Spinal Lymphatic Dysfunction Aggravates the Recovery Process After Spinal Cord Injury.

We aimed to evaluate the role of the spinal lymphatic system in spinal cord injury and whether it has an impact on recovery after spinal cord injury. Flow cytometry was used to evaluate the changes in the number of microvesicles after spinal cord injury. Evans blue extravasation was used to evaluate the function of the lymphatic system. Evans blue extravasation and immunofluorescence were used to evaluate the permeability of blood spinal cord barrier. The spinal cord edema was evaluated by dry and wet weight.Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay was used to evaluate apoptosis after spinal cord injury. Nuclear factor-kappa B pathway was detected by Western blot. Behavioral tests were used to evaluate limb function. Microvesicles released after spinal cord injury can enter the thoracic duct and then enter the blood through the lymph around the spine. After ligation of the thoracic duct, it can aggravate the neuropathological manifestations and limb function after spinal cord injury. The potential mechanism may involve nuclear factor-kappa B pathway.

Lymphatic pathway evaluation in congenital heart disease using 3D whole-heart balanced steady state free precession and T2-weighted cardiovascular magnetic resonance.

BACKGROUND: Due to passive blood flow in palliated single ventricle, central venous pressure increases chronically, ultimately impeding lymphatic drainage. Early visualization and treatment of these malformations is essential to reduce morbidity and mortality. Cardiovascular magnetic resonance (CMR) T2-weighted lymphangiography (T2w) is used for lymphatic assessment, but its low signal-to-noise ratio may result in incomplete visualization of thoracic duct pathway. 3D-balanced steady state free precession (3D-bSSFP) is commonly used to assess congenital cardiac disease anatomy. Here, we aimed to improve diagnostic imaging of thoracic duct pathway using 3D-bSSFP. METHODS: Patients underwent CMR during single ventricle or central lymphatic system assessment using T2w and 3D-bSSFP. T2w parameters included 3D-turbo spin echo (TSE), TE/TR = 600/2500 ms, resolution = 1 × 1 × 1.8 mm, respiratory triggering with bellows. 3D-bSSFP parameters included electrocardiogram triggering and diaphragm navigator, 1.6 mm isotropic resolution, TE/TR = 1.8/3.6 ms. Thoracic duct was identified independently in T2w and 3D-bSSFP images, tracked completely from cisterna chyli to its drainage site, and classified based on severity of lymphatic abnormalities. RESULTS: Forty-eight patients underwent CMR, 46 of whom were included in the study. Forty-five had congenital heart disease with single ventricle physiology. Median age at CMR was 4.3 year (range 0.9-35.1 year, IQR 2.4 year), and median weight was 14.4 kg (range, 7.9-112.9 kg, IQR 5.2 kg). Single ventricle with right dominant ventricle was noted in 31 patients. Thirty-eight patients (84%) were status post bidirectional Glenn and 7 (16%) were status post Fontan anastomosis. Thoracic duct visualization was achieved in 45 patients by T2w and 3D-bSSFP. Complete tracking to drainage site was attained in 11 patients (24%) by T2w vs 25 (54%) by 3D-bSSFP and in 28 (61%) by both. Classification of lymphatics was performed in 31 patients. CONCLUSION: Thoracic duct pathway can be visualized by 3D-bSSFP combined with T2w lymphangiography. Cardiac triggering and respiratory navigation likely help retain lymphatic signal in the retrocardiac area by 3D-bSSFP. Visualizing lymphatic system leaks is challenging on 3D-bSSFP images alone, but 3D-bSSFP offers good visualization of duct anatomy and landmark structures to help plan interventions. Together, these sequences can define abnormal lymphatic pathway following single ventricle palliative surgery, thus guiding lymphatic interventional procedures.

Use of Contrast-Enhanced Ultrasound to Determine Thoracic Duct Patency.

The aim of this study was to determine the feasibility of using contrast-enhanced ultrasound (CEUS) evaluation to determine thoracic duct (TD) outlet patency. Nine patients referred for lymphatic imaging and intervention underwent percutaneous intranodal ultrasound contrast injection and conventional lymphangiography (CL). Eight of 9 patients had a patent TD by CEUS and CL. One patient did not have a patent TD. There was 100% agreement between CEUS and CL. These results suggest that CEUS is an imaging modality that might be as accurate as CL in determining TD patency.

Innominate Vein Turn-down Procedure for Failing Fontan Circulation.

