Diadenosine polyphosphates are selective vasoconstrictors in human coronary artery bypass grafts.

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 alphabetamethyleneATP-sensitive receptor. Responses to both Ap(5)A and alphabetamethyleneATP 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.

Total arterial revascularisation: effect of avoiding cardiopulmonary bypass on in-hospital mortality and morbidity in a propensity-matched cohort.

OBJECTIVE: The combination of total arterial revascularisation and avoidance of cardiopulmonary bypass may provide additional benefits to patients receiving complete arterial grafting with cardiopulmonary bypass. We performed a propensity-matched cohort study of complete arterial off-pump and on-pump coronary surgery and examined differences in in-hospital mortality and morbidity. METHODS: Three hundred and sixty patients who underwent off-pump coronary surgery with complete arterial grafting between April 1997 and September 2002 were matched to 360 patients who received coronary surgery with cardiopulmonary bypass and complete arterial grafting. To match off-pump with unique on-pump patients, logistic regression was used to develop a propensity score for off-pump surgery. The C statistic for this model was 0.79. Off-pump patients were matched to unique on-pump patients with an identical 5-digit propensity score. If this could not be done, we then proceeded to a 4-, 3-, 2-, or 1-digit match. RESULTS: Patient characteristics were well matched. There was no difference in in-hospital mortality between the groups. Off-pump patients were less likely to develop sternal wound infections compared to the on-pump group (2.5 versus 5.8%; P=0.03), and had significantly lower blood loss (675 versus 780 ml; P<0.001), red blood cell unit transfusion (8.6 versus 38.9%; P<0.001), enzyme rises (13 versus 23 U/l; P<0.001), inotrope support (11.9 versus 28.9%; P<0.001), and ventilation times (5 versus 8 h; P<0.001). Intensive care unit and hospital stay were also significantly lower in the off-pump patients. CONCLUSIONS: Off-pump coronary surgery with complete arterial revascularisation can significantly reduce in-hospital morbidity and lengths of stay compared to conventional on-pump coronary surgery.

Timing of intra-aortic balloon pump support and 1-year survival.

OBJECTIVE: The relationship between the timing of intra-aortic balloon pump (IABP) support and surgical outcome remains a subject of debate. Peri-operative mechanical circulatory support is commenced either prophylactically or after increasing inotropic support has proved inadequate. This study evaluates the effect timing of IABP support on the 1-year survival of patients undergoing cardiac surgery. METHODS: From April 1997 to September 2002, 7698 consecutive cardiac surgical procedures were performed. This included 5678 isolated coronary artery bypasses (CABGs), 1245 isolated valve procedures and 775 simultaneous CABG and valve procedures. IABP support was required in 237 patients (3.1%). Twenty-seven patients (0.35%) were classed as high-risk and received preoperative IABP support, 25 patients (0.32%) were haemodynamically compromised and required preoperative IABP support, 120 patients (1.56%) required intra-operative IABP support, and 65 patients (0.84%) required post-operative IABP support. Multiple variables were offered to a Cox proportional hazards model and significant predictors of 1-year survival were identified. These were used to risk adjust Kaplan-Meier survival curves. RESULTS: 1-year follow-up was complete and 450 deaths (5.8%) were recorded. The significant independent predictors of increased mortality at 1-year (P<0.05, HR=hazard ratio) were post-operative renal failure (HR=3.5), increasing EuroSCORE (HR=1.2), post-operative myocardial infarction (HR=3.7), post-operative IABP (HR=4.1) intra-operative IABP (HR=2.8), post-operative stroke (HR=2.5), increasing number of valves (HR=1.6), ejection fraction <30% (HR=1.3) and triple-vessel disease (HR=1.3). After risk-adjustment, 1-year survival for patients who required intra-operative IABP support was significantly greater than for those patients who required IABP support in the post-operative period. CONCLUSIONS: Patients who warrant IABP support in the post-operative setting have a significantly increased mortality at 1-year when compared to any other group. Therefore, earlier IABP support as part of surgical strategy may help to improve the outcome.

Effect of prolonged intensive care stay on survival following coronary surgery.

