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OBJECTIVES Translingual neurostimulation (TLNS) studies indicate improved outcomes in neurodegenerative disease or spinal cord injury patients. This study was designed to assess the safety and efficacy of TLNS plus targeted physical therapy (PT) in people with a chronic balance deficit after mild-to-moderate traumatic brain injury (mmTBI). MATERIALS AND METHODS This international, multicenter, randomized study enrolled 122 participants with a chronic balance deficit who had undergone PT following an mmTBI and had plateaued in recovery. Randomized participants received PT plus either high-frequency pulse (HFP; n = 59) or low-frequency pulse (LFP; n = 63) TLNS. The primary efficacy and safety endpoints were the proportion of sensory organization test (SOT) responders (SOT composite score improvement of ≥15 points) and fall frequency after five weeks of treatment, respectively. RESULTS The proportion of SOT responders was significant in the HFP + PT (71.2%) and LFP + PT (63.5%) groups compared with baseline (p

Background Postpartum hemorrhage is a leading cause of maternal mortality globally. A tamponade agent that can be quickly and easily placed in a range of settings could advance the treatment of atonic hemorrhage. Method We adapted a highly effective trauma dressing for use in postpartum hemorrhage. This mini-sponge tamponade device is comprised of two components: compressed mini-sponges contained within a strong mesh pouch and a tubular applicator. Compressed mini-sponges rapidly absorb blood, expand within seconds, and exert sustained pressure uniformly to bleeding sites. The sponges are deployed within a mesh pouch to facilitate simple vaginal removal. Experience We successfully placed the mini-sponge device in nine patients experiencing postpartum hemorrhage after vaginal birth, with resolution of bleeding within 1 minute. The mean time to place the device was 62 seconds. Uterine fill was documented in all cases by ultrasound scan, and device placement was rated as "easy" to "very easy." Mini-sponges were left in place on average for 1 hour (0.5 hours-14 hours). Bleeding did not recur. There were no adverse events; all patients remained afebrile and did not require subsequent surgical intervention. Conclusion This study supports further evaluation of the mini-sponge device for the management of postpartum hemorrhage. Funding This study was funded by OBSTETRX, Inc.

Ultrasound shear wave elastography (SWE) has become a clinically accepted tool for tissue characterization, cancer diagnosis, and therapy assessment. However, it is only commercially available on premium ultrasound scanners and high-performance transducers capable of sustaining high-voltage, long-duration acoustic push-pulses. Mechanical vibration is an alternative method for acoustic radiation force (ARF) to induce shear wave propagation inside soft tissue, thus enabling ultrasound SWE on low-cost and portable systems. One potential application is compartment syndrome (CS), with the acute cases commonly seen in traumatic injuries and chronic cases caused by exercise injuries. CS is a condition in which the increased pressure in the muscle compartment inhibits capillary blood flow and subsequently causes muscle ischemia. To avoid permanent muscle injury, CS must be diagnosed and treated rapidly. In this study, a vibration-enabled SWE prototype was implemented on a commercial scanner and evaluated using an in vivo swine CS model as a proof-of-concept for non-invasive CS detection.

Tropoelastin (TE), the soluble precursor of insoluble elastin fibers, is produced in minimal amounts in adults. Burn injuries result in inflexible collagen-rich scars because of lack of elastin fiber formation. We studied the feasibility of using recombinant human tropoelastin to enable elastin fiber production in burn and surgical scars to improve skin flexibility. In a swine hypertrophic burn scar model, normal skin and 3 × 3-cm partial thickness thermal burns underwent dermatome resection at 1 week post burn and randomized to four subcutaneous injections of saline or TE (either 0.5, 5, or 10 mg/ml) spaced 3 days apart. Two burn sites received TE injections after wound closure (0.5 or 10 mg/ml). At 90 days, skin hardness, flexibility, and histology were evaluated. All injury sites developed hypertrophic scars. New elastin fibers were found in burn scars in all injuries injected after skin closure with low (5/5) and high (6/6) TE doses (P < .05). No elastin fibers were observed without TE treatment. No significant differences in skin hardness, flexibility, or inflammation were observed. This is the first report demonstrating that subcutaneous injections of TE into surgical and burn injuries can safely produce new elastin fibers in scars. Despite the development of new elastin fibers, skin flexibility was not improved, possibly because of insufficient elastin fiber maturation or the hypertrophic model used. The ability to restore elastin fiber formation in adult skin after burns, trauma, and surgery may improve skin regeneration and reduce disabling complications of scar formation.

Pneumothorax (PTX) is a medical and surgical emergency that can lead to hemodynamic instability and life-threatening collapse of the lung. PTX is usually detected using chest X-ray but can be detected using lung ultrasound, which requires interpretation by an expert radiologist. We are developing an AI based algorithm for the automated interpretation of lung ultrasound video to enable fast diagnosis of pneumothorax at the point of care by health care providers without extensive training in ultrasound. In this work, we developed and compared several deep learning methods for identifying pneumothoraces in 3-s ultrasound videos collected with a handheld ultrasound system. The first group of methods were based on convolutional neural networks (CNNs) paired with time-mapping preprocessing algorithms, including reconstructed M-mode and the proposed simplified optical flow transform (SOFT). These preprocessing methods were either used alone or in combination in a single “fusion” CNN. The second class of algorithm used a Deep Learning architecture that combines a CNN for processing spatial information (Inception V3) with a recurrent network (long-short-term-memory, or LSTM) for temporal analysis, enabling raw video to be fed directly into the neural network without preprocessing. We used data from a swine pneumothorax model to train and test the proposed algorithms, comparing their performance. Despite limited data, all algorithms achieved an AUC for pneumothorax detection greater than 0.83.

Following spinal cord injury (SCI), inflammation amplifies damage beyond the initial insult, providing an opportunity for targeted treatments. An ideal protective therapy would reduce both edema within the lesion area and the activation/infiltration of detrimental immune cells. Previous investigations demonstrated the efficacy of intravenous injection of multipotent adult progenitor cells (MAPC®) to modulate immune response following SCI, leading to significant improvements in tissue sparing, locomotor and urological functions. Separate studies have demonstrated that tissue inhibitor of matrix metalloproteinase-3 (TIMP3) reduces blood-brain barrier permeability following traumatic brain injury in a mouse model, leading to improved functional recovery. This study examined whether TIMP3, delivered alone or in concert with MAPC cells, improves functional recovery from a contusion SCI in a rat model. The results suggest that intravenous delivery of MAPC cell therapy 1 day following acute SCI significantly improves tissue sparing and impacts functional recovery. TIMP3 treatment provided no significant benefit, and further, when co-administered with MAPC cells, it abrogated the therapeutic effects of MAPC cell therapy. Importantly, this study demonstrated for the first time that acute treatment of SCI with MAPC cells can significantly reduce the incidence of urinary tract infection (UTI) and the use of antibiotics for UTI treatment.

