Effects of rivaroxaban on myocardial mitophagy in the rat heart.

Background: This study aims to demonstrate the efficacy of rivaroxaban's pharmacokinetic effects on myocardial mitophagy in rats by inducing apoptosis. Methods: In this double-blind experiment, Wistar albino male rats were randomly divided into three groups for an experimental ischemia model: the sham group (Group 1; n=7), the control group (Group 2; n=7), and the drug group (Group 3; n=7). Rivaroxaban was perorally administered with gavage at 2 mg/ kg/day for 28 days in Group 3. The heart was surgically exposed, and ischemia was achieved by compressing the vessel around the proximal part of the left anterior descending coronary artery for 10 min. The heart tissue was then transected, removed, and morphologically and immunohistochemically examined under a light microscope. Results: Heart sections were immunohistochemically marked with caspase 3, caspase 9, APAF1, and Bcl-2 antibodies. Group 1 was compared to the rivaroxaban-treated group, and the pathways inducing apoptosis was increased (caspase 3, caspase 9, APAF1; p<0.015, p<0.004, and p<0.01, respectively) and Bcl-2, the molecule that inhibits apoptosis, was decreased (p<0.01) in Group 3. Conclusion: The present study provides an evidence that the mitophagy response is less in rivaroxaban-treated rats, showing the protective effect of rivaroxaban against acute ischemia. Rivaroxaban-treated rats may have reduced cell death in cardiomyocytes during myocardial infarction and thus have reduced damage to the heart tissue caused by myocardial infarction.

Non-heparin-induced thrombocytopenia in patients after open-heart surgery.

BACKGROUND: Thrombocytopenia (platelet count below 150 x 103/µL) is a common finding after open-heart surgery and can lead to various complications, including patient death. This study aimed to determine the extent of non-heparin-induced thrombocytopenia in open-heart surgery and to highlight the associated factors. MATERIALS AND METHODS: In this cohort study, 842 patients who underwent valve and/or coronary bypass surgery over a 5-year period were retrospectively analyzed. After open-heart surgery, patients whose platelet count was less than 150 x 103/µL on a complete blood count 12 and 24 h after surgery were classified as thrombocytopenic. Three hundred twenty patients without thrombocytopenia and 21 patients with a high probability of heparin-induced thrombocytopenia were excluded from the study. Logistic regression analysis was used to assess the association of independent variables in moderate-severe thrombocytopenia: Age groups, sex, underlying disease, symptoms, type of surgery, pump time, pulsatile or non-pulsatile duration, degree of hypothermia, hemodilution, oxygenator type, use of an intra-aortic balloon, and erythrocyte transfusion counts were included in the analysis. RESULTS: A total of 501 patients were diagnosed as having non-heparin-induced thrombocytopenia, and 64.3% were male. Three hundred seventy-seven (75.2%) patients had mild thrombocytopenia and 124 (24.7%) had moderate-severe thrombocytopenia. The postoperative platelet count was significantly lower than the preoperative platelet count (213 x 103 vs.117 x 103/µL; p < 0.001). Moderate-severe thrombocytopenia was associated with age ≥80 years odds (OR = 9.026, 95% CI: [1.757-46.363]; p = 0.008), isolated valve surgery (OR = 3.090, 95% CI: [1.867-5.114]; p < 0.001), and valve surgery with coronary bypass (OR = 4.938, 95% CI: [1.638-14.889]; p = 0.005) compared to isolated coronary bypass, type of oxygenator (Nipro vital compared with Affinity OR = 11.097, 95% CI: [1.923-64.023]; p = 0.007), erythrocyte transfusion count (OR = 1.219, 95%CI: [1.046-1.420]; p = 0.011). CONCLUSION: Age 80 years or older, surgical procedures including heart-valve surgery, and the number of red blood cell transfusions are associated with the risk of moderate-to-severe thrombocytopenia. This study provides a guide in terms of risk factors that may lead to moderate-to-severe thrombocytopenia after open-heart surgery. However, future multicentre prospective randomized studies may provide more detailed information on this subject.

Predictors of walking capacity in patients with peripheral arterial disease.

