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1.
Front Cardiovasc Med ; 10: 1239153, 2023.
Article in English | MEDLINE | ID: mdl-38107265

ABSTRACT

Background: Open abdominal aortic surgery carries many potential complications, with cardiac adverse events being the most significant concern. The Vascular Study Group Cardiac Risk Index (VSG-CRI) is a commonly used tool for predicting severe cardiac complications and guiding clinical decision-making. However, despite the potential prognostic significance of left ventricular wall motion abnormalities (LVWMAs) and reduced LV ejection fraction (LVEF) for adverse outcomes, the VSG-CRI model has not accounted for them. Hence, the main objective of this study was to analyze the added value of LV wall motion on the discriminatory power of the modified VSG-CRI in predicting major postoperative cardiac complications. Methods: A prospective study was conducted involving 271 patients who underwent elective abdominal aortic surgery between 2019 and 2021. VSG-CRI scores were calculated, and preoperative transthoracic echocardiography was conducted for all patients. Subsequently, a modified version of the VSG-CRI, accounting for reduced LVEF and LVWMAs, was developed and incorporated into the dataset. The postoperative incidence of the composite endpoint of major adverse cardiac events (MACEs), including myocardial infarction, clinically relevant arrhythmias treated with medicaments or by cardioversion, or congestive heart failure, was assessed at discharge from the index hospitalization, with adjudicators blinded to events. The predictive accuracy of both the original and modified VSG-CRI was assessed using C-Statistics. Results: In total, 61 patients (22.5%) experienced MACEs. Among these patients, a significantly higher proportion had preoperative LVWMAs compared to those without (62.3% vs. 32.9%, p < 0.001). Multivariable regression analysis revealed the VSG-CRI [odds ratio (OR) 1.46, 95% confidence interval (CI) 1.21-1.77; p < 0.001] and LVWMA (OR 2.76; 95% CI 1.46-5.23; p = 0.002) as independent predictors of MACEs. Additionally, the modified VSG-CRI model demonstrated superior predictability compared to the baseline VSG-CRI model, suggesting an improved predictive performance for anticipating MACEs following abdominal aortic surgery [area under the curve (AUC) 0.74; 95% CI 0.68-0.81 vs. AUC 0.70; 95% CI 0.63-0.77; respectively]. Conclusion: The findings of this study suggest that incorporating preoperative echocardiography can enhance the predictive accuracy of the VSG-CRI for predicting MACEs after open abdominal aortic surgery. Before its implementation in clinical settings, external validation is necessary to confirm the generalizability of this newly developed predictive model across different populations.

2.
Antioxidants (Basel) ; 10(12)2021 Nov 29.
Article in English | MEDLINE | ID: mdl-34943013

ABSTRACT

Remote ischaemic preconditioning (RIPC) is a medical procedure that consists of repeated brief periods of transient ischaemia and reperfusion of distant organs (limbs) with the ability to provide internal organ protection from ischaemia. Even though RIPC has been successfully applied in patients with myocardial infarction during coronary revascularization (surgery/percutaneous angioplasty), the underlying molecular mechanisms are yet to be clarified. Thus, our study aimed to determine the role of nitric oxide synthase (NOS) isoforms in RIPC-induced protection (3 × 5 min of forearm ischaemia with 5 min of reperfusion) of arterial graft in patients undergoing urgent coronary artery bypass grafting (CABG). We examined RIPC effects on specific expression and immunolocalization of three NOS isoforms - endothelial (eNOS), inducible (iNOS) and neuronal (nNOS) in patients' internal thoracic artery (ITA) used as a graft. We found that the application of RIPC protocol leads to an increased protein expression of eNOS, which was further confirmed with strong eNOS immunopositivity, especially in the endothelium and smooth muscle cells of ITA. The same analysis of two other NOS isoforms, iNOS and nNOS, showed no significant differences between patients undergoing CABG with or without RIPC. Our results demonstrate RIPC-induced upregulation of eNOS in human ITA, pointing to its significance in achieving protective phenotype on a systemic level with important implications for graft patency.

