Intraoperative use of optical coherence tomography to differentiate normal and diseased thyroid and parathyroid tissues from lymph node and fat.

The purpose of this study is twofold: (1) to determine the feasibility of optical coherence tomography (OCT) to differentiate normal and diseased tissue of the neck region intraoperatively and (2) to evaluate how accurately a cohort of test subjects can identify various tissue types when shown a sample set of OCT images. In this in vivo, prospective, single institutional study, an OCT imaging system (Niris, Imalux, Cleveland, OH) was used to image parathyroid, thyroid, lymph node, and fat tissue in 76 patients during neck surgery. Biopsies were performed for comparison of OCT images with histology in select cases (n = 20). Finally, a group of either surgeons or scientists familiar with OCT (n = 17) were shown a sample of OCT images and asked to identify the tissue. A total of 437 OCT images were analyzed, and characteristic features of each tissue type were identified. OCT demonstrated distinct differences in structural architecture and signal intensity that allows differentiation between thyroid and parathyroid tissues, lymph nodes, and fat. OCT images were also compared with histology with good correlation. There was no difference in correctly identifying OCT-imaged tissue type between surgeons and scientists. This study is the first in vivo OCT imaging study to evaluate both normal and diseased tissues that may be encountered during neck surgery. OCT has the potential to become a valuable intraoperative tool to differentiate diseased and normal thyroid tissue intraoperatively to obtain an "optical biopsy" in real time without fixation, staining, or tissue resection.

Osteomyelitis of the hard palate secondary to actinomycosis: a case report.

Osteomyelitis of the hard palate is a rare and difficult-to-eradicate sequela of actinomycosis. In this case report, we illustrate the necessity of aggressive surgical management of actinomycotic infection of the hard palate. The patient was initially treated with multiple local debridements supplemented with oral and then parenteral antibiotics, but his disease progressively worsened. His condition eventually resolved only after a partial palatectomy was performed to remove all the necrotic bone, followed by a prolonged course of intravenous and oral antibiotic treatment.

[Optical coherence tomography applications in otolaryngology]. / Aplicaciones de la tomografía de coherencia óptica en otorrinolaringología.

Optical coherence tomography is a novel imaging technique providing high-resolution bidimensional images of tissue microstructures. Several studies have been published on the use of this technique in different fields of medicine, particularly ophthalmology. There are very few studies in the field of otolaryngology. This paper presents various applications of optical coherence tomography in the different sub-specialties of otolaryngology, as well as the benefits of this technique over traditional diagnostic methods.

Aplicaciones de la tomografía de coherencia óptica en otorrinolaringología / Optical coherence tomography applications in otolaryngology

La tomografía de coherencia óptica es una técnica de imagen innovadora con la cual se pueden obtener imágenes en dos dimensiones de alta resolución sobre la microestructura de los tejidos. Hoy día hay varios estudios sobre el uso de esta técnica en distintas ramas de la medicina, sobre todo en oftalmología. Sin embargo, poco se ha estudiado en la otorrinolaringología. En este trabajo presentamos los diferentes usos de la tomografía de coherencia óptica en los distintos campos de la otorrinolaringología, así como sus beneficios sobre métodos convencionales de diagnóstico (AU)

Optical coherence tomography is a novel imaging technique providing high-resolution bidimensional images of tissue microstructures. Several studies have been published on the use of this technique in different fields of medicine, particularly ophthalmology. There are very few studies in the field of otolaryngology. This paper presents various applications of optical coherence tomography in the different sub-specialties of otolaryngology, as well as the benefits of this technique over traditional diagnostic methods (AU)

The macroscopic and microscopic effects of radiofrequency injury in the porcine tongue: a pilot study.

