scholarly journals Antiarrhythmic effect of ranolazine in combination with selective NCX-inhibition in an experimental model of atrial fibrillation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Wolfes ◽  
C Ellermann ◽  
N Broer ◽  
K Willy ◽  
B Rath ◽  
...  

Abstract Background Previous studies showed an antiarrhythmic effect of ranolazine in different clinical and experimental studies. The aim of this study was to investigate the effects of a combination of ranolazine with different selective NCX-inhibitors in an established experimental model of atrial fibrillation. Methods and results 18 hearts of New Zealand white rabbits were retrogradely perfused. Left and right atrial catheters were used to record monophasic action potentials. Hearts were paced at three different cycle lengths (350ms, 250ms, 150ms). Thereby, cycle-length dependent atrial action potential durations (aAPD90), atrial effective refractory periods (aERP) and atrial post-repolarization refractoriness (aPRR=aERP-aAPD90) were obtained. Vulnerability to AF was tested by a standardized protocol employing several trains of burst pacing. After generating baseline data, the hearts were perfused with a combination of acetylcholine (ACh, 1μM) and isoproterenol (Iso, 1μM) to increase occurrence of AF. Afterwards, the hearts were assigned to two groups and additionally perfused with a combination of 10 μM ranolazine and 1 μM of the selective NCX-inhibitor ORM-10103 (group 1: Rano-ORM) or 10 μM ranolazine and 1 μM of another NCX-inhibitor, SEA0400 (group 2: Rano-SEA). Infusion of ACh/Iso led to a shortening of aAPD90 (group 1/2: −27.2ms/−24.5ms p<0.05), aERP (−29.2ms/−35.6ms p<0.05), aPRR (−12.2ms/−13.7ms p=ns) and the occurrence of AF-Episodes was significantly increased (group 1: baseline 6 episodes to 34 episodes under ACh/Iso p<0.05, group 2: baseline 7 episodes to 26 episodes under ACh/Iso p<0.05). Additional perfusion with ranolazine and ORM-10103 did not alter aAPD90 (−0,47ms) while effective refractory periods (+21.4ms, p<0.05) and aPRR (+43ms, p<0.05) were significantly prolonged and AF episodes were effectively reduced to 15 episodes (p<0.05). In group 2, Rano-SEA led to a slight decrease in aAPD90 (−9.5ms) while aERP (+13.3ms, p<0.05) and aPRR (+19.8ms, p<0.05) were prolonged. The occurrence of AF episodes was reduced to 15 episodes (p=0.1). Conclusion To our knowledge this is the first study investigating the effect of ranolazine combined with different selective NCX-inhibitors in an isolated whole-heart model of AF. Atrial repolarization was not significantly changed with either of the combinations. However, both combinations prolonged aERP and aPRR and thereby suppressed induction of AF. Combining novel cellular targets may therefore lead to new potentially interesting options for antiarrhythmic AF therapy that have to be tested in clinical studies. Funding Acknowledgement Type of funding source: None

2020 ◽  
Vol 13 (10) ◽  
pp. 321
Author(s):  
Julian Wolfes ◽  
Christian Ellermann ◽  
Niklas Broer ◽  
Benjamin Rath ◽  
Kevin Willy ◽  
...  

The aim of this study was to investigate the effects of a combination of ranolazine with different selective inhibitors of the Na+/Ca2+-exchanger (NCX) in an established experimental model of atrial fibrillation (AF). Eighteen hearts of New Zealand white rabbits were retrogradely perfused. Atrial catheters were used to record monophasic action potentials (aPRR). Hearts were paced at three different cycle lengths. Thereby, atrial action potential durations (aAPD90), atrial effective refractory periods (aERP) and atrial post-repolarization refractoriness were obtained. Isoproterenol and acetylcholine were employed to increase the occurrence of AF. Thereafter, the hearts were assigned to two groups (n = 9 each group) and additionally perfused with a combination of 10 µM ranolazine and 1 µM of the selective NCX-inhibitor ORM-10103 (group A: Rano-ORM) or 10 µM ranolazine and 1 µM of another NCX-inhibitor, SEA0400 (group B: Rano-SEA). The infusion of Iso/ACh led to a shortening of aAPD90, aERP, aPRR and the occurrence of AF episodes was significantly increased. Additional perfusion with ranolazine and ORM-10103 (group A) significantly prolonged the refractory periods and aPRR and AF episodes were effectively reduced. In group B, Rano-SEA led to a slight decrease in aAPD90 while aERP and aPRR were prolonged. The occurrence of AF episodes was consecutively reduced. To our knowledge, this is the first study investigating the effect of ranolazine combined with different selective NCX-inhibitors in an isolated whole-heart model of AF. Both combinations prolonged aERP and aPRR and thereby suppressed the induction of AF.


EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
K Etsadashvili ◽  
N Kuridze ◽  
T Kavtiashvili ◽  
T S Chaligava ◽  
V Chumburidze

Abstract Background. According to the recent guidelines, effective anticoagulation is recommended for a minimum of 3 weeks before the cardioversion of Atrial Fibrillation/Atrial Flutter. Transoesophageal echocardiography (TOE) could be considered, but is not mandatory to exclude/confirm the cardiac thrombus before the cardioversion in adequately anticoagulated patients. Aim of the study was to reveal the incidence of thrombus or spontaneous echo contrasting (SEC) by TOE before cardioversion, despite effective anticoagulation. Material and methods. Patients, where TOE was performed to evaluate the evidence of thrombus/SEC before the cardioversion of AF/Atrial flutter at our clinic in period of 2016-2018, were studied. Incidence of intracardiac thrombus and its relation to patients’ gender, age, hypertension, diabetes, atrial diameter, LVEF, duration of Atrial Fibrillation/Atrial flutter, as well as to anticoagulation regimen were evaluated. Results. All patients received recommended anticoagulation therapy, DOACs or VKAs, for a minimum of 3 weeks before the TOE. Finally 180 patients were divided in two groups: group 1 (121 patients) without evidence of thrombus and group 2 (59 patients) where TOE revealed the thrombus. Thrombus was found in 37 (20.5%) patients, and SEC was found in 22 (12.2%) patients. There were no difference between the two groups with respect to: gender (85 male (70%) in group 1 vs. 38 male (64%) in group 2, p = NS), age (62.8 ± 8.73 vs. 63.0 ± 9.04, p = NS), hypertension (78 (64.4%) vs. 44 (74.6%), p = NS), diabetes (17 (14%) vs. 7 (12%), p = NS), CHAD2DS2-VASc score (2.2 ± 1.8 vs. 2.4 ± 4.0, p = NS), LVEF (48.1 ± 7.1% vs. 46.4 ± 7.3%, p = NS), duration of arrhythmia (7.7 ± 11.6 months vs. 9.7 ± 14.0 months, p = NS), type on anticoagulation (DOACs 59 (48.3%) vs. 30 (50.8%), p = NS, VKA (Warfarin) 54 (44.6%) vs. 29 (49.1%), p = NS)) respectively. Only difference in atrial diameter was found statistically significant between the two groups: left atrial diameter (42.6 ± 3.3mm vs. 45.3 ± 3.6mm, p < 0.001) and right atrial diameter (39.4 ± 3.3mm vs. 40.8 ± 2.3mm, p = 0.001) respectively. Conclusion. Thrombus/SEC could persist despite the effective anticoagulation therapy for ≥3 weeks. Therefore all patients should perform TOE before the cardioversion to avoid the incidence of stroke.


Pharmacology ◽  
2018 ◽  
Vol 102 (3-4) ◽  
pp. 138-141 ◽  
Author(s):  
Christian Ellermann ◽  
Anja Kohnke ◽  
Dirk G. Dechering ◽  
Simon Kochhäuser ◽  
Florian Reinke ◽  
...  

Objectives: Levosimendan is a calcium sensitizer that is used as positive inotropic drug in acute decompensated heart failure. An increased incidence of atrial fibrillation after levosimendan-treatment was observed in clinical and experimental studies. Due to the limited range of antiarrhythmic drugs, the aim of the present study was to assess potential antiarrhythmic effects of ranolazine in levosimendan-pretreated isolated rabbit hearts. Methods: Twelve rabbit hearts were excised and retrogradely perfused employing the Langendorff setup. Left and right atrial catheters were used to record monophasic action potentials and to obtain cycle length-dependent atrial action potential durations (aAPD90) and effective refractory periods (aERP). After obtaining baseline data, 0.5 µmol/L levosimendan was infused. Subsequently, 10 µmol/L ranolazine was administered. Results: Infusion of levosimendan led to a reduction of aAPD90 (–9 ms, p < 0.05) and aERP (–13 ms, p < 0.05). Additional treatment with ranolazine prolonged aAPD90 (+23 ms, p < 0.01) and aERP (+30 ms, p < 0.05). Under baseline conditions, a predefined pacing protocol induced 77 episodes of atrial fibrillation. Infusion of levosimendan enhanced the vulnerability to atrial fibrillation (132 episodes, p = 0.14). Further treatment with ranolazine had a significant antiarrhythmic effect (61 episodes, p < 0.05). Conclusions: In this study, ranolazine seems to prevent atrial fibrillation in levosimendan-pretreated hearts. Underlying mechanism is a prolongation of atrial repolarization and aERP.


