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Electron cryomicroscopy and icosahedral reconstruction are used to obtain the three-dimensional structure of the 1250-A-diameter herpesvirus B-capsid. The centers and orientations of particles in focal pairs of 400-kV, spot-scan micrographs are determined and iteratively refined by common-lines-based local and global refinement procedures. We describe the rationale behind choosing shared-memory multiprocessor computers for executing the global refinement, which is the most computationally intensive step in the reconstruction procedure. This refinement has been implemented on three different shared-memory supercomputers. The speedup and efficiency are evaluated by using test data sets with different numbers of particles and processors. Using this parallel refinement program, we refine the herpesvirus B-capsid from 355-particle images to 13-A resolution. The map shows new structural features and interactions of the protein subunits in the three distinct morphological units: penton, hexon, and triplex of this T = 16 icosahedral particle.

Background: High levels of hyperoxemia may have utility in the treatment of regional tissue ischemia, but current methods for its implementation are impractical. A catheter-based method for infusion of O2, dissolved in a crystalloid solution at extremely high concentrations, ie, 1 to 3 mL O2/g (aqueous oxygen [AO]), into blood without bubble nucleation was recently developed for the potential hyperoxemic treatment of regional tissue ischemia., Methods and Results: To test the hypotheses that hypoxemia is correctable and that hyperoxemia can be produced locally by AO infusion, normal saline equilibrated with O2 at 3 MPa (30 bar; 1 mL O2/g) was delivered into arterial blood in two different animal models. In 15 New Zealand White rabbits with systemic hypoxemia, AO was infused into the midabdominal aorta at 1 g/min. Mean distal arterial PO2 increased to 236+/-113 and 593+/-114 mm Hg on 1-hour periods of air and O2 breathing, respectively, from a baseline of 70+/-10 mm Hg (P<.01). In contrast, infusion of ordinary normal saline in a control group (n=7) had no effect on arterial PO2. No differences between groups (P>.05) in temporal changes in blood counts and chemistries were identified. In 10 dogs, low coronary blood flow in the circumflex artery was delivered with a roller pump through the central channel of an occluding balloon catheter. Hypoxemic, normoxemic, and AO-induced hyperoxemic blood perfusates (mean PO2, 52+/-4, 111+/-22, and 504+/-72 mm Hg, respectively) were infused for 3-minute periods in a randomized sequence. Short-axis two-dimensional echocardiography demonstrated a significant decrease (P<.05) in left ventricular ejection fraction compared with baseline physiological values with low-flow hypoxemic and normoxemic perfusion but not with low-flow hyperoxemic perfusion., Conclusions: Intra-arterial AO infusion was effective in these models for regional correction of hypoxemia and production of hyperoxemia.

A 37-year-old man, who had received 3 weeks of antimicrobial therapy for aortic value endocarditis, presented with an acute anteroseptal wall myocardial infarction. Coronary angiography demonstrated occlusion of the mid left anterior descending artery, thought to have been caused by embolization of a sterile vegetation. Following failure of balloon dilation to achieve vessel patency, this was achieved by placement of an intracoronary stent.

The adjoint form of the photon transport equation is applied to a generalized fluorescence detection problem, and its accuracy is empirically tested. This approach can be interpreted as mathematically reversing the temporal flow of fluorescent photons; that is, they are tracked from the detector back to potential sites of origin in the scattering medium. The result is a distribution of potential fluorescing sites that, when properly normalized, gives a probability field of the relative importance of the photon starting position and direction to the resulting signal. This adjoint solution can be combined with the temporally forward-derived distribution of absorbed excitation photons to evaluate the fluorescence excitation detection scheme. This bypasses the normal, temporal derivation wherein the fluorescence transport solution is dependent on the result of the excitation transport solution.

Laser balloon angioplasty (LBA) has been shown to acutely increase angiographic luminal dimensions after conventional balloon angioplasty (PTCA) without a favorable impact on chronic restenosis. Experimentally, laser and thermal energy enhance binding of heparin to the injured arterial wall and to the thrombus. In view of the anticoagulant, antiproliferative, and antifibrotic activities of the drug, a pilot study was performed to evaluate the potential safety and efficacy of LBA combined with local heparin therapy. Ten patients scheduled for elective PTCA were entered in the study. In each patient, a single lesion was treated with a laser balloon and coated with a heparin film (3000 I.U. at a concentration > 100,000 I.U./gm) immediately after optimal PTCA. The mean minimum luminal diameter and mean percent stenosis of the 10 treated lesions after PTCA were 1.62 +/- 0.39 mm and 37% +/- 9%, respectively. After LBA and local heparin therapy, the mean minimal lumen diameter increased to 2.01 +/- 0.34 mm (p < 0.01) and the mean percent stenosis decreased to 20% +/- 10% (p < 0.01). Systemic heparin was discontinued immediately after the procedure in all patients. Acute or inhospital complications, either major or minor, occurred in none (0%) of the 10 patients (95% confidence interval 0% to 31%); all were discharged home on the day after the procedure. All patients remained well and free of cardiac symptoms for at least 2 months after the procedure. However, restenosis developed in six (60%) of the 10 patients (95% confidence interval 26% to 88%) 2 to 6 months after the procedure. The results suggest that LBA and local heparin therapy, with discontinuation of systemic heparin immediately after angioplasty, is a safe treatment modality that yields favorable acute angiographic results.

