PubMed Health⌕ Search

Biomedical subjects

A D Kaye

Publications and source records attributed to A D Kaye.

At least 37 records · Page 2Linked to original sources
PubMed2000

Analysis of responses of garlic derivatives in the pulmonary vascular bed of the rat.

Allicin, an extract from garlic, has been shown to be a systemic and pulmonary arterial vasodilator that acts by an unknown mechanism. In the present experiments, pulmonary vascular responses to allicin (10-100 microg), allyl mercaptan (0.3-1 mg), and diallyl disulfide (0.3-1 mg) were studied in the isolated lung of the rat under constant-flow conditions. When baseline tone in the pulmonary vascular bed of the rat was raised to a high-steady level with the thromboxane A(2) mimic U-46619, dose-related decreases in pulmonary arterial pressure were observed. In terms of the mechanism of action of allicin vasodilator activity in the rat, responses to allicin were not significantly different after administration of the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester, the K(ATP)(+) channel antagonist U-37883A, or the cyclooxygenase inhibitor sodium meclofenamate, or when lung ventilation was interrupted. These data show that allicin has significant vasodilator activity in the pulmonary vascular bed of the rat, whereas allyl mercaptan and diallyl disulfide produced no significant changes in pulmonary arterial perfusion pressure. The present data suggest that pulmonary vasodilator responses to allicin are independent of the synthesis of nitric oxide, ATP-sensitive K(+) channels, activation of cyclooxygenase enzyme, or changes in bronchomotor tone in the pulmonary vascular bed of the rat.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2000

Garlic extract (allium sativum) reduces migration of neutrophils through endothelial cell monolayers.

Leukocytes play an important role during inflammation. They migrate from intravascular spaces into tissues and attack micro-organisms. In a recent study, the inhibitory effects of the non-steroidal anti-inflammatory drug, ibuprofen, on leukocyte transmigration were demonstrated using an in vitro assay. Little is know about the cellular effects of garlic extracts (allium sativum). The aim of the current study was to investigate the influence of garlic extract on leukocyte migration through endothelial cell monolayers and thereby evaluate a possible role in inflammatory processes. Human umbilical endothelial cells were cultured on microporous membranes to make an endothelial cell monolayer (ECM). Freshly isolated neutrophils were used in a recently described migration assay. The amount of untreated neutrophils migrating through the untreated ECM was used as control and set at 100%. Neutrophils and/or ECM were pre-treated with garlic extract using moderate, as well as higher and lower concentrations. Moderate plasma concentrations garlic extract inhibited neutrophil migration through ECM significantly (64 +/- 5.8% SD; P < 0.05), when both cell types were treated, (a situation that may have clinical relevance). Treating either neutrophils or ECM alone showed significant reductions in migratory rate (neutrophils treated alone: 81 +/- 7.7% SD, p < 0.05; ECM alone: 70 +/- 6.7%, p < 0.05). Thus, garlic extract is identified as a potent inhibitor of leukocyte migration through endothelial cell monolayers. Treatment of both cell types has an additive effect. Endothelial cells seem to be more affected than neutrophils. Further investigations are necessary to understand the potential clinical consequences. During inflammation, neutrophils play an important role. They migrate rapidly from the vascular space into tissues to destroy invading micro-organisms. During migration through endothelial cell monolayers (ECM), neutrophils undergo morphologic changes from rounded, relatively smooth cells to elongated, ruffled cells with pseudopodia. Recently, the influence of the non-steroidal anti-inflammatory drug, ibuprofen, on leukocyte function was investigated using an in vitro double chamber migration assay that includes ECM. Garlic extract (allium sativum) is a widely used "over the counter" herbal preparation. The effect of garlic on lipid metabolism is well documented. Previous studies have examined the influence of the extract on leukocyte function, e.g. respiratory burst. The effect of garlic on thrombocyte aggregation has also been recently described as has an anti-fungal effect. To our knowledge, nothing is known about the effect of garlic leukocyte transmigration. Therefore, we aimed to examine the effects of garlic extract on leukocyte transmigration through ECM in an in-vitro cell co-culture system.

Allium↗
PubMed1999

Oral contraceptives that contain ethinyl estradiol (0.035 mg) and cyproterone acetate (2 mg) inhibit leukocyte transmigration through endothelial cell monolayers.

