Biomedical subjects

S Lakshminarayan

Publications and source records attributed to S Lakshminarayan.

At least 19 recordsLinked to original sources

PubMed1992

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↗

PubMed1992

Influence of lung volume and alveolar pressure on reverse pulmonary venous blood flow.

We have reported that left atrial blood refluxes through the pulmonary veins to gas-exchanging tissue after pulmonary artery ligation. This reverse pulmonary venous flow (Qrpv) was observed only when lung volume was changed by ventilation. This was believed to drive Qrpv by alternately distending and compressing the alveolar and extra-alveolar vessels. Because lung and pulmonary vascular compliances change with lung volume, we studied the effect of positive end-expiratory pressure (PEEP) on the magnitude of Qrpv during constant-volume ventilation. In prone anesthetized goats (n = 8), using the right lung to maintain normal blood gases, we ligated the pulmonary and bronchial arterial inflow to the left lung and ventilated each lung separately. A solution of SF6, an inert gas, was infused into the left atrium. SF6 clearance from the left lung was determined by the Fick principle at 0, 5, 10, and 15 and again at 0 cmH2O PEEP and was used to measure Qrpv. Left atrial pressure remained nearly constant at 20 cmH2O because the increasing levels of PEEP were applied to the left lung only. Qrpv was three- to fourfold greater at 10 and 15 than at 0 cmH2O PEEP. At these higher levels of PEEP, there were greater excursions in alveolar pressure for the same ventilatory volume. We believe that larger excursions in transpulmonary pressure during tidal ventilation at higher levels of PEEP, which compressed alveolar vessels, resulted in the reflux of greater volumes of left atrial blood, through relatively noncompliant extra-alveolar veins into alveolar corner vessels, and more compliant extra-alveolar arteries.

Animals↗

PubMed1991

Comparison of estimates of cardiac output by indicator dilution and freon 22 uptake during gas mixing in dogs.

STUDY OBJECTIVE: The aim was to measure cardiac output while rebreathing tidal volumes, by correction of soluble gas uptake for gaseous mixing. DESIGN: Simultaneous measurements of cardiac output by indocyanin green and freon 22 uptake during rebreathing were made. Mixing for a hypothetical gas of identical gaseous diffusivity to freon 22 was calculated by interpolation between concentrations of two insoluble gases, helium and sulphur hexafluoride. Mixing efficiency was estimated by the number of breaths for helium to become 99% equilibrated with lung gas (n99-He). EXPERIMENTAL MATERIAL: Five anaesthetised dogs rebreathed at intervals with 300 ml of test gas. MEASUREMENTS AND MAIN RESULTS: 63 comparisons of cardiac output using indocyanin green and freon 22 uptake (over breaths 7-13 using the mean mixed volume of distribution), gave a mean (95% confidence interval) underestimation of 0.345 (0.093-0.597) litre.min-1 (14%). Exclusion of 12 points in which n99-He was greater than 15 resulted in a mean underestimation of 0.052(-0.163-0.267) litre.min-1 (2%). Without correction for gaseous mixing, freon 22 uptake for these data overestimated blood flow by a mean of 1.31 litre.min-1 (overestimation = 2.7 over breaths 5-11). Use of the equilibrium volume of distribution resulted in an overestimation of blood flow relative to green dye of 1.2 litre.min-1 (breaths 5-11) and 0.76 litre.min-1 (breaths 7-13). CONCLUSIONS: Estimates of cardiac output by soluble gas uptake are optimal when correction is made for mixing of gas of identical diffusivity. The mean mixed gas volume gives the best correlation with the reference method, implying a selective distribution of blood flow to the better ventilated areas.

Animals↗

PubMed1991

Influence of lung volume and left atrial pressure on reverse pulmonary venous blood flow.

Infarction of the lung is uncommon even when both the pulmonary and the bronchial blood supplies are interrupted. We studied the possibility that a tidal reverse pulmonary venous flow is driven by the alternating distension and compression of alveolar and extra-alveolar vessels with the lung volume changes of breathing and also that a pulsatile reverse flow is caused by left atrial pressure transients. We infused SF6, a relatively insoluble inert gas, into the left atrium of anesthetized goats in which we had interrupted the left pulmonary artery and the bronchial circulation. SF6 was measured in the left lung exhalate as a reflection of the reverse pulmonary venous flow. No SF6 was exhaled when the pulmonary veins were occluded. SF6 was exhaled in increasing amounts as left atrial pressure, tidal volume, and ventilatory rates rose during mechanical ventilation. SF6 was not excreted when we increased left atrial pressure transients by causing mitral insufficiency in the absence of lung volume changes (continuous flow ventilation). Markers injected into the left atrial blood reached the alveolar capillaries. We conclude that reverse pulmonary venous flow is driven by tidal ventilation but not by left atrial pressure transients. It reaches the alveoli and could nourish the alveolar tissues when there is no inflow of arterial blood.

