The role of 5-HT7 receptors on isoproterenol-induced myocardial infarction in rats with high-fat diet exacerbated coronary endothelial dysfunction.

The presence of 5-HT7r's in both human and rat cardiovascular and immune tissues and their contribution to inflammatory conditions prompted us to hypothesize that these receptors contribute in acute myocardial infarction (MI) with underlying chronic endothelial dysfunction. We investigated the role of 5-HT7 receptors on heart tissue that damaged by isoproterenol (ISO)-induced MI in rats with high-fat diet (HFD). In vitro and in vivo effects of 5-HT7r agonist (LP44) and antagonist (SB269970) have been investigated on the H9C2 cell line and rats, respectively. For in vivo analyses, rats were fed with HFD for 8 weeks and after this period ISO-induced MI model has been applied to rat. To investigate the role of 5-HT7r's, two different doses of LP44 and SB269970 were evaluated and compared with standard hypolipidemic agent, atorvastatin. In vitro studies showed that LP44 has protective and proliferative effects on rat cardiomyocytes. Also in in vivo studies stimulating 5-HT7r's by LP44 improved blood lipid profile (decreased total cholesterol, low-density lipoprotein-C, and triglyceride, increased high-density lipoprotein), decreased cardiac damage markers (creatine kinase and troponin-I), and corrected inflammatory status (tumor necrosis factor-α, interleukin-6). Our results showed significant improvement in LP44 administered rats in terms of histopathologic analyses. In damaged tissues, 5-HT7 mRNA expression increased and agonist administration decreased this elevation significantly. We determined for the first time that 5-HT7r's are overexpressed in ISO-induced MI of rats with underlying HFD-induced endothelial dysfunction. Restoration of this overexpression by LP44, a 5-HT7r agonist, ameliorated heart tissue in physiopathologic, enzymatic, and molecular level, showing the cardiac role of these receptors and suggesting them as future potential therapeutic targets.

Expression of the Bone Morphogenetic Protein-2 (BMP2) in the Human Cumulus Cells as a Biomarker of Oocytes and Embryo Quality.

BACKGROUND: The members of the transforming growth factor-B superfamily, as the bone morphogenetic proteins (BMPs) subfamily and anti-Müllerian hormone (AMH), play a role during follicular development, and the bone morphogenetic protein-2 (BMP2), AMH, and THY1 are expressed in ovaries. AIM: This study was designed to define whether or not the expressions of these proteins in human cumulus cells (CCs) can be used as predictors of the oocyte and embryo competence. SETTINGS AND DESIGN: The study included nine female patients who were diagnosed as idiopathic infertility, aged 25-33 years (median 30 years) and underwent Assisted Reproductive Technologies. MATERIALS AND METHODS: The CCs from 60 oocyte-cumulus complexes obtained from the nine patients were evaluated with immunofluorescence staining in respect of BMPs, AMH and THY1 markers. The CCs surrounding the same oocytes were evaluated separately according to the oocyte and embryo quality. STATISTICAL ANALYSIS: Quantitative data were statistically analyzed for differences using the two-sided Mann-Whitney U test (P < 0.05). RESULTS AND CONCLUSIONS: Significant differences in immunofluorescence staining were observed in oocyte quality and embryo quality for the BMP2 only (P < 0.05). No significant differences were observed for AMH or CD90/THY1. CONCLUSION: These results demonstrated that there is a significant difference in the expression of BMP2 in the CCs of good quality oocytes and subsequently a good embryo.

Expression profiling of stem cell signaling alters with spheroid formation in CD133high/CD44high prostate cancer stem cells.

