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Biomedical subjects

S Rounds

Publications and source records attributed to S Rounds.

At least 55 records · Page 3Linked to original sources
PubMed1990

Unilateral lung hyperinflation and herniation as a manifestation of intrinsic PEEP.

In a 64-year-old ventilated patient with severe chronic obstructive pulmonary disease and extensive unilateral pneumonia, intrinsic PEEP became recognized when the chest roentgenogram showed unilateral lung hyperinflation and herniation of a large bulla to the contralateral hemithorax. The use of an on-line suction catheter may have contributed to the development of intrinsic PEEP. Removal of the catheter resulted in roentgenographic and clinical improvement.

Hernia↗
PubMed1989

Pulmonary response to foreign body microemboli in dogs: release of neutrophil chemoattractant activity by vascular endothelial cells.

Pulmonary hypertension and foreign body granulomas are complications of the chronic intravenous injection of crushed, suspended pentazocine (Talwin) tablets. To evaluate the early cellular mechanisms underlying the response of the lung to foreign body microemboli, we examined lung histopathology and bronchoalveolar lavage (BAL) fluid in dogs for accumulation of inflammatory cells shortly after the injection of crushed, suspended pentazocine tablets. We found that the injection of suspended pentazocine tablets is associated with the rapid accumulation of neutrophils around intravascular talc crystals but not within the alveolar airspaces. To determine the cause of the observed neutrophil accumulation, we assayed plasma and lavage fluid for neutrophil chemoattractant activity (NCA). NCA appeared in pulmonary arterial (PA) and left ventricular (LV) plasma within 60 s of injection of the suspended tablets. However, there was no evidence of NCA in BAL. To determine whether appearance of chemoattractant activity found in plasma was modified by inhibitors of arachidonic acid metabolism, we infused dogs with indomethacin, diethylcarbamazine (DEC), or FPL 55712 and assayed plasma for NCA after the injection of suspended pentazocine tablets. We found that the appearance of NCA is prevented by the infusion of either DEC or FPL 55712 but not by the infusion of indomethacin. We found that cultured pulmonary arterial or aortic endothelial cells also release NCA when incubated with either the suspended pentazocine tablets or talc. Extraction with acidified diethyl ether partitioned all the NCA into the organic phase. The release of NCA from cultured endothelial cells was likewise prevented by coincubation with DEC or FPL 55712 but not by coincubation with indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Studies on the mechanism of decreased neutrophil adherence to postconfluent cultured endothelial cells.

The adherence of neutrophils (PMN) to endothelium is a crucial early step in neutrophil-mediated vascular injury. However, vascular injury is not a necessary event in inflammatory states, which suggests that endogenous mechanisms may protect endothelial cells from neutrophil-mediated injury. Previous studies suggested that leukocytes adhered in greater numbers to vascular endothelium in vivo and in vitro, where the contiguity of the cells was disrupted and where endothelial cells were actively migrating and proliferating. We studied the effect of development of a confluent monolayer on adherence of human PMN to cultured bovine calf aortic endothelial cells and investigated several mechanisms by which this effect might occur. We found that adherence of quiescent and activated PMN decreased with development of a confluent endothelial cell monolayer. A similar effect was found using human umbilical-vein endothelial cells. In contrast, adherence of nylon wool-nonadherent, thymus-derived lymphocytes increased. Variation in neutrophil adherence was not due to adherence of PMN to exposed tissue culture plastic or to exposed matrix components in preconfluent cultures, nor due to products released into culture supernatants. Diminished PMN adherence to postconfluent monolayers may have been related to changes in endothelial cell glycoproteins because neuraminidase or cycloheximide pretreatment augmented PMN adherence to postconfluent cultures more than to preconfluent cultures. However, the extent of total cell surface sialation, as assessed by neuraminidase-releasable [3H]glucosamine from metabolically labeled monolayers, did not differ between pre- and postconfluent cultures, suggesting that some specific sialated cell surface constituent is responsible for decreased PMN adherence to postconfluent monolayers.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Effect of ambient oxygen on cultured endothelial cells from different vascular beds.

By the use of production of neutrophil chemoattractant activity as a marker, we investigated the responsiveness of endothelial cells of four different anatomic origins to altered ambient oxygen tension to determine whether genetic or conditioned variation existed. The ability of bovine aortic, bovine pulmonary arterial, bovine coronary arterial, and human umbilical vein endothelial cells incubated in decreased oxygen concentrations to release neutrophil chemoattractant activity was assessed. Bovine aortic, human umbilical vein, and bovine coronary arterial endothelial cells produce neutrophil chemoattractant activity in response to 10 or 3% ambient oxygen in vitro. In contrast, 0% ambient oxygen is required for appearance of neutrophil chemoattractant activity from pulmonary artery endothelial cells. These studies suggest that there may be genetic or conditioned variations in the response of endothelium from different vascular beds to decreased oxygen tensions. Furthermore, endothelial cells may play a role in neutrophil-mediated tissue injury during ischemia.