OBJECTIVE: To investigate the influence of ethinyl estradiol and cyproterone acetate in oral contraceptives on leukocyte migration through endothelial cell monolayers. DESIGN: Experimental in vitro prospective study. SETTING: An academic research laboratory. INTERVENTION(S): Endothelial cells were cultured on microporous membranes to produce monolayers. Polymorphonuclear leukocytes were used in a previously described migration assay (n = 7). The amount of untreated polymorphonuclear leukocytes that migrated through untreated endothelial cell monolayers was used as a control and set at 100%. In addition, a leukocyte adhesion assay was used. MAIN OUTCOME MEASURE(S): Leukocyte adhesion to and transmigration through endothelial cell monolayers. RESULT(S): Ethinyl estradiol and cyproterone acetate inhibited the migration of polymorphonuclear leukocytes through endothelial cell monolayers significantly (67% +/- 6.4%) when both cell types were treated to simulate in vivo conditions. The adhesion assay produced similar results. CONCLUSION(S): Ethinyl estradiol and cyproterone acetate were identified as potent inhibitors of leukocyte migration through endothelial cell monolayers.

Cell Adhesion↗
PubMed1999

Introducers and protective sleeves may increase thrombogenicity of pulmonary artery catheters.

OBJECTIVE: To investigate the cause of clot formation on the surface of non-heparin coated/bonded pulmonary artery catheters. DESIGN: A controlled, unblinded, open-labeled study. SETTING: Research laboratory at Tulane School of Medicine, New Orleans, LA. PARTICIPANTS: Rhesus and African Green monkeys. INTERVENTIONS: Anesthetized monkeys (n = 24) were assigned to one of two groups. The first group (group A) had a pulmonary artery catheter inserted into a femoral vein through a cutdown without passage through an introducer or protective sleeve before insertion. In the second group (group B), the pulmonary artery catheter was passed through an introducer and protective sleeve before insertion in the femoral vein. After the study, the animals were returned to the primate breeding colony. Laboratory values were measured for each animal, and electron micrographs were taken of selected pulmonary artery catheters before and after passage of these catheters through the introducer sheath and/or protective sleeve. MEASUREMENTS AND MAIN RESULTS: Between the two groups, there was a significant difference in fibrinogen level, but not in hematocrit, prothrombin time, partial thromboplastin time, and platelet count. Clots were visible on 11 of 12 catheters in group B, which was statistically significant (p < 0.01), compared with only 3 of 12 catheters in group A. The average clot weight was 0.014+/-0.014 g in group A (range, 0.00 to 0.170 g), which was statistically significant (p < 0.01), compared with 0.216 < 0.058 g in group B (range, 0.000 to 0.620 g). Electron micrographs taken after catheters were passed through an introducer and/or protective sleeve showed that both significantly altered the surface of the catheter. The surface of the catheter was smooth and homogenous in appearance before insertion. Conversely, both the introducer and protective sleeve produced marked furrowing and a nodular appearance on the catheter surface, as shown by electron micrographs. CONCLUSION: The data from this study show that the incidence of clot formation and amount of clot formed on the surface of non-heparin-coated pulmonary artery catheters are significantly greater after passage through an introducer and/or protective sleeve. The electron micrographs also show that both introducers and protective sleeves abraded the catheters and were associated with thrombus formation on the catheter. Designing less traumatic valves on these devices is warranted and recommended.

Animals↗
PubMed1999

Do anticoagulation with heparin and protamine reversal alter thrombogenicity of coated and noncoated pulmonary artery catheters?

