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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was carried out to investigate the possible contribution of endogenous prostaglandin (PG) production to failure of contractile recovery following reperfusion of hypoperfused isolated rat hearts. A 90% reduction in coronary flow rate for 60 min resulted in a time-dependent depression of contractile force and an elevation in resting tension. Reperfusion produced a slight (approximately 11%) recovery of contractile force, whereas resting tension remained elevated. Reperfusion was a potent stimulus for PG (as assessed by 6 keto-PGF1 alpha) release and resulted in levels that were significantly higher than those observed prior to ischemia. When PG synthesis was inhibited by the nonsteroidal anti-inflammatory drugs ibuprofen, indomethacin, or acetylsalicylic acid (ASA), recovery of ventricular contractility on reperfusion was significantly higher than that seen in the absence of drugs. Ibuprofen was the most effective, producing an average recovery of 70% (P less than 0.05 from control). Indomethacin and ASA produced approximately a 40% (P less than 0.05) and 35% (P less than 0.05) recovery of contractile force, respectively. The improved recovery in contractility was significantly depressed by the addition of low concentrations of prostacyclin (PGI2) and PGF2 alpha, whereas PGE2 and 6 keto-PGF1 alpha, the hydrolysis product of PGI2, were ineffective. The effects on resting tension were inconsistent. PG release during reperfusion was unrelated either to the length of the initial period of reduced coronary flow or the degree of contractile recovery; it was attenuated either by a reduction in or by an elevation of Ca concentration. These results indicate that endogenous PGs mediate, at least in part, reperfusion-associated failure of ventricular function.
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PMID:Contribution of prostaglandins to reperfusion-induced ventricular failure in isolated rat hearts. 308 30

The effects of intracoronary injection of nitroglycerin, adenosine, nifedipine and prostacyclin on restoring coronary perfusion during flow-reducing partial coronary obstruction in anesthetized dogs were studied. Coronary obstruction was obtained by inflation of an intraluminal balloon to decrease coronary blood flow and rate of rise in left ventricular pressure (dP/dt) by approximately 30 to 40 and 10%, respectively. Nitroglycerin (0.01 to 10 micrograms/kg per min) increased coronary blood flow and distal coronary pressure and decreased stenosis resistance associated with improved left ventricular dP/dt depending on its dose. In contrast, adenosine (0.3 to 1.0 micrograms/kg per min) decreased coronary blood flow and distal coronary pressure and intensified stenosis resistance associated with depression of left ventricular dP/dt. Nifedipine and prostacyclin caused divergent effects on the coronary circulation related to each dose. Nifedipine (0.01 and 0.1 micrograms/kg per min) and prostacyclin (0.01 micrograms/kg per min) increased coronary blood flow and distal coronary pressure and reduced stenosis resistance. Nifedipine (1.0 micrograms/kg per min) and prostacyclin (0.3 micrograms/kg per min) did not increase coronary blood flow, but reduced distal coronary pressure and intensified stenosis resistance. Thus, the vasodilators produced different effects on restoration of coronary perfusion during pliable severe coronary stenosis. Nitroglycerin and lower doses of nifedipine and prostacyclin improved coronary perfusion due to selective or preferential dilation of large coronary arteries. Adenosine and higher doses of nifedipine and prostacyclin had deleterious effects on the coronary circulation due to potent arteriolar vasodilation.
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PMID:Comparative effects of intracoronary vasodilators on restoring coronary perfusion during flow-reducing coronary stenosis in the dog. 309 16

