Prediction value of EuroSCORE II in total arterial revascularization and its usage in the evaluation of postoperative complications: Single-center experience.

BACKGROUND: Total arterial revascularization is the most durable and technically the most demanding type of coronary artery bypass grafting procedure. It has proven long-term supremacy in comparison to conventional coronary artery bypass grafting. In our study, we investigated the reliability of EuroSCORE II as a predictor of intrahospital death. We showed its impact on adverse perioperative events. METHODS: In this nonrandomized prospective study, we analyzed 116 consecutive patients who underwent the total arterial revascularization procedure at our Institute from January 2011 until the present. For myocardial revascularization, the most suitable combinations with left internal mammary artery, right internal mammary artery, and radial artery grafts were used. Main fact in this research was intrahospital mortality value in comparison with the value predicted. RESULTS: There were 104 (89.7%) males and 12 (10.3%) females. Mean preoperative EuroSCORE II prediction value was 1.98% and postoperative we obtained 1.72%. Postoperative redo for bleeding was 6%. Positive correlation was proven between the EuoroSCORE II value and intensive care unit stay (0.452; p < 0.001). Among patients who received two internal mammary arteries, the highest EuroSCORE II was among those with presternal wound infection (p = 0.005). Patients with bilateral internal mammary arteries and diabetes showed that they have the highest values of EuroSCORE II and, at the same time, that they are extremely prone to wound problems. CONCLUSIONS: We achieved a lower intrahospital mortality level than it was predicted with preoperative EuroSCORE II value. This tool is a reliable method for preoperative death risk calculation in this group of patients.

Mechanisms underlying the vasorelaxant effect of hydrogen sulfide on human saphenous vein.

Hydrogen sulfide (H2 S) represents the third and the youngest member of the gaseous transmitters family. The dominant effect of H2 S on isolated vessels is vasodilation. As the mechanism of H2 S-induced relaxation in human vessels remains unclear, the present study aimed to investigate the effects of H2 S donor, sodium hydrosulfide (NaHS), on isolated human saphenous vein (HSV) and to determine the mechanism of action. Our results showed that NaHS (1 µM-3 mM) induced a concentration-dependent relaxation of endothelium-intact HSV rings pre-contracted by phenylephrine. Pre-treatment with L-NAME, ODQ and KT5823 significantly inhibited NaHS-induced relaxation, while indomethacin induced partial inhibition. Among K+ channel blockers, the combination of apamin and TRAM-34 significantly affected the relaxation produced by NaHS, while iberiotoxin and glibenclamide only reduced maximal relaxation of HSV. NaHS partially relaxed endothelium-intact rings pre-contracted by high K+ , as well as phenylephrine-contracted rings in the presence of nifedipine. Additionally, the incubation of HSV rings with NaHS increased NO production. These results demonstrate that NaHS produces the concentration- and endothelium-dependent relaxation of isolated HSV. Vasorelaxation to NaHS probably involves activation of NO/cGMP/PKG pathway and partially prostacyclin. In addition, different K+ channels subtypes, especially SKCa and IKCa , as well as BKCa and KATP channels in high concentrations of NaHS, probably participate in the NaHS-induced vasorelaxation.

Mechanisms of endothelium-dependent vasorelaxation induced by procyanidin B2 in venous bypass graft.

