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Biomedical subjects

S Lakshminarayan

Publications and source records attributed to S Lakshminarayan.

At least 19 recordsLinked to original sources

Structure and size of bronchopulmonary anastomoses in sheep lung.

The distribution and drainage of bronchial arterial blood flow are complex. We used two different methods to study the bronchial-pulmonary anastomoses in sheep lung. Initially, we injected two different sizes of fluorescent microspheres (15 and 100 microm diameter) into the bronchial artery and histologically determined where the different-size microspheres were entrapped in the lung. In a second series of animals, we injected Microfil into the bronchial artery to observe the anastomotic vessels. The microsphere data confirmed the existence of bronchial-to-pulmonary anastomoses. No microspheres were found in the systemic organs (heart and kidney), confirming the absence of large bronchial artery-to-pulmonary vein anastomoses. Unexpectedly, proportionately more large microspheres (100 microm) lodged in the alveolar parenchyma when compared to 15 microm microspheres. This suggests that there are many more small bronchial (< 100 microm) arterioles feeding the airway mucosa than the larger anastomotic vessels feeding into the parenchyma. In the Microfil cast lungs, we observed four types of anastomotic vessels: bronchial arteries/arterioles that anastomose with pulmonary arteries/arterioles that accompany airways; bronchial arterioles that anastomose directly with parenchymal (and eventually alveolar) vessels; bronchial arterioles that anastomose with blood vessels that do not accompany airways; and bronchial arterioles that anastomose with bronchial veins. Based on our in vivo microsphere data, the vessels that do not accompany the airways are most likely bronchial venules, not pulmonary venules.

Animals↗

Soluble gas exchange in the pulmonary airways of sheep.

We studied the airway gas exchange properties of five inert gases with different blood solubilities in the lungs of anesthetized sheep. Animals were ventilated through a bifurcated endobronchial tube to allow independent ventilation and collection of exhaled gases from each lung. An aortic pouch at the origin of the bronchial artery was created to control perfusion and enable infusion of a solution of inert gases into the bronchial circulation. Occlusion of the left pulmonary artery prevented pulmonary perfusion of that lung so that gas exchange occurred predominantly via the bronchial circulation. Excretion from the bronchial circulation (defined as the partial pressure of gas in exhaled gas divided by the partial pressure of gas in bronchial arterial blood) increased with increasing gas solubility (ranging from a mean of 4.2 x 10(-5) for SF6 to 4.8 x 10(-2) for ether) and increasing bronchial blood flow. Excretion was inversely affected by molecular weight (MW), demonstrating a dependence on diffusion. Excretions of the higher MW gases, halothane (MW = 194) and SF6 (MW = 146), were depressed relative to excretion of the lower MW gases ethane, cyclopropane, and ether (MW = 30, 42, 74, respectively). All results were consistent with previous studies of gas exchange in the isolated in situ trachea.

Animals↗

Sleep apnea in adults with traumatic brain injury: a preliminary investigation.

OBJECTIVE: To determine the occurrence and nature of sleep-related breathing disorders in adults with traumatic brain injury (TBI). DESIGN: Prospective, observational, consecutive sample enrollment of subjects admitted for rehabilitation after TBI. SETTING: Inpatient rehabilitation and subacute rehabilitation units of a tertiary care university medical system. PARTICIPANTS: Subjects (n = 28) included adults with TBI and a Rancho Los Amigos Scale level of 3 or greater who were less than 3 months postinjury and admitted for comprehensive inpatient rehabilitation. INTERVENTIONS: Overnight sleep study using portable 6-channel monitoring system. MAIN OUTCOME MEASURE: Respiratory disturbance index (RDI), which is the number of apneic and hypopneic episodes per hour of sleep. RESULTS: Evidence of sleep apnea was found in 10 of 28 (36%) subjects as measured by a RDI level of 5 or greater and in 3 of 28 (11%) subjects as measured by a RDI level of 10 or greater. This rate of sleep apnea is significantly (p =.002) higher than would be predicted based on population norms. No correlation was found between the occurrence of significant sleep apnea and measures of TBI severity or other demographic variables. Sleep-related breathing disorders were primarily central though obstructive apneas were also noted. CONCLUSION: In this preliminary investigation, sleep-related breathing disorders as defined by a respiratory disturbance index of 5 or greater appears to be common in adult subjects with TBI.

