Biomedical subjects

M Younes

Publications and source records attributed to M Younes.

At least 109 records · Page 6Linked to original sources

PubMed1992

Effect of breathing pattern and level of ventilation on pulmonary fluid filtration in dog lung.

The effect of breathing pattern and level of ventilation on fluid filtration in the lung under edema forming conditions was studied in an in situ left upper lobe (LUL) canine preparation. LUL weight was continuously monitored. In Group 1, rate of edema formation (delta W/delta t) was measured In seven dogs at two vascular pressures (35 and 45 mm Hg) while the LUL was randomly ventilated under six conditions. At equivalent vascular pressures and mean airway pressures (Paw) (and hence, mean operating lung volume), increasing respiratory frequency (f) enhanced delta W/delta t. This was reversed when minute ventilation (VE) was returned to baseline by reducing tidal volume (VT), even when Paw were matched to baseline. Increasing VT also enhanced delta W/delta t whether VE was increased (J Appl Physiol 1988; 64:1900) or not (present study) and whether Paw was matched to baseline. In Group 2 delta W/delta t was measured at fixed VT and f while inspiratory/expiratory time ratio (TI/TE) was switched from 1:1 to 1:6. Shortening inspiratory time by increasing inspiratory flow rate had no effect on delta W/delta t. We conclude that increasing VE, whether by raising VT or f, promotes greater edema formation by mechanisms that are independent of vascular pressure or operating lung volume. Increasing VT appears to have an additional adverse effect over and above that of increased VE.

Animals↗

PubMed1992

Effect of inspiratory flow rate on respiratory output in normal subjects.

We wished to determine the independent effect of inspiratory flow rate (VI) on respiratory output in the awake state. Seven normal subjects were connected to a volume-cycled ventilator in the assist/control mode. While the tidal volume setting remained constant, inspiratory flow rate was increased in steps (3 to 4 min each) from 30 to 90 L/min and then back to 30 L/min. Flow pattern was square, and all breaths were subject-triggered. Spontaneous respiratory rate (f) increased in all subjects as VI increased. Mean (+/- SD) f at 30 and 90 L/min were 8.8 (+/- 1.7) and 14.1 (+/- 4.4) min-1, respectively (p less than 0.01). VE increased (10.1 +/- 1.9 at 30 L/min to 16.3 +/- 5.6 at 90 L/min p less than 0.01) and the percentage of end-tidal CO2 decreased (4.7 (+/- 0.5) at 30 L/min to 3.3 (+/- 0.7) at 90 L/min (p less than 0.01)). The response was graded and reversible. The change in f was nearly complete within the first two breaths after transition, and there was no systematic tendency for f to change beyond this early response. The rate of change in airway pressure prior to triggering (dp/dt) increased as VI increased (5.3 +/- 2.0 cm H2O/s at 30 L/min to 10.8 +/- 2.6 cm H2O/s at 90 L/min; p less than 0.01). We conclude that inspiratory flow rate exerts an excitatory effect on respiratory frequency and on the rate of rise of inspiratory activity in conscious humans. This may be relevant to the mechanism of ventilatory response to various respiratory stimuli and to the management of patients receiving mechanical ventilation.

Adult↗

PubMed1991

The involvement of oxygen radicals in acute pancreatitis.

The purpose of this study was to assess the involvement of oxygen radicals in acute edematous and hemorrhagic pancreatitis. Acute pancreatitis was induced in rats by the CCK-analogue cerulein (5 micrograms/kg/h) and by retrograde injection of 5% sodium taurocholate for 30 min, 3.5 h, and 12 h. At the end of the infusion and observation time, serum enzymes, conjugated dienes, and malondialdehyde in the tissue were measured. Moreover, the tissue samples underwent light microscopical examination. In cerulein pancreatitis, an interstitial edema and intravascular margination of granulocytes in the pancreatic gland were observed after 3.5 h. After 12 h, the histological evaluation revealed a pronounced zymogen degranulation, extensive tissue necrosis and migration of granulocytes into the tissue. Parallelly, amylase and lipase increased by 15 and 35 times, respectively. In contrast, conjugated dienes and malondialdehyde increased in cerulein pancreatitis and reached their highest level after 3.5 h and decreased to normal levels after 12 h. The development of the histological damages and serum enzyme levels with sodium taurocholate pancreatitis was similar as compared to the cerulein pancreatitis, however, the development was faster and more traumatic. Already after 3.5 h an extensive zymogen degranulation and cell necrosis was observed. Concomitantly, the amylase and lipase levels increased by 90 and 30 times, respectively. Treatment with superoxide dismutase (100,000 U/kg/h) and catalase (400,000 U/kg/h) prevented lipid peroxidation and reduced zymogen degranulation and tissue necrosis. Tissue edema and inflammatory response were not affected in both models of acute pancreatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1991