Animals↗

PubMed1990

The drainage routes of the bronchial blood flow in anesthetized dogs.

It is generally accepted that the bronchial blood flow from extrapulmonary airways drains to the systemic veins through the bronchial veins, while that from the intrapulmonary airways drains into the pulmonary vasculature and eventually the left heart. This concept has not been confirmed by physiologic studies in live animals. We measured the routes taken by radionuclide-labeled Diethylenetriamine pentaacetate (DTPA) deposited in the extrapulmonary and the intrapulmonary airways in dogs. In living, anesthetized open chest animals, the pulmonary circulation of the left lower lobe was isolated and perfused with autologous heparinized blood. 99mTc DTPA was deposited on the mucosa of the extrapulmonary left mainstem bronchus just beyond the main carina (extrapulmonary deposition) and 111In DTPA on that of an intrapulmonary left lower lobe segmental bronchus (intrapulmonary deposition). Sequential blood samples from the right heart and from the isolated left lower lobe pulmonary circuit were counted for radioactivity, corrected for the volume in which they were distributed and for the bronchial blood that flowed into the isolated left lower lobe circuit, and expressed as the ratio of systemic to pulmonary drainage from each deposition site. The extrapulmonary tracer drained mostly to the systemic veins (84% of total) but also into the pulmonary circulation (16% of total). The intrapulmonary tracer drained mostly into the pulmonary circulation (70% of total) but also into the right heart (30% of total). Since tracers from both deposition sites drained to both circulations, the bronchial vasculature is continuous between the systemic (right heart) and the pulmonary circulation. Thus, it may provide a pathway for blood flow between the right and left heart.

Anesthesia↗

PubMed1990

The effect of bronchial venous pressure on pulmonary edema in the dog.

We examined the effect of elevating systemic venous pressure on the rate of edema formation in the left lower lobes (LLL) of anesthetized, open-chested dogs. The pulmonary circulation of the LLL was isolated using cannulae in the artery and vein which were attached to blood-filled reservoirs. The LLL was distended to an alveolar pressure of 25 cm H2O with 5% CO2 and air, and suspended from a strain gauge which allowed continuous weight recording. The pulmonary vascular pressures were raised so all of the LLL was in zone III. The rate of weight change occurring over the last 4 minutes of a 6 minute period of this pulmonary vascular pressure rise was taken to represent the control transvascular fluid flux. The rate of weight gain of the LLL was then determined with the same pulmonary vascular pressure elevation only when downstream bronchial venous pressure alone, downstream lymphatic pressure alone, or when both downstream lymphatic and bronchial venous pressures were elevated. The transvascular fluid flux was increased when downstream bronchial venous pressure was elevated. When only downstream lymphatic pressure was elevated there was no augmentation of transvascular fluid flux. These findings suggest that when a lung is already subjected to raised pulmonary vascular pressure sufficient to cause edema, acute elevation of bronchial systemic venous pressure augments the net rate of outward fluid flux, while downstream lymphatic pressure elevation does not.

Animals↗

PubMed1990

Vagal cooling and positive end-expiratory pressure reduce systemic to pulmonary bronchial blood flow in dogs.

Positive end-expiratory pressure (PEEP) reduces systemic to pulmonary bronchial blood flow [Qbr(s-p)] presumably because it increases bronchial vascular resistance. Since PEEP increases lung volume and thus could stimulate pulmonary stretch receptors, we investigated the hypothesis that the PEEP-related decrease in bronchial blood flow was due to a reflex mediated by the vagus. In open-chest dogs the left lower lobe (LLL) was isolated, independently ventilated, perfused in situ with a closed pulmonary vascular circuit and weighed continuously. Qbr(s-p) was measured as LLL vascular circuit overflow and changes in LLL weight. When LLL PEEP was increased from 5 to 15 cm H2O in a group of 11 dogs Qbr(s-p) was reduced by half from 60.8 +/- 10.5 to 31.6 +/- 6.1 ml/min/100 g dry lobe weight. In another group of 7 dogs Qbr(s-p) was 46.5 +/- 6.9 with PEEP = 5 cm H2O; it decreased to 28.3 +/- 6.8 with bilateral cervical vagal cooling (0-1.5 degrees C) and did not decrease further after increasing PEEP to 15 cm H2O. We conclude that the effect of resting vagal tone is to increase Qbr(s-p) and that the effect of PEEP on Qbr(s-p) may be mediated at least partially by vagal influences.