Background Polidocanol foam (PF), used clinically as a venous sclerosant, has recently been studied as a safe and inexpensive means for permanent contraception. Delivering the sclerosant to the fallopian tubes as a foam rather than a liquid increases the surface areas and thus enhances the desired epithelial disrupting activity of the agent. However, the foam is inherently unstable and degrades with time. Therefore, increasing foam stability and thus duration of the agent exposure time could increase epithelial effect while allowing reduction in agent concentration and potential toxicity. Materials and Methods We studied methods to improve foam properties that might improve safety and efficacy of PF for intrauterine application. Several types of microporous filters adapted to a syringe-based foaming device were used to study the effect of pore structures on the formation of PF. The foam drainage time and bubble size were characterized. The addition of benzalkonium chloride (BZK) to polidocanol was also investigated for its effects on foam characteristics. Results A syringe-based foaming device adapted with an inline filter produced smaller bubble PF with a longer foam drainage time. PF generated with a circular pore filter lasts longer than with a noncircular pore filter. The addition of 0.01% of BZK also improved the stability of PF. Conclusion The stability of PF is affected by the pore characteristics of the filter used for foam generation and enhanced by the presence of a small amount of BZK. The improved foam, if shown to be efficacious in animal models of contraception, could lead to a safe, simple and inexpensive method alternative to surgical contraception.

Ultrasound imaging can be used to identify a variety of lung pathologies, including pneumonia, pneumothorax, pleural effusion, and acute respiratory distress syndrome (ARDS). Ultrasound lung images of sufficient quality are relatively easy to acquire, but can be difficult to interpret as the relevant features are mostly non-structural and require expert interpretation. In this work, we developed a convolutional neural network (CNN) algorithm to identify five key lung features linked to pathological lung conditions: B-lines, merged B-lines, lack of lung sliding, consolidation and pleural effusion. The algorithm was trained using short ultrasound videos of in vivo swine models with carefully controlled lung conditions. Key lung features were annotated by expert radiologists and snonographers. Pneumothorax (absence of lung sliding) was detected with an Inception V3 CNN using simulated M-mode images. A single shot detection (SSD) framework was used to detect the remaining features. Our results indicate that deep learning algorithms can successfully detect lung abnormalities in ultrasound imagery. Computer-assisted ultrasound interpretation can place expert-level diagnostic accuracy in the hands of low-resource health care providers.

Background Although uterine tamponade is an effective treatment for postpartum hemorrhage (PPH), current methods have key limitations in their use, particularly in low resource settings. The XStat™ Mini Sponge Dressing (MSD) is approved for the management of non-compressible wounds in the battlefield/trauma setting. The MSD applies highly compressed medical sponges capable of stopping high-flow arterial bleeding within seconds. The objective of our study was to adopt the MSD for use in managing PPH. Methods We performed desktop testing using a uterine model with pressure sensors to compare key design elements of the obstetrical prototype MSD (fundal pressure achieved, reduction in fluid loss, time to deploy, and time to remove) with alternativetechniques (uterine packing, balloon tamponade). To evaluate safety, we delivered the fetus of pregnant ewes by cesarean section and used the prototype to deliver the MSD into one uterine horn, and closed the hysterotomy. We followed the clinical recovery of animals (n = 3) over 24 h, and then removed the reproductive tract for histologic evaluation. To evaluate late effects, we surgically removed the MSDs after 24 h, and followed the clinical recovery of animals (n = 6) for an additional seven days before tissue removal. Results The obstetrical prototype has a long tapered delivery system designed to be deployed during vaginal examination, and administers three times the volume of the approved MSD trauma bandage. The MSD are deployed within a mesh bag to facilitate removal by vaginaltraction. On desktop testing, the MSD resulted in the highest average fundal pressure (113 mmHg), followed by the MSD bag device (85.8 mmHg), gauze packing (15.5 mmHg), and the uterine balloon (8.2 mmHg). The MSD bag test group achieved the largest fluid flow reduction of −74%, followed by gauze packing (−55%), MSD (−35%), and uterine balloon (−19%). Animal testing demonstrated good uterine fill with no evidence of adverse clinical recovery, uterine trauma or infection at 24 h, or up to 7 days following device removal. Conclusion We adapted a highly effective trauma dressing and applicator for use in the treatment of severe PPH. Preliminary desktop and animal testing provide a basis for initial clinical trials in women. Electronic supplementary material The online version of this article (doi:10.1186/s12884-017-1373-x) contains supplementary material, which is available to authorized users.

Bleeding from the liver surface is common after hepatic resection. Animal studies have demonstrated superiority of argon beam coagulation (ABC) and 38% human serum albumin when applied together after partial liver resection when compared to ABC alone. There are no data addressing the combination of albumin and argon beam coagulation (ABCA) applied to the bleeding liver after resection in humans. The aim of this study was to evaluate the safety and efficacy of ABCA on hemostasis when applied to the surface of the liver remnant post-hepatic resection.Ten patients underwent liver resection and were treated with ABCA immediately after the liver was divided. The liver surface was coated with albumin and ABC applied simultaneously, the liver was covered with gauze for 3 min, and ABCA was repeated if necessary. Number of rebleeding episodes requiring re-application of ABCA, time of ABCA application, overall blood loss, and liver functions were monitored. Patients were followed for at least 6 months.Nine of 10 patients required a single application of ABCA, and one patient required two treatments. Average time of ABC use was 5 ± 3 min. Median blood loss was 230 ml. Liver functions returned to near normal within 4 days of resection.ABCA performed well with respect to hemostatic properties, much like previous observations in animal studies. Further clinical trials are justified using this technique.

Drs.Bachtell,Grunkemeier,andJinarewithProvidenceHealthSystem;T.GoodelliswithOregonHealthS and Dr. Gregory is with Oregon Medical Laser Center, Portland, Oregon. Background.Bleedingfromcoagulopathichemodialysispuncturesitescancontributetoanemiaindialysispatients,andcurrent compressive dressings may contribute to graft thrombosis. We studied the safety and efficacy of a new chitosan-based bandage with an active clotting surface and compared its time to hemostasis and compression strap usage in dialysis access puncture wounds with that of conventional gauze dressings. Methods. Fifty patients received both the chitosan-based and conventional gauze dressings in random order on 2 successive visits. Time to hemostasis and compression strap usage were compared between the visits. Time to hemostasis was analyzed using the binary response variable at 2 and 4 minutes. A compression strap wasused if dressing application was unsuccessful at 4 minutes. Covariates included coagulation state as measured by laboratory analysis and anticoagulation therapy. Results.Hemostasiswasachievedby2minutesin30%ofthechitosan-basedand38%oftheconventionaldressings(p ¼0.608) andby4minutesin86%ofthechitosan-basedand72%oftheconventionaldressings(p ¼0.040).Compressionstrapusagewas reducedby50%inthechitosan-basedgroupcomparedtotheconventionalgroup(7vs.14patients;p ¼0.052).Noadverseevents were reported with either dressing. Conclusions. The chitosan-based bandage from HemCon is a safe and effective hemostatic agent to reduce prolonged posthemodialysis puncture site bleeding and may reduce the use of occlusive compression straps.

