Relaxant and antiadrenergic effects of ranolazine in human saphenous vein.

OBJECTIVES: Ranolazine improves vascular function in animal models. We evaluate the effects of ranolazine on vascular function and adrenergic response in human saphenous vein. METHODS: Rings from 53 patients undergoing coronary artery bypass grafting were mounted in organ baths. Concentration-response curves to ranolazine were constructed in rings precontracted with phenylephrine, endothelin-1, vasopressin, KCl and the thromboxane A2 analogue U-46619. In rings precontracted with phenylephrine, relaxation to ranolazine was tested in the absence and presence of endothelial factors inhibitors, K+ channel blockers and verapamil. The effects of ranolazine on frequency-response and concentration-response curves to phenylephrine were performed in the absence and presence of endothelial factors inhibitors and K+ channel blockers. Endothelial nitric oxide synthase, α1 adrenergic receptor and large conductance Ca2+-activated K+ channel protein expressions were measured by Western blotting. RESULTS: Ranolazine (10-9-10-4 M) produced a concentration-dependent relaxation only in rings precontracted with phenylephrine that was reduced by endothelial denudation, NG-nitro-l-arginine methyl ester (10-4 M), charybdotoxin (10-7 M) and verapamil (10-6 M). Ranolazine diminished adrenergic contractions induced by electrical field stimulation (2-4 Hz) and phenylephrine (10-9-10-5 M) that were prevented by tetraethylammonium (10-3 M) and charybdotoxin (10-7 M). Ranolazine significantly decreased α1 adrenergic receptor and increased large conductance Ca2+-activated K+ channel protein expression in the saphenous vein. CONCLUSIONS: Ranolazine diminishes the adrenergic vasoconstriction, acting as α1 antagonist, and by increasing large conductance Ca2+-activated K+ channel involvement. The relaxant effects of ranolazine are partially mediated by endothelial nitric oxide, large conductance Ca2+-activated K+ channels and the blockade of voltage-dependent Ca2+ channels.

mRNA PGC-1α levels in blood samples reliably correlates with its myocardial expression: study in patients undergoing cardiac surgery.

OBJECTIVE: Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a transcriptional coactivator that has been proposed to play a protective role in mouse models of cardiac ischemia and heart failure, suggesting that PGC-1α could be relevant as a prognostic marker. Our previous studies showed that the estimation of peripheral mRNA PGC-1α expression was feasible and that its induction correlated with the extent of myocardial necrosis and left ventricular remodeling in patients with myocardial infarction. In this study, we sought to determine if the myocardial and peripheral expressions of PGC-1α are well correlated and to analyze the variability of PGC-1α expression depending on the prevalence of some metabolic disorders. METHODS: This was a cohort of 35 consecutive stable heart failure patients with severe aortic stenosis who underwent an elective aortic valve replacement surgery. mRNA PGC-1α expression was simultaneously determined from myocardial biopsy specimens and blood samples obtained during surgery by quantitative PCR, and a correlation between samples was made using the Kappa index. Patients were divided into two groups according to the detection of baseline expression levels of PGC-1α in blood samples, and comparisons between both groups were made by chi-square test or unpaired Student's t-test as appropriate. RESULTS: Based on myocardial biopsies, we found that mRNA PGC-1α expression in blood samples showed a statistically significant correlation with myocardial expression (Kappa index 0.66, p<0.001). The presence of higher systemic PGC-1α expression was associated with a greater expression of some target genes such as silent information regulator 2 homolog-1 (x-fold expression in blood samples: 4.43±5.22 vs. 1.09±0.14, p=0.044) and better antioxidant status in these patients (concentration of Trolox: 0.40±0.05 vs. 0.34±0.65, p=0.006). CONCLUSIONS: Most patients with higher peripheral expression also had increased myocardial expression, so we conclude that the non-invasive estimation of mRNA PGC-1α expression from blood samples provides a good approach of the constitutive status of the mitochondrial protection system regulated by PGC-1α and that this could be used as prognostic indicator in cardiovascular disease.

Is off-pump technique a safer procedure for coronary revascularization? A propensity score analysis of 20 years of experience.