BACKGROUND: Walking capacity is severely impaired in patients with peripheral arterial disease (PAD). Given the prognostic importance of walking capacity, the level of evidence on possible predictors of walking capacity in patients with PAD is insufficient. AIMS: To investigate the predictors of walking capacity in patients with PAD. METHODS: A total of 51 patients with PAD were included in this cross-sectional study. Walking capacity was determined with 6­minute walk test (6MWT) and walking impairment questionnaire (WIQ). Functional mobility was assessed with repeated sit-to-stand test (RSS) and timed up and go test (TUG). Hand-held dynamometer was used to measurement lower extremity muscle strength. Balance was assessed with Biodex Balance System-limit of stability (BBS-LOS). Fatigue was evaluated with fatigue impact scale (FIS). RESULTS: There was a strong correlation between 6MWT walking distance and WIQ, two methods of assessing walking capacity (r = 0.835 p < 0.001). The 6MWT was correlated with RSS, TUG, lower extremity muscle strength, BBS-LOS and FIS. The WIQ was correlated with RSS, TUG, BBS-LOS and FIS. The RSS and FIS were independent determinants of the 6MWT and WIQ, accounting for 68% and 57% of the variance, respectively. CONCLUSION: This study demonstrated that functional mobility and fatigue were independent predictors of walking capacity in patients with PAD. Both subjective and objective measurement methods can be used for determining the level of walking capacity in the patients with PAD.

Evaluation of Surgical Outcomes of Type A Intramural Hematoma

Abstract Introduction: In this study, we aimed to retrospectively evaluate the results of type A intramural hematoma (TA-IMH) cases that underwent ascending aortic surgery. Methods: One hundred ninety-four patients who underwent aortic surgery between 2010 and 2018 were included in this study. TA-IMH was differentiated according to tomography angiographic images. Demographic data, operation type, hypothermic circulatory arrest times, echocardiographic findings, wall thickness of IMH, complications, and prognosis were retrospectively analyzed. Results: TA-IMH (n=14) or type A aortic dissection (AD) (n=35) data were collected from patients' files and 49 cases were enrolled into the study. Bentall operation was performed in eight patients (type A AD = six [17.1%], TA-IMH = two [14.3%]); 41 patients underwent tubular graft interposition of ascending aorta (AD = 29 [82.9%], TA-IMH = 12 [85.7%]). There was no significant difference in terms of age, gender distribution, aortic dimensions, cardiopulmonary bypass times, hypothermic circulatory arrest times, hospital ward stay, and intensive care unit stay between the two groups. The mortality rate of AD group was 34.4% and of TA-IMH group was 14.3%. There was no significant difference in terms of mortality between the groups. In our study, 45.7% of patients had hypertension and that rate was lower than the one found in the literature. In addition, bicuspid aorta was not observed in both groups. Connective tissue disease was not detected in any group. Conclusion: Surgical treatment of aorta is beneficial for TA-IMH. Our aortic surgical indications comply with the European aortic surgical guidelines. Hypertension control should be provided aggressively.

Evaluation of Surgical Outcomes of Type A Intramural Hematoma.

INTRODUCTION: In this study, we aimed to retrospectively evaluate the results of type A intramural hematoma (TA-IMH) cases that underwent ascending aortic surgery. METHODS: One hundred ninety-four patients who underwent aortic surgery between 2010 and 2018 were included in this study. TA-IMH was differentiated according to tomography angiographic images. Demographic data, operation type, hypothermic circulatory arrest times, echocardiographic findings, wall thickness of IMH, complications, and prognosis were retrospectively analyzed. RESULTS: TA-IMH (n=14) or type A aortic dissection (AD) (n=35) data were collected from patients' files and 49 cases were enrolled into the study. Bentall operation was performed in eight patients (type A AD = six [17.1%], TA-IMH = two [14.3%]); 41 patients underwent tubular graft interposition of ascending aorta (AD = 29 [82.9%], TA-IMH = 12 [85.7%]). There was no significant difference in terms of age, gender distribution, aortic dimensions, cardiopulmonary bypass times, hypothermic circulatory arrest times, hospital ward stay, and intensive care unit stay between the two groups. The mortality rate of AD group was 34.4% and of TA-IMH group was 14.3%. There was no significant difference in terms of mortality between the groups. In our study, 45.7% of patients had hypertension and that rate was lower than the one found in the literature. In addition, bicuspid aorta was not observed in both groups. Connective tissue disease was not detected in any group. CONCLUSION: Surgical treatment of aorta is beneficial for TA-IMH. Our aortic surgical indications comply with the European aortic surgical guidelines. Hypertension control should be provided aggressively.

Effect of bivalirudin on neointimal hyperplasia and endothelial proliferation in rabbit.

