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E W Spannhake

Publications and source records attributed to E W Spannhake.

72 records · Page 4Linked to original sources
PubMed1980

Prostaglandins evoke a whole variety of responses in the lung.

Rapid intravenous (IV) injections of the prostaglandin precursor arachidonic acid (AA) increase pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) in a variety of species. It has recently been reported that infusions of AA decrease PAP. The purpose of this report is to contrast responses to bolus injections and infusions of AA in the anesthetized dog. In all experiments rapid IV injections of AA increased PAP and PVR; however, infusions of 68 to 680 microgram/min produced variable responses. In 10 of 19 animals, AA infusion decreased PAP and PVR, and this response was enhanced when pulmonary vascular tone was actively increased by vasoconstrictor agents or alveolar hypoxia. In the other nine animals, the predominant response was an increase in PAP and PVR. In all experiments infusions of larger amounts of AA (1.4 to 3.4 mg/min) increased PAP. Both pressor and depressor responses to AA were inhibited to meclofenamate. This study shows that infusion of small amounts of AA dilates or constricts the pulmonary vascular bed. In contrast, infusion of larger amounts of AA always causes vasoconstriction. These data suggest that at low infusion rate, PGI2, which is a vasodilator, is the predominant metabolite formed from AA in some animals. However, at higher concentrations, the production of constrictor products predominates. These experiments also suggest that the products formed and the response observed may be dependent on a number of factors including the amount of tone present in the pulmonary vascular bed.

Animals↗
PubMed1980

Differential actions of the prostaglandins on the pulmonary vascular bed.

We have reported that administration of cyclooxygenase inhibitors such as indomethacin and meclofenamate results in a slow gradual increase in pulmonary vascular resistance in the intact dog (21). It has been shown that a PGI2, "like" substance is continually released by the lung (6). We have, therefore, suggested that under resting conditions, the pulmonary vascular bed is maintained in a dilated state by production of a vasodilator product in the cyclooxygenase pathway (10,21). Recent evidence suggests that this vasodilator product in the cyclooxygenase pathway is a PGI2 'like" substance (6,13,20).

Animals↗
PubMed1978

Altered state of cardiac sympathetic nerves during immunologically induced anemia.

Cardiac norepinephrine (NE) levels exhibit a marked reduction in rats suffering from hemolytic anemia induced with antibodies against rat red blood cells. Administration of antiserum via tail vein resulted in a highly reproducible 70% drop in hemoglobin levels by 72 h. At 96 h cardiac NE levels were decreased by 67%; NE levels in vas deferens and submaxillary gland were not decreased. Within 10 days, both hemoglobin and cardia NE returned to near control levels. Hearts from anemic rats showed a 68% decrease in their ability to accumulate 3H-NE administered in tracer doses at 72 h of anemia. Cardiac NE turnover rates were increased 88% in 72 h anemic animals. These results are consistent with an anemia-induced activation of cardiac sympathetic nerves. Cardiac monoamine oxidase and dopamine-beta-hydroxylase activities in whole heart homogenates were similar in control and anemic animals at 72 h. These results suggest that NE depletion is not the result of decreased synthetic capacity of the nerves or degeneration of existing terminals. The data suggest that cardiac NE depletion during anemic stress is associated with the combined effects of increased NE release and a decrease in the effective NE uptake or binding capacity of sympathetic nerves. Anemia-induced depletion may, therefore, be different from the depletion associated with other forms of cardiovascular stress.

Anemia↗
PubMed1978

Effect of dihomo-gamma-linolenic acid on the canine pulmonary vascular bed.