OBJECTIVE: To clarify the role of anticoagulation with heparin and protamine reversal on the effectiveness of heparin bonding or coating of pulmonary artery catheters in preventing thrombus formation in the Rhesus monkey. DESIGN: A controlled, unblinded, open-labeled study. SETTING: A research laboratory at Tulane School of Medicine (New Orleans, LA). PARTICIPANTS: Twenty-four anesthetized Rhesus monkeys. INTERVENTIONS: The monkeys were assigned to one of four groups. In the first group (group A), non-heparin-coated catheters were inserted into a femoral vein through an incision, advanced proximally for a distance of 30 cm, and left in place for 1 hour. In the second group (group B), heparin-coated catheters were placed and evaluated in the same manner as in group A. In the third group (group C), the primates received 3 mg/kg of heparin intravenously (i.v.) before insertion of a non-heparin-coated pulmonary artery catheter. After the catheter had been in place for 1 hour, protamine, 3 mg/kg i.v., was administered, and the catheter was left in place for an additional hour. In the final group (group D), the primates received 3 mg/kg of heparin i.v. before insertion of a heparin-coated pulmonary artery catheter. After the catheter had been in place for 1 hour, protamine, 3 mg/kg i.v., was administered, and the catheter was left in place for an additional hour. In each group, the catheter was withdrawn with the balloon inflated to minimize any stripping of thrombus from the surface of the catheter. Thrombus was removed from the catheter through a femoral vein cutdown and weighed. Laboratory values were determined for each animal, and clot formation was evaluated in each group. After completion of the study, the animals were returned to the primate breeding colony. MEASUREMENTS AND MAIN RESULTS: There were no significant differences in hematocrit, prothrombin time, partial thromboplastin time, or platelet levels among the four groups; therefore, the data were pooled. Clots were observed on five of six catheters in both groups A and C; however, clot formation was seen in one of six catheters in group B and three of six catheters in group D. There was a statistically significant difference (p < 0.01) in mean clot weight in group A (265 +/- 68 mg; range, 0 to 447 mg) compared with 13 +/- 13 mg in group B (range, 0 to 80 mg). There was no significant difference in mean clot weight in group C (104 +/- 35 mg; range, 0 to 202 mg) compared with group D (24 +/- 16 mg, range, 0 to 98 mg). Additionally, in group C, the mean clot weight was significantly less than in group A. CONCLUSION: Anticoagulation of primates with heparin before catheter insertion imparts some protection to non-coated catheters, and protamine reversal of anticoagulation with heparin may partially negate the protective effect seen with heparin-coated pulmonary artery catheters.

Animals↗
PubMed1999

Responses to propofol in the pulmonary vascular bed of the rat.

BACKGROUND: Although a great deal is known about responses to propofol, controversy remains about its mechanism of action. The present study was undertaken to investigate the direct effects of 2,6-diisopropyl phenol, disodium edetate, and its intralipid emulsion in the rat pulmonary vascular bed and to better understand the mechanisms involved in propofol-mediated responses. METHODS: The effects of N omega-l-nitro-l-arginine benzyl ester (L-NABE), an inhibitor of nitric oxide synthase, of the cyclooxygenase blocker, meclofenamate, and the K + ATP channel antagonist, U-37883A, an ATP-sensitive potassium channel antagonist, on responses to propofol, acetylcholine, nitroglycerin, and isoproterenol were investigated in the isolated blood-perfused rat lung under low tone and high steady-state tone. RESULTS: Propofol produced a dose-dependent decrease in pulmonary arterial perfusion pressure. L-NABE significantly reduced vasodilator responses to acetylcholine, whereas the nitric oxide synthase inhibitor had no significant effect on responses to propofol. Meclofenamate significantly reduced vasodilator responses to arachidonic acid without effecting responses to propofol. Responses to propofol were not significantly changed in the presence of U-37883A, whereas U-37883A reduced vasodilator responses to levcromakalim. Additionally, 2,6-diisopropylphenol in a pure preparation as well as an intralipid preparation similar to propofol emulsion had no significant effect while disodium edetate had a dose-dependent depressor effect under high steady-state tone. CONCLUSION: Propofol has significant vasodilator activity in the pulmonary vascular bed of the rat but responses to propofol are not mediated or modulated by the release of nitric oxide, opening of K + ATP channels, or the release of vasodilator cyclooxygenase products.

Acetylcholine↗
PubMed1999

Effect of anticoagulation on blood membrane interactions during hemodialysis.