The aim of the study was to examine midterm survival in patients who required prolonged recovery in the intensive care unit. The 5,186 consecutive patients who underwent isolated coronary surgery between April 1997 and March 2002 were retrospectively analyzed. Patients were classified as having prolonged (>3 days) or normal (

Phenoxybenzamine treatment is insufficient to prevent spasm in the radial artery: the effect of other vasodilators.

OBJECTIVES: After its reintroduction as an arterial graft in coronary artery surgery, the radial artery is now established as an alternative arterial conduit, with good early and midterm patency. However, because of the concern about its vasospasticity, numerous vasodilator strategies have been used. Recently the use of the irreversible alpha-adrenergic antagonist phenoxybenzamine has been proposed. Although this treatment is effective in eliminating the vasoconstriction mediated by noradrenaline, the contribution of other circulating vasoconstrictors to vasospasm could be as important. This study investigates the response of radial arteries treated with phenoxybenzamine to vasoconstrictor stimuli and possible preventative strategies. METHODS: In vitro, sections of radial artery, pretreated with phenoxybenzamine after harvesting, were stimulated with maximal concentrations of the vasoconstrictors noradrenaline, vasopressin, angiotensin II, KCl, and endothelin-1. In matched segments of artery, vasoconstrictor responses were recorded in the presence of diltiazem, glyceryl trinitrate, and papaverine and compared with phenoxybenzamine-treated samples. RESULTS: Phenoxybenzamine-treated radial artery failed to respond to noradrenaline but did respond to vasopressin, angiotensin II, endothelin-1, and KCl. Diltiazem was largely ineffective against contractile stimuli apart from KCl. Glyceryl trinitrate and papaverine significantly reduced responses to all of the vasoconstrictors tested. CONCLUSION: In phenoxybenzamine-treated sections of radial artery, circulating vasoconstrictor agonists may still contribute to the induction of spasm. Additional vasodilator strategies may be required to completely prevent vasospasm.

Effect of preoperative aspirin use in off-pump coronary artery bypass operations.

BACKGROUND: The effect of preoperative aspirin use until the day of operation on mortality rate and bleeding risks in patients who had on-pump coronary artery bypass operation has been well documented. However, the effect of aspirin use in patients undergoing off-pump coronary artery bypass operation (OPCAB) with regard to postoperative blood loss and morbidity has not been studied. We aimed to determine the effects of continuing aspirin therapy preoperatively. METHODS: We performed a retrospective study of 340 patients who had first-time OPCAB between January 1998 and September 2001. A propensity score for receiving aspirin until the day of operation was constructed from core patient characteristics. All aspirin users (n = 170) were matched with unique 170 nonaspirin users by identical propensity score. The primary outcome measures were in-hospital mortality rate and hemorrhage-related outcomes (postoperative blood loss in the intensive care unit, reexploration for bleeding, and blood product requirements). Secondary outcome measures were stroke, myocardial infarction, gastrointestinal bleeding, and sternal wound infections. RESULTS: There were no differences in patient characteristics between aspirin users and nonaspirin users. The average postoperative blood loss (845 mL versus 775 mL; p = 0.157) and the rate of reexploration for bleeding (3.5% versus 3.5%; p > 0.99) were similar in aspirin users and nonaspirin users. We found no significant difference between blood product requirements for the two groups. Similarly, we found no significant difference in the incidence of the secondary outcomes. CONCLUSIONS: Preoperative aspirin did not increase bleeding-related complications, mortality rate, or other morbidities in patients who had off-pump coronary artery operation.

Coronary surgery in patients with peripheral vascular disease: effect of avoiding cardiopulmonary bypass.

