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Background: Radioactive stents have been reported to reduce in-stent neointimal thickening. An unexpected increase in neointimal response was observed, however, at the stent-to-artery transitions, the so-called "edge effect." To investigate the factors involved in this edge effect, we studied stents with 1 radioactive half and 1 regular nonradioactive half, thereby creating a midstent radioactive dose-falloff zone next to a nonradioactive stent-artery transition at one side and a radioactive stent-artery transition at the other side., Methods and Results: Half-radioactive stents (n=20) and nonradioactive control stents (n=10) were implanted in the coronary arteries of Yucatan micropigs. Animals received aspirin and clopidogrel as antithrombotics. After 4 weeks, a significant midstent stenosis was observed by angiography in the half-radioactive stents. Two animals died suddenly because of coronary occlusion at this mid zone at 8 and 10 weeks. At 12-week follow-up angiography, intravascular ultrasound and histomorphometry showed a significant neointimal thickening at the midstent dose-falloff zone of the half-radioactive stents, but not at the stent-to-artery transitions at both extremities. Such a midstent response (mean angiographic late loss 1.0 mm) was not observed in the nonradioactive stents (mean loss 0.4 to 0.6 mm; P< 0.01)., Conclusions: The edge effect of high-dose radioactive stents in porcine coronary arteries is associated with the combination of stent injury and radioactive dose falloff.

Background: True 3D reconstruction of coronary arteries in patients based on intravascular ultrasound (IVUS) may be achieved by fusing angiographic and IVUS information (ANGUS). The clinical applicability of ANGUS was tested, and its accuracy was evaluated quantitatively. METHODS AND REUSLTS: In 16 patients who were investigated 6 months after stent implantation, a sheath-based catheter was used to acquire IVUS images during an R-wave-triggered, motorized stepped pullback. First, a single set of end-diastolic biplane angiographic images documented the 3D location of the catheter at the beginning of pullback. From this set, the 3D pullback trajectory was predicted. Second, contours of the lumen or stent obtained from IVUS were fused with the 3D trajectory. Third, the angular rotation of the reconstruction was optimized by quantitative matching of the silhouettes of the 3D reconstruction with the actual biplane images. Reconstructions were obtained in 12 patients. The number of pullback steps, which determines the pullback length, closely agreed with the reconstructed path length (r=0.99). Geometric measurements in silhouette images of the 3D reconstructions showed high correlation (0.84 to 0.97) with corresponding measurements in the actual biplane angiographic images., Conclusions: With ANGUS, 3D reconstructions of coronary arteries can be successfully and accurately obtained in the majority of patients.

Background: Inhomogeneity of dose distribution and anatomic aspects of the atherosclerotic plaque may influence the outcome of irradiated lesions after balloon angioplasty (BA). We evaluated the influence of delivered dose and morphological characteristics of coronary stenoses treated with beta-radiation after BA., Methods and Results: Eighteen consecutive patients treated according to the Beta Energy Restenosis Trial 1.5 were included in the study. The site of angioplasty was irradiated with the use of a beta-emitting (90)Sr/(90)Y source. With the side branches used as anatomic landmarks, the irradiated area was identified and volumetric assessment was performed by 3D intracoronary ultrasound imaging after treatment and at 6 months. The type of tissue, the presence of dissection, and the vessel volumes were assessed every 2 mm within the irradiated area. The minimal dose absorbed by 90% of the adventitial volume (D(v90)Adv) was calculated in each 2-mm segment. Diffuse calcified subsegments and those containing side branches were excluded. Two hundred six coronary subsegments were studied. Of those, 55 were defined as soft, 129 as hard, and 22 as normal/intimal thickening. Plaque volume showed less increase in hard segments as compared with soft and normal/intimal thickening segments (P<0.0001). D(v90)Adv was associated with plaque volume at follow-up after a polynomial equation with linear and nonlinear components (r = 0.71; P = 0.0001). The multivariate regression analysis identified the independent predictors of the plaque volume at follow-up: plaque volume after treatment, D(v90)Adv, and type of plaque., Conclusions: Residual plaque burden, delivered dose, and tiss composition play a fundamental role in the volumetric outcome at 6-month follow-up after beta-radiation therapy and BA.