BACKGROUND: The aim of this study was to investigate the effects of bivalirudin on endothelial cell proliferation and neointimal hyperplasia in a rabbit carotid artery model. METHODS: "New Zealand rabbits (n = 12)" weighing 2-3 kg were randomly divided into two groups. Arteriotomy was performed to the rabbit carotid artery and closed with continuous suture technique. Group B (n = 6) as a control group received 150 U/kg heparin sodium; however, group A (n = 6) was given 0.75 mg/kg bivalirudin i.v. bolus and infusion 1.75 mg/kg/hour (B01AE06-Bivalirudin 250 mg) during perioperation period. At the end of the 28th day, the carotid artery segment was excised and evaluated histologically. RESULTS: All histological and immune staining analyzes were performed by two blind researchers in the treatment of rabbits. In the control group rabbit carotid artery sections, tunica intima was observed to thicken. In the bivalirudin group, intimal hyperplasia was less observed compared to the control group. No significant difference was observed between groups in tunica media thickness. Lumen diameter and lumen area were found to be wider in the experimental group. P value was found to be less than 0.05. CONCLUSION: Our study demonstrates that bivalirudin significantly affects and prevents neointimal hyperplasia and endothelial cell proliferation.

Efficiency of Minimized Circuits of a Heart Roller Pump on Systemic Inflammatory Response Syndrome and Multiorgan Effects in a Rat Model.

BACKGROUND: The aim of this study is to compare the effects of tubing length on systemic inflammatory response syndrome and myocardial protection in a rat model of cardiopulmonary bypass (CPB) from a histological standpoint. METHODS: Twelve adult male Wistar Albino rats weighing >180 g were randomly selected and divided into 2 groups. In 1 group, the pump lines were kept 1 m shorter than standard. The right jugular vein and tail artery were cannulated using a 16-gauge catheter. Animals received 500 IU/kg intravenous heparin. Cardiac index and rectal temperature were set at 2.4 mL and 36°C, respectively. Total line volume was maintained at 8 mL. A roller pump was adjusted to supply a blood flow of 6 to 28 mL/min (mean 10 mL/min), similar to the typical cardiac output of rats. CPB duration was 15 minutes throughout the experiment. After sacrifice, tissue samples were collected from heart, liver, and kidney for histomorphologic examination. RESULTS: All histochemical and histomorphologic analyses, performed by 2 blinded researchers, revealed band loss in cardiomyocytes, mononuclear (MNL) cell infiltration, and impaired fibrillar organization in the standard-line group. Additionally in that group, sinusoidal dilatation in the liver, low-level congestion, focal necrosis, and periportal MNL infiltration were noted. In the shorter-line group, on the other hand, MNL cell infiltration, band loss in myofibrils, and cardiomyocyte degeneration were rarely observed. Higher liver congestion and lower MNL cell infiltration were observed in the shorter-line group. No significant differences were found in kidney samples. CONCLUSION: In a shorter-line roller pump test model, less multiorgan damage and fewer systemic inflammatory responses were observed. It may be applicable to keep CPB lines as close to the table as possible, especially in pediatric cardiac surgery cases.

Effects of carbon dioxide insufflation on anastomosis remodeling at a carotid artery site in rabbits.

INTRODUCTION: Use of carbon dioxide (CO2) insufflation (CDI) on the surgical field during heart surgery has become widespread, and in some units routine. AIM: To assess the effects of CDI on endothelial dysfunction in a carotid artery model in rabbits. MATERIAL AND METHODS: Twelve randomly selected rabbits were divided into two groups. Right carotid arteries of the animals were transected and sutured with running suture technique. Then, 1 l/min CO2 insufflation was initiated with a 45° angle. In the control group, the anastomotic field was irrigated with 0.1 ml/s flow of 0.9% saline. At day 28, the carotid artery segments were removed and prepared for histological specimens. RESULTS: In the cross-sections of the control group vessel samples, thickening of the tunica intima was observed. Scoring the quantity of endothelial nitric oxide synthase (e-NOS) and α-smooth muscle actin (α-SMA) positive staining revealed a nonsignificant difference between the experimental groups (p = 0.07). In the CO2 group, the intimal hyperplasia (p = 0.2) and the thickness of the tunica media (p = 0.2) were indistinguishable when compared to the control group. The mean luminal diameters and luminal areas of the experimental groups were all evaluated by histomorphometry and a significant differences was found between luminal areas (p = 0.016). On the other hand, no significant difference was found between mean luminal diameters (p = 0.055). CONCLUSIONS: Our study indicated that CDI can affect endothelial cell damage and the mean luminal diameters.

Effects of rivaroxaban on intimal hyperplasia and smooth muscle cell proliferation at the carotid artery anastomosis site in rabbits.

