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H Wong

Publications and source records attributed to H Wong.

At least 91 records · Page 5Linked to original sources
PubMed1997

A molecular biology-based approach to resolve the subunit orientation of lipoprotein lipase.

The subunit orientation of a dimeric enzyme influences the mechanism of action and function. To determine the subunit arrangement of lipoprotein lipase (LPL), a molecular biology-based approach was initiated. An eight amino acid linker region was engineered between two LPL monomers and expressed in COS-7 cells. The resultant tandem-repeat molecule (LPLTR) was lipolytically active and had kinetic parameters, salt inhibition, cofactor-dependent activity, heparin-binding characteristics, and a functional unit size very similar to the expressed native human enzyme. By these criteria, LPLTR was the functional equivalent of native LPL. Considering the length of the linker peptide (no more than 24 A), monomers in the tethered molecule were restricted to a head-to-tail subunit arrangement. Since LPLTR demonstrated native enzyme-like properties while constrained to this subunit arrangement, these results provide the first compelling evidence that native LPL monomers are arranged in a head-to-tail subunit orientation within the active dimer. Thus, LPL function in physiology, lipolysis, and binding to cell-surface components must now be addressed with this subunit orientation in mind. The utility of the tandem-repeat approach to resolve the subunit arrangement of an obligate dimer has been demonstrated with LPL and could be generalized for use with other oligomeric enzymes.

Animals↗
PubMed1997

Early pulmonary cytokine responses to zinc oxide fume inhalation.

Zinc oxide inhalation causes metal fume fever, a flu-like syndrome common among welders. Proinflammatory pulmonary cytokines play a role in mediating this occupational illness. The goal of this investigation was to characterize early pulmonary cytokine responses after experimental human exposure to inhaled purified zinc oxide fume. We quantified bronchoalveolar lavage (BAL) cytokine concentrations in 15 healthy volunteers 3 hr after inhalation of zinc oxide fume. We compared postexposure cytokine responses with postsham exposure responses in the same 15 subjects. We also compared cytokine responses with those of 14 "late follow-up" subjects previously studied by BAL 20 hr after zinc oxide fume exposure. Zinc oxide exposure was a statistically significant, dose-dependent predictor of increases in BAL TNF (mean exposure-sham difference +/- SE = 9.5 +/- 3.6 pg/mL, P = 0.02), IL-6 (mean exposure-sham difference +/- SE = 5.5 +/- 1.8 pg/mL, P = 0.009), and IL-8 (mean exposure-sham difference +/- SE = 64.1 +/- 23.9 pg/mL, P = 0.02). The TNF response was significantly greater at 3 hr follow-up compared with 20 hr follow-up, after adjusting for smoking status, zinc dose, and BAL macrophages (P = 0.004). Our findings provide evidence for a pulmonary inflammatory response 3 hr after inhalation of zinc oxide fume characterized by dose-dependent increases in BAL proinflammatory cytokine concentrations. These data indicate that TNF plays an important initial role in mediating metal fume fever.

Adult↗
PubMed1997

Lipase engineering: a window into structure-function relationships.

Utilization of genetic engineering techniques to create novel functional lipases has increased knowledge of structure-function relationships in this important class of enzymes. The examples of engineered lipases presented in this chapter addressed the investigation of domain-specific properties, heparin binding, and subunit orientation. Conclusions reached are credible because the designed lipases retained catalytic activity, implying native, or near-native, conformation. This approach has demonstrated vigor by determining the domain location of several important enzyme functions and by providing the first evidence that LPL subunits are arranged in a head-to-tail orientation. In conjunction with physical techniques, such as crystallography and nuclear magnetic resonance spectroscopy, the engineered lipase approach could reveal new insights into the mechanism by which lipolysis is accomplished. The studies described here represent only the first attempts to explore that subject; more sophisticated lipase engineering will be used in future as a window into structure-function relationships.

Amino Acid Sequence↗
PubMed1997

Immunohistochemical localization of gastrin/CCK-B receptors in the dog and guinea-pig stomach.

