Endogenous Vasoactive Substances Research Articles

Inappropriately elevated endothelin‐1 plays a role in the pathogenesis of intradialytic hypertension

The aim of this study is to investigate the effects of endogenous vasoactive substances on the occurrence of intradialytic hypertension (IDH) in patients during maintenance hemodialysis. Thirty-four maintenance hemodialysis patients were enrolled in this trial, and 17 of them were diagnosed with IDH (defined as an increase in blood pressure of at least 10 mmHg during or immediately after a hemodialysis session), while 17 age-matched and sex-matched controls without IDH were selected for a retrospective comparison. We collected patients' blood samples before and after a dialysis session and measured the plasma levels of N-terminal fragment brain natriuretic peptide, renin, angiotensin-II, aldosterone (ALD), angiotensin-converting enzyme (ACE), endothelin-1 (ET-1), nitric oxide (NO), norepinephrine (NOR), and adrenomedullin. The post-dialysis serum ET-1 concentrations were significantly higher (4.09 ± 2.06 vs. 2.75 ± 1.34 pg/mL, P < 0.05), while the post-dialysis ratio of NO to ET-1 was lower (17.79 ± 5.65 vs. 24.78 ± 12.04, P < 0.05) in IDH patients compared with the control group. Post-dialysis ALD and NOR values were significantly lower (P < 0.01) and ACE levels were significantly higher (P < 0.01) than the pre-dialysis concentrations only in the control and not in the IDH group. All other measured factors did not differ significantly between the groups and between pre-dialysis and post-dialysis determinations. Compared with blood angiotensin-II, ALD, ACE, NOR, adrenomedullin, N-terminal fragment brain natriuretic peptide, and NO status, inappropriately elevated ET-1 plasma concentrations may play a predominant role in the pathogenesis of IDH.

Hemodynamic Effects of Albumin Dialysis in Patients With Liver Failure: For Better or For Worse?

Liver failure, irrespective of is cause, is frequently associated with multi-organ dysfunction, including hemodynamic instability, and renal and cerebral insufficiency. As a result of the combined impact of these complications, liver failure carries an exceptionally high risk of mortality. A central role in the etiopathogenesis of different end-organ manifestations, as well as in the aggravation of the underlying liver failure, has been attributed to the hyperdynamic (hypotensive) state, which is characterized by a reduced systemic vascular resistance and mean arterial pressure, as well as an increased cardiac index, heart rate, and total plasma volume. Since the accumulation of toxins due to the decreased detoxification capacity by the failing liver is considered vital herein, the emergence of extracorporeal liver support has provided a rational basis for the potential reversal of these phenomena. The present article critically reviews data with regard to the hemodynamic effects of artificial liver support in the context of liver failure. Although these are scarce for acute liver failure, several uncontrolled series and small randomized trials have clearly documented that artificial liver support is able to improve both portal hypertension and the associated systemic circulatory dysfunction in patients with acute-on-chronic liver failure. The molecular basis for these effects have been related to temporary changes and/or elimination in endogenous vasoactive substances, improved albumin binding capacity, or restoration of oxidative stress-mediated damage to albumin.

Vasoconstrictor-induced hypertension following multiple blood transfusions in children with congenital hemolytic anemia.

Introduction. The mechanism by which blood transfusion increases blood pressure in a substantial proportion of patients with congenital hemolytic anemia is unknown. Vascular endothelium dysfunction and increased endogenous vasoactive substances have been postulated in the pathogenesis of hypertension following multiple blood transfusions. The present study was undertaken to test the hypothesis whether increased circulating vasoconstrictors following blood transfusions, if documented, is a potent modulator of hypertension in patients with congenital anemia. Materials and Methods. Four children with congenital hemolytic anemia developed severe hypertension and convulsions 2 to 4 days after they received multiple blood transfusions. None had a history of prior hypertension, kidney disease or seizures before the blood transfusion. Baseline blood and urine samples were obtained for routine renal function studies. Blood samples were also drawn during and 2 weeks after the clinical events for determination of epinephrine, norepinephrine, dopamine, and plasma renin activity. Results. Kidney function was normal in all the 4 patients. All had elevated plasma renin activity and increased blood epinephrine, norepinephrine, and dopamine concentrations during hypertensive crises. Hypertension responded to antihypertensive drugs with the patients remaining normotensive 3 to 6 days after commencing therapy. All recovered without further seizures. The elevated plasma renin activity, epinephrine, norepinephrine, and dopamine levels returned to reference levels 2 weeks after completion of the last blood transfusion. Conclusions. These data suggest that increased activity of vasoconstrictors in the recipient plasma may be responsible for the development of hypertension after multiple blood transfusions.

