Prostanoid release from ex vivo perfused canine arteries and veins: effects of prolonged perfusion, intermittent perfusion, as well as exposure to exogenous arachidonic acid, thrombin and bradykinin

Regulation of prostanoid release from ex vivo perfused vessel segments is not fully understood. A series of perfusion experiments were performed with canine arteries and veins to define certain regulatory phenomena. Arteries were perfused with pulsatile flow of 90 ml/min at a pressure of 100 mmHg, and veins with nonpulsatile flow of 90 ml/min at a pressure of 7 mmHg. Segments were perfused with Hanks' balanced salt solution for five 15-min periods with the perfusate exchanged after each study period. With onset of perfusion, there was an initial burst of prostacyclin release to 127 +/- 40 pg/mm2, declining to 32 +/- 10 pg/mm2 after 60 minutes (p less than 0.005). If perfusion continued for 5.5 hours, there was a stable release period between 1 and 3 hours, followed by a very slow decline. At that time addition of arachidonic acid (AA) increased prostacyclin release six-fold (p less than 0.01). Vessels perfused for 1 hour and then rested for another hour, responded to reperfusion at the second onset of flow with a two-fold increase in prostacyclin release (p less than 0.01). Vessels perfused with thrombin, bradykinin or AA (either added to each perfusate or only to the last perfusate) exhibited greater prostacyclin release than did control segments. Release of thromboxane steadily declined with time in all parts of the study, and only increased with the addition of AA to the perfusate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Eicosapentaenoic acid potentiates the production of prostacyclin-like material in the arachidonic acid perfused human umbilical vein

The production of prostacyclin (PGI2)-like material in human umbilical veins perfused continuously at 37 degrees C with Hanks buffer solution with 1% human albumin (HBA) was studied by bioassay. Subsequent perfusion resulted in a time dependent significant decrease in production of PGI2-like material. After addition of 20 mumol/l arachidonic acid (HBA-AA) the production of PGI2-like material increased significantly. The production of PGI2-like material was significant greater when the vein was perfused with HBA-AA than when perfused with HBA with 20 mumol/l eicosapentaenoic acid (HBA-EPA). Examination of the HBA-EPA perfusate by thin layer chromatography showed that it contained a substance that comigrated with genuine 6-keto-PGF1 alpha and a substance that comigrated with delta 17-6-keto-PGF1 alpha. Finally, perfusion with HBA containing 10 mumol/l AA plus 10 mumol/l EPA resulted in a significant greater production of PGI2-like material than perfusion with HBA-AA alone. These results support the hypothesis that EPA has beneficial antithrombotic properties in human.     

The involvement of prostaglandins and thromboxanes in the response to pulmonary embolism in anaesthetized rabbits and isolated perfused lungs

Embolisation of blood clots produced an increased pulmonary artery pressure in vitro and systemic hypotension in vivo. In control anaesthetized animals, systemic blood pressure fell by 44.9 +/- 28.0 mm Hg following embolisation and 40% of the animals died within 5 minutes of embolisation. Plasma concentrations of thromboxane B2 (TXB222222 2) and 6-keto-prostaglandin F 1 alpha (6-keto-PGF 1 alpha) were increased by 0.54 +/- 0.13 ng/ml and 0.41 +/- 0.25 ng/ml, respectively. Pretreatment of animals with aspirin (ASA), 5 mg/kg or 250 mg/kg, reduced the hypotensive response and the TXB 2 and 6-keto-PGF 1 alpha release. Embolisation of isolated lungs perfused with blood-free medium induced an increase in pulmonary artery pressure of 32.7 +/- 21.0 mm Hg and significantly increased the content of TXB 2 and 6-keto-PGF 1 alpha in the perfusate. Pretreatment of lungs with indomethacin, 10 micrograms/ml, reduced the mean pulmonary pressure response to embolisation to 10.6 +/- 4.9 mm Hg and blocked the appearance of TXB 2 in the perfusate. Embolisation with an agarose clot induced only a 2.58 +/- 0.8 mm Hg increase in pressure and no detectable TXB 2 release. These results indicate that embolisation of lungs with a blood clot induces the release of TXB 2 and 6-keto-PGF 1 alpha. The release of these mediators, the hemodynamic responses and mortality were blocked by ASA pretreatment.     