2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
E Pilichowska ◽  
J Baran ◽  
P Kulakowski ◽  
B Zaborska

Abstract PURPOSE Left atrial (LA) fibrosis is the hallmark of LA remodeling in atrial fibrillation (AF), alters LA function and may predict poor catheter ablation (CA) outcome. LA fibrosis may be assessed invasively using electroanatomical mapping (EAM) during electrophysiological study. The aim was to assess LA function parameters in relation to degree of LA fibrosis derived from EAM in patients with AF. METHODS Patients (pts) n = 39 (79% males, mean age 56+/-10) with non-valvular AF were studied with TTE and TEE before first CA during sinus rhythm. LA strain (LAS) and strain rate (LASR) were analyzed in reservoir (r), conduit (cd) and contractile (ct) phases. The velocities of mitral A, E" and A" were measured with Doppler. E/E" and LA stiffness index - the ratio of E/E" to LASr were assessed. LA appendage flow velocity (LAAv) was measured in TEE. LA volume using biplane area-length method was calculated. The EAM of LA was build using Carto System before CA. Low amplitude potentials area (LAPA) was quantitatively analyzed and expressed as a percentage of LA surface using the cut-off &lt;0.5 mV to detect sites of fibrosis. LA parameters were compared between mild (LAPA &lt;10%) moderate (LAPA 10-40%) and extensive degree of LA fibrosis (LAPA &gt;40%) (table). RESULTS The mean LA volume was 35 ± 11 mL/m². The LAPA ranged from 2 to 78 % of LA surface. Reduced LA function was observed in the LAPA &gt;40% group. Extensive LAPA altered mainly LA compliance parameters. Traditional LA systolic function parameters did not differ in relation to degree of LAPA. CONCLUSION LA compliance is mostly affected by LA fibrosis, thus LA diastolic parameters may be useful in the noninvasive assessment of LA fibrosis. Whether these parameters should be a part of the proper selection of candidates for CA requires further studies. LA function parameters LA parameters Group 1 LAPA &lt;10% n = 13 Group 2 LAPA &gt;10% &lt;40% n = 13 Group 3 LAPA &gt;40% n = 13 P-value Group 1 + 2 vs 3 Mitral A 0.55 ± 0.10 0.55 ± 0.24 0.73 ± 0.32 0.077 A" 9.19 ± 1.74 7.85 ± 1.43 7.92 ± 2.40 0.376 LASr 31.48 ± 4.52 26.48 ± 8.79 19.63 ± 6.76 &lt;0.001 LAScd 17.30 ± 3.05 15.44 ± 6.93 10.91 ± 4.04 0.003 LASct 14.18 ± 5.36 11.05 ± 3.67 8.72 ± 4.78 0.024 LASRr 1.22 ± 0.19 1.24 ± 0.21 0.92 ± 0.20 &lt;0.001 LASRct -1.71 ± 0.46 -1.37 ± 0.34 -1.04 ± 0.33 &lt;0.001 LA stiffness 0.20 ± 0.07 0.34 ± 0.17 0.63 ± 0.29 &lt;0.001 LAAv 0.83 ± 0.18 0.55 ± 0.17 0.60 ± 0.16 0.178