Vanadate-induced toxicity towards isolated perfused rat livers: the role of lipid peroxidation.

The toxic potential of sodium orthovanadate towards isolated perfused rat livers was investigated at a dose of 2 mmol/l. In livers from fasted rats, vanadate led to a release of cytosolic (glutamate-pyruvate-transaminase (GPT) and lactate dehydrogenase (LDH] and mitochondrial (glutamate dehydrogenase (GLDH] enzymes, an accumulation of calcium in the liver, a marked depletion of hepatic glutathione and an enhanced release of it into the perfusate, as well as an augmented formation and release of thiobarbituric acid-reactive material by the liver. Furthermore, a marked inhibition of oxygen consumption was observed. Vanadate-induced vasoconstriction resulted in a progressive decrease in perfusate flow rate. Control experiments with similarly reduced flow rates led to a comparable reduction in oxygen consumption. GPT and LDH release and hepatic glutathione depletion were also evident, though to a lesser extent than in the presence of vanadate, but no increase in GLDH release, in tissue calcium content or TBA-reactive material in the liver or the perfusate were observed. Thus, indirect toxic effects due to a reduced flow rate contribute only partly to vanadate hepatotoxicity and do not affect mitochondrial integrity. Omission of calcium from the perfusate did not prevent hepatotoxic responses to vanadate, although less calcium was present in the treated livers than in the control organs, indicating that calcium influx is not involved in vanadate-induced hepatotoxicity in the intact organ, in contrast to isolated hepatocytes. Feeding the animals, resulting in an activation of anaerobic energy conservation reactions, strongly attenuated vanadate hepatotoxicity indicating that the energetic status of the liver is the main target of vanadate. Superoxide dismutase did not affect the hepatotoxic responses of livers from fasted rats towards vanadate, while allopurinol and deferrioxamine inhibited lipid peroxidation and hepatotoxicity due to vanadate. The strong correlation between induction of lipid peroxidation and hepatotoxicity and the inhibition of both processes in parallel by antioxidants are suggestive of a causative role for lipid peroxidation in vanadate-induced hepatotoxicity.

Alanine Transaminase↗

PubMed1991

Effect of antioxidants on vanadate-induced toxicity towards isolated perfused rat livers.

The effect of trolox C, a water soluble vitamin E analogue, propyl gallate and ascorbate on vanadate hepatotoxicity was investigated in vitro. In isolated perfused livers from fasted rats, sodium orthovanadate (2 mmol/l) led to toxic responses including reduction of oxygen consumption, release of cytosolic (glutamate-pyruvate-transaminase (GPT) and lactate dehydrogenase (LDH)) and mitochondrial (glutamate-dehydrogenase (GLDH)) enzymes, intracellular accumulation of calcium, a marked depletion of glutathione (GSH) and an enhanced formation and release of thiobarbituric acid- (TBA) reactive material. Trolox C and propyl gallate inhibited the release of GPT and LDH partially and that of GLDH totally, but had no influence on vanadate-induced calcium accumulation or on the reduction of oxygen consumption. Both agents suppressed vanadate-induced lipid peroxidation (LPO) and partially prevented GSH depletion. Ascorbate failed to provide any protection probably due to the interference of its pro-oxidant potential with its antioxidant activity. The protection, mainly of mitochondria, afforded by those agents which also inhibited LPO substantiates our previous findings that the pro-oxidant activity of vanadate is mainly responsible for its direct hepatotoxic actions [2]. Besides, reduction of organ perfusion rate due to vasoconstriction also contributes to vanadate toxicity, but oxidative stress is not involved in this indirect toxic activity.