ETB receptor agonist, IRL 1620, does not affect paclitaxel plasma pharmacokinetics in breast tumour bearing rats

Endothelins are potent endogenous vasoactive substances. We have found that intravenous administration of endothelin (ET)B receptor agonist, IRL 1620 (N-suc-[Glu9, Ala(11,15)]ET-1 (8-21)) to tumour bearing rats increases blood perfusion and enhances delivery of chemotherapeutic agents to the tumour tissue. This study was conducted to determine whether IRL 1620, an ET(B) receptor selective agonist, alters pharmacokinetics of paclitaxel in breast tumour bearing rats. Breast tumours were induced in female Sprague-Dawley rats by N-methyl-n-nitrosourea (50 mg kg(-1), i.p). Saline (0.3 mL kg(-1), i.v.) or IRL 1620 (3 nmol kg(-1), i.v.), was administered to the tumour bearing rats via the tail vein. Paclitaxel (3 mg kg(-1), i.v.) was administered 15 min after saline or IRL 1620 injection. Serial plasma samples were collected up to 10 h after paclitaxel administration and analysed using an HPLC-UV assay. In a similar study [3H]-paclitaxel (40 microCi, i.v.) was administered after saline or IRL 1620 injection as described above and serial plasma samples were collected until 24 h. Data was fitted to a three-compartment model and pharmacokinetic parameters were generated using WinNonlin software. The AUC(0-infinity) (9.42 +/- 3.18 microg h mL(-1)), clearance (0.69 +/- 0.17 L h(-1) kg(-1)), volume of distribution (10.31 +/- 4.54 L kg(-1)) and half life (1.00 +/- 0.32 h) of [3H]-paclitaxel in tumour rats were similar in rats treated with IRL 1620 or vehicle. Tumour concentration of [3H]-paclitaxel was determined in rats treated with IRL 1620 or vehicle and there was a significant increase in tumour paclitaxel concentration (308.59 +/- 24.42%) in rats treated with IRL 1620 compared with vehicle. It is concluded that IRL 1620, an ET(B) receptor agonist, does not alter paclitaxel pharmacokinetics and can selectively augment the delivery of paclitaxel to the tumour tissue.

A Correlation of Catecholamine and Vasoactive Peptide Release With Hemodynamics in Patients Undergoing Resection of Arteriovenous Malformations

Control of blood pressure can be a problem for intracranial procedures. To investigate the relationship between hemodynamic variables and endogenous vasoactive substances, we studied patients undergoing resection of arteriovenous malformations (AVMs). This was a nonrandomized, prospective study of six patients who had resection of an intracranial AVM and six patients who had clipping of an intracranial aneurysm (ICA) that had not bled. Operative and postoperative blood pressure was controlled with sodium nitroprusside. Heart rate (HR), mean arterial pressure, pulmonary capillary wedge pressure, and cardiac index (CI) were measured after induction of anesthesia; before, during, and after hypotensive anesthesia; immediately postoperatively; and at 12, 24, and 36 hours postoperatively. Blood samples were drawn simultaneously in the AVM group to measure levels of norepinephrine, epinephrine, renin, aldosterone, vasopressin, angiotensin I, and angiotensin II and correlated with significant hemodynamic changes. HR and CI increased significantly among patients with AVMs compared with patients with ICAs (p<0.001 and p=0.05, respectively). HR was significantly correlated with renin (r=0.60), norepinephrine (r=1.00), and vasopressin (r=0.66). CI was significantly correlated with epinephrine (r=1.00), renin (r=0.77), angiotensin II (r=0.71), and vasopressin (r=0.82). Patients with AVMs had a hyperdynamic state characterized by increases in HR and CI. These increases were accompanied by increased renin, norepinephrine, vasopressin, epinephrine, and angiotensin II serum concentrates. There were no significant differences in blood pressure changes between patients who had resection for AVM and those who had clipping of ICA, probably due to the use of sodium nitroprusside in the AVM group. Patients with AVMs had a hyperdynamic state with increases in epinephrine, norepinephrine, angiotensin II, plasma renin activity, and vasopressin. Whether this hyperdynamic state is caused by the resection of the AVM or the use of sodium nitroprusside (SNP) cannot be concluded. Blockage of these mediators preoperatively may help control blood pressure without sodium nitroprusside.