OBJECTIVE: Current treatment protocols for obstructive sleep apnea/hypopnea syndrome with radiofrequency ablation of the base of the tongue are empiric. Injecting local anesthetics and saline into the treatment site is believed to shorten treatment duration and improve results. Our objective is to compare lesions at different energy levels, both macroscopically and histologically, and to determine if electrolyte solution injection results in a larger lesion. STUDY DESIGN: A prospective, experimental animal study. SETTING: University-affiliated institution. SUBJECTS AND METHODS: Five pigs each received four treatments on the right and four on the left side of the tongue. Three of four treatments were applied sequentially by increasing length of exposure (15, 30, or 60 seconds), and the fourth was conducted over 15 seconds after injecting 1 cc of a 1:1 local anesthetic-saline solution into the treatment site. The animals were recovered for three days and then sacrificed. Macroscopic measurements for each lesion were analyzed, and histological comparison was performed. RESULTS: The average volume of the lesions was 57.36, 65.18, and 60.50 mm(3) for treatment durations of 60, 30, and 15 seconds, respectively, and there was no significant difference. Lesion volume at sites where anesthetic-saline was injected had a mean volume of 36.72 mm(3). Paired comparison against the three treatment durations revealed significantly smaller lesion volume size (P = 0.0041, 0.0007, 0.0047, respectively). CONCLUSION: The lesions created with radiofrequency energy were consistent and predictable. The volumes of the lesions did not differ significantly with regard to different energy levels. The lesion was significantly smaller after injection of anesthetic-saline at the treatment site.

Functional endoscopic dilatation of the sinuses: patient satisfaction, postoperative pain, and cost.

BACKGROUND: The purpose of this study was to determine how functional endoscopic dilatation of the sinuses (FEDS) compares with functional endoscopic sinus surgery (FESS) in a select group of patients with respect to (1) elimination of symptoms, (2) patient satisfaction, (3) postoperative narcotic use, and (4) cost. A retrospective study was performed of 70 patients with chronic rhinosinusitis who underwent FEDS or FESS as primary or revision treatment. METHODS: Symptoms and satisfaction based on the Sino-Nasal Outcome Test (SNOT-20) questionnaires and global patient assessment, postoperative narcotic use, and costs were compared after 3-month follow-up. RESULTS: SNOT-20 change scores indicated that both FEDS and FESS had clinically meaningful treatment responses. Patient satisfaction was higher and postoperative narcotics usage was less with FEDS. The cost for primary procedures was similar, whereas the cost for revision surgery using FEDS was considerably less. Turbinate lateralization and scarring was more common in the FEDS group, particularly early in the study. The incidence of recurrent sinus infections during the follow-up period was similar for both groups. Only one patient in the FEDS group required a repeat intervention within the short-term follow-up period. CONCLUSION: Both FEDS and FESS resulted in significant improvement in SNOT-20 scores for selected patients with mild disease. Patient satisfaction and postoperative narcotic use of FEDS compare favorably with FESS. Cost of FEDS was comparable with FESS for primary procedures but was less than FESS for revision procedures. Long-term efficacy and final cost of FEDS remain to be addressed, taking into account the need for revision procedures after initial FEDS, by means of long-term studies and objective outcome measures.

Palatal implants for the treatment of snoring and obstructive sleep apnea/hypopnea syndrome.

OBJECTIVE: Randomized, double-blinded, placebo-controlled, clinical trial to determine the effectiveness of palatal implants for treatment of mild/moderate obstructive sleep apnea/hypopnea syndrome (OSAHS). STUDY DESIGN AND SETTING: Sixty-two non-obese adults with history of snoring, daytime sleepiness, and mild/moderate OSAHS, were randomized to receive palatal implants (n = 31) or placebo procedure (n = 31). Complete follow-up including quality of life (QOL, SF-36), snoring visual analog scale (VAS), and Epworth Sleepiness Scale (ESS) data were obtained in 62 patients. Seven patients refused follow-up polysomnography for a total of 55 patients (29 implant and 26 placebo). RESULTS: The treatment group (change in score of -7.9 +/- 7.7) was significantly improved compared with the placebo group (change in score of 0.9 +/- 4.3) for apnea/hypopnea index (AHI) (P < 0.0001), QOL, SF-36 (P < 0.0001), snoring VAS (P < 0.0001), and ESS (P = 0.0002). CONCLUSIONS: Palatal implants improve AHI, QOL, snoring intensity, and daytime sleepiness for selected patients with mild/moderate OSAHS.

Middle turbinate medialization with bovine serum albumin tissue adhesive (BioGlue).

Middle turbinate (MT) medialization without resection is an approach designed to both preserve the MT and prevent lateralization, which may cause obstruction of the outflow of the ethmoid, maxillary, and frontal sinuses after endoscopic sinus surgery. Many techniques for medialization have been described. We present a quick and easy technique that involves using the microdebrider to create small areas of denuded mucosa on opposite surfaces of the MT and the nasal septum followed by an application of a bovine serum albumin tissue adhesive to promote the formation of controlled synechiae without the need for nasal packing.

