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Prostaglandin release by slow reacting substance from guinea pig and human lung tissue.

Slow reacting substance (SRS) injected into the pulmonary artery released prostaglandins E (PGE) and F2alpha (PGF2alpha) and the 15-keto-13, 14-dihydro PG metabolites from non-sensitized and ovalbumin sensitized, isolated, perfused guinea pig lungs. PGs were also released from lungs incubated with SRS. Sensitized lungs released more PGs in both types of preparations. Indomethacin inhibited the effect of SRS. Passively sensitized human lung fragments, in parallel to guinea pig lung, released PGE, PGF2alpha and the metabolites when incubated with SRS or antigen. In in vivo experiments, SRS and arachidonic acid given intravenously increased the airway insufflation pressure in anesthetized quinea pigs. These effects, but not the action of injected PGF2alpha and histamine, were abolished by indomethacin. The results indicate that one of the modes of SRS action is by release of PGs, and are consistent with the hypothesis that PGs are predominantly "secondary" mediators (in the temporal sense) of the antigen-antibody reaction.

Airway Resistance↗

Direct and reflex myocardial effects of intracoronary administered contrast materials in the anesthetized and conscious dog: comparison of standard and newer contrast materials.

The direct and indirect actions on left ventricular dynamics of contrast material (sodium meglumine diatrizoate) currently used for coronary arteriography, modified ionic material (sodium meglumine calcium metrizoate) and non-ionic material (metrizamide) were assessed in conscious and anesthetized dogs. In both anesthetized and conscious animals, the diatrizoate compound caused an early (3--10 sec after injection) decrease in peak dp/dt and dp/dt/LVP40, followed by late (10--20 sec after injection) increases in these variables. The predominant early and later effects of the calcium metrizoate compound were increases in parameters of LV contractile state. Metrizamide produced no significant early alterations, but later induced a small increase in these variables. The positive inotropic actions of each of the contrast materials were attenuated by beta adrenergic blockade. The early effects of the contrast materials were similar in the presence of segmental ischemia. The late positive inotropic effects in response to the diatrizoate compound and metrizamide were not observed in the ischemic state, while the positive inotropic response induced by the calcium metrizoate compound was significantly reduced. Thus intracoronary administration of sodium meglumine diatrizoate produced direct myocardial depression, followed by adrenergically mediated myocardial stimulation. Calcium metrizoate caused prominent direct and adrenergically mediated augmentation in contractile state. Metrizamide induced the least alteration in LV contractile state.

Adrenergic beta-Antagonists↗

A pharmacological analysis of the contractile action of histamine upon the ileal region of the isolated, blood-perfused small intestine of the rat.

1. The mode of action of histamine was investigated on the rat isolated small intestine perfused at a fixed flow rate through the superior mesenteric artery with blood from the carotid artery of a heparinized donor rat. Compounds were closely injected into the superior mesenteric artery. 2. Increasing doses (1 to 100 micrograms) of histamine caused a monophasic fast contraction of the ileum. 3. The fast contraction was abolished by tetrodotoxin, hexamethonium, morphine or mepyramine, but was not prevented by atropine. 4. The present study indicates that histamine produces the fast contraction of the ileum by primarily acting on the myenteric nerve plexus involving cholinergic interneurones.

Animals↗

Interaction of the chemoreflex and the pulmonary inflation reflex in the regulation of coronary circulation in conscious dogs.

The interaction of chemoreflex and pulmonary inflation reflex control of the coronary circulation was examined in conscious dogs by comparing the responses to chemoreflex stimulation (intracarotid injection of nicotine) when ventilation was allowed to increase with those when ventilation was controlled. The responses were also compared with those elicited by both forced mechanical and spontaneous hyperinflation. When the heart rate was constant, intracarotidly administered nicotine induced an increase in the depth of respiration followed closely by an increase in late diastolic coronary flow from 48 +/- 2 to 106 +/- 8 ml/min and a reduction in late diastolic coronary resistance from 1.62 +/- 0.08 to 0.78 +/- 0.06 mm Hg/ml min-1. After beta-receptor and cholinergic blockade, a similar coronary dilation in response to nicotine occurred only when ventilation was allowed to increase. However, when ventilation was controlled, intracarotidly administered nicotine increased coronary resistance after combined beta-receptor and cholinergic blockade. The reflex coronary dilation was not observed after carotid sinus nerve section or after alpha-receptor blockade. Thus, nicotine stimulation of the carotid chemoreflex results in a striking coronary dilation that has two components. The minor component involves a chemoreflex with its efferent pathway in tthe vagi. The major component of coronary dilation follows an increase in the depth of respiration, and its efferent component appears to involve withdrawal of alpha-adrenergic constrictor tone. An almost identical period of reflex coronary dilation followed either forced mechanical or spontaneous hyperinflation in the conscious dog.

Adrenergic alpha-Antagonists↗

A contribution to the physiology of the perilymph. Part IV: Effect of histamine on the cochlear microcirculation.