Purpose: To determine the accuracy and reproducibility of luminal dimension measurements of a newly developed method of quantitative angioscopy., Methods: A method was developed for quantitation of luminal dimensions during angioscopy, as variation in magnification with lens-object distance and ambiguity associated with identification of corresponding points about the circumference of a given discrete cross-section render subjective estimates unreliable. A transverse ring of fiberoptically transmitted light was emitted from a guidewire or its housing at a known distance from the distal end of an angioscope and discrete cross-sections of interest were observed as the ring of light was reflected from the luminal surface. Caliper measurement of the diameter of the light ring image (< 50 mW at 488/515 nm), obtained on angioscopic video recordings of cylindrical phantom vessels of known dimensions, was performed by three observers on five occasions., Results: The mean absolute difference between measured and known luminal diameter (n = 405 observations) was 65 microns +/- 35 microns and the mean coefficient of variation was 4.2%, and the mean difference between measured and known areas (n = 195 observations) was 0.4 mm2, with a mean coefficient of variation of 6.5%., Conclusion: By use of this new lightwire method, luminal dimensions can now be measured in vitro with a high degree of accuracy and reproducibility during angioscopy.

This study was designed to assess the potential relationship between the late loss of angiographic luminal diameter and biochemical abnormalities of arterial wall collagen in rabbits subjected to angioplasty, and to test the hypothesis that beta-aminopropionitrile (beta APN), an inhibitor of lysyl oxidase, would inhibit such changes when administered orally for 1 mo after angioplasty. Endovascular injury was induced in rabbit iliac arteries by ipsilateral balloon angioplasty (BA) and by contralateral balloon angioplasty accompanied by exposure to continuous wave neodymium: yttrium aluminum garnet laser radiation (LBA). Computer measurement of angiographic luminal diameter demonstrated significant vessel narrowing at 1 and 6 mo after both procedures. By quantitative histology, the majority of the 1-mo loss in angiographic diameter could not be attributed to neointimal thickening. Analysis of collagen cross-linking by HPLC in collagen obtained from the LBA-injured segments of the arteries 1 mo after angioplasty revealed a significant increase, relative to values from uninjured arteries (P < 0.05), in the difunctional cross-link dihydroxylysinonorleucine (DHLNL). 6 mo after angioplasty, the content of hydroxypyridinium, the trifunctional maturational product of DHLNL, was significantly elevated in both BA- and LBA-treated arteries compared with values from uninjured arteries (P < 0.05). In animals administered beta APN, luminal narrowing at 1 mo, compared with controls, was attenuated (P < 0.01) and DHLNL content was decreased (P < 0.05) in arteries subjected to LBA, but not in arteries subjected to BA. The results suggest that lathyrogenic agents may be efficacious in favorably modulating LBA-induced alterations in vessel diameter and mural connective tissue.

Experimentally, heparin inhibits mechanisms that promote fibrosis, neointimal cellular proliferation, and thrombin bound to fibrin at the surface of intraluminal thrombus, but only in relatively high concentrations. A preliminary hypothesis was tested and confirmed in vitro that initial binding of 3H-heparin to mechanically injured porcine aorta is concentration-dependent over a 1,000-50,000 units/ml range (r = 0.9). The hypothesis was then tested in vitro that thermal exposure during contact of heparin to arterial tissue and to clot would enhance binding of the drug. 3H-heparin binding to clot, whole blood particulates, and washed erythrocytes was markedly enhanced by exposure to temperatures > 70 degrees C. Thermal exposure (80 degrees C x 40 s) also enhanced tissue persistence of the drug within porcine aorta subjected to a shear rate of 1,100(-1) in an annular Baumgartner chamber perfused with normal saline at 37 degrees C for 48 h. Heparin in vitro anticoagulant activity persisted after thermal exposure and binding to tissues. A new method was developed for local application of a heparin film that provides a maximum concentration with a tolerable systemic dose during an angioplasty procedure. In an in vivo rabbit model of mural fibrosis after iliac artery angioplasty, the 1-month mean angiographic luminal diameter loss (23% compared to the acute postangioplasty result by computer image analysis) in response to conventional balloon angioplasty (BA) and laser balloon angioplasty (LBA) was the same (P > 0.05). Local application of a heparin film (3,000 units at a concentration > 100,000 units/g), however, reduced the mean % loss in diameter 1 month after LBA (12%), but not after BA (29%), compared to arteries subjected to angioplasty without local heparin (P < .05). The results are consistent with the hypothesis that thermal energy enhances heparin binding to tissues and that local application of a heparin film favorably modulates arterial luminal responses to LBA, but not to BA, in this animal model.

