Quality of Life in Patients of Different Age Groups Six Months after Coronary Artery by-pass Surgery

K. Bozovic, V. Andrijasevic
University of Pristina, Institute of Internal Medicine

Introduction: Examination of the preoperative and postoperative quality of life relation to the patients’ (pts) age – group and determination weather the patient’s age could be predictor of the QOL changes after CABG.

Material and Methods: From February to May 2002, we administered the Nottingham Health Profile Questionnaire part I in a consecutive series of patients (243 pts, 195 men) who underwent elective CABG. It contains 38 subjective statements divided into six sections: physical mobility (PM), social isolation (SI), emotional reaction (ER), energy (En), pain and sleep. The questionnaire was distributed before and six months after CABG, to all patients.

Results: Four age groups were studied: Conclusion: Older patients had worse preoperative QOL. More significant improvement was registered in patients who had worse QOL preoperatively (older pts). Younger age is the independent predictor of QOL improvement in the section of pain after CABG.

Advanced Glycation Endproducts and Their Role in the Field of Vascular Surgery

E.A.H. Loeffen, R.B. Saleem, F. Stelma, R. Meerwaldt, J.D. Lefrandt, A.J. Smit, C.J. Zeebregts
University Medical Center Groningen, Department of Surgery (Division of Vascular Surgery)

Introduction: The formation of advanced glycation endproducts (AGEs) is the result of the non enzymatic reaction of reducing sugars with free amino groups of proteins, lipids and nucleic acids. They represent the cumulative burden of hyperglycaemia, hyperlipidaemia, and oxidative and carbonyl stress. Previous studies have shown direct relations between level of AGEs as detected by skin autofluorescence and progression of vascular stenosis and plaque vulnerability, and they predict future cardiovascular morbidity and mortality. This study intends to examine the exact role of AGEs in the field of vascular surgery. First of all, is the level of AGEs increased in patients suffering from severe atherosclerotic disease? Furthermore, the skin AGE level differences between aneurismal and atherosclerotic occlusive disease will be examined, as well as the differences between preoperative and postoperative patients.

Material and Methods: Between September 2007 and February 2008 non-invasive AGEs measurements were proposed to all patients attending the out-patient clinics of the Division of Vascular Surgery of our hospital. The tissue accumulation of AGEs was measured with an AutoFluorescence Reader (Diagnoptics BV, Groningen, The Netherlands), designed to noninvasively and rapidly measure skin auto fluorescence and so AGE accumulation. Patients with diabetes or varicose veins were excluded from this study.

Results: The present study group consisted of 359 patients, 275 male (77%) and 84 female (23%) (ratio 3:1). The average age was 67 years, ranging from 23 to 89 years. Regarding the first aim of this study, our study group showed a higher level of skin AGEs than the normal distribution (2.74 arbitrary units (AI) vs. 2.38, respectively). With a p value smaller than 0.001, this is a significant difference.

No difference (p=0.44) was found between aneurismal (n=121, 2.71) and atherosclerotic occlusive (n=214, 2.74) disease.

With regard to the third aim of the study, approximately half of the study group (n=193, 54%) underwent vascular surgery before AGEs measurement. Although a slight difference between preoperative (2.71) and postoperative (2.77) values was found, this difference was not significant (p=0.40).

Conclusion: It can be concluded that AGE accumulation is increased in patients suffering from severe atherosclerotic disease. This implicates a strongly raised cardiovascular risk and increased mortality. These AGE levels however, do not seem to be affected by the nature of vascular disease, nor by a surgical intervention.
Further evaluation will be needed to define the exact role of AGEs in the field of vascular surgery.

Preoperative Statin Therapy in Surgical Ablation of Atrial Fibrillation in Patients Undergoing Concomitant Cardiac Surgery

M.J. Borys, O.J. Liakopoulos, P.L. Haldenwang, J. Strauch, Y.H. Choi, T. Wittwer, J. Wippermann, T. Wahlers
University Hospital of Cologne

Introduction: Statin therapy reduces the incidence of atrial fibrillation (AF) after cardiac surgery through anti-inflammatory effects. We hypothesized that statin use prior to surgical ablation for AF during concomitant cardiac procedures can improve early ablation outcomes.

