A different technique for sutureless coronary bypass grafting.

Introduction: Many coronary anastomotic devices have been designed to replace manual stitching in coronary surgery; however, interestingly, none of them became widespread. Our aim was to work out an easy and fast endoluminal vessel-to-vessel stent bridge distal anastomotic technique. Materials and methods: Ten coronary arteries of eight fresh human hearts were used in this study. The anastomosis was performed with the implantation of a graft vessel into the lumen of the coronary artery by performing stent fixation. The technique is described and photo documented in detail. The durability and the conductibility of the anastomosis were examined with intraluminal endoscopy, functional streaming test, and a coloring of the vessels. Results: The anastomosis had great results in all cases. Obstruction, dissection, or dislocation of the vessels was not observable. Conclusions: This study confirmed the ex-vivo feasibility of the described technique. This method can be an easy, fast, and reliable method applied in the endoscopic distal coronary artery anastomosis surgery. The development of stents adapted to this method and the in-vivo testing of this technique are necessary for the future.

The Janus face of adenosine: antiarrhythmic and proarrhythmic actions.

Adenosine is a ubiquitous, endogenous purine involved in a variety of physiological and pathophysiological regulatory mechanisms. Adenosine has been proposed as an endogenous antiarrhythmic substance to prevent hypoxia/ischemia-induced arrhythmias. Adenosine (and its precursor, ATP) has been used in the therapy of various cardiac arrhythmias over the past six decades. Its primary indication is treatment of paroxysmal supraventricular tachycardia, but it can be effective in other forms of supraventricular and ventricular arrhythmias, like sinus node reentry based tachycardia, triggered atrial tachycardia, atrioventricular nodal reentry tachycardia, or ventricular tachycardia based on a cAMP-mediated triggered activity. The main advantage is the rapid onset and the short half life (1- 10 sec). Adenosine exerts its antiarrhythmic actions by activation of A1 adenosine receptors located in the sinoatrial and atrioventricular nodes, as well as in activated ventricular myocardium. However, adenosine can also elicit A2A, A2B and A3 adenosine receptor-mediated global side reactions (flushing, dyspnea, chest discomfort), but it may display also proarrhythmic actions mediated by primarily A1 adenosine receptors (e.g. bradyarrhythmia or atrial fibrillation). To avoid the non-specific global adverse reactions, A1 adenosine receptor- selective full agonists (tecadenoson, selodenoson, trabodenoson) have been developed, which agents are currently under clinical trial. During long-term administration with orthosteric agonists, adenosine receptors can be internalized and desensitized. To avoid desensitization, proarrhythmic actions, or global adverse reactions, partial A1 adenosine receptor agonists, like CVT-2759, were developed. In addition, the pharmacologically "silent" site- and event specific adenosinergic drugs, such as adenosine regulating agents and allosteric modulators, might provide attractive opportunity to increase the effectiveness of beneficial actions of adenosine and avoid the adverse reactions.

Approximation of A1 adenosine receptor reserve appertaining to the direct negative inotropic effect of adenosine in hyperthyroid guinea pig left atria.

Hyperthyroidism elevates cardiovascular mortality by several mechanisms, including increased risk of ischemic heart disease. Therefore, therapeutic strategies, which enhance tolerance of heart to ischemia-reperfusion injury, may be particularly useful for hyperthyroid patients. One promising cardioprotective approach is use of agents that cause (directly or indirectly) A1 adenosine receptor (A1 receptor) activation, since A1 adenosinergic pathways initiate protective mechanisms such as ischemic preconditioning. However, previously we found great A1 receptor reserve for the direct negative inotropic effect of adenosine in isolated guinea pig atria. This phenomenon suggests that weakening of atria is a possible side effect of A1 adenosinergic stimulant agents. Thus, the goal of the present investigation was to explore this receptor reserve in hyperthyroidism. Our recently developed method was used that prevents the rapid intracellular elimination of adenosine, allowing sufficient time for exogenous adenosine administered for the generation of concentration-response curves to exert its effect. Our method also allowed correction for the bias caused by the consequent endogenous adenosine accumulation. Our results demonstrate that thyroxine treatment does not substantially affect the A1 receptor reserve for the direct negative inotropic effect of adenosine. Consequently, if an agent causing A1 receptor activation is administered for any indication, the most probable adverse effect affecting the heart may be a decrease of atrial contractility in both eu- and hyperthyroid conditions.