The effect of laser irradiation on the thrombogenicity of thrombus was evaluated by treating thrombi, formed in-vitro from canine blood, with two different doses of cw Nd:YAG laser energy at 1064 nm. The thrombi were then incubated with whole blood, and the plasma levels of fibrinogen and thrombin-antithrombin III-complexes were measured. A statistically significant decrease (p < 0.05) in the thrombogenicity was indicated by a reduction in both fibrinogen consumption and levels of thrombin-antithrombin III-complexes in the high dose group (600 joules, 100 degrees C peak temperature) in comparison to the low dose group (300 joules, 70 degrees C peak temperature) and the untreated thrombi. These findings suggest that laser irradiation of thrombus at an appropriate dose may substantially reduce its thrombogenicity and ability to modulate hemostasis.

Background: Radiofrequency catheter ablation of left-sided accessory pathways is becoming the first line of therapy for patients with symptomatic Wolff-Parkinson-White syndrome. Nevertheless, alternative ablation techniques merit development, at least as supplementary modalities for cases in which conventional ablation approaches may prove unsuccessful. We recently reported the short-term results with transcatheter laser balloon ablation from the coronary sinus in a canine model, proving that the procedure is feasible for the potential ablation of left-sided accessory pathways. We now report the effects of percutaneous transcatheter laser balloon ablation in a chronic canine model., Methods and Results: Twenty adult mongrel dogs were studied. After baseline coronary arteriography, left ventriculography, and coronary sinus angiography were obtained, 15 dogs received two or three consecutive laser doses from the coronary sinus of 30-40 W for 15-30 seconds, for a total cumulative energy of 1,200-2,400 J. The five remaining animals underwent a procedure consisting of balloon sham inflation without laser exposure and served as controls. After a mean follow-up of 6 weeks, the angiographic procedures were repeated, and the animals were killed. The mean extent of the fibrotic lesion was 15 mm long, 6 mm wide, and 4.5 mm deep and involved the coronary sinus wall, atrium, and, frequently, the summit of the posterior left ventricular wall. Six animals (four in the study group and two in the control group) showed asymptomatic narrowing of the coronary sinus lumen but always with total angiographic reconstitution due to extensive collateral circulation. The circumflex artery and mitral valve were intact angiographically and histologically in all animals., Conclusions: Percutaneous transcatheter laser balloon ablation via the coronary sinus produces a lesion that may be anatomically well suited for left-sided accessory pathway ablation. Although coronary sinus narrowing may occur, adverse physiological effects are unlikely due to the development of extensive collateral circulation. Systematic clinical studies of this new approach to catheter ablation appear warranted.

A 35-yr-old woman with known valvular heart disease presented with acute myocardial infarction. Angiography demonstrated a totally occluded distal left anterior descending coronary artery. Though initially successful, angioplasty ultimately failed to maintain arterial patency, leaving a more distal total occlusion after several balloon inflations. In spite of this, PTCA possibly provided a more localized infarction via a peripheral mobilization of the embolus.

To determine whether anesthesiologists can manually detect significant changes in pulmonary compliance in neonates using an "educated hand," the authors tested whether clinicians could detect clamping of an endotracheal tube connecting a neonatal lung model to one of three anesthesia breathing circuits. The test lungs corresponded to the lung of a full-term neonate (large lung) or a premature neonate (small lung), and the circuits were a disposable Mapleson D and a disposable pediatric circle system with and without a humidifier. Clinicians having four levels of expertise (inexperienced anesthesia residents, experienced anesthesia residents, faculty not specializing in pediatric anesthesia, and specialized pediatric anesthesia faculty) were permitted to choose fresh gas flows, ventilatory pattern, and rate. After an acclimation period, the endotracheal tube connecting the test lung to the circuit was occluded once for 30 s. Clinicians were credited with a successful detection if they reported the occlusion within 15 s and had fewer than one false positive per minute. With the large lung model, only 4 of 24 clinicians detected occlusion with the Mapleson D circuit; similar results were obtained with the other circuits. With the small lung model, the only successful detection occurred with the Mapleson D circuit. Success at detecting occlusion was similarly low for clinicians with different levels of expertise. The authors conclude that the commonly held belief that the "educated hand" permits clinicians to detect subtle changes in pulmonary compliance in neonates during anesthesia (necessitating manual rather than mechanical ventilation) is not true.