BACKGROUND: An increasing number of patients with peripheral vascular disease are undergoing coronary artery bypass grafting. Such patients have an increased risk of adverse outcomes. Our aim was to quantify the effect of avoiding cardiopulmonary bypass in this group of patients. METHODS: Between April 1997 and March 2002, 3,771 consecutive patients underwent coronary artery bypass grafting performed by five surgeons. Four hundred and twenty-two (11.2%) had peripheral vascular disease and of these, 211 (50%) received off-pump surgery. We used multivariate logistic regression analysis to assess the effect of off-pump surgery on in-hospital mortality and morbidity, while adjusting for treatment selection bias. Treatment selection bias was controlled for by constructing a propensity score, which was the probability of receiving off-pump surgery and included core patient characteristics. The C statistic for this model was 0.8. RESULTS: Off-pump patients were more likely to have preoperative renal dysfunction, previous gastrointestinal surgery, and less extensive disease. The left internal mammary artery was used more in off-pump compared to on-pump cases (90.1% vs 82.9%; p = 0.033). In the univariate analyses, off-pump patients were less likely to have a postoperative stroke (p = 0.007), and had shorter postoperative hospital stays (p < 0.001). However, the incidence of new atrial arrhythmia was higher (p = 0.028). After adjustment for differences in case-mix (propensity score), avoidance of cardiopulmonary bypass was still associated with a significant reduction in postoperative stroke (adjusted odds ratio 0.09 [95% confidence interval 0.02 to 0.50]; p = 0.005), and shorter postoperative hospital stay (p = 0.001). CONCLUSIONS: Off-pump coronary surgery is safe in patients with peripheral vascular disease, with acceptable results. The incidence of postoperative stroke is substantially reduced when avoiding cardiopulmonary bypass in patients with peripheral vascular disease.

Effect of avoiding cardiopulmonary bypass in non-elective coronary artery bypass surgery: a propensity score analysis.

OBJECTIVE: Non-elective coronary artery surgery (emergent/salvage or urgent) carries an increased risk in most risk-stratification models. Off-pump coronary surgery is increasingly used in non-elective cases. We aimed to investigate the effect of avoiding cardiopulmonary bypass on outcomes following non-elective coronary surgery. METHODS: Of the 3771 consecutive coronary artery bypass procedures performed by five surgeons between April 1997 and March 2002, 828 (22%) were non-elective and 417 (50.4%) of these patients had off-pump surgery. Multivariate logistic regression was used to assess the effect of off-pump on in-hospital outcomes, while adjusting for treatment selection bias. Treatment selection bias was controlled for by constructing a propensity score from core patient characteristics, which was the probability of avoiding cardiopulmonary bypass. The C statistic for this model was 0.8. RESULTS: Off-pump patients were more likely to be hypertensive, stable, had less extensive disease and better left ventricular function. The left internal mammary artery was used in 91.8% (n=383) of off-pump patients compared to 79.3% (n=326) of on-pump cases (P<0.001). After adjusting for the propensity score, no difference in in-hospital mortality was observed between off-pump and on-pump (adjusted odds ratio (OR) 0.83 (95% confidence intervals (CI) 0.36-1.93); P=0.667). Off-pump patients were less likely to require intra-aortic balloon pump support (adjusted OR 0.44 (95% CI 0.21-0.96); P=0.039), less likely to have renal failure (adjusted OR 0.44 (95% CI 0.22-0.90); P=0.025), and have shorter lengths of stay (adjusted OR 0.51 (95% CI 0.37-0.70); P<0.001). Other morbidity outcomes were similar in both groups. CONCLUSIONS: In this experience, off-pump coronary surgery in non-elective patients is safe with acceptable results. Non-elective off-pump patients have a significantly reduced incidence of renal failure, and shorter post-operative stays compared to on-pump coronary artery bypass surgery.

Attenuation of receptor-dependent and -independent vasoconstriction in the human radial artery.

BACKGROUND: Vasodilator strategies used to treat bypass grafts in the operating theatre, such as nitrates, phosphodiesterase inhibitors and calcium channel antagonists have a broad but short-lived effect against a variety of vasoconstrictor stimuli. Treatments that react irreversibly with proteins modulating vasoconstriction have the advantage that their effects can last well into the postoperative period. In addition systemic effects are avoided as the treatment is localised to the treated graft. This study investigated the use of two clinically applied drugs; fluphenazine (SKF7171A, HCl), an irreversible calmodulin antagonist and minoxidil sulphate, an irreversible potassium channel opener. Treatments were tested against receptor and non-receptor-mediated contraction in the human radial artery. METHOD: Isometric tension was measured in response to angiotensin II, KCl and vasopressin in 108 radial artery rings (taken from 31 patients undergoing coronary artery bypass grafting). Control responses were compared with rings pretreated with fluphenazine or minoxidil sulphate. Vasopressin responses were also compared in the presence of glyceryl trinitrate or the reversible Rho kinase inhibitor Y27632. RESULTS: Fluphenazine pretreatment significantly suppressed vasoconstriction to all agonists tested. Maximal responses to angiotensin II, vasopressin and KCl were reduced by 42+/-19%, 35+/-8% and 48+/-15% respectively, without any measurable effect on the EC(50). Minoxidil sulphate showed no discernable effect. Vasopressin-induced contraction was also reduced by high levels of glyceryl trinitrate (220 microM; 50 microg/ml) or 10 microM Y27632. CONCLUSIONS: The irreversible calmodulin antagonist fluphenazine has potential to be developed as an inhibitor of contraction in arterial graft vessels. The involvement of Rho kinase indicates that other vasoconstrictors and surgical stress can sensitize radial artery to vasopressin-induced contraction. Strategies targeting this pathway also have future potential.

