High dose rate intracoronary radiation for inhibition of neointimal formation in the stented and balloon-injured porcine models of restenosis: angiographic, morphometric, and histopathologic analyses.

PURPOSE: We examined the effects of intracoronary irradiation delivered at a high dose rate on neointimal hyperplasia after injury induced by two methods: balloon overstretch injury, and stent implantation in a porcine model of coronary restenosis. METHODS AND MATERIALS: In 34 Hanford miniature swine, a segment of each coronary artery was targeted for injury and treatment. The artery segments were treated with 192Ir at doses of 10 Gy over 4 min (eight animals), 15 Gy over 6 min (nine animals), 25 Gy over 10 min (nine animals) or control (simulation wire only; eight animals). The treated segments were subjected to stent implantation (left anterior descending and right coronary artery) or balloon overstretch (circumflex) injury. Twenty-eight days later, repeat coronary angiography and sacrifice were done. Quantitative coronary angiography, morphometry, and extensive histopathologic analyses were carried out in a blinded fashion. RESULTS: The change in minimal lumen diameter from postinjury to presacrifice in the stent-injured left anterior descending was -0.79 +/- 0.34 (mean: +/- SD) mm in the control group, compared to -0.43 +/- 0.35 mm in the 15 Gy (p = 0.04) and -0.21 +/- 0.50 mm in the 25 Gy (p = 0.01) groups; and in the balloon-injured circumflex was -0.31 +/- 0.22 mm in the control group compared to -0.03 +/- 0.18 mm in the 10 Gy (p = 0.05) and 0.00 +/- 0.33 in the 15 Gy (p = 0.01) groups. Percent area stenosis in the left anterior descending was 36 +/- 9% in the control group compared to 18 +/- 12% in the 15 Gy (p = 0.003) and 11 +/- 11% in the 25 Gy (p < 0.001) groups; and in the circumflex was 16 +/- 10% in the control groups, compared to 5 +/- 5% in the 15 Gy (p = 0.02) and 2 +/- 2% in the 25 Gy (p = 0.009) groups. Histopathology showed a striking reduction in the amount of neointima in the irradiated arteries compared with control vessels. Other radiation effects were stromal fibrin exudate, thinning of the media, and adventitial fibrosis and leukocyte infiltration in the radiated arterial segments. CONCLUSIONS: High dose rate intracoronary irradiation with 192Ir effectively inhibits intimal proliferation after stent-induced as well as balloon-overstretch injury. This shorter treatment time (4 to 10 min) may provide a clinically practical approach to the prevention of restenosis after angioplasty.

Comparison of echocardiographic assessment of cardiac hemodynamics in the intensive care unit with right-sided cardiac catheterization.

Estimation of left ventricular filling pressure and cardiac index is important in the management of patients requiring right heart catheterization. Doppler echocardiography can provide a noninvasive measure of these parameters, but its accuracy in individual measurements, predicting hemodynamic subgroups, and in tracking serial changes in critically ill patients remains to be elucidated. Left ventricular filling pressure and cardiac index were assessed in 49 critically ill patients requiring right heart catheterization and Doppler echocardiographic studies. Two or more serial studies were performed in 18 of these subjects. Patients were placed into 1 of 4 hemodynamic subgroups for each technique based on the acquired hemodynamic parameters. Left ventricular filling pressure and cardiac index by Doppler echocardiography and right heart catheterization were similar (21 +/- 8 vs 20 +/- 8 mm Hg; 3.0 +/- 1.2 vs 2.9 +/- 1.2 L/min/m2, respectively) and correlated well with each other (left ventricular filling pressure, r = 0.88; cardiac index, r = 0.92). The Doppler technique accurately placed 73 of 76 studies into the correct hemodynamic subgroup. The noninvasive technique also reliably tracked serial hemodynamic measurements. We conclude that Doppler echocardiography accurately assesses left heart hemodynamics in critically ill patients. Since this technique can be readily acquired, it can be ideal for the rapid assessment of hemodynamic parameters in critically ill patients, especially when right heart catheterization is delayed or is problematic.

Fate of side branches after intracoronary implantation of the Gianturco-Roubin flex-stent for acute or threatened closure after percutaneous transluminal coronary angioplasty.

Side branch occlusion may occur in the course of percutaneous transluminal coronary angioplasty (PTCA), particularly if complicated by site dissection. Concern that the additional placement of a stent may further jeopardize side branches is logical. Consequently, this study analyzed pre-PTCA, post-PTCA, poststent, and 6-month follow-up angiograms of 100 consecutive patients in whom 103 Gianturco-Roubin stents were implanted for acute or threatened closure after PTCA. Side branches were defined as major (> 50% of the stented vessel diameter) and minor (< 50%). Minor branches, often < 1 mm in diameter, were assessed only for patency. One hundred eight major branches, of which 33 were diseased (> 50% stenosis), and 129 minor branches were analyzed. Seven major branches (6%), all of which were diseased before PTCA, and 23 minor branches (18%) were lost after PTCA. Immediately after stent insertion, only 1 additional major and 1 minor branch were lost, whereas 2 of 7 major (29%) and 9 of 23 minor (39%) branches reappeared. At follow-up angiography, 7 major branches (6%) were more stenosed and 6 (6%) were improved compared with the angiogram before PTCA. Only 2 major (2%) and 5 minor (4%) branches remained occluded. Additionally, 2 major and 1 minor branch, which were patent after PTCA and stenting, were occluded at follow-up as a result of total occlusion of the stented segment.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of low-dose aspirin on in vitro platelet aggregation in the early minutes after ingestion in normal subjects.

Aspirin interferes with platelet aggregation by inhibiting the metabolism of arachidonic acid to thromboxane A2. Although both high- and low-dose aspirin therapies are effective for secondary prophylaxis in patients with atherosclerotic vascular disease, the acute response to low-dose aspirin therapy is controversial. Eighteen volunteer subjects ingested 81, 162, or 324 mg of aspirin in a longitudinal crossover study design. Initial doses were randomly assigned and dosing intervals were separated by 2 weeks. Platelet aggregation in response to 0.9 mM arachidonic acid was measured at baseline, 15, 30, 60, and 90 minutes after ingestion. Thromboxane B2 production was assayed on simultaneously obtained samples after stimulation with arachidonic acid. The median inhibition of aggregation was 97%, 97%, and 97% 15 minutes after ingestion of 81, 162, and 324 mg, respectively. Four subjects had < 20% inhibition 15 minutes after ingesting 81 mg, but all 4 had > 90% inhibition after 30 minutes. Thromboxane B2 production declined by > 93% in all subjects at each dose. There was no difference between doses in inhibition of thromboxane B2 production.