Impact of treatment of gastroesophageal reflux on obstructive sleep apnea-hypopnea syndrome.

OBJECTIVES: We test the hypothesis that treatment of gastroesophageal reflux disease (GERD) can improve obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: One hundred forty-six patients with OSAHS underwent a complete history-taking, physical examination, and laboratory testing, including questions related to GERD symptoms. Full-night attended polysomnography, 24-hour wireless pH study at the upper esophagus, snoring level evaluation, Epworth Sleepiness Scale, and quality-of-life surveys were completed for each patient. Patients who tested positive for GERD were treated with esomeprazole magnesium 40 mg once daily for 2 to 12 months. The 24-hour pH study was repeated, and those patients with elimination of GERD were reevaluated by polysomnography, snoring level evaluation, Epworth Sleepiness Scale, quality-of-life surveys, and subjective data collection. RESULTS: Forty-one patients completed single-dose treatment with esomeprazole, but the repeat 24-hour pH study showed that 9 patients had persistent GERD. In the 29 patients who completed phase 2 with normal pH study findings, the snoring level decreased from 9.7 +/- 0.5 to 7.9 +/- 1.3 (p < .0001), the Epworth Sleepiness Scale score decreased from 14.2 +/- 2.5 to 11.1 +/- 2.4 (p < .0001), the apnea-hypopnea index decreased from 37.9 +/- 19.1 to 28.8 +/- 11.5 (p = .006), and the minimum saturation of oxygen increased from 84.1% +/- 7.8% to 86.9% +/- 5.0% (p = .055). CONCLUSIONS: Treatment of GERD had a significant impact on the reduction of the apnea-hypopnea index, snoring, and daytime sleepiness. Elimination of GERD should be part of a comprehensive treatment plan for patients with OSAHS.

Guidelines for radioguided parathyroid surgery.

OBJECTIVE: To confirm or refute the notion that only parathyroid adenomas have radioactivity higher than 20% of background. DESIGN: Retrospective analysis of a prospective patient data set. SETTING: Tertiary care referral center. PATIENTS: Forty-six patients (9 men and 37 women; mean +/- SD age, 53.7 +/- 12.1 years) underwent thyroid and parathyroid surgery between December 2005 and December 2006 to collect data on ex vivo radioactivity percentages on a variety of tissues. INTERVENTIONS: Patients were injected with 296 to 925 MBq of technetium Tc 99m sestamibi 1(1/2) to 3(1/2) hours before surgery. Biopsy specimens were taken of normal parathyroid glands, normal thyroid tissue, and lymph nodes and ex vivo radioactivity was recorded. Hyperplastic parathyroid glands and adenomatous glands were excised. Finally, some enlarged glands were cut into segments, and radioactivity counts were recorded and compared with the weight of the tissue. MAIN OUTCOME MEASURES: All counts were compared with radioactivity percentages in the surrounding tissues, and results were expressed as a function of these background radioactive counts. RESULTS: The mean +/- SD ex vivo background radioactivity of parathyroid adenomas was 148.5% +/- 83.1% of background activity (range, 40.1%-388.9% but never less than 40%). The mean +/- SD ex vivo background radioactivity of hyperplastic parathyroid glands was 74.6% +/- 18.0% (range, 49.5%-109.1% but never less than 40%). A significant difference was found in ex vivo background radioactivity between pathologic parathyroid tissue and the other tissue specimens studied (normal parathyroid glands [2.4% +/- 1.8%], thyroid tissue [4.5% +/- 2.8%], lymph nodes [1.6% +/- 0.8%], and fat [0.4% +/- 0.3%]). CONCLUSIONS: Ex vivo radioactivity percentages can differentiate hyperactive parathyroid tissue from any other tissue, but they cannot differentiate adenoma from hyperplasia and thus are not helpful in ruling out multiglandular disease. Interpretation of ex vivo radioactivity percentages should take into consideration the size of the specimen.

Wireless upper esophageal monitoring for laryngopharyngeal reflux (LPR).

