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Biomedical subjects

D Shepro

Publications and source records attributed to D Shepro.

At least 145 records · Page 8Linked to original sources
PubMed1982

Inhibition of permeability edema with imidazole.

Acute respiratory failure (ARF) with permeability edema and increased physiologic shunting (QS/QT) occurs after complement activation. Leukocytes aggregate, become entrapped in the lungs, and release vasotoxic agents. This study of 31 sheep infused with zymosan-activated plasma (ZAP) tests the hypothesis tha thromboxane (Tx) A2, a proaggregator and bronchoconstrictor, is an intermediate in complement-induced ARF. Group I animals (n = 11) were untreated controls. An imidazole infusion, 25 mg/kg . hr was started 1 hour before a ZAP infusion in group II (n = 10). Prostacyclin (PGi2) was given to group III sheep (n = 10) in a dose of 100 ng/kg . min 3- minutes before the ZAP infusion. Within 5 minutes ZAP led to a decrease in the leukocyte count to 2900/mm3 (P less than 0.001), a rise in plasma TxB2 concentration (the stable degradation product of TxA2) from 14 to 246 pg/ml (P less than 0.001), a rise in lymph TxB2 from 24 to 609 pg/ml (P less than 0.001), a rise in QS/QT from 13% to 31% (P less than 0.01), and a rise in mean pulmonary arterial pressure from 17 to 43 mm Hg. Both imidazole and PGI2 prevented the increase in TxB2 and QS/QT and limited the increases in MPAP to 25 and 30 mm Hg, respectively--values below those of untreated controls (P less than 0.05). Imidazole, but not PGI2, prevented the increase in lymph flow, which in controls increased from 2.8 +/- 8.5 ml/30 min (P less than 0.01), and lymph albumin clearance, which increased from 2.2 to 6.0 ml/30 min (P less than 0.01). The high lymph concentrations of TxA2 suggest a pulmonary site of production, and its bronchoconstrictive action may account for the increase in QS/QT. However, TxA2 is only partially responsible for the pulmonary hypertension and is apparently unrelated to changes in permeability. The protective action of infused imidazole against increased permeability appears to be independent of its inhibition of Tx synthetase.

Animals↗
PubMed1981

Maintenance of cardiodynamics with aspirin during abdominal aortic aneurysmectomy (AAA).

The importance of prostacyclin (PGI2) and thromboxane (Tx) medication of depressed cardiac performance during abdominal aortic aneurysm operative surgery was studied by contrasting the effects of 650 mg aspirin administered 12 hours before operation to that of a placebo. In 11 patients who received a placebo, the stable metabolite of PGI2, 6-keto-PGF1 alpha rose from 0.050 +/- 0.032 eta grams/ml to 0.419 +/- 0.257 eta grams/ml (p less than 0.01) 30 minutes after the skin incision. The stable metabolite of TxA2, TxB2 did not increase until the aorta was clamped when TxB2 rose from 0.089 +/- 0.054 eta grams/ml to 0.193 +/- 0.138 eta grams/ml (p less than 0.05); this was prior to blood transfusion. During aortic clamping cardiac output decreased 27% (p less than 0.001). In vitro testing of patient plasma showed: 1) depressed developed tension (Tpd) of a rat papillary muscle by 16% (p less than 0.05); 3) reduction of Ca++-ATPase and Mg++-ATPase activity in a rat myocardial subfraction of sarcoplasmic reticulum (p less than 0.05); 3) reduction of Ca++-ATPase in a rat myocardial subfraction of myofibrils (p less than 0.01). Aspirin administered to 11 patients produced no measurable changes in blood loss or fluid requirements. Aspirin lowered preoperative 6-keto-PGF1 alpha and TxB2 levels (p less than 0.01) and prevented an increase of either agent during operation. The low Tx levels were associated with a stable cardiac output during aortic clamping. Further, plasma obtained from aspirin-treated patients did not depress papillary muscle contractility nor decrease ATPase activity of either myocardial subfraction. The observation that TxB2 when added to a papillary muscle or myocardial subfractions, did not decrease Tpd or ATPase suggests that TxB2 plays an indirect role in altering cardiac muscle activity. The results indicate that Txs modulate cardiac depression, which can be prevented with 650 mg aspirin before operation.

6-Ketoprostaglandin F1 alpha↗
PubMed1981

Inhibition of thrombocytopenic petechiae by exogenous serotonin administration.

The effect of serotonin on vascular fragility, visible as petechiae, was examined in antiplatelet serum-induced thrombocytopenic hamsters. Serotonin was administered intravenously or intraperitoneally, and following a single injection of 0.5 mg/100 g body weight, a temporary inhibition of petechial formation for approximately 1 h was observed. Repeated serotonin injections maintained animals free of petechiae for the 4-hour period of administration. Plasma levels of serotonin and the effect of serotonin on cutaneous perfusion were not significant factors in the observed inhibition of petechiae. The data suggest that in normal animals platelet serotonin may contribute more to maintaining microvascular structural integrity than platelet adhesion.

Animals↗
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↗