An in vivo and in vitro comparison of the effects of vasoactive mediators on pulpal blood vessels in rat incisors

The effects of endogenous vasoactive substances were evaluated in anaesthetized rats using a laser Doppler flowmeter to monitor changes in pulpal blood flow, as well as directly in isolated pulpal arteriole preparations utilising a microperfusion and monitoring system to observe changes in vessel diameter. In anaesthetized rats, while systemic arterial blood pressure remained relatively stable, intra-arterial delivery of adrenaline (epinephrine) (A), noradrenaline (norepinephrine) (NA), phenylephrine (PHE), dopamine (DOPA), 5-hydroxytryptamine (5-HT), or endothelin-1 (ET-1) produced a dose-dependent reduction in pulpal blood flow (order of potency: ET-1⪢A=NA>PHE=DOPA=5-HT); acetylcholine induced a dose-dependent increase in pulpal blood flow; histamine, isoproterenol and adenosine produced no significant changes. In isolated arteriole preparations, intraluminal delivery of A, NA, PHE, DOPA or 5-HT produced dose-dependent vasoconstriction (A=NA>PHE=DOPA=5-HT). Acetylcholine relaxed NA-precontracted vessels dose-dependently. Histamine and isoproterenol produced a small vasodilatation. Intraluminal ET-1 produced a small vasoconstriction at 10 −8 M, whereas extraluminal ET-1 produced a dose-dependent vasoconstriction from 10 −10 M and above. Intraluminal adenosine failed to dilate vessels precontracted with ET-1, whereas extraluminal adenosine caused a complete relaxation. These combined in vivo and in vitro data suggest that, in the rat incisor, the pulpal microcirculation is capable of functional regulation and that pulpal blood flow may be modulated by endothelium-related factors, metabolic (tissue-related) factors, as well as humoral (blood-borne) factors.

Endothelium-derived nitric oxide regulates arterial elasticity in human arteries in vivo.

Arterial elasticity is determined by structural characteristics of the artery wall and by vascular smooth muscle tone. The identity of endogenous vasoactive substances that regulate elasticity has not been defined in humans. We hypothesized that NO, a vasodilator released constitutively by the endothelium, augments arterial elasticity. Seven healthy young men were studied. A 20-MHz intravascular ultrasound catheter was introduced through an arterial sheath to measure brachial artery cross-sectional area, wall thickness, and intra-arterial pressure. After control was established, indices of elasticity (pressure-area relationship, instantaneous compliance, and stress-strain, pressure-incremental elastic modulus (E(inc)), and pressure-pulse wave velocity relationships) were examined over 0 to 100 mm Hg transmural pressure obtained by inflation of an external cuff. Thereafter, the basal production of endothelium-derived NO was inhibited by N(G)-monomethyl-L-arginine (L-NMMA) (4 and 8 mg/min). Finally, nitroglycerin (2.5 and 12.5 microgram/min), an exogenous donor of NO, was given to relax the vascular smooth muscle. Elasticity was measured under all of these conditions. L-NMMA (8 mg/min) decreased brachial artery area (P=0.016) and compliance (P<0.0001) and increased E(inc) (P<0.01) and pulse wave velocity (P<0.0001). Nitroglycerin (12.5 microgram/min) increased brachial artery area (P<0.001) and compliance (P<0.001) and decreased pulse wave velocity (P=0.02). NO, an endothelium-derived vasodilator, augments arterial elasticity in the human brachial artery. Loss of constitutively released NO associated with cardiovascular risk factors may adversely affect arterial elasticity in humans.