Cardioprotective abilities of procyanidins, might, at least in part, attribute to their vasodilator properties. The present study was undertaken to assess the vasorelaxant effect of procyanidin B2 on isolated human saphenous vein (HSV) and its underlying mechanisms. Procyanidin B2 relaxed phenylephrine-induced contraction of HSV rings in concentration-dependent manner. The relaxation was dependent on the presence of endothelium and was strongly affected by l-NAME, hydroxocobalamin or ODQ, the inhibitors of NO/cGMP pathway. Indomethacin significantly affected only the relaxation produced by the highest concentrations of procyanidin B2. Apamin and TRAM-34 combination, in the presence of l-NAME and indomethacin, did not additionally decreased procyanidin B2-induced relaxation. In the presence of K+ channel blockers, relaxation induced by procyanidin B2 was partially attenuated by 4-aminopyridine, significantly inhibited by glibenclamide and almost abolished by iberiotoxin. Procyanidin B2 also relaxed the contractions induced by phenylephrine or caffeine in Ca2+-free solution. Finally, nifedipine slightly, while thapsigargin strongly antagonized HSV relaxation. Our results indicate that procyanidin B2 induces endothelium-dependent relaxation of HSV, which results primarily from stimulation of NO production, as well K+ channels opening, especially BKCa, and partially KATP and KV. Regulation of the intracellular Ca2+ release and inhibition of Ca2+ influx probably contribute to procyanidin B2-induced relaxation.

The role of ministernotomy in aortic valve surgery-A prospective randomized study.

BACKGROUND AND AIMS: The purpose of this prospective randomized study was to compare the early and midterm outcomes of aortic valve replacement (AVR) through upper ministernotomy with conventional AVR through median sternotomy. METHODS: One hundred patients undergoing elective AVR were randomized into two groups: the M group (upper ministernotomy group, n = 50) and the C group (conventional sternotomy group, n = 50). The operative data, major adverse outcomes, and postoperative variables were compared between the two groups of patients. A cross-sectional follow-up was performed 24.9 ± 5.8 months after surgery. RESULTS: The aortic cross-clamp time and cardiopulmonary bypass time were significantly longer in the M group. Similar incidences of major cardiac, neurologic and renal complications were recorded in both groups. Two patients (4%) in the C group developed wound infections. The length of ICU stay was similar in both groups. The patients in the M group had a shorter hospital stay compared with the patients in the C group (7.6 ± 2 days vs 9.3 ± 4.8 days; P = 0.022). Follow-up revealed that the time period needed to reach full recovery was significantly shorter in the ministernotomy group (1.7 ± 1.2 months vs 2.8 ± 1.6 months; P = 0.001). Morbidity and mortality data did not differ between the two groups. CONCLUSIONS: There was no difference in the major outcomes between the patients who underwent upper ministernotomy and those who underwent full sternotomy. The benefits of the minimally invasive approach were the shorter hospital stay and significantly faster recovery of patients after discharge from the hospital.

Correlation of structural defects in the ascending aortic wall to ultrasound parameters: benefits for decision-making process in aortic valve surgery.

BACKGROUND: Histopathological changes in the ascending aorta wall in patients with severe tricuspid aortic valve (TAV) stenosis were graded and correlated to echocardiographic parameters. Objective was to associate threshold echocardiographic values with structural defects in the ascending aorta providing a tool to improve decision-making process in cases when simultaneous aortic valve replacement (AVR) and ascending aorta replacement is considered. METHODS: Biopsies from 108 TAV stenosis patients subjected to AVR were graded into three grades according to severity of aortic wall changes. Echocardiographic parameters obtained preoperatively and correlated to grade, age, gender and risk factors, were diameters of ventriculo-aortic junction (AA), sinus Valsalva (SV), sinotubular junction (STJ), the largest diameter of the visualized ascending aorta (AscA) as well as indexes: sinus Valsalva (SVI), sinotubular junction (STJI), AscA/AA and STJ/AA. RESULTS: Two echocardiographic parameters portrayed grades with statistical significance: STJ (F = 5.417; p = 0.006 (p < 0.05)) and AscA (F = 3.924; p = 0.023 (p < 0.05)). By using multiple predictors in the setting of Regression analysis, statistically significant differences among grades were reached for AA, SV, STJ, AscA and SVI. With further ROC curves analysis, threshold values for different grades were recognized. Grade 2 is identified in patients with AscA > 3.3 cm, while Grade 3 is identified in patients with values of AscA > 3.5 cm, STJ > 2.9 cm and STJI > 1. CONCLUSIONS: Hemodynamic stress induced by TAV stenosis leads to elastic lamellae disruption in the aortic wall. Those changes could be graded and correlated with echocardiographic parameters of the aortic root and ascending aorta, providing a tool for decision to replace ascending aorta concomitantly with AVR.