Material and Methods: One-hundred patients (69±10 years;69% men) with paroxysmal (34%) or permanent (66%) AF undergoing cardiac surgery (CABG 55%, valve surgery 65% and aortic surgery 4%) and surgical ablation were retrospectively analyzed. Applied energy sources for AF ablation were radiofrequency (84%) and ultrasound (16%). Fifty patients (50%) were on preoperative statins (statin group) before surgery. Early conversion rates to SR (OR, ICU, hospital discharge, 3 months), freedom from anti-arrhythmic therapy and pro-inflammatory C-reactive protein (CRP) levels were recorded.

Results: Intraoperative conversion rate to SR was 92% and 94% in statin and control patients. SR was preserved in 82% vs. 80% of patients at ICU, 52% vs 56% at discharge and 55% vs 62% at 3 months in statin pretreated and control patients (p=n.s). Similarly, there was no difference in electrical cardioversion rates (8% control vs 16% statins) and freedom from antiarrhythmic therapy (56% control vs 42% statins) between treatment groups. Preoperative statin use was not linked to reduced CRP levels after surgical ablation (maximal CRP 165±68 (control) vs. 177±67 mg/dl (statin); p=n.s.).

Conclusion: Our preliminary data suggests that preoperative statin therapy is not associated with improved early ablation outcome in patients undergoing cardiac surgery with surgical ablation for AF. Data from RCT with extended follow-up periods are needed to allow definite conclusions.

Ultrasound Anatomy of Venous System of Posterior Compartment of the Thigh

Ż. Żabicka, K. Krasowska
Medical University of Warsaw Department of Anatomy

Introduction: Disturbances of venous outflow from the posterior compartment of the thigh can result in formation of varicose veins and teleangiectasias on the posterior aspect of the thigh. In case of increased venous pressure in veins of sciatic nerve, patients often complain of the symptoms of ischialgia due to sciatic nerve ischemia. Presence of sciatic perforating veins and cranial extension of short saphenous vein (CESSV) can promote the recurrence of varicose veins. Diagnostic imaging of these vessels bases nowadays on ultrasound visualization accompanied by Power Doppler and Color Doppler. The study aimed to describe the most common patterns of venous outflow from the posterior muscular compartment of the thigh with a special attention to CESSV.

Material and Methods: Research was carried out on ultrasonographic examinations of 42 lower extremities of 21 healthy volunteers aged 20-34 years (12 males, 9 females). Ultrasonographic examinations were done using GE Voluson 730 Expert scanner equipped with 7,5 MHz linear transducer in B-mode, including PW Doppler, Power Doppler and Color Doppler studies. In case of problems in identification of a vessel compliance test and Power Doppler were used.

Results: Ultrasound studies showed the presence of CESSV in 37 limbs (20 right, 17 left). In 11 cases (7 right, 4 left) it continued toward great saphenous vein as intersaphenous vein of Giacomini. Subfascial course of CESSV with its drainage into deep veins of the thigh was observed in 17 extremities (11 right, 6 left). It was impossible to determine exactly in which of deep veins CESSV terminated. In 9 cases (2 right, 7 left) the CESSV anastomosed epifascially with superficial veins and disappeared on posterior surface of the thigh.

Conclusion: (1) CEESV was present in majority of examined extremities. (2) CESSV can be visualized using ultrasound examination. Power Doppler and Color Doppler are useful to ease visualization and assess direction of blood flow. Course of CESSV is easy to visualize especially in cases where Giacomini’s vein is present. (3) Termination of CESSV draining to deep venous system is usually difficult to visualize.

The Relationship Between a Novel Tissue Doppler Index and NTproBNP Levels in Patients with Left Ventricular Dysfunction

C.M. Georgescu, R.J. Joikits
University of Medicine and Pharmacy ”Victor Babeş”

Introduction: N-terminal pro-brain natriuretic peptide (NTproBNP) is recognized as a reliable marker of systolic and diastolic left ventricular (LV) function. The ratio between early diastolic transmitral velocity and early mitral annular diastolic velocity (E/Ea) reflects LV filling pressure in a variety of cardiac diseases. However this relationship was not validated in some categories of patients. We belive that combining the index of diastolic function (E/Ea) and a parameter that explores LV systolic performance (Sa, peak systolic velocity of mitral annulus) provides a close prediction of NTproBNP.