The surmountable effect of FSCPX, an irreversible A(1) adenosine receptor antagonist, on the negative inotropic action of A(1) adenosine receptor full agonists in isolated guinea pig left atria.

A1 adenosine receptors (A1 receptors) are widely expressed in mammalian tissues; therefore attaining proper tissue selectivity is a cornerstone of drug development. The fact that partial agonists chiefly act on tissues with great receptor reserve can be exploited to achieve an appropriate degree of tissue selectivity. To the best of our knowledge, the A1 receptor reserve has not been yet quantified for the atrial contractility. A1 receptor reserve was determined for the direct negative inotropic effect of three A1 receptor full agonists (NECA, CPA and CHA) in isolated, paced guinea pig left atria, with the use of FSCPX, an irreversible A1 receptor antagonist. FSCPX caused an apparently pure dextral displacement of the concentration-response curves of A1 receptor agonists. Accordingly, the atrial A1 receptor function converging to inotropy showed a considerably great, approximately 80-92 % of receptor reserve for a near maximal (about 91-96 %) effect, which is greater than historical atrial A1 receptor reserve data for any effects other than inotropy. Consequently, the guinea pig atrial contractility is very sensitive to A1 receptor stimulation. Thus, it is worthwhile considering that even partial A1 receptor agonists, given in any indication, might decrease the atrial contractile force, as an undesirable side effect, in humans.

Thyroid hormones decrease the affinity of 8-cyclopentyl-1,3-dipropylxanthine (CPX), a competitive antagonist, for the guinea pig atrial A(1) adenosine receptor.

The aim of the present study was to investigate whether or not thyroxine (T(4)) treatment affects K(B), the equilibrium dissociation constant of the antagonist-receptor complex, for the interaction between CPX, a selective and competitive orthosteric antagonist, and the guinea pig atrial A1 adenosine receptor A1 receptor). The inotropic response to adenosine, a nonselective adenosine receptor agonist, or CPA, a selective A1 receptor agonist, was investigated in the absence or presence of CPX in paced left atria isolated from 8-day solvent- or T(4)-treated guinea pigs. To obtain K(B) values, adenosine and CPA concentration-response curves were evaluated by Schild analysis. CPA but not adenosine obeyed the requirements of the Schild analysis to provide correct K(B) values for CPX. According to the CPA concentration-response curves, affinity of CPX for the hyperthyroid guinea pig atrial A1 receptor (K(B) = 44.16 nM) was lower than that for the euthyroid one (K(B) = 16.63 nM). Regarding the intense reduction in the negative inotropic effect of adenosine and CPA in hyperthyroid atria, it is reasonable to assume that the moderate decrease in affinity of the guinea pig atrial A1 receptor is only in part responsible for the diminished A1 receptor-mediated effect in hyperthyroidism.

Various clinical scenarios leading to development of the string sign of the internal thoracic artery after coronary bypass surgery: the role of competitive flow, a case series.

BACKGROUND: The left internal mammary artery (LIMA) is the choice for grafting of the left anterior descending coronary artery (LAD). One possible mechanism of the rare graft failure involve the presence of competitive flow. METHOD: 105 patients who had undergone coronary bypass grafting between 1998 and 2000 were included in this observational study. The recatheterizations were performed 28 months after the operations. The rate of patency the LIMA grafts was determined, and the cases with graft failure were analyzed. RESULTS: The LIMA graft was patent in 99 patients (94%). Six patients (6%) exhibited diffuse involution of the graft (string sign). The string sign was always associated with competitive flow as the basis of the LIMA graft involution. In one case quantitative re-evaluation of the preoperative coronary angiography revealed merely less than 50% diameter stenosis on the LAD with a nonligated side-branch of the LIMA. At recatheterization in two patients the pressure wire measurements demonstrated only a non-significant decrease of the fractional flow reserve (0.83 and 0.89), despite the 53% and 57% diameter stenosis in the angiogram. Another patient displayeda significant regression of the LAD lesion between the pre- and postoperative coronary angiography (from 76% to 44%) as the cause of the development of the competitive flow. In one instance, a radial artery graft on the LAD during a redo bypass operation resulted in competitive flow in the radial graft due to the greater diameter than that of the LIMA. In a further patient, competitive flow developed from a short sequential part of the LIMA graft between the nonsignificantly stenosed diagonal branch and the LAD, with involution of the main part of the graft to the diagonal branch. CONCLUSIONS: The most common cause of the development of the string sign of a LIMA graft due to competitive flow is overassessment of the lesion of the LAD. Regression of a previous lesion or some other neighboring graft can also cause the phenomenon.