Animals↗

PubMed1990

The pulmonary sequelae associated with accidental inhalation of chlorine gas.

Twenty previously healthy individuals were accidentally exposed to high concentrations of chlorine gas in 1975. Pulmonary function tests were performed on these individuals on several occasions over the next 12 years. On average, each subject was followed up for 8.5 years and 13 of the 20 exposed persons were tested 12 years following the exposure. Pulmonary function tests obtained one day following the accident were most notable for the high prevalence of airflow obstruction and air trapping. Over the ensuing years, the airflow obstruction persisted; however, the high prevalence of air trapping resolved. Of note, the prevalence of a low residual volume consistently increased during the follow-up period (p less than 0.001) and at year 12, 67 percent of those tested had residual volumes below 80 percent of their predicted value. We also found that five of 13 subjects tested at year 12 had an increase in airway reactivity (greater than 15 percent decline in FEV1) to inhaled methacholine. Those individuals with reactive airways were older (p = 0.004) and had more marked airflow obstruction (p = 0.03) and air trapping (p = 0.03) immediately following the exposure. These data suggest that exposure to high concentrations of chlorine gas may result in long-term pulmonary complications that are characterized by a reduced residual volume. Unfortunately, these data preclude us from determining whether the chlorine exposure led to the development of airway reactivity or the presence of reactive airways accounted for the air trapping that was observed following the exposure to chlorine gas.

Accidents, Occupational↗

PubMed1990

The effect of diet or exercise on plasma norepinephrine kinetics in moderately obese young men.

An increase in sympathetic nervous system (SNS) activity in the obese has been described by some but not all investigators. It is possible that an increase in SNS tone may play a role in the predisposition to atherosclerotic cardiovascular disease noted in the obese. The effect of dietary weight loss or exercise training on resting SNS activity in moderately obese subjects has not been extensively studied and the results of previous studies are conflicting. Therefore, we prospectively evaluated resting SNS activity in healthy moderately obese subjects randomized to either a three month dietary weight loss (n = 13) or endurance exercise training (n = 18). All subjects were weight stabilized on a constant composition diet for 10 days prior to study both before and after the interventions. Although both groups lost weight, weight loss was greater in the diet group (-13.6 +/- 6.7 vs -2.3 +/- 3.4 kg, P less than 0.001). The composition of weight loss was also different with 32 percent of total weight loss as fat free mass (FFM) in the dieters compared to no significant change in FFM in the exercisers. The caloric requirement for weight stabilization declined after the diet but increased following exercise training (-247 vs + 202 kcal/day, P less than 0.001). No significant changes in blood pressure occurred in either group, and neither group had a significant change in resting plasma norepinephrine concentration. Plasma epinephrine concentrations were also unchanged. However, SNS activity as reflected by arterialized plasma NE kinetics revealed that NE appearance rate declined by 17 percent after dietary weight loss (P less than 0.01), but was not significantly changed after exercise training. These results suggest that dietary weight loss is more effective than exercise training in reducing overall resting SNS activity in normotensive subjects. Since exercise training is known to reduce the SNS response to a given submaximal workload, a combination of diet plus exercise might be the most effective way to reduce overall SNS activity and its possible role in the premature atherosclerosis associated with obesity.

Adolescent↗

PubMed1990

Reflux pulmonary vein flow prevents pulmonary infarction after pulmonary artery obstruction.

Küttner showed in 1874 that simultaneous ligation of the pulmonary veins increased the frequency and severity of lung infarctions after pulmonary artery obstruction. The authors studied the possibility that a tidal pulmonary venous blood flow reflux from the left atrium could nourish the alveolar tissue. This could be driven by left atrial pressure transients and alternate expansion and compression of alveolar and extra alveolar vessels due to tidal lung volume changes. 5 anesthetized, closed chest goats were studied in the prone position after left pulmonary artery ligation and the obstruction of all bronchial blood flow to the left lung, checked by systemic microsphere injection. The inert, insoluble gas SF6 was infused into the left atrium and the exhaled gas from left and right lungs was collected separately. SF6 was found in the gas exhaled from the left lung, showing that left atrial blood had reached the alveolar tissues. The effective reflux blood flow was increased from control levels (no ventilation, normal left atrial pulses) by tidal volume changes, and by increased left atrial pressure transients (balloon induced mitral insufficiency). This venous reflux flow could explain why alveolar tissues do not suffer more severe injury when the pulmonary artery is obstructed.