Adult↗

Recertification of respiratory therapists' intubation skills one year after initial training: an analysis of skill retention and retraining.

Allied health personnel and nonanesthesiologist physicians often undergo training in tracheal intubation but then may actually use the skill relatively infrequently. This study assessed retention of skills one year after initial training and identified specific areas of knowledge critical to successful performance of intubation. Eleven respiratory therapists on the staff of a 253-bed hospital, each of whom had been trained one year previously in airway management, were evaluated. Prior to returning to the operating room for skills assessment and recertification, each respiratory therapist took a 21-question written exam. Therapists then went to the operating room and a trained observer (anesthesiologist) monitored the intubations performed to see whether critical steps were followed, while a second observer monitored a checklist of skills performed. The attending anesthesiologist recertified the therapist only when all steps were correctly performed and the intubation was successful. There was a poor correlation (r = -0.25, p > 0.1) between the number of intubations performed by the therapists for emergencies in the previous year and the number of intubations needed to be recertified. There was a negative correlation (r = -0.8, p < 0.05) between the score on the written test and the number of intubations required for recertification-a higher score meant fewer intubations were needed to achieve recertification. First-pass success occurred significantly more frequently if all skills tested were performed correctly (50/75 first-pass successes had all skills performed correctly vs 10/28 for failed first-pass, p < 0.01). The most common errors were levering the blade on the upper teeth (12/91) and tube not inserted from the right side of the mouth (28/104). When the blade was levered, 8 of 10 intubations failed. When the tube was not inserted from the right side of the face, 6 of 12 failed. The useful findings of this study are: (1) occasional performance of intubation did not ensure skill maintenance; (2) cognitive and procedural abilities correlated, suggesting benefits to study as well as to practical training; and (3) two specific mistakes were associated with a high incidence of failure.

Allied Health Personnel↗

Pulmonary and bronchial circulatory responses to segmental lung injury.

In regional lung injury, pulmonary blood flow decreases to the injured regions, and anastomotic bronchial blood flow and total bronchial blood flow increase. However, the pattern of redistribution of the two blood flows to the injured and noninjured areas is not known. In six anesthetized sheep, pulmonary and bronchial blood flows were measured with 15-microm fluorescent microspheres by using the reference flow method. Blood flows were measured in the control state and 1 h after instilling 1 ml/kg of 0. 1 N hydrochloric acid into a dependent segment of the left lung. The lungs were then removed, dried, and cubed into approximately 2-cm cubes while spatial coordinates were noted. Blood flow to each piece was calculated. Mean pulmonary blood flow to the noninjured pieces went from 730 +/- 246 to 574 +/- 347 ml/min (P = 0.22), whereas in the injured pieces the pulmonary blood flow decreased from 246 +/- 143 to 56 +/- 46 ml/min (P < 0.01). In contrast, bronchial blood flow to the injured pieces increased from 0.51 +/- 0.1 to 1.43 +/- 0. 85 ml/min (P = 0.005). We measured the change in flow as it related to the distance from the center of the injured area. Pulmonary blood flow decreased most at the center of the injury, whereas bronchial blood flow doubled at the center of injury and decreased with the distance away from the injury. The absolute increase in bronchial blood flow was substantially less than the decrease in pulmonary blood flow in the injured pieces. We also partitioned the observed variation in pulmonary and bronchial blood flow into that attributable to structure and that due to lung injury and found that 48% of the variation in pulmonary blood flow could be attributed to structure, whereas in the bronchial circulation 70% was attributable to structure. The reasons for these differences are not known and may reflect the intrinsic properties of the systemic and pulmonary circulations.