Animals↗
PubMed1987

The binding of cationic probes to apical and basal surfaces of rat lung capillary endothelium and of endothelial cells in tissue culture.

The reasons for greater lung vascular permeability to anionic macromolecules are not understood. In order to determine whether the luminal or abluminal surfaces of lung capillary endothelial cells differ with respect to surface charge, we compared the binding of cationic ferritin, an electron dense probe, with these cell surfaces in lung capillaries. Because lung capillaries are not normally permeable to cationic ferritin, lungs were examined from rats with increased permeability edema caused by pretreatment with alpha-naphthylthiourea (ANTU). We found that more cationic ferritin particles bound to the luminal than to the abluminal surfaces of lung capillary endothelium. In order to determine whether this was due to inaccessibility of cationic ferritin to the lung interstitium, we also compared cationic ferritin binding to the apical and basal surfaces of bovine calf aortic and main pulmonary arterial endothelial cells in tissue culture. We found that more cationic ferritin bound to the apical than to the basal surface of the cultured cells. The binding of cationic ferritin to cultured endothelial cells was due to charge since native, anionic ferritin did not bind to either surface and binding was decreased by neuraminidase pretreatment of cultures. Cultures incubated with thiourea, another thiocarbamide that causes increased permeability edema in vivo, also showed greater binding of cationic ferritin to the apical cell surface, suggesting that the differences seen in vivo were not due to thiocarbamide injury. However, another cationic probe, ruthenium red, bound to both the apical and basal surfaces of cultured endothelial cells. These results suggest that the basal endothelial cell surface does not lack anionic sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Chylomicron metabolism by normal and injured isolated rat lungs.

Since the lung is the first highly vascularized organ to which chylomicrons are exposed, we sought to determine whether the lung vasculature is capable of metabolizing triglyceride contained in circulating, native chylomicrons. In addition, since acute lung injury can depress other endothelial cell associated metabolic functions, we determined whether acute injury due to alpha-naphthylthiourea (ANTU) changed chylomicron triglyceride metabolism by lungs. We compared the hydrolysis of radiolabelled chylomicrons from rat mesenteric lymph by perfused lungs isolated from rats pretreated with ANTU; with the vehicle, Tween 80, alone; or untreated control rats. In all groups of lungs, we found that perfusate content and concentration of triglyceride decreased over 30 minutes of perfusion, while that of free fatty acid increased, indicating that isolated lungs are able to hydrolyze chylomicron triglyceride. Despite enhancement of hydrolysis by perfusates containing 6 gm/100 ml of bovine serum albumin, there were no differences among the groups of lungs in the extent or rate of triglyceride metabolism. The [1-14C]-oleate from chylomicron triglyceride was taken up into lung tissue during 30 minutes of perfusion and incorporated into neutral lipid, phosphatidylcholine, and phosphatidylethanolamine to a similar degree by ANTU-injured and control lungs. Lipoprotein lipase activity in homogenates of lungs from ANTU and Tween treated rats did not differ. We conclude that lungs are capable of hydrolysis of triglyceride contained in chylomicrons and that this endothelial cell associated metabolic function is not altered by acute lung injury caused by ANTU.

Animals↗
PubMed1986

Generation of, lipid neutrophil chemoattractant activity by histamine-stimulated cultured endothelial cells.

Endothelial cell-neutrophil interactions are an important aspect of inflammatory responses. Because vascular endothelial cells respond to the inflammatory mediator histamine, these studies determined whether histamine could induce endothelial cells to release substances that affect human neutrophil migration. Cultured bovine and human endothelial cells incubated with histamine released neutrophil chemoattractant activity within 1 min; peak levels were noted in 45 min. Cimetidine, an H2 receptor antagonist, blocked chemoattractant production, whereas diphenhydramine, an H1 receptor antagonist, did not. Cycloheximide did not inhibit release of chemoattractant activity, suggesting de novo protein synthesis was not necessary for its appearance. Extraction with acidified diethyl ether partitioned all neutrophil chemoattractant activity into the organic phase. The lipoxygenase pathway inhibitors, diethylcarbamazine and 5,8,11,14 eicosatetraynoic acid, inhibited generation of this lipophilic chemoattractant activity, whereas indomethacin, a cyclo-oxygenase inhibitor, did not. Resolution of the histamine-induced endothelial cell-derived chemoattractant activity by reverse-phase high pressure liquid chromatography yielded several peaks of chemoattractant activity, none of which co-eluted with leukotriene B4, platelet-activating factor, or two mono-hydroxyeicostetraenoic acids. These findings suggest that endothelial cells release lipid neutrophil chemoattractant activity that may play a role in inflammatory responses associated with histamine.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1985

Bovine and human endothelial cell production of neutrophil chemoattractant activity in response to components of the angiotensin system.