Haematocrit, leukocyte and platelet counts and the severity of the ovarian hyperstimulation syndrome.

Previous studies have shown that severe ovarian hyperstimulation syndrome (OHSS) is secondary to circulatory dysfunction due to the simultaneous occurrence of increased vascular permeability and marked arteriolar vasodilation which lead to an intense homeostatic stimulation of the renin-aldosterone and sympathetic nervous systems and antidiuretic hormone (ADH). In the present report, we have investigated the correlation between changes in haematocrit concentration, and white blood cell (WBC) and platelet counts and the severity of OHSS, as assessed by these markers of effective intra-arterial blood volume, in a series of 50 patients. In comparison with recovery values (4-5 weeks after hospital discharge), OHSS patients showed arterial hypotension, tachycardia, oliguria, very high plasma concentrations of renin, aldosterone, norepinephrine and ADH, and increased mean haematocrit values and WBC and platelet counts. The haematocrit concentration values were directly related to the plasma concentrations of vasoactive substances (plasma renin activity, aldosterone, norepinephrine and ADH) during OHSS (P < 0.001). In contrast, no correlation was evident between WBC or platelet counts and neurohormonal measurements during the syndrome. It is concluded that haematocrit, but not WBC or platelet counts, can act as a biological marker of the severity of OHSS as indicated by plasma measurement of volume-dependent endogenous vasoactive substances.

Treatment of severe ovarian hyperstimulation syndrome by a conservative medical approach.

To assess the value of a conservative medical therapeutic approach in the management of severe ovarian hyperstimulation syndrome (OHSS). Prospective longitudinal study. Assisted Reproduction Unit of the Hospital Clínic i Provincial de Barcelona, a tertiary care setting. Twenty-five women with ascites because of OHSS. Patients were treated by strict bed rest, low-sodium diet (60 mEq/day), plasma volume expansion with albumin (50 g/day of salt-poor albumin) and diuretics (20 mg of furosemide given intravenously every 8-12 hours). Measurement at admission and 48 hours after commencement of treatment of the following: body weight, mean arterial pressure, heart rate, hematocrit, hemoglobin concentration, leukocyte and platelet counts, urine volume, sodium excretion, serum sodium, serum creatinine, plasma renin activity, and plasma aldosterone, norepinephrine, antidiuretic hormone, and atrial natriuretic peptide concentrations. After 2 days of therapy there was marked improvement in clinical symptoms, standard laboratory parameters, diuresis and urinary sodium excretion in all patients. There was also a significant decrease in the plasma levels of volume-dependent endogenous vasoactive substances in the five patients in whom these measurements were repeated during treatment. The length of treatment with albumin plus furosemide ranged between 2 and 6 days with an average of 3.3 and it correlated directly with the severity of the syndrome. The hospital stay ranged from 4 to 10 days (mean 6.5 days). All patients recovered without any complication. Severe ovarian hyperstimulation syndrome can be managed using the proposed conservative medical approach.

Nitric oxide mediates fluid accumulation during cardiopulmonary bypass

Fluid accumulation during cardiopulmonary bypass may be related to the production of endogenous vasoactive substances. We investigated the role of nitric oxide in mediating fluid accumulation during cardiopulmonary bypass. Normothermic cardiopulmonary bypass was carried out for 3 hours in male Sprague-Dawley rats with constant, nonpulsatile flow and hemodilution. Fluid accumulation (rate of change of external reservoir volume) was measured under three experimental conditions: saline solution control ( n = 8), l-arginine infusion ( n = 6), and N -nitro- l-arginine methyl ester infusion ( n = 6). At the end of the experiments, body weight and organ wet/dry ratios were examined. Percentage weight gain was 77% greater in the N -nitro- l-arginine methyl ester group and 23% less in the l-arginine group compared with control values. Fluid accumulation was increased with N -nitro- l-arginine methyl ester after 30 minutes ( p < 0.01) and reduced with l-arginine after 120 minutes ( p < 0.01) compared with control animals. Water content was significantly decreased in the heart, lung, skin, muscle and peritoneum in rats receiving l-arginine. These data suggest that endogenous nitric oxide plays an important role in minimizing fluid accumulation during cardiopulmonary bypass. (J T horac C ardiovasc S urg 1996;112:168-74)

