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Biomedical subjects

D Morley

Publications and source records attributed to D Morley.

At least 19 recordsLinked to original sources
PubMed1991

Intravenous cocaine causes epicardial coronary vasoconstriction in the intact dog.

The effect of intravenous cocaine on coronary artery dynamics in 23 closed-chest dogs was examined. To determine dose-related effects, intravenous cocaine was administered in doses of 1, 3, 6, and 9 mg/kg; saline solution was used in control dogs. Heart rate, aortic pressure, and left anterior descending coronary artery cross-sectional area were measured before and for 60 minutes after each injection. Myocardial blood flow was measured with 15 microns radioactive microspheres at baseline and 30 minutes after administration of cocaine or saline solution. Plasma cocaine, benzoyl ecgonine, and norepinephrine concentrations were measured and correlated with physiologic changes. Cocaine caused sustained dose-dependent vasoconstriction of the left anterior descending coronary artery, which was significant at 15 minutes and maximum at 60 minutes (control = 2 +/- 10%; cocaine, 9 mg/kg = 46 +/- 10% cross-sectional area reduction). There was an immediate but transient reduction in aortic pressure and an elevation of heart rate after the 6 and 9 mg/kg doses and no hemodynamic changes with lower doses. Coronary blood flow was reduced 30 minutes after the 3, 6, and 9 mg/kg doses. Two dogs had refractory ventricular tachycardia after injection of cocaine and were not included in the analysis. Results of this investigation demonstrate angiographic evidence of dose-dependent, cocaine-induced epicardial coronary vasoconstriction and deleterious hemodynamic abnormalities at commonly used doses of cocaine. These results demonstrate a mechanism for the development of angina and myocardial infarction associated with cocaine use.

Animals↗
PubMed1991

Complexes of .NO with nucleophiles as agents for the controlled biological release of nitric oxide. Vasorelaxant effects.

Selected nucleophile/nitric oxide adducts [compounds which contain the anionic moiety, XN(O-)N = O] were studied for their ability to release nitric oxide spontaneously in aqueous solution and for possible vasoactivity. The diversity of structures chosen included those in which the nucleophile residue, X, was that of a secondary amine [Et2N, as in [Et2NN(N = O)O]Na, 1], a primary amine [iPrHN, as in [iPrHNN(N = O)O]Na, 2], a polyamine, spermine [as in the zwitterion H2N(CH2)3NH2+(CH2)4N[N(N = O)O-](CH2)3NH2, 3], oxide [as in Na[ON(N = O)O]Na, 4], and sulfite [as in NH4[O3SN(N = O)O]NH4, 5]. The rate constants (k) for decomposition in pH 7.4 phosphate buffer at 37 degrees C, as measured by following loss of chromophore at 230-260 nm, were as follows: 1, 5.4 x 10(-3) s-1; 2, 5.1 x 10(-3) s-1; 3, 0.30 x 10(-3) s-1; 4, 5.0 x 10(-3) s-1; and 5, 1.7 x 10(-3) s-1. The corresponding extents of nitric oxide release (ENO) were 1.5, 0.73, 1.9, 0.54, and 0.001 mol/mol of starting material consumed, respectively, as determined from the integrated chemiluminescence response. Vasodilatory activities expressed as the concentrations required to induce 50% relaxation in norepinephrine-constricted aortic rings bathed in pH 7.4 buffer at 37 degrees C (EC50) were as follows: 1, 0.19 microM; 2, 0.45 microM; 3, 6.2 microM; 4, 0.59 microM; and 5, 62 microM. Vasorelaxant potency (expressed as 1/EC50) was strongly correlated with the quantity of .NO calculated from the physicochemical data to be released in the interval required to achieve maximum relaxation at the EC50 doses (r = 0.995). This suggests that such nucleophile/.NO adducts might generally be useful as vehicles for the nonenzymatic generation of nitric oxide, in predictable amounts and at predictable rates, for biological purposes. The particular significance for possible drug design is underscored in the very favorable potency comparison between several of these agents and the established nitrovasodilators sodium nitroprusside and glyceryl trinitrate (EC50 values of 2.0 and greater than 10 microM, respectively) in parallel aortic ring tests.

Animals↗
PubMed1991

Importance of endothelial function in stenotic haemodynamic responses.

STUDY OBJECTIVE: The aim was to examine endothelium mediated flow dependence in a dynamic stenosis. DESIGN: The coronary circulation was modelled as a proximal compliant stenosis and a fixed distal resistance. Pressures and flow were calculated using standard haemodynamic equations. Within the stenosis, the vessel wall was composed of normal and rigid sections, and the normal section dilated proportionally with flow. From this theoretical analysis, three perfusion pressures (150, 100, and 75 mm Hg) and two distal resistances (high and low) were examined. MAIN RESULTS: In a stenotic artery (93% area reduction) with high flow dependence, decreasing distal resistance increased flow substantially. At 75 mm Hg perfusion pressure, flow increased from 40.8 to 81.6 ml.min-1. With moderate flow dependence, flow increases were attenuated. Without flow dependence, flow increases were smaller, and at low perfusion pressure, flow paradoxically decreased (39.0 to 0.0 ml.min-1) when distal resistance decreased. Vasoconstriction responses with and without flow dependence were analysed. In a stenotic artery, vasoconstrictors caused a concentration dependent decrease in flow. Without flow dependence, the flow dose-response curve was shifted to the left: a lower level of arterial vasoconstriction resulted in a greater flow decrease. CONCLUSIONS: The theoretical analysis shows significantly different flow responses to decreasing distal resistance and to vasoconstriction depending on endothelial function. Endothelial dysfunction may be important in the pathophysiology of angina pectoris.

