Effects of hydrostatic distention on in vitro vasoreactivity of radial artery conduits

Background

Surgical preparation of coronary conduits may affect early and long-term patency through endothelial and smooth muscle injury. We investigated the effect of hydrostatic distention on the in vitro endothelial function and contractile properties of the human radial artery.

Methods

Human radial arteries were harvested and distended to physiologic pressure or suprasystemic pressure (>300 mm Hg) by using heparinized whole blood for 2 minutes. Distal segments were retrieved and prepared into 3-mm rings. These were mounted and stretched to optimum resting tension in oxygenated Krebs solution at 37°C. Contraction responses to potassium, norepinephrine, and serotonin and relaxation responses to acetylcholine and nitroprusside were evaluated. Undistended radial artery segments were used as controls.

Results

Vasocontraction to all 3 contractile agonists was significantly different between groups. The radial artery subjected to suprasystemic pressure distention achieved the lowest percentage of maximum contraction (potassium, P < .001; norepinephrine, P < .05; serotonin, P < .05). The median effective concentration was also significantly reduced in this group, indicating increased sensitivity to all 3 agonists. Receptor-mediated contractility was significantly reduced in both distended groups when compared with controls. Relaxation to acetylcholine and nitroprusside was significantly reduced in the suprasystemic pressure-distended group, which had a tendency to vasospasm when exposed to a physiologic concentration of acetylcholine (10⁻⁶ mol/L). Median effective concentrations for both acetylcholine and nitroprusside were not different between groups.

Conclusions

Excessive distention of the radial artery leads to a significant reduction in vasoreactivity, which may be attributed to a disruption of the vascular endothelium and media, with a propensity for graft spasm with exposure to acetylcholine.     

不同血管保存液对人桡动脉血管移植物的抗痉挛作用

目的 研究不同的血管保存液对人离体桡动脉痉挛的缓解与预防能力。方法 非体外循环冠状动脉旁路手术(OPCAB)19例患者,应用“无接触(No Touch)”外科技术获取自体桡动脉,保留未处理的远段0.8～1.5cm。应用血管环灌流技术(Organ Bath)比较不同保存液的抗痉挛作用和预防痉挛作用。结果 血管环灌流实验显示,在对痉挛状态桡动脉的舒张能力方面,PS、VG、DG、NG溶液均可以在10min内100％舒张血管,舒张曲线显示舒张能力依次为VG、DG、NG、PS,但差异无显著性(P>0.05),在预先浸泡处理桡动脉45～60min后,除对照组(Ringer's Solution)外,所有血管保存液均可以有效地预防离体桡动脉的痉挛,各组间差异无显著性(P>0.05)。结论 罂粟碱溶液、VG、DG、NG溶液均有较好的抗血管痉挛作用,单从抗血管痉挛角度考虑可以用作CABG手术中桡动脉的准备液。     

Skeletonization of radial and gastroepiploic conduits in coronary artery bypass surgery

The use of a skeletonized internal thoracic artery in coronary artery bypass graft surgery has been shown to confer certain advantages over a traditional pedicled technique, particularly in certain patient groups. Recent reports indicate that radial and gastroepiploic arteries can also be harvested using a skeletonized technique. The aim of this study is to systematically review the available evidence regarding the use of skeletonized radial and gastroepiploic arteries within coronary artery bypass surgery, focusing specifically on it's effect on conduit length and flow, levels of endothelial damage, graft patency and clinical outcome. Four electronic databases were systematically searched for studies reporting the utilisation of the skeletonization technique within coronary revascularisation surgery in humans. Reference lists of all identified studies were checked for any missing publications. There appears to be some evidence that skeletonization may improve angiographic patency, when compared with pedicled vessels in the short to mid-term. We have found no suggestion of increased complication rates or increased operating time. Skeletonization may increase the length of the conduit, and the number of sequential graft sites, but no clear clinical benefits are apparent. Our study suggests that there is not enough high quality or consistent evidence to currently advocate the application of this technique to radial or gastroepiploic conduits ahead of a traditional pedicled technique.     

Brief pretreatment of radial artery conduits with phenoxybenzamine prevents vasoconstriction long term

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 2,3-butadione 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 μmol/L or by phenylephrine (0.300 to 1.5 μmol/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 receptor-independent 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.     

Histopathology and morphometry of radial artery conduits: basic study and clinical application

Background

The purpose of this study was to determine the pathohistology, morphometry, and risk factors for the development of intimal hyperplasia, calcification, and arteriosclerosis in the radial artery and to compare the morphometry of the distal and proximal radial arteries.