Influence of antithrombin on ischemia/reperfusion injury in the isolated blood-free perfused rat heart

INTRODUCTION: Antithrombin (AT) is well known as an important inhibitor of the coagulation system. An interesting new hypothesis is that antithrombin exerts specific anti-inflammatory effects by stimulating the production of prostacyclin in endothelial cells. Recent studies report beneficial influence on ischemia/reperfusion injury in several organs. These effects are independent of the coagulation system. We investigated the influence of antithrombin on ischemia/reperfusion injury and prostacyclin release in the isolated rat heart. Since the perfusion of the hearts was without blood, the used model essentially describes effects of antithrombin on endothelial cells. MATERIAL AND METHODS: Experiments were performed using the temperature-controlled and pressure-constant Langendorff apparatus. The hearts of 32 male Sprague-Dawley rats were subjected to 20 min of global ischemia followed by 30 min of reperfusion. Antithrombin was administered in three different concentrations (1, 4 and 8 U/ml) 15 min prior to global ischemia. Cardiac contractility parameters and biochemical parameters were measured. RESULTS: Treatment with antithrombin did not increase the release of prostacyclin significantly after ischemia. Antithrombin at a concentration of 8 U/ml led to a significant increase in creatine kinase (CK; p<0.05) and troponin I (p<0.05), whereas measurements of lactate dehydrogenase (LDH) revealed no significant differences between treated and untreated hearts. CONCLUSION: Our study shows that antithrombin did not reduce ischemia/reperfusion injury in the isolated heart, and prostacyclin is not significantly released following antithrombin treatment. High concentrations of antithrombin, however, might have a negative influence on the reperfused heart. The underlying mechanism remains unclear.     

Eicosanoids in rat brain during ischemia and reperfusion--correlation to DC depolarization

The effects of complete ischemia on cerebral arachidonic acid (AA) metabolism were investigated in the isolated perfused rat brain. During 12.5 min of ischemia, AA, 5-hydroxy-6,8,11,14-eicosatetraenoic acid, and 15-hydroxy-5,8,11,13-eicosatetraenoic acid increased 129-, 4-, and 10-fold, respectively, while subsequent reperfusion for 30 min resulted in normalized levels independently of the duration of preceding ischemia. Prostaglandin (PG) F2 alpha, PGE2, PGD2, 6-keto-PGF1 alpha, and thromboxane (Tx) B2 remained at preischemic levels during 12.5 min of complete ischemia. However, at the end of subsequent reperfusion for 30 min, the levels of the prostanoids PGF2 alpha, PGE2, PGD2, 6-keto-PGF1 alpha, and TxB2 increased according to the preceding ischemic time. The levels reached a maximum after 7.5 min of ischemia and were elevated by 7-, 14-, 48-, 3-, and 30-fold, respectively. A prolongation of ischemia of up to 12.5 min was not associated with further increases of prostanoids at the end of reperfusion. The mechanisms underlying the metabolism of eicosanoids are discussed in relation to the changes of cortical direct current potential.     

Effects of plasma on PGI2 release from prolonged perfused canine veins

Prostacyclin release from endothelial cells in culture appears increased by the presence of plasma, but occurrence of a similar phenomenon in intact vessels has not been established. In the present investigation release of 6-keto-PGF1 alpha, the stable breakdown product of prostacyclin, was quantitated from canine veins perfused ex vivo for 15 minute periods, using three different perfusates: 1) Hank's balanced salt solution (HBSS), 2) 20% platelet poor plasma (PPP) derived from heparinized blood, in HBSS, and 3) 20% PPP in HBSS with added arachidonic acid (AA). No differences in initial 6-keto-PGF1 alpha release existed among the three perfusates. However, PPP and PPP + AA solutions were associated with lesser declines in release, than occurred with HBSS alone, these differences being statistically significant after 60 min of perfusion (p less than 0.05). When PPP derived from heparinized and citrated blood rather than from only heparinized blood was used, there was a significantly lower release of prostacyclin (p less than 0.05). The latter may be due to citrate binding of calcium. These data indicate that autologous plasma does not alter initial prostacyclin release from freshly harvested canine veins, but that it weakens the decline in release usually following prolonged periods of perfusion.     

Eicosanoid production in the caudate nucleus and dorsal hippocampus after forebrain ischemia: a microdialysis study.