Differences in angiotensin convertase enzyme (ACE) activity and expression may contribute to shorter event free period after coronary artery bypass graft surgery.

AIMS: The goal of this study was to investigate the importance of the vascular angiotensin convertase enzyme (ACE) in coronary artery bypass graft surgery (CABG) patients. METHODS: Vascular tissue (distal saphenous vein [n= 163] and/or radial artery [n= 120] segments) and blood samples were collected from CABG patients (n= 81). We studied (i) the potency of angiotensin I (AngI) and angiotensin II (AngII) to evoke vascular contractions; (ii) vascular and plasma ACE concentrations; and (iii) ACE genotype of the patients enrolled. RESULTS: The ratio of the potencies (EC(50) ) of AngII and AngI was significantly lower in radial artery compared to the saphenous vein (0.17 ± 0.03 nM and 0.51 ± 0.14 nM, respectively, P= 0.003), suggesting a 3-fold more effective AngI conversion in saphenous vein samples. Angiotensin constrictions were inhibited with telmisartan and captopril in both saphenous veins and radial arteries. Vascular ACE expression was significantly higher in saphenous vein compared to radial artery (9.7 ± 1.0 ng/mg and 5.3 ± 0.7 ng/mg, respectively, P= 0.01). Serum but no tissue ACE concentration was determined by ACE insertion/deletion polymorphism. Accordingly, no relation was found between serum and tissue ACE expression. CONCLUSION: ACE-inhibitor therapy targeting tissue located ACE may be beneficial to patients with saphenous vein grafts after CABG surgery.

Red cells, hemoglobin, heme, iron, and atherogenesis.

OBJECTIVE: We investigated whether red cell infiltration of atheromatous lesions promotes the later stages of atherosclerosis. METHODS AND RESULTS: We find that oxidation of ferro (FeII) hemoglobin in ruptured advanced lesions occurs generating ferri (FeIII) hemoglobin and via more extensive oxidation ferrylhemoglobin (FeIII/FeIV=O). The protein oxidation marker dityrosine accumulates in complicated lesions, accompanied by the formation of cross-linked hemoglobin, a hallmark of ferrylhemoglobin. Exposure of normal red cells to lipids derived from atheromatous lesions causes hemolysis and oxidation of liberated hemoglobin. In the interactions between hemoglobin and atheroma lipids, hemoglobin and heme promote further lipid oxidation and subsequently endothelial reactions such as upregulation of heme oxygenase-1 and cytotoxicity to endothelium. Oxidative scission of heme leads to release of iron and a feed-forward process of iron-driven plaque lipid oxidation. The inhibition of heme release from globin by haptoglobin and sequestration of heme by hemopexin suppress hemoglobin-mediated oxidation of lipids of atheromatous lesions and attenuate endothelial cytotoxicity. CONCLUSIONS: The interior of advanced atheromatous lesions is a prooxidant environment in which erythrocytes lyse, hemoglobin is oxidized to ferri- and ferrylhemoglobin, and released heme and iron promote further oxidation of lipids. These events amplify the endothelial cell cytotoxicity of plaque components.

The diagnosis, morphological particularities, and surgical technique in a case of intravascular leiomyoma extended to the right heart chambers.

Intravenous leiomyoma is a benign smooth muscle cell tumor of uterine origin that may grow into the pelvic veins and the inferior vena cava. It usually affects premenopausal women and the majority (90%) are parous. Because cardiac involvement is present in up to 10% of cases, it may be misdiagnosed as a primary cardiac tumor or a venous thrombus-in-transit. We describe a case of intravascular leiomyomatosis with cardiac extension and the morphological particularities of the removed tumor.