(-)-Epicatechin-induced relaxation of isolated human saphenous vein: Roles of K+ and Ca2+ channels.

In this study, we aimed to investigate relaxant effect of flavanol (-)-epicatechin on the isolated human saphenous vein (HSV), as a part of its cardioprotective action, and to define the mechanisms underlying this vasorelaxation. (-)-Epicatechin induced a concentration-dependent relaxation of HSV pre-contracted by phenylephrine. Among K+ channel blockers, 4-aminopyridine, margatoxin, and iberiotoxin significantly inhibited relaxation of HSV, while glibenclamide considerably reduced effects of the high concentrations of (-)-epicatechin. Additionally, (-)-epicatechin relaxed contraction induced by 80 mM K+ , whereas in the presence of nifedipine produced partial relaxation of HSV rings pre-contracted by phenylephrine. In Ca2+ -free solution, (-)-epicatechin relaxed contraction induced by phenylephrine, but had no effect on contraction induced by caffeine. A sarcoplasmic reticulum Ca2+ -ATPase inhibitor, thapsigargin, significantly reduced relaxation of HSV produced by (-)-epicatechin. These results demonstrate that (-)-epicatechin produces endothelium-independent relaxation of isolated HSV rings. Vasorelaxation to (-)-epicatechin probably involves activation of 4-aminopyridine- and margatoxin-sensitive KV channels, BKCa channels, and at least partly, KATP channels. In addition, not only the inhibition of extracellular Ca2+ influx, but regulation of the intracellular Ca2+ release, via inositol-trisphosphate receptors and reuptake into sarcoplasmic reticulum, via stimulation of Ca2+ -ATPase, as well, most likely participate in (-)-epicatechin-induced relaxation of HSV.

Endothelium-dependent vasorelaxant effect of procyanidin B2 on human internal mammary artery.

The aim of the present study was to investigate and characterize vasorelaxant effect of procyanidin B2 on human internal mammary artery (HIMA) as one of the mechanisms of its protective effect against vascular risk. Procyanidin B2 induced strong concentration-dependent relaxation of HIMA rings pre-contracted by phenylephrine. Pretreatment with L-NAME, a NO synthase inhibitor, hydroxocobalamin, a NO scavenger, and ODQ, an inhibitor of soluble guanylate cyclase, significantly inhibited procyanidin B2-induced relaxation of HIMA, while indomethacin, a cyclooxygenase inhibitor, considerably reduced effects of low concentrations. Among K+ channel blockers, iberiotoxin, a selective blocker of large conductance Ca2+-activated K+ channels (BKCa), abolished procyanidin B2-induced relaxation, glibenclamide, a selective ATP-sensitive K+(KATP) channels blocker, induced partial inhibition, while 4-aminopyridine, a blocker of voltage-gated K+(KV) channels, and TRAM-34, an inhibitor of intermediate-conductance Ca2+-activated K+(IKCa) channels, slightly reduced maximal relaxation of HIMA. Further, procyanidin B2 relaxed contraction induced by phenylephrine in Ca2+-free Krebs solution, but had no effect on contraction induced by caffeine. Finally, thapsigargin, a sarcoplasmic reticulum Ca2+-ATPase inhibitor, significantly reduced relaxation of HIMA produced by procyanidin B2. These results demonstrate that procyanidin B2 produces endothelium-dependent relaxation of HIMA pre-contracted by phenylephrine. This effect is primarily the result of an increased NO synthesis and secretion by endothelial cells and partially of prostacyclin, although it involves activation of BKCa and KATP, as well as KV and IKCa channels in high concentrations of procyanidin B2.

Preoperative Insight Into the Quality of Radial Artery Grafts.