Thromboxane (Tx)B2 and 6-keto-prostaglandin (6-keto-PG) F1 alpha formation in the hippocampus and caudate nucleus were evaluated by microdialysis during and following forebrain ischemia. Spontaneously hypertensive rats were subjected to bilateral carotid artery occlusion with simultaneous hypotension for 8, 14, or 20 min. Dialysate was collected during the ischemic interval and during the reperfusion period. TxB2 and 6-keto-PGF1 alpha levels were measured by radioimmunoassay. In both structures, TxB2 production increased significantly during the reperfusion period in all three ischemic groups. By contrast, increased 6-keto-PGF1 alpha elaboration was observed after only the longest ischemic duration. While TxB2 levels gradually decreased during the 3-h reperfusion period in all groups, the levels in the group subjected to 8 min of ischemia returned to control values most rapidly. A relationship between the duration of ischemia and TxB2 production was therefore evident. 6-Keto-PGF1 alpha levels increased in only the group subjected to 20 min of ischemia and, by contrast to the pattern of TxB2 change, 6-keto-PGF1 alpha levels remained elevated throughout the reperfusion period. During reperfusion, the ratio of TxB2 to 6-keto-PGF1 alpha increased substantially versus the preischemic period in both structures. The data demonstrate that eicosanoid elaboration following cerebral ischemia can be evaluated by the microdialysis technique. In addition, they indicate that the thresholds (duration of ischemia) for the postischemic production and the temporal profiles of TxB2 and 6-keto-PGF1 alpha in the caudate and hippocampus differ. They also demonstrate that there is regional heterogeneity in the patterns of eicosanoid elaboration after forebrain ischemia.     

Effect of a peptide derived from fibrinogen degraded by leukocyte elastase on isolated bovine mesenteric arteries

A peptide derived from fibrinogen degraded by leukocyte elastase, and corresponding to amino acids 30-43 in the B beta-chain of fibrinogen, was evaluated concerning its effects on isolated bovine mesenteric arteries. This peptide induced dilation of the arteries and an increase in both cyclic AMP and cyclic GMP in the vessels. In addition there was an increase in 6-keto-PGF1 alpha indicating an increased release of prostacyclin. The increase in cyclic nucleotides and 6-keto-PGF1 alpha was inhibited by indomethacin, as was the vasodilation. The increase in cyclic GMP was much larger than the increase in cyclic AMP. The effects of the studied peptide are similar to the effects of other vasoactive peptides with a similar structure, such as bradykinin, neurotensin and substance P. The increase in cyclic AMP is probably caused by prostacyclin, a probable mediator of vasodilation. In addition, in certain species vasodilation may be caused by an increase in cyclic GMP.     

Changes in endogenous prostacyclin in the rat brain during clinical death and after resuscitation.

By means of the radioimmunologic method changes of concentration of 6-keto-prostaglandin F1 alpha (PGF1 alpha)--the stable metabolite of prostacyclin in the rat brain have been evaluated during 5-min clinical death and up to 2 hrs after resuscitation. Ischemia did not produce significant changes of 6-keto-PGF1 alpha concentration in the brain. In the early postresuscitation period the concentration of 6-keto-PGF1 in the and 7-fold control values. Later the concentration of 6-keto-PGF1 alpha in the brain decreased reaching in 30 min a 3-fold the control level, and in 60 and 120 min after resuscitation control values. The reasons of unsuccessful therapy of ischemic stroke with prostacyclin are discussed.     

Effects of calcium entry blocker emopamil on postischemic energy metabolism of the isolated perfused rat brain

The effects of emopamil on postischemic energy metabolism and electroencephalographic (EEG) recovery were investigated in the isolated rat brain perfused at either constant pressure or, alternatively, at constant flow rate. Flow rate and perfusion pressure were monitored continuously. The brains were perfused with a fluorocarbon emulsion for 30 min, and after 30 min of ischemia, perfusion was reinstituted for 5, 30, or 60 min. Global cerebral perfusion rate was increased by emopamil throughout the perfusion period and, accordingly, in brains perfused at a constant flow rate, perfusion pressure was reduced by the drug. At constant pressure perfusion, after 5 min after ischemia, cortical levels of creatine-phosphate, adenosine triphosphate (ATR), glucose, glucose-6-phosphate, and fructose-6-phosphate were higher in emopamil-treated brains than in controls, although the levels of adenosine diphosphate (ADP) and adenosine monophosphate (AMP) were reduced. When brains were perfused at constant flow rate, however, emopamil exhibited no effect on brain energy metabolism in the early reperfusion period. Postischemic restoration of high-energy phosphates proved to depend on the flow rate used. After 30 min of postischemic reperfusion, cortical levels of lactate were lower in emopamil-treated brains compared to controls at both constant pressure and constant volume perfusion. Postischemic lactate levels were independent of flow rate and were also reduced when emopamil was only present during reperfusion. The postischemic restoration of cortical EEG activity was improved by the calcium entry blocker.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thromboxane and prostacyclin formation in patients with deep vein thrombosis