OBJECTIVES: To confirm feasibility of transnasal placement of a wireless pH-monitoring capsule in the upper esophagus, and to determine the positive predictive value of LPR and GERD signs and symptoms for diagnosis of LPR in patients with OSAHS. STUDY DESIGN: Prospective, nonrandomized, IRB-approved study of 89 OSAHS patients with and without symptoms and signs of LPR. METHODS: After complete history including QOL survey and fiberoptic laryngoscopy, patients underwent transnasal placement of the pH-monitoring capsule and wireless data collection for 24 hours. RESULTS: 77 of 89 consecutive patients underwent successful placement of wireless pH-monitoring capsule (86.5% success rate) and completed the study. 55 (71.4%) OSAHS patients had positive pH studies. 10.4% of these patients reported no symptoms or signs of LPR, indicating occult disease. CONCLUSION: Success rates of placement, tolerability, morbidity, and complications are excellent. Wireless upper esophageal pH monitoring is safe and effective for diagnosing LPR in patients with OSAHS.

Surgery of the palate and oropharynx.

Progress in successful surgical treatment of the obstructive sleep apnea/hypopnea syndrome (OSAHS) has been based on adjunctive treatment of the hypopharynx. Still the palate and oropharynx are the major areas of intervention, and certainly the most commonly operated upon. To ensure a successful outcome, appropriate surgical candidates must be identified. The authors present a method of clinical staging based on the position of the tongue relative to the soft palate as well as the size of the tonsils, aimed at identifying the most likely level of obstruction in patients who have OSAHS. We also present several surgical techniques that address obstruction at the level of the soft palate and oropharynx.

Bone marrow mononuclear cells stimulate angiogenesis when transplanted into surgically induced fibrocollagenous tunnels: results from a canine ischemic hindlimb model.

Progenitor cell transplantation has been considered as a potential angiogenesis therapy for the ischemic hindlimb. In this work we performed an ischemic hindlimb model in dogs. We ligated the middle sacra and the external right iliac arteries. After 7 days, the femoral artery was ligated and removed, and three Silastic tubes were inserted into the gracilis muscle to create fibrocollagenous tunnels. After Silastic implantation, we administered saline or granulocyte colony stimulating factor (G-CSF) subcutaneously daily during 5 days. Fourteen days after device positioning we transplanted bone marrow mononuclear cells (BMMC) into the tunnels previously formed by Silastic tube reaction. Twenty-eight days later, contrasted angiographies were performed and angiographic scores were calculated. Also, vessels and endothelial cells and proliferating cells were identified by immunochemistry of muscle sections. Results demonstrated that BMMC transplantation enriched by G-CSF administration significantly stimulates angiogenesis in the ischemic hindlimb, and more than BMMC transplantation alone. Transplantation of progenitor cells in an appropriate extracellular matrix is a potential therapy for hindlimb ischemia.

Palatal stiffening after failed uvulopalatopharyngoplasty with the Pillar Implant System.

OBJECTIVE/HYPOTHESIS: The objective of this study was to measure subjective and objective improvement after palatal stiffening in patients after uvulopalatopharyngoplasty (UPPP) who were experiencing persistence or recurrence of snoring with or without daytime sleepiness symptoms. STUDY DESIGN: The authors conducted a prospective, nonrandomized study of 26 patients after UPPP who underwent the Pillar Implant Technique (PIT) as a revision procedure. METHODS: Patients were selected to undergo revision PIT if they presented with recurrence or persistence of snoring after UPPP. Patients had mild or moderate obstructive sleep apnea-hypopnea syndrome (OSAHS) (apnea-hypopnea index [AHI] >5 and < or =40), persistent retropalatal obstruction, and a residual palate > or =2 cm. Some patients experienced daytime somnolence as well. Patients with severe OSAHS (AHI > or =40), Friedman anatomic stage IV, and/or nasopharyngeal stenosis were excluded. Pre-/postoperative snoring levels, Epworth Sleepiness Scale (ESS), SF-36v2 Quality of Life (QOL) questionnaires, and polysomnograms were obtained. RESULTS: We completed data on 23 patients. Postoperative snoring levels (3.4 +/- 1.8) and ESS (8.7 +/- 1.8) significantly improved (P < .0001) compared with preoperative values (8.7 +/- 1.8 and 13.2 +/- 2.9). A total of 73.9% of patients improved subjectively. Seven of eight SF-36v2 QOL domains showed significant improvement (P < .05). Postoperative AHI and minimum oxygen saturation also improved significantly (P < .05). Objective cure was only achieved in 21.7% of patients. CONCLUSIONS: Revision PIT is effective in achieving subjective improvement of recurrent symptoms after UPPP. Objective cure was only obtained in 21.7% of patients. As a result of the safety and low morbidity of the procedure, it is an alternative to improve symptoms, especially snoring, in patients not willing to accept continuous positive airway pressure permanently or patients who refuse revision surgery.