Although there is growing evidence that angiotensin II affects macrophage-mediated inflammatory responses, it is unclear whether it can affect neutrophil-mediated inflammatory responses. Because vascular endothelial cells are capable of releasing neutrophil chemoattractant activity, we attempted to determine whether components of the angiotensin system could affect neutrophil-mediated responses indirectly by stimulating endothelial cells to release neutrophil chemoattractant substances. Cultured bovine and human endothelial cells incubated with angiotensin II released neutrophil chemoattractant activity. This activity appeared within 1 minute of exposure to angiotensin II, and was blocked by saralasin, an angiotensin II antagonist. Angiotensin I also caused release of neutrophil chemoattractant activity, but its effect required conversion to angiotensin II. Bradykinin, another substrate for angiotensin-converting enzyme, did not stimulate appearance of chemoattractant. Chemoattractant generation was not inhibited by indomethacin but was blocked by diethylcarbamazine and 5,8,11,14-eicosatetraynoic acid. This study demonstrates that angiotensin II may influence neutrophil accumulation, via production of neutrophil chemoattractant activity by vascular endothelial cells.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1985

Effects of endothelial cell injury on pulmonary vascular reactivity.

Using the thiocarbamide model of acute lung injury in rats, we found that alpha-naphthylthiourea (ANTU) caused lung endothelial cell injury, as evidenced by increased permeability edema and decreased angiotensin I conversion. These effects were associated with enhanced pulmonary vascular reactivity. Recurrent ANTU lung injury caused pulmonary hypertension. The water-soluble thiocarbamide thiourea caused cultured vascular endothelial cells to release neutrophil chemoattractant activity. We speculate that endothelial cell injury may modulate the function of vascular smooth muscle and blood leukocytes.

Angiotensin II↗
PubMed1985

Studies on the mechanism of decreased angiotensin I conversion in rat lungs injured with alpha-naphthylthiourea.

Lung endothelial cell injury may be an important early event in the pathogenesis of increased permeability pulmonary edema. Since angiotensin converting enzyme (ACE) is located on the luminal surface of the endothelial cell membrane, we sought to determine whether the conversion of angiotensin I (AI) to angiotensin II is decreased after acute lung injury to rats, induced by alpha-naphthylthiourea (ANTU), and we investigated the mechanism of the decrease. We found that lungs isolated from rats treated 4 h earlier with ANTU at a dose of 15 mg/kg body weight (BW) had decreased AI conversion when perfused with Krebs-Henseleit at a constant flow rate of 30 ml/min/kg BW. When perfusate flow rate was increased from 30 to 50 ml/min/kg BW, lungs isolated from rats treated with 10 mg/kg BW ANTU also had decreased AI conversion when compared to controls treated with a vehicle, Tween 80. Investigating the mechanism of decreased AI conversion, there were no differences among experimental groups in pulmonary arterial pressures or effluent perfusate pH or pO2. There was no correlation between lung wet/dry weight ratios and the extent of AI conversion among control rat lungs. Lung homogenate and serum ACE activity did not differ among control rats and rats pretreated with the two doses of ANTU. Ultrastructural studies revealed an increased percentage of capillaries with blebbing of endothelial cells in lungs injured with ANTU, as compared to controls, but no evidence of increased endothelial cell denudation in injured lungs. We conclude that angiotensin I conversion is decreased after ANTU lung injury and that the extent of decrease is related to the dose of ANTU and to perfusate flow rate. Although we cannot exclude decreased vascular surface area perfused as a cause of decreased conversion, we speculate that subtle changes in the luminal endothelial cell membrane may have caused decreased AI conversion after ANTU lung injury.

Angiotensin I↗
PubMed1984

Repeated lung injury due to alpha-naphthylthiourea causes right ventricular hypertrophy in rats.