BACKGROUND: Adequate anticoagulation is a precondition to prevent extracorporeal blood clotting and to improve biocompatibility during hemodialysis. In this study, we performed a morphologic analysis by using scanning electron microscopy to compare three modes of anticoagulation-conventional unfractionated heparin (UFH), low molecular weight heparin (LMWH; dalteparin sodium), or sodium citrate during hemodialysis-on membrane-associated coagulation activation. METHODS: Fifteen patients on regular hemodialysis therapy were investigated. Five patients received UFH, five patients LMWH, and five patients sodium citrate as an anticoagulant during a standardized hemodialysis protocol using a single-use polysulfone capillary dialyzer. Membrane-associated clotting was evaluated using a scanning electron microscope. A dialyzer clotting score was used for quantitative description of coagulation activation on membrane segments. RESULTS: Using UFH as an anticoagulant revealed the most pronounced cell adhesion and thrombus formation and the highest dialyzer clotting score (11.5 +/- 1.3 of a maximal 20 points). LMWH had a lower dialyzer clotting score than UFH (10.4 +/- 1.2 of 20 points). During the use of sodium citrate, a negligible thrombus formation and the lowest dialyzer clotting score (1.6 +/- 0.6 of 20 points, P < 0.05) were observed. CONCLUSION: The results of this investigation indicate that using sodium citrate as an anticoagulant during hemodialysis induces a lower activation of coagulation than both conventional and fractionated heparin, which might contribute to an improvement of biocompatibility of hemodialysis extracorporeal circulation.

Adult↗
PubMed1999

Amoxycillin/clavulanic acid combinations increase transmigration of leucocytes through endothelial cell monolayers: endothelial cells play a key role.

Postoperative inflammation is still viewed as an unresolved problem. During inflammation, leucocytes play a tremendous role and migrate from intravascular spaces into the tissue to attack microorganisms. Different agents, e.g. anaesthetic drugs, are able to influence leucocyte recruitment. Previous studies have investigated the influence of amoxycillin on chemotaxis of leucocytes alone. The aim of our study was to examine the effect of amoxycillin/clavulanic acid (co-amoxiclav) on leucocyte migration through endothelial cell monolayers (ECMs). Human umbilical endothelial cells were cultured on microporous membranes, achieving a monolayer. Polymorphonuclear neutrophil leucocytes (PMNLs) were used in a migration assay. The numbers of untreated PMNLs migrating through untreated ECMs were used as control and set as 100%. PMNLs and/or ECMs were pretreated with co-amoxiclav using clinically relevant as well as higher and lower concentrations. Co-amoxiclav was able to increase PMNL migration through ECMs significantly (P<0.05) when both cell types were treated (291+/-18.7%). When PMNLs or ECMs were treated alone, it could be shown that ECMs were more affected than PMNLs. The greatest effect was shown when both cell types, PMNLs and ECMs, were treated. In conclusion, co-amoxiclav was identified as a potent drug to increase leucocyte transmigration through ECMs. ECMs were also critically involved. Co-amoxiclav also affects endothelial cells.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed1999

Changes in compliance predict pulmonary morbidity in patients undergoing abdominal plication.

The incidence and severity of the effects of pulmonary compliance changes were investigated in patients undergoing abdominal plication surgery. A total of 20 healthy adults scheduled for abdominal plication surgery who had no significant history of pulmonary disease and 20 adults scheduled for nonabdominal, nonthoracic surgery (control group) underwent general endotracheal anesthesia; neuromuscular blockade was confirmed with electrical twitch monitoring. Before abdominal plication, the mean airway compliance was measured under total neuromuscular blockade at 33.4 +/- 2.1 ml/cm water, which was not significant when compared with control patient values. After abdominal plication was performed, the mean airway compliance was remeasured under total neuromuscular blockade; it was significantly decreased at 24.0 +/- 1.8 ml/cm water when compared with values for control patients (32.6 +/- 1.6 ml/cm) and with preplication values. Patients with airway compliance changes of less than 4 ml/cm water (when compared with preplication pulmonary mechanics) had far less incidence of atelectasis, requirements for supplemental oxygen at 24 hours or longer, or hypoxia when compared with patients with compliance changes of greater than 4 ml/cm water. Patients with compliance changes greater than 9 ml/cm water had the highest incidence of pulmonary morbidity. These data suggest that significant changes in pulmonary compliance occur after abdominal plication and that these airway compliance changes are associated with a clinically increased incidence of pulmonary morbidity in the postoperative period.

Abdominal Muscles↗
PubMed1999

The immune system and the effects of non-volatile anesthetics on neutrophil transmigration through endothelial cell monolayers.