Gastrin/CCK-B receptors are involved in the regulation of several types of cells of the gastric mucosa, including the parietal cells, the ECL cells and the D cells. In this study, we aimed at localizing such receptors in the gastric mucosa. For this purpose, we prepared monospecific antibodies against two sequences of the canine gastrin/CCK-B receptor. Sections of formalin-fixed, paraffin-embedded corpus and antrum from dog and guinea-pig were immunostained with these antibodies. In parallel, sections were stained with antibodies against somatostatin. Staining with gastrin/CCK-B receptor antibodies was observed in a few, small epithelial cells in the bottom part of the corpus mucosa. Immunoreactive cells of the antral mucosa were structurally similar, but more frequent. The same cells also stained with somatostatin antibodies. In addition one of the gastrin/CCK-B antibodies reacted with canine submucosal smooth muscle cells. No staining was observed in sections exposed to antibodies that were pre-absorbed with the corresponding antigen. We conclude that gastrin/CCK-B receptors are present in D cells of the gastric mucosa and in submucosal smooth muscle cells.

Animals↗
PubMed1997

Both CD4+ and CD8+ human lymphocytes are activated and proliferate in response to Cryptococcus neoformans.

The current studies were performed to determine the contribution of T-cell subsets to lymphocyte proliferation in response to Cryptococcus neoformans, the most common invasive mycosis in acquired immune deficiency syndrome. We demonstrate for the first time that both human CD4 and CD8 cells are activated in response to C. neoformans. Both CD4 and CD8 cells express interleukin-2 receptor alpha (IL-2R alpha) and transferrin receptor and proliferate in response to C, neoformans, however proliferation of CD8 cells was dependent upon CD4 cells. The requirement for CD4 cells was complex, since CD8 enriched cells failed to express mRNA for IL-2, suggesting that CD4-dependent IL-2 production was required for CD8-cell proliferation. However, IL-2 was not sufficient to restore CD8-cell proliferation. These studies provide experimental evidence in humans to support the clinical impression that CD4 cells are important in cryptococcosis, and suggest that the appropriate CD4-derived signals could allow CD8 cells to assist in host defence.

Adult↗
PubMed1997

Comparison of Ho:YAG versus Nd:YAG thoracoscopic laser treatment of pulmonary bullae in a rabbit model.

OBJECTIVE: To determine the relative efficacy and morbidity of Ho:YAG versus Nd:YAG laser treatment of bullous lung disease in an animal model. SUMMARY BACKGROUND DATA: Laser coagulation procedures for treatment of emphysematous pulmonary bullae and heterogeneous emphysema continue to evolve. The role of lasers in lung volume reduction surgery remains controversial due to issues of relative efficacy and morbidity. The Nd:YAG laser is most commonly used for these procedures. We hypothesized that the shallower penetration of the Ho:YAG laser may be better suited for laser bullae coagulation and emphysema lung volume reduction with increased efficacy and reduced lung injury. METHODS: Thirty New Zealand White rabbits (15 normal rabbits; 15 with bullous lung disease) were evaluated with Ho:YAG compared to Nd:YAG laser exposures. Bullae were coagulated by either Ho:YAG or Nd:YAG treatment. In all animals (bullous-induced and normals), unaffected lung tissue in the upper lobes and contralateral lungs were treated with 5 spot exposures of Nd:YAG and Ho:YAG, each to assess depth of lung injury. Animals were sacrificed at Days 0, 7, and 21 and their lungs were examined histologically. RESULTS: Ho:YAG and Nd:YAG exposures caused equivalent lung injury to normal lung tissue. In the acute phase, parenchymal necrosis depth was similar for both Ho:YAG and Nd:YAG (850 +/- 273 microns vs. 900 +/- 270 microns respectively, p = 0.7). By Day 7, lung necrosis depth was 925 +/- 133 microns Ho:YAG vs. 1225 +/- 235 microns Nd:YAG (p = 0.33), and lung fibrosis depth was 300 +/- 134 microns Ho:YAG vs. 558 +/- 127 microns Nd:YAG (p = 0.11). By Day 21, pulmonary parenchymal necrosis was not seen. Pleural fibrosis depth was maximal at Day 21, reaching 250 +/- 102 microns for Ho:YAG vs. 300 +/- 156 microns Nd:YAG (P = 0.88). Pleural necrosis depth was 67 +/- 42 microns Ho:YAG vs 48 +/- 34 microns Nd:YAG (p = 0.42) on Day 7 and resolved by Day 21. During surgical coagulation procedures, the Ho:YAG laser was dramatically more efficient in coagulating bullae. The Ho:YAG laser required less exposure at equivalent power and resulted in immediate desiccation of bullae, in sharp contrast to the Nd:YAG laser. CONCLUSIONS: Because the Ho:YAG was more effective and did not result in more acute lung injury than the standard Nd:YAG laser in this study, Ho:YAG lasers may have improved potential for laser treatment of bullae or lung volume reduction surgery (LVRS) compared to Nd:YAG lasers.