The aim of this study is to assess the relationship between a new parameter, E/(Ea?—Sa), and NTproBNP level in patients with LV dysfunction.

Material and Methods: We screened 145 consecutive patients with LV dysfunction in sinusal rhythm referred for LV cathetherism. Patients with inadequate echocardiographic image, paced rhythm, mitral stenosis, significant primary or organic mitral regurgitation, mitral prosthesis, severe mitral annular calcification, pericardial disease, acute coronary syndrome, coronary artery by-pass within 72 hours or renal failure were excluded. The remaining 113 patients (78 with heart failure with reduced ejection fraction –HFREF, 12 with HF with normal EF, 23 with isolated diastolic dysfunction) formed our study group. Echocardiography was performed simultaneously with NTproBNP measurement. E/Ea and E/(Ea?—Sa) were calculated; the average of the velocities of septal and lateral mitral annulus was used.

Results: Simple regression analysis demonstrated a significant linear correlation between E/(Ea?—Sa) and NTproBNP (r=0,70, p<0<0<01200 pg/ml was 1,6 (sensitivity=83%, specificity=75%). Among analyzed parameters, E/(Ea?—Sa) was best correlated with NTproBNP levels in patients with HF with normal EF (r=0,77, p<0<0<0Conclusion: E/(Ea?—Sa) had a good correlation with plasma NTproBNP level and can be a simple, reproductible and accurate echocardiographic index in patients with LV dysfunction in sinusal rhythm.

InflammatoryResponse to Myocardial Ischemia Reperfusion Injury in Patients with and Without Pre-existing Heart Failure

K.A. Kortekaas, J.H.N. Lindeman, R.J.M. Klautz

Introduction: Myocardial Ischemia Reperfusion Injury (MIRI) is the paradoxical exacerbation of myocardial damage upon restoration of blood flow to previously ischemic myocardial tissue. MIRI is held responsible for Systemic Inflammatory Response Syndrome (SIRS) after cardiac surgery. For unknown reasons is SIRS more common in patients with pre-existing heart failure. We hypothesize that this discrepancy is caused by a different myocardial inflammatory response to MIRI. In a pilot study we examined the local inflammatory response in patients with and without pre-existing heart failure, and we determined the feasibility of the study and the optimal times for blood sampling.

Material and Methods: Arteriovenous concentration differences were used to specifically measure myocardial inflammatory responses. Paired blood samples, of five patients with and five without pre-existing heart failure undergoing mitral valve surgery, were obtained at fixed time-points until twenty-four hours after reperfusion by using a coronary sinus (CS) catheter. For a comprehensive analysis we measured a panel of cytokines using the Bio-Plex human cytokine 27-plex panel to investigate inflammatory pathways. Endothelial activation was established by ICAM-1 and vWF.

Results: Feasibility of sampling out of the CS was confirmed by measurement of oxygen saturation, which was in CS blood almost 10% lower than in central venous blood. Significant release of IL-1β (p = 0,036), IL-6 (p = 0,001) and IL-9 (p = 0,005) twenty-four hours after reperfusion was shown. Our study did not reveal significant differences for other cytokines, neither arteriovenous nor between patients with and without pre-existing heart failure. Endothelial activation was not established by measuring ICAM-1 and vWF.

Conclusion: Feasibility of sampling from the CS and optimal times for blood sampling were confirmed with this pilot study. Arteriovenous differences for IL-1β, IL-6 and IL-9 were found, indicating a cardiac origin of these cytokines. Indications for plasma concentration differences of cytokines between patients with and without pre-existing heart failure were found, but the differences were not significant. The hypothesis that a different response to MIRI underlies the more frequent development of SIRS in patients with pre-existing heart failure needs further investigation.