The urinary excretion of 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha (the major urinary metabolites of thromboxane B2 and prostacyclin) was measured in ten patients with confirmed deep vein thrombosis, using specific methods based on gas chromatography - mass spectrometry with deuterium-labelled internal standards. Measurements of these major urinary metabolites makes it possible to monitor the in vivo formation of thromboxane A2 and prostacyclin. The results demonstrate an abnormally high and very variable excretion of 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha in patients with deep vein thrombosis. This indicate that both thromboxane A2 and prostacyclin are involved in the course of events associated with this disease.     

Release of tissue-type plasminogen activator (t-PA) in the splanchnic circulation of the anaesthetised pig during high sympathetic tone

Background

There is a substantial local release of tissue-type plasminogen activator (t-PA) in the splanchnic vascular bed, and this release is increased at high sympathetic tone. Coronary t-PA release is also significant, and this release increases during cardiac nerve stimulation and during reperfusion after 10 min of local myocardial ischemia. However, by repeated cycles of myocardial ischemia/reperfusion coronary t-PA release progressively declines.

Objectives

Accordingly, we hypothesised that splanchnic t-PA release might decrease after an initial peak during maintained and long-lasting sympathetic stimulation.

Methods

In 6 anaesthetised pigs sympathetic tone was augmented by bleeding (20-25 mL/kg over 30 minutes). During the subsequent 2 hours period portal vein (draining the splanchnic vasular bed) - and arterial blood samples were drawn every 20 min and portal vein blood flow was recorded continuously in order to estimate t-PA release in the splanchnic vascular bed.

Results

Relatively stable haemodynamic conditions were obtained after bleeding with mean arterial blood pressure at 50 to 65 mmHg and a portal vein flow at about the 50% of baseline value. Net splanchnic t-PA release rose to a peak 40 min after bleeding, but subsequently declined towards baseline values. Arterial t-PA activity rose after the bleeding period and to a peak value at end of the observation period.

Conclusions

Net splanchnic t-PA release increased only transiently during the period with increased sympathetic stimulation, whereas the arterial t-PA level remained elevated. During a strong and longlasting sympathetic stimulation the lack of a continuously augmented splanchnic t-PA release might increase the risk for intravenous splanchnic thrombosis.     

Release of plasminogen activator from isolated perfused dog heart

The release and the local activity of plasminogen activator (PA) were studied in isolated perfused dog hearts, without or with intimal injury induced by means of a balloon catheter inserted into the left anterior descending coronary artery (LAD). Thrombin but not DFP-thrombin induced a dose-dependent PA release in doses of 8 to 32 units. ADP 20 or 200 mumol but not ergonovine 20 or 200 micrograms induced a weak PA release. The local PA activity was much lower in the LAD at 1 or 4 weeks after this injury than in the intact LAD. However, the release of PA from the hearts after intimal injury was similar to findings in the intact hearts. We conclude from this study that thrombin plays an important role in regulating the coagulation-fibrinolysis system in endothelial cells and that changes in the properties of the endothelial cells may lead to initiation and enhancement of atherosclerosis.     

Effects of cerebral ischemia and reperfusion on prostanoid accumulation in unanesthetized and pentobarbital-treated gerbils

Cerebral ischemia was induced in unanesthetized gerbils using bilateral carotid artery ligations. The effects of 20 min of global ischemia on the concentrations of prostaglandin F2 alpha (PGF2 alpha), PGE2, 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), and thromboxane B2 were determined after 0-24 h of reperfusion. Ischemia had little effect on eicosanoid production, but significant increases were observed by 5 min of reperfusion, with maximal levels reached by 15 min of reperfusion. PGF2 alpha was the most concentrated prostaglandin in postischemic brain, whereas PGE2 was most concentrated in control cerebra. Pretreatment with anesthetic doses of pentobarbital supported increased accumulation of PGF2 alpha in postischemic cerebra, increased accumulation of 6-keto-PGF1 alpha during the ischemic episode, and decreased accumulation of PGE2 at 120 min of reperfusion. It appears that the protective effects of barbiturate anesthesia are not expressed by the reduced accumulation of the above eicosanoids.     