Animals↗
PubMed1997

Intraislet regulation of pancreatic polypeptide secretion in the isolated perfused rat pancreas.

The present study is to determine if intraislet insulin or somatostatin regulate pancreatic polypeptide (PP) secretion in the isolated perfused rat pancreas by infusing insulin or somatostatin antisera. Isolated rat pancreata were stimulated with either 16.7 mM glucose (G) alone, G with antisomatostatin antibody (G + SA), or G with antiinsulin antibody (G + IA). G inhibited PP secretion -22 +/- 9.5 pM below basal, a decrease of 9 +/- 6.3% (n = 6; p = NS), G + IA inhibited PP secretion -10 +/- 27.2 pM below basal, a decrease of 20 +/- 15% (n = 7, p = NS), and G + SA stimulated PP secretion 18 +/- 7.1 pM above basal, an increase of 26 +/- 5% (n = 6; p < 0.05). G stimulated insulin secretion 3,144 +/- 210 pM above basal (n = 6, p < 0.05), and G + SA stimulated insulin secretion 2,695 +/- 195 pM above basal (n = 7; p < 0.05 vs. baseline, p = NS vs. G alone). G stimulated C-peptide secretion 886 +/- 175 pM above basal (n = 6; p < 0.05), G + SA stimulated C-peptide secretion 847 +/- 102 pM above basal (n = 7; p < 0.05, p = NS vs. G alone), and G + IA stimulated C-peptide secretion 834 +/- 93 pM above basal (n = 7; p < 0.05, p = NS vs. G alone). These data demonstrate that infusion of SA results in significant stimulation of PP secretion during high-G infusion, whereas IA has no effect. Infusions of SA or IA at the doses used have no effect on G-stimulated insulin or C-peptide secretion. This suggests that intraislet somatostatin may be an inhibitory regulator of PP secretion in the isolated perfused rat pancreas.

Animals↗
PubMed1997

Pulmonary responses after wood chip mulch exposure.

Organic Dust Toxic Syndrome (ODTS) is a flu-like syndrome that can occur after inhalation of cotton, grain, wood chip dusts, or other organic dusts or aerosols. We investigated whether inflammatory pulmonary responses occur, even after relatively brief, low-level wood chip mulch exposure. Six volunteers were exposed to wood chip mulch dust. Total dust and/or endotoxin levels were measured in five subjects. Pulmonary function and peripheral blood counts were measured before and after exposure in each subject. Bronchoalveolar lavage (BAL) was performed in each subject after exposure, and cell, cytokine, and protein concentrations were measured. Control BAL without previous exposure was also performed on three of the subjects. Three of six subjects had symptoms consistent with ODTS. No clinically relevant or statistically significant changes in pulmonary function tests after exposure were found. Three subjects manifested a marked elevation in neutrophil percentage in their BAL (range, 10 to 57%). When these three subjects underwent control BAL, the postexposure comparison demonstrated an increase in neutrophil levels of 154 +/- 89 x 10(3)/mL (mean +/- standard error; P = 0.22). The mean increase in BAL interleukin-8 levels after exposure, compared with paired control values, was 11.2 +/- SE 2.5 pg/mL (P = 0.047). There was also an increase in BAL interleukin-6 levels that reached borderline significance (6.4 +/- SE 2.0 pg/mL; P = 0.08). Tumor necrosis factor levels were increased in all three subjects' BAL as well (0.4 +/- SE 0.2 pg/mL), but this change was not statistically significant (P = 0.2). Our findings of increased BAL proinflammatory cytokine and neutrophil levels are consistent with the theory that cytokine networking in the lung may mediate ODTS.