Animals↗

PubMed1989

Pulmonary artery infusion of prostacyclin increases lobar bronchial blood flow.

Intrapulmonary systemic to pulmonary bronchial blood flow [Qbr (s-p)] decreases with administration of cyclooxygenase inhibitors. This effect may be due to a decrease in the production of vasodilating prostaglandins and reflect either a decrease in the total intrapulmonary bronchial blood flow (Qbr), or a redistribution of the intrapulmonary systemic venous return. In nine open chested dogs the left lower lobe (LLL) was isolated and perfused in situ. Blood flow to the extrapulmonary airways (Qep), and Qbr were measured by the reference flow technique. Qbr (s-p) was measured as the overflow from the closed LLL perfusion circuit. After ibuprofen, PG-I2 was infused into the LLL PA and the Qbr (s-p) was continuously monitored. Qbr, and Qep were measured before and after ibuprofen, and during and after the PG-I2 infusion. The upstream pressure for Qbr (s-p) was estimated with and without PG-I2 infusion. After ibuprofen the Qep, Qbr, and Qbr (s-p) fell to 45, 22, and 17%, respectively, of the pre-ibuprofen values (P less than 0.05). PG-I2 increased the Qbr (s-p) and Qbr (P less than 0.05), while Qep was unchanged. During all experimental conditions the simultaneous measurements of Qbr and Qbr (s-p) were not different from each other (P less than 0.001). The upstream pressure for Qbr (s-p) increased from 30 to 50 cm H2O (P less than 0.05). Intralobar bronchial blood flow is drained almost entirely through the pulmonary circulation, and PG-I2 in the LLL pulmonary circulation increases systemic blood flow to the LLL, probably acting at the level of a systemic arteriole.

Animals↗

PubMed1986

Ipratropium bromide in chronic bronchitis/emphysema. A review of the literature.

Many studies have evaluated the efficacy of ipratropium bromide in chronic obstructive pulmonary disease (COPD). Single-agent studies have shown ipratropium to be both safe and effective in COPD. Several studies have compared ipratropium with sympathomimetic agents or methylxanthines in patients with chronic bronchitis or emphysema; all of these studies have shown at least an equal, and in most instances a superior, bronchodilator action with ipratropium in terms of duration of action as well as peak bronchodilator effect in patients with COPD. In some patients with COPD, beta agonists, theophylline, or corticosteroids may have some additive, but not synergistic, bronchodilator effects when given with ipratropium.

Atropine Derivatives↗

PubMed1979

Pulmonary injuries associated with acute sulfur dioxide inhalation.

This report describes an industrial accident in which 5 previously healthy persons were acutely exposed to very high concentrations of sulfur dioxide. Of these 5 subjects, the 2 with the highest exposure died immediately; histologic examination of the lungs revealed extensive sloughing of the mucosa of large and small airways along with hemorrhagic alveolar edema. The 3 survivors were evaluated with pulmonary function tests performed at regular intervals. One subject subsequently developed symptomatic severe airway obstruction unresponsive to bronchodilators; another subject developed asymptomatic mild obstructive and restrictive disease, and the third subject continued to be asymptomatic with normal pulmonary function tests. This report severe to document the histologic features of fatal exposure to sulfur dioxide and stresses the need to follow parameters of pulmonary function in the nonfatal cases.

Accidents, Occupational↗

PubMed1979

The significance of wheezing in chronic airflow obstruction.

Eighty-three patients with chronic airflow obstruction were examined prospectively to determine the relationships among wheezing intensity, severity of obstruction, and response to inhaled isoproterenol. For each patient, expiratory wheezing scores were assigned during deep unforced breathing and during forced vital capacity efforts at spirometry. Unforced wheezing scores were independently correlated with severity of obstruction (r = 0.42) and bronchodilator response (r = 0.46), but these correlations did not permit consistent prediction of either variable for clinical purposes. The highest wheezing scores, however, were uniformly associated with moderate or severe obstruction. Twenty-nine of 48 patients with wheezing but only 3 of 35 patients without wheezing demonstrated 15% or greater improvement in one-second forced expiratory volume after bronchodilator inhalation (p less than 0.001). Wheezing during forced exhalation was not correlated with either degree of obstruction or bronchodilator response.

Aged↗

PubMed1979

Increased surface tension favors pulmonary edema formation in anesthetized dogs' lungs.