Background: A recognized limitation of endovascular beta-radiation therapy is the development of new stenosis at the edges of the irradiated area. The combination of injury and low-dose radiation may be the precursor of this phenomenon. We translated the radio-oncological concept of "geographic miss" to define cases in which the radiation source did not fully cover the injured area. The aims of the study were to determine the incidence and causes of geographic miss and evaluate the impact of this inadequate treatment on the outcome of patients treated with intracoronary beta-radiation., Methods and Results: We analyzed 50 consecutive patients treated with beta-radiation after percutaneous coronary intervention. The prescribed dose ranged between 12 and 20 Gy at 2 mm from the source axis. By means of quantitative coronary angiography, the irradiated segment (IRS) and both edges were studied before and after intervention and at 6-month follow-up. Edges that were injured during the procedure constituted the geographic miss edges. Twenty-two edges were injured during the intervention, mainly because of procedural complications that extended the treatment beyond the margins of the IRS. Late loss was significantly higher in geographic miss edges than in IRSs and uninjured edges (0.84+/-0.6 versus 0.15+/-0.4 and 0.09+/-0.4 mm, respectively; P<0.0001). Similarly, restenosis rate was significantly higher in the injured edges (10% within IRS, 40.9% in geographic miss edges, and 1.9% in uninjured edges; P<0.001)., Conclusions: These data support the hypothesis that the combination of injury and low-dose beta-radiation induces deleterious outcome.

Background: This study represents the Heart Center Rotterdam's contribution to the Isostents for Restenosis Intervention Study, a nonrandomized multicenter trial evaluating the safety and feasibility of the radioactive Isostent in patients with single coronary artery disease. Restenosis after stent implantation is primarily caused by neointimal hyperplasia. In animal studies, beta-particle-emitting radioactive stents decrease neointimal hyperplasia by inhibiting smooth muscle cell proliferation., Methods and Results: The radioisotope (32)P, a beta-particle emitter with a half-life of 14.3 days, was directly embedded into the Isostent. The calculated range of radioactivity was 0.75 to 1.5 microCi. Quantitative coronary angiography measurements were performed before and after the procedure and at 6-month follow-up. A total of 31 radioactive stents were used in 26 patients; 30 (97%) were successfully implanted, and 1 was embolized. Treated lesions were in the left anterior descending coronary artery (n=12), the right coronary artery (n=8), or the left circumflex coronary artery (n=6). Five patients received additional, nonradioactive stents. Treated lesion lengths were 13+/-4 mm, with a reference diameter of 2.93+/-0. 47 mm. Minimum lumen diameter increased from 0.87+/-0.28 mm preprocedure to 2.84+/-0.35 mm postprocedure. No in-hospital adverse cardiac events occurred. All patients received aspirin indefinitely and ticlopidine for 4 weeks. Twenty-three patients (88%) returned for 6-month angiographic follow-up; 17% of them had in-stent restenosis, and 13% had repeat revascularization. No restenosis was observed at the stent edges. Minimum lumen diameter at follow-up averaged 1.85+/-0.69 mm, which resulted in a late loss of 0.99+/-0. 59 mm and a late loss index of 0.53+/-0.35. No other major cardiac events occurred during the 6-month follow-up., Conclusions: The use of radioactive stents with an activity of 0.75 to 1.5 microCi is safe and feasible.