The effects and molar potency of iloprost, U46619 and sodium nitroprusside on capsular and vascular smooth muscle of the isolated perfused canine spleen

The isolated canine spleen was perfused at constant flow with continuous recording of splenic arterial perfusion pressure (SAPP) and spleen weight. Intra-arterial injections of the thromboxane A 2 (TXA 2) mimetic U46619 caused dose-related increases in splenic arterial perfusion pressure (SAPP) of short duration (ED 50 0.31 nmol). There were very small changes in spleen weight accompanying any of the vasoconstrictor responses to U46619. The stable analogue of prostacyclin, iloprost, caused dose-dependent reductions in SAPP (ED 50 1.3 nmol) indicating vasodilatation. There were no changes in spleen weight to any doses of iloprost indicating a lack of action on capsular smooth muscle. Similarly, the nitric oxide (NO) mimetic sodium nitroprusside caused dose-related reductions in SAPP of short duration (ED 50 5.8 nmol). No changes in spleen weight accompanied splenic vasodilator responses to any dose of sodium nitroprusside (SNP). The results indicate the potential actions and intrinsic potency of three endogenous vasoactive substances and provide information about their relative roles in the control of the splenic microcirculation in situations when they are released.

Endogenous vasoactive substances and oxygen-derived free radicals in pulpal haemodynamics

An adequate blood supply to the dental pulp is essential to the health of the tooth. A recent concept is that repeated stimulation of sensitive teeth may induce pulpal changes; this could occur through induction of neurogenic inflammation and alteration of pulpal blood flow. One possibility is that production of oxygen-derived free radicals at sites of inflammation contributes to alterations in local blood flow. The first target of free radicals, generated in several pathological processes, is the vascular system (essentially the endothelium). Although the exact mechanism by which free radicals induce changes in vascular conductance is still uncertain, they may act directly on vascular smooth muscle or modify vascular tone by interacting with the production and/or biological activity of endogenous vasoactive mediators. Recent data indicate that the oxygen-derived, free radical-generating system can decrease pulpal blood flow in the dog via endothelial dysfunction when applied locally in deep dentinal cavities. In addition to the part played by oxygen-derived free radicals, the measurement of pulpal blood flow and the effects of endogenous vasoactive substances on flow are discussed.

Effect of high ethanol intake on vascular reactivity to serotonin, vasopressin and acetylcholine in normotensive rats.

Chronic ethanol administration causes hypertension and alterations of vascular reactivity in rats. In several models of hypertension, alterations of vascular reactivity are believed to be secondary to the sustained increase in blood pressure. The present study investigated the effects of serotonin (5-hydroxytryptamine [5-HT]), vasopressin and acetylcholine (ACh) in the isolated perfused mesenteric arteries from Wistar rats submitted to an 8-week course of chronic ethanol intake (8 g/kg.day). No significant differences were observed in the dose-response curves with regard to: pressor effect of 0.04-10.0 nmole 5-HT; relaxant effect of 0.05-50.0 nmole ACh; or the pressor effects of two 1.5-nmole doses of vasopressin between control rats and ethanol-fed rats. These results suggest that modifications in arterial reactivity to endogenous vasoactive substances (observed in other studies involving more prolonged ethanol treatment in rats) may be, in part, secondary to the increase in blood pressure.

