bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feasibility of serial intracoronary ultrasound imaging for assessment of progression of intimal proliferation in cardiac transplant recipients.
Authors: Pinto F J , Chenzbraun A , Botas J , Valantine H A , St Goar F G , Alderman E L , Oesterle S N , Schroeder J S , Popp R L 
Published: June 2012

BACKGROUND
Serial quantitative coronary angiography is used to assess progression of coronary disease; however, pathology studies have demonstrated angiographic insensitivity for determining atheroma. Intracoronary ultrasound (ICUS) can define and measure the components of the arterial wall and offers the potential for precise quantitative assessment of disease progression on serial examinations. The present study was done to test the feasibility of serially assessing intimal proliferation at the same coronary site with ICUS imaging in cardiac transplant recipients.

METHODS AND RESULTS
ICUS imaging was done with a 30-MHz, 5F or 4.3F ultrasound imaging catheter at the time of angiography in 70 cardiac allografts (3.8 sites per patient) initially and 1 year later. Mean intimal thickness (IT), luminal area (LA), and total area (TA) of lumen plus intima and an index of intimal thickness (II = TA - LA/TA) were measured at each site. Additionally, vessels were graded using a scale incorporating criteria of intimal thickness and circumferential involvement. Side-by-side comparisons of paired angiograms were performed both to verify the similarity of ICUS imaging site and to detect new angiographic abnormalities. At least one site could be assessed serially by ICUS in 100% of patients, but only 189 of the original 263 coronary sites (72%) (2.7 sites per patient) could be matched satisfactorily on the second study. Thirty-nine patients (56%) had mild IT and 31 patients (44%) had moderate or severe IT on the initial study. Both groups showed the same IT progression the following year (delta = 0.05 +/- 0.13 versus 0.07 +/- 0.15 mm; P = NS). Twenty-seven of the 70 patients (39%) showed progression by ICUS. The 23 patients with ICUS progression and angiographically normal vessels had the same progression in intimal thickening as the 4 patients with ICUS progression but showing angiographic disease (delta = 0.17 +/- 0.13 versus 0.22 +/- 0.10 mm; P = NS).

CONCLUSIONS
Replication of the intracoronary imaging site by judgment of two observers at an initial study and at a second study 1 year later was possible in at least one vessel site in 100% of the 70 patients and in 72% (189 of 263) of the original imaging sites (2.7 sites per patient). Serial ICUS demonstrates progression of intimal thickening at specific sites in only some cardiac transplant patients. Progression of intimal proliferation can occur in individuals in the presence or absence of initially increased intimal thickening or of angiographic disease at the time of the initial studies. Angiography is insensitive for recognizing early intimal thickening of the coronary vessels.
Time course of coronary endothelial healing after injury due to ischemia and reperfusion.
Authors: Horwitz L D , Kaufman D , Keller M W , Kong Y 
Published: June 2012

BACKGROUND
Although it has been demonstrated in short-term preparations that ischemia with early reperfusion results in coronary vascular injury manifested by abnormal endothelium-dependent relaxation and increased permeability to plasma proteins, it has not been clear whether these abnormalities are permanent or reversible.

METHODS AND RESULTS
In a canine model, regional coronary ischemia was accomplished by 1 hour of left anterior descending coronary artery ligation, and follow-up studies were performed after reperfusion for 1 hour, 48 hours, 2 weeks, or 9 weeks. Vasorelaxation was measured in vitro with preconstricted epicardial coronary artery rings subjected to increasing concentrations of the endothelium-dependent vasodilator ADP and the endothelium-independent vasodilator nitroprusside. At 1 and 48 hours of reperfusion, relaxation of rings from the ischemic reperfused artery to ADP was blunted, but relaxation to nitroprusside was normal. At 2 weeks there was a nonsignificant trend toward a blunted response to ADP in the ischemic/reperfused rings, and at 9 weeks a completely normal response to ADP was observed. Coronary microvascular permeability was assessed by measurement of protein leak index (PLI), by using a double-isotope technique with autologous radiolabeled transferrin and erythrocytes. At 1 and 48 hours of reperfusion there were substantial increases in PLI in the previously ischemic regions, indicative of increased extravascular transferrin. There was a small increase in PLI at 2 weeks but a completely normal measurement at 9 weeks. Electron microscopy of ischemic/reperfused vessels demonstrated endothelial cell swelling and other abnormalities in epicardial arteries and the microcirculation at 48 hours of reperfusion but normal endothelium at 2 weeks of reperfusion.