Background: Abnormal endothelium-dependent coronary vasomotion has been reported after balloon angioplasty (BA), as well as after intracoronary radiation. However, the long-term effect on coronary vasomotion is not known. The aim of this study was to evaluate the long-term vasomotion of coronary segments treated with BA and brachytherapy., Methods and Results: Patients with single de novo lesions treated either with BA followed by intracoronary beta-irradiation (according to the Beta Energy Restenosis Trial-1.5) or with BA alone were eligible. Of these groups, those patients in stable condition who returned for 6-month angiographic follow-up formed the study population (n=19, irradiated group and n=11, control group). Endothelium-dependent coronary vasomotion was assessed by selective infusion of serial doses of acetylcholine (ACh) proximally to the treated area. Mean luminal diameter was calculated by quantitative coronary angiography both in the treated area and in distal segments. Endothelial dysfunction was defined as a vasoconstriction after the maximal dose of ACh (10(-6) mol/L). Seventeen irradiated segments (89.5%) demonstrated normal endothelial function. In contrast, 10 distal nonirradiated segments (53%) and 5 control segments (45%) demonstrated endothelium-dependent vasoconstriction (-19+/-17% and -9.0+/-5%, respectively). Mean percentage of change in mean luminal diameter after ACh was significantly higher in irradiated segments (P=0.01)., Conclusions: Endothelium-dependent vasomotion of coronary segments treated with BA followed by beta-radiation is restored in the majority of stable patients at 6-month follow-up. This functional response appeared to be better than those documented both in the distal segments and in segments treated with BA alone.

Background: Endovascular radiation appears to inhibit intimal thickening after overstretching balloon injury in animal models. The effect of brachytherapy on vascular remodeling is unknown. The aim of the study was to determine the evolution of coronary vessel dimensions after intracoronary irradiation after successful balloon angioplasty in humans., Methods and Results: Twenty-one consecutive patients treated with balloon angioplasty and beta-radiation according to the Beta Energy Restenosis Trial-1.5 were included in the study. Volumetric assessment of the irradiated segment and both edges was performed after brachytherapy and at 6-month follow-up. Intravascular ultrasound images were acquired by means of ECG-triggered pullback, and 3-D reconstruction was performed by automated edge detection, allowing the calculation of lumen, plaque, and external elastic membrane (EEM) volumes. In the irradiated segments, mean EEM and plaque volumes increased significantly (451+/-128 to 490.9+/-159 mm(3) and 201.2+/-59 to 241.7+/-74 mm(3); P=0.01 and P=0.001, respectively), whereas luminal volume remained unchanged (250.8+/-91 to 249.2+/-102 mm(3); P=NS). The edges demonstrated an increase in mean plaque volume (26.8+/-12 to 32. 6+/-10 mm(3), P=0.0001) and no net change in mean EEM volume (71. 4+/-24 to 70.9+/-24 mm(3), P=NS), resulting in a decrease in mean luminal volume (44.6+/-16 to 38.3+/-16 mm(3), P=0.01)., Conclusions: A different pattern of remodeling is observed in coronary segments treated with beta-radiation after successful balloon angioplasty. In the irradiated segments, the adaptive increase of EEM volume appears to be the major contributor to the luminal volume at follow-up. Conversely, both edges showed an increase in plaque volume without a net change in EEM volume.

Background: Intracoronary brachytherapy appears to be a promising technology to prevent restenosis. Presently, limited data are available regarding the late safety of this therapeutic modality. The aim of the study was to determine the incidence of late (>1 month) thrombosis after PTCA and radiotherapy., Methods and Results: From April 1997 to March 1999, we successfully treated 108 patients with PTCA followed by intracoronary beta-radiation. Ninety-one patients have completed at least 2 months of clinical follow-up. Of these patients, 6.6% (6 patients) presented with sudden thrombotic events confirmed by angiography 2 to 15 months after intervention (2 balloon angioplasty and 4 stent). Some factors (overlapping stents, unhealed dissection) may have triggered the thrombosis process, but the timing of the event is extremely unusual. Therefore, the effect of radiation on delaying the healing process and maintaining a thrombogenic coronary surface is proposed as the most plausible mechanism to explain such late events., Conclusions: Late and sudden thrombosis after PTCA followed by intracoronary radiotherapy is a new phenomenon in interventional cardiology.