OBJECTIVES: We aim to describe our experience in coronary artery bypass grafting (CABG) with or without cardiopulmonary bypass by comparing intraoperative and postoperative outcomes. METHODS: From January 1993 to June 2013, 3097 patients underwent consecutive emergency and scheduled CABG surgery. A total of 1770 patients underwent on-pump CABG (ONCABG) and 1327 off-pump CABG (OPCABG). A propensity score matching was performed to identify appropriate matched-pair patients; univariable and multivariable logistic regression analyses were performed to assess significant predictors of hospital and 30-day morbidity and mortality composite end-points. Morbidity composite end-point was defined as any renal, pulmonary, cardiovascular and neurological complication that occurred during hospital stay. We collected all-cause mortality data during the study period. RESULTS: We identified 1004 patients in each group. There were no significant differences in thirty day mortality, 2.8 vs 3.8%, in OPCABG and ONCABG, respectively (P = 0.21). Cardiovascular, neurological, respiratory and renal complications were more frequent in the ONCABG group: 13.9 vs 8.7% (P < 0.001), 3.9 vs 2.2% (P = 0.03), 13.5 vs 7.5% (P < 0.001), 7.1 vs 5.3% (P = 0.095), respectively. The long-term all-cause mortality rate was 12.3 vs 12.9% in the OPCABG versus ONCABG group (P = 0.42), respectively. In both uni- and multivariable analysis preoperative renal failure, chronic obstructive pulmonary disease and ONCABG were independent predictors of mortality and morbidity composite end-points. CONCLUSIONS: OPCABG is associated with less postoperative morbimortality and shorter hospital and intensive care unit length of stay. ONCABG resulted as an independent predictor of morbidity and mortality composite end-point. No statistically significant differences were observed in long-term all-cause mortality between groups.

Impact of increasing degrees of renal impairment on outcomes of coronary artery bypass grafting: the off-pump advantage.

OBJECTIVES: Increasing degrees of renal impairment are associated with higher rates of morbimortality after coronary artery bypass grafting (CABG). This incremental risk has not been well studied in off-pump procedures (OPCAB). We assessed its impact on OPCAB and on-pump CABG (ONCAB). METHODS: A total of 1769 patients undergoing primary CABG (January 1995 through June 2011) had complete data on glomerular filtration rate (eGFR). 930 patients had Stage 2 renal insufficiency, 330 Stage 3, 27 Stage 4 and 465 normal renal function (Stage 1). Seventeen patients with end-stage disease (Stage 5) were excluded. The OPCAB technique was selectively used in 350 high-risk patients. Preoperative variables and postoperative outcomes were compared among eGFR subgroups and between matched and unmatched OPCAB vs ONCAB groups. RESULTS: Stages 3-4 patients were older (P < 0.0001), with higher prevalence of diabetes (36.8, 35.0, 39.7 and 74.1%, P < 0.01, 1-4 eGFR groups) peripheral arteriopathy (6.0, 9.0, 15.8 and 29.6%, P < 0.0001) and lower left ventricular ejection fraction (LVEF) (GFR-LVEF correlation: Pearson: 0.12, P < 0.0001). On-pump GFR groups had increasingly higher in-hospital mortality (1.0, 1.2, 3.5 and 15.4%, P < 0.0001), but no differences were observed in OPCAB (5.5, 4.8, 5.4 and 7.1%, P = 0.97). Similar trends on in-hospital morbidity were observed in ONCAB vs OPCAB groups: low cardiac output (P < 0.01), pneumonia (P < 0.01) and stroke (P < 0.05). GFR only predicted mortality in ONCAB patients (odds ratio (OR): 0.96, 95% CI: 0.94-0.98; P < 0.01). Patients with higher eGFR stages had statistically more reduced long-term survival, and this pattern was similar in the three treatment groups, also including the OPCAB group, who had the lowest survival in patients with eGFR stage 4. CONCLUSIONS: Patients with low GFR (Stages 3-4) undergoing ONCAB were at increased risk of early morbimortality. In contrast, there were no significant differences in operative morbimortality among eGFR groups in OPCAB patients. This 'off-pump advantage' on early outcomes was not observed at the long-term follow-up.

Minimally invasive aortic valve surgery. A safe and useful technique beyond the cosmetic benefits.