Methods

A total of 190 proximal and distal radial artery specimens obtained from patients who underwent myocardial revascularization were exposed to histopathologic and morphometric analysis. The severity of disease was evaluated on the basis of the percentage of luminal narrowing, intimal thickness index, and intima-to-media ratio.

Results

Sixty-two proximal (32.6%) and 22 distal (11.5%) radial artery segments were indicated as histologically normal. Morphometric analysis (Z test) revealed a lesser degree of intimal hyperplasia and luminal narrowing in the proximal segments compared with the distal segments (p < 0.001). The incidence of intimal hyperplasia, medial calcification, and arteriosclerosis in the distal radial arteries was 76.3%, 6.3%, and 5.78%, respectively. Using multivariate logistic regression, we have identified three significant predictors for intimal hyperplasia. Expressed as an odds ratio with a 95% confidence interval, these included (i) age greater than 50 years (1.052; 1.000-1.106, p = 0.052), (ii) smoking (14.073; 5.293-37.414, p = 0.000), and (iii) hypertension (2.777; 1.171-6.583, p = 0.020). Factors associated with an increased likelihood of medial calcification and arteriosclerosis included a history of smoking, diabetes, hypercholesterolemia, peripheral arterial disease, and chronic renal failure (p < 0.05).

Conclusions

The great majority of radial artery conduits indicate preexisting intimal hyperplasia mostly affecting the distal portion. Therefore in cases of longer diseased segments of radial arteries, the discarded segments should be the distal end. Care should be taken when selecting radial artery as a conduit in myocardial revascularization, particularly in elderly males, diabetics, smokers, hypertensive patients, and in those with associated peripheral vascular disease.     

Vasoreactivity of arterial grafts in the patient with diabetes mellitus: investigations on internal thoracic artery and radial artery conduits.

OBJECTIVE: Arterial revascularization with either internal thoracic artery (ITA) or radial artery (RA) appears to be particularly attractive in diabetic patients. Previous investigations have shown that endothelial dysfunction and artherosclerosis are seen more often in these patients. The aim of this study was to compare the vasoreactive properties of ITA and RA grafts in diabetic and non-diabetic patients. METHODS: Arterial rings were harvested from 57 patients who underwent complete arterial revascularization. The patients were divided into a non-diabetic group (I: n = 30) and patients with diabetes mellitus (II: n = 27). Arterial rings of the ITA (I: n = 30; II: n = 27) and RA (I: n = 28; II: n = 19) were mounted on a strain gauge in oxygenated, normothermic Krebs's--Henseleit solution at optimal resting tension. With KCL (80 mM) serving as the control, assessment of force of contraction (norepinephrine), endothelium-dependent relaxation (acetylcholine) and smooth muscle-dependent relaxation (glyceroltrinitrate) were obtained. RESULTS: After KCL, the RA showed a trend to lower maximum contraction forces in diabetics (I: 76 +/- 25 mN; II: 69 +/- 29 mN), which was pronounced in patients with diabetes of more than 10 years duration (55 +/- 23 mN; P = 0.1). Maximum contraction force of the ITA was similar in both groups (I: 41 +/- 20 mN; II: 34 +/- 19 mN) and not influenced by the duration of diabetes. The two groups showed no significant differences of the relative vasoconstriction after norepinephrine in RA (I: 53 +/- 18%; II: 61 +/- 19%) and ITA rings (I: 70 +/- 23%; II: 69 +/- 25%). Also, endothelium-dependent relaxation with acetylcholine in RA (I: 53 +/- 14%; II: 57 +/- 16%) and ITA rings (I: 42 +/- 17%; II: 44 +/- 20%), and smooth muscle relaxation with glyceroltrinitrate of RA (I: 72 +/- 8%; II: 73 +/- 12%) and ITA rings (I: 64 +/- 12%; II: 58 +/- 20%) was comparable in both groups. No influence of duration of the diabetic disease was noted. CONCLUSIONS: Although RA rings of patients with a long duration of diabetes have decreased maximum contraction forces, their relative vasoconstriction after norepinephrine, endothelium-dependent relaxation and smooth muscle relaxation was similar to non-diabetic patients. We thus conclude that the RA is an adequate arterial conduit in the patient with diabetes mellitus.     