Mitigation of adverse biologic reactivity after balloon angioplasty is necessary before the incidence of restenosis can be appreciably reduced. A brief review of experimental evidence supports the hypothesis that the thrombogenicity of the injured arterial wall can be reduced by a suitable level of thermal denaturation or cross-linking of thrombogenic proteins. In addition, the concept of local pharmacologic therapy, which can be provided with laser balloon angioplasty at the site of arterial injury, is introduced. Preliminary in vitro and in vivo data suggest that guide catheter-injected albumin-heparin conjugates fabricated as water-insoluble microspheres remain adherent to the injured luminal surface and deeper arterial layers after physical trapping by the inflated balloon and subsequent laser/thermal exposure. The combination of initially adequate luminal morphology, reduction of the thrombogenicity of the injured arterial wall and application of local pharmacologic therapy with laser balloon angioplasty may eventually prove helpful in reducing the incidence of restenosis.

Unlike conventional transluminal percutaneous angioplasty (PTCA), which applies only intraluminal pressure, laser balloon angioplasty (LBA) employs simultaneous heat and pressure to reopen heavily occluded arterial lumens. The circumferential irradiation of Nd:YAG (1.06 microns) laser light is directly absorbed by approximately 1 to 2 mm of arterial tissue immediately adjacent to the inflated balloon. Such heating by LBA is able to seal disrupted luminal flaps, thermally remodel the luminal surface topology, reduce arterial recoil, selectively (partially) dehydrate thrombus, and possibly even reduce thrombogenicity at atherosclerotic sites. Criteria for successful LBA are defined based on earlier fundamental in vitro experiments to determine effective welding temperature, laser power doses, and exposure period; in addition, the derivation and validity of a three-part optical-thermal model and its application in parametric dosimetry analysis are presented. Though the lumen remodeled by LBA is acutely satisfactory, recurrence of the lesion is problematic chronically. Because of this, LBA is currently most useful as an adjunctive procedure whenever PTCA fails to produce optimal results or causes acute vessel closure. Perhaps, another potential application of the LBA system is to aid localized delivery of pharmacologic agents and their thermal adhesion to superficial tissue at angioplastied sites.

A multicenter clinical trial was initiated to test the potential safety and short-term efficacy of a percutaneous coronary application of laser balloon angioplasty, which has been shown experimentally to alleviate the common causes (dissection, recoil, thrombus) of suboptimal luminal results of conventional balloon angioplasty. Fifty-five patients, the majority (62%) of whom had relatively high risk lesions, were treated in 10 centers with a laser balloon that was identical in size (3 x 20 mm) to a balloon used for conventional balloon angioplasty performed on the same lesion immediately before laser balloon angioplasty. One or more neodymium:yttrium aluminum garnet (Nd:YAG) (1,060 nm) laser doses of 250 to 450 J were each delivered over a 20 s duration per exposure. Immediately and 1 day after laser balloon angioplasty no significant adverse effects on the arterial lumen were noted in any patient. By computerized image analysis of cineangiograms initial conventional balloon angioplasty failed to achieve a minimal luminal diameter greater than 1.5 mm in 14 patients (25%), including 3 patients with acute closure. However, after subsequent laser balloon angioplasty, minimal luminal diameter exceeded this value in all patients including this subgroup. Overall, minimal luminal diameter increased from 1.74 +/- 0.46 mm after conventional balloon angioplasty to 2.32 +/- 0.31 mm after laser balloon angioplasty (p less than 0.001) with no change found on 1 day and 1 month follow-up angiograms. Thus, laser balloon angioplasty is a safe, effective procedure for improving luminal dimensions after conventional balloon angioplasty.

Abrupt coronary occlusion and long-term restenosis continue to be the major problems associated with percutaneous transluminal coronary angioplasty (PTCA). Laser balloon angioplasty (LBA) is a technique designed to potentially alleviate these problems by sealing arterial dissections, smoothing the luminal surfaces, dehydrating thrombi, and reducing the elastic properties that tend to recoil the stretched artery to its original state. During LBA, laser energy is delivered circumferentially by a 100-microns optical fiber that terminates in a central diffusing tip within an angioplasty balloon. LBA is performed for 20 seconds during the final inflation of the angioplasty balloon. Achieved with decremental ramped laser dosimetry, Nd:YAG laser energy has been shown to be effective in welding experimental arterial dissections over a therapeutic temperature range of 95 degrees-120 degrees C. LBA treatment of rabbit iliac arteries has been superior to balloon angioplasty in inhibiting elastic recoil and causing acute and long-term luminal increment. LBA has also been effective for sealing acute dissections in atherosclerotic rabbit iliac arteries. Additionally, in a canine model, safety in the coronary circulation has been shown, that is, even at 1 month after LBA, angiography demonstrated a cast of the LBA balloon without luminal compromise. Since March 1988, more than 250 patients with symptomatic coronary artery disease have been treated with LBA with nearly uniform clinical success, including frequent reversal of abrupt closure. LBA seems to be a safe modality that may decrease the need for emergency operative procedures and late coronary revascularization after PTCA.