OBJECTIVE: This study aimed to assess the effect of new generation oral, direct factor Xa inhibitor rivaroxaban on intimal hyperplasia and smooth muscle cell proliferation at the carotid artery anastomosis site of rabbits. METHODS: In total, 14 New Zealand male rabbits weighing 3-3.5 kg were randomized into two groups. Group A (7 rabbits) served as the control group and received no medication. Rivaroxaban was perorally administered to group B (7 rabbits) mg/kg/day for 28 days. Following anesthesia induction, carotid arteries were dissected through a right neck incision. following heparinization at 100 IU/kg, vertical full thickness arteriotomy was performed, then was repaired continuously with 8-0 polypropylene. At day 28, all rabbits were sacrificed and the anastomosed carotid artery segments were analyzed using light microcopy. Hematoxylin-eosin and Masson's trichrome stained images were analyzed using a digital image analysis program, and lumen diameter, lumen area, intimal and medial thickness, and media areas were measured and results were compared. RESULTS: In the serial sections, the average lumen diameter of group B was higher than that of group A (p=0.001). The lumen areas of group B were also higher than those of group A (p=0.004). The intimal thickness of group B was lower than that of group A (p=0.001). When the section series were evaluated for media thickness, the thickness of group B was lesser than that of group A; the difference was statistically significant (p=0.002). CONCLUSION: This study may imply a potential midterm benefit of rivaroxaban following arterial anastomosis by reducing intimal proliferation and restenosis.

Phenotype distribution of the paraoxonase gene in patients with cardiac disease.

INTRODUCTION: Paraoxonase (PON1) is an enigmatic enzyme with multiple enzymatic properties including arylesterase and lactonase activities besides its ability to hydrolyze the toxic metabolite of parathion, paraoxon. The aim of this study was to determine the phenotype distribution of PON1 in patients with cardiac disease who were classified in coronary artery bypass grafting (CABG), heart valve disease (HVD), heart failure (HF) and ST elevation myocardial infarction (STEMI) groups and healthy subjects as a control group. MATERIAL AND METHODS: A total of 300 people (100 cardiac surgery (70 CABG and 30 HVD), 70 HF, 30 STEMI patients and 100 healthy controls) were admitted to this study. Individual variations in PON1 were determined using the dual substrate (paraoxon and phenylacetate) method. RESULTS: The following phenotype distributions were found in the cardiac disease and control groups: cardiac disease group (n = 200): 48.5% (QQ), 42.5% (QR), 9% (RR) and control group (n = 100): 58% (QQ), 39% (QR), 3% (RR). RR (high activity) phenotypic distribution was more common in the cardiac disease group than in controls (p = 0.04). In particular, the frequency of the RR phenotype was two- to three-fold higher in the STEMI and HF patients compared to the controls as well as CABG and HVD groups. CONCLUSIONS: We found a higher percentage of RR phenotype in STEMI and HF patients compared to a large control group as well as compared to two other groups of cardiac disease patients.

Use of percutaneous aspiration thrombectomy vs. anticoagulation therapy to treat acute iliofemoral venous thrombosis: 1-year follow-up results of a randomised, clinical trial.

PURPOSE: The purpose of this study was to compare the efficacy of percutaneous aspiration thrombectomy (PAT) followed by standard anticoagulant therapy, with anticoagulation therapy alone, for the treatment of acute proximal lower extremity deep vein thrombosis. METHODS: In this randomised, prospective study, 42 patients with acute proximal iliofemoral deep vein thrombosis documented via Doppler ultrasound examination, were separated into an interventional treatment group (16 males, 5 females, average age 51 years) and a medical treatment group (13 males, 8 females, average age 59 years). In the interventional group, PAT with large-lumen 9-F diameter catheterisation was applied, after initiation of standard anticoagulant therapy. Balloon angioplasty (n 19) and stent implementation (n: 14) were used to treat patients with residual stenosis (>50 %) after PAT. Prophylactic IVC filters were placed in two patients. The thrombus clearance status of the venous system was evaluated by venography. In both the medical and interventional groups, venous patency rates and clinical symptom scores were evaluated at months 1, 3, and 12 after treatment. RESULTS: Deep venous systems became totally cleared of thrombi in 12 patients treated with PAT. The venous patency rates in month 12 were 57.1 and 4.76 % in the interventional and medical treatment groups, respectively. A statistically significant improvement was observed in clinical symptom scores of the interventional group (PAT) with or without stenting (4.23 ± 0.51 before treatment; 0.81 ± 0.92 at month 12) compared with the medical treatment group (4.00 ± 0.63 before treatment; 2.43 ± 0.67 at month 12). During follow-up, four patients in the medical treatment and one in the interventional group developed pulmonary embolisms. CONCLUSIONS: For treatment of acute deep vein thrombosis, PAT with or without stenting is superior to anticoagulant therapy alone in terms of both ensuring venous patency and improving clinical symptoms. PAT is a safe, inexpensive, and easily performed method of endovascular treatment with a low rate of major complications. Our present findings and literature data suggest that PAT can be used as first-line treatment in proximal deep vein thrombosis patients, especially when thrombolytic treatment is contraindicated.