INTRODUCTION AND OBJECTIVES: The aim of this study was to compare the in-hospital clinical outcomes of minimally invasive, isolated aortic valve replacement vs median sternotomy. METHODS: Between 2005 and 2012, 615 patients underwent aortic valve replacement at a single institution, 532 by a median sternotomy (E group) and 83 by a J-shaped ministernotomy (M group). RESULTS: No significant differences were found between the E and M groups in terms of age (69.27 [9.31] years vs 69.40 [10.24] years, respectively), logistic EuroSCORE (6.27 [2.91] vs 5.64 [2.17], respectively), size of implanted valve prosthesis (21.94 [2.04] mm vs 21.79 [2.01] mm, respectively), or the incidence of diabetes, hypercholesterolemia, high blood pressure, or chronic obstructive pulmonary disease. Mean cardiopulmonary bypass time was 102.90 (41.68) min for the E group vs 81.37 (25.41) min for the M group (P<.001). Mean cross-clamp time was 77.31 (29.20) min vs 63.45 (17.71) min for the S and M groups, respectively (P<.001). Mortality in the E group was 4.88% (26). There were no deaths in the M group (P<.05). The E group was associated with longer intensive care unit and hospital stays: 4.17 (5.23) days vs 3.22 (2.01) days (P=.045) and 9.58 (7.66) days vs 7.27 (3.83) days (P<.001), respectively. E group patients had more postoperative respiratory complications (42 [8%] vs 1 [1.2%]; P<.05). There were no differences when postoperative hemodynamic, neurologic, and renal complications, systemic infection, and wound infection were analyzed. CONCLUSIONS: In terms of morbidity, mortality, and operative times, outcomes after minimally invasive surgery for aortic valve replacement are at least comparable to those achieved with median sternotomy. The length of the hospital stay was reduced by minimally invasive surgery in our single-institution experience. The retrospective nature of this study warrants further randomized prospective trials to validate our results.

Resultados a corto y mediano plazo del tratamiento de la obstrucción al tracto de salida del ventrículo izquierdo mediante miectomía videoasistida / Video assisted myectomy for relief of left ventricular tract obstruction in patients with Obstructive Hypertrophic Cardiomyopathy

Objetivo: Describir nuestra experiencia y evaluar los resultados a corto y mediano plazo de la miecto-mía videoasistida en el tratamiento de la obstrucción del tracto de salida del ventrículo izquierdo (OTSVI) en pacientes con miocardiopatía hipertrófica. Materiales y métodos: 52 pacientes con edad media de 56,2 (rango 12 - 83) y Euroscore de riesgo de 4,1 +/- 1,92 con diagnóstico de OTSVI fueron intervenidos de manera consecutiva en un mismo centro mediante miectomía videoasistida. Se realizó seguimiento clínico y ecocardiográfico con controles al mes y al año del postoperatorio. Resultados: Entre las patologías asociadas encontramos 11 pacientes con valvulopatía aórtica, 2 con valvulopatía mitral, 3 con cardiopatía isquémica, 1 con aneurisma de aorta ascendente y 1 con foramen oval permeable resueltos en el mismo acto quirúrgico. La mortalidad hospitalaria global fue de 5,8 por ciento (3 pacientes). En el momento de la intervención, 8 (15,4 por ciento) se encontraban en clase funcional II de la NYHA, 42 (80,8 por ciento) en clase III y 2 (3,8 por ciento) en clase IV. El gradiente máximo subaórtico disminuyó de 80,7 mmHg +/- 29,43 en el preoperatorio a 19,0 mmHg +/- 15,57 (p<0,001) en el postoperatorio inmediato, manteniéndose en 14,6 mmHg +/- 8,88 al mes (p<0,001 en relación al preoperatorio) y al año en 13,9 mmHg +/- 7,69 (p<0,001 en relación al preoperatorio). Además, se registró una disminución del grosor del tabique interventricular en diástole de 19,4 mm +/- 3,78 en el preoperatorio a 12,9 mm +/- 2,35 (p<0,001) en el postoperatorio. Todos los pacientes se encontraban en clase funcional I-II al final del seguimiento. Conclusión: Los resultados demuestran que la miectomía videoasistida es un tratamiento seguro para la OTSVI con el que se obtienen resultados favorables a corto y mediano plazo, tanto en parámetros clínicos, como ecocardiográficos.