The possibility that surface tension may affect the hydrostatic transmural pressure of pulmonary vessels and the development of pulmonary edema was studied in anesthetized, open-chested dogs. Isogravimetric pressure (the static intravascular pressure at which transmural osmotic and hydrostatic pressures are balanced such that net fluid flux is zero and lung weight is constant) was measured in nine animals under three conditions: (a) control, normal surface tension, at an alveolar pressure of 30 cm H2O with the apenic lung at room temperature; (b) after increasing surface tension by cooling and ventilating at a low functional residual capacity, at an alveolar pressure sufficient to produce the same lung volume present during control measurements; and (c) after restoring surface tension by rewarming while holding the lung at a high inflation volume, again at the control lung volume. Lung volumes were established from external dimensions and confirmed +/- 10% by deflation spirometry. The isogravimetric pressure (relative to alveolar pressure) was significantly less with increased surface tension than during either the initial control condition (P less than 0.01), or when the surface tension has been restored (P less than 0.01). Similar changes occurred in each of three additional studies performed with control alveolar pressures of 10 cm H2O. Thus, increased surface tension favors fluid leakage presumably because it increases the microvascular transmural pressure.

Anesthesia↗

PubMed1978

Lung injury following a 50-metre fall into water.

The pulmonary complications of a 50-metre fall to the water (a form of suicide attempt producing 87% mortality) were studied in 15 survivors. Presenting findings included crackles, haemoptysis, and hypotension. The alveolar-arterial oxygen difference was greater than 150 mmHg (20 kPa) in nine subjects on admission. Ventilatory failure developed in 10 of the patients, including all of those with massive haemoptysis. Radiographic findings included pneumothorax and diffuse pulmonary opacities adjacent to the area of impact. Pneumothorax developed within 12 hours of admission in 10 of 15 subjects but was associated with rib fractures in only four subjects. The clinical course of the condition is consistent with the hypothesis that the traumatic pulmonary tears produced interstitial emphysema, with subsequent development of pneumomediastinum, subcutaneous emphysema, and pneumothorax. Pneumothorax is a common complication of severe lung contusion even in the absence of penetrating pleural injury.

Adult↗

PubMed1978

Fluid leaks from extra-alveolar vessels in living dog lungs.

Edema transudation from extra-alveolar vessels was investigated in anesthetized, open-chested dogs. Fluid accumulation at different alveolar and extra-alveolar vascular pressures was assessed by continuous lung weighing and microscopy. The left (experimental) lung was distended with 6% CO2 and air while normal arterial blood gases were maintained by separately ventilating the right lung. Extra-alveolar vessels were isolated by compressing alveolar vessels with alveolar pressures high enough to stop blood flow. Weight increased steadily (edemogenesis) when pulmonary arterial and/or pulmonary venous pressure was 1 cmH2O below this pressure. Because some alveolar vessels at the lung base could have remained open and leaked, extra-alveolar vessels were also separated from alveolar vessels by glass bead embolization sufficient to stop perfusion. Lung weight gains followed selective pulmonary arterial or venous pressure elevations. Electron microscopy demonstrated edema in experimental lobes which was not present in control lobes with undistended extra-alveolar vessels at the same alveolar pressure. Thus pulmonary edema can be caused by fluid leaking from extra-alveolar vessels.

Animals↗

PubMed1978

Effect of aminophylline on ventilatory responses in normal man.

The bronchodilator effects of aminophylline have been well documented but its effect on ventilatory drives has not been systematically evaluated. Accordingly, the ventilatory responses to hypoxia and to hypercapnia were measured before and after the intravenous administration of 5 mg of aminophylline per kg of body weight to 6 normal subjects. Hypoxic ventilatory response, as measured by an index of the relation between ventilation and hypoxia (parameter A) increased from a mean +/- SE control value of 146 +/- 25 to 254 +/- 35 75 min after the infusion (P less than 0.05). Significant increases in A were also noticed immediately after and 35 and 50 min after the aminophylline infusion. Oxygen consumption increased from a control value of 235 +/- 21 to 263 +/- 21 ml per min STPD (P less than 0.03), and CO2 production increased from 184 +/- 12 to 202 +/- 13 ml per min STPD (P less than 0.01) after aminophylline. Hypercapnic ventilatory response, measured as the slope of the ventilatory response to hypercapnia, was not altered after the aminophylline. Thus, in addition to bronchodilation, the augmentation of the ventilatory response to hypoxia may be a useful factor when this drug is used in acute respiratory failure secondary to airway obstruction.

Adult↗