1 We compared the effects of endotoxin on pulmonary prostaglandin E1 (PGE1) removal in groups of rabbits pretreated with the cyclo-oxygenase inhibitor, indomethacin, or nafazatrom (Bay g 6575), which has been shown to increase plasma prostacyclin concentrations. 2 In untreated animals, endotoxin transiently decreased pulmonary removal of [3H]-PGE1, caused pulmonary hypertension, systemic hypotension and increased plasma concentrations of PGE2 and 6-keto-PGF1 alpha. 3 Indomethacin pretreatment prevented the transient decrease in pulmonary removal of [3H]-PGE1 in response to endotoxin, prevented the haemodynamic effects and inhibited prostaglandin synthesis. Pretreatment with nafazatrom did not affect the decreased pulmonary removal of [3H]-PGE1, exacerbated the haemodynamic response, reduced survival and potentiated the increase in circulating 6-keto-PGF1 alpha. 4 We conclude that indomethacin acts to prevent the depression of pulmonary [3H]-PGE1 removal by eliminating surface area changes associated with endotoxin-induced pulmonary vasoconstriction. 5 These data suggest that nafazatrom treatment results in exacerbation of the endotoxin-induced systemic hypotension presumably due to its effect on increased plasma prostacyclin during the later phase of endotoxaemia.
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PMID:Effect of nafazatrom and indomethacin on pulmonary removal of prostaglandin E1 after endotoxin in rabbits. 331 Dec 63

Cardiac and coronary effects of trapidil (Rocornal) and some derivatives were investigated in isolated heart preparations and rabbit hearts in vivo. All substances showed a comparable increase of the coronary flow. Contrary to the cardiotonic influence of trapidil the trapidil derivates induced a negative inotropic effect, possibly due to a weak calcium antagonism. Heart rate was slightly diminished, but in some cases higher doses caused an acute tachycardia. I.v. application of the substances to rabbits in doses of 10 mg/kg and 30 mg/kg induced an initial depression of blood pressure normalizing within 3-5 min. An increase of the myocardial prostacyclin biosynthesis is only demonstrable under trapidil. The results indicate that the cardiac effects of trapidil derivatives are possibly caused by a direct influence on the contractile system and the membrane potential of the cardiac muscle cell.
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PMID:[The effectiveness of trapidil and some derivatives on heart function under in vitro and in vivo conditions]. 331 38

In the guinea-pig terminal ileum a maximally effective concentration of prostacyclin (PGI2) (1 mumol/l) induced contractions that were partially resistant to tetrodotoxin (TTX) 0.1 mumol/l, to low temperature (20 degrees C) and to atropine (30 nmol/l). Half maximum contractions evoked by PGI2 (20 nmol/l) were abolished by TTX and by low temperature, which did not modify the response to exogenous acetylcholine (ACh), as well as by atropine. Procaine (5-500 mumol/l) caused a concentration-dependent inhibition of contractions induced by PGI2 (20 nmol/l and 1 mumol/l) and by equieffective concentrations of ACh (20 nmol/l and 0.4 mumol/l, respectively). The order of magnitude for this inhibition was ACh 20 nmol/l = PGI2 20 nmol/l greater than PGI2(1) mumol/l greater than ACh 0.4 mumol/l. In preparations exposed to TTX or to low temperature procaine (50 mumol/l) did not affect the residual response to PGI2 (1 mumol/l). Quercetin (1 and 5 mumol/l) inhibited the effect of PGI2 and, at higher concentrations, it also caused partial depression of the responses to ACh. Quercetin did not alter TTX-resistant and low temperature-resistant contractions induced by PGI2 1 mumol/l. Carbonyl cyanide-trifluoro-methoxyphenyl hydrazone (FCCP) (0.1-1 mumol/l) reduced the effect of PGI2 and of ACh to approximately the same extent and inhibited the residual response to PGI2 1 mumol/l in preparations treated with TTX or expressed to low temperature. The present results show that PGI2, besides acting on cholinergic neurons, also exerts a direct effect on smooth muscle cells and FCCP can be used to block this effect. In contrast procaine and quercetin selectively inhibit the ACh-mediated component of PGI2 action.
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PMID:Target sites for the inhibition of prostacyclin effect in guinea-pig ileum. 332 10

