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Biomedical subjects

R Dean

Publications and source records attributed to R Dean.

80 records · Page 5Linked to original sources
PubMedDate not supplied

Thromboxane A2 does not contribute to arrhythmogenesis during evolving canine myocardial infarction.

During the healing phase of evolving myocardial infarction, inflammatory cells invade the affected region and produce metabolites that may influence electrophysiological parameters and the genesis of malignant arrhythmias. We have recently shown an increased synthetic capacity within an evolving infarct for thromboxane A2 (TXA2), a metabolite that has been implicated in arrhythmias associated with early ischemia. The present study used both in vivo and in vitro procedures to define the electrophysiological and arrhythmogenic effects, if any, of thromboxane during evolving myocardial infarction. Thirty-three dogs divided into three groups were studied 3-7 days after transient left anterior descending coronary artery ligation. One group (n = 24) was examined by programmed electrical stimulation in the conscious state and, of the five dogs in this group with sustained ventricular tachycardia (VT), none demonstrated consistent limitation of inducibility by selective inhibition of thromboxane synthetase using three different agents. In the second group, (n = 5) regional conduction velocity was assessed using detailed three-dimensional activation analysis from 232 simultaneous intramyocardial sites, and no change was induced by the thromboxane synthetase inhibitor OKY-1581 in either normal or infarcted myocardial zones during sinus rhythm or with pacing. In the third group (n = 4), isolated ventricular muscle was studied in vitro using both intracellular transmembrane action potential recordings and surface extracellular maps from 48 simultaneous points. Neither intracellular action potential parameters nor extracellularly recorded activation patterns were altered by superfusion with the stable thromboxane analog STA2, the activity of which was verified by bioassay. Thus, despite increased synthetic capacity for thromboxane generation, the presence of TXA2 does not directly influence either electrophysiological indices or arrhythmogenesis.

Action Potentials↗
PubMedDate not supplied

Cellular localization of endothelin receptor subtypes in the rat kidney following in vitro labelling.

1. We have previously shown that [125I]-endothelin (ET) receptor binding is localized almost exclusively to the fenestrated endothelial cells of glomerular capillaries and peritubular capillaries in the rat kidney following systemic administration of the radioligand in vivo. Because of the lack of specific ET receptor binding in other glomerular and tubular structures following in vivo labelling, we undertook further studies, using electron microscopic autoradiography and ET receptor subtype selective ligands, to investigate whether other renal components also contain ET receptor binding and, if so, to determine the cellular localization of the ET receptor subtypes, ETA and ETB, following in vitro labelling. 2. At the electron microscopic level, ET binding sites were localized primarily to the fenestrated endothelium of glomerular and peritubular capillaries of the cortex, inner stripe of the outer medulla and the inner medulla. ET binding sites also occurred overlying renomedullary interstitial cells (RMIC) of the inner medulla. 3. The ETB receptor selective agonist, sarafotoxin 6c (S6c), abolished ET binding in the vascular endothelium throughout the kidney, while the ETA receptor selective antagonist, BQ123, was without effect. Both BQ123 and S6c partially inhibited the binding in the RMIC of the inner medulla. 4. These results indicate that ET receptor binding in the fenestrated endothelium in the glomerular capillaries and peritubular capillaries belongs mainly to the ETB subtype, whereas both ETA and ETB subtypes are present in the RMIC.

Animals↗
PubMedDate not supplied

The effect of intentional hemodilution on P50.

Ten patients (Group I) scheduled for major vascular surgery received banked blood and twelve patients (Group II) also scheduled for major vascular surgery were administered intentional hemodilution with autologous blood. Both groups of patients were studied to determine the effects of banked blood and autologous blood respectively on P50. The mean pre-operative P50 for Group I and Group II patients were 26.2 mmHg and 26.3 mmHg respectively. The mean postoperative P50 for Group I and Group II patients were 24.7 mmHg and 28.4 mmHg respectively. There was a significant increase in P50 in patients (Group II) who received autologous blood when compared with Group I patients who received banked blood (p less than 0.001). Our data on P50 in Group I patients who received banked blood showed that there was a significant decrease confirming the results of previously published studies. The Authors conclude that intentional hemodilution is an efficacious alternative technique to banked blood administration for patients undergoing major vascular surgery.

Blood Transfusion↗
PubMedDate not supplied

Phenytoin-oxacillin interactions in normal and uremic sera.

Displacement of phenytoin (90% bound to albumin) by other strongly albumin-bound drugs such as salicylate and valproic acid may result in an increase in pharmacologically active free concentrations. The antibiotic oxacillin is also strongly bound to albumin and is often administered to patients receiving phenytoin. Oxacillin at a concentration of 15 micrograms/ml caused no significant displacement of phenytoin in a serum pool prepared from patients receiving phenytoin. However, a significant increase in the free phenytoin concentration was seen at an oxacillin concentration of 50 micrograms/ml. We also prepared a serum pool from uremic patients and another from patients with hypoalbuminemia and supplemented both of them with phenytoin. Significant increases in the free phenytoin concentration occurred with both 15- and 50-microgram/ml concentrations of oxacillin. In one hypoalbuminemic patient receiving both phenytoin and intravenous high-dose oxacillin, the free phenytoin fraction was 22.5% before oxacillin therapy, 24.1% 12 hours after first dose of oxacillin, and 27.2% after 60 hours, indicating the possibility of in vivo displacement of phenytoin by oxacillin. We conclude that the phenytoin-oxacillin interaction is not significant at lower dosages of oxacillin usually prescribed for oral therapy. However, the interaction may be significant at high concentrations of oxacillin, especially in patients with hypoalbuminemia or uremia.

Anticonvulsants↗