Algorithms↗

Efficacy and safety of a 10-day course of 400 or 600 milligrams of grepafloxacin once daily for treatment of acute bacterial exacerbations of chronic bronchitis: comparison with a 10-day course of 500 milligrams of ciprofloxacin twice daily.

A randomized, prospective, double-blind, double-dummy, multicenter study investigated the efficacy and safety of 10 days of oral therapy with grepafloxacin at 400 mg once daily, grepafloxacin at 600 mg once daily, or ciprofloxacin at 500 mg twice daily in 624 patients with acute bacterial exacerbations of chronic bronchitis. At the end of treatment, clinical success (cure or improvement) was achieved for 93% (140 of 151), 88% (137 of 156), and 91% (145 of 160) of patients in the groups receiving grepafloxacin at 400 mg, grepafloxacin at 600 mg, and ciprofloxacin, respectively (clinically evaluable population). At follow-up (14 to 28 days posttreatment), the clinical success rates were 87% (124 of 143), 81% (122 of 151), and 80% (123 of 154) in the groups receiving grepafloxacin at 400 mg and 600 mg and ciprofloxacin, respectively. A total of 379 pathogens were isolated from 290 patients, with the most common isolates being Moraxella catarrhalis (21%), Staphylococcus aureus (20%), Haemophilus influenzae (18%), and Streptococcus pneumoniae (7%). For the evaluable population, successful bacteriologic response was obtained at the end of treatment for 96% (92 of 96), 98% (87 of 89), and 92% (82 of 90) of patients receiving grepafloxacin at 400 mg, grepafloxacin at 600 mg, and ciprofloxacin, respectively, and was maintained in 86% (82 of 95), 88% (78 of 89), and 82% (69 of 84) of patients, respectively, at follow-up. All pretreatment S. pneumoniae isolates were susceptible to grepafloxacin, but two strains were resistant to ciprofloxacin. All treatments were well tolerated, with the most frequently reported drug-related adverse events being nausea, taste perversion, and headache. All drug-related adverse events in the grepafloxacin groups were mild or moderate in severity. This study demonstrates that 10-day courses of grepafloxacin given at 400 or 600 mg once daily were as effective, clinically and bacteriologically, as ciprofloxacin given at 500 mg twice daily for the treatment of acute bacterial exacerbations of chronic bronchitis.

Acute Disease↗

Effect of aerosolized acetylcholine on bronchial blood flow.

We studied the effects of aerosolized as well as intravenous infusion of acetylcholine on bronchial blood flow in six anesthetized sheep. Intravenous infusion of acetylcholine, at a dose of 2 microg/kg, increased bronchial blood flow from 45 +/- 15 (SE) to 74 +/- 30 ml/min, and vascular conductance increased by 76 +/- 22%. In contrast, aerosolized acetylcholine at doses of 2 and 20 microg/kg decreased bronchial vascular conductance by approximately 10%. At an aerosolized dose of 200 microg/kg, the bronchial vascular conductance increased by approximately 15%, and there was no further increase in conductance when the aerosolized dose was increased to 2,000 microg/kg. Pretreatment of animals with a nitric oxide synthase inhibitor, Nomega-nitro-L-arginine methyl ester hydrochloride, partially blocked the vasodilatory effects of intravenous acetylcholine and completely blocked the vasodilatory effects of high-dose aerosolized acetylcholine. These data suggest that aerosolized acetylcholine does not readily penetrate the vascular wall of bronchial circulatory system and, therefore, has minimal vasodilatory effects on the bronchial vasculature.

Acetylcholine↗

Nitric oxide and beta-adrenergic agonist-induced bronchial arterial vasodilation.