The peroxynitrite evoked contractile depression can be partially reversed by antioxidants in human cardiomyocytes.

In this study, we aimed to determine the contribution of peroxynitrite-dependent sulfhydryl group (SH) oxidation to the contractile dysfunction in permeabilized left ventricular human cardiomyocytes using a comparative approach with the SH-oxidant 2,2'-dithiodipyridine (DTDP). Additionally, different antioxidants: dithiothreitol (DTT), reduced glutathione (GSH) or N-acetyl-L-cysteine (NAC) were employed to test reversibility. Maximal isometric active force production (F(o)) and the maximal turnover rate of the cross-bridge cycle (k(tr,max)) illustrated cardiomyocyte mechanics. SH oxidation was monitored by a semi-quantitative Ellman's assay and by SH-specific protein biotinylation. Both peroxynitrite and DTDP diminished F(o) in a concentration-dependent manner (EC(50,peroxynitrite) = 49 microM; EC(50,DTDP) = 2.75 mM). However, k(tr,max) was decreased only by 2.5-mM DTDP, but not by 50 microM peroxynitrite. The diminution of F(o) to zero by DTDP was paralleled by the complete elimination of the free SH groups, while the peroxynitrite-induced maximal reduction in free SH groups was only to 58 +/- 6% of the control (100%). The diminutions in F(o) and free SH groups evoked by 2.5-mM DTDP were completely reverted by DTT. In contrast, DTT induced only a partial restoration in F(o) (DeltaF(o,): approximately 13%; P < 0.05) despite full reversion in protein SH content after 50 microM peroxynitrite. Although, NAC or DTT were equally effective on F(o) after peroxynitrite exposures, NAC or GSH did not restore F(o) or k(tr,max) after DTDP treatments. Our results revealed that the peroxynitrite-evoked cardiomyocyte dysfunction has a small, but significant component resulting from reversible SH oxidation, and thereby illustrated the potential benefit of antioxidants during cardiac pathologies with excess peroxynitrite production.

[Results of vacuum-assisted wound closure system in the treatment of sternotomy wound infections following cardiac surgery]. / A vákuumtámogatott sebkezelés eredményei szívmutétet követo sternotomiás sebfertozésekben.

In the last decade a new and more effective method--the vacuum assisted wound closure (VAC)--was introduced for the treatment of the mediastinal wound infections following open heart operations. This technique gained a widespread acceptance in many countries of the world. The Centre of Cardiac Surgery of the University of Debrecen was the first to apply this treatment in Hungary. The authors evaluated the VAC therapy in a retrospective study at their institute. Between September 2002 and December 2005 62 consecutive patients were treated with this method because of wound infection in median sternotomy. Median age of 42 males and 20 females was 63,1 +/- 6,8 years (42-75). All patients had heart surgery (cardio pulmonary bypass) before they developed superficial or deep wound infection in their sternotomy site. Following exploration and radical debridement of the sternotomy wounds, VAC method was used for the treatment of infected wounds until suppuration stopped. When the wound had become macroscopically clear, reconstruction of the sternal defect was performed. This was carried out with well vascularized soft tissue flap(s) (major pectoral muscle and/or omental or pericardial fat pad) in 34 patients, sternal refixation was performed in 13 cases, while 11 patients underwent delayed secondary wound reconstruction with sutures. In one case Ley-prosthesis (sternal stabilisator metal prosthesis) was implanted. Three patients died before the sternal wound reconstruction. As a result of VAC therapy, all infected mediastinal wound cleaned up rapidly and formation of granulation tissue began. The mean period of time from the first sign of the infection to hospital discharge of the patients was 42.2 +/- 18.5 (5-185) days, while the same between sternal reconstruction and discharge was 19.9 +/- 9.6 (1-63) days. The mean duration of VAC therapy was 7.9 +/- 3.4 (1-21) days. The hospital mortality was 11.3% (7/62). Recurrence of the infection occurred in two patients (3.6%). These results suggest that Vacuum-assisted Closure system is an effective and safe method for the treatment of sternotomy wound infections following cardiac surgery. This method facilitates early clean up of infected sternotomy wounds and decreases the recurrence rate significantly.