3.
N Engl J Med ; 380(13): 1214-1225, 2019 03 28.
Article in English | MEDLINE | ID: mdl-30888743

ABSTRACT

BACKGROUND: Volatile (inhaled) anesthetic agents have cardioprotective effects, which might improve clinical outcomes in patients undergoing coronary-artery bypass grafting (CABG). METHODS: We conducted a pragmatic, multicenter, single-blind, controlled trial at 36 centers in 13 countries. Patients scheduled to undergo elective CABG were randomly assigned to an intraoperative anesthetic regimen that included a volatile anesthetic (desflurane, isoflurane, or sevoflurane) or to total intravenous anesthesia. The primary outcome was death from any cause at 1 year. RESULTS: A total of 5400 patients were randomly assigned: 2709 to the volatile anesthetics group and 2691 to the total intravenous anesthesia group. On-pump CABG was performed in 64% of patients, with a mean duration of cardiopulmonary bypass of 79 minutes. The two groups were similar with respect to demographic and clinical characteristics at baseline, the duration of cardiopulmonary bypass, and the number of grafts. At the time of the second interim analysis, the data and safety monitoring board advised that the trial should be stopped for futility. No significant difference between the groups with respect to deaths from any cause was seen at 1 year (2.8% in the volatile anesthetics group and 3.0% in the total intravenous anesthesia group; relative risk, 0.94; 95% confidence interval [CI], 0.69 to 1.29; P = 0.71), with data available for 5353 patients (99.1%), or at 30 days (1.4% and 1.3%, respectively; relative risk, 1.11; 95% CI, 0.70 to 1.76), with data available for 5398 patients (99.9%). There were no significant differences between the groups in any of the secondary outcomes or in the incidence of prespecified adverse events, including myocardial infarction. CONCLUSIONS: Among patients undergoing elective CABG, anesthesia with a volatile agent did not result in significantly fewer deaths at 1 year than total intravenous anesthesia. (Funded by the Italian Ministry of Health; MYRIAD ClinicalTrials.gov number, NCT02105610.).


Subject(s)
Anesthesia, Intravenous , Anesthetics, General/pharmacology , Coronary Artery Bypass , Coronary Artery Disease/surgery , Administration, Inhalation , Aged , Anesthesia, General , Anesthetics, Intravenous , Coronary Artery Disease/mortality , Coronary Artery Disease/physiopathology , Elective Surgical Procedures , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Mortality , Single-Blind Method , Stroke Volume
4.
N. Engl. j. med ; 380(13): 1214-1225, Mar. 2019. gráfico, tabela
Article in English | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1024163

ABSTRACT

BACKGROUND: Volatile (inhaled) anesthetic agents have cardioprotective effects, which might improve clinical outcomes in patients undergoing coronary-artery bypass grafting (CABG). METHODS: We conducted a pragmatic, multicenter, single-blind, controlled trial at 36 centers in 13 countries. Patients scheduled to undergo elective CABG were randomly assigned to an intraoperative anesthetic regimen that included a volatile anesthetic (desflurane, isoflurane, or sevoflurane) or to total intravenous anesthesia. The primary outcome was death from any cause at 1 year. RESULTS: A total of 5400 patients were randomly assigned: 2709 to the volatile anesthetics group and 2691 to the total intravenous anesthesia group. On-pump CABG was performed in 64% of patients, with a mean duration of cardiopulmonary bypass of 79 minutes. The two groups were similar with respect to demographic and clinical characteristics at baseline, the duration of cardiopulmonary bypass, and the number of grafts. At the time of the second interim analysis, the data and safety monitoring board advised that the trial should be stopped for futility. No significant difference between the groups with respect to deaths from any cause was seen at 1 year (2.8% in the volatile anesthetics group and 3.0% in the total intravenous anesthesia group; relative risk, 0.94; 95% confidence interval [CI], 0.69 to 1.29; P = 0.71), with data available for 5353 patients (99.1%), or at 30 days (1.4% and 1.3%, respectively; relative risk, 1.11; 95% CI, 0.70 to 1.76), with data available for 5398 patients (99.9%). There were no significant differences between the groups in any of the secondary outcomes or in the incidence of prespecified adverse events, including myocardial infarction. CONCLUSIONS: Among patients undergoing elective CABG, anesthesia with a volatile agent did not result in significantly fewer deaths at 1 year than total intravenous anesthesia. (Funded by the Italian Ministry of Health; MYRIAD ClinicalTrials.gov number, NCT02105610.). (AU)