Chronic estrogen alters contractile responsiveness to angiotensin II and norepinephrine in female rat aorta

Sex hormones have been postulated to play an important role in the modulation of vascular responsiveness to endogenous vasoactive substances. This study was designed to establish the effects of chronic treatment with estrogen in vivo on subsequent contractile responsiveness of aortic rings to angiotensin II or norepinephrine in vitro. Concentration-response curves for angiotensin II were compared in aortic rings with or without endothelium isolated from ovariectomized rats (275–299 g) pretreated with 17β-estradiol (≈ 1 mg/kg per day) or placebo for 14 days and from normal prepubertal female rats (125–149 g) pretreated with 17β-estradiol (≈ 5 mg/kg per day) or placebo for 14 days. Whether or not endothelium was present, angiotensin II-induced contraction was significantly depressed in rings from 17β-estradiol-treated ovariectomized or prepubertal rats when compared to controls, and the pattern of the effects of 17β-estradiol-treatment on the concentration-response curves for angiotensin II was similar in the two models. In contrast to angiotensin II-induced contraction, norepinephrine-induced contraction was significantly enhanced in aortic rings with or without endothelium from ovariectomized rats pretreated with 17β-estradiol (≈ 1 mg/kg per day, 14 days) and from normal prepubertal female rats pretreated with 17β-estradiol (≈ 5 mg/kg per day, 14 days) when compared to controls. The results demonstrate that chronic treatment with 17β-estradiol selectively reduced and enhanced contractile responsiveness of aortic rings to angiotensin II and norepinephrine, respectively. Further, the results indicate that the normal prepubertal female rat is an efficient model to investigate modulation by estrogen of aortic responsiveness to vasoactive agents in vitro.

Effects of cocaine on epicardial coronary artery reactivity in miniature swine after endothelial injury and high cholesterol feeding. In vivo and in vitro analysis.

The purpose of this study was to determine the effects of cocaine on vasoreactivity in the swine model. Eight miniature pigs underwent regional endothelial denudation of the left anterior descending coronary artery and were then fed a high cholesterol diet. Cross-sectional area (CSA) of coronary arteries was measured by quantitative angiography. Before denudation, intravenous cocaine (1, 3, and 10 mg/kg) decreased CSA of epicardial vessels by 19-44%. At 3 mo after the denudation, the percent reduction in CSA of the denuded vessels induced by the 10 mg/kg dose was significantly augmented compared to nondenuded vessels (59 +/- 5% vs. 48 +/- 4%, P less than 0.05). Under in vitro conditions where isometric force of isolated ring segments was measured, methoxamine (an alpha 1 agonist) or BHT-920 (an alpha 2 agonist) produced similar degrees of contraction of denuded and control vessels; however, cocaine in concentrations up to 3 x 10(-3) M did not produce contraction. These responses were unaffected by removal of the endothelium. Histologically, myointimal thickening was noted at the denuded site. The present study demonstrates an enhanced vasoreactivity of atherosclerotic coronary arteries to cocaine in vivo, the mechanism of which appears to be mediated by endogenous vasoactive substances rather than by a direct action of cocaine on vascular smooth muscle.

Differential responses of uterine and umbilical vasculatures to angiotensin II and norepinephrine

Although the uterine vascular responses to endogenous vasoactive substances have been extensively investigated in pregnant sheep, the fetal umbilical responses to angiotensin II (ANG II) and norepinephrine (NE) have not been well characterized. Twenty-five pregnant ewes between 105 and 115 days of gestation were anesthetized and instrumented for hemodynamic measurements, systemic fetal and maternal intravenous infusions, and local maternal uterine arterial infusions of ANG II and NE. Fetal and maternal arterial pressure and heart rate, maternal uterine blood flow (total of left and right middle uterine arteries), and fetoplacental blood flow (common umbilical artery) were measured during continuous infusions of ANG II or NE. Fetal infusions of ANG II (0.03-1.0 micrograms.min-1.kg estimated fetal body wt-1) increased fetal arterial blood pressure by as much as 44% over base-line values, decreased umbilical blood flow by as much as 63%, and increased umbilical vascular resistance by up to 345%. Fetal infusions of NE (0.1-3 micrograms.min-1.kg-1) increased fetal arterial pressure 42% and increased umbilical vascular resistance by up to 38% but did not significantly alter fetoplacental blood flow. No significant maternal changes were observed during fetal infusions. Maternal infusion of ANG II increased maternal arterial pressure by as much as 59% and significantly increased uterine vascular resistance at the two highest doses but significantly decreased uterine blood flow only at the highest dose (17%; P less than 0.05). Maternal infusions of NE increased arterial pressure by as much as 113%, decreased uterine blood flow by as much as 76%, and increased uterine vascular resistance 3- to 10-fold over the base-line value.(ABSTRACT TRUNCATED AT 250 WORDS)

