Comparison of slow oscillating versus fast balloon inflation strategies for coronary angioplasty.

Previous studies suggest that slow and/or oscillating balloon inflation during coronary angioplasty may decrease the incidence of coronary dissection and improve clinical outcomes. To compare the effect of slow oscillating versus conventional fast inflation techniques on the incidence of severe coronary dissection during angioplasty, 622 patients were randomized to slow oscillating inflation versus fast inflation. Angiographic outcomes of the procedures and in-hospital clinical events were recorded. The primary end point of severe (type C, D, E, F) dissection occurred in 7.7% of patients undergoing slow oscillation and 6.6% of patients undergoing fast inflation (p = 0.87). Major complications (death, urgent coronary artery bypass graft surgery, stroke, abrupt closure, or Q-wave myocardial infarction) occurred in 4.7% of patients undergoing slow oscillation and 3.5% of patients undergoing fast inflation (p = 0.45). The 2 inflation strategies did not differ in the pressure at which the balloon achieved full expansion, angiographic success rate, residual stenosis, and incidence of all minor and/or major complications. We conclude that there is no benefit of slow oscillating inflation over routine fast inflation in angioplasty. Slow oscillating inflation did not dilate lesions at lower pressures, decrease the incidence of dissection or severe dissection, or reduce the incidence of adverse clinical outcomes.

Reduction in angioplasty complications after the introduction of coronary stents: results from a consecutive series of 2242 patients.

The introduction of coronary stents for the treatment of acute vessel closure has probably improved the safety of angioplasty, but little data are available regarding angioplasty complication rates when bailout stenting is available. Therefore baseline and patient outcome data for 2242 consecutive patients treated at a single tertiary referral center were compared before and after bailout coronary stenting was introduced. Patients treated after stents became available were more likely to have diabetes (16% prestent availability vs 19% poststent, p < 0.05), unstable angina (61% prestent vs 70% poststent, p < 0.01), and to have received intravenous nitroglycerin before the procedure (22% prestent vs 28% poststent, p < 0.01). Major complications occurred in 4.1% of patients before stent availability and 2.0% afterwards (p < 0.01). These complications included in-hospital death (1.1% prestent vs 0.7% poststent, p = not significant [NS]), Q wave myocardial infarction (0.5% prestent vs 0.3% poststent, p = NS), and emergency bypass surgery (2.9% prestent vs 1.1% poststent, p < 0.01). The introduction of coronary stents was associated with a > 50% reduction in major complications despite greater patient acuity. The traditionally reported complication rates for angioplasty appear not to apply when ballout stenting is available.

Decreased type II/type I TGF-beta receptor ratio in cells derived from human atherosclerotic lesions. Conversion from an antiproliferative to profibrotic response to TGF-beta1.

Atherosclerosis and postangioplasty restenosis may result from abnormal wound healing. The present studies report that normal human smooth muscle cells are growth inhibited by TGF-beta1, a potent wound healing agent, and show little induction of collagen synthesis to TGF-beta1, yet cells grown from human vascular lesions are growth stimulated by TGF-beta1 and markedly increase collagen synthesis. Both cell types increase plasminogen activator inhibitor-1 production, switch actin phenotypes in response to TGF-beta1, and produce similar levels of TGF-beta activity. Membrane cross-linking of 125I-TGF-beta1 indicates that normal human smooth muscle cells express type I, II, and III receptors. The type II receptor is strikingly decreased in lesion cells, with little change in the type I or III receptors. RT-PCR confirmed that the type II TGF-beta1 receptor mRNA is reduced in lesion cells. Transfection of the type II receptor into lesion cells restores the growth inhibitory response to TGF-beta1, implying that signaling remains responsive. Because TGF-beta1 is overexpressed in fibroproliferative vascular lesions, receptor-variant cells would be allowed to grow in a slow, but uncontrolled fashion, while overproducing extracellular matrix components. This TGF-beta1 receptor dysfunction may be relevant for atherosclerosis, restenosis and related fibroproliferative diseases.

Specific inhibition of eIF-5A and collagen hydroxylation by a single agent. Antiproliferative and fibrosuppressive effects on smooth muscle cells from human coronary arteries.

Restenosis occurs in 35% of patients within months after balloon angioplasty, due to a fibroproliferative response to vascular injury. These studies describe a combined fibrosuppressive/antiproliferative strategy on smooth muscle cells cultured from human primary atherosclerotic and restenotic coronary arteries and from normal rat aortas. L-Mimosine suppressed the posttranslational hydroxylation of the precursors for collagen and for eukaryotic initiation factor-5A (eIF-5A) by directly inhibiting the specific protein hydroxylases involved, prolyl 4-hydroxylase (E.C. 1.14.11.2) and deoxyhypusyl hydroxylase (E.C. 1.14.99.29), respectively. Inhibition of deoxyhypusyl hydroxylation correlated with a dose-dependent inhibition of DNA synthesis. Inhibition of prolyl hydroxylation caused a dose-dependent reduction in the secretion of hydroxyproline-containing protein and decreased the formation of procollagen types I and III. The antifibroproliferative action could not be attributed to nonspecific or toxic effects of mimosine, appeared to be selective for the hydroxylation step in the biosynthesis of the procollagens and of eIF-5A, and was reversible upon removal of the compound. The strategy of targeting these two protein hydroxylases has important implications for the pathophysiology of restenosis and for the development of agents to control fibroproliferative diseases.

Management of the arterial puncture site.