Subject(s)
Humans , Male , Female , Middle Aged , Coronary Artery Bypass , Anesthetics, Inhalation , Anesthesia, General , Anesthesia, Intravenous
5.
J Cardiothorac Vasc Anesth ; 30(5): 1386-95, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27499346

ABSTRACT

OBJECTIVES: Democracy-based medicine is a combination of evidence-based medicine (systematic review), expert assessment, and worldwide voting by physicians to express their opinions and self-reported practice via the Internet. The authors applied democracy-based medicine to key trials in critical care medicine. DESIGN AND SETTING: A systematic review of literature followed by web-based voting on findings of a consensus conference. PARTICIPANTS: A total of 555 clinicians from 61 countries. INTERVENTIONS: The authors performed a systematic literature review (via searching MEDLINE/PubMed, Scopus, and Embase) and selected all multicenter randomized clinical trials in critical care that reported a significant effect on survival and were endorsed by expert clinicians. Then they solicited voting and self-reported practice on such evidence via an interactive Internet questionnaire. Relationships among trial sample size, design, and respondents' agreement were investigated. The gap between agreement and use/avoidance and the influence of country origin on physicians' approach to interventions also were investigated. MEASUREMENTS AND MAIN RESULTS: According to 24 multicenter randomized controlled trials, 15 interventions affecting mortality were identified. Wide variabilities in both the level of agreement and reported practice among different interventions and countries were found. Moreover, agreement and reported practice often did not coincide. Finally, a positive correlation among agreement, trial sample size, and number of included centers was found. On the contrary, trial design did not influence clinicians' agreement. CONCLUSIONS: Physicians' clinical practice and agreement with the literature vary among different interventions and countries. The role of these interventions in affecting survival should be further investigated to reduce both the gap between evidence and clinical practice and transnational differences.


Subject(s)
Critical Care/methods , Evidence-Based Medicine/methods , Hospital Mortality , Internationality , Multicenter Studies as Topic/statistics & numerical data , Randomized Controlled Trials as Topic/statistics & numerical data , Critical Illness , Humans , Physicians
7.
Angiology ; 67(10): 951-960, 2016 11.
Article in English | MEDLINE | ID: mdl-26843542

ABSTRACT

Copeptin is a sensitive and more stable surrogate marker for arginine vasopressin. In this study, we evaluated copeptin levels in carotid endarterectomy (CEA) patients, perioperatively, to determine whether copeptin levels can be related to carotid artery cross clamping (CC) time and to postoperative neurological outcomes. Copeptin, interleukin 6, C-reactive protein, cortisol, and brain natriuretic peptide were measured preoperatively (T1) and 3 hours postoperatively (T3) as well as intraoperatively (T2). We recruited 77 patients. Values of copeptin rose gradually over the observed times: T1 = 7.9 (6.4-9.6), T2 = 12.6 (9.3-16.8), and T3 = 72.3 (49.1-111.2) pmol/L. There was a significant difference for repeated measurement ( P = .000, P = .000, and P = .000). Duration of carotid artery CC during CEA does not affect postoperative copeptin level (CC ≤ 13 minutes: 106.8 ± 93.6 pmol/L, CC > 13 minutes: 96.7 ± 89.1 pmol/L; P = .634). Preoperative copeptin level was significantly higher in patients with ulcerated plaque morphology. Activation of the stress axis in patients undergoing CEA results in copeptin elevation. Duration of CC during CEA does not affect postoperative copeptin levels.


Subject(s)
Anesthesia, General , Brain Ischemia/blood , Endarterectomy, Carotid , Glycopeptides/blood , Operative Time , Surgical Instruments , Aged , Arginine Vasopressin/blood , Carotid Stenosis/blood , Carotid Stenosis/surgery , Female , Humans , Male , Middle Aged , Postoperative Complications/blood , Prognosis , Prospective Studies , Risk Factors , Statistics as Topic
8.
Srp Arh Celok Lek ; 143(7-8): 464-6, 2015.
Article in English | MEDLINE | ID: mdl-26506759