CONCLUSIONS
After 1 hour of regional coronary ischemia, coronary endothelial injury occurs early in reperfusion with abnormalities in epicardial coronary artery endothelium-dependent relaxation, coronary microvascular permeability, and both epicardial coronary artery and microvascular histology. This pattern of injury persists for at least 48 hours, but there is partial functional and complete histological recovery within 2 weeks and complete functional recovery within 9 weeks.
Mithramycin inhibits myointimal proliferation after balloon injury of the rat carotid artery in vivo.
Authors: Chen S J , Chen Y F , Miller D M , Li H , Oparil S 
Published: June 2012

BACKGROUND
Smooth muscle proliferation and extracellular matrix formation in the subintimal region of blood vessels that have been subjected to intimal injury are responsible for restenosis following balloon angioplasty of the coronary arteries and for accelerated atherosclerosis in a variety of other pathophysiological states. The immediate early-response gene c-myc is overexpressed in proliferating vascular smooth muscle cells in vitro, and c-myc antisense oligomers have been shown to reduce c-myc expression and to inhibit proliferation of vascular smooth muscle cells in culture. Mithramycin is a commercially available G-C-specific DNA binding drug that selectively inhibits transcription of genes, such as c-myc, that have G-C-rich promoter sequences. This study tested the hypothesis that mithramycin inhibits transcription of the c-myc proto-oncogene and prevents myointimal proliferation after balloon injury of the rat carotid artery in vivo.

METHODS AND RESULTS
Ten-week-old male Sprague-Dawley rats received mithramycin (150 micrograms/kg IP) or distilled H2O 1 hour before and 1 hour after balloon injury of the right common carotid artery. After 2 weeks, the rats were killed by overdose of pentobarbital, and the injured right and uninjured control left arteries were pressure-fixed and subjected to morphological analysis for evaluation of the degree of myointimal thickening. Separate groups of rats were killed at 2 and 6 hours after vascular injury, and total RNA from injured and control vessels of mithramycin- and vehicle-treated rats was subjected to Northern analysis for assessment of steady-state c-myc mRNA levels. The areas of neointima and the ratios of neointimal to medial area were significantly less in mithramycin-treated than in control rats (0.6 +/- 0.1 versus 1.2 +/- 0.1 mm2, P < .01 and 95 +/- 16% versus 190 +/- 14%, P < .01). Lumen size was significantly greater in mithramycin-treated than in control rats (1.5 +/- 0.1 versus 0.8 +/- 0.1 mm2, P < .01). Steady-state c-myc mRNA levels were increased 10-fold and 2-fold (compared with undamaged carotid arteries) at 2 and 6 hours after balloon injury, respectively; mithramycin treatment reduced c-myc mRNA levels at 2 and 6 hours by 66% and 53%, respectively.

CONCLUSIONS
These results support the hypothesis that systemic administration of mithramycin immediately (1 hour before and after intervention effectively inhibits transcription of the c-myc proto-oncogene and prevents myointimal proliferation after balloon injury of the rat carotid artery in vivo. Because mithramycin has been shown to be well tolerated by humans and to effectively inhibit transcription of c-myc in proliferating human cells, this agent may be useful in the prevention of coronary restenosis.
Local delivery of r-hirudin by a double-balloon perfusion catheter prevents mural thrombosis and minimizes platelet deposition after angioplasty.
Authors: Meyer B J , Fernández-Ortiz A , Mailhac A , Falk E , Badimon L , Michael A D , Chesebro J H , Fuster V , Badimon J J 
Published: June 2012

BACKGROUND
The major morbidity of percutaneous transluminal coronary angioplasty is acute thrombosis and restenosis of the dilated lesion. Platelet-thrombus deposition occurs within minutes after injury, is primarily mediated by thrombin, causes acute occlusion, and contributes to late restenosis. Experimentally, specific thrombin inhibitors have prevented mural thrombosis. However, local therapy may be more effective than systemic treatment. We tested the hypothesis that high local concentrations of an antithrombin drug at the site of arterial injury following balloon angioplasty inhibit platelet thrombus formation equally or better than conventional systemic treatment and at lower systemic anticoagulant levels.

METHODS AND RESULTS
Balloon angioplasty of the carotid arteries of 29 pigs was performed using systemic intravenous treatment with heparin (100 U/kg, groups I and II), suboptimal r-hirudin (0.3 mg/kg, group III), and higher-dose r-hirudin (0.7 mg/kg, group IV), which is the lowest dose that completely inhibited arterial thrombosis in the pig. Immediately after balloon angioplasty of the first carotid, additional local therapy with placebo (group I) or r-hirudin (groups II, III, and IV; 0.3 mg/kg in 1 mL) was administered with distal perfusion through a new percutaneous double-balloon catheter. After 1 hour of local drug delivery, angioplasty of the contralateral carotid was performed. Reflow for 1 hour was permitted to both carotids to compare the short-term effect of local plus systemic treatment with systemic treatment on quantitative 111In-labeled platelet deposition and macroscopic mural thrombus formation on deeply injured carotid segments. Local drug delivery of placebo compared with systemic heparin treatment resulted in no change of platelet deposition (x 10(6)/cm2, mean +/- SEM) in controls (group I, 91.0 +/- 23.5 versus 80.8 +/- 19.4), but local delivery of r-hirudin resulted in a significant reduction in group II (15 +/- 2.5 versus 71.3 +/- 14.5; P < .02) and group III (11.4 +/- 2.5 versus 80.5 +/- 11.4; P < .01) and was borderline in group IV (7.4 +/- 1.8 versus 14.1 +/- 7.4; P = .05), respectively. The incidence of macroscopic mural thrombus formation with local and systemic treatment was 86% and 75% in group I, 16% and 70% in group II, 14% and 71% in group III, and 0% and 16% in group IV, respectively.