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Demenko ◽  
G.A Chumakova

Abstract Background Mental disorders in patients with cardiovascular disease have a significant impact on the course, the prognosis of the underlying disease and quality of life (QOL). Objective We aimed to examine the prevalence of anxiety and depressive disorders and their impact on the quality of life in patients with atrial fibrillation (AF). Materials and methods In 52 with permanent AF and 50 with paroxysmal AF patients, we administered the depression scale Tsung, the scale of situational anxiety (SA) and personal anxiety (PA) Spielberger-Hanin; QOL was assessed the SF-36 quality of life assessment scale. Correlation analysis using Spearman's rank correlation coefficient. Results The prevalence symptoms mild depression situational or neurotic genesis was 21.1% (12 patients) in Group 1 and 12.0% (6 patients) in Group 2 (p&gt;0.05). Subdepressive state was two percents of patients in Group 1 and Group 2. The incidence SA was 59.6% (31 patients) in Group 1 and 52.0% (26 patients) in Group 2. The incidence PA was 74.0% (37 patients) in Group 2 and 67.3% (35 patients) in Group 1. The average score the physical component of health (PCH) was 29,8±4,3 in Group 1, the mental component of health (MCH) – 49.5±7.4 points; p&lt;0.05. In Group 2: PCH – 44.8±6.6 points, MCH – 26.6±7.5 points; p&lt;0.05. Correlation analysis showed negative strong correlations between SA and MCH (r=−0.64, p=0.0005) and between PA and MCH (r=−0.69, p&lt;0.0001), between SA and PCH (r=−0.71, p=0.0001), between depression and PCH (r=−0.69, p=0.023). Negative statistically significant correlation between depression and MCH (r=−0.69, p=0.54) and negative medium correlation between depression and PCH (r=−0.64, p=0.23). Conclusion These findings suggest that we did not identify patients with symptoms of a true depressive (that can cause pseudodementia and influenced to complete tests). 16.5% patients with AF had mild depression of situational or neurotic genesis. Depression may be a pathogenetic factor of AF or develop because of paroxysms AF – psychological stress. More than 50% patients in Group 1 and Group 2 had an increased anxiety score. SA is more common in patients with permanent AF, probably because older people difficult to adapt to a new situation. PA is more common in patient with paroxysmal AF, probably because disease is sudden and causes anxiety. The PCH of QOL is more impairment in patients with permanent AF, because complications (for example heart failure) impairment physical activity. However, PCH also reduced in patient with paroxysmal AF, because disease is sudden may occur during physical activity. The MCH of QOL is more impairment in patients with paroxysmal AF, because waiting attack effect on mental health and social functioning. An increased level of anxiety and depression negatively affected the mental and physical health of patients with AF. Funding Acknowledgement Type of funding source: None


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Di Cori ◽  
L Segreti ◽  
G Zucchelli ◽  
S Viani ◽  
F Tarasco ◽  
...  

Abstract Background Contact force catheter ablation is the gold standard for treatment of atrial fibrillation (AF). Local tissue impedance (LI) evaluation has been recently studied to evaluate lesion formation during radiofrequency ablation. Purpose Aim of the study was to assess the outcomes of an irrigated catether with LI alghorithm compared to contact force (CF)-sensing catheters in the treatment of symptomatic AF. Methods A prospective, single-center, nonrandomized study was conducted, to compare outcomes between CF-AF ablation (Group 1) and LI-AF ablation (Group 2). For Group 1 ablation was performed using the Carto 3© System with the SmartTouch SF catheter and, as ablation target, an ablation index value of 500 anterior and 400 posterior. For Group 2, ablation was performed using the Rhythmia™ System with novel ablation catheter with a dedicated algorithm (DirectSense) used to measure LI at the distal electrode of this catheter. An absolute impedance drop greater than 20Ω was used at each targeted. According to the Close Protocol, ablation included a point by point pulmonary vein isolation (PVI) with an Inter-lesion space ≤5 mm in both Groups. Procedural endpoint was PVI, with confirmed bidirectional block. Results A total of 116 patients were enrolled, 59 patients in Group 1 (CF) and 57 in Group 2 (LI), 65 (63%) with a paroxismal AF and 36 (37%) with a persistent AF. Baseline patients features were not different between groups (P=ns). LI-Group showed a comparable procedural time (180±89 vs 180±56, P=0.59) but with a longer fluoroscopy time (20±12 vs 13±9 min, P=0.002). Wide antral isolation was more often observed in CF-Group (95% vs 80%, P=0.022), while LI-Group 2 required frequently additional right or left carina ablation (28% vs 14%, P=0.013). The mean LI was 106±14Ω prior to ablation and 92.5±11Ω after ablation (mean LI drop of 13.5±8Ω) during a median RF time of 26 [19–34] sec for each ablation spot. No steam pops or complications during the procedures were reported. The acute procedural success was 100%, with all PVs successfully isolated in all study patients. Regarding safety, only minor vascular complications were observed (5%), without differences between groups (p=0.97). During follow up, 9-month freedom from atrial fibrillation/atrial flutter/atrial tachycardia recurrence was 86% in Group 1 and 75% in Group 2 (P=0.2). Conclusions An LI-guided PV ablation strategy seems to be safe and effective, with acute and mid-term outcomes comparable to the current contact force strategy. LI monitoring could be a promising complementary parameter to evaluate not only wall contact but also lesion formation during power delivery. Procedural Outcomes Funding Acknowledgement Type of funding source: None


2018 ◽  
Vol 24 (9_suppl) ◽  
pp. 188S-193S
Author(s):  
Jen-Hung Huang ◽  
Yung-Kuo Lin ◽  
Cheng-Chih Chung ◽  
Ming-Hsiung Hsieh ◽  
Wan-Chun Chiu ◽  
...  