Phenoxybenzamine treatment can lead to loss of endothelial cell viability.

Phenoxybenzamine, an irreversible alpha-adrenoceptor antagonist, is used as a topical treatment against catecholamine-induced contraction in radial artery bypass grafts. Published data suggest that a wide range of phenoxybenzamine doses may be equally effective. This study aimed to investigate whether lower doses of phenoxybenzamine would benefit grafts by better preserving endothelium. To this end human vascular endothelial cells were isolated from sections of radial artery or saphenous vein, and treated with phenoxybenzamine for 30 min. Cells were then washed free of drug and viability assayed using a resazurin-based toxicology assay or returned to culture for assay at 24 h. Phenoxybenzamine treatment showed a dose-dependent effect on cell viability over several clinically employed concentrations. Concentrations above 0.1 mM led to a loss of viability, which became more pronounced with time. The loss of viability was shown to be independent of the carrier used, as results were identical when phenoxybenzamine was dissolved in dimethylsulphoxide, which alone did not affect viability. Changes in pH alone were also not sufficient to affect viability. In conclusion, phenoxybenzamine treatment is likely to cause damage to graft endothelium if employed at concentrations above 0.1 mM (0.03 mg/ml). Phenoxybenzamine may be safely used at lower doses with no potential loss of endothelial cell viability.

Temperature changes stimulate contraction in the human radial artery and affect response to vasoconstrictors.

BACKGROUND: Radial artery conduits are increasingly used in coronary artery bypass grafting as an additional arterial graft to the internal thoracic artery. Their reactive nature remains a concern, often necessitating the routine use of topically applied vasodilators, such as glyceryl trinitrate, papaverine, phenoxybenzamine, or calcium channel antagonists, in theatre. During preparation prior to surgery and grafting, radial artery conduits are exposed to cooling and rewarming. We investigated how these temperature changes would affect radial artery contractility and how commonly used topical treatments might be used to prevent this. METHODS: Human radial artery was obtained excess to surgery and arterial sections used in organ bath tension experiments or for the culture of smooth muscle cells from medial explants. RESULTS: The radial artery responded to rapid cooling by the addition of 22 degrees C buffer with contraction. Gradual cooling, over a 20 to 30 minute period, reduced basal tension and the response to potassium chloride (KCl) and noradrenaline. Subsequent rewarming from 22 degrees C to 37 degrees C reestablished contraction at precooled levels and led to an elevation of the basal tension. Increases in tension measured in the radial artery were paralleled by increases in intracellular calcium in smooth muscle cells. Contraction induced by rapid temperature changes could be blocked by glyceryl trinitrate but not by phenoxybenzamine. Papaverine and calcium channel blockers had only limited activity. CONCLUSIONS: Temperature changes commonly encountered in theatre during the preparation of radial artery grafts are likely to cause contraction. If rapid temperature change cannot be avoided during graft preparation, then topically applied glyceryl trinitrate will block these responses.

Preoperative calculation of risk for prolonged intensive care unit stay following coronary artery bypass grafting.