Reversal of preexisting vasospasm in coronary artery conduits

BACKGROUND: To reverse preexisting coronary graft spasm, we investigated the vasodilative effect of the average therapeutic plasma concentration of nitroglycerin (NTG) alone and various calcium antagonists in combination with NTG in human arterial and venous conduits. METHODS: Vasodilative effects of 2 x 10(-8) mol/L NTG alone and 10(-8) mol/L NTG in combination with 2.2 x 10(-7) mol/L diltiazem, 2.8 x 10(-7) mol/L nifedipine, 10(-7) mol/L verapamil, or 5.6 x 10(-8) mol/L nicardipine were assessed in human radial artery, internal thoracic artery, and saphenous vein segments precontracted with a mixture of ten times the maximum plasma concentrations of endothelin-1 (8.6 x 10(-13) mol/L), angiotensin II (36 x 10(-11) mol/L), 5-hydroxytryptamine (3.4 x 10(-7) mol/L), and norepinephrine (1.7 x 10(-8) mol/L). The studies were done in organ baths. RESULTS: The therapeutic concentration of NTG alone or nifedipine, verapamil, diltiazem, or nicardipine in combination with NTG caused equal relaxation in a particular group of vascular segments (average vasodilation: radial artery, 83% to 95% [p = 0.7608 by analysis of variancel; saphenous vein, 47% to 70% [p = 0.3142]; internal thoracic artery, 54% to 79% [p = 0.27831). These combinations were not equally effective when compared between different groups of vascular segments (vasodilation; radial artery > internal thoracic artery > saphenous vein [p < 0.0001 by analysis of variance]). Although not significant, in comparison with NTG alone, NTG in combination with a calcium antagonist caused less vasodilation in any group of vascular segments. CONCLUSIONS: Nitroglycerin alone or in combination with nifedipine, verapamil, diltiazem, or nicardipine effectively reverses preexisting vasospasm in coronary artery conduits.     

Effects of radial artery harvesting on forearm function and blood flow

BACKGROUND: There is little information on the effects of radial artery harvesting on postoperative forearm function and blood flow. We evaluated the early changes in forearm neural sensation, circumference, grip power, cyclical exercise fatigue, and blood flow after radial artery harvesting for coronary artery bypass graft (CABG) surgery. METHODS: Twenty-three patients with negative Allen's test of the nondominant forearm were recruited preoperatively and underwent assessment of bilateral forearm function (soft touch and pin-prick neural sensation, circumference, handgrip power, cyclical exercise fatigue) and blood flow measurements (forearm plethysmography). All vasoactive drugs were stopped 24 hours before assessments. Identical follow-up assessments were conducted (mean +/- SEM) 3.4 +/- 0.4 months postoperatively. RESULTS: At the time of postoperative assessment all harvested forearm wounds were healed. There was no reduction of postoperative soft touch sensation but in 3 patients objective pinprick sensation was reduced in the distribution of the lateral antebrachial cutaneous nerve of the harvested forearms. Postoperative forearm circumference (p < 0.05) and grip power (p < 0.05) were significantly reduced in both forearms, however cyclical exercise fatigue was improved in both forearms. Preoperative and postoperative forearm blood flow at rest and in exercise-induced ischemic reperfusion were not significantly different in both forearms. CONCLUSIONS: In patients with a negative Allen's test, harvesting of the radial artery does not adversely affect subsequent forearm function or blood flow to a clinically significant degree.     

Effects of lung preservation solutions on PMN activation in vitro

Polymorphonuclear leukocyte (PMN) activation and PMN-endothelial cell interactions may cause graft failure due to ischemia-reperfusion injury after lung transplantation. We investigated the effects of Euro-Collins solution (EC), low-potassium dextran solution (LPD), and EC plus pentoxifylline (EC-PTXF) on adhesion molecule (CD11b/CD18 and L-selectin) expression, chemotaxis, and oxidative burst of PMN. PMN from healthy human volunteers were incubated with EC, LPD, and EC-PTXF, and, in controls, without preservation solution. LPD exerted a suppressive effect on PMN chemotaxis as compared to EC (P < 0.05), but had no attenuating effect on the increase of CD11b/CD18, the shedding of L-selectin, and intracellular oxidant generation. EC-PTXF attenuated the expression of CD11b/CD18 and the oxidative burst as compared to EC alone (P < 0.05). These effects of LPD and PTXF on PMN function may contribute to successful organ preservation in transplantation. Received 22 June 98 Received after revision: 30 December 1998 Accepted: 19 January 99     

Effects of intravenous anesthetics on the human radial artery used as a coronary artery bypass graft