After the Fontan, systemic venous hypertension induces pathophysiologic changes in the lymphatic system that can result in complications of pleural effusion, ascites, plastic bronchitis, and protein losing enteropathy. Advances in medical therapy and novel interventional approaches have not substantially improved the poor prognosis of these complications. A more physiological approach has been developed by decompression of the thoracic duct to the lower pressure common atrium with a concomitant increase of preload. Diverting the innominate vein to the common atrium increases the transport capacity of the thoracic duct, which in most patients enters the circulation at the left subclavian-jugular vein junction. Contrary to the fenestrated Fontan circulation, in which the thoracic duct is drained into the high pressure Fontan circulation, turn down of the innominate vein to the common atrium effectively decompresses the thoracic duct to the lower pressure system with "diastolic suctioning" of lymph. Innominate vein turn-down may be considered for medical-refractory post-Fontan lymphatic complications of persistent chylothorax, plastic bronchitis, and protein losing enteropathy. Prophylactic innominate vein turn-down may also be considered at time of the Fontan operation for patients that are higher risk for lymphatic complications.

Decompression of the thoracic duct: A novel transcatheter approach.

In patients with total cavopulmonary connections, elevated central venous pressures (CVP) have detrimental effects on the lymphatic system causing an imbalance in fluid production and drainage of the interstitium. This combination may result in life-threatening lymphatic complications including plastic bronchitis (PB), protein losing enteropathy (PLE), chylothorax, and ascites. While embolization of the abnormal lymphatics has greatly improved outcomes from these complications, alternative treatment strategies have been proposed that would result in improved lymphatic drainage while leaving the lymphatic system intact. We report two novel transcatheter approaches for thoracic duct (TD) decompression in two patients who developed PLE after completion of the Fontan procedure as part of staged palliation for congenital heart disease. In addition, one patient had severe concurrent PB. In both patients, a connection was created between a left superior vena cava (LSVC) to the left atrium allowing for a nonsurgical method to decompress the TD. This procedure resulted in significant clinical and laboratory improvement of both patients' PLE and other symptoms of lymphatic dysfunction.

Clinical approach and review of causes of a chylothorax.

A chylothorax, also known as chylous pleural effusion, is an uncommon cause of pleural effusion with a wide differential diagnosis characterized by the accumulation of bacteriostatic chyle in the pleural space. The pleural fluid will have either or both triglycerides >110 mg/dL and the presence of chylomicrons. It may be encountered following a surgical intervention, usually in the chest, or underlying disease process. Management of a chylothorax requires a multidisciplinary approach employing medical therapy and possibly surgical intervention for post-operative patients and patients who have failed medical therapy. In this review, we aim to discuss the anatomy, fluid characteristics, etiology, and approach to the diagnosis of a chylothorax.

Morphology and Function of the Lymphatic Vasculature in Patients With a Fontan Circulation.

BACKGROUND: The Fontan procedure has revolutionized the treatment of univentricular hearts. However, it is associated with severe complications such as protein-losing enteropathy, plastic bronchitis, and peripheral edema that may involve the lymphatic circulation. We aimed to assess lymphatic function and morphology in patients with a univentricular circulation. METHODS: The functional state of lymphatic vessels in the lower extremities of patients with a Fontan circulation (n=10) was investigated using the novel technique near-infrared fluorescence imaging and compared with an age-, sex-, and weight-matched control group of healthy volunteers (n=10). The lymphatic morphology was described using T2-weighted magnetic resonance imaging, and microvascular permeability was estimated by strain gauge plethysmography. RESULTS: The Fontan patients had 17% lower lymphatic pumping pressure (50±3.1 mm Hg) compared with controls (60±2.8 mm Hg; P=0.0341) and a 62% higher contraction frequency (0.8±0.1 min-1) compared with the healthy controls (0.5±0.1 min-1; P=0.0432). Velocity by which the lymph is moved and refill time after manual emptying of the lymphatic vessels showed no differences between the 2 groups. The thoracic duct was elongated 10% ( P=0.0409) and with an abnormal course in the Fontan patients compared with normal. No difference in microvascular permeability was found between the 2 groups. CONCLUSIONS: Patients with a Fontan circulation have an impaired lymphatic pumping capacity and morphologically changed thoracic duct. Our results indicate a challenged lymphatic vasculature in the Fontan circulation and may play a role in the pathogenesis of the complications that are seen in Fontan patients. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03379805.

Vascular and lymphatic complications after thoracic duct cannulation.