Adult↗
PubMed1997

Subtypes Y1 and Y2 of the neuropeptide Y receptor are respectively expressed in pro-opiomelanocortin- and neuropeptide-Y-containing neurons of the rat hypothalamic arcuate nucleus.

The arcuate nucleus of the hypothalamus houses a number of neurochemically different cell populations. Among these, a dense cluster of small neuropeptide-Y (NPY)-expressing neurons is located in its ventromedial subdivision and a pro-opiomelanocortin (POMC)-expressing neuron population in its ventrolateral part. Furthermore, both neuropeptide Y Y1 and Y2 receptors (Y1-Rs and Y2-Rs) are expressed in the arcuate nucleus. Here we analyse the co-expression of NPY and POMC/adrenocorticotropic hormone with the Y1-R and Y2-R in arcuate neurons using immunohistochemistry and in situ hybridization. Many, but not all, POMC neurons expressed Y1-R mRNA and protein. Conversely, several Y1-R-positive, POMC-negative neurons were found. NPY-positive nerve terminals were found in close apposition to Y1-R-like immunoreactivity localized close to the dendritic and somatic cell membranes. Y2-R mRNA was found in almost all NPY mRNA-expressing neurons, but also in a group of NPY mRNA-negative cells. These results show that the POMC neurons are targets for NPY, which is presumably present in, and released from, fibres originating in the ventromedial arcuate nucleus and which may play a role in NPY-induced feeding. Release of NPY, and possible coexisting messengers, may be controlled by presynaptic Y2-R expressed in NPY neurons. Taken together, the findings support the division of Y1-Rs and Y2-Rs into post- and presynaptic receptors, respectively.

Adrenocorticotropic Hormone↗
PubMed1997

Objective predictors of response for staple versus laser emphysematous lung reduction.

Recently described surgical approaches to the treatment of emphysema, including buttressed stapled volume reduction and laser coagulation, are associated with variable clinical outcomes. We examined objective preoperative factors as predictors of response to treatment in patients enrolled in a randomized trial of staple versus laser volume-reduction surgery in order to help define patient selection criteria for these procedures. Seventy-two patients with severe symptomatic emphysema without bullae were entered into the protocol (39 staple, 33 laser). Preoperative objective variables (pulmonary function tests, smoking history, demographics, and graded chest computed tomographic [CT] scans) were evaluated as predictors of response to treatment (defined as a change in FEV1) at 3- to 6-mo follow-up, using linear and multivariate regression analysis. Follow-up pulmonary function was obtained on 90% of the 68 patients surviving at 6 mo. Overall improvement was significant only for staple-treated patients, and improved outcome correlated with greater smoking history and younger age for staple-treated patients. When physiologic variables were analyzed, greater smoking history, lower DL(CO), and younger age predicted improved outcome for laser-treated patients. Preoperative FEV1 and gas-exchange variables did not predict outcome in staple-treated patients. When CT scan grading was included in multivariate regression analysis, hyperinflation (increased thoracic gas volume) was the primary predictor of response for laser-treated patients. These findings suggest that younger patients with evidence of advanced emphysematous lung disease and hyperinflation are optimal candidates for lung-volume-reduction surgery, particularly by staple-reduction techniques. Additional studies with long-term follow-up, bilateral procedures, and assessment of other outcome measures must be performed to further define operative criteria for lung-volume-reduction surgery for emphysema.