Fibrin glue: an alternative technique for nerve coaptation--Part I. Wave amplitude, conduction velocity, and plantar-length factors.

The search for better surgical repair of nerve injuries should be aimed at uncovering alternatives that not only are efficient, but also enhance nerve growth. The purpose of this study was to compare functional nerve responses following repair with either a traditional microsuture technique or Quixil human fibrin sealant. Thirty female Lewis rats received transection of the right sciatic nerve. Nerve repair was achieved with either epineurial microsuture (n = 15) or Quixil fibrin glue (n = 15). Functional results were assessed at 2, 6, and 12 weeks postoperatively with walking-track analysis. Electrophysiologic nerve recordings were also performed 12 weeks postoperatively. Rats receiving Quixil nerve repair returned to baseline performance on the walking-track analysis significantly faster than those with microsuture repairs (6 and 12 weeks postoperatively; p < 0.0001). Recovery of nerve conduction velocities and wave amplitudes was also significantly better in the nerves repaired with Quixil than in those repaired with microsuture (p's < 0.0001). Quixil human fibrin sealant is a good alternative to traditional microsuture nerve repair techniques.

Fibrin glue: an alternative technique for nerve coaptation--Part II. Nerve regeneration and histomorphometric assessment.

The results of nerve repair with fibrin glue and microsuture were evaluated in rat nerve transection models. Ninety Wistar-Furth rat median nerves were exposed, transected, and repaired in an end-to-end fashion with one of four substances/techniques: 1) human fibrin sealant (Quixil); 2) autologous graft and human fibrin sealant (Quixil); 3) bovine fibrin sealant (Tissucol); and 4) nylon microsuture, epineurial technique. Histologic analyses were performed at 3-, 6-, and 9-month postoperative intervals, and factors evaluated included: presence of inflammatory cells (i.e., macrophages and T cells); number of Schwann cells at the repair site; number of blood vessels; fibrosis; axonal regeneration; and fiber alignment. An additional group underwent histologic analysis at 3 weeks following repair with Quixil. Surgical time of repair was also measured. Nerve repairs performed with fibrin sealants produced less inflammatory response and fibrosis, and better axonal regeneration and fiber alignment than nerve repairs performed with microsuture. In addition, the fibrin sealant techniques were quicker and easier to use. The authors conclude that fibrin sealant represents a good alternative technique to microsuture for peripheral-nerve repair.

Arteriovenous access: managing common problems.

The creation and maintenance of hemoaccess occupies a significant portion of most vascular and general surgery practices. In this article, the methods used to detect hemoaccess at risk for failure and the endovascular and surgical techniques used to prolong or restore their patency are reviewed. Also, the management of hemoaccess infection, aneurysmal degeneration, false aneurysm formation, and symptomatic arterial steal syndrome are described.

Homozygous deletion of early growth response 1 gene and critical limb ischemia after vascular ligation in mice: evidence for a central role in vascular homeostasis.

BACKGROUND: The early growth response 1 gene (Egr1) encodes for an immediate to early response transcription factor that is upregulated by changes in vascular strain and hypoxia and in turn upregulates the downstream expressions of a number of angiogenic growth factors. We therefore hypothesized that early growth response 1 may be a critical early messenger governing revascularization in the setting of acute vascular occlusions. METHODS: C57 BL/6 mice deficient in the Egr1 gene (knockout) and their wild-type litter mates underwent ligation and excision of the femoral artery with or without the previous administration of 2.7 x 10(9) particle units of an adenoviral vector coding for the vascular endothelial growth factor gene (VEGF) or Egr1. Distal hind limb perfusion was serially measured in these animals with laser Doppler perfusion imaging. RESULTS: Wild-type mice (n = 9) had nearly complete restitution of hind limb perfusion by day 35 after ligation. In contrast, all noninjected Egr1 knockout mice (n = 5) had severe ipsilateral limb necrosis develop between 1 and 4 days after ligation (P <.0001). Egr1 knockout mice injected with VEGF vector (n = 4) demonstrated significantly improved perfusion relative to baseline by postligation day 28, which persisted to postligation day 35 (P <.05). Egr1 knockout animals injected with Egr1 vector (n = 7) demonstrated a partial recovery of hind limb perfusion relative to VEGF vector-treated knockout animals at postligation day 4 (P <.01), which persisted to day 35. CONCLUSIONS: These findings suggest that early growth response 1 plays a pivotal role in reperfusion responses to vascular occlusion in mice and possibly other mammals.