Aim: To report a clinical experience and to evaluate early and mid term results of video assisted myec-tomy for relief of left ventricular tract obstruction (LVOTO) in patients with Obstructive Hypertrophic Cardiomyopathy. Methods: 52 patients with Obstructive Car-diomyopathy and a mean age 56.2 years (12 - 83) carrying a Euro score risk of 4.1 +/- (SD 1.92), were consecutively operated on in a single center. Relief of LVOTO was performed with video assisted myec-tomy. Clinical and echocardiographic follow up to 1 year postoperatively was carried out. Results: Apart from the Obstructive Cardiomyo-pathy, 11 patients had aortic valve disease, 2 mitral valve disease, 3 ischemic heart disease, 1 an ascending aortic aneurysm and 1 a patent foramen ovale. All these lesions were surgically repaired in the same surgical act. In hospital mortality was 5.8 percent (3 patients). Pre-operatively 15.4 percent of patients were in NYHA Class II, 80.8 per cent in Class III and 3.8 percent in Class IV. After surgery peak sub aortic gradient decreased from 80.7+/-29.43mmHg to 19.0 +/- 15.57 (p<0.001). Corresponding values were 14.6 +/- 8.88 at 1month and 13.9 +/- 7.69 at 1 year post operatively. Interven-tricular septal thickness in diastole decreased from 19.4 +/- 3.78 mm to 12.9 +/- 2.35 mm after surgery (p<0.001). All patients were Class I or II at the end of follow up. Conclusion: Video assisted myectomy is safe and effective for relief of LVOTO in patients with hypertrophic cardiomyopathy. Good results are maintained one year after surgery.

Myocardial oxidative stress protection by sevoflurane vs. propofol: a randomised controlled study in patients undergoing off-pump coronary artery bypass graft surgery.

CONTEXT: Myocardial oxidative stress plays an essential role in the pathogenesis of ischaemia-reperfusion injury associated with coronary artery bypass grafting (CABG). Both propofol and volatile anaesthetics have been shown to reduce reactive oxygen species in experimental and clinical studies. MAIN OBJECTIVE: To compare the influence of sevoflurane and propofol on myocardial oxidative stress markers (F2-isoprostanes and nitrates/nitrites) in coronary sinus blood samples from patients undergoing off-pump CABG. DESIGN AND SETTING: Randomised controlled clinical study of patients scheduled for off-pump CABG in a tertiary academic university hospital from June 2007 to August 2009. Forty patients consented to enrolment and were assigned to receive either propofol or sevoflurane. INTERVENTIONS: Upon completion of the proximal anastomosis, a retroplegia cannula was inserted in the coronary sinus to obtain blood samples, according to the study protocol. MAIN OUTCOME MEASURES: Markers of lipoperoxidation (F2-isoprostanes) and nitrosative stress (nitrates/nitrites) were measured in coronary sinus blood samples at three time points: after the end of the proximal anastomosis (T1), after completion of all grafts (T2) and 15 min after revascularisation (T3). RESULTS: Of the 40 recruited patients, 38 fully completed the study. In the sevoflurane group (n = 20), concentrations of oxidative stress markers in the coronary sinus remained almost constant and were significantly lower than those in the propofol group (n = 18) at all time points. F2-isoprostanes concentrations were as follows at T1: sevoflurane group 37.2 ±â€Š27.5 pg ml vs. propofol group 170.7 ±â€Š30.9 pg ml [95% confidence interval (CI) 112.16-155.08, P < 0.0001); at T2: sevoflurane group 31.94 ±â€Š24.6 pg ml vs. propofol group 171.6 ±â€Š29.7 pg ml (95% CI 119.78-159.63, P < 0.0001); and at T3: sevoflurane group 23.8 ±â€Š13.0 pg ml vs. propofol group 43.6 ±â€Š31 pg ml (95% CI 2.87-36.63, P = 0.023). CONCLUSION: In patients undergoing off-pump CABG, sevoflurane showed better antioxidative properties than propofol.

A novel SDHD mutation associated with neck paraganglioma.

The aim of this study was to describe a previously unreported mutation in the SDHD gene, which has been linked to familial paraganglioma. Clinical data were collected from all members of the family, which had four siblings affected with paraganglioma. For the index patient, genomic DNA extraction from whole blood was performed using the High Pure PCR Template Preparation kit. The nucleotide sequence in the index patient revealed a deletion in the SDHD gene, c.165_169 + 14del. The loss of nucleotides in the DNA led to production of an anomalous protein. RNA analysis showed the absence of exon 2 in the sequence that corresponded to the mRNA from the index case. Genetic testing of this deletion was extended to the symptomatic and asymptomatic brothers and sisters of the index patient and other family members at risk. The deletion was detected in both symptomatic brothers, in accordance with their phenotype, but not in the asymptomatic sister. In the other asymptomatic brother (II.7) the deletion was detected and magnetic resonance angiography revealed the vascular characteristics of two tumors in both carotid bifurcations. Thus, we report a novel punctual mutation in the SDHD gene, which is related to familial paraganglioma: the deletion was c.165_169 + 14del.

Factors for development of late significant tricuspid regurgitation after mitral valve replacement: the impact of subvalvular preservation.