Background and Objectives: The success of laser tissue welding or soldering depends on optimal laser settings, solder material, and tissue type and geometry. To develop a practical laser welding technique for ureteral repair, an intraluminal albumin stent was designed to enhance the welding effects on ureteral end to end anastomosis. Study Design/Materials and Methods: In vitro porcine ureters were anastomosed using an albumin stent alone, the albumin stent plus a solder, and the solder alone. All welding was performed with an 810-nm diode laser with either a continuous wave (1 W, CW) or two pulse modes (2 W, 3.3 Hz; 1 W, 5 Hz). Laser parameters, tensile strength (TS) and burst pressure (BP) of the ureteral anastomosis, and tissue thermal injury were measured. Results: In the 2-W pulse mode, BP in the albumin stent plus solder group (mean 185 mmHg) and the stent only group (mean 133 mmHg) were significantly higher than the solder only group (mean 77 mmHg, P < 0.05). Laser ureteral anastomosis with the stent plus solder group at 1-W CW and 2-W pulse laser modes yielded the highest TS (mean 97, 82 g) and BP (mean 183, 185 mmHg). Among the three modes, the 1 W pulse delivered the lowest energy and yielded the lowest TS and BP in ureteral anastomosis. There was no significant difference in the thermal damage to the tissue among the modes and groups. Conclusions: Using the albumin stent increased the reliability of ureter end-to-end laser anastomosis. Further studies will be warranted in vivo and other tubular organs as well. Lasers Surg. Med. 31:225–229, 2002. 2002 Wiley-Liss, Inc.

Background/Objective: Laser thrombolysis is the selective removal of thrombus from occluded blood vessels using laser energy. A reconstituted clot model with reproducible optical absorption properties was de- veloped to evaluate the effect of various laser parame- ters on thrombus removal rate. Study Design/Materials and Methods: Reconstituted clots were made with known fibrinogen concentra- tions and hematocrits. Ex vivo clots were collected from ten swine. Four red gelatin phantoms were prepared. Mass removal rates and ablation efficiencies were de- termined using a 577 nm, 1 µsec pulsed dye laser. The ablation efficiencies of the three clot models were com- pared at an energy of 25 mJ and a repetition rate of 4 Hz. In addition, the reconstituted clot model was ablated as pulse energy and repetition rate were varied with aver- age power held constant at 100 mW. Results: The mean ablation efficiency for ex vivo clots ranged from 0.4 ± 0.1 to 3.4 ± 0.7 µg/mJ/pulse, with sig- nificant differences between groups (ANOVA p < 0.05). Reconstituted clots of varied fibrinogen content had ab- lation efficiencies of 1.5 ± 0.2 to 1.6 ± 0.3 µg/mJ/pulse at this energy and repetition rate. Gelatin ablation efficiency was inversely proportional to protein con- tent and ranged from 0.5 ± 0.3 to 2.0 ± 0.7 µg/mJ/pulse. Reconstituted clot mass removal rates (in µg/s) were clinically similar for settings ranging from 13 mJ at 8 Hz to 33 mJ at 3 Hz. Conclusions: The reconstituted model clot is a repro- ducible and biologically relevant thrombolysis target. Ex vivo clot lacks reproducibility between individu- als and gelatin phantoms lack clinical relevance. At a constant average power, varying laser parameters did not affect mass removal rates to a clinically significant degree.

An esophageal injury with significant tissue loss is very difficult to repair. We conducted an in vivo study to test our elastin based acellular biomaterial patch to repair such defect. The patch was made from porcine aorta, by decellularization and sterilization. Collagen fibers were preserved to retain mechanical strength and enhance cellular in-growth. Ten domestic pigs underwent right thoracotomy. A 2 cm circular defect was made on the distal esophagus, excising half its circumference, and was repaired using the biomaterial patch and sutures. Soon after the procedure, the animals resumed oral feeding. They were followed for clinical status, weight gain, barium studies, and endoscopic studies, and were killed after 6 weeks to 4 months. All ten animals survived long term, with a procedure success rate of 100% (10 of 10). With the exception of one pneumothorax, no complications occurred, and all animals resumed oral feeding and gained weight. Endoscopic studies showed mucosal coverage by 6 weeks, with minimal stricture at the repair site. Excised specimens showed complete mucosal coverage with regeneration of all three layers. Our biomaterial patch can be used safely and reliably for repair of esophageal injury with significant tissue loss when repaired immediately as in our experiment.

Laser tissue welding is a sutureless method of wound closure that has been used successfully in nerve, skin and arterial anastomoses. An elastin-based biomaterial patch was welded to the intimai surface of porcine aorta in the present study. The aorta was stained with indocyanine green dye to efficiently absorb the 808 nm diode laser light. Laser welding with a pulsed diode laser thermally confines heating to the stained portion of tissue, minimizing adjacent tissue damage. Laser welds of stained aorta to biomaterial were attempted by sandwiching the samples between glass slides and applying pressures ranging from 4 to 20 N cm-2 for 5 ms pulse durations and 83 mJ mm-2 radiant exposure. Bleaching of the indocyanine green by as much as 85% was observed after exposure laser irradiation. Finally, successful welds required 5 N cm-2 of pressure between the elastin biomaterial and aorta.

Background Noncompressible hemorrhage is the leading cause of preventable death caused by hemorrhage on the battlefield. Currently, there are no hemostatic agents with the ability to control noncompressible hemorrhage. A wound stasis dressing based upon rapidly expanding cellulose minisponges (MS) was developed and tested in a lethal noncompressible model in swine, by fully transecting subclavian artery and vein. MS were compared with conventional hemostasis dressings, Combat Gauze (CG), in a randomized comparison. Methods Sixteen 40-kg swine underwent transection of the subclavian artery and vein through a 4.5-cm aperture. After 30-second free bleeding, randomly selected MS or CG (n = 8 per group) were administered by an independent medical officer. The wound cavity was filled with either MS + no external pressure or one CG + one KERLIX gauze with 3 minutes of external pressure. One reapplication was allowed for CG. Mean arterial pressure was maintained at 60 mm Hg with 500-mL Hextend and lactated Ringer's solution intravenously administered up to a maximum of 10-L until study termination at 1 hour. Results Mean pretreatment blood loss was similar for MS (719 mL) and CG (702 mL). Primary end points, namely, hemostasis at 4 minutes (MS, 75%; CG, 25%; p = 0.13), hemostasis at 60 minutes (MS, 100%; CG, 25%; p = 0.007), and survival at 60 minutes (MS, 100%; CG, 37.5%; p = 0.026), were improved with MS as were secondary end points, namely, total blood loss (MS, 118 mL; CG 1,242 mL; p = 0.021) and length of application time (MS, 25 seconds; CG, 420 seconds; p = 0.004). Conclusion The use of MS is a novel approach for the rapid, simple treatment of severe noncompressible hemorrhage, which provided statistically significant improvement in hemostasis and survival 60 minutes after injury and a large reduction in blood loss, resuscitation fluid requirement, and medic treatment time compared with conventional hemorrhage control dressings in a swine model.

Adult bone marrow mononuclear cells (BM-MNCs) are a potential resource for making Schwann cells to repair damaged peripheral nerves. However, many methods of producing Schwann-like cells can be laborious with the cells lacking a functional phenotype. The objective of this study was to develop a simple and rapid method using autologous BM-MNCs to produce a phenotypic and functional Schwann-like cell. Adult porcine bone marrow was collected and enriched for BM-MNCs using a SEPAX device, then cells cultured in Neurobasal media, 4 mM L-glutamine and 20% serum. After 6–8 days, the cultures expressed Schwann cell markers, S-100, O4, GFAP, were FluoroMyelin positive, but had low p75(NGF) expression. Addition of neuregulin (1–25 nM) increased p75(NGF) levels at 24–48 hrs. We found ATP dose-dependently increased intracellular calcium [Ca2+]i, with nucleotide potency being . Suramin blocked the ATP-induced [Ca2+]ibutα,β,-methylene-ATP had little effect suggesting an ATP purinergic P2Y2 G-protein-coupled receptor is present. Both the Schwann cell markers and ATP-induced [Ca2+]isensitivity decreased in cells passaged >20 times. Our studies indicate that autologous BM-MNCs can be induced to form a phenotypic and functional Schwann-like cell which could be used for peripheral nerve repair.