Cardiac response to norepinephrine and sympathetic nerve stimulation following experimental subarachnoid hemorrhage

This study aimed to investigate the cardiac response to sympathetic stimulation and norepinephrine exposure following subarachnoid hemorrhage (SAH). Cardiac functional response was assessed 3 days following an injection of 300 microl of homologous blood in the cisterna magna using an in situ perfused, innervated rat heart model. Sympathetic nervous activity was indirectly assessed from measurements of arterial plasma and tissue norepinephrine concentration and cardiac beta-receptor density. In in situ perfused hearts, sympathetic nerve stimulation (2, 4 and 8 Hz, 1 min duration) induced a frequency-dependent increase in left ventricular pressure (VP), with the response being more pronounced in the SAH group of animals at the higher frequency (P<0.05). However, the concomitant release of norepinephrine was identical in the two groups of animals. Increasing doses of norepinephrine (10(-9) to 10(-5) M) added to the perfusate induced a dose-dependent increase in VP and its first derivative (dP/dt). Both responses were greater in the SAH animals compared to the sham rats (P<0.01). ECG recordings from SAH animals presented a higher incidence of different types of arrhythmias, both at rest and when submitted to electrical stimulation or norepinephrine exposure. No difference was found between groups in left ventricle norepinephrine content, plasma norepinephrine nor left ventricle beta-receptor density. In conclusion, hearts from animals following acute experimental SAH exhibit enhanced sensitivity to norepinephrine infusion and sympathetic nerve stimulation, and are more prone to develop arrhythmias. However, hypersensitivity of the heart may not be explained by changes in norepinephrine release or by beta-receptor density.     

Release of calcitonin gene-related peptide from the isolated mouse heart: methodological validation of a new model

Calcitonin gene-related peptide (CGRP), a potent vasodilator released from a subset of sensory Adelta- and C-fiber afferents, has been suggested to play a beneficial role in myocardial ischemia. Variations in CGRP release can possibly be correlated with diseases that involve changes in activity or degeneration of cardial afferent fibers. The aim of the present study was to evaluate a simple and easily reproducible model for measuring stimulated CGRP release from cardial afferents. For this reason freshly isolated mouse hearts were passed through incubations in series of 25 min. Solutions consisting of oxygenated synthetic interstitial fluid. Dissolved substances such as capsaicin, bradykinin and potassium chloride were used as excitatory test stimuli. For comparison, isolated mouse hearts were perfused with the same solutions through a cannula inserted into the rising aorta. The eluates were processed using an enzyme immuno-assay for measurement of CGRP concentrations. Capsaicin, bradykinin and the potassium solution caused concentration-dependent increases in CGRP release. There were no differences in CGRP release when oxygen was replaced by nitrogen in the solutions. Immersion of hearts caused significantly more CGRP release than perfusion with same solutions. The results suggest that mouse heart immersion is more effective than coronary perfusion in measuring stimulated CGRP release from cardial afferents which are widely distributed in the epicardium but rare in deeper myocardial layers. The results are discussed with respect to the potentially important vasodilatory and cardioprotective functions of CGRP released from activated epicardial afferents.     

Effects of prostacyclin during cardiopulmonary bypass in men on plasma levels of beta-thromboglobulin, platelet factor 4, thromboxane B2, 6-keto-prostaglandin F1 alpha and heparin

A randomized double-blind study was carried out on 40 male patients requiring aorto-coronary bypass surgery. 20 patients received a constant dose of 8 ng kg-1 min-1 of prostacyclin (PGI2), beginning two minutes before extracorporeal circulation (ECC) and ending together with ECC. Compared to the placebo-treated patient group (n = 20), PGI2-treatment significantly reduced the ECC-induced release of platelet alpha-granule proteins, beta-thromboglobulin (1178 ng/ml vs. 1926 ng/ml) and platelet factor 4 (837 ng/ml vs. 1245 ng/ml) into plasma (mean of max. values). Furthermore the decrease of platelet counts during ECC was less pronounced in PGI2-treated patients. Application of PGI2 had no effect on the increase in thromboxane B2 (TxB2) plasma levels, which amounted to 0.6 ng/ml at the end of ECC. PGI2-treatment resulted in significantly elevated plasma concentrations of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) (2.1 ng/ml) throughout the infusion off prostacyclin. 6-keto-PGF1 alpha plasma levels increased up to 1.2 ng/ml in the control group patients, indicating a stimulation of endogenous PGI2 formation during ECC.     