Supported by NHF grant 2007B150

Warming Due to Hydration of DMSO is the Cause of Hypotension Following Intra Peritoneal Injection in Rat

B. Heshmatian, F. Moloudi, E. Saboori
Urmia University of Medical Science

Introduction: Dimethyl sulfoxide (DMSO) is one of the most common solvents of organic substances and has multidisciplinary utilization due to its therapeutic effects and several laboratory properties. Some cardiovascular side effects of DMSO have been reported. We accidentally found that it has a major hypotensive effect. In this study we investigated the mechanism of hypotesion following intra peritoneal injection of DMSO.

Materials & Methods: In urethane anesthetized rats, direct measurement of arterial blood pressure and intra peritoneum temperature were performed. We investigated the effects of DMSO on blood pressure by intra peritoneal (IP) injection of 1gr/kg pure DMSO (100%) or saline diluted DMSO (80%, 60% and 50%) in a way that in all cases equal amount of DMSO was injected. In other group, 3ml of 42ċ normal saline was injected for evaluation of peritoneum warming on blood pressure. Following all injections, arterial blood pressure and intra peritoneum temperature were measured. We also investigated the effects of pre-treatment with histamine receptor antagonists (Chlorpheniramine 4mg/kg), nitric oxide synthase inhibitor (L-NAME, 40 mg/kg) or vagotomy on hypotensive effects of DMSO and warm saline.

Results: This study shows that the IP injection of 100%, 80% and 60% of DMSO lead to ±5, ±6 and ±4 reduction in mean arterial pressure respectively, accompanied by increasing of the intra peritoneum temperature at the range of 3±0.2 ċ,1.5±0.1 ċ and 1.2±0.3ċ respectively. The 50% DMSO didn’t change blood pressure or peritoneum temperature. Pre-treatment with L-NAME and vagotomy partially attenuated effects of non hydrated DMSO and warm saline on blood pressure but cholorpheniramine inhibited this effect completely.

Conclusion: According to our results, DMSO hydration in peritoneum increases temperature that results in mesenteric vascular dilation and hypotension by reduction of peripheral resistance against blood flow. Mesenteric thermoregulatory mechanisms are mediated by local release of histamine and nitric oxide and/or neural parasympathetic reflexes. IP injection of warm saline causes similar effects to DMSO, whereas completely hydrated DMSO has no effect. This study for the first time reveals the biological effects of DMSO which is due to its thermogenic properties following hydration. Thermogenic hydration of DMSO is the probable cause of some side effects, such as bradycardia, heart block, cardiac arrest and hemolysis. Regarding to frequent

clinical use of DMSO, further investigation is needed to clarify concern about this phenomenon.

The Effect of Psychosocial Factors on the Recovery of Patients after Cardia Surgery

A. Toth, R. Toth, Dr. A. Szekely, T. Breuer, E. Losoncz, P. Balogh, Zs. Cserep
Semmelweis University

Introduction: Anxiety has been shown to predict long-term mortality after myocardial infarction and cardiac surgery. We have hypothesized that psychosocial factors contribute to in-hospital mortality and morbidity.

Material and Methods: After Institutional Review Board Approval 271 patients undergoing elective cardiac operation were enrolled into the study between November 20, 2006 and November 19, 2007. Preoperative anxiety was measured by Spielberger State Trait Inventory test, depression was tested by Beck Depression Inventory (BDI) test. Somatic severity score, self-rated health were recorded beside clinical risk factors, EuroSCORE and perioperative characteristics. End points were death and length of stay at the intensive care unit ≥3 days.

Results: Four patients (1.5%) died and 36 patients (13.3%) were ≥3 days at the ICU days. EuroSCORE (3.8±2.8 vs. 4.9±2.9; p=0.026) and somatic severity score (7.8±5.4 vs. 10.3±6.3; p=0.038) were significantly different in patients who needed ICU stay ≥3 days compared to patients who stayed less. Independent predictors of prolonged intensive care were EuroSCORE [1.14 (1.01-1.28), p=0.041], somatic severity [1.08 (1.01-1.15). p=0.020] and BDI score [1.06 (1.00-1.12), p=0.044]. C index of the multivariate model was higher, when psychosocial factors were included (AUC: 0.70) compared to the model of clinical factors only (AUC: 0.61).