Alanine Transaminase↗

PubMed1991

Infection of T but not B lymphocytes by cytomegalovirus in lymph node. An immunophenotypic study.

A 45-year-old black man presented with fever, night sweats, weight loss, and cervical lymphadenopathy. Biopsy of an enlarged node showed partial effacement of the nodal architecture by numerous cells with typical cytomegalovirus (CMV) inclusions. These were also seen by electron microscopy. CMV titers were not elevated, and he tested negative for HIV. An immunophenotypic study done on both paraffin-embedded and frozen tissue showed that the infected cells were of T-lymphocyte phenotype. These cells were remarkable for the lack of HLA-DR and IL-2R antigens, which were expressed by numerous neighboring apparently uninfected cells. The lack of HLA-DR and IL-2R expression by CMV-infected T lymphocytes may be one of the mechanism by which CMV causes immunosuppression.

Cytomegalovirus↗

PubMed1991

Involvement of neutrophils in postischaemic damage to the small intestine.

Haemorrhagic mucosal lesions are produced during intestinal ischaemia and after reperfusion probably mediated by oxygen radicals. Oxygen radicals react with cell membrane lipids and induce cell damage by peroxidation and induce accumulation of polymorphonuclear leucocytes in the tissue. The aim of the study was to elucidate the involvement of polymorphonuclear leucocytes in post-ischaemic intestinal damage. Intestinal ischaemia was induced in cats by partial occlusion of the superior mesenteric artery. Samples from the small intestine were excised before and at the end of the two hour hypotensive period as well as 10 minutes and 60 minutes after reperfusion. Conjugated dienes, myeloperoxidase, and the purine metabolites were determined in the samples. The tissue was also examined histologically. Seven cats were treated before reperfusion with a monoclonal antibody (IB4) which inhibits leucocyte adherence to endothelial cells and its subsequent activation. After reperfusion myeloperoxidase activity increased and the ischaemic mucosal lesions worsened significantly. IB4 treatment prevented an increase in post-hypotensive myeloperoxidase activity and attenuated the normally observed severe mucosal lesions. We conclude that the severe post-ischaemic lesions are induced by polymorphonuclear leucocytes. Such mucosal injury may be appreciably reduced by blocking leucocyte adherence with IB4.

Animals↗

PubMed1991

Effect of slowly increasing elastic load on breathing in conscious humans.

Because the detection of added loads is a function of the step change in load relative to background level of load (Weber's law), we reasoned that detection may be delayed if the load is increased in very small steps over a protracted period. This would permit the study of subliminal load responses over a greater range than would otherwise be possible. In 13 healthy males, an external elastic load (delta E) was added in very small steps (load increased every few seconds) such that delta E increased from zero to 6.0 cmH2O/l in 18 min. Each subject underwent a control study in which an identical protocol was followed but no load was added. Five subjects sensed the load after a variable period of load application. Their results were discarded. In the remaining eight subjects, there was no perception of increased load throughout the 18 min. By comparison with the control studies in the same subjects, there was a progressive reduction in tidal volume and breath duration with loading. To assess the response to an increase in load associated with perception, in five of the eight "nonsensers" the load was suddenly doubled (delta E = 6 cmH2O/l) at the end of the 18 min of progressive nonsensed loading. This evoked perception in all subjects and was associated with highly variable responses in tidal volume and breath duration. We conclude that tachypnea associated with elastic loading in conscious humans is a reflex response that is facilitated by consciousness but does not require perception.

Adult↗

PubMed1991

Exercise endurance and arterial desaturation in normobaric hypoxia with increased chemosensitivity.