OBJECTIVE: The objective of this study was to determine the incidence of vascular and lymphatic complications after attempted transabdominal thoracic duct cannulation. METHODS: There were 58 patients who underwent attempted thoracic duct cannulation. Patients presented with chyle leak in the chest (n = 40), abdomen (n = 9), neck (n = 8), and pelvis (n = 1). Vertebral body level and geographic access, needle gauge, additional access for treatment, technical success, intervention performed, immediate and delayed complications, and follow-up duration were recorded. Imaging and electronic medical records were reviewed at follow-up for complications and treatment success. RESULTS: Access into the lymphatic system was obtained at L1 (n = 21), T12 (n = 17), L2 (n = 14), L3 (n = 3), T11 (n = 1), L4 (n = 1), and L5 (n = 1). Lymphatic access was achieved in the center (n = 28), on the right (n = 16), or on the left (n = 14) of the vertebral body; 21-, 22-, and 25-gauge needles were used in 45 patients, 12 patients, and 1 patient, respectively. Arm venous and percutaneous supraclavicular access was successful in 15 patients and eight patients, respectively. Cannulation of the thoracic duct was achieved in 52 (89.7%) patients. Embolization, disruption, and stenting were performed in 41 (70.7%), 12 (20.7%), and 2 (3.4%) patients; 3 (5.2%) patients had normal thoracic ducts after successful cannulation. Immediate complications consisted of shearing of the access wire in two (3.4%) patients. Retrospective analysis of initial follow-up imaging in 49 (84.5%) patients revealed the following late complications: inferior vena cava and right renal vein thrombosis and one perinephric lymphatic collection. CONCLUSIONS: Of 58 patients who had attempted thoracic duct cannulation, successful access was achieved in 90% of patients. Early and delayed complications occurred in 3.4% and 4% of patients, respectively. Thoracic duct cannulation represents a highly successful technique that aids in the treatment of chyle leaks in medically complex patients.

Embolization of the Thoracic Duct by Direct Injection of N-Butyl-2-Cyanoacrylate Glue via a Puncture Needle.

PURPOSE: To report embolization of the thoracic duct by direct injection of N-butyl-2-cyanoacrylate (NBCA) glue via a puncture needle. MATERIALS AND METHODS: Two cases of high output chylothorax were successfully treated with direct injection of N-butyl-2-cyanoacrylate (NBCA) glue via a puncture needle. In them, conventional thoracic duct embolization (TDE) was attempted, but the cisterna chyli was absent on intranodal lymphangiography, and probably for this reason catheterization of the thoracic duct was unsuccessful. Contrast material injection via a puncture needle, however, clearly showed a leak from the thoracic duct, prompting us to attempt embolization of the thoracic duct by direct injection of NBCA glue via the needle. RESULTS: Thoracic duct embolization by direct injection of NBCA glue via a puncture needle was technically successful in both patients. No minor or major complication occurred. Both patients disappeared chylothorax after this treatment. CONCLUSION: This embolization method can be useful for treatment of chylothorax when conventional TDE is not achievable.

Endolymphatic Thoracic Duct Stent-Graft Reconstruction for Chylothorax: Approach, Technical Success, Safety, and Short-term Outcomes.

BACKGROUND: To report approach, technical success, safety, and short-term outcomes of thoracic duct stent-graft reconstruction for the treatment of chylothorax. METHODS: Two patients, 1 (50%) male and 1 (50%) female, with mean age of 38 years (range: 16-59 years) underwent endolymphatic thoracic duct stent-graft reconstruction between September 2016 and July 2017. Patients had radiographic left-sided chylothoraces (n = 2) from idiopathic causes (n = 1) and heart transplantation (n = 1). In both (100%) patients, antegrade lymphatic access was used to opacify the thoracic duct after which retrograde access was used for thoracic duct stent-graft placement. Pelvic lymphangiography technical success, antegrade cisterna chyli cannulation technical success, thoracic duct opacification technical success, retrograde thoracic duct access technical success, thoracic duct stent-graft reconstruction technical success, ethiodized oil volume, contrast volume, estimated blood loss, procedure time, fluoroscopy time, radiation dose, clinical success, complications, deaths, and follow-up were recorded. RESULTS: Pelvic lymphangiography, antegrade cisterna chyli cannulation, thoracic duct opacification, retrograde thoracic duct access, and thoracic duct stent-graft reconstruction were technically successful in both (100%) patients. Mean ethiodized oil volume was 8 mL (range: 5-10 mL). Mean contrast volume was 13 mL (range: 5-20 mL). Mean estimated blood loss was 13 mL (range: 10-15 mL). Mean fluoroscopy time was 50.4 min (range: 31.2-69.7 min). Mean dose area product and reference air kerma were 954.4 µGmy2 (range: 701-1,208 µGmy2) and 83.5 mGy (range: 59-108 mGy), respectively. Chylothorax resolved in both (100%) patients. There were no minor or major complications directly related to the procedure. CONCLUSIONS: Thoracic duct stent-graft reconstruction may be a technically successful and safe alternative to thoracic duct embolization, disruption, and surgical ligation for the treatment of chylothorax. Additional studies are warranted.