We investigated the impact of preoperative ultrasonography of the forearm circulation on radial artery conduit selection. Preoperative ultrasound of the forearm circulation was performed routinely in 536 patients planned for radial artery harvesting. The safety assessment of the harvest included the following algorithm of tests: the ultrasound, the Allen test, and pulse oximetry. The quality criteria that were used to exclude a radial artery from harvesting were small size of the artery, diffuse atherosclerosis, calcifications, and severe neointimal hyperplasia. The overall rejection rate due to safety reasons was 16.4%. Seventy-one (13.2%) radial arteries did not fulfill the conduit quality criteria and consequently these arteries were not harvested. In 13.4% of radial arteries, localized arterial wall disease was found in the distal third of the artery. The distal part of the artery was discarded and the rest was used as a conduit. Our results indicate that the ultrasound provides an accurate preoperative insight into the radial artery morphology, enabling selection of the arteries with favorable morphological features.

Effect of Elective Bentall Procedure on Left Ventricular Systolic Function and Functional Status: Long-Term Follow-Up in 90 patients.

Because there are so few data on the long-term effects on left ventricular systolic function and functional status in patients who electively undergo Bentall procedures, we established a retrospective study group of 90 consecutive patients. This group consisted of 71 male and 19 female patients (mean age, 54 ± 10 yr) who had undergone the Bentall procedure to correct aortic valve disease and aneurysm of the ascending aorta, from 1997 through 2003 in a single tertiary-care center. We monitored these patients for a mean period of 117 ± 41 months for death, left ventricular ejection fraction and volume indices, and functional capacity as determined by New York Heart Association (NYHA) class. There were no operative deaths. The survival rate was 73.3% during follow-up. There were 10 cardiac and 13 noncardiac deaths, and 1 death of unknown cause. Echocardiography was performed before the index procedure and again after 117 ± 41 months. In surviving patients, statistically significant improvement in left ventricular ejection fraction, in comparison with preoperative values (0.49 ± 0.11 vs 0.41 ± 0.11; P <0.0001), was noted at follow-up. Similarly, we observed statistically significant reductions in left ventricular end-systolic (39.24 ± 28.7 vs 48.77 ± 28.62 mL/m(2)) and end-diastolic volumes (54.63 ± 6.97 vs 59.17 ± 8.92 mL/m(2); both P <0.0001). Most patients (53/66 [80.3%]) progressed from a higher to a lower NYHA class during the follow-up period. The Bentall procedure significantly improved long-term left ventricular systolic function and functional status in surviving patients who underwent operation on a nonemergency basis.

Radial artery vs saphenous vein graft used as the second conduit for surgical myocardial revascularization: long-term clinical follow-up.

BACKGROUND: There is ongoing debate regarding the efficacy of the radial artery (RA) as an aortocoronary conduit, with few solid data regarding long-term clinical results. We sought to determine if the use of the RA as the second arterial conduit, beside left internal thoracic artery (LITA), would improve long-term clinical outcome after CABG as compared to saphenous vein graft (SVG). METHODS: Between March 2001 and November 2003, 200 patients underwent isolated CABG and were randomized in 1:1 fashion to receive either LITA and RA grafts or LITA and SVGs. The primary end point was composite of cardiovascular mortality, non-fatal myocardial infarction and need for repeat myocardial revascularization (either surgical or percutaneous). RESULTS: There was no significant difference in absolute survival, with 12 deaths in each group during the study period (log rank = 0.01, p = 0.979). There were 3 and 2 cardiac deaths in RA and SVG groups, respectively. There was no difference in long-term clinical outcome between the groups (log rank = 0.450, p = 0.509). Eleven patients in RA group had one or more non-fatal events; 7 patients suffered a myocardial infarction, 9 patients underwent percutaneous coronary angioplasty, and 1 patient required redo coronary surgery. Likewise, 13 patients in SVG group had non-fatal event; 7 patients had myocardial infarction, 13 patients had percutaneous coronary intervention and 3 patients required redo coronary surgery. Angiograms were performed in 23 patients in RA group (patency rate 92 %) and 24 in SVG group (patency rate 86 %) (p = 0.67). CONCLUSION: In this small randomised study our data indicate that there is no difference in the 8 year clinical outcomes in relatively young patients between those having a RA or a saphenous vein graft used as a second conduit, beside LITA, for surgical myocardial revascularisation.