Background: With the thrombogenic tendency and permanent implant nature of metallic stents, synthetic polymers have been proposed as candidate materials for stents and local drug delivery designs. We investigated the biocompatibility of several synthetic polymers after experimental placement in the coronary artery., Methods and Results: Five different biodegradable polymers (polyglycolic acid/polylactic acid [PGLA], polycaprolactone [PCL], polyhydroxybutyrate valerate [PHBV], polyorthoester [POE], and polyethyleneoxide/polybutylene terephthalate [PEO/ PBTP]) and three nonbiodegradable polymers (polyurethane [PUR], silicone [SIL], and polyethylene terephthalate [PETP]) were tested as strips deployed longitudinally across 90 degrees of the circumferential surface of coil wire stents. Appropriately sized polymer-loaded stents were implanted in porcine coronary arteries of 2.5- to 3.0-mm diameter. Four weeks after implantation, stent patency was assessed by angiography followed by microscopic examination of the coronary arteries. The biodegradable PCL, PHBV, and POE and the nonbiodegradable PUR and SIL evoked extensive inflammatory responses and fibrocellular proliferation (thickness of tissue response: 0.79 +/- 0.22, 1.12 +/- 0.01, 2.36 +/- 0.60, 1.24 +/- 0.36, and 1.43 +/- 0.15 mm, respectively). Less but still severe responses were observed for the biodegradable PGLA and PEO/PBTP (0.46 +/- 0.18 and 0.61 +/- 0.23 mm, respectively) and for the nonbiodegradable PETP (0.46 +/- 0.11 mm)., Conclusions: An array of both biodegradable and nonbiodegradable polymers has been demonstrated to induce a marked inflammatory reaction within the coronary artery with subsequent neointimal thickening, which was not expected on the basis of in vitro tests. The observed tissue response may be attributable to a combination of parent polymer compound, biodegradation products, and possibly implant geometry.

Background: The new, less shortening, self-expanding Wallstent is characterized by longitudinal flexibility, a protective membrane, a low profile, and a customized range of diameters (3.5 to 6.0 mm). The recent modification of the braiding angle of the Wallstent has resulted in a new device with less shortening on expansion and a concomitant reduction in radial force. We hypothesized that the enforced mechanical remodeling produced by the selection of an oversized Wallstent might result in improved accommodation of subsequent reactive intimal hyperplasia and prevention of chronic recoil of the vessel., Methods and Results: To prove this hypothesis, we recently implanted 44 new, less shortening Wallstents in 35 native coronary arteries in 35 patients with acute or threatened closure after balloon angioplasty, according to a strategy of oversizing of Wallstent diameter and complete coverage of the lesion length. The initial and 6-month follow-up angiograms were analyzed with a computer-based quantitative coronary angiography (QCA) system. Acute gain (minimal luminal diameter [MLD] post minus MLD pre) and late loss (MLD post minus MLD at follow-up) were examined. Stent deployment was successful in 44 of 44 attempts (100%). Nominal stent diameter used was 1.40 mm larger than the maximal vessel diameter. One patient (3%) with a dilated but unstented lesion proximal to the stented segment sustained a subacute occlusion on day 1 associated with myocardial infarction. Event-free survival at 30 days after stent implantation was 97% (34 of 35 patients). Of the 34 patients eligible for 6-month angiographic follow-up, 3 who were asymptomatic declined repeat angiography. MLD (and percent diameter stenosis [% DS]) changed from 0.83 +/- 0.50 mm (72%) pre through 3.06 +/- 0.48 mm (15%) post to 2.27 +/- 0.74 mm (28%) at follow-up. Acute gain was 2.23 +/- 0.63 mm, and late loss was 0.78 +/- 0.61 mm. Angiographic restenosis ( > 50% DS) was observed in 5 of 31 patients (16%) at 6 months, all of whom underwent repeat angioplasty. Thus, the overall event-free survival at 6-month follow-up was 83% (29 of 35 patients)., Conclusions: The oversized Wallstent implantation with complete coverage of the lesion length conveyed a favorable 6-month clinical and angiographic outcome. The large acute gain obtained by the Wallstent afforded greater accommodation of the subsequent late loss. The enforced mechanical remodeling by oversized new Wallstents may result in prevention of acute and chronic recoil of the vessel wall and subsequently a lower restenosis rate at follow-up.