Age Factors↗
PubMed1997

Human pulmonary responses to experimental inhalation of high concentration fine and ultrafine magnesium oxide particles.

Exposure to air polluted with particles less than 2.5 micron in size is associated epidemiologically with adverse cardiopulmonary health consequences in humans. The goal of this study was to characterize human pulmonary responses to controlled experimental high-dose exposure to fine and ultrafine magnesium oxide particles. We quantified bronchoalveolar lavage (BAL) cell and cytokine concentrations, pulmonary function, and peripheral blood neutrophil concentrations in six healthy volunteers 18 to 20 hr after inhalation of fine and ultrafine magnesium oxide particles produced from a furnace system model. We compared postexposure studies with control studies from the same six subjects. Mean +/- standard deviation (SD) cumulative magnesium dose was 4,138 +/- 2,163 min x mg/m3. By weight, 28% of fume particles were ultrafine (<0.1 micron in diameter) and over 98% of fume particles were fine (<2.5 micron in diameter). There were no significant differences in BAL inflammatory cell concentrations, BAL interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor, pulmonary function, or peripheral blood neutrophil concentrations postexposure compared with control. Our findings suggest that high-dose fine and ultrafine magnesium oxide particle exposure does not produce a measurable pulmonary inflammatory response. These findings are in marked contrast with the well-described pulmonary inflammatory response following zinc oxide particle inhalation. We conclude that fine and ultrafine particle inhalation does not result in toxicity in a generic manner independent of particle composition. Our findings support the concept that particle chemical composition, in addition to particle size, is an important determinant of respiratory effects.

Adult↗
PubMed1996

Deposition and Thinning of the Human Tear Film

The exposed part of the eyeball is covered by a tear film, which is vital for the proper function of the eye. The film thickness has been measured to be roughly 10 &mu;m; however, how a tear film of this thickness is generated has not been clearly explained. It is proposed that the tear film is deposited analogous to a coating process by the rising meniscus of the upper lid during a blink. A coating model is formulated that not only predicts correctly the film thickness, but also captures the postblink lipid spreading commonly observed in experiments. A deposited tear film thins rapidly near the tear meniscus surrounding the film. Numerical simulation of this thinning reveals that the minimum film height obeys a power law. When the minimum height reaches the effective range of dewetting intermolecular forces, the film ruptures. The thinning time therefore defines a breakup time, and the thinning law shows explicitly how this breakup time is related to tear viscosity, surface tension, meniscus radius, and initial and final film thicknesses. The calculated breakup time agrees with those observed experimentally.

Journal Article↗
PubMed1996

Characterization of antisera specific to NK1, NK2, and NK3 neurokinin receptors and their utilization to localize receptors in the rat gastrointestinal tract.

Understanding the physiological role of tachykinins requires precise cellular and subcellular localization of their receptors. We raised antisera by immunizing rabbits with peptides corresponding to portions of the intracellular tails of the rat neurokinin 1, 2, and 3 receptors (NK1-R, NK2-R, NK3-R). Receptors were localized by immunofluorescence and confocal microscopy. NK1-R, NK2-R, and NK3-R were detected at the plasma membrane of transfected cells with minimal intracellular stores. Staining was abolished by preabsorption of the antisera with the peptides used for immunization. Nontransfected cells were unstained. Each antiserum only stained cells transfected with the appropriate receptor and did not stain cells transfected with the other receptors. Therefore, the antisera are specific and do not cross-react with other neurokinin receptors. We examined the distribution of the neurokinin receptors in the gastrointestinal tract of the rat. NK1-R was detected in myenteric and submucosal neurons and in interstitial cells of Cajal. NK2-R was localized to circular and longitudinal muscle cells and to nerve endings in the plexuses. NK3-R was detected in numerous myenteric and submucosal neurons. Some neurons expressed both NK1-R and NK3-R. Receptors were detected at the plasma membrane and in endosomes. Cells expressing the receptors were closely associated with tachykinin-containing nerve fibers. Thus, NK1-R and NK3-R mediate neurotransmission by tachykinins within enteric nerve plexuses, and NK1-R and NK2-R mediate the effects of tachykinins on interstitial and smooth muscle cells, respectively.