The effect of dihomo-gamma-linolenic acid (DGLA), the precursor of the monoenoic prostaglandins (PG), F1alpha and E1, on the pulmonary vascular bed of the intact dog was studied under conditions of controlled pulmonary blood flow. DGLA increased pulmonary vascular resistance in a dose-related manner by constricting intrapulmonary veins and upstream segments, presumably pulmonary arteries. Intrapulmonary injection of DGLA also increased transpulmonary injection of DGLA also increased transpulmonary airway pressure, presumably by increasing airway resistance and decreasing lung compliance or both. The vasoconstrictor response, however, was independent of changes in transpulmonary pressure since similar pressor responses were obtained in ventilated and nonventilated lungs. Further, the response was not dependent on factors or elements in whole blood, since the increase in pulmonary vascular resistance occurred during perfusion with saline or dextran and was enhanced in these media. Conversion of DGLA to PGs by a lung cyclo-oxygenase appears to mediate the response, since it was blocked by indomethacin and dose not occur with injection of nonprecursor long-chain fatty acids. These data suggest that the response to DGLA is due to formation of vasoactive products in the monoenoic PG pathway.

8,11,14-Eicosatrienoic Acid↗
PubMed1978

Effects of arachidonic acid and prostaglandins on lung function in the intact dog.

The effects of the prostaglandin (PG) precursor, arachidonic acid (AA), and the primary PG's, PGF2alpha, and PGD2, on lung function were compared in 39 intact-chest, paralyzed, artificially ventilated dogs. Intravenous AA decreased dynamic compliance (Cdyn) and functional residual capacity and increased airway resistance (Rl) and transpulmonary pressure at end-passive expiration. The decrease in Cdyn correlated closely with a rise in pulmonary arterial pressure (Ppa). Indomethacin abolished airway and vascular responses to AA, but did not attenuate responses to the PG's. The effects of AA, PGD2, and PGF2alpha on lung function and Ppa were similar, whereas PGE2 had little effect. Vagotomy attentuated the RL increase in response to AA, PGE2alpha, and PGD2 and the Cdyn decrease in response to the PG's. The effects of the PG's on compliance were greater than those produced by mechanically increasing pulmonary venous pressure. The present studies suggest that the PG precursor is rapidly converted to agents that have marked effect on both pulmonary vessels and airways, particularly peripheral airways, in the dog.

Airway Resistance↗
PubMed1978

Pulmonary and systemic vasodilator effects of the newly discovered prostaglandin, PGI2.

The effects of the newly discovered bicyclic prostaglandin, prostacyclin (PGI2), on the pulmonary and systemic vascular beds were investigated in the anesthetized dog. PGI2 decreased systemic and pulmonary arterial pressures in a dose-related manner when injected into the vena cava in doses of 1--30 microgram. Since left ventricular end-diastolic, left atrial, and right atrial pressures were unchanged, and since cardiac output was increased or unchanged, pulmonary and systemic vascular resistances were decreased. PGI2 was 10 times more potent than prostaglandins E1 or E2 in decreasing aortic pressure when injected intravenously, and the effects of PGI2 on the systemic vascular bed were similar when injected into the vena cava or the left atrium. These data indicate that inactivation of PGI2 is minimal in the lung. The stable prostacyclin metabolite, 6-keto-PGF1alpha, had little hemodynamic effects, suggesting that responses to PGI2 were not due to formation of this metabolite. PGI2 produced dose-dependent increases in blood flow in the mesenteric and renal vascular beds. These data demonstrate that PGI2 has marked vasodilator activity in the pulmonary and systemic vascular beds and suggest that prostacyclin is the only known metabolite of arachidonic acid that dilates the pulmonary and systemic circulations.

Animals↗
PubMed1978

Modification of pulmonary vascular responses to arachidonic acid by alterations in physiologic state.