OBJECTIVE: Development of late significant tricuspid regurgitation (TR) after successful mitral valve replacement (MVR) is not infrequent. The impact of different aetiologies or diverse surgical procedures has not been adequately investigated. We studied the influence of subvalvular preservation techniques during MVR on the incidence of late TR. METHODS: A total of 801 patients with grade ≤ 2+/4+ preoperative TR underwent MVR without associated tricuspid procedures from January 1994 to August 2008. In 595 patients, only posterior mitral leaflet preservation was performed (group A). In the remaining 206 patients, both anterior and posterior leaflets were retained (group B). Postoperative development of significant TR was defined as a TR increase by more than one grade from preoperative or final TR grade ≥ 3+/4+ at follow-up. RESULTS: The global incidence of postoperative significant TR was 8.6%, with higher incidence in females (9.4% vs 6.7%, p=0.12), rheumatic disease (9.7% vs 6.5%, p=0.07), patients with previous AF (11.8% vs 3.8%, p<0.001) and, especially, in group A (10.8% vs 2.4%, p<0.001). The Maze procedure was protective in patients with AF (the incidence with and without associated Maze was 6.7% vs 13.2%, p=0.04). Preoperative left-atrial diameters were higher in patients with postoperative development of TR (56 ± 9 mm vs 51 ± 12 mm, p=0.01). Group A (p=0.04) and preoperative atrial fibrillation (p=0.001) were significant predictors of late postoperative TR. Late functional TR decreased free survival from chronic heart failure. CONCLUSIONS: Several clinical and operative factors are associated with the development of significant TR after MVR. Although early surgical intervention for TR may be recommended in selected patients, complete subvalvular preservation of the mitral valve and routine surgical ablation of atrial fibrillation can significantly reduce its incidence.

The folding leaflet: a simple method for neochordal repair.

We present a simple technique for facilitating accurate polytetrafluoroethylene chordal height adjustment in surgical repair of myxomatous mitral valve disease. This approach is based on the annulus as the reference level. The artificial chordae are first fixed to the corresponding papillary muscle. Each chordal pair is then attached to the free edge of the prolapsed leaflet, and subsequently, the leaflet edge is also attached to the adjacent annulus by temporary fixing sutures. As a result, the leaflet is gently folded. Finally, the polytetrafluoroethylene suture is knotted during proper apposition of the free edge of the leaflet to the annulus.

[Surgical treatment of renal tumours with venous extension]. / Tratamiento quirúrgico del tumor renal con extensión venosa.

OBJECTIVES: Renal carcinoma accounts for 3% of malignant urological tumors. The existence of tumor thrombus in the venous system is more infrequent, and, despite it was believed until recently its presence worsened the diagnosis of the disease, currently it is accepted that in the absence of metastatic or lymph node disease, surgery is the treatment of choice and potentially curative for these tumors. METHODS: Between June 2003 and November 2007 eight patients with renal disease and venous thrombus underwent surgery; two of them wereT3c and six T3b; in five of them surgery was carried out in association with the heart surgery team in our centre. Three of them underwent surgery with extracorporeal circulation. Mean patient age was 56 years. RESULTS: Tumor thrombus was grade I in one patient, grade II in 4 patients, grade III in one patient, and grade IV in two patients. In all patients with tumor grade > or = III, as well as two with grade II, surgery was performed in conjunction with the department of heart surgery. The operation with extracorporeal circulation, deep hypothermia, cardioplegia, and antegrade and retrograde brain perfusion was performed in grades III and IV. Midline incision was performed, with or without sternotomy, depending on the level of the thrombus. Hemorrhage was the most frequent perioperative complication. DISCUSSION: It is essential to know the exact level of the cephalic extreme of the tumor thrombus to design the proper surgical strategy; for that, we can use MRI, CT scan or ultrasound. Therefore, surgical approach, multidisciplinary cooperation and use of extracorporeal circulation will depend on such extension of the thrombus and concurrent factors of the patient. A good surgical strategy, as well as early surgery may avoid the use of venous filters preoperatively. CONCLUSIONS: Venous wall invasion seems to be related with a greater incidence of lymph node disease, but these patients are candidates to intention-to-cure radical surgery. Thrombus level is not a prognostic factor per se, but it should be taken into consideration for surgical planning. After radical surgery survival rates achieved are similar to those of tumors without venous thrombus.

Mitral valve replacement in rheumatic patients: effects of chordal preservation.