Mechanisms underlying the vasorelaxation of human internal mammary artery induced by (-)-epicatechin.

Evidences have suggested that flavanol compound (-)-epicatechin is associated with reduced risk of cardiovascular diseases. One of the mechanisms of its cardioprotective effect is vasodilation. However, the exact mechanisms by which (-)-epicatechin causes vasodilation are not yet clearly defined. The aims of the present study were to investigate relaxant effect of flavanol (-)-epicatechin on the isolated human internal mammary artery (HIMA) and to determine the mechanisms underlying its vasorelaxation. Our results showed that (-)-epicatechin induced a concentration-dependent relaxation of HIMA rings pre-contracted by phenylephrine. Among the K(+) channel blockers, 4-aminopyridine (4-AP) and margatoxin, blockers of voltage-gated K(+) (KV) channels, and glibenclamide, a selective ATP-sensitive K(+) (KATP) channels blocker, partly inhibited the (-)-epicatechin-induced relaxation of HIMA, while iberiotoxin, a most selective blocker of large conductance Ca(2+)-activated K(+) channels (BKCa), almost completely inhibited the relaxation. In rings pre-contracted by 80mM K(+), (-)-epicatechin induced partial relaxation of HIMA, whereas in Ca(2+)-free medium, (-)-epicatechin completely relaxed HIMA rings pre-contracted by phenylephrine and caffeine. Finally, thapsigargin, a sarcoplasmic reticulum Ca(2+)-ATPase inhibitor, slightly antagonized (-)-epicatechin-induced relaxation of HIMA pre-contracted by phenylephrine. These results suggest that (-)-epicatechin induces strong endothelium-independent relaxation of HIMA pre-contracted by phenylephrine whilst 4-AP- and margatoxin-sensitive KV channels, as well as BKCa and KATP channels, located in vascular smooth muscle, mediate this relaxation. In addition, it seems that (-)-epicatechin could inhibit influx of extracellular Ca(2+), interfere with intracellular Ca(2+) release and re-uptake by the sarcoplasmic reticulum.

Nicorandil directly and cyclic GMP-dependently opens K+ channels in human bypass grafts.

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.

Simultaneous hybrid carotid stenting and coronary bypass surgery versus concomitant open carotid and coronary bypass surgery: a pilot, feasibility study.

OBJECTIVES: Concomitant carotid and cardiac surgery carries an increased perioperative morbidity and mortality risk. Whether the hybrid procedure of carotid artery stenting (CAS) and coronary bypass surgery decreases the risk of stroke and other complications is still unknown. The aim of this study was to assess early outcomes after simultaneous hybrid CAS and coronary bypass grafting versus open concomitant carotid and coronary bypass surgery. METHODS: We included 20 patients in this study. According to the protocol, all the patients were divided into two groups: Group 1 (10 patients) with hybrid CAS and coronary bypass surgery and Group 2 (10 patients) with concomitant carotid and coronary surgery. Different preoperative, intraoperative and postoperative variables were compared. The primary end point was combined incidence of stroke and death 30 days after surgery or during initial hospitalization. The secondary end points were myocardial infarction, atrial fibrillation, blood loss and need for blood transfusion and duration of intensive care unit and hospital stay. RESULTS: Groups 1 and 2 were similar in preoperative characteristics including age (65.3 ± 6.8 vs 70.7 ± 7.0, P = 0.191) New York Heart Association class (2.3 ± 0.5 vs 1.8 ± 0.7, P = 0.218), EuroSCORE (2.8 ± 2.0 vs 3.6 ± 2.3, P = 0.547), the degree of carotid stenosis (79 ± 12 vs 87 ± 13%, P = 0.224) and average left ventricular ejection fraction (44.3 ± 12.4 vs 43.4 ± 13.3%, P = 0.896). Also, the groups did not differ in intraoperative variables with an exception of extracorporeal circulation time (65.7 ± 14.1 vs 90.0 + 17.4 min, P = 0.023), which was significantly shorter in Group 1. Although rare, and without significant difference, primary end point occurred only in Group 2 (1 stroke and 1 death, 20%). There was no difference in the duration of mechanical ventilation, need for transfusion and duration of intensive care unit and hospital stay between the two groups. CONCLUSIONS: Although limited by a small sample size, our results show that the hybrid procedure of carotid stenting and coronary surgery might be a good therapeutic option but further extended studies are needed to assess its real value.