Arterial Occlusive Diseases↗
PubMed1989

Inhibition of platelet and red blood cell accumulation on damaged arterial surfaces with albumin pretreatment.

Damaged arterial surfaces initiate platelet accumulation which leads to thrombus formation. On artificial surfaces, albumin pretreatment inhibits platelet deposition. To investigate albumin pretreatment on damaged vessel surfaces, 16 carotid arteries were obtained from 8 anesthetized dogs (11-15 kg). Each artery was divided into 2 segments. Each segment was mounted in a perfusion system, distended to 100 mmHg, and the middle section damaged. One segment was perfused with Tyrodes solution plus bovine albumin (5 g/100 ml), while the other segment was perfused only with Tyrodes solution. After 120 mins, both segments were perfused with whole citrated blood containing Indium-111 labeled platelets. Without albumin pretreatment, the proximal section contained 11 +/- 8 (X +/- SEM) percent of total blood radioactivity, while the damaged section contained 53 +/- 11 percent (p less than 0.01). Albumin pretreatment significantly reduced platelet deposition in the damaged section (53 +/- 11 versus 9 +/- 6 percent, p less than 0.01). Further, with albumin pretreatment the radioactive counts in the damaged section were not significantly different from the nondamaged proximal section (9 +/- 6 vs 8 +/- 7 percent, p greater than .8). Quantitative examination of the scanning electron micrographs demonstrated significantly more platelet and red blood cell coverage of the damaged segments (60 +/- 12.8 percent) than of the albumin treated segments (12.9 +/- 5 percent). In four additional experiments, we pretreated arterial segments with albumin for varying time intervals. After 15, 30 and 60 mins of albumin pretreatment, each artery was perfused with radiolabeled platelets and whole blood for 5 mins at 100 mmHg perfusion pressure. Radioactive evidence of platelet deposition on arterial segments treated with albumin for 15, 30, and 60 minutes was also significantly less than control (p less than .05). Beneficial effects of albumin were apparent up to 30 mins of blood flow at 100 mm Hg. Our results suggest that albumin may inhibit platelet and red blood cell deposition on damaged arteries. This could be an adjunct therapy for vessel preservation during artery bypass procedures.

Albumins↗
PubMed1988

An in vitro model of platelet aggregation in stenotic arteries.

Clinical and experimental evidence suggest a strong relationship between arterial stenosis, platelet aggregation, and subsequent thrombus formation. To facilitate the study of platelet accumulation in stenotic arteries, we developed an in vitro preparation. Arterial segments were perfused with whole citrated blood. A stenosis was created by applying an external plastic constrictor to the artery. Platelet accumulation within the stenosis was assessed by scanning electron microscopy and by radioactive counts from Indium-111 labeled platelets. Utilizing this preparation, 30 carotid arterial segments from 10 mongrel dogs were perfused at 100 mmHg for 15 min. In 10 arteries without a stenosis, scanning electron microscopy and radioactive counts demonstrated little platelet accumulation. In contrast, extensive platelet aggregation was observed in 10 arteries with stenoses. Moreover, in 10 stenotic arteries exposed to the thromboxane mimetic, U46619 (Upjohn Diagnostic Group), scanning electron microscopy and radioactive counts demonstrated a significant increase in platelet deposition. Conversely, we demonstrated a dimunition of platelet accumulation in stenosed arterial segments exposed to the prostacyclin analogue platelet inhibitor, Iloprost (Berlex Laboratories, Inc.). The in vitro preparation allows precise control of hemodynamic variables and makes it possible to perform multiple tests on segments of the same vessel from the same animal.

Animals↗
PubMed1987

Effect of membrane thickness of collodion coated activated charcoal on adsorption of small and middle molecules.

Different thicknesses of a cellulose nitrate (CN) coating were applied to petroleum pitch bead activated charcoal. The effect of this on the adsorption of small and middle molecules in vitro was studied. This was done by measuring the rate of adsorption of Vitamin B12, creatinine and uric acid from aqueous solution by activated charcoal having CN coatings of varying thickness (0.1% to 4.0% by weight). A CN coating weight of up to 0.2% caused negligible or no decrease in the rate of adsorption of all three solutes as compared with uncoated charcoal. Coating weights greater than 0.2% caused a significant decrease in the rate of adsorption of Vitamin B12, and uric acid but had little effect on the rate of adsorption of creatinine. Coating weights greater than 1.8% caused a significant decrease in the rate of adsorption of creatinine.

Adsorption↗