BACKGROUND: Subvalvular preservation is beneficial in patients undergoing mitral valve replacement, especially in degenerative mitral regurgitation. Its feasibility and benefit is less evident in rheumatic disease. Our aim was to study the impact of preservation techniques in rheumatic patients and determine risk factors for mortality. METHODS: Five hundred sixty-six rheumatic patients undergoing mitral valve replacement between 1996 and 2006 have been included. One hundred fifty-six patients had complete excision of the subvalvular apparatus (group 1), 248 had preservation of the posterior leaflet (group 2), and 162 had total chordal preservation (group 3). Echocardiography was performed preoperatively, at discharge, at 1 year, and at late follow-up. RESULTS: Reduction of ventricular volume was greater in groups 2 and 3, especially if previous mitral regurgitation or mixed disease were present. In mitral stenosis, valve resection caused postoperative increase of volume. Ventricular ejection and pulmonary hypertension had better outcome with valve preservation. Valve resection was associated with late mortality (hazard ratio, 2.64; p < 0.05), and complete chordal preservation was protective (hazard ratio, 0.31; p = 0.13). Actuarial survival (130 months) was better in group 3: 77.18% +/- 0.04%, 85.38% +/- 0.03%, and 93.22% +/- 0.02%, respectively (p < 0.01 group 1 versus group 3). Group 1 exhibited more low cardiac output syndrome (p < 0.01) and more patients in New York Heart Association functional class III and IV at last follow-up: 17.8% versus 3.9% and 2.0% (p < 0.001). CONCLUSIONS: Complete chordal preservation is possible in a large percentage of rheumatic patients. Greater decrease of ventricular volume is obtained for mitral regurgitation. In mitral stenosis, subvalvular preservation may avoid postoperative ventricular dilatation. Consequently, ventricular ejection, pulmonary hypertension, and clinical outcomes may improve with time.

Intraoperative cryoablation of atrial fibrillation with the old-fashioned cryode tips: a simple, effective, and inexpensive method.

Nowadays atrial fibrillation is usually treated simultaneously with cardiac procedures, and new cryo-systems have been developed for performing easier and faster intraoperative ablation. However, the old cryode designs can still be useful in surgical practice and represent a more cost-effective method. In this article we present a technique using old-fashioned cryodes for intraoperative treatment of atrial fibrillation and comment on its advantages and limitations.

Prosthesis - patient mismatch with latest generation supra-annular prostheses. The beginning of the end?

Most studies about prosthesis-patient mismatch (PPM) were conducted before the introduction of new high-performance prostheses. Nowadays, PPM could become unfrequent. Our aim was to study the impact of new prostheses on PPM in comparison with previous experience. Prosthetic Indexed Effective Orifice Area (EOAi) was estimated in two historical cohorts. Group A: 339 patients undergoing AVR from Mar 94-Nov 01. Group B: 404 operated on during the last three years when latest generation prostheses were implanted. Incidence, determinants of PPM and clinical results were studied. Moderate PPM (EOAi

Role of Ca2+-activated K+ channels on adrenergic responses of human saphenous vein.

BACKGROUND: We studied the participation of K(+) channels on the adrenergic responses in human saphenous veins as well as the intervention of dihydropyridine-sensitive Ca(2+) channels on modulation of adrenergic responses by K(+) channels blockade. METHODS: Saphenous vein rings were obtained from 40 patients undergoing coronary artery bypass surgery. The vein rings were suspended in organ bath chambers for isometric recording of tension. RESULTS: Iberiotoxin (10(-7) mol/L), an inhibitor of large conductance Ca(2+)-activated K(+) channels, and charybdotoxin (10(-7) mol/L), an inhibitor of both large and intermediate conductance Ca(2+)-activated K(+) channels, enhanced the contractions elicited by electrical field stimulation and produced a leftward shift of the concentration-response curve to norepinephrine. In contrast, the inhibitor of small conductance Ca(2+)-activated K(+) channels apamin (10(-6) mol/L) did not modify the contractile response to electrical field stimulation or norepinephrine. In the presence of the dihydropyridine Ca(2+)-channel blocker nifedipine (10(-6) mol/L), iberiotoxin and charybdotoxin failed to enhance the contractile responses to electrical field stimulation and norepinephrine. CONCLUSIONS: The results suggest that large conductance Ca(2+)-activated K(+) channels are activated by stimulation with norepinephrine to counteract the adrenergic-induced contractions of human saphenous vein. Thus, inhibition of these channels increases significantly the contraction, an effect that appears to be mediated by an increase in Ca(2+) entry through L-type voltage-dependent Ca(2+) channels.