In a 12-day treatment schedule, 5 ponies were given orally a paste formulation of phenylbutazone (PBZ) and 5 matched ponies were given equivalent doses of a placebo paste. On day 12, a mild, nonimmune inflammatory reaction was induced subcutaneously in the neck of each pony by inserting sterile, polyester sponge strips soaked in a 2% carrageenan solution. Exudate was collected at 4, 8, 12, and 24 hours by serial removal of sponges. There were no significant (P less than 0.05) differences in exudate protein concentration and leukocyte numbers between the treatment groups, but the group given PBZ had significantly reduced exudate concentrations of eicosanoids 6-keto-prostaglandin F 1 alpha (the stable metabolite of prostacyclin) at 4, 8, and 12 hours; thromboxane B2 at 8, 12, and 24 hours; and bicyclic prostaglandin E2 at 8 hours. The maximal depression of eicosanoid synthesis occurred at times of peak exudate concentrations of PBZ (8 and 12 hours). Phenylbutazone was cleared more slowly from exudate than from plasma. Changes in surface skin temperature were measured by infrared thermometry. Lesional temperatures were recorded 1 cm below the base of the incision line, and mean increases were significantly (P less than 0.05) less in PBZ-treated than in placebo-treated ponies between 4 and 24 hours. The importance of the findings for the clinical efficacy of this dosage schedule is considered.
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PMID:Effects of a phenylbutazone paste in ponies: model of acute nonimmune inflammation. 346 61

The in vitro spontaneous isometric-developed tension (IDT) of uterine horns obtained from diestrous rats exhibited, after 60 min of post-isolation activity, a clear decrease in magnitude, averaging 18.2 +/- 5.2%. In presence of tolbutamide, a concentration-dependent decrease of IDT, significantly greater than the spontaneous reduction (75.1 +/- 5.4%, with tolbutamide at 10(-4) M), was observed. Incubation with propranolol (10(-6) M) or with sotalol (10(-4) M) failed to alter the negative inotropism evoked by tolbutamide. On the other hand, the sulfonylurea (10(-4) M) shifted most points of the dose-response curve to the right for the contractile stimulation elicited by oxytocin, an influence not altered by the simultaneous presence of propranolol or sotalol. Tolbutamide failed to influence the negative inotropic dose-response curve for isoproterenol and did not modify the decrease in contractions evoked by theophylline (10(-4) M). It was also found that tolbutamide was devoid of action on the basal release of prostaglandin E2 from uterine strips and on the positive inotropic dose-response curve for added PGE2 or PGF2 alpha, constructed in presence of indomethacin (5 X 10(-6) M). The present findings do not permit a simple explanation regarding possible factors underlying the negative uterine inotropic influence of tolbutamide in the rat uterus. However, it appears that alterations in the integrity of tissue excitability and contractile apparatus, adrenergic implications, changes in uterine cAMP levels, inhibition of cyclo-oxygenase or low PEG2 synthesis and release, are not plausible mechanisms to explain the negative inotropism of tolbutamide. Therefore, it is suggested that the contractile depression evoked by tolbutamide and its action on the contractile effect of oxytocin might be linked to the impaired synthesis of other prostanoids, namely PGF2 alpha, PGI2 or PGD2, although the participation of not yet determined factor(s), namely changes in Ca2+ ion movements, cannot be discarded.
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PMID:Tolbutamide in vitro diminishes spontaneous and oxytocin-induced contractions of uterine smooth muscle from diestrous rats. 348 42