Direct pharmacological action of vasoactive substances on pulpal blood flow: An analysis and critique

An adequate blood supply to the dental pulp is essential to the health of the tooth; therefore, there have been a number of efforts to study pulpal blood flow and the factors which influence it. However, blood flow to the dental pulp is relatively inaccessible and apparently quite low. Consequently, it is difficult to obtain accurate flow measurements, partly owing to methodological difficulties with the small size of the tissue and its enclosure within rigid walls. In this study, the effects of locally applied vasoactive substances and their specific antagonists on pulpal blood flow have been examined by laser Doppler flowmetry. It is the purpose of this article to examine, in-depth, the involvement of endogenous vasoactive substances in the regulatory mechanism of blood flow within the dental pulp and expand our knowledge of pulpal microcirculatory hemodynamics.

Altered concentrations of terminal complement complexes, anaphylatoxins, and leukotrienes in the coronary sinus during cardiopulmonary bypass

The aim of this study was to determine if the hypoperfused heart activates complement with formation of anaphylatoxins, terminal complement complexes (TCC), or leukotrienes during cardiopulmonary bypass. Fifteen patients undergoing elective cardiopulmonary bypass surgery were studied regarding complement and leukotriene activation. Blood samples were drawn serially from the radial artery and coronary sinus. The plasma concentrations of the complement components C1 INH, C3, C4, and C5 decreased during the procedure, whereas C3a and TCC increased. Protamine reversal of heparin further increased the plasma levels of C3a and TCC. No significant changes in plasma levels of C5a and leukotriene C 4 were observed during cardiopulmonary bypass. The activity of the anaphylatoxin inactivator (Al) decreased in both the radial artery and the coronary sinus. There were no significant differences between the concentrations of complement components and leukotriene C 4 in blood from the radial artery and coronary sinus. The levels of C3a and TCC increased and C11NH, C3, C4, C5, and the anaphylatoxin inactivator activity decreased to the same extent in the coronary sinus and the radial artery. Thus, the heart does not appear to be the primary site for the altered concentrations of these endogenous vasoactive substances.

S-1-1 - Endogenous vasoactive substances possibly related to coronary vasospasm.

S-1-1 - Endogenous vasoactive substances possibly related to coronary vasospasm.

Potassium-induced release of endothelium-derived relaxing factor from canine femoral arteries.

Experiments were designed in a bioassay system to analyze the effect of elevated (from 5.9 mM to 7.5-45.9 mM) extracellular K+ concentration on the release of endothelium-derived relaxing factor. Segments of canine femoral artery with endothelium (donor segment) were mounted in an organ bath and perfused with modified Krebs-Ringer bicarbonate solution; the effluent from the donor segment was used to superfuse a canine coronary artery ring without endothelium (bioassay tissue). Elevation of perfusate K+ concentration by 1.6-15 mM by intraluminal infusion of potassium chloride upstream of the donor segment evoked further contractions of bioassay rings contracted with prostaglandin F2 alpha. In contrast, the bioassay rings progressively relaxed when increasing concentrations of potassium chloride (10-40 mM) were added extraluminally to the organ bath where the perfused segment was mounted. Extraluminal application of phenylephrine or prostaglandin F2 alpha did not evoke relaxations in the bioassay ring. Removal of the endothelium from the donor segment or selective exposure of the segment (but not the bioassay ring) to Ca2+-deficient solution prevented the K+-induced relaxations. Treatment of the donor segment and the bioassay ring with inhibitors of known endogenous vasoactive substances (acetylcholine, norepinephrine, adenine nucleotides, and prostanoids) had no significant effect on the relaxation of the bioassay ring evoked by extraluminal application of potassium chloride. Simultaneous measurements of changes in isometric force in the donor segment and bioassay ring revealed that extraluminal elevation of K+ concentration relaxed the segments as well and that the relaxations could not be prevented by simultaneous intraluminal infusion of potassium chloride.(ABSTRACT TRUNCATED AT 250 WORDS)