CONCLUSIONS
Local therapy with the specific thrombin inhibitor r-hirudin significantly reduces short-term quantitative platelet deposition and macroscopic mural thrombus formation following balloon angioplasty compared with systemic treatment of conventional doses of heparin and hirudin and requires a significantly smaller amount of the recombinant drug.
Angiotensinergic versus nonangiotensinergic hemodynamic effects of converting enzyme inhibition in patients with chronic heart failure. Assessment by acute renin and converting enzyme inhibition.
Authors: Kiowski W , Beermann J , Rickenbacher P , Haemmerli R , Thomas M , Burkart F , Meinertz T 
Published: June 2012

BACKGROUND
The contribution of nonangiotensinergic effects of converting enzyme inhibitors to their hemodynamic effects in patients with chronic heart failure is not clear. A comparison of the effects of renin and converting enzyme inhibition should help to clarify this issue.

METHODS AND RESULTS
Thirty-six patients with chronic heart failure (New York Heart Association class II or III) were randomly assigned to receive double-blind either intravenous placebo, the renin inhibitor remikiren, or the converting enzyme inhibitor enalaprilat followed by coinfusion of a second placebo infusion, the addition of remikiren to enalaprilat, or the addition of enalaprilat to remikiren, respectively. Systemic hemodynamics (Swan-Ganz and radial artery catheters) were measured before (rest and submaximal recumbent bicycle ergometry), during (rest), and at the end (rest and exercise) of each 45-minute single- or combination-infusion period. Placebo did not change hemodynamics or renin activity. Effective inhibition of the renin-angiotensin system by remikiren and enalaprilat was indicated by increases of plasma immunoreactive renin together with rapid and complete inhibition of renin activity after remikiren and an increase after enalaprilat (all P < or = .05). Remikiren and enalaprilat rapidly and to a similar extent reduced resting blood pressure through a reduction of systemic vascular resistance, and these changes were significantly correlated to baseline plasma renin activity. Both compounds also decreased pulmonary artery, pulmonary capillary wedge, and right atrial pressures to a similar extent (P < .05). During exercise, pulmonary capillary wedge and right atrial pressures were equally reduced and stroke volume index was increased with remikiren and enalaprilat (P < .05) for both). The combination of converting enzyme with renin inhibition or vice versa did not cause additional hemodynamic changes.

CONCLUSIONS
Specific renin inhibition in patients with chronic heart failure produces short-term hemodynamic effects that are almost indistinguishable from those of converting enzyme inhibition. This finding and the lack of additional effects of converting enzyme inhibition added to renin inhibition suggest that nonangiotensinergic effects of converting enzyme inhibitors do not play a significant role in their short-term hemodynamic effects in patients with chronic heart failure.
Radiofrequency ablation of atrial flutter. Efficacy of an anatomically guided approach.
Authors: Kirkorian G , Moncada E , Chevalier P , Canu G , Claudel J P , Bellon C , Lyon L , Touboul P 
Published: June 2012

BACKGROUND
Previous reports have shown that radiofrequency ablation can terminate atrial flutter and prevent recurrences. However, different methods have been used, and the current experience remains limited. The objective of the present study was to determine the efficacy of radiofrequency ablation of atrial tissue in patients with atrial flutter using an anatomically guided approach.

METHODS AND RESULTS
We treated 22 patients aged 30 to 73 years. Atrial flutter was recurrent for a mean of 5 years despite the administration of multiple antiarrhythmic drugs. Radiofrequency current was directed to the atrial isthmus between the inferior vena cava and the tricuspid ring, regardless of the morphology of local electrograms. Radiofrequency energy was applied during typical atrial flutter in 12 patients, atypical atrial flutter in 2 patients, and successively both forms in 8 patients. In 19 patients, atrial flutter abruptly terminated. In 3 patients, atrial flutter persisted despite 37, 48, and 25 applications, respectively. Atrial recordings demonstrated that atrial flutter termination occurred as a consequence of conduction block at the site of radiofrequency energy application, regardless of the type of atrial flutter. The number of applications before termination ranged from 1 to 82 (mean, 32). Atrial flutter could no longer be induced in every case. There were no complications. During a 13-month mean follow-up, atrial flutter recurred in only 2 of the 19 patients who had a successful ablation. Four patients experienced chronic atrial fibrillation, and 2 of them returned to sinus rhythm with antiarrhythmic therapy.

CONCLUSIONS
Radiofrequency ablation of atrial flutter using anatomic guidance is feasible and effective. Further experience is needed to delineate its role as an alternative approach to the management of refractory atrial flutter.