Acute lung injury due to alpha-naphthylthiourea (ANTU) is associated with increased permeability edema, transient pulmonary hypertension, and increased vascular reactivity. We sought to determine whether repeated administration of ANTU caused right ventricular hypertrophy. Rats were injected weekly for 4 wk with ANTU or an equivalent volume of the vehicle Tween 80. Rats injected repeatedly with ANTU in doses of 5-10 mg/kg body wt had increased ratios of right ventricular to left ventricular plus septal weights. The right ventricular hypertrophy in ANTU-treated rats was associated with right ventricular systolic hypertension. Repeated injections of ANTU also caused transient pulmonary edema after each dose, as evidenced by increased wet-to-dry lung weight ratios after 4 h, which returned to normal by 24 h. Lungs isolated from ANTU-injected rats had greater pressor responses to hypoxia and to angiotensin II than lungs from Tween 80-injected rats. Pressure-flow curves of isolated lungs, arterial blood gases, and hematocrits were similar in rats treated repetitively with ANTU or Tween alone. Lung histology was also similar in ANTU and control lungs, as were measurements of arterial medial thickness and ratios of numbers of arteries/100 alveoli, indicating that substantial vascular remodeling had not occurred. Thus, four weekly ANTU injections in rats caused right ventricular hypertrophy, probably due to pulmonary hypertension. We speculate that the pulmonary hypertension was due, at least in part, to sustained vasoconstriction, which somehow resulted from repeated acute lung injury.

Animals↗
PubMed1984

Binding of charged ferritin to alveolar wall components and charge selectivity of macromolecular transport in permeability pulmonary edema in rats.

Rat lungs were inflated and incubated in either anionic or cationic ferritin, and alveolar and capillary basement membranes were examined by electron microscopy. Cationic ferritin bound to heparan sulfate proteoglycans on the external surface of the alveolar basement membrane, whereas cationic ferritin bound to the lamina densa of the capillary basement membranes. Anionic and cationic ferritin was also perfused through the pulmonary circulation of lungs isolated from control rats and rats previously injected with alpha-naphthylthiourea, which produces permeability pulmonary edema. Neither anionic nor cationic ferritin leaked from the pulmonary capillaries in perfused controls; cationic, but not anionic, ferritin adhered to endothelial cell surfaces. In lungs with alpha-naphthylthiourea pulmonary edema, perfused for 2-15 minutes, anionic ferritin leaked from pulmonary capillaries into the alveolar interstitium and alveolar space, while cationic ferritin remained within the capillary lumen. Five times as much anionic ferritin appeared in the capillary basement membranes on the thick side of the alveolar wall, as in the alveolar basement membranes on the thin side of the alveolar wall. In alpha-naphthylthiourea lungs perfused for 45-60 minutes, cationic ferritin also leaked through the injured endothelium and bound twice as much to the alveolar as the capillary basement membranes. The negatively charged pulmonary capillary endothelium, the positively charged capillary basement membranes, and the negatively charged alveolar basement membranes may influence the transport of macromolecules from the pulmonary circulation in permeability pulmonary edema.

Animals↗
PubMed1984

Thiourea causes endothelial cells in tissue culture to produce neutrophil chemoattractant activity.

We describe neutrophil chemoattractant activity that is produced by cultured bovine aortic and pulmonary arterial endothelial cells when incubated with thiourea, a substance that causes increased permeability pulmonary edema in animals. The chemoattractant activity was present in culture supernates and cell lysates of endothelial cells incubated with thiourea but was not present in untreated cells. Production of chemoattractant activity was not associated with cell death; viable cell counts and cell homogenate angiotensin converting enzyme levels were not affected, and Cr release was only slightly elevated after incubation with thiourea. At least 1.5 h of incubation with 0.5 mM thiourea was necessary for generation of neutrophil chemoattractant activity. Culture supernates from pulmonary vascular smooth muscle cells and lung fibroblasts did not show increased neutrophil chemoattractant activity after incubation with thiourea. The chemoattractant had both chemokinetic and chemotactic properties, was heat stable, and was extractable into organic solvents. Meclofenamate, a cyclooxygenase inhibitor, minimally inhibited chemoattractant production, whereas 5,8,11,14-eicosatetraynoic acid (ETYA), an inhibitor of both cyclooxygenase and lipoxygenase, completely abolished generation of chemoattractant activity, suggesting that the activity could be a product of arachidonic acid metabolism. These results demonstrate that endothelial cells can produce a substance(s) with neutrophil chemotactic activity. Production of neutrophil chemoattractant activity by endothelial cells could be important in polymorphonuclear leukocyte accumulation at injured vascular sites.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1984

Pulmonary hypertensive diseases.