Transcatheter direct current electrical shocks for ablation of left-sided accessory pathways in Wolff-Parkinson-White patients have led to serious complications. We report the feasibility of percutaneous transcatheter laser balloon ablation of left-sided accessory pathways from the coronary sinus using a 1,064-nm, continuous wave Nd:YAG laser triple lumen catheter with an optical fiber terminating in a cylindrical diffusing tip within a 2-cm-long, 3-mm-diameter balloon transparent to Nd:YAG laser radiation. In eight mongrel dogs (18 to 31 kg), the laser balloon catheter was positioned via an 8 French guide catheter in the distal and proximal coronary sinus. During balloon inflation, two to three consecutive laser doses of 30 W x 20 sec were applied to each site (cumulative energy, 1,200 to 1,800 J). Coronary angiography, left ventriculography, and coronary sinus injection were performed before and after laser exposure. After percutaneous transcatheter laser balloon ablation, there was no evidence of mitral regurgitation, left circumflex artery, coronary sinus obstruction, or perforation. Coagulation necrosis and/or polymorphonuclear infiltrates involving the atrioventricular groove and left atrial wall over a mean length of 17 mm were present in all eight dogs sacrificed 6 +/- 1 hr postablation. In conclusion, percutaneous transcatheter laser balloon ablation from the coronary sinus is free of immediate major complications and may be feasible for potential interruption of left-sided accessory pathways.

Fluorescence of hematoporphyrin derivative (HPD) has been used clinically to localize malignant neoplasms because of its selective accumulation in these tissues. We tested the hypothesis that HPD may also be selectively concentrated within atheromatous plaques. 48 h after HPD injection in a variety of species, selective fluorescence of atheromatous plaques of the aorta was seen in each animal (rabbits and Patas monkey) exhibiting such lesions. No fluorescence could be demonstrated in aortic segments free of atheromatous involvement. Since the efficacy of photodynamic destruction of malignant tumors with HPD has been demonstrated in clinical studies, the observations of the present study may have therapeutic implications in atheromatosis.

Laser dosimetry for thermal fusion of plaque-wall separations during laser balloon angioplasty (LBA) is dependent upon the optical properties of the atheromatous arterial wall during one or more exposures to cw Nd:YAG laser radiation. An integrating sphere technique was used to measure relative transmission and reflection continuously during irradiation of human postmortem atheromatous aortic sections. Tissue luminal surface temperature was recorded continuously with a thermographic video imager during repetitive 20-30-sec, 8-15-watt exposure of a 3-mm nominal spot. In all specimens, transmission fell progressively during each exposure by 10-70% of baseline values. This effect was reversible with normalization of transmission during the initial phase of each subsequent exposure. Changes in transmission were inversely related to temperature over a 50-170 degrees C range, whereas relative reflection remained constant. Accompanying reversible transmission changes was the observation that the weld strength of plaque-aortic wall separations was unchanged by repetitive laser welding and tissue separation of individual sections. In conclusion, temperature-dependent reversible optical and physical properties of plaque occur during exposure to 1.06 microns cw laser radiation.

Laser Balloon Angioplasty (LBA) is a technique that may improve the results of balloon angioplasty by thermally sealing arterial dissections and reducing elastic recoil. To define the relationship between laser-exposure duration and the strength of thermal welds made between separated layers of arterial wall, 360 1-cm discs of human postmortem aorta were lased for six different exposure intervals at three different temperature ranges, comparing shear strength of thermal welds in the different groups. Twenty discs were lased to achieve plateau adventitial temperatures of 95 degrees C-104 degrees C (group A), 105 degrees C-114 degrees C (group B), or 115 degrees C-124 degrees C (group C) at each of the exposure periods (5, 10, 15, 20, 25, and 30 sec). A 400-micron fiberoptic coupled to a 1.06 micron continuous wave neodymium:YAG laser was placed perpendicularly 8 mm above the luminal surface of each disc, which had been split midway between the intimal and adventitial surface and reapposed. Mean laser energy ranged 78-378 J delivered in a decremental stepwise fashion to achieve quickly and maintain the target plateau tissue temperature. Mean weld strength increased in relation to both achieved tissue temperature and laser-exposure duration, with at least 10 sec necessary, at temperatures greater than 95 degrees C, for reliable thermal welding. Laser exposure for greater than 20 sec provided no statistical increment in weld strength. In the anticipated clinical performance of LBA, these data suggest that when thermal fusion of disrupted arterial tissues is desired, a laser-exposure duration of 10-20 sec is optimal.