[Cardiovascular actions of a standardized polyphenol concentrate on patients undergoing coronary bypass grafting: a randomized, double-blind, placebo-controlled study]. / Standardizált polifenol-koncentrátum keringési hatásai koszorúérmutéten átesett betegeken: randomizált, kettos vak-, placebokontrollos vizsgálat.

In this study the authors analyzed the action of Flavon Max product on the cardiovascular system of patients with severe coronary disease. Two randomized, double-blind, placebo controlled trials were carried out using impedance-cardiography, arteriography, vascular Doppler and biochemical laboratory methods. The results demonstrate that Augmentation Index measured with arteriography and C reactive protein (CRP) levels were significantly ameliorated after 2 x 2 months Flavon Max therapy. In conclusion, this product is beneficial as adjuvant in the treatment of atherosclerotic coronary disease.

[Simple surgical method for intraoperative evaluation of adequacy of tricuspid annuloplasty]. / Egyszeru sebészi módszer a tricuspidalis annuloplasztika eredményének mutét alatti értékelésére.

In tricuspid annuloplasty intraoperative "real time" evaluation using transoesophageal echocardiography requires normal flow to get reliable result. It means that the patient has to be already weaned from the cardiopulmonary bypass by the time of evaluation. In the authors' experience a well functioning tricuspid annuloplasty prevents back-flow through the valve. It can be observed on on-pump beating heart. If the tricuspid valve is competent, it is unnecessary to suck the blood flowing back through the coronary sinus while closing the right atrium. This observation seems to correlate well with post cardiopulmonary bypass transoesophageal echocardiography measurements and the control transthoracic echocardiography right before discharging the patients. These statements are based on a group of 72 patients. Sixty-nine patients (95.8%) were discharged (early mortality 4.2%). Only in one case we could observe a discrepancy between the intraoperative surgical observation and the postoperative echocardiographic finding. Development of functional tricuspid regurgitation in left-sided heart disease is a warning sign for myocardial impairment, which is an indication for surgery. Tricuspid annuloplasty can be performed even with moderate to medium grade regurgitation because it improves the early and late outcome. The described method is an adequate method for intraoperative evaluation of the repaired tricuspid valve competency.

[Excision of the calcified mitral valve with ultrasound scalpel]. / A meszes mitralis billentyu sebészi kimetszése ultrahangvágóval.

Mitral valve excision using ultrasound device has not been a routine procedure yet. We used an ultrasonic scalpel for the excision of the calcified mitral valves, which shorten operation time. Further, this technique permits an excision of the valve without applying traction or elevation of the valve from the level of the annulus. This method was first tested on twenty fresh porcine hearts. Subsequently, this technique was carried out with very good results in 15 consecutive patients with calcified or scarred, and distorted mitral valves. Histological samples were taken from the excised human and porcine valves. In porcine histological specimens the destructive effect of the ultrasonic scalpel was measured of an average of 0.7 mm (minimum 0.5 mms, maximum 0.8 mms). However, in the human heart, this effect was an average of 1.1 mms (minimum 0.6 mms, maximum 2.2 mms). There were no early or late complications observed in any case. The authors recommend this technique for excision of calcified mitral valves in cardiac surgery.

[Minimally invasive direct cardiac surgery with the jakoscope retractor]. / Minimálisan invazív direkt szívsebészet jakoszkóp feltáróval.

The authors present a surgical retractor named jakoscope, useful in the field of abdominal, urological, vascular, thoracic and cardiac surgery procedures. This multifunctional device offers the possibility to utilize Minimally Invasive Direct Access Surgical Technology (MIDAST) in the above mentioned surgical specialties. In their department the authors use the jakoscope retractor for aortic valve replacement, off-pump coronary bypass operations and radiofrequency pulmonary vein ablation by mini-thoracotomy approach. In this report they published for the first time their experience with jakoscope device in the field of cardiac surgery. In these operations the device assured adequate minimally invasive direct access, without complications.

Modulation of adenosine-induced responses in the guinea-pig trachea during long-term caffeine treatment: possible role of epithelium.