ABSTRACT

INTRODUCTION: Hybrid procedures represent staged or simultaneous endovascular and open surgical techniques in the treatment of complex pathologies of the thoracic and abdominal aorta. We are presenting a patient with previous abdominal aortic surgery in whom hybrid vascular procedure for descending aorta and left subclavian artery aneurysm was performed. CASE OUTLINE: A 63-year-old female patient was admitted for computed tomography angiography. Descending aorta aneurysm (7.6 cm) as well as aneurysm of the left subclavian artery (LSA) was noted. Eight years ago she underwent abdominal aortic aneurysm resection and aortoiliac bypass. Standard TEVAR (thoracic endovascular aortic repair) procedure couldn't be done due to small dimensions of previous "Y" graft (12x6 mm), so first we did LSA transposition and after three days hybrid procedure. After "Y" graft exposure, anastomosis between the corps of "Y" graft and tubular graft 10 mm was created and through this conduit thoracic stent-graft was placed followed by complete "Y"graft replacement. After 6 months angiography showed regular postoperative findings. CONCLUSION: Combined surgical and endovascular procedures in thoracic aorta pathology treatment could be useful solutions with favorable outcome.


Subject(s)
Aortic Aneurysm, Thoracic/surgery , Aortic Dissection/surgery , Endovascular Procedures/methods , Subclavian Artery/surgery , Aortic Dissection/diagnostic imaging , Aorta, Abdominal/surgery , Aortic Aneurysm, Thoracic/diagnostic imaging , Blood Vessel Prosthesis Implantation/methods , Female , Humans , Middle Aged , Subclavian Artery/diagnostic imaging , Tomography, X-Ray Computed
9.
J Pharmacol Sci ; 128(2): 59-64, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25850381

ABSTRACT

As we previously demonstrated the role of different K(+) channels in the action of nicorandil on human saphenous vein (HSV) and human internal mammary artery (HIMA), this study aimed to analyse the contribution of the cGMP pathway in nicorandil-induced vasorelaxation and to determine the involvement of cGMP in the K(+) channel-activating effect of nicorandil. An inhibitor of soluble guanylate cyclase (GC), ODQ, significantly inhibited nicorandil-induced relaxation, while ODQ plus glibenclamide, a selective ATP-sensitive K(+) (KATP) channel inhibitor, produced a further inhibition of both vessels. In HSV, ODQ in combination with 4-aminopyridine, a blocker of voltage-gated K(+) (KV) channels, did not modify the concentration-response to nicorandil compared with ODQ, whereas in HIMA, ODQ plus iberiotoxin, a selective blocker of large-conductance Ca(2+)-activated K(+) (BKCa) channels, produced greater inhibition than ODQ alone. We showed that the cGMP pathway plays a significant role in the vasorelaxant effect of nicorandil on HSV and HIMA. It seems that nicorandil directly opens KATP channels in both vessels and BKCa channels in HIMA, although it is possible that stimulation of GC contributes to KATP channels activation in HIMA. Contrary, the activation of KV channels in HSV is probably due to GC activation and increased levels of cGMP.


Subject(s)
Cyclic GMP/physiology , Mammary Arteries/drug effects , Nicorandil/pharmacology , Potassium Channels/metabolism , Saphenous Vein/drug effects , Signal Transduction/drug effects , Signal Transduction/physiology , Vasodilation/drug effects , Vasodilator Agents/pharmacology , Aged , Coronary Artery Bypass , Guanylate Cyclase/physiology , Humans , In Vitro Techniques , KATP Channels/metabolism , Male , Middle Aged , Potassium Channels, Calcium-Activated , Potassium Channels, Voltage-Gated
12.
Med Pregl ; 66(1-2): 64-9, 2013.
Article in English | MEDLINE | ID: mdl-23534303

ABSTRACT

INTRODUCTION: Patients on dialysis for end-stage renal failure are subjected to cardiac surgery with increasing frequency. End-stage renal failure is known to be an important risk factor for complications of cardiac operations performed with cardiopulmonary bypass. The aim of this study was to determine the impact of preoperative clinical status and operative variables on perioperative morbidity and mortality in hemodialysis-dependent patients subjected to a cardiac surgery. MATERIAL AND METHODS: The following operative variables were examined: urgency, type and duration of surgery and duration of extracorporeal circulation. The study is a retrospective analysis of consecutive patients with end-stage renal failure dependent on maintenance hemodialysis who underwent cardiac surgery during four years. RESULTS: The study included 46 patients. Operations performed included isolated coronary artery bypass grafting (CABG, n = 24), valve surgery alone (n = 6), and combined valve surgery or coronary artery bypass grafting and valve surgery (n = 16). The perioperative mortality rate was 13% with four fatal outcomes in patients who had undergone combined cardiac surgery. We found age > 70 years, preoperative New York Heart Association class IV, preoperative anemia, combined surgery and emergent surgery to be associated with a higher relative risk for perioperative death. CONCLUSION: Patients on dialysis have an increased morbidity and mortality following cardiac surgery; however, we believe that end-stage renal failure should not be regarded as a contraindication to cardiac surgery or cardiopulmonary bypass.