We studied whether exercise endurance under normobaric hypoxia can be enhanced by increasing hypoxic ventilatory sensitivity with almitrine bismesylate (ALM). On both ALM and placebo (PL) days, resting subjects breathed a hypoxic gas mixture (an inspired O2 fraction of 10.4-13.2%), which lowered resting arterial O2 saturation (SaO2) to 80%. After 15 min of rest there was a 3-min warm-up period of exercise at 50 W (light) on a cycle ergometer, followed by a step increase in load to 60% of the previously determined maximum power output with room-air breathing (moderate), which was maintained until exhaustion. With PL, SaO2 decreased rapidly with the onset of exercise and continued to fall slowly during moderate exercise, averaging 71.0 +/- 1.8% (SE) at exhaustion. With ALM, saturation did not differ from PL during air breathing but significantly exceeded SaO2 with PL, by 3.4% during resting hypoxia, by 4.0% at the start of exercise, and by 5.9% at exhaustion. Ventilation was not affected by ALM during air breathing and was slightly, although not significantly, increased during hypoxic rest and exercise. ALM was associated with an increased heart rate during room air breathing but not during hypoxia. Endurance time was 20.6 +/- 1.6 min with ALM and 21.3 +/- 0.9 min with PL. During hypoxic exercise, the potential benefit of greater saturation with ALM is apparently offset by other unidentified factors.

Adult↗

PubMed1991

Short-term effect of tidal pleural pressure swings on pulmonary blood flow during rest and exercise.

Because pleural pressure (Ppl) has important effects on venous return and left ventricular function, it is possible that the magnitude of respiratory fluctuations in Ppl importantly influences cardiac output (pulmonary blood flow, QL) during exercise. To examine this question, we increased (+15 cmH2O) and decreased (-11 cmH2O) the amplitude of fluctuations in Ppl by elastic loading and unloading, respectively, during steady-state exercise (50 W) and estimated the corresponding changes in QL from measurement of breath-by-breath alveolar O2 consumption [(Vo2)A] by a modification of the technique of Beaver et al. (J. Appl. Physiol. 51: 1662-1675, 1981). Load changes were applied for three breaths. Using oscilloscopic volume feedback, subjects maintained constant breathing pattern and end-expiratory volume during control and experimental breaths. This procedure minimized errors in computing (Vo2)A. Furthermore, because over the brief period of load change (especially the first 1 or 2 breaths) mixed venous and arterial O2 contents were not likely to have changed, changes in (Vo2)A reflected changes in QL according to the Fick principle. In six normal subjects, neither loading nor unloading had any effect on (Vo2)A in the first, second, or third breath (P greater than 0.5). Additional studies at rest produced equally negative results. We conclude that the magnitude of respiratory fluctuations in Ppl has no short-term effect on pulmonary blood flow at rest or during mild exercise.

Adult↗

PubMed1990

The usefulness of the level of the muscularis mucosae in the staging of invasive transitional cell carcinoma of the urinary bladder.

The initial biopsy specimens from 50 patients with high-grade invasive transitional cell carcinoma of the urinary bladder were evaluated for depth of invasion. Stages were assigned according to the following system: T1A, invasion of connective tissue superficial to the level of the muscularis mucosae; T1B, invasion to the level of the muscularis mucosae; T1C, invasion through the level of the muscularis mucosae but superficial to the muscularis propria; and B, invasion into the muscularis propria. Follow-up from the Yale Tumor Registry at a median time of 4.6 years showed that tumors invasive to levels T1A and T1B had a 75% 5-year survival, but tumors invasive through the level of the muscularis mucosae but apparently superficial to the muscularis propria (level T1C) had an 11% 5-year survival, which was comparable with the survival of patients with tumors invasive of the muscularis propria. This study suggests the prognostic importance of assessing the depth of invasion in initial biopsy specimens, even when the specimens lack a muscularis propria.

Adult↗

PubMed1990

The role of iron in t-butyl hydroperoxide-induced lipid peroxidation and hepatotoxicity in rats.

Treatment of rats with 100 mg kg-1 t-butyl hydroperoxide led to an enhanced ethane exhalation as a marker of in vivo lipid peroxidation, as well as a moderate hepatoxicity as evidenced by a rise in plasma activities of liver-specific enzymes (glutamate-pyruvate transaminase and sorbitol dehydrogenase) and an increase in hepatic calcium content. Furthermore, a depletion of hepatic glutathione by 17% was observed. Apart from the loss of glutathione, all these effects were antagonized by pretreatment of rats with the potent iron chelator deferrioxamine and potentiated by pretreatment with low concentrations of FeSO4 having no pro-oxidant activity per se; this was also the case in rats under conditions of iron overload (experimental haemochromatosis). These data indicate a close relationship between t-butyl hydroperoxide-induced lipid peroxidation and its hepatotoxicity, and point out the importance of iron in catalysing reinitiation (propagation) reactions of lipid peroxidation in vivo.

