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Biomedical subjects

D Shepro

Publications and source records attributed to D Shepro.

At least 163 records · Page 9Linked to original sources
PubMed1981

Prostacyclin reversal of lethal endotoxemia in dogs.

Severe endotoxemia, a condition where microembolization and intravascular coagulation are thought to play important roles, was treated experimentally with prostacyclin (PGI(2)). In a study of 24 dogs, 8 control animals injected with 1.75 mg.kg(-1) of endotoxin died within 24 h. Six animals given intravenous aspirin 100 mg/kg, 30 min after endotoxin died. 9 of 10 dogs infused with 100 ng PGI(2).kg(-1).min(-1) for 3 h, given 30 min after the injection of endotoxin survived 24 h (P < 0.025). Injection of endotoxin resulted in a: (a) maximal 62% fall in mean arterial pressure (P < 0.001); (b) transient doubling of mean pulmonary arterial pressure (P < 0.001); (c) initial 70% drop in cardiac index (P < 0.001); (d) decline in blood platelets from 213,700 to 13,700/mm(3) (P < 0.001), and leukocytes from 7,719 to < 750/mm(3) (P < 0.001); (e) depressed urine output (P < 0.001); (f) 34% decrease in blood fibrinogen (P < 0.01) and an increase in fibrin degradation products > 50 mug/ml (P < 0.001); (g) fivefold increase in circulating cathepsin D titer (P < 0.005) and (h) increase in blood norepinephrine (P < 0.005), dopamine (P < 0.005), and epinephrine (P < 0.001). Aspirin treatment led to an increase in mean arterial pressure (P < 0.001) and mean pulmonary arterial pressure (P < 0.005), but cardiac index, urine flow, platelets, leukocytes, fibrin degradation products, and cathepsin D levels remained similar to untreated controls. After infusion of PGI(2) there was a: (a) prompt increase of cardiac index to base-line levels; (b) late increase in mean arterial pressure (P < 0.005) after the discontinuation of PGI(2) treatment (c) restoration of urine output; (d) increase in circulating platelets to levels still below base line but above untreated control animals (P < 0.05); (e) no effect on circulating leukocyte levels; (f) fall in fibrin degradation products to 11.2 mug/ml (P < 0.05); (g) decline in cathepsin D levels to values 60% lower than the untreated controls (P < 0.025); and (h) reduction in plasma norepinephrine levels to base line at 4 h (P < 0.005). Although the mode of PGI(2) action is not clear, it is effective in the treatment of experimental endotoxemia.

Animals↗
PubMed1981

Serotonin uptake by isolated adipose capillary endothelium.

The uptake of serotinin (5-hydroxytryptamine, 5-HT) by endothelial cells was studied in freshly isolated capillary and other microvessel (< 50 micrometers, inner diameter) endothelium obtained from rat epididymal fat pads. Endothelial cells incubated with [3H]-5-HT removed 60 pmol of [3H]-5-HT per mg of protein at 1 hr, an apparent Km of 3 X 10(-7) M and a Vmax of 20 pmol/mg of protein, measured at 15 min, were obtained. Uptake of 5-HT (10(-6) of M) was inhibited by ouabain, selected metabolic inhibitors (iodoacetate, 2--4 dinitrophenol and sodium azide), 4 degrees C, tryptamine (10(-5) M and the 5-HT antagonists, fluoxetine and imipramine (10(-5) M and 10(-4) M, respectively). At concentrations of 5-HT greater than Km value, uptake appears to be principally by nonfacilitative diffusion rather than by carrier-mediated transport.

Adipose Tissue↗
PubMed1979

Effect of sodium chloride on limulus amebocyte lysate. Inhibition of endotoxin activation of procoagulase.

Concentrations of sodium chloride up to 3 M increase the time necessary for the clot formation from Limulus amebocyte lysate (LAL) induced with endotoxin. Sodium chloride at a concentration of 4 M prevents clot formation by either precipitation or denaturation of procoagulase. The time necessary for the activation of procoagulase by endotoxin is increased by a change in the sodium chloride concentration from 0.15 M to 0.588 M. No effect on the proteolytic phase or the polymerization phase of the clotting reaction is detected by the increase in sodium chloride concentration from 0.15 M to 0.588 M. The authors conclude that increased sodium chloride concentrations may aid the isolation of procoagulase.

Animals↗
PubMed1979

Presence of negative inotropic agents in canine plasma during positive end-expiratory pressure.

Application of positive end-expiratory pressure (PEEP) will reduce cardiac output (CO). Humoral mediation of this event by circulating negative inotropic agents was examined using a rat papillary muscle bioassay. Twenty-seven dogs were anesthetized with an iv pentobarbital infusion. Plasma was obtained before and after 30 minutes of PEEP. The plasma was oxygenated in a small (4.5-ml) papillary muscle chamber using a diffusion membrane. An average PO2 of 416 mm Hg was achieved. PEEP plasma reduced developed tension (Tpd) from 2.16 +/- 1.0 to 1.90 +/- 1.05 g (P less than 0.0001). A fall in Tpd was observed whether or not CO was maintained constant with fluid infusion. Resting tension was unchanged. The percent reduction in Tpd correlated with the fall in CO (r = 0.63, P less than 0.01) when fluid was not infused to maintain CO. Reapplication of control plasma restored Tpd. Barbiturate levels in anesthetized dogs rose from 17.3 to 19.4 microns/ml during PEEP (P less than 0.1). Addition of pentobarbital to normal plasma led to a slight decrease in Tpd only when the concentration exceeded 99 microns/ml. In three experiments on ex vivo perfused hearts, application of PEEP led to lowering of peak systolic pressure (PSP) within 5 minutes. Removal of PEEP restored PSP in a similar time. The results support the hypothesis that the decline in CO with PEEP is mediated in part by a circulating negative inotropic agent.

Acid-Base Equilibrium↗
PubMed1978

Ornithine decarboxylase activity in cultured endothelial cells stimulated by serum, thrombin and serotonin.

Ornithine decarboxylase (ODC) activity, the rate-limiting step in the synthesis of polyamines, can be demonstrated in cultured, bovine, aortic endothelial cells (EC). Serum, serotonin and thrombin produce a rise in ODC activity. The serotonin-induced ODC activity is significantly blocked by imipramine (10(-5) M) or Lilly 110140 (10(-6) M). Preincubation of EC with these blockers together almost completely depresses the 5-HT-stimulated ODC activity. These observations suggest a manner by which platelets may maintain EC structural and metabolic soundness.

Animals↗