A formal analysis of the error associated with the use of radiographic diameter measurements in estimating the luminal area of an elliptically-shaped coronary cross-section was performed. When two views are available, the maximum potential error was found to decrease rapidly as the angle between the views increased to 90 degrees, but this error was small (less than 25%) for orthogonal views only for mild degrees of ellipticity (major/minor axis ratio less than 2). Since, for each successive doubling of the number of radiographic views, a stepwise reduction in the potential error by an approximate factor of only one-half was found, a large number of views is required to eliminate the potential error associated with diameter assessment of highly elliptical lumena.

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.

The feasibility of in vivo coronary angioscopy was tested utilizing a 1.8 mm angioscope in vessels where blood had been replaced by optically clear liquids, including a new perfluorocarbon emulsion. After trials in postmortem canine and human coronary arteries, in vivo intraluminal visualization was accomplished in the dog with a catheterization technique and in patients during open heart surgery. The results demonstrate the feasibility and potential clinical usefulness of direct visualization of intravascular anatomy and disease, analogous to endoscopy of other organ systems.

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.

Thermal fusion of intimal plaque with the arterial wall during coronary balloon angioplasty may significantly reduce the incidence of abrupt closure and may reduce the occurrence of delayed restenosis by improvement of luminal size and shape. Although Nd:YAG laser energy has been shown to be effective in the thermal fusion of plaque-arterial wall separations in vitro, the most efficient manner of energy delivery for rapid achievement of therapeutically useful equilibrium tissue temperature during laser exposure has not been defined. A comparison of weld strength achieved was therefore made between two formats of laser delivery: constant power vs. decremental power with an initial high dose followed by the minimal serial decrements necessary to maintain tissue temperature constant for 15 seconds. One hundred sixty-six tissue discs of human postmortem aorta of 11 mm diameter were studied. Intimal plaque was separated from the media, the two layers were juxtaposed, a force of 4 pounds was applied, and a fiberoptic-delivered laser beam was directed perpendicular to the tissue over a 3-mm-diameter nominal spot size. Weld strength was measured as the shear force required to separate completely the two tissue layers. The mean weld strength (75 g) achieved by use of the decremental power format was significantly higher (P less than .01) than the mean strength (32 g and 56 g) achieved by using constant power for 20 and 30 seconds, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Three-dimensional reconstruction of the coronary tree from a conventional cineangiographic study is limited, in part, by the small number of available cineangiographic views. The potential utility of a maximum entropy iterative algorithm (MENT) for reconstruction of myocardial planes perpendicular to the axis of cineangiographic rotation from a small number (n = 6-18) of cineangiographic views was tested in vitro. The coronary arteries of postmortem human, canine, and calf hearts were filled with a silicone/thorium oxide mold to simulate in vivo angiographic contrast. Thirty-five-millimeter cineradiographs of each heart were obtained at 10 degrees intervals over 180 degrees about a myocardial central axis of rotation under exposure conditions which simulated the clinical setting. Projection data were derived from cinedensitometric scans across the entire myocardial shadow, perpendicular to the axis of rotation in each view, after 512 X 512 digitization with a vidicon camera/digitizer interfaced to a VAX computer. Comparison of MENT-reconstructed images with corresponding anatomic myocardial cross sections indicate that as few as 6 to 12 views can be used to reconstruct the cross sections of the multiple coronary branches (n = 6-11) within a plane of reconstruction.

In recent years, rapid progress in the application of lasers to the percutaneous treatment of atherosclerosis has been made. An overview of this progress is provided herein in terms of a description of promising laser approaches and problems to be solved. Direct vaporization of obstructing atheroma with fiberoptic delivery of laser energy has been associated with a high incidence of mural perforation, but each of a variety of techniques, including those for improved energy delivery, plaque recognition, alignment of the fiberoptic, and, perhaps, reduction of unnecessary thermal injury, has shown promise for reducing this complication. Nonablation applications of laser energy may also have a role in the treatment of atherosclerosis. During laser balloon angioplasty, the tissue coagulation effects of laser-thermal energy may be used during balloon inflation to eliminate arterial dissections and to reduce elastic recoil, thereby potentially eliminating abrupt reclosure and, perhaps, reducing the incidence of restenosis associated with conventional balloon angioplasty. Photochemical destruction of viable plaque tissue and vasa vasorum with porphyrins and intraarterial light represents a nonthermal, laser-based approach that could have a prophylactic role in slowing progression of diffuse atherosclerotic disease. The remarkable versatility of lasers is responsible for the multiplicity of approaches being investigated and for the current optimism that lasers will eventually play an important role in the percutaneous treatment of atherosclerosis.

