Attenuation of receptor-dependent and -independent vasoconstriction in the human radial artery☆ (original) (raw)
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The Journal of Thoracic and Cardiovascular Surgery, 2000
ly classified all arterial grafts into 3 types according to their pharmacological reactivity and embryological origins 1 : type I (somatic arteries), type II (splanchnic arteries), and type III (limb arteries). In this classification on arterial grafts, the radial artery (RA) belongs to the type III, a type that is more spastic than the type I artery, such as the internal thoracic artery (ITA). 1-4 Considering the more spastic biological characteristics of this artery, taken together with the history of the abandonment of the RA because of its vasospasm problem, 5,6 antispastic therapy for this arterial graft in CABG is particularly important. 7,8 In fact, the revival of the RA largely resulted from the use of calcium antagonists. 5 However, the use of calcium antagonists may be contraindicated in patients with poor left ventricular function and bradycardia. The search for the best antispastic method for the RA is therefore clinically important. In addition, although many vasodilators such as calcium antagonists, ACE-inhibitors, and long-lasting A utologous arteries have been used as grafts for coronary artery bypass grafting (CABG). We have recent-Objective: The radial artery is a spastic coronary bypass graft. We investigated the effect of the phosphodiesterase III inhibitor milrinone on the human radial artery. Methods: Radial artery segments (n = 76) taken from 15 patients were studied in an organ chamber. Concentration-relaxation curves for milrinone were established in the radial artery precontracted with 3 vasoconstrictors (phenylephrine, K + , and U46619). In radial artery rings incubated with therapeutic plasma concentrations of milrinone (7 and 70 µmol/L) for 10 minutes, concentration-contraction curves for the 3 vasoconstrictors were constructed. Results: Milrinone caused a submaximal relaxation in phenylephrine-(98.6% ± 1.4%), K +-(89.1 ± 4.5%), or U46619-(74.2 ± 8.0%) precontracted radial arteries at-4.5 log 10 M. The EC 50 was higher against K + (-5.85 ± 0.24 log 10 M, P = .02) or U46619 (-5.21 ± 0.61 log 10 M, P = .03) than phenylephrine (-6.68 ± 0.11 log 10 M). Pretreatment with milrinone depressed the contraction by phenylephrine from 70.0% ± 7.9% to 23.5% ± 9.3% (P = .003) and by K + from 138.6% ± 5.8% to 73.0% ± 13.9% (P = .006) and shifted the EC 50 3.8-fold higher (P = .03) for phenylephrine and 2.2-fold higher for K + (P = .01). Milrinone reduced the U46619 contraction at low concentration (-8.5 log 10 M) but had little effect on the maximal contraction. Conclusion: Milrinone is a potent vasodilator for the radial artery, with possibly higher potency in α-adrenoceptorand depolarizing agent K +-mediated, but less potency in thromboxane A 2-mediated, contraction. Because it also has a positive inotropic effect, this vasodilator may be particularly indicated for use in patients receiving radial artery grafts in coronary artery bypass grafting.
The Annals of Thoracic Surgery, 2001
Background. Radial artery bypass conduits are prone to early vasospasm or "string sign" with use of vasopressor therapy intraoperatively and postoperatively, causing increased resistance in coronary artery grafts. Current intraoperative treatment with papaverine fails to provide sustained inhibition of vasoconstriction. We tested the hypothesis that a 30-minute pretreatment of radial artery segments with the ␣-adrenergic antagonist phenoxybenzamine (PB) or the putative protein phosphatase 2,3butadione monoxime (BDM) attenuates vasoconstriction induced by the vasopressors phenylephrine or norepinephrine for as long as 48 hours compared with papaverine. Methods. Canine radial arteries were harvested, incubated in control buffer or solutions of papaverine 10 ؊6 M, BDM 10 ؊6 M or phenoxybenzamine 10 ؊6 M for 30 minutes, washed, and stored in drug-free culture medium for 2, 24, or 48 hours. After storage, constriction was induced by norepinephrine at incremental concentrations ranging from 0.7 to 3.5 mol/L or by phenylephrine (0.300 to 1.5 mol/L) with or without the inhibitors, and the degree of vasoconstriction