The thoracic duct and the Fontan patient.

BACKGROUND: Ultrasound imaging of adults with heart failure and increased central venous pressure (CVP) has shown significant thoracic duct (TD) dilation from impedance in lymphatic drainage. Elevated CVP and abnormal lymphatic drainage are implicated in severe Fontan complications, including protein losing enteropathy (PLE) and plastic bronchitis (PB). Systematic studies of TD and lymphatic circulation in children are limited, and their cervical TD normative values have not been established. METHODS: Thoracic duct imaging was attempted prospectively during routine echocardiograms performed 7/2014-9/2016 in children 5-21 years old with normal cardiovascular physiology and Fontan palliation. TD insertion to the central venous system (lympho-venous junction) was assessed with an S12-4 MHz transducer. For the first 34 patients, only TD ostia were measured, but ostium shape variability at the lympho-venous junction led to including the TD arch 5-10 mm proximal to the ostium for the remaining cohort. RESULTS: Seventy-nine total subjects were studied: 58 controls, 13 Fontan patients with normal systemic ventricular ejection fraction (EF) (>50%), and 8 Fontan patients with decreased EF (≤50%). Combined Fontan subjects had larger TD ostial diameters compared to controls when normalized by body surface area (median 2.6 mm/m2 vs. 2 mm/m2 ) (P=.04). CONCLUSION: To our knowledge, this is the first systematic study of ultrasonographic TD imaging in children. Fontan patients have larger TD diameters, reflecting the impaired lymphatic circulation in patients with this physiology. Further research may provide important associations between sonographic TD features with the functional status of patients with Fontan circulation.

Superselective retrograde lymphatic duct embolization for management of postoperative lymphatic leak.

Lymphatic leak is a well-documented complication following neck dissection surgeries. When conservative methods fail to control the leak, thoracic duct embolization becomes an option. Transabdominal access is the standard for this procedure; however, it is not always feasible. We discuss a technique of selective lymphatic vessel embolization utilizing retrograde transvenous access.

Polydom Is an Extracellular Matrix Protein Involved in Lymphatic Vessel Remodeling.

RATIONALE: Lymphatic vasculature constitutes a second vascular system essential for immune surveillance and tissue fluid homeostasis. Maturation of the hierarchical vascular structure, with a highly branched network of capillaries and ducts, is crucial for its function. Environmental cues mediate the remodeling process, but the mechanism that underlies this process is largely unknown. OBJECTIVE: Polydom (also called Svep1) is an extracellular matrix protein identified as a high-affinity ligand for integrin α9ß1. However, its physiological function is unclear. Here, we investigated the role of Polydom in lymphatic development. METHODS AND RESULTS: We generated Polydom-deficient mice. Polydom-/- mice showed severe edema and died immediately after birth because of respiratory failure. We found that although a primitive lymphatic plexus was formed, it failed to undergo remodeling in Polydom-/- embryos, including sprouting of new capillaries and formation of collecting lymphatic vessels. Impaired lymphatic development was also observed after knockdown/knockout of polydom in zebrafish. Polydom was deposited around lymphatic vessels, but secreted from surrounding mesenchymal cells. Expression of Foxc2 (forkhead box protein c2), a transcription factor involved in lymphatic remodeling, was decreased in Polydom-/- mice. Polydom bound to the lymphangiogenic factor Ang-2 (angiopoietin-2), which was found to upregulate Foxc2 expression in cultured lymphatic endothelial cells. Expressions of Tie1/Tie2 receptors for angiopoietins were also decreased in Polydom-/- mice. CONCLUSIONS: Polydom affects remodeling of lymphatic vessels in both mouse and zebrafish. Polydom deposited around lymphatic vessels seems to ensure Foxc2 upregulation in lymphatic endothelial cells, possibly via the Ang-2 and Tie1/Tie2 receptor system.

Lymphangiography for Thoracic Duct Interventions.