OBJECTIVE: Patients who have prolonged stay in intensive care unit (ICU) are associated with adverse outcomes. Such patients have cost implications and can lead to shortage of ICU beds. We aimed to develop a preoperative risk prediction tool for prolonged ICU stay following coronary artery surgery (CABG). METHODS: 5,186 patients who underwent CABG between 1st April 1997 and 31st March 2002 were analysed in a development dataset. Logistic regression was used with forward stepwise technique to identify preoperative risk factors for prolonged ICU stay; defined as patients staying longer than 3 days on ICU. Variables examined included presentation history, co-morbidities, catheter and demographic details. The use of cardiopulmonary bypass (CPB) was also recorded. The prediction tool was tested on validation dataset (1197 CABG patients between 1st April 2003 and 31st March 2004). The area under the receiver operating characteristic (ROC) curve was calculated to assess the performance of the prediction tool. RESULTS: 475 (9.2%) patients had a prolonged ICU stay in the development dataset. Variables identified as risk factors for a prolonged ICU stay included renal dysfunction, unstable angina, poor ejection fraction, peripheral vascular disease, obesity, increasing age, smoking, diabetes, priority, hypercholesterolaemia, hypertension, and use of CPB. In the validation dataset, 8.1% patients had a prolonged ICU stay compared to 8.7% expected. The ROC curve for the development and validation datasets was 0.72 and 0.74 respectively. CONCLUSION: A prediction tool has been developed which is reliable and valid. The tool is being piloted at our institution to aid resource management.

Preoperative white blood cell count is independently associated with higher perioperative cardiac enzyme release and increased 1-year mortality after coronary artery bypass grafting.

BACKGROUND: Elevated preprocedural systemic markers of inflammation, including white blood cell count, have been associated with adverse clinical outcomes after percutaneous coronary intervention. The relationship between preoperative white blood cell count and clinical outcomes after coronary artery bypass grafting is less clear despite increasing evidence that neutrophils participate in reperfusion injury. We sought to determine the relationship between preoperative white blood cell count and in hospital major morbidity and 1-year survival after coronary artery bypass grafting. METHODS: We prospectively studied 3,024 consecutive isolated coronary artery bypass graft procedures. Preoperative white blood cell count was determined by automated counter, perioperative cardiac enzyme release by the creatine kinase-myocardial band isoenzyme, and all-cause mortality over the first postoperative year taken from a national death registry. Multivariate logistic regression and Cox proportional hazards analyses were performed. RESULTS: Preoperative white blood cell count offered as a continuous variable and as five predetermined groups was independently associated with cardiac enzyme release three or more times the upper limit of the reference range (adjusted odds ratio = 1.5 per 10 x 10(9)/L increase, 95% confidence interval: 1.2 to 2.0, p = 0.002) and higher 1-year mortality (adjusted hazard ratio = 1.6 per 10 x 10(9)/L increase, 95% confidence interval: 1.2 to 2.1, p < 0.001). CONCLUSIONS: Higher preoperative white blood cell count is independently associated with higher perioperative myonecrosis and 1-year mortality after coronary artery bypass grafting.

Left internal mammary artery use in patients with poor left ventricular ejection fraction: a propensity-matched analysis of mid-term survival.

We aimed to determine whether the use of left internal mammary artery (LIMA) to the left anterior descending (LAD) artery during coronary artery bypass grafting (CABG) confers an improved survival benefit to patients with an impaired preoperative left ventricular ejection fraction (LVEF). Between April 1997 and March 2004, 7198 consecutive patients underwent first time CABG to the LAD. There were 627 patients who had an LVEF <30% and of these, 548 patients (87.4%) received a LIMA graft, while 79 patients (12.6%) did not. A propensity-matched analysis was performed to provide matched cohorts for analysis of deaths occurring over time, which were described using Kaplan-Meier techniques. Propensity-matching produced two cohorts of 77 patients with or without the use of LIMA. Patient characteristics were reasonably matched between the groups. Forty-six (29.9%) deaths occurred in the propensity-matched groups. Freedom from death in patients with LIMA used at 4-years was 77.1%, compared with 60.7% for the patients with no LIMA used (P=0.026). The use of the LIMA as a bypass conduit is not contraindicated in patients with a poor preoperative LVEF. The usage of LIMA markedly improves survival.

Anomalous course of the right coronary artery in the right atrial wall: a word of caution.

We report a case of anomalous course of the right coronary artery in the wall of right atrium which was encountered during coronary artery bypass surgery. As the stenotic lesion in the vessel was proximal, the large posterior descending branch of the right coronary was grafted. Such an anomalous course of the right coronary artery has not been previously described in the literature and lack of knowledge of such an abnormal course may result in inadvertant damage during cannulation of the inferior vena cava or coronary sinus.