Blood transfusion in cardiac surgery--does the choice of anesthesia or type of surgery matter?

BACKGROUND/AIM: In spite of the evidence suggesting a significant morbidity associated with blood transfusions, the use of blood and blood products remain high in cardiac surgery. To successfully minimize the need for blood transfusion, a systematic approach is needed. The aim of this study was to investigate the influence of different anesthetic techniques, general vs combine epidural and general anesthesia, as well as different surgery strategies, on-pump vs off-pump, on postoperative bleeding complications and the need for blood transfusions during perioperative period. METHODS: Eighty-two consecutive patients scheduled for coronary artery bypass surgery were randomized according to surgical and anesthetic techniques into 4 different groups: group 1 (patients operated on off-pump, under general anesthesia); group 2 (patients operated on off-pump, with combined general and high thoracic epidural anesthesia); group 3 (patients operated on using standard revascularization technique, with the use of extracorporeal circulation, under general anesthesia), and group 4 (patients operated on using standard revascularization technique, with the use of extracorporeal circulation, with combined general and high thoracic epidural anesthesia). Indications for transfusion were based on clinical judgment, but a restrictive policy was encouraged. Bleeding was considered significant if it required transfusion of blood or blood products, or reopening of the chest. The quantity of transfused blood or blood products was specifically noted. RESULTS: None of the patients was transfused blood or blood products during the surgery, and as many as 70/81 (86.4%) patients were not transfused at all during hospital stay. No difference in postoperative bleeding or blood transfusion was noted in relation to the type of surgery and anesthetic technique applied. If red blood cells were transfused, postoperative bleeding was the most influential parameter for making clinical decision. CONCLUSION: No influence of off-pump surgery or epidural anesthesia on blood transfusion requirements during a perioperative period was confirmed by this study. It seems, however, that encouraging lower hemoglobin triggers in clinical decision-making could result in less transfusions during surgery or hospital stay.

High thoracic epidural anesthesia in patients with synchronous carotid endarterectomy and off-pump coronary artery revascularization.

BACKGROUND/AIM: In order to reduce the risk of cerebrovascular insults (CVI), the latest recommendations suggest that carotid endarterectomy (CEA) is strongly indicated in patients scheduled for coronary surgery when significant carotid artery stenosis is symptomatic and/or bilateral. The best results are obtained in small studies with CEA performed immediately prior to off-pump coronary bypass (OPCAB). We present 16 consecutive patients who underwent synchronous CEA and OPCAB under general anesthesia combined with high thoracic epidural anesthesia (TEA) in order to evaluate the safety and potential benefits of such anesthetic management. METHODS: A total of 16 consecutive patients scheduled for simultaneous CEA and OPCAB with no contraindication for TEA were enrolled in the study. All the patients were anesthetized with TEA combined with general anesthesia. Early extubation was planed in all the patients for early assessment of neurological outcome. Demographics, comorbidity, quality of postoperative recovery, duration of mechanical ventilation, successful early extubation, outcome, length of Intensive Care Unit (ICU) and hospital stay were recorded. RESULTS: Only two patients did not fulfill the criteria for early extubation. The average duration of mechanical ventilation for patients who fulfilled criteria for early extubation was 87.9 +/- 85.0 (0-255) min. Five (31.25%) patients were extubated in the operating theater at the end of surgery. There were no deaths, nor neurological complications of TEA. Seven (43.7%) patients had at least one of the postoperative complications considered significant. None of them had CVI. None of the early extubated patients was reintubated or had postoperative respiratory failure. CONCLUSION: Our study revealed that a combination of general anesthesia with TEA appears to be good choice in synchronous CEA and OPCAB due to advantages of early extubation and early neurological assessment. Larger studies are necessary to determine real benefits on both short and long-term outcomes of such anesthetic management in synchronous CEA and OPCAB.