Angiogenic pretreatment improves the efficacy of cellular cardiomyoplasty performed with fetal cardiomyocyte implantation.

BACKGROUND: Cell implantation into areas of myocardial infarction (cellular cardiomyoplasty) may be limited in efficacy because of the lack of blood supply to these areas of myocardium, resulting in early loss of transplanted cells. We therefore tested the hypothesis that pretreatment of infarcted myocardium with angiogenic therapy, followed by cell transplant, would be more effective than the application of either strategy alone. METHODS: Fischer 344 rats underwent left coronary artery ligation and injection of an adenovirus encoding VEGF 121, an empty expression cassette control vector, or saline solution. Capillary density in the infarcted region was determined in preliminary studies. Cardiomyocytes harvested from syngeneic Fischer rat fetuses were prelabeled and then injected directly into the infarct area 3 weeks after vector administration. Exercise treadmill testing was performed 2 weeks after cell transplantation, after which a cell viability index was calculated as the number of implanted (prelabeled) nuclei divided by the number of coadministered microspheres detected in sections of implanted myocardium. RESULTS: Capillary density in the area of infarction was significantly greater in adenovirus encoding VEGF 121 compared with rats injected with saline solution (P =.001). The cell survival index was also greater in adenovirus encoding VEGF 121 compared with animals injected with empty expression cassette control or saline solution (P =.0045). Exercise tolerance was nearly doubled in animals receiving adenovirus encoding VEGF 121 3 weeks prior to cell implantation compared with animals receiving adenovirus encoding VEGF 121 or cells alone or those receiving adenovirus encoding VEGF 121 at the time of cell implantation (P <.001). CONCLUSIONS: Pretreatment of an infarcted region of the heart with angiogenic mediators such as VEGF can enhance the efficacy of cellular cardiomyoplasty, presumably by creating a more favorable environment for the survival of transplanted cells.

Adenoviral-mediated transfer of vascular endothelial growth factor 121 cDNA enhances myocardial perfusion and exercise performance in the nonischemic state.

BACKGROUND: Angiogenic gene therapy has been demonstrated to enhance perfusion to ischemic tissues, but it is unknown whether the administration of angiogenic growth factors will increase blood flow to nonischemic tissues. This study investigates whether enhanced myocardial perfusion can be mediated by adenovirus-mediated transfer of vascular endothelial growth factor 121 cDNA to nonischemic myocardium. METHODS: New Zealand White rabbits received adenovirus (5 x 10(10) particle units) encoding for vascular endothelial growth factor 121 (n = 14) or a control vector without a transgene (n = 13) or saline solution (n = 9) via direct myocardial injection. Fluorescent microsphere perfusion studies and histologic analyses were performed 4 weeks later. In a parallel study, exercise treadmill testing was performed to assess the functional effects of this therapy in Sprague-Dawley rats. RESULTS: Microsphere assessment of myocardial perfusion in rabbits 4 weeks after adenovirus-encoding vascular endothelial growth factor administration was greater than that for rats injected with control vector without a transgene or saline solution (3.2 +/- 0.5 vs 2.7 +/- 0.7 and 2.4 +/- 0.4, respectively; P <.03). The endothelial cell count per high power field was increased in animals injected with adenovirus-encoding vascular endothelial growth factor versus animals injected with control vector without a transgene or saline solution (147 +/- 27 vs 123 +/- 14 and 125 +/- 16 cells, respectively), although this did not reach statistical significance (P =.12). Rats treated with adenovirus-encoding vascular endothelial growth factor also demonstrated prolonged exercise tolerance compared with rats injected with control vector without a transgene or saline solution (exhaustion time: 26 +/- 5 minutes vs 19 +/- 2 minutes and 20 +/- 3 minutes, respectively; P =.006). CONCLUSIONS: Adenovirus encoding-mediated transfer of vascular endothelial growth factor 121 induces an enhancement in regional perfusion in nonischemic myocardium that corresponds to changes in exercise tolerance. Adenovirus-encoding vascular endothelial growth factor therapy may be useful for inducing angiogenesis in the nonischemic state, such as for prophylactic therapy of early coronary artery disease.