Alanine Transaminase↗

PubMed1990

The role of iron and glutathione in t-butyl hydroperoxide-induced damage towards isolated perfused rat livers.

The hepatotoxic and lipid peroxidative potentials of t-butyl hydroperoxide (t-BuOOH) towards isolated perfused rat livers were investigated at doses of 1 and 3 mmol l-1. t-BuOOH led to a concentration-dependent release of cytosolic (glutamate-pyruvate transaminase and lactate dehydrogenase) and mitochondrial (glutamate dehydrogenase) enzymes, an accumulation of calcium in the liver, a marked depletion of hepatic glutathione and an enhanced release of it into the perfusate, as well as an enhanced formation and release of malondialdehyde (MDA) by the liver. These effects were blocked in the presence of the potent iron chelator deferrioxamine, and enhanced in livers from iron-overloaded as well as in livers from glutathione-depleted rats. Our results indicate that the hepatotoxic and pro-oxidant actions of organic hydroperoxides depend upon the presence of ionized iron as a catalyst of radical-forming breakdown reactions, and are potentiated by impairment of glutathione-dependent detoxification reactions.

Alanine Transaminase↗

PubMed1990

Protection by exogenous glutathione against hypoxic and cyanide-induced damage to isolated perfused rat livers.

In experiments with isolated perfused livers from fasted rats, addition of 2 mmol/l glutathione (GSH) to the perfusion medium protected against hepatic damage induced by cyanide or hypoxia and reoxygenation as evidenced by leakage of lactate dehydrogenase and hepatic calcium accumulation. In control experiments as well as in experiments with cyanide or hypoxia and reoxygenation, exogenous glutathione resulted in an augmentation of cellular glutathione content, indicating either direct uptake of GSH or stimulation of its intracellular synthesis. The protective effects of glutathione against hypoxic and cyanide-induced hepatotoxicity substantiate the role of oxidative stress in both types of injury.

Animals↗

PubMed1990

Oxygen free radicals in acute pancreatitis of the rat.

This study aimed to assess the role of oxygen free radicals in acute pancreatitis. Acute pancreatitis was induced in rats by infusion of the CCK-analogue cerulein (5 micrograms/kg per hour) for 30 minutes, 3.5 hours, and 12 hours. After the infusion, serum enzymes and conjugated tissue dienes and malondialdehyde were measured and tissue samples were subjected to electron and light microscopy. Electron microscopy after 30 minutes showed moderate intracellular alterations. After 3.5 hours of cerulein infusion interstitial oedema and intravascular margination of granulocytes in the pancreatic gland were seen. After 12 hours histological evaluation showed pronounced zymogen degranulation, extensive tissue necrosis, and migration of granulocytes into the tissue. Amylase and lipase activities increased 15 and 35-fold respectively during this time. After 30 minutes of cerulein infusion conjugated dienes and malondialdehyde increased, they reached their peak after 3.5 hours and decreased to normal values after 12 hours. Treatment with superoxide dismutase (100,000 U/kg/hour) and catalase (400,000 U/kg/hour) either before or after the start of the cerulein infusion prevented lipid peroxidation and reduced zymogen degranulation and tissue necrosis. Tissue oedema and inflammatory response, however, were not affected in any of the treated rats. Oxygen free radicals are instrumental in the development of acute pancreatitis. Even after its onset, scavenger treatment reduced the tissue damage normally observed.

Acute Disease↗

PubMed1990

Ventilatory effects of high and pulsatile blood flow in the pulmonary circulation.