Vasoconstriction is a clinical problem associated with invasive vascular procedures, microvascular reconstruction and subarachnoid hemorrhage. We sought to characterize the ability of pulsed-dye laser irradiation to reverse and prevent vasoconstriction in an anesthetized rabbit model of surgically and pharmacologically induced vasoconstriction. Five groups of experiments were performed to study the effect of pulsed-dye laser irradiation delivered through a 320 microns core ball-tip fiber into the femoral artery. The studies demonstrated that pulsed-dye irradiation can reproducibly cause vascular dilatation. The zone of vasodilatation propagated equally proximal and distal to the site of irradiation within the vessel. When saline was infused into the vessel to replace flowing blood during delivery of laser irradiation, no significant vasodilatation occurred. After laser irradiation reversed surgical and pharmacologic vasoconstriction, the vessel was resistant to further pharmacologic vasoconstriction. This resistance to pharmacologic vasoconstriction did not occur if the vessel was pharmacologically predilated before delivery of laser irradiation. Pathologic analysis of the vessels revealed endothelial damage and mild to moderate medial necrosis, most significant at the site of energy delivery. These studies provide characterization of pulsed-dye laser-mediated vasodilatation in an in vivo model. Delivery of pulsed-dye laser energy has potential clinical application and warrants further investigation.

Photo acoustic drug delivery is a technique for localized drug delivery by laser-induced hydrodynamic pressure following cavitation bubble expansion and collapse. Photoacoustic drug delivery was investigated on gelatin-based thrombus models with planar and cylindrical geometries by use of one microsecond laser pulses. Solutions of a hydrophobic dye in mineral oil permitted monitoring of delivered colored oil into clear gelatin-based thrombus models. Cavitation bubble development and photoacoustic drug delivery were visualized with flash photography. This study demonstrated that cavitation is the governing mechanism for photoacoustic drug delivery, and the deepest penetration of colored oil in gels followed the bubble collapse. Spatial distribution measurements revealed that colored oil could be driven a few millimeters into the gels in both axial and radial directions, and the penetration was less than 500 µm when the gelatin structure was not fractured.

Intravascular ultrasound imaging catheters and forward firing laser atherectomy systems are both being used in the coronary vascular tree of man. When used in conjunction, ultrasound imaging may reduce the probability of perforation and dissection related to laser atherectomy. A novel system is presented which combines ultrasound imaging and laser atherectomy capabilities on the same catheter. The system incorporates a holmium YAG laser directed perpendicular to the long axis of the catheter along with a co-directional ultrasound sensor. Ultrasound images are assembled by computer using the angle of the catheter tip and its linear advance associated with each ultrasound echo signal. In vivo experimental results are presented.

This PDF file contains the front matter associated with SPIE Proceedings Volume 6842, including the Title Page, Copyright information, Table of Contents, Introduction (if any), and the Conference Committee listing.© (2008) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Laser angioplasty systems with laser energy preferentially absorbed by atherosclerotic plaque may offer a safe method of plaque removal. This study evaluated the effect of blood upon selective energy absorption using a pulsed dye laser at 480 nm. Intra-arterial laser irradiation of normal rabbit femoral arteries demonstrated a perforation threshold energy with blood perfusion of 13.1 mJ per pulse compared to 87.9 mJ with saline (P less than .0001), indicating a deleterious effect in the presence of blood. An adverse effect upon arterial healing at 3 days was noted in sheep following intra-arterial irradiation during blood but not saline perfusion. Normal and atherosclerotic human aorta ablation thresholds differed significantly (P less than .0002) under saline (plaque: 20 mJ and normal: 120 mJ) but the difference under blood (plaque: 5 mJ and normal: 20 mJ) was not significant. We conclude that absorption of laser energy by blood can reduce the effect of differential absorption by endogenous chromophores in normal and pathologic vascular tissues and, therefore, removal of blood may be a prerequisite for selective ablation of atherosclerotic plaques.

It is shown that delivery of laser energy to intravascular targets through a flowing fluid-core laser angioplasty catheter offers new design possibilities and solutions to current practical problems facing laser angioplasty. Fluid-core catheters using iodinated radiographic contrast material as the core fluid can transmit high-peak-power visible laser pulses at high efficiencies while offering improved imaging of the target and distal vasculature. These catheters are simple to produce, are optically and mechanically stable, and are compatible with conventional angioplasty equipment and techniques. In canine coronary arteries in vivo, the catheters proved to be flexible, atraumatic, and able to deliver ablative high-peak-power laser pulses. >

Background and Objectives: Laser-assisted end to end vascular anastomosis of an elastin heterograft to native artery may prevent problems associated with currently available vascular synthetic grafts and conventional suture anastomosis. Study Design/Materials and Methods: A total of 21 anastomoses in the carotid arteries of 7 domestic swine were performed with an 800 nm laser and an albumin stent plus solder. There were 5 artery to artery and 16 elastin heterograft to native artery anastomoses. Operative parameters, vascular patency, and histology of the anastomoses were evaluated. Results: Out of 21 anastomoses, 16 were patent for 3 hours. One artery to artery anastomosis was thrombosed and four elastin heterograft to artery anastomoses were excluded from the study due to heterograft burst. The average amount of applied energy was 212 J for artery to artery anastomosis and 273 J for elastin heterograft to native artery. Histology shows coagulative necrosis of the adventitia, hypereosinophilic contraction band in the media of native arteries and no changes in elastin heterografts. Conclusions: Laser-assisted vascular anastomosis (LAVA) of elastin heterograft to medium size vessel using an albumin stent is feasible. Chronic studies are warranted to determine long-term patency and histology of the LAVA. Lasers Surg. Med. 35:201–205, 2004. 2004 Wiley-Liss, Inc.

Laser-assisted end-to-end vascular anastomosis of an elastin heterograft to native artery may avoid the problems associated with currently available vascular synthetic grafts and conventional suture anastomosis.A total of 21 anastomoses in the carotid arteries of seven domestic pigs were performed with an 800-nm laser and an albumin stent plus solder. There were five artery to artery and 16 elastin heterograft to native artery anastomoses. Operative parameters, vascular patency, and histology of the anastomoses were evaluated.Out of 21 anastomoses, 20 were patent at 3 h. The average amount of total energy used was 212 Joules in artery to artery anastomosis and 273 Joules in elastin heterograft to native artery. Histology shows coagulative necrosis of the adventitia, hypereosinophilic contraction band in the media in native artery, and no change in elastin heterografts.Laser-assisted vascular anastomosis of elastin heterograft to medium size vessel is possible. Albumin stent played an important role in strength of the anastomosis. Chronic studies are warranted to determine long-term patency and histology of the laser-assisted vascular anastomosis.