Improving mortality of coronary surgery over first four years of independent practice: retrospective examination of prospectively collected data from 15 surgeons.

OBJECTIVE: To study the "learning curve" associated with independent practice in coronary artery surgery. DESIGN: Retrospective analysis of prospectively collected data. SETTING: All NHS centres in north west England that carry out cardiac surgery in adults. PARTICIPANTS: 18 913 patients undergoing coronary artery surgery for the first time between April 1997 and March 2003, 5678 of whom were operated on by 15 surgeons in the first four years after their consultant appointment. MAIN OUTCOME MEASURES: Observed and predicted mortality (EuroSCORE) for surgeons in their first, second, third, and fourth years after appointment as a consultant compared with figures for established surgeons. RESULTS: Overall mortality decreased over the six years of study (P = 0.01). Of the patients operated on by established surgeons or newly appointed consultants, 265/13,235 (2.0%) and 109/5678 (1.9%), respectively, died (P = 0.71). There was a progressive decrease in observed mortality with time after appointment as a consultant from 2.2% in the first year to 1.2% in the fourth year (P = 0.049). This result remained significant after adjustment for time and case mix (P = 0.019). CONCLUSIONS: Mortality in patients operated on by newly appointed consultant surgeons is similar to mortality in patients operated on by established surgeons. There are significant decreases in crude and risk adjusted mortality in the four years after appointment. These findings should influence the nature of practice in newly appointed surgeons.

Is off-pump coronary surgery justified in EuroSCORE high-risk cases? A propensity score analysis.

We aimed to quantify the effect of avoiding cardiopulmonary bypass on outcomes in high-risk patients. Of the 2079 consecutive CABG's performed by three surgeons between April 1997 and September 2002, 389 were classified as high-risk according to the European System for Cardiac Operative Risk Evaluation (EuroSCORE) risk stratification, with a score of >5. The off-pump group had 196 patients and the on-pump group had 193 patients. Multivariate logistic regression was used to assess the effect of off-pump on in-hospital outcomes, while adjusting for treatment selection bias with a propensity score. The incidence of hypertension, hypercholesterolaemia, and renal dysfunction were higher in the off-pump group. The median EuroSCORE for off-pump patients was 7 (6-8), while for the on-pump patients was 7 (6-8; P=0.31). After adjusting for the propensity score, off-pump patients were less likely to have stroke (OR 0.17; P=0.041), renal failure (OR 0.35; P=0.029), blood transfusion (OR 0.12; P<0.001), prolonged mechanical ventilation (OR 0.36; P=0.021), and inotrope support (OR 0.35; P<0.001). Off-pump patients also had significantly shorter post-operative hospital stays. There was no significant difference between off-pump and on-pump patients in terms of in-hospital and mid-term mortality. Off-pump CABG is justified in EuroSCORE high-risk cases.

Endothelin receptors in cultured and native human radial artery smooth muscle.

In human vascular smooth muscle cells endothelin-1, acting at both endothelin A and endothelin B receptors, has been demonstrated to be both a potent vasoconstrictor and mitogen. Our aim was to study the functional expression of endothelin receptors in human radial artery smooth muscle using both native tissue and cultured cells (RASMCs). Radial artery smooth muscle cells were cultured from arterial explants and loaded with the calcium fluorescent dye fura-2. Cells responded to endothelin-1 and a variety of other vasoconstrictors with rises in cytoplasmic calcium ([Ca2+]c). Arterial rings responded to endothelin-1 with an increase in tension. The response of both cells and arterial rings to endothelin-1 was characterized using the selective endothelin A receptor antagonist BQ123 and the endothelin B receptor antagonist BQ788. The RASMCs were found to express [Ca2+]c responses consistent with the expression of only the endothelin A receptor. Endothelin-1-mediated vasoconstriction in radial artery rings was unaffected by BQ788 but was completely blocked by BQ123. Using the selective radioligands [125I]-PD151242 and [125I]-BQ3020 and a combination of in vitro receptor autoradiography and isolated cell preparations, endothelin A receptors were confirmed to be present on RASMCs and on arterial sections, whereas endothelin B binding was barely detectable on native smooth muscle and on RASMCs.