Subject(s)
Cardiac Surgical Procedures , Kidney Failure, Chronic/therapy , Renal Dialysis , Adult , Aged , Cardiac Surgical Procedures/mortality , Female , Humans , Male , Middle Aged , Postoperative Complications , Risk Factors
14.
Med Arch ; 66(5): 340-3, 2012.
Article in English | MEDLINE | ID: mdl-23097975

ABSTRACT

Use of thoracic epidurals is widespread for intraoperative and postoperative analgesia. Thoracic epidural anaesthesia (TEA) reduces sympathetic activity and thereby influences perioperative function of vital organ systems. A results of recent studies suggest that TEA decreases postoperative morbidity and mortality. There is better pain control with TEA in a wide range of surgical procedures. Use of TEA is associated with the risk of harm, but also the other methods used to control perioperative pain and stress response carry specific risks. Timely diagnosis and treatment of spinal compression or infection are crucial to ensure patient safety with TEA. The benefits of TEA outweigh the risks with respect to the perioperative outcome and organ protection, if basic guidelines are followed.


Subject(s)
Anesthesia, Epidural , Anesthesia, Epidural/adverse effects , Blood Coagulation/drug effects , Cardiovascular System/drug effects , Cardiovascular System/physiopathology , Hematoma, Epidural, Cranial/etiology , Hematoma, Epidural, Cranial/prevention & control , Humans , Intraoperative Period , Pain, Postoperative/therapy , Postoperative Complications , Respiratory System/drug effects , Respiratory System/physiopathology
15.
Cell Physiol Biochem ; 29(1-2): 131-42, 2012.
Article in English | MEDLINE | ID: mdl-22415082

ABSTRACT

BACKGROUND/AIMS: Study elucidates and compares the mitochondrial bioenergetic-related molecular basis of sevoflurane and propofol cardioprotection during aortic valve replacement surgery due to aortic valve stenosis. METHODS: Twenty-two patients were prospectively randomized in two groups regarding the anesthetic regime: sevoflurane and propofol. Hemodynamic parameters, biomarkers of cardiac injury and brain natriuretic peptide (BNP) were measured preoperatively and postoperatively. In tissue samples, taken from the interventricular septum, key mitochondrial molecules were determined by Western blot, real time PCR, as well as confocal microscopy and immunohisto- and immunocyto-chemical analysis. RESULTS: The protein levels of cytochrome c oxidase and ATP synthase were higher in sevoflurane than in propofol group. Nevertheless, cytochrome c protein content was higher in propofol than sevoflurane receiving patients. Propofol group also showed higher protein level of connexin 43 (Cx43) than sevoflurane group. Besides, immunogold analysis showed its mitochondrial localization. The mRNA level of mtDNA and uncoupling protein (UCP2) were higher in propofol than sevoflurane patients, as well. On the other hand, there were no significant differences between groups in hemodynamic assessment, intensive care unit length of stay, troponin I and BNP level. CONCLUSIONS: Our data indicate that sevoflurane and propofol lead to cardiac protection via different mitochondrially related molecular mechanisms. It appears that sevoflurane acts regulating cytochrome c oxidase and ATP synthase, while the effects of propofol occur through regulation of cytochrome c, Cx43, mtDNA transcription and UCP2.