Laser tissue welding with albumin solder/indocyanine green (ICG) dye is an effective technique in surgical reconstruction. This study was carried out in vitro to find optimal ICG concentration and power density (PD) in laser assisted vascular anastomosis (LAVA). Fresh porcine carotid arteries incised into vascular strips (n = 120) were welded by diode laser in end-to-end with 50% albumin solder of 0.01, 0.1, and 1.0 mM ICG and at power density of 27.7, 56.7, and 76.9 W/cm2. Direct temperature was measured by inserting thermocouples outside and inside vessel. Tensile strength was tested immediately and histological study was performed. Temperature (both outside and inside vessel) significantly gradually decreasd (p < 0.01) with the increasing of ICG concentration at PD 56.7 W/cm2. Tensile strength significantly gradually decreased (p < 0.01) with increasing of ICG concentration at PD 56.7 W/cm2. Histological study showed minimal thermal injury limited to adventitia of vessels and no appreciable difference in all groups. We find that ICG concentration within solder is most important factor affecting both tissue temperature and tensile strength during laser vessel welding. The optimal balance between stronger strength and minimal thermal injury of vessel may be achieved primarily by using PD 56.7 W/cm2 at 0.01 mM ICG within solder during LAVA.

Background and Objectives We compared ureteral anastomosis using a laser and intraluminal albumin stent with both conventional suturing and laser soldering techniques. Study Design/Materials and Methods Twelve pigs underwent bilateral ureteral anastomoses (N = 24) using one of the three anastomotic methods: (1) laser welding with intraluminal albumin stent (N = 11); (2) with albumin solder (N = 8); and (3) conventional suturing (N = 5). Operative parameters, leakage rate, intrapelvic perfusion pressure, urography, and histology of the anastomoses were examined. Results Operative time for ureteral anastomosis in the stent and solder groups were significantly shorter than the suture group (means 370 seconds and 360 vs. 710 seconds, both P = 0.02). Leakage rate of the anastomoses was lower in the stent group (9%, 1/11) as compared to the solder group (25%, 2/8). The Whitaker test showed that the intrapelvic perfusion pressure elevated gradually after anastomosis and significantly increased at 4 weeks postoperatively in all three methods. Various degrees of hydronephrosis were also noticed in three groups after 4 weeks of surgery. Conclusions Use of the intraluminal albumin stent increased the reliability of laser welding for ureteral anastomosis. The clinical significance of using this technique should be investigated further. Lasers Surg. Med. 32:294–298, 2003. © 2003 Wiley-Liss, Inc

Background: Hemorrhage is a leading cause of death from trauma. An advanced hemostatic dressing could aug- ment available hemostatic methods. We studied the effects of a new chitosan dressing on blood loss, survival, and fluid use after severe hepatic injury in swine. Methods: Swine received chitosan dressings or gauze sponges. Standardized, severe liver injuries were induced. After 30 seconds, dressings were applied and resuscitation initiated. Blood loss, hemostasis, resuscitation volume, and 60- minute survival were quantified. Results: Posttreatment blood loss was reduced ( p less than 0.01) in the chitosan group (264 mL; 95% confidence interval [CI], 82 852 mL) compared with the gauze group (2,879 mL; 95% CI, 788 10,513 mL). Fluid use was reduced (p = 0.03) in the chitosan group (1,793 mL; 95% CI, 749 4,291) compared with the gauze group (6,614 mL; 95% CI, 2,519 17,363 mL). Survival was seven of eight and two of even in the chitosan and gauze groups ( p = 0.04), respectively. Hemostasis was improved in the chitosan group (p = 0.03). Conclusion: A chitosan dressing reduced hemorrhage and improved survival after severe liver injury in swine. Further studies are warranted.

Angiographic lesion morphology remains an important predictor of acute and long-term clinical outcomes after percutaneous coronary interventional (PCI) procedures even in the current era of the stent. Chronic total occlusions and thrombus-containing lesions present perhaps the greatest risk for failed PCI due to technical issues or procedural-related clinical events such as noflow or distal embolization [1]. These lesion subsets may indeed benefit form a novel mechanical solution to address the technical limitations of existing devices applied to the treatment of these pesky lesion subsets. Thrombus-containing lesions represent a subset of lesions with a high risk for procedural-related thrombotic or flow-mediated complications. Thrombolytic and anticoagulant therapies have generally proven unreliable in preventing procedural-related thrombotic events and improving clinical outcomes. Antiplatelet therapies with GP IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban) have been shown to improve clinical outcome with PCI in patients with acute coronary syndromes by reducing procedural-related myocardial infarctions. Only anecdotal evidence supports the use of GP IIb/IIIa inhibitors for PCI of thrombus-containing lesions [1]. Several mechanical solutions have been proposed for intracoronary thrombectomy. The transluminal extraction catheter (TEC) was the first device developed for the purpose of cutting and aspirating thrombus [2]. The physical properties (profile and flexibility) of the TEC catheter, however, substantially limited clinical adoption of the device and caused a high frequency of dissections as well as distal embolic events. The incompatibility of the TEC catheter with contemporary-sized (6–8 Fr) guide catheters and guidewires also impacted negatively on the clinical integration of this device. The POSSIS Angiojet rheolytic thrombectomy system has been developed for peripheral vascular and selected coronary arterial lesion subsets [3]. The POSSIS catheter utilizes a unique high-pressure fluid jet and aspiration system to remove thrombus. The device is well proven for the treatment of thrombotic occlusion of peripheral vascular grafts and native vessels. The device, however, has limited application for intracoronary thrombus due to profile and a high probability for bradyarrhythmias as well as adverse hemodynamic consequences. The X-Sizer (EndiCor Medical, San Clemente, CA), as described by Kwok et al. [4], is an 8 Fr–compatible excisional thrombo-atherectomy catheter with 2.0 and 2.3 mm tip sizes. The X-Sizer removes thrombo-embolic debris by cutting with a rotating helical cutter (2,100 rpm) while aspirating the material away from the lesion through the central catheter lumen into a vacuum bottle. This excisional atherectomy device, unlike the TEC, is compatible with off-the-shelf 0.014 guidewires. Kwok et al. [4] report a retrospective angiographic analysis of the initial clinical application of the X-Sizer for the treatment of 14 complex noncalcified and thrombus-containing lesions as part of an 85-patient international multicenter phase I clinical trial [5]. Patients treated with GP IIb/IIIa inhibitors were excluded from this retrospective study. The report of Kwok et al. [4], unfortunately, reminds one of past experiences with similarly designed thrombo-atherectomy devices. The acute gain after thrombo-atherectomy with the X-Sizer was approximately 1 mm, which equates to 50% or less of the cutter dimensions (2.0 or 2.3 mm). The cut-and-suck approach effectively removed the entire thrombus in four of nine patients (40%), while three patients (33%) had persistent thrombus after the X-Sizer and adjunctive therapy with PTCA or stenting. Distal embolization occurred in only one of 14 patients; unfortunately, periprocedural CPK data and the incidence of myocardial infarction were not reported in this angiographic study. Kwok et al. [4] identify yet another potential mechanical approach for dealing with complex or thrombus-containing lesions. These feasibility data must be supported by clinical efficacy documented in the randomized multicenter trial comparing the X-Sizer with PTCA while employing contemporary mechanical (stents, embolic protection) and pharmacological therapies (GP IIb/IIIa inhibitors). An approach harmonizing mechanical and pharmacological therapies will likely prove more efficacious than simply aspirating thrombus. Catheterization and Cardiovascular Interventions 55:140–141 (2002)

Efficacy studies are required for regulatory approval of new medical treatments in the United States and elsewhere. Although efficacy studies may demonstrate safety and efficacy, they are not always sufficient for characterizing the effects of a treatment in actual clinical practice. Ongoing outcomes research is necessary to identify outcomes of treatment and treatment patterns in actual clinical practice. Criteria for evaluating palliative treatments in outcomes research must reflect the treatment's capacity to relieve symptoms while entailing minimal risks and adverse effects. However, the measurement of symptom relief as a result of treatment is prone to error because symptoms are inherently subjective and may be influenced by a variety ofnon-treatment factors, such as individual perception, physical exertion, and concurrent symptom management strategies. PDT patients treated with Photofrin® and 630-nm light at our center have had reduced dysphagia grade and stable performance status for approximately one month after PDT (N= 7-26), but these effects did not necessarily persist at the three-month followup interval. Preliminary data on five patients collected in a pilot study of a new symptom burden measurement tool suggest that the perceived burden ofphotosensitivity may increase with time. Fatigue, poor appetite and decreased overall quality of life appear to be the most troubling symptoms for our late-stage esophageal cancer PDT patients. The least burdensome symptoms were anxiety, pain and depression.