Animals↗
PubMed1996

Electron microscopic analysis of synaptic inputs from the median preoptic nucleus and adjacent regions to the supraoptic nucleus in the rat.

The median preoptic nucleus (MnPo) is critical for normal fluid balance, mediating osmotically evoked drinking and neurohypophysial hormone secretion. The influence of the MnPo on vasopressin and oxytocin release is in part through direct connections to the supraoptic and paraventricular nucleus. In the present investigation the synaptic contacts between the MnPo and supraoptic neurons were investigated in rats by ultrastructural examination of terminals labeled anterogradely with the tracers Phaseolus vulgaris-leucoagglutinin or biotinylated dextran. At the light microscopic level, labeled fibers within the supraoptic nucleus branched frequently, were punctuated by varicosities, and were distributed throughout the nucleus without preference for the known distributions of oxytocin and vasopressin neurons. At the ultrastructural level, synapses were associated with many of these varicosities. The ratio of labeled axodendritic to axosomatic synapses encountered was roughly consistent with a uniform innervation of dendrites and somata. The great majority of synapses were characterized by symmetrical contacts. Similar results were found for a few injections made in the organum vasculosum of the lamina terminalis, just rostral to the MnPo, and in the immediately adjacent periventricular preoptic area. Coupled with other recent anatomical and electrophysiological evidence, these results suggest there is a strong monosynaptic pathway from structures along the ventral lamina terminalis to the supraoptic nucleus.

Animals↗
PubMed1996

Human hepatic lipase subunit structure determination.

Chinese hamster ovary cells were stably transfected with a human hepatic lipase (HL) cDNA. The recombinant enzyme was purified from culture medium in milligram quantities and shown to have a molecular weight, specific activity, and heparin affinity equivalent to HL present in human post-heparin plasma. The techniques of intensity light scattering, sedimentation equilibrium, and radiation inactivation were employed to assess the subunit structure of HL. For intensity light scattering, purified enzyme was subjected to size exclusion chromatography coupled to three detectors in series: an ultraviolet absorbance monitor, a differential refractometer, and a light scattering photometer. The polypeptide molecular weight (without carbohydrate contributions) was calculated using the measurements from the three detectors combined with the extinction coefficient of human HL. A single protein peak containing HL activity was identified and calculated to have a molecular mass of 107,000 in excellent agreement with the expected value for a dimer of HL (106.8 kDa). In addition, sedimentation equilibrium studies revealed that HL had a molecular mass (with carbohydrate contributions) of 121 kDa. Finally, to determine the smallest structural unit required for lipolytic activity, HL was subjected to radiation inactivation. Purified HL was exposed to various doses of high energy electrons at -135 degrees C; lipase activity decreased as a single exponential function of the radiation dose to less than 0.01% remaining activity. The target size of functional HL was calculated to be 109 kDa, whereas the size of the structural unit was determined to be 63 kDa. These data indicate that two HL monomer subunits are required for lipolytic activity, consistent with an HL homodimer. A model for active dimeric hepatic lipase is presented with implications for physiological function.

Animals↗
PubMed1996

Peroxynitrite-mediated DNA strand breakage activates poly-adenosine diphosphate ribosyl synthetase and causes cellular energy depletion in macrophages stimulated with bacterial lipopolysaccharide.