Pulmonary hypertension may occur as a primary disorder of the pulmonary vasculature or secondary to a variety of cardiac or pulmonary diseases. The reversibility of pulmonary hypertension is dependent on the relative contribution of reversible vasoconstriction and irreversible structural changes in the pulmonary vessels. Despite recent advances in the understanding of pulmonary vascular physiology, knowledge of the pathogenesis and natural history of pulmonary hypertension has been limited by an inability to measure pulmonary arterial pressure noninvasively. Thus, when patients have symptoms or signs of pulmonary hypertension, the disease is usually at an advanced stage. It is possible that early in the course of hypoxic pulmonary disease, pulmonary hypertension may be protective in optimizing matching of ventilation and perfusion. It is not known at what point pulmonary hypertension per se becomes harmful. Certainly, treatment directed at underlying cardiac or pulmonary disease is indicated. It also seems reasonable to treat severe degrees of pulmonary hypertension complicated by right ventricular dysfunction. With the advent of orally effective pulmonary vasodilators, direct treatment of primary and secondary pulmonary hypertension may now be possible. Hopefully, with careful clinical evaluation of the response to vasodilator therapy, we will learn whether these drugs prolong life and reduce morbidity in primary and secondary pulmonary hypertension. In the meantime, much more information is needed regarding the mechanisms of acute pulmonary vasoconstriction and sustained pulmonary hypertension. In addition, a means of early identification of patients with mild hypertension is needed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Vascular reactivity is increased in rat lungs injured with alpha-naphthylthiourea.

We investigated the effects of lung injury due to alpha-naphthylthiourea (ANTU) on pulmonary vascular reactivity. Rats were treated with ANTU (10 mg/kg ip) or the vehicle Tween 80. Four hours later, lungs from ANTU-treated rats had increased wet-to-dry weight ratios, bronchial lavage protein concentrations, and perivascular edema. To test vascular reactivity, lungs were isolated and perfused with blood at constant flow rate, while mean pulmonary arterial pressure was monitored. ANTU-treated lungs vasoconstricted earlier than Tween-treated lungs in response to severe airway hypoxia (fractional inspired O2 0%). ANTU-treated lungs vasoconstricted in response to 10% O2, while Tween-treated lungs failed to respond to 10% O2, indicating that the threshold for hypoxic vasoconstriction was decreased by ANTU. ANTU also decreased the threshold for and increased the magnitude of angiotensin II pressor responses, indicating that the increased vasoreactivity was not specific for hypoxia. Addition of meclofenamate to perfusates increased the rate and magnitude of responses to 0% O2 in Tween-treated lungs, but did not change the responses of ANTU-treated lungs. Light microscopy of ANTU-treated lungs showed no pulmonary arterial obstruction, and electron microscopy revealed mild capillary endothelial cell injury. We conclude that enhanced pulmonary vascular reactivity accompanies the increased-permeability pulmonary edema caused by ANTU. A similar increase in vasoreactivity might contribute to pulmonary hypertension observed in patients with the adult respiratory distress syndrome.

Angiotensin II↗
PubMed1983

Amrinone dilates pulmonary vessels and blunts hypoxic vasoconstriction in isolated rat lungs.

The direct effects of the cardiotonic agent amrinone (WIN 40680) on pulmonary vasoreactivity were studied in isolated, blood-perfused, rat lungs. Lungs were perfused at constant flow and ventilated with normoxic gas, while mean pulmonary arterial pressure was monitored. Pressor responses to hypoxic gas (3% O2, 5% CO2) and angiotensin II (0.25 microgram/0.1 ml) were elicited after amrinone or saline was added to the perfusate. Pressor responses were blunted when calculated amrinone perfusate concentration was increased to 10 micrograms/ml. Pressor responses to hypoxia fell from 8 +/- 1 mm Hg (mean +/- SE, n = 8) before, to 2 +/- 1 mm Hg after amrinone (10 micrograms/ml), while responses to angiotensin II fell from 7 +/- 1 to 3 +/- 1 mm Hg (n = 8). Pressor responses in saline controls did not change. Pulmonary arterial pressure dropped within minutes following injection of amrinone (300 micrograms) into the pulmonary arterial cannula, with a greater drop during hypoxia than during normoxia. Meclofenamate did not prevent blunting of pressor responses by amrinone. Amrinone is a rapidly acting vasodilator which blunts vasoconstriction due to hypoxia or angiotensin II. Since it combines cardiotonic and pulmonary vasodilator actions, amrinone may have therapeutic potential for patients with cor pulmonale and pulmonary hypertension.

Aminopyridines↗