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Biomedical subjects

D W Landry

Publications and source records attributed to D W Landry.

44 records · Page 3Linked to original sources
PubMed1992

The ATP-sensitive K+ channel mediates hypotension in endotoxemia and hypoxic lactic acidosis in dog.

Endotoxemia causes hypotension characterized by vasodilation and resistance to vasopressor agents. The molecular mechanisms responsible for these changes are unclear. The ATP-regulated K+ (K+ATP) channel has recently been found to be an important modulator of vascular smooth muscle tone which may transduce local metabolic changes into alterations of vascular flow. We report here that in endotoxic hypotension, the sulfonylurea glyburide, a specific inhibitor for the K+ATP channel, caused vasoconstriction and restoration of blood pressure. Glyburide also induced vasoconstriction and restoration of blood pressure in the vasodilatory hypotension caused by hypoxic lactic acidosis, while it was ineffective in the hypotension induced by sodium nitroprusside. Thus, vasodilation and hypotension in septic shock are, at least in part, due to activation of the K+ATP channel in vascular smooth muscle, and anaerobic metabolism with acidosis is a sufficient stimulus for channel activation. Because anaerobic metabolism and acidosis are common features in shock of any etiology, sulfonylureas may be effective therapeutic agents in the treatment of shock.

Acidosis, Lactic↗
PubMed1989

Purification and reconstitution of chloride channels from kidney and trachea.

Chloride channels mediate absorption and secretion of fluid in epithelia, and the regulation of these channels is now known to be defective in cystic fibrosis. Indanyl-oxyacetic acid 94 (IAA-94) is a high-affinity ligand for the chloride channel, and an affinity resin based on that structure was developed. Solubilized proteins from kidney and trachea membranes were applied to the affinity matrix, and four proteins with apparent molecular masses of 97, 64, 40, and 27 kilodaltons were eluted from the column by excess IAA-94. A potential-dependent 36Cl- uptake was observed after reconstituting these proteins into liposomes. Three types of chloride channels with single-channel conductances of 26, 100, and 400 picosiemens were observed after fusion of these liposomes with planar lipid bilayers. Similar types of chloride channels have been observed in epithelia.

Animals↗
PubMed1987

Epithelial chloride channel. Development of inhibitory ligands.

Chloride channels are present in the majority of epithelial cells, where they mediate absorption or secretion of NaCl. Although the absorptive and secretory channels are well characterized in terms of their electrophysiological behavior, there is a lack of pharmacological ligands that can aid us in further functional and eventually molecular characterization. To obtain such ligands, we prepared membrane vesicles from bovine kidney cortex and apical membrane vesicles from trachea and found that they contain a chloride transport process that is electrically conductive. This conductance was reduced by preincubating the vesicles in media containing ATP or ATP-gamma-S, but not beta-methylene ATP, which suggests that the membranes contain a kinase that can close the channels. We then screened compounds derived from three classes: indanyloxyacetic acid (IAA), anthranilic acid (AA), and ethacrynic acid. We identified potent inhibitors from the IAA and the AA series. We tritiated IAA-94 and measured binding of this ligand to the kidney cortex membrane vesicles and found a high-affinity binding site whose dissociation constant (0.6 microM) was similar to the inhibition constant (1 microM). There was a good correlation between the inhibitory potency of several IAA derivatives and their efficacy in displacing [3H]IAA-94 from its binding site. Further, other chloride channel inhibitors, including AA derivatives, ethacrynic acid, bumetanide, and DIDS, also displaced the ligand from its binding site. A similar conductance was found in apical membrane vesicles from bovine trachea that was also inhibited by IAA-94 and AA-130B, but the inhibitory effects of these compounds were weaker than their effects on the renal cortex channel. The two drugs were also less potent in displacing [3H]IAA-94 from the tracheal binding site.

Animals↗
PubMed1981

Cholinergic receptor interactions and their effects on long-term memory processing.

Mice were treated on active avoidance to determine the effect of cholinergic and anticholinergic drugs on retention. All drugs were administered intraventricularly after training and one week prior to testing retention. A dose-response curve was determined for each drug. The results indicate that each of 6 anticholinergics impaired retention. The 8 cholinergic drugs tested all yielded U-shaped dose-response curves with controls showing poor retention, low doses of the drugs yielding good retention and high doses resulting in poor retention.

Animals↗
PubMed1981

Long-term memory: disruption by inhibitors of protein synthesis and cytoplasmic flow.

Colchicine (60 micrograms/kg), an inhibitor of axoplasmic transport, administered subcutaneously to mice had no detectable effect on retention when given shortly after active avoidance training, nor did a pretraining injection of anisomycin (ANI) have an amnesic effect. However, when ANI was administered shortly prior to training and colchicine was administered after training, retention performance was impaired. The amnesic effect was dependent on the time at which colchicine was administered. The amnesic effect was also obtained when ANI was combined with either vinblastine (6 micrograms/kg) or podophyllotoxin (3 micrograms/kg), drugs that inhibit axoplasmic transport. Intracerebral injections of colchicine (60 ng to 60 pg) caused amnesia in subjects pretreated with ANI, but not in subjects pretreated with saline. Lumicolchicine, an isomer of colchicine, which has similar central nervous system effects but has a low binding affinity for microtubule protein, did not impair retention in ANI pretreated mice. It is suggested that axonal transport of recently synthesized protein is required for long-term memory storage.

Animals↗
PubMedDate not supplied

Use of a pulsatile right ventricular assist device and continuous arteriovenous hemodialysis in a 57-year-old man with a pulsatile left ventricular assist device.

BACKGROUND: Despite advances in the perioperative treatment of both heart transplant and left ventricular assist device recipients, right-sided circulatory failure refractory to medical management remains a major source of morbidity in the immediate postoperative period. In addition, hypervolemia is a frequent complication encountered in the treatment of these patients because of their large fluid intake requirements and relative potential for kidney failure. METHODS: Previous reports have documented the use of continuous-flow devices to support the failing right-sided circulation of patients after both left ventricular assist device insertion and orthotopic heart transplantation. However, such continuous-flow devices may carry the attendant risks of hemolysis and bleeding and may further require 24-hour monitoring by trained personnel. We report the temporary-use pulsatile Abiomed BVS 5000 right ventricular assist device and continuous arteriovenous hemodialysis in the recipient of a pulsatile TCI HeartMate 1000 IP left ventricular assist device both after left ventricular assist device implantation and after orthotopic heart transplantation. RESULTS: The patient was well at 13 months follow-up. CONCLUSIONS: The use of right ventricular assist devices and continuous arteriovenous hemodialysis in both transplant and left ventricular assist device recipients undoubtedly will remain important as the popularity of these two therapeutic modalities continues to grow.

Equipment Design↗