The responses to adenosine were studied on isolated, methacholine-precontracted tracheal strips of guinea pigs in the course of long-term caffeine or solvent treatment. Guinea pigs were fed caffeine for 10 weeks (average serum caffeine concentration: 39.1 +/- 3.9 microM). In epithelium-intact tracheal preparations (EITPs), sensititization to adenosine-induced relaxation (AIR) developed. It attained a maximum in week 1 of caffeine treatment, and then its level diminished and disappeared completely by weeks 4 - 6. In epithelium-denuded tracheal preparations (EDTPs), an increase in the sensitivity to adenosine was observed from week 1 to week 10 (a 4 - 6-fold reduction in EC50). Use of a coaxial bioassay system confirmed the role of epithelium in this process. The enhancement of the AIR of the EITPs was not modified by inhibitors of cyclooxygenase and lipoxygenase. Following depletion of the neuropeptides by acute capsaicin pretreatment, the AIR of the EITPs was strongly enhanced after caffeine treatment for 6 weeks. In chronically caffeine-treated EITPs, the inhibition of neutral endopeptidase led to dramatic reduction of the AIR. On the basis of the results by inhibiting nitric oxide synthase, it can be supposed that nitric oxide released from EITPs of long-lasting caffeine-treated animals operated as a constrictor agent. Our results show that chronic caffeine treatment gives rise to an initial sensitization to adenosine of the EITPs, this being followed by the development of a specific adaptive process in the epithelial cells, which counterbalances the increased tracheal sensitivity to adenosine.

Activation of the poly(ADP-ribose) polymerase pathway in human heart failure.

Poly(ADP-ribose) polymerase (PARP) activation has been implicated in the pathogenesis of acute and chronic myocardial dysfunction and heart failure. The goal of the present study was to investigate PARP activation in human heart failure, and to correlate PARP activation with various indices of apoptosis and oxidative and nitrosative stress in healthy (donor) and failing (NYHA class III-IV) human heart tissue samples. Higher levels of oxidized protein end-products were found in failing hearts compared with donor heart samples. On the other hand, no differences in tyrosine nitration (a marker of peroxynitrite generation) were detected. Activation of PARP was demonstrated in the failing hearts by an increased abundance of poly-ADP ribosylated proteins. Immunohistochemical analysis revealed that PARP activation was localized to the nucleus of the cardiomyocytes from the failing hearts. The expression of full-length PARP-1 was not significantly different in donor and failing hearts. The expression of caspase-9, in contrast, was significantly higher in the failing than in the donor hearts. Immunohistochemical analysis was used to detect the activation of mitochondrial apoptotic pathways. We found no significant translocation of apoptosis-inducing factor (AIF) into the nucleus. Overall, the current data provide evidence of oxidative stress and PARP activation in human heart failure. Interventional studies with antioxidants or PARP inhibitors are required to define the specific roles of these factors in the pathogenesis of human heart failure.

Hand perfusion with 99mTc-HSA in patients expecting to undergo coronary bypass surgery: elaboration of a new complex diagnostic protocol for the safe removal of a radial artery graft.

BACKGROUND: The Allen test is used worldwide for radial artery graft removal. The postoperative examination of our patients' hand function and circulation proved that beside the transient neurological complications chronic hand circulatory disorders may arise. AIM: To develop a non-invasive method suitable for an objective evaluation of the hand's circulation to make it possible to use radial arteries safely for the revascularization of coronary arteries. METHODS: We examined 35 patients. After selective compression of the radial and ulnar arteries of both hands, we injected 400 MBq (99m)Tc-HSA intravenously and acquired 240 images, each of 1 s. After 30 s we released the ulnar artery first, and after 120 s the radial artery, too. Then computer analysis was performed. RESULTS: The patients could be divided into two groups. In the majority of them, releasing only the ulnar artery resulted in a good circulation of the fingers. It meant that the time-activity curve rapidly reached its maximum, and the activity did not change even after releasing the radial artery. In a smaller proportion of the patients the activity of the fingers increased only slowly, and did not reach a plateau even after 30 s. Following the release of the radial artery a further increase in the activity could be observed. We assume that the latter patient group is at risk of consequent circulatory disorder of the fingers after the removal of the radial artery, whereas in the former group the artery could be removed safely. CONCLUSIONS: Hand perfusion with (99m)Tc-HSA is useful in patients selected for coronary bypass operations, so we recommend the introduction of this method as a routine examination before the removal of the radial artery in patients with an abnormal Allen test.