The purpose of this study was to test a new prototype pulsed CO2 laser to be used for transmyocardial laser revascularization (TMR). We wanted to determine whether it can reduce thermal damage and mitigate induced ischemia with improvement in contractile reserve of the heart as evidenced by contrast echocardiography at rest and under dobutamine stress. TMR is an emerging surgical strategy for treatment of myocardial ischemia not amenable to conventional percutaneous or surgical revascularization. Eleven pigs underwent ameroid occluder placement at the origin of the circumflex coronary artery. Six weeks later, occlusion of the circumflex coronary artery was documented. TMR was then carried out on 10 pigs by using a prototype pulsed CO2 laser that delivered 8-12 joules in 1.5 ms with a spot size of 1 mm. Six weeks after TMR, the pigs were restudied. The animals developed significant ischemia after 6 weeks of ameroid occlusion, at rest (p = 0.01) and at peak stress (p = 0.004). Wall motion for the ischemic segments improved significantly 6 weeks after TMR at peak stress (p = 0.02). TMR results in an improvement in wall motion in our model of chronic ischemia and improves wall motion score index more during induced stress than at rest.

Major duodenal injury with significant tissue loss causes high morbidity and mortality. Our new elastin based heterograft combined with small intestinal submucosa (SIS) and biodegradable glue could be used for repair of such defects. Twenty-four domestic pigs were anesthetized and underwent celiotomy .A2c mcircular defect was created at the second portion of the duodenum with scissors, excising one‐ half of its circumference. Our elastin patch, combined with SIS, was applied to cover the defect using biodegradable cyanoacrylate glue and a few sutures. It was then covered with omentum. Animals were followed by weight gain, endoscopic evaluation, and upper GI barium studies. After 2‐5 months, animals were sacrificed to obtain specimens. One failed in 3 days due to a technical problem, and one failed in 20 days due to an abdominal abscess. The other 22 animals (22/24, 91.7%) did well, gaining weight. Early endoscopic studies (5‐14 d) showed an intact patch. Upper GI studies showed varying degrees of stenosis at the repair site at 3‐ 4 months. Sacrifice after 2‐5 months showed complete healing of the defect and a dissolved patch. Our new elastin patch material provides a reliable barrier for repair of duodenal injury, and the biodegradable glue provides quick and easy watertight tissue fusion for our patch. ASAIO Journal 2000; 46: 409 ‐ 414. Surgical repair of major injury to the second portion of the duodenum with significant tissue loss requires innovative surgical techniques and is associated with significant morbidity and mortality.1 Segmental resection and primary end-to-end anastomosis is not possible in this region due to its close proximity to the head of pancreas and connections with the common bile duct and pancreatic duct. Small defects can be repaired by primary closure, which will result in stricture of the duodenum, depending upon the amount of tissue loss. Large defects cannot be repaired this way; they will require innovative techniques, such as creation of a jejunal patch, duodenojejunostomy, serosal onlay patch, pyloric exclusion with gastrojejunostomy, or even pancreatico-duodenectomy. The last procedure is fairly extensive, and is not likely to be tolerated by acute trauma patients with multiple injuries. The first three procedures can be done, but they still require prolonged operative time involving additional bowel anastomosis, and are feasible only when the jejunum is intact. Pyloric exclusion is accompanied by prolonged external drainage of the duodenal content, which makes it difficult to manage fluid and electrolyte balance, and a high incidence of intra‐abdominal infection, sepsis, and chronic fistula formation, predisposing the victim to prolonged intensive care, parenteral nutrition, hospitalization, and disability. This is due to the high content of electrolytes and digestive enzymes in the duodenal fluid, which comes mainly from bile and pancreatic excretion. As a result, prolonged leakage from the duodenum is associated with prolonged and extensive tissue loss and sepsis. Recent developments in antibiotics and intensive care has significantly reduced the mortality rate from this condition, but morbidity is still high. If we could develop a technique that can easily, quickly, and reliably close the duodenal injury without compromising the lumen, we can expect much faster recovery with fewer complications and less morbidity and mortality. The elastin based heterograft we developed at the Oregon Medical Laser Center could be used to repair such a defect in the duodenum without compromising the lumen, need for other bowel anastomosis, or extensive resection. In our laboratory, this material was shown to be biologically inert, inducing minimal immunologic response, and resistant to infection and hydrochloric acid. SIS has been experimentally used to replace arteries and veins with success,2,3 and has been shown to serve as an excellent scaffold for the regeneration of tissue when used to repair the urinary bladder. 4‐6 We speculated that the combined patch of elastin and SIS will serve as an effective physical and chemical barrier for duodenal contents owing to the property of elastin, whereas SIS serves as scaffold for tissue growth (Figure 1). Use of biodegradable cyanoacrylate glue was proposed to achieve a quick and easy way to secure the patch in place and provide watertight fusion instantly.

We used reconstructed SIS (ReSIS), a photocrosslinked biomaterial, to create grafts in various shapes and sizes. Sheets of ReSIS were placed in 14 swine to repair bladder defects, and ReSIS tubes were placed in six swine to replace a segment of excised ureter. Histologic analysis of the bladder repair revealed transitional urothelial cells lining the ReSIS by 1 week. After 2 weeks, fibroblasts and mononuclear cells had infiltrated the ReSIS, neovascularization had occurred, and the urothelial lining was more complex, containing multiple cell layers. After 4 weeks, a definite submucosa was present and the ReSIS was starting to degrade. An initial muscular regeneration was demonstrated at 12 weeks. No foreign body reaction, calcification, or sedimentation was noted in any animal. The ureteral implants showed identical histologic changes, without obstruction or leakage of the replaced segment. The ReSIS allowed rapid urothelial regeneration, ingrowth of new blood vessels, and the orderly deposition and organization of new collagen. Our study demonstrates that the photocrosslinking technique used to create larger sheets and tubes of this biomaterial (ReSIS) does not detract from the positive attributes of the SIS and should improve its usefulness in accomplishing larger bladder augmentations and ureter replacements.