A randomized, double-blind study was designed to evaluate the therapeutic effect and safety of prostacyclin (epoprostenol) in patients undergoing cardiopulmonary bypass. One hundred patients having isolated coronary bypass grafting received 300 units/kg of heparin and then either prostacyclin (12.5 ng/kg/min from heparinization until cardiopulmonary bypass, 25 ng/kg/min during bypass) or buffer/diluent in a similar manner. Standardized anesthetic, perfusion, and surgical techniques were used. Drug and placebo groups were similar in demographic data and bypass times, and there were no deaths. Activated coagulation time and platelet count were significantly higher during cardiopulmonary bypass in patients receiving prostacyclin. Platelet count remained significantly higher 24 hours after bypass in the active drug group. Immediately after operation, there was significantly less prolongation of bleeding time (1.3 versus 2.9 minutes; p = 0.009) in the patients receiving prostacyclin. Blood loss was significantly reduced during the first 4 hours postoperatively in the prostacyclin group (261 +/- 159 versus 347 +/- 197 ml; p = 0.02). There was no significant difference between the groups when total blood loss was compared (710 +/- 351 versus 869 +/- 498 ml; p = 0.07). Patients receiving prostacyclin required an average of 257 ml less blood transfused in the intensive care unit (p = 0.02). We conclude that the clinical impact of prostacyclin in patients undergoing coronary artery operations was demonstrable, but small. Prostacyclin may provide clinical benefits in patients undergoing cardiopulmonary bypass when there are contraindications to or other difficulties with blood transfusion. With prostacyclin, reduced heparin dose is possible and therefore reduced protamine requirement would offer a potential benefit of less cardiovascular depression immediately after bypass. However, the advantages offered by prostacyclin are not sufficient to recommend its routine use during cardiopulmonary bypass.
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PMID:A prospective, randomized study of the effects of prostacyclin on platelets and blood loss during coronary bypass operations. 351 19

Complete cerebral ischemia (CCI) was evoked by closing the brachiocephalic trunk, the left subclavicular artery and both internal thoracic arteries with simultaneous depression of systemic arterial pressure (SAP) to 70-50 mm Hg. The experiments were performed with three groups of rabbits. The first group consisted of animals with 15 and 20 min CCI, not receiving PGI2. In the second group PGI2 was given for 15 min before and during 15 min CCI. The third group with 15 and 20 min CCI received PGI2 3 min before, during and for 15 min after ischemia. The recovery of ECoG and the activities of the respiratory and vasomotor centres were evaluated as were reflex reactions. In 38 percent of the second group of rabbits improvement of the neurological condition after CCI was noted, as compared with animals of the control groups and a faster recovery of the ECoG. In the third group the neurological state improved in 100 percent of cases with simultaneous significantly quicker recovery of the first symptoms of brain cortex bioelectric activity and continuous activity in ECoG records. Between groups 1 and 2, and group 3 there were differences concerning the time of recovery of ECoG, and the intensity of reflexes. The influence of PGI2 on the brain bioelectric activity of the animals after CCI was found to be favourable.
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PMID:The influence of prostacyclin on the recovery of bioelectric cerebral activity after complete ischemia. 351 77

Ventilation with positive end-expiratory pressure (PEEP) is employed in clinical and aviation medicine. The widespread application of PEEP, however, is limited principally because of its adverse effect on cardiac output (CO) and systemic arterial blood pressure (BP). Recently, it has been suggested that this PEEP-induced cardiovascular depression may be mediated by vasoactive agents, possibly prostaglandin in nature. This study examined the possible involvement of PGI2 in the PEEP-induced decreases in CO and BP. Chloralose-anesthetized mechanically ventilated dogs were subjected to brief intervals (75 s) of PEEP 10 or 20 mm Hg. Arterial levels of 6-keto-PGF1 alpha (stable metabolite of PGI2) were monitored by radioimmunoassay. These parameters were compared before and during PEEP application. During PEEP, tracheal pressure-related decreases in both CO and BP were noted. Application of either PEEP 10 or 20 mm Hg resulted in an increase in circulating 6-keto-PGF1 alpha levels in three animals while a decrease was noted in two others. Overall, application of PEEP did not result in a significant change from baseline levels. Furthermore, there was no correlation between changes in either CO or BP with changes in arterial 6-keto-PGF1 alpha levels. These results do not support the hypothesis that the short term PEEP-induced changes in CO or BP are mediated by endogenously released PGI2.
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PMID:The possible involvement of PGI2 in the PEEP-induced changes in cardiac output and blood pressure. 352 37


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