Background: The use of stents improves the result after balloon coronary angioplasty. Thrombogenicity of stents is, however, a concern. In the present study, we compared stents with an antithrombotic coating with regular stents., Methods and Results: Regular stents were placed in coronary arteries of pigs receiving no aspirin (group 1; n = 8) or aspirin over 4 weeks (group 2, n = 10) or 12 weeks (group 3, n = 9). Stents coated with heparin (antithrombin III uptake, 5 pmol/stent) were placed in 7 pigs that did not receive aspirin (group 4). The other animals received aspirin and coated stents with a heparin activity of 12 pmol antithrombin III/stent (group 5, n = 10) or 20 pmol/stent (group 6, n = 10; group 7, n = 10). Quantitative arteriography was performed at implantation and after 4 (groups 1, 2, and 4 through 6) or 12 weeks (groups 3 and 7). In an additional 5 animals, five regular and five coated stents (20 pmol/stent) were placed and explanted after 5 days for examination of the early responses to the implants. Thrombotic occlusion of the regular stent occurred in 9 of 27 in groups 1 through 3. However, in 0 of 30 of the animals receiving high-activity heparin-coated stents (groups 5 through 7), thrombotic stent occlusion was observed (P < .001). Histological analysis at 4 weeks showed that the neointima in group 6 was thicker compared with its control group 2 (259 +/- 104 and 117 +/- 36 microns, P < .01), but at 12 weeks the thickness was similar (152 +/- 61 and 198 +/- 49 microns, respectively). Comparison at 5 days suggested delayed endothelialization of the coating., Conclusions: High-activity heparin coating of stents eliminates subacute thrombosis in porcine coronary arteries.

Background: The purpose of the Benestent-II Pilot Study was to evaluate the safety of delaying and eliminating anticoagulant therapy in patients receiving a heparin-coated stent in conjunction with antiplatelet drugs., Methods and Results: The study consisted of three initial phases (I, II, III) during which resumption of heparin therapy after sheath removal was progressively deferred by 6, 12, and 36 hours. In phase IV, coumadin and heparin were replaced by 250 mg ticlopidine and 100 mg aspirin. Of the 207 patients with stable angina pectoris and a de novo lesion in whom heparin-coated stent implantation was attempted, implantation was successful in 202 patients (98%). Stent thrombosis did not occur during all four phases, and the overall clinical success rate at discharge was 99%. Bleeding complications requiring blood transfusion or surgery fell from 7.9% in phase I to 5.9%, 4%, and 0% in the three following phases. Hospital stay was 7.4, 6.1, 7.2, and 3.1 days for the consecutive phases. The restenosis rate for the combined four phases was 13% (15% in phase I, 20% in phase II, 11% in phase III, and 6% in phase IV). The overall rate of reintervention for the four phases was 8.9%. At 6 months, 84%, 75%, 94%, and 92% of the patients of phases I to IV, respectively, were event free. For the four phases, the event-free rate was 86%, which compares favorably with the rate observed in the Benestent-I study (80%; relative risk, 0.68 [0.45 to 1.04])., Conclusions: The implantation of stents coated with polyamine and end-point-attached heparin in stable patients with one significant de novo coronary lesion is well tolerated, is associated with no (sub)acute stent thrombosis, and results in a favorable event-free survival after 6 months.