The purpose of this study was to evaluate laser soldering using liquid albumin for welding liver lacerations and sealing raw surfaces created by segmental resection of a lobe. Major liver trauma has a high mortality due to immediate exsanguination and a delayed morbidity and mortality from septicemia, peritonitis, biliary fistulae and delayed secondary hemorrhage. Eight laceration injuries (6 cm long X 2 cm deep) and eight non-anatomical resection injuries (raw surface 6 cm X 2 cm) were repaired. An 805 nm laser was used to weld 53% liquid albumin-ICG solder to the liver surface, reinforcing it with a free autologous omental scaffold. The animals were heparinized to simulate coagulation failure and hepatic inflow occlusion was used for vascular control. For both laceration and resection injuries, eight soldering repairs each were evaluated at three hours. A single suture repair of each type was evaluated at three hours. All 16 laser mediated liver repairs were accompanied by minimal blood loss as compared to the suture controls. No dehiscence, hemorrhage or bile leakage was seen in any of the laser repairs after three hours. In conclusion laser fusion repair of the liver is a quick and reliable technique to gain hemostasis on the cut surface as well as weld lacerations.

Stroke is the leading cause of disability and is the third leading cause of morbidity in the United States. Approved therapies are limited. A novel therapy utilizing laser energy delivered through a fluid core catheter in the ablation of embolic thrombus in acute stroke is currently being tested in a clinical trial. In order to optimize the efficiency of clot removal by this system, an in vitro method to measure the effects of varying the laser parameters on the efficiency of clot removal was developed. Included in this model is a new reconstituted clot target that has reproducible mechanical and optical properties which allow reliable spectrophotometric measurement of the mass ablated. In this study the parameters of energy and repetition rate were adjusted while the average power remained constant at approximately 100 mW. The energy levels and repetition rates tested were 36 mJ at 3 Hz, 25 mJ at 4 Hz, 20 mJ at 5 Hz, 15 mJ at 7 Hz, and 12.4 mJ at 8 Hz. We demonstrate that the efficiency of clot removal achieved at higher pulse energies and low repetition rates can be maintained at a lower energy and higher repetition rate. These results are in agreement with previous studies using gel phantoms. This study demonstrates the reproducibility of the reconstituted clot and supports the use of this model as a clinically relevant method to investigate the efficiency of laser thrombolysis.

Transmyocardial revascularization (TMR) has been investigated as a means of reperfusing ischemic heart tissue by introducing channels in the myocardium. In percutaneous TMR (P TMR), the channels are made from within the left ventricle by introducing an excimer laser catheter via the femoral artery. There is currently no means of determining the limits of ablation in P TMR so that the epicardium is not perforated. We used an optical coherence tomography (OCT) signal to detect the epicardial surface during excimer laser ablation of the myocardium in porcine hearts. A XeCl excimer laser operating at 308 nm with a pulse duration of 125 - 200 ns and a pulse energy of 21/mJ at 25 Hz was used to ablate channels in porcine hearts ex vivo. The OCT system was connected to an optical fiber guidewire that was introduced coaxially with the ablation fiber. The OCT signal was monitored on a computer during the ablation process. The epicardial surface was detected within 600 micrometer of perforation.

The purpose of this study was to test a new prototype pulsed CO2 laser to be used for transmyocardial laserrevascularization (TMR). We want to determine whether it can reduce thermal damage and mitigate induced ischemia withimprovement in contractile reserve of the heart as evidenced by contrast echocardiography at rest and under dobutamine stress.TMR is an emerging surgical strategy for treatment of myocardial ischemia not amenable to conventional percutaneous orsurgical revascularization. Eleven pigs underwent ameroid occiuder placement on the origin of the circumflex coronary artery.Six weeks later occlusion of the circumflex coronary artery was documented. TMR was then done on ten pigs using a prototypepulsed CO2 laser that delivered 8—l2joules energy in I.5ms with a spot size of 1mm. Six weeks after TMR the pigs wererestudied and sacrificed. The animals developed significant ischemia after six weeks of ameroid occlusion, at rest (p=O.O1) andat peak stress (p=O.OO4). Wall motion for the ischemic segments improved significantly six weeks after TMR at peak stress(p=O.O2). TMR results in an improvement in wall motion in our model of chronic ischemia and improves WMSI significantlyduring induced stress than at rest.Key word List: Transmyocardial laser revascularization; Myocardial contrast echocardiography; CO2 Laser; Dobutaminestress echocardiography; Ameroid occluder; Epicardial echocardiography, TMR.

This paper considers some issues pertinent to laser welding of elastin-based biomaterials to tissues using a pulsed diode laser (lO-is pulse) and indocyanine green (ICG) as an absorbing chromophore to localize laser heating to the "weld surface", the elastin/tissue interface where welding occurs. Experiments involved laser welding of elastin heterographs to the intimal surface of the carotid artery (in vitro, porcine) as a '-4x5 spotweld, then determining the breaking strength when the two tissues were pulled in a direction parallel to the plane of the spot weld while submerged in water. The questions answered are: . WHAT IS THE PEAK TEMPERATURE REQUIRED FOR WELDING ELASTIN HETEROGRAPH TO THE INTIMAL SURFACE OF CAROTID ARTERY? ANSWER: 3OO °C threshold, -6OO °C for maximum strength. This estimate is based on optical measurements of dye accumulation in stain layer and measurements of thickness of stain layer via fluorescence microscope examination. . WHATIS THE DEPENDENCE OF WELD STRENGTH ON THE LASER EXPOSURE? ANSWER: Breaking force (g) = Max*(1 exp(-(E Eth)/U67)), where Max is the maximum strength achievable by laser welding, expressed as the breaking force in g when elastin heterograph and tissue are pulled. E is the laser pulse energy. Eth is the apparent threshold laser pulse energy that will break the weld. Uth is the laser energy above threshold which achieves 67% of Max. Max was about 15 g for the -2O --2weld area of our experiments. Eth was 0.8 J. U67 was 1 .44 J. . DOES WELD STRENGTH DEPEND ON HYDRATION CONDITIONS? ANSWER: Not on the amount of excess unbound water. There was no significant difference in weld strength between welding dripping wet tissues vs well blotted tissues. S WHAT DIFFERENCE IS THERE BETWEEN IRRADIATING THE WELD SURFACE THROUGH THE BIOMATERIAL VS THROUGH THE TISSUE, WHEN THE BIOMATERIAL IS PARTIALLY STAINED WITH ICG? ANSWER: There is a difference if the stain layer is heavily stained. Irradiation through the tissue allows direct irradiation on the weld surface which achieves the highest peak temperatures for the least laser pulse energy. Irradiation through the elastin heterograph causes direct irradiation of the rear surface of the stain layer, within the biomaterial and away from the weld surface, and thermal diffusion must bring the heat to the weld surface. This difference occurs only when the absorption by the stain layer is sufficiently high that little laser energy directly reaches the weld surface.

The use of pulsed laser energy to clear arteries obstructed by thrombus (blood clot) and plaque has emerged as a promising method for the treatment of cardiovascular diseases such as myocardial infarction and stroke. Current techniques for laser thrombolysis are limited because they cannot completely clear the clot in arteries, especially where a large volume clot is presented. Mural clot is a potent stimulus for reocclusion. We suggest that the combination of laser thrombolysis and localized intramural delivery of clot-dissolving drugs during the procedure may be a solution to this limitation. Ninety pulses of 30 - 70 mJ were delivered onto gelatin-based thrombus model with a flushing catheter. A solution of 1 micrometer fluorescent particles as a drug model was injected at a rate of 4 mL/min in coincidence with the laser delivery. The controls were performed by injecting drug after laser thrombolysis. We measured the penetration of the particles in gelatin and the sizes of the lumen and stained areas. The results of this study demonstrated the possibility of enhancing laser thrombolysis by delivering drugs into thrombus. It was found that the particles could be driven several hundred micron in gelatin, and the lumen areas would be increased up to 25% if the areas were dissolved by the drugs.