was quantified in organ chambers. Responses to norepinephrine or phenylephrine were compared to constriction with receptorindependent potassium chloride KC1 (30 mmol/L). Results. Maximum responses to phenylephrine and norepinephrine were comparable at 2, 24, and 48 hours after harvest in the control group (phenylephrine: 67% ؎ 4%, 62% ؎ 6%, 65% ؎ 6% of KC1 response; norepinephrine: 75% ؎ 4%, 62% ؎ 1%, 58% ؎ 7%, respectively). Papaverine failed to attenuate constriction to phenylephrine and norepinephrine 2, 24, or 48 hours posttreatment. Pretreatment with BDM did not reduce vasoconstriction responses to phenylephrine or norepinephrine 2 hours after incubation but did reduce constriction responses thereafter. In contrast, phenoxybenzamine completely attenuated constriction to both phenylephrine (19% ؎ 8%, 1% ؎ 4%, ؊12% ؎ 4%) and norepinephrine (7.1% ؎ 1%, ؊5% ؎ 5%, ؊20% ؎ 5%) at 2, 24, and 48 hours posttreatment, respectively. Phenoxybenzamine did not alter endothelial function relative to controls at any time point. Conclusions. Thirty-minute pretreatment of RA conduits with 10 ؊6 M phenoxybenzamine completely inhibits vasoconstriction to phenylephrine and norepinephrine for as long as 48 hours. Soaking radial artery grafts briefly in phenoxybenzamine solution before implantation may be effective in preventing postoperative vasospasm caused by two common ␣-adrenergic agonists used in postoperative hemodynamic management.
The Journal of Thoracic and Cardiovascular Surgery, 2003
Background: Although the radial artery bypass conduit has excellent intermediateterm patency, it has a proclivity to vasospasm. We tested the hypothesis that brief pretreatment of a radial artery graft with the irreversible adrenergic antagonist phenoxybenzamine attenuates the vasoconstrictor response to the vasopressors phenylephrine and norepinephrine compared with the currently used papaverine/ lidocaine.
Prostaglandins & Other Lipid Mediators, 2017
Radial artery graft spasm in the perioperative or postoperative period of coronary bypass surgery necessitates urgent treatment due to risk of graft failure and mortality. Herein, we evaluated the effect of iloprost, a prostacyclin (PGI 2) analogue, against the contractions produced by noradrenaline and potassium chloride on isolated human radial artery. Following the determination of endothelial and vascular relaxing capacities of the arteries, iloprost (10 −9 M-10 −6 M) was cumulatively applied on rings precontracted submaximally with the spasmogens. In some rings, the response to iloprost was assessed following pretreatment with nitric oxide (NO) synthase inhibitor, L-NAME (3 × 10 −4 M,30 min). Iloprost produced complete relaxations on radial artery rings precontracted with noradrenaline whereas, only moderate relaxations against the contractions induced by potassium chloride. Notably, the relaxation to iloprost was remarkably blunted in radial arteries with impaired endothelial function. Moreover, the relaxation to iloprost was unchanged in rings pretreated with L-NAME. Our results demonstrated that iloprost could be a potent relaxant agent in reversing radial artery spasm, particularly initiated by noradrenaline, possibly acting via an endothelium-mediated mechanism unrelated to NO.
Clinical Science, 1995
1. The effect of vasopressin receptor antagonists varies between analogues (peptide, non-peptide) and across species. In this study the effect of the novel non-peptide vasopressin V1a receptor antagonist SR 49059 on human internal mammary arteries was investigated. 2. SR 49059 produced a potent, concentration-dependent, inhibitory effect on vasopressin-induced contraction of human coronary bypass graft internal mammary arteries. Both SR 49059 (1 μmol/l) and a peptide selective V1a antagonist {[d(CH2)5sarcosine7]arginine vasopressin} (1 μmol/l) abolished vasopressin-induced contraction. The non-peptide V1a receptor antagonist OPC-21268 (1 μmol/l) had no effect on vasopressin-induced contraction. 3. The effect of SR 49059 was specific to vascular vasopressin receptors as noradrenaline-induced contraction was not influenced by SR 49059. 4. The results of this study in vitro indicate that the non-peptide SR 49059 is a potent, specific vasopressin V1a receptor antagonist in the human int...