Activated cranial cervical cord neurons affect left ventricular infarct size and the potential for sudden cardiac death

To evaluate whether cervical spinal neurons can influence cardiac indices and myocyte viability in the acutely ischemic heart, the hearts of anesthetized rabbits subjected to 30 min of LAD coronary arterial occlusion (CAO) were studied 3h after reperfusion. Control animals were compared to those exposed to pre-emptive high cervical cord stimulation (SCS; the dorsal aspect of the C1-C2 spinal cord was stimulated electrically at 50 Hz; 0.2 ms; 90% of motor threshold, starting 15 min prior to and continuing throughout CAO). Four groups of animals were so tested: 1) neuroaxis intact; 2) prior cervical vagotomy; 3) prior transection of the dorsal spinal columns at C6; and 4) following pharmacological treatment [muscarinic (atropine) or adrenergic (atenolol, prazosin or yohimbine) receptor blockade]. Infarct size (IS) was measured by tetrazolium, expressed as percentage of risk zone. C1-C2 SCS reduced acute ischemia induced IS by 43%, without changing the incidence of sudden cardiac death (SCD). While SCS-induced reduction in IS was unaffected by vagotomy, it was no longer evident following transection of C6 dorsal columns or atropinization. Beta-adrenoceptor blockade eliminated ischemia induced SCD, while alpha-receptor blockade doubled its incidence. During SCS, myocardial ischemia induced SCD was eliminated following vagotomy while remaining unaffected by atropinization. These data indicate that, in contrast to thoracic spinal neurons, i) cranial cervical spinal neurons affect both adrenergic and cholinergic motor outflows to the heart such that ii) their activation modifies ventricular infarct size and lethal arrhythmogenesis.     

Head injury induces increased prostaglandin synthesis in rat brain

Head injury was induced in the left hemisphere of rats. The rats were killed at various time intervals after trauma (immediately, 15 min, 1 and 18 h, and 4 and 10 days), and the rates of synthesis and release of prostaglandin PGE2, 6-keto-PGF1 alpha, and thromboxane TXB2 from cortical slices of both hemispheres were studied. The rate of synthesis of PGE2 after 18 h was six and four times higher than control in the contused and contralateral hemispheres, respectively. By 10 days post-trauma, both hemispheres had normal rate of PGE2 release. TXB2 and 6-keto-PGF1 alpha synthetases were affected already 15 min after the injury, and a similarly elevated rate of synthesis was found in both hemispheres. The maximal effect was detected after 1 or 18 h with return to normal after 4 or 10 days for TXB2 and 6-keto-PGF1 alpha, respectively. Tissue specific gravity was determined for both hemispheres using linear gradient columns. The results of these determinations indicate that development of edema occurs in the contused hemisphere as early as 15 min post trauma; it reaches its maximal level at 18 h and returns to normal at 10 days. Arterial pressure was monitored, and a transient increase was found at 10 min post trauma. We suggest that the production of edema after brain injury may be related to the increased rate of PGE2 and PGI2 synthesis, which occurs at similar time intervals after injury.     

Accumulation of prostacyclin in rat brain during haemorrhagic hypotension--possible role of PGI2 in autoregulation

The effect of haemorrhagic hypotension on the levels of prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and 6-keto prostaglandin F1 alpha (6-keto-PGF1 alpha) in cortical tissue of rats was studied. Lightly anesthetized rats were subjected to steady-state hypotension for 15 min, with a mean arterial blood pressure of 80, 60, and 40 mm Hg, and compared to a control group of normotensive rats. No significant change was found in the levels of PGE2 and TXB2. The level of 6-keto-PGF1 alpha increased from 7.8 +/- 0.9 to 14.1 +/- 1.9 pg/mg protein (p less than 0.02) at 80 mm Hg. Our findings suggest that prostacyclin, which is a potent vasodilator, might play a role in setting the lower limit of the autoregulation range.