The mechanism of ventilatory stimulation that accompanies increases in cardiac output is unknown. Previous studies addressing this issue have been inconclusive. However, only steady pulmonary blood flow was used. The effect of flow pulsatility merits consideration, because increasing cardiac output raises not only mean pulmonary arterial pressure but also pulse pressure; mechanoreceptors with an important dynamic component to their responses may cause a response to pulsatile, but not steady, flow. Studies were done on anesthetized cats (n = 4) and dogs (n = 4). The right pulmonary artery was cannulated within the pericardium, and systemic blood was pumped from the left atrium to the right pulmonary artery. The right pulmonary circulation was perfused at different levels of flow, which was either steady or pulsatile. Steady-state flow of up to 150 ml.kg-1.min-1 (270 ml.kg-1.min-1 when corrected for the proportion of lung tissue perfused) did not affect breathing pattern. When high pulmonary flow was made pulsatile (pulse pressure approximately 23 mmHg), breath duration decreased from 3.7 +/- 0.72 to 3.4 +/- 0.81 (SD) s (P less than 0.01), representing a change in frequency of only 9%. There was no change in peak inspiratory activity. It was concluded that pulmonary vascular mechanoreceptors are not likely to contribute significantly to the increase in ventilation in association with increases in cardiac output.

Animals↗

PubMed1990

Distensibility and pressure-flow relationship of the pulmonary circulation. I. Single-vessel model.

To ascertain the relative contributions of vascular distensibility and nonhomogeneous behavior within the pulmonary circulation to the distinctive nonlinear relationship between inflow pressure (Pin) and flow [pressure-flow (P-F) relationship] and between Pin and outflow pressure (Pout) at constant flow (Pin-Pout relationship), we developed a multibranched model in which the elastic behavior of, and forces acting on, individual branches can be varied independently. The response of the multibranched model is described in the companion article (J. Appl. Physiol. 68: 1514-1527, 1990). Here we describe the methods used and the responses of single components of the larger model. Perivascular pressure is modeled as a function of intravascular and transpulmonary pressures (Pv and Ptp, respectively) and vessel length as a function of lung volume. These and the relationship between vascular area (A) and transmural pressure (Ptm) were modeled primarily from the dog data of Smith and Mitzner (J. Appl. Physiol. 48: 450-467, 1980). Vasomotor tone is modeled as a radial collapsing pressure (Pt) in the same plane as Ptm. In view of lack of information about the relationship between Pt and A for a given active state, different patterns were assumed that span a wide range of possible relationships. The P-F and Pin-Pout relationships of single vessels were very similar to those reported for the entire intact circulation. Of note, the slope of the Pin-Pout relationship in the low Pout range (0-5 Torr) was very low (less than 0.25) and increased gradually with Pout toward unity. Vasomotor tone caused an apparent parallel shift in the P-F relationship in the physiological flow range of the dog (2-8 l/min) regardless of the pattern used to model the Pt vs. A relationship; different patterns affected the P-F relationship only over the low flow range before the parallel shift was established.

Animals↗

PubMed1990

Distensibility and pressure-flow relationship of the pulmonary circulation. II. Multibranched model.

The contribution of distensibility and recruitment to the distinctive behavior of the pulmonary circulation is not known. To examine this question we developed a multibranched model in which an arterial vascular bed bifurcates sequentially up to 8 parallel channels that converge and reunite at the venous side to end in the left atrium. Eight resistors representing the capillary bed separate the arterial and venous beds. The elastic behavior of capillaries and extra-alveolar vessels was modeled after Fung and Sobin (Circ. Res. 30: 451-490, 1972) and Smith and Mitzner (J. Appl. Physiol. 48: 450-467, 1980), respectively. Forces acting on each component are modified and calculated individually, thus enabling the user to explore the effects of parallel and longitudinal heterogeneities in applied forces (e.g., gravity, vasomotor tone). Model predictions indicate that the contribution of distensibility to nonlinearities in the pressure-flow (P-F) and atrial-pulmonary arterial pressure (Pla-Ppa) relationships is substantial, whereas gravity-related recruitment contributes very little to these relationships. In addition, Pla-Ppa relationships, obtained at a constant flow, have no discriminating ability in identifying the presence or absence of a waterfall along the circulation. The P-F relationship is routinely shifted in a parallel fashion, within the physiological flow range, whenever extra forces (e.g., lung volume, tone) are applied uniformly at one or more branching levels, regardless of whether a waterfall is created. For a given applied force, the magnitude of parallel shift varies with proportion of the circulation subjected to the added force and with Pla.

Animals↗