Mitochondrial molecular basis of sevoflurane and propofol cardioprotection in patients undergoing aortic valve replacement with cardiopulmonary bypass.

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.

Different potassium channels are involved in relaxation of rat renal artery induced by P1075.

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.

[Simultaneous carotid and coronary surgery without use of extracorporeal circulation--personal experience]. / Simultane karotidne i koronarne operacije bez upotrebe vantelesnog krvotoka - Nase iskustvo.

OBJECTIVES: There is still a dilemma about best treatment option for patients with severe carotid and coronary artery disease. Reviving of beating heart revascularization technique and using of carotid stenting makes things even more difficult. Discussion about this subject is getting more and more profound. This is analysis of our initial experience with simultaneous carotid and off pump coronary procedures. MATERIALS AND METHODS: This is retrospective analysis of 18 patients operated using this technique in a period from 2001-2003 yrs. Follow up was done by telephone interview. For survivors specially designed questionaire was fulfilled. RESULTS: We operated total number of 18 patients with average age 60,6+/-9.32 years. Carotid recontruction was performed by eversion technique in all patients. Average number of coronary grafts was 2,67+/-0.88. During postoperative period 1 patient (5.55%) had verified perioperative infarction and 1 patient (5.55%) suffered from stroke. Average number of days in hospital was 9.95+/-4.74. During follow up period of 21 months two more patients died from cardiovascular causes. There was no need for repeat coronary angiogram or reintervention on carotid or coronary arteries. CONCLUSION: Simultaneous carotid and coronary operation performed on beating heart is safe and efficent method of treatment for patients with severe concomitant carotid and coronary artery disease.

Different K+ channels are involved in relaxation of arterial and venous graft induced by nicorandil.

The drug nicorandil is a vasodilator approved for the treatment of angina. In addition to its well-known effect on the opening of ATP-sensitive K (KATP) channels, nicorandil-induced vasorelaxation also involves the opening of Ca-activated K channels. The aim of this study was to investigate the effects of nicorandil on the isolated human internal mammary artery (HIMA) and the human saphenous vein (HSV) and to define the contribution of different K channel subtypes in the nicorandil action on these arterial and venous grafts. Our results show that nicorandil induced a concentration-dependent relaxation of HSV and HIMA rings precontracted by phenylephrine. Glibenclamide, a selective KATP channels inhibitor, partially inhibited the response to nicorandil in both HSV and HIMA. Iberiotoxin, a most selective blocker of large-conductance Ca-activated K (BKCa) channels, partly antagonized relaxation of HIMA. A nonselective blocker of voltage-gated K channels, 4-aminopyridine caused partial inhibition of the nicorandil-induced relaxation of HSV but did not antagonize relaxation of HIMA induced by nicorandil. Margatoxin, a potent inhibitor of KV1.3 channels, did not abolish the effect of nicorandil on HSV and HIMA. Our results showed that nicorandil induced strong endothelium-independent relaxation of HSV and HIMA contracted by phenylephrine. It seems that KATP and 4-aminopyridine-sensitive K channels located in the smooth muscle of HSV mediated relaxation induced by nicorandil. In addition, KATP and BKCa channels are probably involved in the nicorandil action on HIMA.