Problems related to the precision of computerized measurement and analysis of blood vessel diameter from digitized cineangiographic vessel images are described, and shortcomings of the conventional definition of percent stenosis are discussed. Formulae for the precision of percent stenosis, for the minimum significant measurable changes in blood vessel diameter, for the necessary scanning resolution, and for absolute vessel diameter measurement are provided. A Monte Carlo procedure-based technique for assessing the effect of radiographic noise on the location of vessel boundaries within the transverse densitometric image profile is presented and applied to contrast-filled cylindrical phantoms. The results demonstrate the feasibility for achieving subpixel resolution in computerized detection of vessel edges and diameter measurement.

Subjective estimates of the angiographic severity of coronary artery stenoses show variability and inaccuracy. We therefore tested the accuracy of a newly developed computerized image analysis system for quantitating vessel diameter from cineangiograms. Fourteen cylindrical phantoms of known diameter were filled with contrast medium and filmed over a wide range of clinically relevant radiographic conditions in order to develop regression equations that related computer-derived to anatomic diameters. Computer measurements of vessel diameter were unaffected by vessel size, magnification, focal spot size, thickness of scattering medium, kilovolt peak, or location within the radiographic field, but a correction factor was necessary for a small but significant (p less than .01) linear dependence on contrast medium concentration. The accuracy of computerized vessel diameter measurements ranged between +/- 59 and +/- 137 mu for all conditions except for rapid vessel motion and contrast medium concentrations of 50% or less meglumine diatrizoate (Renografin 76), both of which resulted in reduced accuracy as well as in the inability to locate lumen edges of vessels less than 1 mm in diameter.

Restenosis after percutaneous transluminal coronary angioplasty may result primarily from the combination of a thrombogenic surface and local flow separation produced by disruption of the arterial wall and lumen. Elastic recoil and, perhaps, cellular proliferation further contribute to luminal compromise after percutaneous transluminal coronary angioplasty. Laser balloon angioplasty, performed during the final inflation of an otherwise conventional balloon angioplasty procedure, uses the coagulative properties of Nd:YAG laser radiation to weld together disrupted tissue elements thermally, to reduce elastic recoil and to destroy viable arterial tissue. Studies in human postmortem atheromatous arteries and in animal models in vivo indicate that laser balloon angioplasty, by creating a lumen that approximates the size and smooth cylindrical shape of the balloon, should be effective in the treatment of important causes of restenosis.

Reproduction of a human atherosclerotic lumen within the arterial lumen of an intact animal would facilitate angiographic and hemodynamic studies of stenoses. Accordingly, a male silicone rubber cast of a human atherosclerotic lumen was obtained from a cadaver artery, and a thin-walled replicate arterial phantom was constructed from the cast by use of a rapidly polymerizing liquid plastic. The casting properties of both materials were such that the topography of the arterial lumen was duplicated precisely in the phantom with 20 x microscopic detail preserved. The phantom was coated with a banzalkonium-heparin solution and introduced over a guidewire into an epicardial segment of a coronary lumen of the dog. Similarly, a larger phantom was placed within the dog femoral artery either directly via an arteriotomy or indirectly via a catheterization technique. Since the plastic material used to make a phantom had the same radiographic density of tissue, the angiographic appearance of an intra-arterial phantom was that of a human stenosis.

Reduction of vascular recoil is an important goal of laser balloon angioplasty (LBA), wherein Nd:YAG laser radiation is delivered radially during balloon inflation. To define the acute and chronic effects of LBA on the normal arterial lumen in comparison with those of balloon angioplasty (BA), 36 New Zealand White male rabbits (3-4 kg) were subjected to LBA of an external iliac artery and to BA of the contralateral artery with two 1-minute balloon inflations. During LBA, which was performed during the second balloon inflation, either 300 (n = 26) or 176 (n = 10) J were delivered to achieve high and moderate laser doses, respectively, in different LBA groups. Angiography was performed pre- and post-LBA/BA and subsequently at intervals of either 1, 2, 7, 28, 48, or 223 days. Automated analysis of digitized images was used to measure lumen diameter. No instance of perforation or thrombosis occurred. LBA-treated arteries acutely showed an increase in mean diameter over baseline (+ .5 mm, P less than .01) and that of BA-treated arteries (+ .4 mm, P less than .01). While arteries treated with the high laser dose showed a loss of the initial gain in lumen diameter by 1 month, caused by both extravascular fibrosis of the thinwalled (less than 0.1 mm) artery and mild neointimal proliferation which were not reduced by daily administration of aspirin in seven rabbits, arteries treated with the moderate laser dose retained the increment in mean diameter at 1 month over that of BA-treated arteries (+ .5 mm, P less than .05). Thus, unlike BA, LBA increases luminal diameter acutely and, at a moderate laser dose, chronically.