In anesthetized sheep, we measured bronchial blood flow (Qbr) by an ultrasonic flow probe to investigate the interaction between inhaled nitric oxide (NO; 100 parts/million) given for 5 min and 5 ml of aerosolized isoetharine (1.49 x 10(-2) M concentration). NO and isoetharine increased Qbr from 26.5 +/- 6.5 to 39.1 (SE) +/- 10.6 and 39.7 +/- 10.7 ml/min, respectively (n = 5). Administration of NO immediately after isoetharine further increased Qbr to 57.3 +/- 15.1 ml/min. NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME; 30 mg/kg, in 20 ml saline given i.v.) decreased Qbr to 14.6 +/- 2.6 ml/min. NO given three times alternately with isoetharine progressively increased Qbr from 14.6 +/- 2.6 to 74.3 +/- 17.0 ml/min, suggesting that NO and isoetharine potentiate vasodilator effects of each other. In three other sheep, after L-NAME three sequential doses of isoetharine increased Qbr from 10.2 +/- 3.4 to 11.5 +/- 5.7, 11.7 +/- 4.7, and 13.3 +/- 5.7 ml/min, respectively, indicating that effects of isoetharine are predominantly mediated through synthesis of NO. When this was followed by three sequential administrations of NO, Qbr increased by 146, 172, and 185%, respectively. Thus in the bronchial circulation, there seems to be a close interaction between adenosine 3',5'-cyclic monophosphate- and guanosine 3',5'-cyclic monophosphate-mediated vasodilation.

Animals↗

Bronchial circulation in the marsupial opossum, Didelphis marsupialis.

This study characterizes the existence of a bronchial circulation in a marsupial, an animal which does not undergo placental development and does not have a ductus arteriosus. Direct perfusion of the lung by the pulmonary vasculature during the fetal development of opossums may occur, potentially eliminating the need for a bronchial circulation. We used radio- and fluorescent-labeled microspheres in conjunction with postmortem intravascular casting to determine if opossums have a systemic (bronchial) blood supply to the lung (n = 9). Gross postmortem examination of the intravascular casts showed a well-developed common bronchial artery. The histological distribution pattern of fluorescent microspheres was primarily to the airways. A few fluorescent microspheres were observed in the alveolar capillaries, indicating that a precapillary bronchial-to-pulmonary anastomosis exists in the opossum. Using the reference flow technique, total bronchial blood flow to the left lung averaged 0.95 +/- 0.58 SE ml/min. The presence of a bronchial circulation in the opossum suggests that it is more than a vestigial structure from embryonic development, potentially supporting its functional importance for carrying nutrients to the airway.

Animals↗

Distribution of pulmonary and bronchial blood supply to airways measured by fluorescent microspheres.

This study determined the relative contributions of systemic (bronchial) and pulmonary blood flow to the intraparenchymal airways >1 mm in diameter by using 15-mu m fluorescent microspheres and fluorescence microscopy in four dogs. Fluorescent microspheres of one color were injected into the inferior vena cava as a pulmonary blood flow marker, and fluorescent microspheres of another color were injected into the left ventricle as a systemic blood flow marker. After the second injection, the animals were killed and the lungs were excised and air dried at total lung capacity. The left lung was sliced into transverse planes and then sectioned into smaller blocks containing airways down to 1 mm in diameter. The blocks were then sectioned using a Vibratome and examined with a fluorescence microscope. Pulmonary and systemic blood flow markers were counted in airway walls, and the diameter of each airway was measured to determine the bronchial tissue volume. After a correction for the number of blood flow markers injected into each circulation, the average ratio of pulmonary to systemic blood flow markers seen in airway walls was 1:37, indicating that 97% of the blood supply to the intraparenchymal airways down to 1 mm in diameter was from the bronchial circulation. Furthermore, on the basis of a weighted least squares regression analysis, systemic (bronchial) blood flow per unit tissue volume increased as airway diameter decreased (P = 0.03).