The effects of bolus injections of arachidonic acid and prostaglandins (PG) E2 and F2a on the pulmonary vascular bed were compared under resting conditions and after alteration in the physiologic state of the lung. Studies were carried out in the vascularly isolated lung lobe of the intact, anesthetized dog under conditions of controlled blood flow. Arachidonic acid, PGE2 and PGF2a increased pulmonary vascular resistance by constricting intrapulmonary veins and arteries in a dose-related manner, as did an analog of the endoperoxide, PGH2, whereas PGI2 dilated the pulmonary vascular bed. The response to arachidonate was associated with a 2- to 3-fold increase in levels of PGE- and PGF-like substances in pulmonary venous blood and was blocked by indomethacin. The effects of arachidonic acid, but not the PGs, were greatly enhanced during perfusion with either dextran or saline and the enhanced response in saline was associated with a 15 to 20-fold increase in levels of PG-like substances in the pulmonary effluent. Responses to arachidonate were not dependent upon the presence of formed elements in blood but were related to perfusate protein concentration. Alveolar hypoxia decreased responses to the precursor while those to PGE2 and PGF2a were enhanced. Responses to the PGs, but not those to arachidonate, were affected by changes in blood pH. Sublethal doses of Escherichic coli endotoxin increased the response to arachidonic acid, but not those to PGE2 and PGF2a. Results of the present study indicate that the effects of bolus injection of arachidonic acid on the pulmonary vascular bed are due mainly to formation of constrictor metabolites which may overshadow the actions of any dilator (PGI2) formed and suggest that metabolism of the precursor is altered by changes in physiologic state.

Animals↗
PubMed1977

Comparative effects of endoperoxide PGH2 and an analog on the pulmonary vascular bed.

The effects of the prostaglandin endoperoxide, PGH2, and a stable endoperoxide analog were compared on the canine pulmonary vascular bed under conditions of controlled blood flow. The analog produced dose-related increases in lobar arterial and small vein pressure when injected into the perfused lobar artery. The increase in resistance in response to the analog was greater during retrograde perfusion than during forward perfusion. These data suggest that the analog increases resistance to flow by constricting pulmonary veins and upstream vessels. The increase in resistance was similar when the lung was perfused with dextran or blood and the response was not different when the lung was ventilated or collapsed. The response was notattenuated by indomethacin, an inhibitor of prostaglandin synthesis. These data suggest that the response to the analog is not related to changes in bronchomotor tone, platelet aggregation, or enhanced prostaglandin synthesis. Although the analog was a potent pressor substance, PGH2 itself produced only small increases in pulmonary vascular resistance. However, PGH2 had greater contractile activity than the analog on isolated helical segments of canine intrapulmonary vein. The present study suggests that endoperoxides may represent an active form of the prostaglandins in the lung but that their effects would be localized in the tissue in which they are formed because of their extremely short biologic half-life.

Animals↗
PubMedDate not supplied

Down-regulation of canine airway mast cell function following exposure to ozone in vivo.

The influence of ozone on the function of airway cells involved in allergic responses is of particular interest due to the increasing prevalence of this environmental oxidant pollutant. In the present studies, the peripheral airways of Ascaris-sensitive dogs were expose to ozone (1 ppm, 5 min) or air (control) and the exposed segments were lavaged 30 min later. The kinetics and magnitude of release of PGD2 and histamine from canine peripheral airway mast cells (PAMC) was determined following in vitro challenge with Ascaris antigen or calcium ionophore approximately 4 h from the time of the in vivo exposures. Histamine content was significantly lower in PAMC retrieved from ozone- versus air-exposed segments (3.0 +/- 0.1 vs. 5.2 +/- 0.5 pg/cell). Absolute release of histamine at 20 min was decreased by 47 and 43% in ozone-exposed cells stimulated with antigen or ionophore, respectively. Maximal synthesis and release of PGD2 in response to antigen (345 +/- 22 pg/10(3) PAMC) or ionophore (1055 +/- 104 pg/10(3) PAMC) was inhibited by 32 and 55%, respectively, in cells from ozone-exposed segments. Inhibition of prostanoid synthesis was not observed in alveolar macrophages in the lavage samples, nor could decreased PGD2 be attributed to enhanced catabolism. These data indicate a differential down-regulatory influence of ozone on subsequent release of granular mediators and newly synthesized PGD2 from PAMC following brief in vivo exposure that lasts for several hours.

Animals↗