Background: Inefficacy of systemic drug administration for restenosis prevention may partially relate to insufficient local drug concentration. This study aimed to evaluate the acute feasibility and long-term outcome of using an infusion-perfusion coil balloon, Dispatch., Methods and Results: In 22 patients after balloon angioplasty, the coil balloon was studied for (1) feasibility of local heparin delivery, (2) symptoms and signs of ischemia during prolonged deployment compared with angioplasty balloon occlusion, (3) coronary pressure and flow distal to the inflated device, and (4) long-term clinical and angiographic results. During prolonged intracoronary deployment of the coil balloon (29 +/- 8 minutes), 5 of 22 patients developed mild chest pain versus 20 of 22 during angioplasty (275 +/- 283 seconds). Neither hemodynamic nor vectorcardiographic signs of ischemia were detected, in contrast to angioplasty balloon occlusion. Baseline flow across the coil balloon was 44 +/- 31 mL/min, increasing by a factor of 1.8 +/- 0.7 during pharmacologically induced hyperemia. A mean volume of 14.2 +/- 6.1 mL containing 1416 +/- 608 IU of heparin was infused locally at a pressure of 122 +/- 54 mm Hg. At 7 +/- 1-month follow-up, 1 asymptomatic patient had died, and of the remaining 21, 17 (81%) were asymptomatic. Angiographic follow-up was obtained in 15 of 21 patients (71%), including all 4 symptomatic patients. Mean minimal luminal diameter after the procedure was 2.16 +/- 0.49 mm and at follow-up, 1.89 +/- 0.45 mm, which corresponds to a restenosis rate (diameter stenosis > or = 50%) of 7% (1/15)., Conclusions: Intracoronary use of the coil balloon after balloon angioplasty proved to be feasible and subjectively as well as objectively well tolerated during prolonged deployment by virtue of its perfusion properties. High volumes of heparin solution can be infused locally at very low pressure. No unfavorable clinical or angiographic long-term effects were observed.

Background: Balloon angioplasty damages endothelial cells and stimulates smooth muscle cell proliferation. The effects of local cytotoxic drug therapy on formation of neointima and late endothelial function are not known. This study was designed to determine whether direct infusion of mitomycin C via a microporous balloon catheter could significantly reduce formation of neointima after angioplasty. Furthermore, we investigated whether endothelial cell function is normal 7 weeks after the initial microporous angioplasty procedure., Methods: In 34 New Zealand white rabbits, bilateral external iliac arteries underwent balloon angioplasty, followed by either high-dose (0.66 mg/kg) or low-dose (0.025 mg/kg) mitomycin C in one iliac artery and saline infusion in the contralateral artery, and a control group was given saline in both vessels. Formation of neointima was measured in the iliac arteries after 7 weeks by morphometry. Before sacrifice of 17 'angioplasty' rabbits and three undamaged rabbits, graded doses of acetylcholine and isosorbide dinitrate were infused in the distal aorta, and the iliac artery diameter was measured by computerized quantitative angiography., Results: No significant differences in the absolute area of the intima or the intima: media ratio were demonstrated between control arteries and arteries that were directly infused with either high-dose or low-dose mitomycin. However, within the high-dose group, the mitomycin-treated vessel had a significantly lesser extent of formation of intimal hyperplasia (0.17 +/- 0.03 versus 0.27 +/- 0.03 mm2, P < 0.03) and lower intima: media area ratio (0.60 +/- 0.31 versus 1.09 +/- 0.42, P < 0.03) than the contralateral saline-treated vessel. Significant increases in mean luminal iliac artery diameter [0.18 mm (10.5%) at 1 min and 0.23 mm (13%) at 3 min, P < 0.05)] from baseline values following acetylcholine were observed in previously damaged iliac arteries. This vasodilatory response was not different from that in undamaged arteries., Conclusions: Local delivery of mitomycin C had no favorable effect on the inhibition of intimal hyperplasia compared with control saline-treated arteries. Normal endothelial function, determined on the basis of dilatory response to acetylcholine, can be demonstrated 7 weeks after balloon angioplasty injury.