Lymph leaks resulting in chylous pleural effusions can be life-threatening. Minimally invasive thoracic duct embolization and disruption have been gaining acceptance as first-line treatment for these leaks. This review discusses the techniques for both pedal and intranodal lymphangiography in detail. It also discusses the use of lymphangiography as a means of targeting a retroperitoneal lymphatic to facilitate thoracic duct interventions for chyle leaks. Finally, outcomes and adverse events pertaining to these thoracic duct interventions are discussed.

Nontraumatic Chylothorax: Diagnostic Algorithm and Treatment Options.

Nontraumatic chylothorax is a relatively rare condition in which the intestinal lymph (chyle) leaks into the pleural cavity. Nontraumatic chylothorax is more difficult to treat than the more common traumatic chylothorax because the site of chylous leak may occur in less predictable locations. In the past, patients with nontraumatic chylothoraces were offered traditional fluoroscopically guided lymphangiography and thoracic duct embolization similar to traumatic chylothorax. However, the observation that thoracic duct embolization outcomes for nontraumatic chylothorax differed based on the imaging findings during lymphangiography has led to the development of a treatment algorithm, which incorporates noninvasive diagnostic studies, such as magnetic resonance lymphangiography. The development of this systematic approach allows better delineation of the source of the chylous leak and selection of the appropriate method of embolization. In this article, we will review the etiologies of nontraumatic chylothorax, the diagnostic work-up for managing this condition, and the treatment algorithm to care for these patients.

[Review of evidence-based modern treatment for chylothorax]. / A chylothorax modern kezelésének bizonyítékalapú áttekintése.

Chylothorax is a multi-factorial complication, frequently of an operation or an accident, but rarely of a tumour. In the absence of prospective or randomised studies evidence-based treatment is normally based on personal experience, ideally in the possession of retrospective analyses using the "best practice" method. The aim of the authors was the review the up-to-date chylothorax treatments. They performed the PubMed database's "chylothorax" keyword search of the publications reported in the last ten years. They put emphasis on articles that included a comparative analysis of the various treatment options. During the critical analysis of the methods and recommendations, the authors relied on their own joint experience amounting to 39 years. The results showed that the success of the initial conservative treatment indicates a significant deviation depending on the etiology (3-90%). The success rate of non-invasive or semi-invasive interventions is between 50-100%, again depending on the etiology. The standard surgical treatment following an unsuccessful conservative treatment of an operable patient includes the fitting of a (thoracoscopic) knot to the ductus thoracicus, pleurodesis, insertion of a permanent chest drain or a pleuroperitoneal shunt. The success rate of these interventions is between 64-100%, with a morbidity index and mortality index exceeding 25%. Conservative treatment should be the first step, which should then be followed by a gradually increased aggressive therapy, during which the decisions should be made according to the patient's condition and the drain volume. Interventional radiology procedures are safe, successful and they can be offered concurrently with conservative or operative treatment, although they are available only in a few centres.

Blunted flow-mediated responses and diminished nitric oxide synthase expression in lymphatic thoracic ducts of a rat model of metabolic syndrome.

Shear-dependent inhibition of lymphatic thoracic duct (TD) contractility is principally mediated by nitric oxide (NO). Endothelial dysfunction and poor NO bioavailability are hallmarks of vasculature dysfunction in states of insulin resistance and metabolic syndrome (MetSyn). We tested the hypothesis that flow-dependent regulation of lymphatic contractility is impaired under conditions of MetSyn. We utilized a 7-wk high-fructose-fed male Sprague-Dawley rat model of MetSyn and determined the stretch- and flow-dependent contractile responses in an isobaric ex vivo TD preparation. TD diameters were tracked and contractile parameters were determined in response to different transmural pressures, imposed flow, exogenous NO stimulation by S-nitro-N-acetylpenicillamine (SNAP), and inhibition of NO synthase (NOS) by l-nitro-arginine methyl ester (l-NAME) and the reactive oxygen species (ROS) scavenging molecule 4-hydroxy-tempo (tempol). Expression of endothelial NO synthase (eNOS) in TD was determined using Western blot. Approximately 25% of the normal flow-mediated inhibition of contraction frequency was lost in TDs isolated from MetSyn rats despite a comparable SNAP response. Inhibition of NOS with l-NAME abolished the differences in the shear-dependent contraction frequency regulation between control and MetSyn TDs, whereas tempol did not restore the flow responses in MetSyn TDs. We found a significant reduction in eNOS expression in MetSyn TDs suggesting that diminished NO production is partially responsible for impaired flow response. Thus our data provide the first evidence that MetSyn conditions diminish eNOS expression in TD endothelium, thereby affecting the flow-mediated changes in TD lymphatic function.