With more complex interventional procedures, such as intracoronary stent placement, there is a higher incidence of procedural related peripheral vascular complications including pseudoaneurysm and hemorrhage. In these procedures, the amount of anticoagulation as well as the use of thrombolytic agents intraprocedurally increases the risk of complication. Meticulous care during vascular access, careful use and monitoring of anticoagulation, and patient selection are helpful in reducing the risk. Newer vascular hemostatic devices utilizing biodegradable collagen plugs might be of advantage since they allow early sheath removal without interrupting anticoagulation and, therefore, early ambulation. However, it remains to be determined, whether these devices are effective in reducing complications, duration of bed rest and hospitalization, or improvement of stent patency. Newer designs, e.g., coated or biodegradable stents, or different deployment strategies might reduce the need of anticoagulation and lower the risk of peripheral vascular complications.

Percutaneous transluminal coronary angioplasty of a right coronary artery arising from the left main coronary artery.

Angioplasty of anomalous coronary arteries presents unique technical challenges. Correct guiding catheter selection is important to ensure adequate access to the anomalous vessel and to provide support to cross the lesion. A case of successful PTCA of a lesion in an anomalous right coronary artery arising from the left main coronary artery is presented.

Uptake of hematoporphyrin derivative by atheromatous plaques: studies in human in vitro and rabbit in vivo.

Hematoporphyrin derivative, a photosensitive material used to identify and treat neoplastic tissue in humans, has been found to localize in atheromatous plaques in animals and has recently been found in postmortem human atherosclerotic plaques. It is not known whether human plaques take up hematoporphyrin derivative in vivo. In five patients undergoing surgical vascular procedures, specimens containing atheromatous plaques were removed and immediately incubated in autologous oxygenated blood at 37 degrees C with hematoporphyrin derivative at a clinically relevant concentration for 2 hours. On exposure to ultraviolet light, porphyrin fluorescence was noted throughout each plaque, whereas adjacent plaque-free tissue showed no fluorescence. To compare in vitro with in vivo hematoporphyrin derivative uptake by plaques, the fluorescence of three types of arterial lesions (induced by a high cholesterol diet, catheters or balloon injury) was studied in 16 New Zealand White rabbits. Each lesion fluoresced selectively with the same intensity whether hematoporphyrin derivative exposure was performed in vitro or in vivo. Fluorescence microscopy did not show a difference in the pattern of hematoporphyrin derivative fluorescence between in vitro and in vivo specimens. The results suggest that human atheromatous plaques should take up hematoporphyrin derivative in vivo and are, therefore, potentially suitable for photochemical treatment as a new therapeutic approach to atherosclerosis.

Uptake of hematoporphyrin derivative by valvular vegetations in experimental infective endocarditis.

Drugs that localize in valvular vegetations may be useful in the diagnosis and treatment of infective endocarditis. We therefore tested the hypothesis that parenterally injected hematoporphyrin derivative (HPD), which is concentrated in tumors and atherosclerotic plaques, localizes in the vegetations of experimental infective endocarditis. In 14 rabbits, various bacteria were given intra-arterially immediately after injury to the aortic valve. In 12 additional rabbits, sterile vegetations on the aortic valve were produced by the trauma caused by an indwelling catheter that had been in place over a long period. HPD, 2.5 mg/kg, was injected intravenously 1 to 2 days before the animals were killed in six rabbits with sterile vegetations and in seven rabbits with infected vegetations. In all rabbits, multiple vegetations on the aortic valve leaflets were identified. On exposure to ultraviolet light, strong porphyrin fluorescence of all vegetations, whether sterile or infected, was observed only in rabbits given HPD. In two rabbits given HPD 10 weeks after catheter implantation across the aortic valve, however, only mild fluorescence could be detected in healing endocardial vegetations. In frozen sections of HPD-laden lesions, a patchy distribution of fluorescence was observed that was similar to the pattern of HPD localization in atheromatous plaques. Since vegetations in experimental infective endocarditis selectively concentrate HPD, porphyrins could be useful in the diagnosis and treatment of infective endocarditis.

Coronary angioscopy during cardiac catheterization.

Coronary angioscopy should permit direct inspection of the luminal cross section and identification of disease. The feasibility of introducing a 5F Olympus Ultrathin fiberscope into the obstructed right coronary artery in five patients after routine cardiac catheterization by the brachial approach was therefore tested. An 8.3F USCI woven Dacron angioplasty guiding catheter was modified to enlarge its lumen. After engaging the right coronary ostium with the catheter, an attempt was made to pass the angioscope coaxially to the tip of the catheter. Visualization of the coronary lumen was then achieved in three patients by manually injecting 5 to 10 cc of normal saline solution through the guiding catheter at 2 to 3 cc/s. White atheromatous plaque could be seen near the site of obstruction in each case. In two patients, a lack of sufficient flexibility in the distal 2 cm of the angioscope prevented passage to the catheter tip. Preliminary experience with a videoendoscopic system suggests that this monitoring technique is essential for the adequate performance of angioscopy and for recording dynamic changes during blood displacement. Geometric distortion of the image and nonlinearities in magnification and light reflex with a decreasing lens to object distance make quantitative evaluation of the lumen difficult. Lack of an angulation system further contributes to this problem and, more importantly, restricts passage of the angioscope to the proximal 1 to 2 cm segments of coronary arteries. Although coronary angioscopy may have research and clinical applications in the future, these technical problems should first be addressed.