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.

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.

Early biventricular molecular responses to an acute myocardial infarction.

BACKGROUND: Acute myocardial infarction (AMI) remains as one of the most common lethal diseases in the world and therefore it is necessary to understand its effect on molecular basis. Genome-wide microarray analysis provides us to predict potential biomarkers and signaling pathways for this purpose. OBJECTIVES: The aim of this study is to understand the molecular basis of the immediate right ventricular cellular response to left ventricular AMI. MATERIAL AND METHODS: A rat model of left anterior descending coronary artery ligation was used to assess the effect of left ventricular AMI on both the right ventricle as a remote zone and the left ventricle as an ischemic/infarct zone. Microarray technology was applied to detect the gene expression. Gene Ontology and KEGG pathways analysis were done to identify effected pathways and related genes. RESULTS: We found that immune response, cell chemotaxis, inflammation, cytoskeleton organization are significantly deregulated in ischemic zone as early response within 30 min. Unexpectedly, there were several affected signaling pathways such as cell chemotaxis, regulation of endothelial cell proliferation, and regulation of caveolea regulation of anti-apoptosis, regulation of cytoskeleton organization and cell adhesion on the remote zone in the right ventricle. CONCLUSION: This data demonstrates that there is an immediate molecular response in both ventricles after an AMI. Although the ischemia did not histologically involve the right ventricle; there is a clear molecular response to the infarct in the left ventricle. This provides us new insights to understand molecular mechanisms behind AMI and to find more effective drug targets.

Pulmonary segmental artery ratio: an alternative to the pulmonary artery index in patients with tetralogy of fallot.

The objective of this study was to determine a reliable, alternative ratio to the pulmonary artery (PA) index, which will help to estimate the adequacy of postoperative pulmonary blood flow in patients with tetralogy of Fallot. We propose the pulmonary segmental artery ratio (PSAR), which is an angiographic measure for the quantitative standardization of the total number of pulmonary segmental arteries in a patient. The expected value of the PSAR is 1 and it is constant after the 16(th) week of intrauterine life. Retrospective analysis of the PSAR and PA index calculations in patients with tetralogy of Fallot was conducted. Sixty-one patients were assigned to a moderate or low risk group according to their PSAR; the low risk group included 31 patients whose PSAR was between 0.75-1 (group 1) while the moderate risk group included 30 patients whose PSAR was between 0.50-0.75 (group 2). High risk patients whose PSAR was less than 0.50 were excluded from the study. Postoperative peak right ventricular pressure, the pulmonary artery to systemic pressure ratio, and peripheral arterial oxygen saturation preoperatively after cardiopulmonary bypass were analyzed separately in groups 1 and 2. Postoperative peak right ventricular pressure was lower in group 1 than group 2, while the pulmonary artery to systemic pressure ratio and peripheral arterial oxygen saturation were higher in group 1 than group 2 (P < 0.01). Based on the present findings, it is concluded that PSAR is not as reliable as the Nakata index. However, in cases in which the PSAR and PA index are not correlated, PSAR may be helpful for determining the adequacy of postoperative pulmonary blood flow and postoperative outcomes of patients with hypoplastic pulmonary arteries.

Early protective effects of iloprost, a stable prostacyclin analog, during spinal cord ischemia in a rabbit model.

Spinal cord ischemia may develop into paraplegia in some cases during operation of the thoracoabdominal aorta. This is attributable to the vulnerability of spinal motor neurons to ischemia. In this study, iloprost was used as an agent to decrease the severity of ischemia and reperfusion injury to the spinal cord motor neurons. Twenty-one rabbits were randomized into three groups of seven animals each: group A (iloprost not administered), group B (25 ng/kg per minute iloprost), and group S (sham-operated). The spinal cord ischemia model was created by a 15-min occlusion of the aorta just caudal to the renal artery with a balloon catheter. Administration of iloprost began 10 min before occlusion of the aorta, and continued thereafter for 60 min. The pre- and postocclusion arterial pressure and heart rate recordings, results of blood gas analyses, and hematocrit and glucose levels were recorded. The spinal cords were removed after 8-h monitoring of neurologic function. Viable and nonviable motor neurons in the anterior horn of the spinal cord were counted under light microscopy. Any significant alteration in hemodynamics, blood gases, and other physiologic parameters could not be detected within the groups. Iloprost had a moderately hypotensive effect. Neurologic function in terms of Johnson scoring was significantly better in the iloprost group (P<0.05). The number of viable cells was higher, whereas the number of nonviable cells was lower in iloprost group, when compared with the control group (P<0.05). Higher numbers of viable motor neurons were consistent with the neurological findings. As a result of this study we concluded that iloprost infused during clamping of the aorta mitigates the spinal cord injury due to ischemia and reperfusion, and has a significant protective effect.