Inflammation represents the consequence of capillary dilation with accumulation of fluid and transmigration of leukocytes into the surrounding tissue. Leukocytes play a major role in the defense system of the body against invading microorganisms. This defense system has a non-specific branch consisting of granulocytes and macrophages and a specific branch of lymphocytes. Granulocytes release cytotoxic compounds from their intracellular granules into their local environment when encountering microorganisms. This random destruction happens rapidly, but it may also harm healthy tissue of the body. Leukocytes patrol the body by circulating through the blood and lymphatic system ensuring a continuous surveillance which is a prerequisite for an efficient defense. Upon tissue damage and inflammation, leukocytes are recruited from the blood to sites of injury, and this trafficking displays exquisite specificity. In the late 1890 s, Metchnikoff noted the power of certain blood cells to move towards microorganisms and ingest them. In fact, leukocytes adhere to the endothelium of the blood vessels, and subsequently leave the circulation by transmigration through the intercellular junctions of the endothelial cell monolayer. Transmigration is driven by chemoattractants, a process known as diapedesis. Reversible adherence of leukocytes to the endothelium, basement membranes, and other surfaces is an essential event in the establishment of inflammation, whose molecular basis is beginning to be understood. Inflammation may become chronic in many pathophysiologic processes and disease states. In long-term mechanically ventilated critically ill patients, non-volatile anesthetics are needed over a prolonged time period. Perioperative infections are a major cause of morbidity and mortality in critically ill patients. Therefore, the influence of non-volatile anesthetics and opioid agents on the immune system is of high interest. After presentation of the different effectors of the immune system and their fluxes through the body, the aim of this review is to propose a general model of leukocyte transmigration through endothelial cell monolayers. It emphasizes in which way different non-volatile anesthetic drugs may affect the non-specific branch of the immune system, i.e. the leukocyte transmigration through endothelial cell monolayers.

Anesthetics↗
PubMed1998

Pulmonary vasodilation by ketamine is mediated in part by L-type calcium channels.

UNLABELLED: We studied the effects of ketamine in the isolated rat lung under conditions of increased pulmonary arterial pressure using the thromboxane A2 mimic, U46619, and in response to ventilatory hypoxia. Ketamine caused dose-dependent vasodilation, and possible mechanisms were evaluated using verapamil, meclofenamate, N(omega)-L-nitro-L-arginine benzyl ester (an inhibitor of nitric oxide synthase), and U-38883A (an ATP-sensitive potassium channel antagonist) in the isolated blood-perfused rat lung. Under increased tone conditions, N(omega)-L-nitro-L-arginine benzyl ester, meclofenamate, and U-38883A had no significant effect in attenuating ketamine-induced vasodilator responses. In a final series of experiments, verapamil significantly attenuated ketamine-induced vasodilator responses. These data suggest that ketamine has significant vasodilator activity in the pulmonary vascular bed of the rat, which seems to be mediated by an L-type calcium channel-sensitive pathway. These responses are not mediated or modulated by the release of nitric oxide, the activation of K+ ATP channels, or the release of vasodilator cyclooxygenase products. IMPLICATIONS: In this study, we examined the mechanism of the vasodilator effects of ketamine in the blood-perfused rat lung. The results of the present study suggest that ketamine-induced vasodilator responses are mediated by an L-type calcium channel-sensitive pathway.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1998

Analysis of responses to angiotensin I (3-10) and Leu3 angiotensin (3-8) in the pulmonary vascular bed of the cat.

Pulmonary vascular responses to angiotensin (3-8) (Ang IV), leu3 angiotensin (3-8) (LeuAng IV), an Ang IV analog and angiotensin I (3-10) [Ang I (3-10)], the precursor for Ang IV, were investigated in the intact-chest cat under conditions of controlled blood flow. Intralobar injections of Ang IV, LeuAng IV, and Ang I (3-10) caused dosage-related increases in lobar arterial pressure. When responses were compared, Ang IV, LeuAng IV, and Ang I (3-10) were equipotent and were approximately 100- to 300-fold less potent than Ang II when dosages are expressed on a nanomolar basis. DuP 753, an angiotensin II type 1 (AT1 ) receptor antagonist, attenuated pulmonary vasoconstrictor responses to LeuAng IV, Ang IV, and its precursor, Ang I (3-10), but did not significantly change pressor responses to serotonin, norepinephrine, or U46619. PD 123319, an angiotensin II type 2 (AT2 ) receptor antagonist, and WSU 3033, a putative angiotensin II type 4 (AT4 ) receptor antagonist, did not significantly change pressor responses to LeuAng IV, Ang IV, and its precursor, Ang I (3-10). Captopril, an angiotensin-converting enzyme (ACE) inhibitor, decreased pulmonary vasoconstrictor responses to Ang I (3-10) but did not significantly change responses to serotonin, norepinephrine, U46619, LeuAng IV, or Ang IV. These data show that LeuAng IV, Ang IV, and its precursor, Ang I (3-10), increase pulmonary vascular resistance by activating AT1 receptors, and that Ang I (3-10) is rapidly and efficiently converted by an ACE-dependent pathway into an active peptide. The present data suggest that Ang IV and LeuAng IV increase pulmonary vascular resistance by activating AT1 receptors and that activation of AT2 or AT4 are not involved in mediating or modulating responses to these peptides. These data provide support for the hypothesis that Ang I (3-10) is converted into an active peptide by ACE at or near the site of action within the pulmonary vascular bed.