Objective: To test the hypothesis that the cardiovascular responses of dopamine and dobutamine might be affected by the cardiovascular conditions., Design: Prospective, controlled dose-response comparison of dopamine and dobutamine., Setting: Laboratory for Experimental Cardiology at a university., Subjects: Normal conscious pigs and conscious pigs with chronic left ventricular dysfunction induced by occlusion of a coronary artery 3 to 4 wks before measurements were obtained., Interventions: Intravenous infusions of dopamine and dobutamine at rates of 1 to 25 micrograms/kg/min., Measurements and Main Results: Left ventricular function was characterized by a lower cardiac output in the pigs with left ventricular dysfunction (23%), stroke volume (34%), and left ventricular pressure (15%), and a higher heart rate (16%), peripheral resistance (41%), and left ventricular end-diastolic pressure (96%) than the normal pigs. Dopamine increased cardiac output to the same extent in the animals with failure as in the normal animals; stroke volume increased only in the animals that had left ventricular dysfunction. The vasodilatory response to dopamine was also similar, but the increase in left ventricular pressure was attenuated similar, in the animals with left ventricular dysfunction, compared with normal animals. Dobutamine showed cardiovascular effects equivalent to dopamine. Left ventricular work, depressed at baseline, increased more rapidly during infusion of dopamine (or dobutamine) in the animals with heart failure than in normal animals., Conclusions: Both dopamine and dobutamine increased cardiac output in conscious pigs with chronic heart failure. Unlike the response in normal conscious pigs, in which only heart rate increased, in animals with heart failure, these agents enhanced both stroke volume and heart rate.

Intravenous (i.v.) infusions (1, 2.5, 5, and 10 micrograms/kg/min for 10 min) were used to evaluate the cardiovascular effects of epinine (N-methyl-dopamine) in 8 conscious pigs. Epinine is a nonselective and nonspecific dopamine (DA) agonist, that also stimulates alpha- and beta-adrenoceptors. Epinine (1-5 microgram/kg/min) increased cardiac output (CO) by up to 15 +/- 5% (p less than 0.05), owing to an increase in heart rate (HR, 24 +/- 6%), but an increase in stroke volume (SV, 16 +/- 4%) caused the further increase in CO at 10 micrograms/kg/min. Mean arterial blood pressure decreased gradually from 100 +/- 5 mm Hg to 84 +/- 4 mm Hg during infusions up to 5 microgram/kg/min, but increased to 89 +/- 4 mm Hg during infusion of 10 micrograms/kg/min (p less than 0.05). Systemic vascular resistance had decreased from 36.5 +/- 2.8 to 27.5 +/- 3.0 mm Hg/L/min after infusion of 5 micrograms/kg/min but did not change further during infusion of 10 micrograms/kg/min. LV dP/dtmax increased only at 10 micrograms/kg/min. Myocardial blood flow did not change at any dose, owing to metabolically regulated coronary vasodilatation (myocardial work did not change). Flow to the adrenals (up to 110 +/- 37%) and the spleen (up to 95 +/- 13%) increased dose dependently. Cerebral blood flow increased only at the highest dose (15 +/- 5%, p less than 0.05); flow to the kidneys, liver, small intestine, and skeletal muscle did not change. Flow decreased to the stomach (21 +/- 5%) and skin (for doses less than 2.5 micrograms/kg/min).(ABSTRACT TRUNCATED AT 250 WORDS)

The cardiovascular effects of the phenyldihydropyridine derivative elgodipine (0.3, 1, 3, 10, and 30 microgram/kg/min) were studied in normal conscious pigs and in pigs with chronic left ventricular dysfunction (LVD, caused by coronary artery occlusion) without and after beta-adrenoceptor blockade with propranolol (0.5 mg/kg + 0.5 mg/kg/h). In normal pigs, elgodipine increased cardiac output from 2.57 +/- 0.09 to 5.21 +/- 0.24 L/min (p less than 0.05) as a result of a doubling of the heart rate. Mean arterial blood pressure decreased from 94 +/- 2 to 76 +/- 3 mm Hg (p less than 0.05) as a result of a decrease in systemic vascular resistance. Left ventricular (LV) dP/dtmax increased (by up to 78 +/- 9%), but left ventricular end-diastolic pressure (LVEDP) remained unchanged. After propranolol administration elgodipine did not increase LV dP/dtmax, and the increase in heart rate was attenuated, resulting in a smaller increase in cardiac output (from 2.11 +/- 0.13 to 3.09 +/- 0.23 L/min, p less than 0.05), but an unchanged vasodilator response. In pigs with LVD, elgodipine increased cardiac output and LV dP/dtmax less than in normal animals, but the vasodilator response was not affected. LVEDP decreased from 14.6 +/- 1.6 to 11.7 +/- 2.5 mm Hg (p less than 0.05). In animals with LVD, propranolol caused a more severe depression of systemic hemodynamics, but did not modify the cardiovascular responses to elgodipine. Its cardiovascular profile suggests that elgodipine may not only be useful in the treatment of cardiovascular disorders for which other dihydropyridines are already in use, but also in mild chronic heart failure.