Animals↗

Trypsinogen and other pancreatic enzymes in patients with renal disease: a comparison of high-efficiency hemodialysis and continuous ambulatory peritoneal dialysis.

Although serum amylase and lipase levels have been studied extensively in patients with renal disease, there are fewer data regarding trypsinogen levels in patients with end-stage renal disease (ESRD) treated with different dialytic modalities. We therefore evaluated the blood concentrations of trypsinogen, amylase, and lipase in asymptomatic patients with chronic renal insufficiency (CRI) and ESRD, to determine whether treatment modality or renal handling of these enzymes is important in determining steady-state levels in asymptomatic patients with chronic renal disease. Mean trypsinogen concentration levels were higher in hemodialysis (HD) patients and patients with CRI compared with normal subjects when values in the different groups were compared. There was no difference in the mean trypsinogen levels between patients treated with HD and those with CRI, between patients treated with chronic ambulatory peritoneal dialysis (CAPD) and those treated with HD, or between CAPD patients and patients with CRI. The mean circulating trypsinogen concentration was elevated more frequently and to a higher level than amylase or lipase in patients with CRI and ESRD. HD treatment did not result in a lowering of mean circulating pancreatic enzyme levels. We propose that decreased peripheral clearance, pancreatic overproduction, increased release from the pancreas, or a combination of these mechanisms is responsible, at least in part, for the increased plasma concentration of trypsinogen in patients with CRI, rather than simply a decrease in renal clearance.

Adult↗

Positive end expiratory pressure reduces bronchial blood flow after aspiration injury.

We hypothesized that since added airway pressure compresses bronchial vessels, the airway hyperemia found following airway injury would be reduced by positive end-expiratory pressure (PEEP). Accordingly, we measured the effect of 15 cm H2O PEEP on bronchial and pulmonary blood flows by the radioactive microsphere reference flow technique in closed chested goats (n = 7) before and after aspiration injury to the left lung with 0.1 N HCl. Thirty minutes after aspiration, the pulmonary blood flow to the injured left lung was reduced by one third, whereas the total bronchial blood flow to the left lung (normalized to mean systemic pressure of 100 torr) doubled (11.3 +/- 2.2 to 20.6 +/- 1.0 ml/min 100 torr; p < 0.01). Increasing PEEP from 5 to 15 cm H2O decreased total bronchial blood flow by about half both before (11.3 +/- 2.2 falling to 5.7 +/- 1.4 ml/min/100 torr) and after injury (20.6 +/- 1.0 falling to 10.3 +/- 2.7 ml/min/100 torr). The airway portion (down to 2-3 mm airways) of the total bronchial blood flow of the injured lung increased more than three-fold (1.4 +/- 0.5 rising to 5.5 +/- 1.3 ml/min/100 torr; p < 0.01). This increased flow after aspiration was less affected by PEEP of 15 cm H2O (5.5 +/- 1.3 to 2.8 +/- 0.7 ml/min/100 torr, p = 0.09) than before injury (1.4 +/- 0.5 falling to 0.5 +/- 0.1 ml/min/100 torr; p < 0.05). The increase of the parenchymal portion of the bronchial blood flow after injury, although apparent (9.9 +/- 1.8 increasing to 15.1 +/- 1.2 ml/min/100 torr), was not significant (p = 0.08).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of low-dose endotoxin on pulmonary vascular permeability following acute hemorrhagic shock.

