central raphe) were noted. No calcium dislodgement or aortic ring damage was observed. In autopsy specimens computed tomography provided accurate evaluation of aortic valve morphology, extent of valve calcification, balloon‐leaflet relationship during inflation, and effects of the dilatation on valve leaflets and commissures. Advances in computed tomographic cardiovascular imaging may achieve similar results in the clinical setting, and allow a more rational, individualized approach to the valvuloplasty procedure. (J Interven Cardiol 1988:1:2)

No abstract is provided for this article.

The degranulation response of purified human eosinophils to platelet-activating factor (PAF) has been studied. PAF induced release of eosinophil peroxidase (EPO) and beta-glucuronidase from highly purified human eosinophils with an EC50 of 0.9 nM. The order of release was comparable with that induced by phorbol myristate acetate (PMA). The new specific PAF antagonist 3-[4-(2-chlorophenyl)-9-methyl-H-thieno[3,2-f] [1,2,4]triazolo-[4,3a][1,4]-diazepin-2-yl](4-morpholinyl)- 1-propane-one (WEB 2086) inhibited the PAF-induced enzyme release by human eosinophils in a dose-dependent manner. The viability of eosinophils were unaffected both by PAF and WEB 2086. The results suggest that PAF may amplify allergic and inflammatory reactions by release of preformed proteins from eosinophil granules.

It is well established that atherosclerotic plaques generally develop in low shear stress regions, including curved arterial segments and bifurcations. Once these plaques intrude into the lumen, the shear stress they are exposed to alters with hitherto unknown consequences. We hypothesize that in the more advanced stages of the disease, shear stress has an important impact on plaque composition in such a way that high shear stress enhances plaque vulnerability through its biological impact on the endothelium. We investigated this hypothesis by studying the relationship between shear stress and strain, a marker for plaque composition, in human coronary arteries.

Peter Barnes and colleagues show that corticosteroids have a potent inhibitory effect on GATA-3 via two interacting mechanisms that suppress Th2 cytokine expression. This novel mechanism of corticosteroid action may help explain the efficacy of corticosteroids in allergic diseases.