Rivaroxaban, a direct factor Xa inhibitor, is widely used to reduce the chance of stroke in patients with atrial fibrillation (AF). It is not clear why the prothrombin time (PT) of the international normalized ratio (INR) fails to correlate with treatment using rivaroxaban in patients with AF. In this study, patient characteristics, the rivaroxaban dosage, AF type, drug history, biochemical properties, and hematological profiles were assessed in patients treated with rivaroxaban. In 69 patients with AF receiving rivaroxaban, 27 (39.1%) patients had a normal INR (≤1.1, group 1), 27 (39.1%) patients had a slightly prolonged INR (1.1∼1.5, group 2), and 15 (21.7%) patients had a significantly prolonged INR (>1.5, group 3). Group 1 patients had a higher incidence of a stroke history than did patients in group 2 ( P = .026) and group 3 ( P = .032). We scored patients with a persistent AF pattern (1 point), paroxysmal AF pattern (0 point), renal function (ie, the creatinine clearance rate in mL/min/1.73 m2 of >60 as 0 points, of 30∼60 as 1 point, and of <30 as 2 points), and no history of stroke (1 point), and we found that group 3 had a higher score than groups 2 or 1 (2.9 ± 0.8, 2.4 ± 0.7, and 2 ± 0.7, respectively; P < .05). There were similar incidences of bleeding, stroke, and unexpected hospitalizations among the 3 groups. The PT of the INR is determined by multiple variables in patients with AF receiving rivaroxaban. Rivaroxaban-treated patients with AF having different INR values may have similar clinical outcomes.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Mahajan ◽  
D.R Prakash Chand Negi

Abstract Introduction Juvenile rheumatic heart disease (RHD) refers to RHD in patients &lt;20 years of age. There are no contemporary data highlighting the differences between juvenile and older RHD patients. Purpose We aim to report the age related differences in the pattern, and consequencies of valvular dysfunction in patients of RHD. Methods The 2475 consecutive patients of RHD diagnosed using clinical and echocardiographic criteria were registered prospectively from 2011 till December 2019. Patients were divided into 3 groups according to their age: Group 1 (Juvenile RHD), Group 2 (21–50 years), and Group 2 (&gt;51 years).The data concerning the socio-demographic and clinical profile were recorded systematically, and the nature and severity of valvular dysfunction was assessed by echocardiography. The data were analyzed using the Epi-InfoTM Software. Results Out of 2475 RHD patients, Juvenile RHD comprised of 211 (8.5%) patients. Group 2 and 3 comprised of 1691 (68.3%) and 573 (23.2%) patients respectively. Overall, 1767 (71.4%) patients were females, however this female predilection was less pronounced in juvenile RHD (55.5% females vs 44.5% males) as compared to older groups. Past history of acute rheumatic fever was more commonly recorded in Juvenile RHD group (37.9% vs 18.8% in group 2 and 10% in group 3, p=0.0001). At the time of registration, the presence of advanced heart failure symptoms (dyspnea class III and IV) (11.4% group 1 vs 13.9% group 2 vs 20.6% group 3, p&lt;0.0001), right heart failure symptoms (0.9% group 1 vs 2.5% group 2 vs 7.3% group 3, p&lt;0.01), thromboembolic events (0% group 1 vs 4.1% group 2 vs 3.3% group 3, p&lt;0.01), atrial fibrillation (2.8% group 1 vs 24.5% group 2 vs 45.9% group 3, p&lt;0.0001), and pulmonary hypertension (27.1% group 1 vs 40.3% group 2 vs 51.9% group 3, p&lt;0.01), were all more commonly recorded in non-juvenile older RHD groups. Multivalvular involvement was also less common in juvenile RHD (34.6% vs 42.4% and 44.5%, p=0.04). Mitral regurgitation was the most common lesion in Juvenile RHD followed by aortic regurgitation (68.7% and 40.2% respectively). Stenotic lesions (both mitral and aortic) were present more commonly in older age groups. Conclusion RHD is predominantly a disease of females, however the predilection is less common in juvenile patients. Juvenile RHD predominantly affects the mitral valve and mainly leads to regurgitant lesions. As the age advances, the complications of RHD, mainly heart failure symptoms, thromboembolic events, pulmonary hypertension, and atrial fibrillation, become more common. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Self sponsored registry