Proposal for Prevention or Alleviation of Protein/Lymph-Losing Enteropathy (PLE/LLE) After Fontan Circulation Treatment of Univentricular Hearts: Restoration of Lymph Balance With a "Lymphatic Right-to-Left Shunt."

In Fontan circulations created for univentricular hearts, systemic venous return is diverted to the lungs before returning to the heart. The Total Cavopulmonary Connection (TCPC) is often the preferred surgical procedure whereby a 4-way anastomosis is created with inflow from the superior vena cava (SVC) and inferior vena cava (IVC) and outflow to the right and left branches of the pulmonary artery. In this arrangement, the systemic venous pressure must be elevated sufficiently to perfuse the lungs passively without the normal boost of the right ventricle. Hence, unlike surgical corrections for other congenital heart conditions, the systemic venous pressures in a Fontan circuit must be elevated to make the circulation work. It is proposed here that the incidence of PLE/LLE is directly related to elevated venous and lymphatic pressures, which cause leakage of proteins/lymph into the gastrointestinal tract (GIT) and expulsion from the body. It is commonly held that elevated venous pressures are relatively better tolerated in the upper body, but much less so in the heptatosplanchnic circulation and the lower body. It is also well established that elevated venous pressure increases lymph formation, most of which is produced in the hepatosplanchnic region (liver and intestine). It is further argued here that the increase in lymph filling pressure arising from the higher lymph flow, in association with the backpressure exerted by elevated venous pressure at the main drainage point into the venous system, results in a substantial increase in pressure in the thoracic duct. This pressure is transmitted back to the intestinal lymphatics, causing dilatation with lacteal rupture and protein or bulk lymph leakage into the intestine. We propose in this paper a new approach, based on experimental evidence, to prevent and/or alleviate this condition by draining or redirecting the thoracic duct (or, alternatively, a more localized intestinal lymphatic vessel) into one of the pulmonary veins or the left atrium, which are typically at near-normal pressure in a Fontan circulation. This "lymphatic-venous right-to-left" shunt maneuver would significantly reduce the venous backpressure on the lymphatics as well as improve lymph circulation, resulting in a decrease in the intestinal lymphatic pressure and thereby prevent or alleviate protein/lymph loss, i.e. lymph balance would be restored. Moreover, the greatly facilitated lymphatic flow would encourage further capillary filtration to relieve excessive venous pressure in the hepatosplanchnic region and protect the liver and kidneys. This paper is intended as a discussion document for elicitation of comments on the soundness and viability of this proposal as well as on technical challenges and steps to explore and advance it.

Lymphatic pump treatment as an adjunct to antibiotics for pneumonia in a rat model.

BACKGROUND: Lymphatic pump treatment (LPT) is a technique used by osteopathic physicians as an adjunct to antibiotics for patients with respiratory tract infections, and previous studies have demonstrated that LPT reduces bacterial load in the lungs of rats with pneumonia. Currently, it is unknown whether LPT affects drug effcacy. OBJECTIVE: To determine whether the combination of antibiotics and LPT would reduce bacterial load in the lungs of rats with acute pneumonia. METHODS: Rats were infected intranasally with 5×107 colony-forming units (CFU) of Streptococcus pneumoniae. At 24, 48, and 72 hours after infection, the rats received no therapy (control), 4 minutes of sham therapy, or 4 minutes of LPT, followed by subcutaneous injection of 40 mg/kg of levofoxacin or sterile phosphate-buffered saline. At 48, 72, and 96 hours after infection, the spleens and lungs were collected, and S pneumoniae CFU were enumerated. Blood was analyzed for a complete blood cell count and leukocyte differential count. RESULTS: At 48 and 72 hours after infection, no statistically significant differences in pulmonary CFU were found between control, sham therapy, or LPT when phosphate-buffered saline was administered; however, the reduction in CFU was statistically significant in all rats given levofoxacin. The combination of sham therapy and levofoxacin decreased bacterial load at 72 and 96 hours after infection, and LPT and levofoxacin significantly reduced CFU compared with sham therapy and levofoxacin at both time points (P<.05). Colony-forming units were not detected in the spleens at any time. No statistically significant differences in hematologic findings between any treatment groups were found at any time point measured. CONCLUSION: The results suggest that 3 applications of LPT induces an additional protective mechanism when combined with levofoxacin and support its use as an adjunctive therapy for the management of pneumonia; however, the mechanism responsible for this protection is unclear.