Cancer stem cells (CSC) isolated from multiple tumor types differentiate in vivo and in vitro when cultured in serum; however, the factors responsible for their differentiation have not yet been identified. The first aim of the present study was to identify CD133high/CD44high DU145 prostate CSCs and compare their profiles with non-CSCs as bulk counterparts of the population. Subsequently, the two populations continued to be three-dimensional multicellular spheroids. Differentiation was then investigated with stem cell-related genomic characteristics. Polymerase chain reaction array analyses of cell cycle regulation, embryonic and mesenchymal cell lineage-related markers, and telomerase reverse transcriptase (TERT) and Notch signaling were performed. Immunohistochemistry of CD117, Notch1, Jagged1, Delta1, Sox2, c-Myc, Oct4, KLF4, CD90 and SSEA1 were determined in CSC and non-CSC monolayer and spheroid subcultures. Significant gene alterations were observed in the CD133high/CD44high population when cultured as a monolayer and continued as spheroid. In this group, marked gene upregulation was determined in collagen type 9 α1, Islet1 and cyclin D2. Jagged1, Delta-like 3 and Notch1 were respectively upregulated genes in the Notch signaling pathway. According to immunoreactivity, the staining density of Jagged1, Sox2, Oct4 and Klf-4 increased significantly in CSC spheroids. Isolated CSCs alter their cellular characterization over the course of time and exhibit a differentiation profile while maintaining their former surface antigens at a level of transcription or translation. The current study suggested that this differentiation process may be a mechanism responsible for the malignant process and tumor growth.

Preoperative NT-proBNP levels: a reliable parameter to estimate postoperative atrial fibrillation in coronary artery bypass patients.

BACKGROUND: Atrial fibrillation (AF) is one of the most common complications after coronary artery bypass grafting (CABG). This study was designed to evaluate whether the levels of preoperative and postoperative N-terminal pro-brain natriuretic peptide (NT-proBNP) are predictors of postoperative paroxysmal atrial fibrillation in patients who undergo coronary artery bypass surgery. METHODS: A total of 117 patients were prospectively evaluated for new-onset AF after coronary operation. Plasma NT-proBNP values in all patients were measured at five different time points. RESULTS: AF occurred during the hospitalization period in 33 patients (28.2 %). Significantly higher NT-proBNP levels in the preoperative examination were recorded in patients who developed AF postoperatively compared with patients without postoperative AF (329.36 ± 82.93 vs. 230.67 ± 59.93 pg/ml, P < 0.05). Although we detected some higher values in the other group of patients with AF (at T1, T2, T3, T4), the difference was not statistically significant compared to the normal rhythm group. CONCLUSION: The main finding of the current study is a positive correlation between high levels of preoperative NT-proBNP and the risk of new-onset AF after CABG surgery.

Right ventricular outflow obstruction of the patient with biventricular non-compaction.

We present a case of a 16-year-old girl who underwent infundibular myectomy for right ventricular outflow tract obstruction complicated by biventricular non-compaction. The pathogenesis of this condition remains unknown. In pediatric patients non-compaction cardiomyopathy is associated with other cardiac abnormalities and carries a high mortality as a result of heart failure. In view of her improved cardiac performance after operation, we believe that a cardiac repair procedure should be performed based on the usual indications if left ventricular function is preserved.

Protection of saphenous vein graft from arterial pressure: an experimental study.

BACKGROUND: Reoperations for bypass surgery increase the need for new grafts. We investigated early changes in both the normal human saphenous vein and in ectatic varicose veins externally supported by PTFE (polytetrafluoroethylene) graft and exposed to arterial pressure in an IN VITRO non-pulsatile flow model. MATERIAL AND METHODS: A total of 24 saphenous vein pieces (11 of them normal, the other 13 with varicosities) with a length of 6 centimeters were divided into equal parts; half of these parts were wrapped in PTFE grafts. All vein parts were placed in a perfusion circuit. Tissue biopsies were obtained from the vein segments. Light and electron microscopy examinations were performed, and endothelial continuity, elastic laminate continuity, medial connective tissue uniformity, medial smooth muscle uniformity, and adventitial connective tissue uniformity parameters were identified. RESULTS: All parameters in the PTFE protected vein groups were better. The fewest morphological changes among all four groups were detected in the vein walls from normal veins with PTFE protection. There was no significant difference in endothelial continuity and adventitial connective tissue uniformity between the normal vein group and the varicose vein group with PTFE protection. CONCLUSIONS: It is suggested that supporting vein grafts externally with PTFE sufficiently protects the vein walls against damage from exposure to arterial pressure. If varicose veins are used as arterial grafts, supporting them with PTFE may be useful because of the good protection of endothelial and medial connective tissues, resulting in similar parameters to those of normal vein walls.