The purpose of the current study was to determine the effect of low-dose Escherichia coli lipopolysaccharide (LPS) on pulmonary vascular permeability when administered after hemorrhagic shock (40% of baseline cardiac output) followed by resuscitation. Animals were monitored for 3-4 h after LPS infusion. Thirty minutes prior to termination of the experiment, 3 mCi of 125I-human serum albumin was injected intravenously to calculate a permeability index from the left lung lavage and plasma 125I ratios. The two control groups were (1) shock only (no LPS, n = 4), and (2) LPS only (no shock, n = 8). The permeability index for the shock-only group was 0.0015 +/- 0.0007 (mean +/- SE) and that for the LPS-only group was 0.0035 +/- 0.0014. The permeability index for the experimental group (shock followed by LPS, n = 10) was 0.0071 +/- 0.0030 (p > 0.05). Similarly, there was no difference in the wet-to-dry ratios between the three groups. The shock+LPS group required more intravenous fluids to maintain mean arterial blood pressure at control values than the LPS-only group (p < 0.003). We conclude that hemorrhagic shock and resuscitation do not lead to an acute increased permeability of the lung when it is subsequently challenged by a low dose of bacterial LPS.

Animals↗

Acute inhalation injury.

Toxic inhalants cause injury through a variety of different mechanisms, including direct irritation of the respiratory tract mucosa, asphyxiation, and systemic absorption of the toxin. The nature and extent of the acute injury depends on the inhalant's water solubility, aerodynamic features, pH, and concentration. In addition, a patient's underlying respiratory function may affect the clinical response. Smoke inhalation is a particularly challenging clinical problem because patients often are exposed to a large number of inhaled toxins and may suffer thermal injury to the respiratory tract as well. Several chronic respiratory problems have been identified following acute inhalation injuries. Chronic airflow obstruction has been reported in patients exposed to ammonia, chlorine, nitrogen dioxide, and sulfur dioxide; bronchiolitis obliterans may follow exposure to nitrogen dioxide and sulfur dioxide. Inhalation injuries can be difficult to manage because exposures occur infrequently, and the exact toxic agents involved often are not known immediately. Prevention of occupational exposures remains a cornerstone in the overall management of inhalation injuries.

Burns, Inhalation↗

Fifteen micrometer microspheres reflux up the pulmonary veins during pulmonary artery occlusion.

The systemic arterial blood supply to the lung (bronchial blood flow, Qbr) is commonly measured using the reference flow technique by injecting radiolabeled microspheres into the left atrium (LA) and simultaneously collecting a reference blood sample from a large artery such as the aorta. These measurements are often done with the pulmonary artery occluded prior to the time of injection. We have reported previously that left atrial blood refluxes up the pulmonary veins following pulmonary artery (PA) occlusion. We designed this experiment to determine if 15 mu microspheres reflux from the LA into the left lung (i) when the left PA is occluded prior to microsphere injection and (ii) when the left PA is open during the injection. We calculated Qbr to the left lung after simultaneous left ventricular (LV) and LA injections of different radiolabeled microspheres in anesthetized, closed-chest, prone goats. When the PA was open (but occluded 5 sec after the microsphere injection), Qbr calculated from an LA injection differed little from that calculated from an LV injection of microspheres. However, when the PA was occluded prior to injection of the microspheres, Qbr calculated from an LA injection was significantly higher than that calculated from an LV injection suggesting that microspheres reflux from the LA to the lung.

Animals↗

Improvement in mood, physical symptoms, and function with nortriptyline for depression in patients with chronic obstructive pulmonary disease.

Although recent epidemiologic studies have established that patients with chronic medical illness and depressed mood are more disabled than euthymic patients, detailed data on the benefits and risks of antidepressant treatment in medically high-risk patients have been slow to accumulate. The authors have examined multiple outcome indicators in patients with disabling chronic obstructive pulmonary disease and comorbid depression. Thirty patients completed a 12-week, randomized controlled trial of nortriptyline. Nortriptyline was clearly superior to placebo for treatment of depression. Nortriptyline treatment was accompanied by marked improvements in anxiety, certain respiratory symptoms, overall physical comfort, and day-to-day function; placebo effects were negligible. Physiological measures reflecting pulmonary insufficiency were generally unaffected by treatment. These data provide impetus for renewed efforts to improve recognition and treatment of mood disorders in even severely disabled medical patients.

Activities of Daily Living↗