Direct vasodilator effect of milrinone, an inotropic drug, on arterial coronary bypass grafts
The Journal of Thoracic and Cardiovascular Surgery, 1997
Milrinone is an inotropic drug with vasodilator activity that has been shown to be useful in increasing cardiac output and decreasing wedge pressure. Despite these advantages, it is unknown whether this drug can be used for the treatment of perioperative spasm of coronary bypass grafts. This study was undertaken to investigate the in vitro vascular effect of milrinone on internal thoracic arteries obtained from patients under'going coronary artery bypass grafting. The results showed that miMnone produced a potent, concentrationdependent, preventive effect on the norepinephrine-induced contraction of internal thoracic arteries, as well as reversing contraction of internal thoracic arteries by receptor-dependent agents, including the thromboxane A2 mimetic U46619, the vasoconstrictor peptide endothelin-1, and the al-adrenal receptor agonist phenylephrine. The relaxing effect of milrinone was weaker, however, on internal thoracic arteries contracted with 25 mmol/L potassium chloride. Comparison of milrinone with other vasodilators, including papaverine, nitroprusside, and glyceryl trinitrate, showed milrinone to be more potent than papaverine but less potent than nitroprusside and glyceryl trinitrute. The inhibitory effect of milrinone on internal thoracic artery contraction appeared as a reduction in contractile force, not as an increase in the values of concentrations of the agonists causing 50% maximal contraction, which indicates that milrinone exerts its vasodilator effect directly on the smooth muscles, not on the membrane receptors. The results also showed no significant difference in relaxing effect between internal thoracic artery rings with and without endothelium. In conclusion, this study provides experimental evidence that milrinone is a potent, endothelium-independent, direct vasodilator of the human internal thoracic artery and provides the scientific rationale for a future clinical trial with this drug for the perioperative treatment of internal thoracic artery spasm in cardiac surgical patients.
Diadenosine polyphosphates are selective vasoconstrictors in human coronary artery bypass grafts
Vascular Pharmacology, 2008
Diadenosine polyphosphates (Ap n A) are released by degranulating platelets and high, local concentrations may form at sites of platelet activation. Radial artery grafts, now often used alongside the internal mammary artery in coronary artery bypass surgery, are particularly reactive to several vasoconstrictors but the response to Ap n A has not been investigated. This study compared the vasoconstrictor activity of Ap n A in human radial artery with other vessels commonly used as bypass grafts. Radial artery demonstrated robust concentration-dependent vasoconstriction to Ap n A (n =4-6) at concentrations in the micromolar range. In contrast, average responses in internal mammary artery were negligible. Cross-desensitization revealed that Ap n A-mediated vasoconstriction occurred via an αβmethyleneATP-sensitive receptor. Responses to both Ap 5 A and αβmethyleneATP were inhibited by suramin but were insensitive to the P2X 1 receptor antagonist 8,8′-[Carbonylbis(imino-4,1-phenylenecarbonylimino-4,1-phenylenecarbonylimino)] bis-1,3,5-naphthalenetrisulfonic acid (NF279). Pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS) enhanced responses to Ap 5 A. Similar responses were obtained in saphenous vein. In conclusion, diadenosine polyphosphates contract radial artery and saphenous vein by an as yet uncharacterized P2X receptor but have only limited activity in internal mammary artery. The selective activity of diadenosine polyphosphates in radial artery would implicate them as potential mediators of post-operative contraction in this graft.
Effects of potassium channel opener KRN4884 on human conduit arteries used as coronary bypass grafts
British Journal of Clinical Pharmacology, 2000
Aims The effects of a new potassium channel opener KRN4884 on human arteries have not been studied. This study was designed to investigate the effects of KRN4884 on the human internal mammary artery (IMA) in order to provide information on possible clinical applications of KRN4884 for preventing and relieving vasospasm of arterial grafts in coronary artery bypass grafting. Methods IMA segments (n=140) taken from patients undergoing coronary surgery were studied in the organ chamber. Concentration-relaxation curves for KRN4884 were established in the IMA precontracted with noradrenaline (NA), 5-hydroxytryptamine (5-HT), angiotensin II (ANG II), and endothelin-1 (ET-1). The effect of glibenclamide (GBC) on the KRN4884-induced relaxation was also examined in NA or 5-HT-precontracted IMA. Concentration-contraction curves for the four vasoconstrictors were constructed without/with pretreatment of KNR4884 (1 or 30 mM) for 15 min.