Angiotensin I↗
PubMed1997

Differential effects of glibenclamide on responses to thromboxane A2 mimic, U46619, in the pulmonary and hindquarters vascular beds of the cat.

The inhibitory effects of the oral sulfonylurea, glibenclamide, on vasoconstrictor responses to the thromboxane A2 mimic, U46619, were investigated in the pulmonary and hindquarters vascular beds of the cat under constant flow conditions. When lobar arterial tone was at resting conditions (14 +/- 2 mm Hg), intralobar injections of U46619, prostaglandin F2alpha, prostaglandin D2, angiotensin II, norepinephrine, and BAY K 8644 caused dose-related increases in lobar arterial pressure without altering left atrial pressure. Following an intralobar infusion of glibenclamide (5 mg/kg), vasoconstrictor responses to U46619, prostaglandin F2alpha and prostaglandin D2 were significantly reduced, whereas vasoconstrictor responses to norepinephrine and angiotensin II were not altered and responses to BAY K 8644 were significantly enhanced. When tone in the pulmonary vascular bed was raised to a high steady level (36 +/- 3 mm Hg), glibenclamide in a dose of 5 mg/kg i.a. markedly attenuated responses to injections of U46619 and reduced the vasodilator responses to the K+-ATP channel opener, levcromakalim, whereas responses to acetylcholine and S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide donor, were not changed. In the hindquarters vascular bed of the cat, administration of glibenclamide in a dose of 5 mg/kg i.a. had no significant effect on vasoconstrictor responses to U46619, norepinephrine or angiotensin II. Hindquarters vasodilator responses to levcromakalim, but not to nitric oxide, were decreased significantly following administration of glibenclamide. These data suggest that glibenclamide, in addition to inhibiting K+-ATP channels, has thromboxane A2 receptor blocking activity in the pulmonary vascular bed of the cat. These data also suggest that vasoconstrictor responses to U46619 may be mediated by different thromboxane A2 receptors with different binding affinities in the pulmonary and in the hindquarters vascular beds of the cat.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1997

Effects of captopril on responses to bradykinin in the hindquarters vascular bed of the rat.

The effects of captopril, and angiotensin converting enzyme (ACE) inhibitor, on responses to bradykinin (BK), to angiotensin (Ang) I and II, and to other agonists were investigated in the hindquarters vascular bed of the rat. Under conditions of controlled flow, intra-arterial (i.a.) injections of BK in doses of 0.1-1.0 microgram, produced dose related decreases in hindquarters perfusion pressure and evoked decreases in systemic arterial pressure. Intra-arterial injections of Ang I and II produced dose-related increases in hindquarters perfusion pressure. Following administration of captopril in a dose of 2 mg/kg i.v., vasodilator responses to i.a. injections of BK were only slightly enhanced in the hindquarters vascular bed, whereas the evoked systemic vasodepressor responses to i.a. injections of BK were markedly enhanced by the ACE inhibitor. Captopril significantly reduced vasoconstrictor responses to i.a. injections of Ang I, whereas vasoconstrictor responses to i.a. injections of Ang II were significantly enhanced. The ACE inhibitor did not significantly alter vasodilator responses to i.a. injections of acetylcholine, nitroglycerin, nitric oxide, albuterol, or pinacidil. The present data show that BK has potent vasodilator activity in the hindquarters vascular bed of the rat and suggest that the site of action is most likely upstream from the site of inactivation, whereas the site of action of Ang I is at or near the site of conversion to Ang II in the hindquarters vascular bed. The observation that the evoked systemic vasodepressor responses to i.a. injections of BK were greatly enhanced, suggest that the lung is the major site of inactivation of BK.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Exclusion of noninfectious medical waste from the contaminated waste stream.