Psoralen activated by UVA light (PUVA) was investigated as a means of inhibiting smooth muscle cell proliferation resulting from balloon injury. Twenty kilogram domestic swine were anesthetized and underwent balloon angioplasty to create a 133% overstretch injury. Assignments of treatment and control were randomized between the left anterior descending (LAD) and circumflex (LCX) coronaries arteries. The animals were given with 5 mg/kg of 8- methoxypsoralen eternally. Treatment vessels received 600 mJ/cm2 of 364 nm light during balloon inflation to activate the psoralen. Control vessels received drug and balloon injury only. Serum was obtained during the light delivery to assess psoralen levels. At 30 days, animals were sacrificed and the coronary arteries perfusion fixed. Five sections per vessel were analyzed morphometrically to determine percent intimal area and extent of injury. The restenosis injury index was 0.21 plus or minus .02 in treatment vessels and 0.14 plus or minus .01 in the controls with a p-value less than .02. In this large animal model of balloon angioplasty injury, psoralen activated by ultraviolet light increased intimal hyperplasia.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Background Although the relationship between cardiac wavelength (λ) and path length importantly determines the stability of reentrant arrhythmias, the physiological determinants of λ are poorly understood. To investigate the cellular mechanisms that control λ during reentry, we developed an experimental system for continuously monitoring λ within a reentrant circuit with the use of voltage-sensitive dyes and a new guinea pig model of ventricular tachycardia (VT). Methods and Results Action potentials were recorded simultaneously from 128 ventricular sites in Langendorff-perfused hearts (n=15) in which propagation was confined to a two-dimensional rim of epicardium by an endocardial cryoablating procedure. The reentrant path was precisely controlled by creating an epicardial obstacle (2×10 mm) with an argon laser. To control for fiber orientation and rate-dependent membrane properties, λ during reentry was compared with λ during plane wave propagation transverse and longitudinal to cardiac fibers at a stimulus cycle length (CL) comparable to the VT CL. Reentrant VT (CL=97.0±6.2 ms) was reproducibly induced by programmed stimulation in 93% of preparations. λ varied considerably within the reentrant circuit (range, 10.6 to 22.5 mm), because of heterogeneities of conduction rather than action potential duration. λ was significantly shorter during reentrant propagation (ie, with pivoting) parallel to fibers (10.6±4.2 mm) compared with plane wave propagation (ie, without pivoting) parallel to fibers (32.8±6.5 mm, P Conclusions We provide direct experimental evidence that multiple wavelengths are present even within a relatively simple reentrant circuit. Abrupt changes in loading during wave-front pivoting, rather than membrane ionic properties or fiber structure, were a major determinant of λ and, therefore, may play an important role in the stability of reentry.

Photoacoustic drug delivery is a technique for delivering drugs to localized areas by timing laser-induced pressure transients to coincide with a bolus of drug. This study explores the effects of target material, laser energy, absorption coefficient, fiber size, repetition rate, and number of pulses on the spatial distribution of delivered drug. A microsecond flash-lamp pumped dye laser delivered 30-100 mJ pulses through optical fibers with diameters of 300-1000 micrometers . Vapor bubbles were created 1-5 mm above clear gelatin targets submerged in mineral oil containing a hydrophobic dye (D&C Red#17). The absorption coefficient of the oil-dye solution was varied from 50-300 cm-1. Spatially unconfined geometry was investigated. We have found that while the dye can be driven a few millimeters into the gels in both the axial and radial directions, the penetration was less than 500 micrometers when the gel surface remained macroscopically undamaged. Increasing the distance between the fiber tip and target, or decreasing the pulse energy reduced the extend of the delivery.

Laser tissue welding is a sutureless method of wound closure that has been used successfully in nerve, skin, and arterial anastomoses. We welded an elastin-based biomaterial that elicits minimal foreign body reaction to the intimal surface of porcine aorta. The aorta was stained with indocyanine green dye to efficiently absorb the 808 nm diode laser light. Laser welding with a pulsed diode laser thermally confines heating to stained portion of tissue, minimizing adjacent tissue damage. Laser welds of stained aorta to biomaterial were attempted by sandwiching the samples between glass slides and applying pressure ranging from 4 - 20 N/cm 2 for 5 ms pulse durations and 83 mJ/mm 2 radiant exposure. Welds were successful for pressure above 5 N/cm 2 . Transmission measurements of stained aorta were made using radiant exposures of 6 - 129 mJ/mm 2 using pulse durations of 0.5 - 5 ms. Transmission increases and reaches a maximum of 80 - 85% with successive pulses for radiant exposure greater than 26 mJ/mm 2 for a spot size of 9 mm 2 and 13 mJ/mm 2 for a spot size of 36 mm 2 .

CABG thrombosis is a common disorder without adequate therapy. To assess the effects of selective laser thrombolysis (LT) in CABG, aortocoronary bypasses were created and completely thrombosed in nine swine. Maximal thrombus removal was achieved with pulsed dye laser light (577 nm, 1 μs pulse, 3 Hz, 64 mJ/pulse) by fluid catheter for 6.7 ± 1 min. Graft flow and thrombosis were assessed by angio with global and grafted segment myocardial function measured by epicardial echo at constant load. Mean graft size: 8 mm × 6 cm. Prior to therapy, grafts had no flow (TIMIO) and complete thrombosis for 60 min. TIMI flow post LTwas 2.8 ± 0.4 (p l 0.001) with focal residual mural thrombus. 90 min post LT, graft appearance and flow were unchanged. Wall motion (WM) scored from normal (1) to dyskinetic (4). Index = total WM/14 segments. Occlusion 90 min postLT Global EF 0.49 ± 0.09 0.55 ± 0.04 NS Index 1.7 ± 0.1 1.1 ± 0.1 (p l 0.05) Grafted Region Wall Motion 4 1 (p l 0.01) %Wall Thick. - 5 31 (p l 0.01) Conclusions 1) LT is able to rapidly remove large amounts of thrombus in CABG. 2) Thrombus removal by LT does not cause detectable changes in regional cardiac function. 3) High patency rates persist 90 min. post LT.

The design, processing, and sequential testing of a novel cylindrical diffusing optical fiber tip for ultraviolet light delivery is described. This device has been shown to uniformly (+/- 15%) illuminate angioplasty balloons, 20 mm in length, that are used in an experimental photochemotherapeutic treatment of swine intimal hyperplasia. Our experiments show that uniform diffusing tips of < 400 micron diameter can be reliably constructed for this and other interstitial applications. Modeling results indicate that this design is scalable to smaller diameters. The diffusing tips are made by stripping the protective buffer and etching away the cladding over a length of 20 mm from the fiber tip and replacing it with a thin layer of optical epoxy mixed with Al 2 O 3 powder. To improve the uniformity and ease of fabrication, we have evaluated a new device configuration where the tip is etched into a modified conical shape, and the distal end face is polished and then coated with an optically opaque epoxy. This is shown to uniformly scatter ~ 70% of the light launched into the fiber without forward transmission. To our knowledge, we are the first to use this device configuration, and we have achieved a uniform cylindrical pattern of laser energy with the uniformity < ± 15% of the average value.