OBJECTIVE: Intravenous anesthetics are often used for anesthesia, sedation, and analgesia in the intraoperative and postoperative periods of coronary artery bypass graft (CABG) surgery. This study was designed to investigate the direct effects of intravenous anesthetics on the human radial artery (RA). DESIGN: In vitro, prospective with repeated measures. SETTING: University research laboratory. PARTICIPANTS: RA segments (n = 20) were obtained from CABG surgery patients and were divided into 3- to 4-mm vascular rings. INTERVENTIONS: Using the organ bath technique, the endothelium-independent vasodilatation function was tested in vitro by the addition of cumulative concentrations of thiopental, ketamine, etomidate, and propofol after vasocontraction by phenylephrine in the presence of N(G)-nitro-L-arginine methyl ester (L-NAME) and indomethacin. MEASUREMENTS AND MAIN RESULTS: Thiopental (10(-8) to 10(-4) mol/L), ketamine(10(-8) to 10(-4) mol/L), propofol (10(-8) to 3 x 10(-4) mol/L), and etomidate (10(-8) to 3 x 10(-4) mol/L) caused concentration-dependent vasorelaxation in human RA rings precontracted with phenylephrine in the presence of L-NAME and indomethacin (n = 20, for each drug). The pEC(50) and maximum relaxant effect values of thiopental and ketamine were significantly higher than for etomidate and propofol (p < 0.05). CONCLUSIONS: These findings indicate that thiopental, ketamine, etomidate, and propofol produce concentration-dependent relaxation on RA rings from humans. Thiopental and ketamine are more potent relaxant agents than etomidate and propofol. Intravenous anesthetics may be effective as alternative vasodilators for treatment of intraoperative and postoperative spasm of coronary artery grafts.     

Early and mid-term results of all arterial graft coronary artery bypass grafting using bilateral internal thoracic and radial arterial conduits

From March 1996 to May 2000, 41 patients [age 39-78 (mean 63.5 +/- 8.8) years, 90.2% male] underwent all arterial multiple coronary artery bypass grafting (CABG) using bilateral internal thoracic (BiITA) and radial (RA) arterial conduits. The reason for using RA was that the right gastroepiploic artery (RGEA) was small or occluded on preoperative angiography, a history of upper abdominal surgery or disease, or the right coronary arterial lesion was proximal and mild. The BiITA were used as in situ grafts and the proximal anastomosis of RA was to the ascending aorta in all cases. All patients underwent conventional elective CABG with median sternotomy using cardiopulmonary bypass. The mean number of anastomoses was 3.3 +/- 0.5 branches and complete revascularization rate was 80.5%. Postoperative follow-up averaged 20 months and the longest was 50 months. There was no early death, and overall graft patency 2-3 weeks after surgery was 96.2% (LITA 94.0%, RITA 97.6%, RA 97.6%). Four-year actuarial survival rate was 96.4 +/- 3.5% (1 patient: 9 months, no cardiac death), and cardiac event-free rate after surgery was 89.7 +/- 4.9% [4 patients: percutaneous transluminal coronary angioplasty (PTCA)]. However, once patients were discharged from hospital, cardiac event-free rate was 100%. These excellent results suggest that all arterial graft CABG was satisfactory, and RA can be used as a third suitable arterial bypass conduit, if RGEA cannot be used or is unsuitable for use.     

Storage of radial artery grafts in blood increases vessel reactivity to vasoconstrictors in vitro

Background. Although prone to spasm, the radial artery (RA) is commonly used as a graft in coronary artery bypass surgery (CABG). Successful use of the RA as a graft is dependent on techniques to manage vasospasm during operation. We routinely store the RA in a papaverine blood solution after harvesting, a procedure which might damage the endothelium and predispose the RA to postoperative spasm. The aim of the present study was to evaluate the vasodilator and vasoconstrictor responsiveness in freshly obtained and stored segments of RA.

Methods. Discarded segments of RA were obtained at operation from patients undergoing CABG and mounted as 3-mm rings in organ baths for isometric recording of changes in smooth muscle force production. Responses to cumulative additions of acetylcholine, noradrenaline, serotonin, angiotensin II, and the thromboxane A2 mimetic U46619 were normalized to contractions induced by a high potassium solution.

Results. Endothelium-dependent relaxation to acetylcholine was not different between preparations from freshly-obtained and blood-stored RA segments. However, maximum contractions to all vasoconstrictors studied were markedly increased in preparations from stored arteries. The sensitivity (pEC₅₀) of stored arteries to U46619, noradrenaline, and angiotensin were also enhanced when compared to preparations from freshly-obtained segments.

Conclusions. Papaverine blood solutions do not damage the endothelium of the RA. The observed heightened vasoconstrictor reactivity of stored arteries, most likely mediated by elements of the blood, indicates that asangineous storage solutions should be explored.