The purpose of this study was to determine whether any waste was labeled incorrectly as infectious or contained material that could be recycled. Waste generated in preparation for surgery was separated and weighed. Of 530 lbs of operating room waste, 40 lbs were noninfectious, largely plastic and paper. The results of the present study suggest a segment of waste can be removed from the contaminated stream, potentially reducing hospital costs and improving our environment.

Conservation of Natural Resources↗
PubMed1997

Effects of phospholipase A2, 12-lipoxygenase, and cyclooxygenase inhibitors in the feline pulmonary bed.

The effects of phosphonofluoridic acid, methyl-5,8,11,14-eicosatetraenyl ester (MAFP), a phospholipase A2 inhibitor, on pressor responses to angiotensin II (ANG II), norepinephrine (NE), serotonin (5-HT), the calcium channel opener BAY K 8644, and the thromboxane A2 mimic U-46619 were studied in the pulmonary vascular bed of the intact-chest cat. Under conditions of constant lobar blood flow, injections of ANG II, NE, 5-HT, U-46619, and BAY K 8644 into the lobar arterial perfusion circuit caused dose-related increases in lobar arterial pressure that were reproducible with respect to time. Infusion of MAFP into the perfused lobar artery at doses of 100 to 300 microg/kg for 10 min significantly reduced vasoconstrictor responses to ANG II; however, the phospholipase A2 inhibitor did not alter vasoconstrictor responses to BAY K 8644, 5-HT, NE, or U-46619. The combination of the higher dose of the phospholipase A2 inhibitor MAFP with the phospholipase C inhibitor U-73122 significantly affected vasoconstrictor responses to ANG II, NE, and 5-HT but not to BAY K 8644. In a separate series of animals, the effects of a lipoxygenase inhibitor, baicalein, were investigated. Infusion of baicalein into the perfused lobar artery at doses of 100 microg/kg for 10 min significantly reduced vasoconstrictor responses to ANG II but not the vasoconstrictor responses to BAY K 8644, 5-HT, NE, or U-46619. In a final series of experiments, the effects of a cyclooxygenase inhibitor, meclofenamate, were investigated, and intravenous injection of the meclofenamate at a dose of 2.5 mg/kg did not significantly affect vasoconstrictor responses to ANG II, 5-HT, BAY K 8644, NE, or U-46619. These data provide support for the hypothesis that pulmonary vasopressor responses to ANG II are mediated, in part, by the activation of phospholipase A2, phospholipase C, and the lipoxygenase pathway in the pulmonary vascular bed of the cat.

Animals↗
PubMed1997

Effects of charybdotoxin on responses to nitrosovasodilators and hypoxia in the rat lung.

This study investigated the effects of the Ca2+-sensitive K+ channel antagonist charybdotoxin on responses to the nitrosovasodilators nitroglycerin and sodium nitroprusside and on pulmonary pressor responses to ventilatory hypoxia in the isolated blood-perfused rat lung. Injections of nitroglycerin and sodium nitroprusside induced dose-related decreases in pulmonary arterial perfusion pressure when tone was increased with U-46619, whereas ventilatory hypoxia (3% O2-5% CO2-balance N2) increased pulmonary arterial perfusion pressure in a reproducible manner. After administration of charybdotoxin, the pressor response to ventilatory hypoxia was significantly increased, whereas charybdotoxin significantly decreased vasodilator responses to nitroglycerin and sodium nitroprusside but had no effect on the vasodilator responses to albuterol or to isoproterenol when tone was increased with U-46619. The results of the present study show that charybdotoxin enhances the pressor response to ventilatory hypoxia and significantly decreases responses to nitric oxide-donating vasodilator agonists in a selective manner. These data suggest that the response to ventilatory hypoxia is modulated by alterations in Ca2+-sensitive K+ channel activity and suggest that vasodilator responses to the nitric oxide donors nitroglycerin and sodium nitroprusside are dependent on the opening of large-conductance Ca2+-sensitive K+ channels in the pulmonary vascular bed of the rat.

Administration, Inhalation↗