The inducible isoform of nitric oxide (NO) synthase produces large quantities of NO, a cytotoxic free radical. Recent studies show that treatment with exogenous NO produces DNA strand breaks, activating the nuclear repair enzyme poly(ADP)ribosyltransferase (PARS), which results in ADP ribosylation, NAD+ consumption, and exhaustion of intracellular energy stores. Here we have characterized the cytotoxic effect of endogenous NO and peroxynitrite, a reactive oxidant formed from NO and superoxide. Immunostimulation of J774.2 macrophages with endotoxin resulted in the generation of superoxide (within 1 h) and NO (after 8 h). NO production paralleled an increase in peroxynitrite formation and DNA strand breakage, and a decrease in intracellular NAD+ content and mitochondrial respiration. Inhibition of NO synthase by NG-methyl-L-arginine or S-methyl-isothiourea or inhibition of PARS activity by 3-aminobenzamide or nicotinamide prevented the decrease in mitochondrial respiration and the depletion of NAD+. A similar pattern of free radical formation and cytotoxicity was observed in peritoneal macrophages from endotoxemic rats (formation of NO, superoxide, peroxynitrite, and DNA strand breaks). In vivo treatment with 3-aminobenzamide preserved mitochondrial respiration, NAD+, and ATP. Our data suggest that inflammatory cell injury involved DNA strand breakage and PARS, triggering an energy-consuming, futile repair cycle leading to cellular energy depletion. The active species responsible for the development of DNA strand breaks is peroxynitrite, rather than NO, since exogenous peroxynitrite, but not NO, induces DNA strand breaks. Inhibition of PARS may improve cellular energy homeostasis in patho-physiologic conditions associated with peroxynitrite generation.

Adenosine Diphosphate Ribose↗
PubMed1996

Comparison of continuous versus pulsed CO2 and Nd:YAG laser-induced pulmonary parenchymal lung injury in a rabbit model.

BACKGROUND AND OBJECTIVE: Laser techniques have recently been described for treatment of patients with emphysema and bullous lung disease. Laser exposure of the pulmonary parenchyma during these procedures is complicated by laser-induced lung injury with substantial associated morbidity. Animal investigations are needed to develop methods that reduce lung injury. We hypothesized that the depth of injury could be reduced by pulsing laser exposures, with the goal of limiting thermal effects to more superficial tissue levels. In this study, we compared acute and chronic histologic injury resulting from pulsed- versus continuous-mode CO2 and Nd:YAG laser pulmonary parenchymal exposures in rabbits. STUDY DESIGN/MATERIALS AND METHODS: A total of 40 New Zealand White (NZW) rabbits underwent thoracotomy followed by exposure with CO2 laser (n = 10 continuous vs. n = 10 pulsed at 250 Hz with duty cycle 0.15 ms) or ND:YAG laser (n = 10 continuous vs. n = 10 pulsed at 10 Hz with duty cycle 0.10 sec) to the visceral pleural surface using 1 minute of laser exposure (5 watts, defocused to 70 W/cm2 power density) to the exposed lung surface. Rabbits were sacrificed at 4 and 21 days post-injury, and lungs were examined histologically. RESULTS: CO2 and Nd:YAG laser treatment resulted in substantial pulmonary parenchymal injury. While CO2 laser-induced damage was distinct from Nd:YAG histologically, pulsed-mode laser exposures did not reduce lung injury for either laser. Acute edema occurred to depths of 1180 +/- 338 microns for continuous-mode CO2 laser exposures compared to 1,340 +/- 430 microns in pulsed mode (p = .77). For Nd:YAG laser exposure, acute edema depth was 750 +/- 748 microns continuous versus 1120 +/- 367 microns pulsed mode (p = .65). Chronic lung fibrosis depth was 450 +/- 164 microns for CO2 continuous mode compared to 575 +/- 170 microns in pulsed mode (p = .61). Lung fibrosis depth for Nd:YAG was 550 +/- 96 microns, continuous versus 484 +/- 180 microns pulsed mode (p = .76). CONCLUSION: The similarity in injury between pulsed- and continuous-mode exposures suggests that thermal relaxation times are long relative to the selected pulse frequencies in intact living rabbit lungs. Alternatively, brief high-energy pulsations may increase focal temperatures with a tendency to increase injury depth relative to the penetration of the laser light. Thus, pulsed laser modes in these settings appear to be ineffective in reducing laser-induced lung injury in clinical settings.

Animals↗