Background: Intracoronary stents may be effective when used as "bail-out" devices for acute complications after percutaneous transluminal coronary angioplasty. Furthermore, preliminary reports have demonstrated some promising results with stents with regard to the reduction of restenosis. Several stent devices are available for preclinical and clinical evaluation. The use of these stainless-steel stents has been limited by poor visibility during fluoroscopy and thrombogenicity during the first days to weeks after implantation. We therefore investigated the immediate and short-term effects on arterial patency of a new, radiopaque, balloon-expandable coil stent in normal coronary arteries of pigs., Methods and Results: In 10 animals, a stent was placed in two of the three epicardial coronary arteries. During the implantation procedure, the animals received heparin; after the procedure, no antithrombotic drugs were administered. After 1 week (five animals and 10 stents) or 4 weeks (five animals and 10 stents), repeat angiography was performed, followed by pressure-fixation of the coronary arteries for light and electron microscopic examination. Angiographic analysis revealed that all stented coronary segments were patent and without signs of intraluminal defects. Scanning electron microscopy showed complete endothelial covering of all stents within 7 days. Light microscopy showed a reduced tunica media locally under the stent wires, which resulted from exerted pressure. The neointima on top of the stent wires measured 56 microns (range, 42-88 microns) after 1 week and 139 microns (range, 84-250 microns) after 4 weeks., Conclusions: Results from this study show that this radiopaque endoprosthesis can be safely placed in normal coronary arteries of pigs. After 4 weeks, all stents were patent and there was no need for additional antithrombotic treatment, whereas neointimal proliferation was limited.

The acute systemic hemodynamic effects of the calcium antagonist nisoldipine and the pyridazinone-derivative pimobendan, a phosphodiesterase inhibitor with vasodilating as well as positive inotropic properties, were studied in conscious pigs with chronic heart failure. Left ventricular (LV) dysfunction, manifested by a 25% decrease in cardiac output (CO), a 35% increase in systemic vascular resistance (SVR), and a doubling of the left ventricular filling pressure, was induced by a proximal ligation of the left circumflex coronary artery. Two to three weeks after myocardial infarction, cumulative 10-min infusions of either nisoldipine (0.05, 0.1, 0.25, and 0.5 micrograms/kg/min), pimobendan (2.5, 5, 12.5, and 25 micrograms/kg/min) or the solvents were administered. Infusion of the solvents did not affect any of the hemodynamic variables. Both nisoldipine and pimobendan normalized CO and exhibited a similar cardiac profile [systemic vasodilatation, reduction in left ventricular filling pressure, and an increase in heart rate (HR)] except for the significantly (p less than 0.05) larger increase in LVdP/dtmax with pimobendan (85%) than with nisoldipine (45%). In animals with heart failure, lower doses of both nisoldipine (twice) and pimobendan (four times) were needed to elicit a 30% reduction in SVR than in animals with normal pump function. For both drugs, the slope of the line describing the vasodilatory and positive inotropic properties shifted more in favor of the vasodilatory actions during heart failure (p less than 0.05). We conclude that in swine with chronic LV dysfunction nisoldipine, despite its lack of inotropic properties, appeared to improve ventricular function to the same extent as the primary positive inotropic agent pimobendan.