The feasibility of using continuous on-line recording of intraventricular electrical impedance to measure ventricular stroke volume was assessed in 12 patients at cardiac catheterization with a multielectrode impedance catheter and a 1.3 kHz measuring current of 4 microA. Stroke volumes determined by electrical impedance were compared with stroke volumes determined by the thermodilution technique in 10 patients and correlated with an r value of .95. Directional changes in impedance recordings throughout the cardiac cycle were also compared with volume curves obtained from six patients by radionuclide ventriculography, and in all instances the agreement between the two volume recordings was excellent. For all patients, on-line measurements of impedance showed a beat-by-beat decrease in stroke volume with the Valsalva maneuver and the administration of amyl nitrite, as well as an immediate increase in stroke volume in the contraction following an extra-systolic beat. Similar directional changes in stroke volume were recorded in both left and right ventricles. Left ventricular pressure-volume relationships were assessed with simultaneous left ventricular pressure recordings and volume signals recorded from the impedance catheter to determine if impedance measurements of volume can be used clinically. Pressure-volume diagrams were subsequently plotted, and for all patients these diagrams showed characteristic isovolumetric contraction and relaxation phases as well as typical ejection and filling periods. Moreover, beat-by-beat sequential pressure-volume diagrams constructed for patients during the administration of amyl nitrite revealed a linear end-systolic pressure-volume relationship.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

A cinedensitometric technique for extracting luminal cross-sectional area information is described. Linearization of cineangiographic gray scale with contrast medium thickness was achieved by use of a rotating step-wedge technique. Accuracy of the technique was estimated by filming, over the heart, contrast medium-filled cylindrical phantoms of diameters simulating a wide range of stenosis of a coronary artery. Expressed as (per cent stenosis), a mean error of 3.6 +/- 3.4 per cent between measured and known values of 72 cross-sectional area ratios was found (r = 0.981), and was significantly less than a 7.6 +/- 6.5 per cent error associated with area ratios derived from diameter measurements alone (p less than 0.005).

Widespread arteriosclerotic lesions were detected by histological examinations of rats killed at seven or nine weeks after an intrarenal (ir) injection of nickel subsulfide (Ni3S2, 5 mg per rat). Arteriosclerotic plaques were readily visualized by administering hematoporphyrin derivative (HPD) iv to rats at 24 hours before sacrifice. At necropsy, the major arteries were inspected under ultraviolet light, revealing patches of intense HPD-fluorescence in the arterial endothelium of Ni3S2-treated rats, but not in control rats. Consistent with previous reports, the Ni3S2-treated rats developed pronounced erythrocytosis; blood hematocrit values averaged 70 +/- 4 percent at seven weeks after ir injection of Ni3S2 (P less than 0.001 vs corresponding value of 49 +/- 2 percent in vehicle controls). At seven weeks, blood platelet counts averaged 17 percent lower and serum glucose concentrations averaged 23 percent lower in Ni3S2-treated rats than in controls; serum lipids, lipoproteins, non-protein nitrogen constituents, electrolytes, proteins, and enzymes were not significantly affected. Body weights and systolic blood pressures of rats at two, four, and six weeks after ir injection of Ni3S2 did not differ from corresponding values in controls. Addition of egg yolk to the diet caused mild hypercholesterolemia, but it did not enhance the incidence or severity of arterial lesions in Ni3S2-treated rats. These findings exclude hypertension and hyperlipidemia as pathogenic factors in Ni3S2-induced arteriosclerosis.

Dehiscence of portions of atheromatous plaques fractured during percutaneous transluminal coronary angioplasty may contribute to both abrupt reclosure and gradual restenosis. Laser balloon angioplasty has been shown to be effective in welding human plaque-arterial wall separations in vitro by heating tissues with a Nd:YAG laser during balloon inflation. To define the potentially useful therapeutic range of tissue temperature required to achieve thermal welds, 220 1-cm diameter discs of human postmortem atheromatous aortic tissue, the intimal plaque of which had been separated from the media, were exposed to 3-25 watts of Nd:YAG laser radiation delivered over a 12-mm2 nominal spot size for 20 seconds via a 400-micron core optical fiber. As measured with a thermistor, adventitial temperature reflected the temperature at the plaque-media junction to within 10 degrees C. The degree of tissue temperature elevation was related to delivered energy, while effective tissue penetration increased to maximum depth of 3 mm at the highest power density. Strength of tissue welds was defined as the force required to shear opposing layers of welded segments. Adventitial tissue temperatures below 80 degrees C were not associated with appreciable welds, while equilibrium temperatures between 95 degrees C and 140 degrees C were consistently associated with effective mean weld strengths, which increased linearly from 25 to 110 g, respectively. Temperatures greater than 150 degrees C were associated with rapid tissue dehydration and charring. These data suggest that the therapeutic range of tissue temperature that provides effective thermal fusion of intima-media separations is broad and that the depth and degree of thermal coagulation can be controlled by manipulation of laser energy delivery.