Summary--Because of the topography of the perilymphatic vascular network, the cochlear microcirculation is especially sensitive to the effect of vasoactive substances reaching the perilymphatic space. The cochlear microcirculation is mainly controlled humorally, via the activity of the metarterioles and changes in the flow properties of the blood. Intracochlear histamine reduces the cochlear circulation even more markedly than after intracarotid administration. No systematic effects of parenteral administration of vasoactive substances can be expected on the cochlear circulation. Reversible auditory disorders after stapedectomy may be explicable by the intracochlear release of histamine. The internal release of histamine after sunstroke and cold stress may play a part in sudden dusturbances of hearing.

Animals↗

Improvement in arterial oxygenation by saralasin infusion in man.

Simultaneous hemodynamic and blood gas measurements were performed in 26 hypertensive adults, who were cigarette smokers, before and after a 30-minute infusion of saralasin (5 microgram/kg/min) which is a highly specific competitive antagonist of angiotensin II (AII). The arterial pressure fell in nine, rose in seven and was unchanged in ten patients. The mean cardiac index for the entire group remained unchanged. Pulmonary arterial or wedge pressure, pulmonary vascular resistance, arterial PCO2 and pH did not change. Unrelated to the hemodynamic changes, the mean arterial oxygen pressure (PaO2) increased from 68.6 +/- 2.2 mm Hg to 73.9 +/- 2.1 mm Hg (P less than 0.001). In the absence of a significant increase in alveolar ventilation as indicated by an unchanged mean PCO2 and lacking a hemodynamic explanation, the mechanism for the rise in PaO2 is speculative at this stage. The possibility of an improvement in the distribution of ventilataion by saralasin infusion is under investigation.

Adult↗

Substance P-like peptides and vasopressin release from posterior pituitary lobe incubated in situ after intracarotid injections of hypertonic solution in rats.

The experiments were performed on male rats, drinking 2% NaCl solution ad libitum for 12 days instead of tap water. The pituitary gland was exposed by the transpharyngeal approach under urethane-chloralose anaesthesia. The posterior lobe remained in neural and partial vascular connection with the hypothalamus, whereas the anterior lobe was entirely removed. Samples of the outflow medium from the incubated in situ rat posterior pituitary lobe were collected during 30 min intervals. Substance P-like peptides and vasopressin activities were assayed by the biological tests. Injections of hypertonic solution into the internal carotid artery did not change vasopressin release, but induced an increase in Substance P release from the posterior pituitary lobe into the incubation medium. Under conditions of unexcitability of the osmosensitive cells, triggering vasopressin release, the injection of hypertonic solution into the internal carotid artery stimulated the Substance P-like peptides release from the posterior pituitary lobe.

Animals↗

Intraaticular treatment of tarsal degenerative joint disease in cattle.

Tarsal degenerative joint disease (DJD) in 12 cattle was classified as primary or secondary, based on age, evidence of hereditary or congenital joint conformation defects, faulty hindlimb alignment, duration and type of usage joints were subjected to, and history or signs of repeated trauma. Three of the cattle had bilateral primary tarsal DJD, 7 had bilateral secondary tarsal DJD, and 2 had secondary DJD of the left tarsus. Analyses of synovial fluid samples provided a means of characterizing pathologic changes of tarsal DJD, Results of blood and synovial fluid analyses were grouped in compilation of data for cattle affected with either primary or secondary tarsal DJD. Corticosteroids and a long-acting synthetic progestational agent were injected singly or in combination with aqueous antibiotics into affected tarsal joints. Tarsal joints of 5 of the cattle responded favorably to a single intraarticular treatment, as manifested by palliative relief and functionally usable joints. Seven joints of 5 cattle were subjected to repeated intraarticular treatment. Serial synovial fluid analyses in 7 of the cattle provided a means of assessing tarsal joint response to intraarticular treatment or to therapeutic arthrocentesis, exclusive of patient objective response. One cow developed a mild self-limiting bilateral postinjection synovitis that was resolved after the 2nd and final intraarticular injection. Usable function returned to tarsal joints of cattle that responded favorably to intraarticular treatment at different periods after single or repeated injections. Three cattle with advanced tarsal DJD experienced minor temporary relief and were euthanatized at their owner's request. Improvement did not occur in the tarsal joint of 1 cow subjected to therapeutic aspiration only. Intraarticular treatment in all cattle was considered supportive to the animal's well-being rather than curative.

Animals↗

[Treatment of advanced neoplasms in the jaw].

Report is made about the combined therapy with cytostatics (methotrexate - bleomycin) and irradiation in patients with extended tumors in the gnathic region. Ten patients in whom a radical therapy with conventional methods did not promise any success, were treated with intra-arterial infusions of methotrexate and bleomycin and simultaneous irradiation. At present, eight patients are tumor free (observation time 4-14 months after termination of therapy). Although radiation doses and doses of cytostatics were high, only insignificant side effects were stated; consequently, the treatment had to be terminated in none of the patients.

Adult↗