Subject(s)
Anesthetics/therapeutic use , Aortic Valve Stenosis/surgery , Aortic Valve/transplantation , Cardiopulmonary Bypass , Methyl Ethers/therapeutic use , Mitochondria/metabolism , Propofol/therapeutic use , ATP Synthetase Complexes/genetics , ATP Synthetase Complexes/metabolism , Aged , Aortic Valve Stenosis/drug therapy , Aortic Valve Stenosis/pathology , Connexin 43/genetics , Connexin 43/metabolism , Cytochromes c/genetics , Cytochromes c/metabolism , DNA, Mitochondrial/genetics , DNA, Mitochondrial/metabolism , Female , Hemodynamics , Humans , Ion Channels/genetics , Ion Channels/metabolism , Male , Middle Aged , Mitochondria/drug effects , Mitochondrial Proteins/genetics , Mitochondrial Proteins/metabolism , Natriuretic Peptide, Brain/genetics , Natriuretic Peptide, Brain/metabolism , Prospective Studies , Sevoflurane , Troponin I/genetics , Troponin I/metabolism , Uncoupling Protein 2
18.
Eur J Cardiothorac Surg ; 41(5): 1129-31, 2012 May.
Article in English | MEDLINE | ID: mdl-22219486

ABSTRACT

Mitral valve replacement (MVR) in the presence of the extensive calcification of the mitral annulus is a technical challenge. The heavily calcified annulus can cause great difficulty in the insertion of a prosthetic valve and periprosthetic leakage later on. Vigorous annular decalcification may cause circumflex coronary artery injury, atrioventricular rupture and thromboembolic events. We herein describe a surgical technique for MVR in such cases while focusing on partial decalcification of the posterior mitral annulus and its reinforcement and buttressing with the transferred anterior mitral leaflet (AML). At the same time, the transferred AML supports the posterior annular region and maintains ventricular-annular continuity, thus preserving the left ventricular function.


Subject(s)
Calcinosis/surgery , Heart Valve Diseases/surgery , Heart Valve Prosthesis Implantation/methods , Mitral Valve/surgery , Decalcification Technique/methods , Heart Valve Prosthesis , Humans , Suture Techniques
19.
Basic Clin Pharmacol Toxicol ; 111(1): 24-30, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22225832

ABSTRACT

The ATP-sensitive K(+) channels opener (K(ATP)CO), P1075 [N-cyano-N'-(1,1-dimethylpropyl)-N″-3-pyridylguanidine], has been shown to cause relaxation of various isolated animal and human blood vessels by opening of vascular smooth muscle ATP-sensitive K(+) (K(ATP)) channels. In addition to the well-known effect on the opening of K(ATP) channels, it has been reported that vasorelaxation induced by some of the K(ATP)COs includes some other K(+) channel subtypes. Given that there is still no information on other types of K(+) channels possibly involved in the mechanism of relaxation induced by P1075, this study was designed to examine the effects of P1075 on the rat renal artery with endothelium and with denuded endothelium and to define the contribution of different K(+) channel subtypes in the P1075 action on this blood vessel. Our results show that P1075 induced a concentration-dependent relaxation of rat renal artery rings pre-contracted by phenylephrine. Glibenclamide, a selective K(ATP) channels inhibitor, partly antagonized the relaxation of rat renal artery induced by P1075. Tetraethylammonium (TEA), a non-selective inhibitor of Ca(2+)-activated K(+) channels, as well as iberiotoxin, a most selective blocker of large-conductance Ca(2+) -activated K(+) (BK(Ca)) channels, did not abolish the effect of P1075 on rat renal artery. In contrast, a non-selective blocker of voltage-gated K(+) (K(V)) channels, 4-aminopyridine (4-AP), as well as margatoxin, a potent inhibitor of K(V)1.3 channels, caused partial inhibition of the P1075-induced relaxation of rat renal artery. In addition, in this study, P1075 relaxed contractions induced by 20 mM K(+) , but had no effect on contractions induced by 80 mM K(+). Our results showed that P1075 induced strong endothelium-independent relaxation of rat renal artery. It seems that K(ATP), 4-AP- and margatoxin-sensitive K(+) channels located in vascular smooth muscle mediated the relaxation of rat renal artery induced by P1075.


Subject(s)
Guanidines/pharmacology , Potassium Channels/drug effects , Pyridines/pharmacology , Renal Artery/drug effects , Vasodilation/drug effects , Vasodilator Agents/pharmacology , 4-Aminopyridine/pharmacology , Animals , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , Glyburide/pharmacology , Male , Muscle, Smooth, Vascular/drug effects , Phenylephrine/pharmacology , Potassium Channel Blockers/pharmacology , Potassium Channels/metabolism , Rats , Rats, Wistar , Renal Artery/metabolism , Scorpion Venoms/pharmacology , Tetraethylammonium/pharmacology
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