The case of a cyst hydatid localized within the interatrial septum.

The ratio of cardiac involvement of Echinoccocus granulosus is 0.02-2% and although seen rarely, involvement of the interatrial septum has also been reported in the published literature. The present case was a 19-year-old male university student admitted to hospital with complaints of headache and dizziness. Computerized tomography of the cranium revealed a cystic mass located at the frontal region and enucleation of the cyst was performed during surgery. A cystic lesion 5 x 4 cm in size was detected within the interatrial septum on two-dimensional transthoracic echocardiography during the postoperative period and the patient was referred to our clinic. Open heart surgery was performed and a hydatid cyst that involved the interatrial septum was enucleated. The cyst wall was sutured to the interatrial septum. No complications developed during the postoperative period. The patient was discharged on the fifth day of hospitalization and medical therapy was started with albendazole.

Behçet's disease: treatment of popliteal pseudoaneurysm by an endovascular stent graft implantation.

Behçet's disease is a multisystemic chronic autoimmune process that can be responsible for some vascular lesions, in addition to its typical dermatologic lesions. Arterial pseudoaneurysm formation can be diagnosed in this group of patients and generally surgery is indicated. In this report, we discuss an alternative endovascular intervention and its advantages. An endovascular stent graft was placed in the popliteal artery pseudoaneurysm of a 37-year-old male with Behçet's disease. Early results of this procedure are good thus far. Implantation of an endovascular stent graft, an alternative modality in the treatment of pseudoaneurysms, can result in a shorter hospital stay and a significantly shorter period before returning to normal life. General anesthesia and surgical dissection are avoided, thus diminishing morbidity.

Diltiazem provides higher internal mammary artery flow than nitroglycerin during coronary artery bypass grafting surgery.

OBJECTIVES: Perioperative internal mammary artery (IMA) vasospasm in patients undergoing coronary artery bypass grafting (CABG) surgery may lead to morbidity and mortality. Surgical stimulus is one of the common causes of IMA vasospasm. Preventive measures, beside treatment should be taken into consideration to obtain vasospasm free IMA. The effect of a pharmacologic agent on IMA flow when it is administered before harvesting the artery has not been documented. We designed a prospective randomized clinical study to compare the IMA free blood flows in patients receiving either diltiazem or nitroglycerin, starting infusion of study drugs before a surgical stimulus was applied to the IMA region and continuing throughout the isolation period. METHODS: Sixty patients undergoing elective CABG surgery with the left IMA received diltiazem (n=30, 0.05-0.1 mg/kg per hour) or nitroglycerin (n=30, 0.25-2.5 microg/kg per minute) in a randomized manner. Infusions of study drugs were started before applying a surgical stimulus to the IMA region and continued throughout the harvesting period. The first free flow was measured after IMA was cut above its bifurcation and the second after its distal segment was resected. Heart rate, temperature, mean arterial and central venous pressures were recorded. Data were analyzed with Student's t-test and Fischer's exact test. RESULTS: Preoperative and hemodynamic data were similar between the groups. The means of first and second IMA flows in patients treated with diltiazem (53.8+/-30.1 and 72.3+/-35.4 ml/min) were significantly higher than in those treated with nitroglycerin (25.7+/-16.2 and 48.9+/-23.8 ml/min; P=0.000, 0.004, respectively). IMA flows significantly increased after distal segment resection both in diltiazem (34%) and nitroglycerin groups (90%; P= 0.000, 0.000, respectively). CONCLUSIONS: Diltiazem infusion which started prior to harvesting provided higher IMA blood flow compared to nitroglycerin infusion. Considering the percentage of increases in flows after resection of distal segment, the most prone part to vasospasm, we assume that a certain amount of spasm occurred in IMA in spite of infusion of study drugs, such that less with diltiazem and more with nitroglycerin. Diltiazem plays more important role than nitroglycerin in the prevention of vasospasm.