2021 ◽  
Vol 22 (Supplement_3) ◽  
Author(s):  
YR Kim

Abstract Funding Acknowledgements Type of funding sources: None. Background This study aimed to identify the volume left atrium (LA) and left atrial appendage (LAA) calculated by multidetector computed tomography (MDCT) is related to the long term out come of radiofrequency catheter ablation (RFCA) for atrial fibrillation(AF). Methods We analyzed data from 99 consecutive patients who referred for RFCA due to drug-refractory symptomatic AF (age 56 ± 10 years; 74% men; 64% paroxysmal AF). Prior to the procedure, all patients underwent ECG-gated 128 channels MDCT scan for assessment for pulmonary vein  anatomy, LA and LAA volume estimation, and electro-anatomical mapping integration.  Results The volume of LA and LAA calculated by CT was 142.6 ± 32.2 mL and 14.7 ± 6.0 mL, respectively. LA volume was smaller in paroxysmal AF(PAF) than persistent AF(PeAF) (133.9 ± 29.3 mL vs. 158.0 ± 31.4 mL, p &lt; 0.0001) but  LAA volume was not significantly different between PAF and PeAF(13.9 ± 5.0 mL vs. 16.3 ± 7.3 mL, p = 0.09). Patients were classified into 2 groups by the LA volume of 160mL; group 1  (LA volume &lt; 160mL,n = 73) and group 2 (LA volume ≥160mL, n = 26). After a mean follow up 12.6 ± 5.3 months, 78.8% of the patients maintained sinus rhythm after the index ablation. AF free survival was significantly greater in group  1 than group 2 (84.9% vs. 61.5% p = 0.017). No relationship was found between LAA volume and the outcome of RFCA. Multivariate analysis showed that the LA volume &gt;160mL was an independent predictor of arrhythmia-free after ablation (Hazard ration 2.55, 95% confidential interval 1.02-6.35, p = 0.045) Conclusion Higher LA volume is independent risk factor for AF recurrence after RFCA but not LAA volume. The LA volume quickly assessed by MDCT could be a good predictor of long term recurrence after AF ablation.


Perfusion ◽  
2006 ◽  
Vol 21 (6) ◽  
pp. 329-342 ◽  
Author(s):  
Serdar Gunaydin ◽  
Kevin McCusker ◽  
Venkataramana Vijay ◽  
Selim Isbir ◽  
Tamer Sari ◽  
...  

Objectives: The relative benefits of strategic leukofiltration on polymer-coated and low-dose heparin protocol on heparin-coated circuits were studied across EuroSCORE patient risk strata for three different cohorts. Methods: In a prospective, randomized study, 270 patients undergoing coronary artery bypass grafting were allocated into three groups (n = 90): Group 1 -polymethoxyethylacrylate-coated circuits+leukocyte filters; Group 2 -polypeptide-based heparin-bonded circuits with reduced heparinization; and Group 3 -Control: uncoated circuits. Each group was further divided into three subgroups (n = 30), with respect to low- (EuroSCORE 0-2), medium- (3-5), and high- (6+) risk patients. Blood samples were collected at T1: following induction of anesthesia; T2: following heparin administration; T3: 15 min after CPB; T4: before cessation of CPB; T5: 15 min after protamine reversal; and T6: ICU. Results: In high-risk cohorts, leukocyte counts demonstrated significant differences at T4 and T5 in Group 1, and at T4 in Group 2. Platelet counts were preserved significantly better at T4 and T5 in both groups (p <0.05 versus control). Serum IL-2 and C3a levels were significantly lower at T3, T4 and T5 in Group 1, and T4 and T5 in Group 2 (p <0.05). Postoperative bleeding, respiratory support time and incidence of atrial fibrillation were lower in the study groups versus control. Cell counts on filter mesh and heparin-coated fibers/circuits were significantly higher in the high-risk cohorts versus uncoated fibers. Phagocytic capacity increased on filter mesh, especially in high-risk specimens. SEM evaluation demonstrated better preserved coated circuits. Conclusion: Leukofiltration and coating reduced platelet adhesion, protein adsorption, atrial fibrillation and reduced heparinization acted via modulation of systemic inflammatory response in high-risk groups.


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