Conclusion: Length of ICU after cardiac surgery is influenced by preoperative psychosocial factors, like depression or somatic severity score.

Activation of Cardiac Potassium Channel HERG May be a Determinant of Extracellular Potassium Dependency of Block by Terfenadine

K.R. Richter, B. Barrows, J. Schulze, A. Miller
Touro University

Introduction: One form of Long QT syndrome referred to as acquired Long QT syndrome has been shown to primarily result from a reduction in the cardiac potassium channel HERG by a number of pharmaceutical compounds. In some instances Long QT syndrome will degenerate into the potentially lethal arrhythmia torsade de pointes, characterized by a rapid heart rate and compromised cardiac output. Many patients requiring medication present with abnormal serum electrolyte levels due to a variety of conditions including gastrointestinal dysfunction, renal and endocrine disorders, diuretic use, alcoholism and aging. Extracellular electrolytes, in particular extracellular potassium have significant influence on HERG channel behavior and have been shown to alter drug block of HERG. However the mechanisms by which drug block is altered in different extracellular solutions are not well understood.

Material and Methods: We used two electrode voltage clamping of Xenopus oocytes to measure block of both wild type and a HERG mutant (D540K) by terfenadine. cRNA of either WT HERG or the D540K mutant was injected into enzymatically defolliculated oocytes and currents recorded 3-5 days after injection.

Results: We previously reported that block of HERG by terfenadine shows the opposite dependency on extracellular potassium compared to quinidine. HERG block by quinidine is greater in 0 mM K (0K) compared to 20 mM K (20K) whereas block by terfenadine is greater in 20K compared to 0K. In order to determine the mechanism underlying this difference in potassium dependency we measured block by terfenadine of the HERG mutant D540K, an usual mutant which opens with both depolarization and hyperpolarization. Block of D540K by terfenadine showed the opposite dependency on extracellular potassium compared to block of WT HERG by terfenadine. Thus block of D540K by terfenadine is greater in 0K compared to 20K similar to the block of WT HERG by quinidine.

Conclusion: Recent experiments indicate that terfenadine is trapped inside the channel after the channel closes whereas quinidine is not. In addition we have reported that block of HERG by quinidine shows a strong correlation with permeant ion. Together these results suggest that the permeant ion is not able to destabilize a trapped drug but is able to destabilize a drug that is not trapped and indicate a possible role for the activation gate in determining the extracellular potassium dependency of block of HERG.

Autonomic Nervous System Modulations in Paroxysmal Atrial Fibrillation

Dr. M.M. Rogova, N.Y. Mironov, S.F. Sokolov
Russian Cardiology Research Complex

Introduction: Atrial fibrillation (AF) is a major clinical problem involving a growing number of patients with different clinical manifestations and causing a significant social and economic impact. Only a few clinical investigations were made to verify the existence of a link between AF episodes and autonomic nervous system modulations.

Aim: to investigate deviations of autonomic nervous system tonus in patients with AF prior to onset of paroxysm.

Material and Methods: Time-domain statistical heart rate variability analysis used to assess autonomic nervous system modulation in 24-hour ECG of 28 healthy subjects and 21 patients with paroxysmal AF. RMSSD (the square root of mean of the sum of squares of differences between adjacent NN intervals) parameter is known to reflect both sympathetic and vagal activity. RMSSD values in patients with AF for the last 60 minutes prior to onset of paroxysm were compared with healthy subjects values.

Results: Median RMSSD in patients with AF is higher than median RMSSD in healthy subjects (p<0Conclusion: Onset of AF is associated with modulations in autonomic nervous system. Increase in RMSSD observed in the first group reflects the activation of parasympathetic nervous system – patients have vagal-dependant AF paroxysms. Decrease in RMSSD shows sympathetic activation hence the patients of the second group have sympathetic-dependant AF paroxysms. Further studies are needed to investigate the role of vagal activation in the last 10 minutes in onset of AF paroxysm.