Congenitally corrected transposition of the great arteries plus dextrocardia operated with an unusual operative technique.

We describe a case of congenitally corrected transposition of the great arteries plus dextrocardia and normal anatomical abdominal viscera. Systemic (tricuspid) valve replacement was performed due to moderately severe valve regurgitation. An unusual operative technique was used because of the patient's rare morphology. On cardiopulmonary bypass, the systemic valve was approached via a left atriotomy anterior to the left pulmonary veins, whereby the surgeon was positioned on the patient's left side. As the surgeon had excellent exposure from the opposite side of the table, he was able to perform a tricuspid valve replacement through the left atrium. Our aim is to share our limited experience of such cardiac morphology, which may oblige the surgeon to be positioned on the left side of the table to perform systemic valve surgery.

An alternative method of prosthetic mitral valve implantation in the presence of extensive calcification.

Annular calcifications carry some technical difficulties for success in conventional valve surgery. In this paper we present an easy alternative mitral valve replacement method applied for a patient with a heavily calcified mitral annulus. Excision of both leaflets and partial resection of the annular calcification with an ultrasonic dissector allowed the intra-atrial insertion of a 33-mm Omnicarbon monoleaflet prosthetic valve through a smaller opening of the left posterior atrium. The technical difficulties in inserting a prosthetic valve in a patient with a heavily calcified mitral annulus are discussed.

N-terminal ProBNP levels can predict cardiac failure after cardiac surgery.

BACKGROUND: The aim of this study was to evaluate the relationship between the preoperative N-terminal pro-B-type natriuretic peptide (NT-proBNP) level and the need for the inotropic support in the early postoperative period of patients undergoing coronary artery bypass graft surgery. METHODS AND RESULTS: The patients were divided into 2 groups: NT-proBNP level<220 pg/ml (group A, n=26) or >220 pg/ml (group B, n=26). The normal value for NT-proBNP level was accepted as <220 pg/ml. The cardiac output was measured on arrival in intensive care and at the 16th hour. The groups were compared with respect to early postoperative hemodynamic measurements, urinary output, use of inotropic agents and requirement for additional cardiac-assist devices. Left ventricular ejection fraction, cardiac output and cardiac index were lower in group B and inotropic agents were used for a longer period of time and at higher doses in this group (p<0.05). CONCLUSION: Measurement of the NT-proBNP level in the period before cardiac surgery can indicate the postoperative prognosis of the patient and may be a predictor of the need for postoperative inotropic treatment.

The effect of cardiopulmonary bypass on the expression of inducible nitric oxide synthase, endothelial nitric oxide synthase, and vascular endothelial growth factor in the internal mammary artery.

OBJECTIVE: Endothelial function of a vessel may be impaired by local or systemic inflammation initiated by cardiopulmonary bypass (CPB) during coronary artery bypass graft (CABG) surgery. The present study was designed to investigate the early effects of CPB on nitric oxide production and vascular endothelial growth factor (VEGF) expression in internal mammary artery (IMA). DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Twenty patients who were scheduled for elective CABG with CPB. INTERVENTIONS: IMA sections were studied immunohistochemically from these patients. The samples were taken from the distal end of the IMA before the institution of CPB and just before the construction of the IMA-left anterior descending artery anastomosis. MEASUREMENT AND MAIN RESULTS: After CPB, VEGF and endothelial nitric oxide synthase immunoreactivity increased significantly when compared with baseline values in the endothelium (p = 0.0156, p = 0.0313) and adventitia (p = 0.0313, p = 0.0001), respectively. No significant change was observed in inducible nitric oxide synthase immunoreactivity. CONCLUSIONS: The increase in eNOS expression may have been induced by the inflammation caused by CPB.

Surgical treatment of cardiogenic shock due to huge right atrial thromboembolus.

An unusual case is reported of thromboembolus in the right atrium associated with cardiogenic shock and multiple pulmonary micro-embolisms. Two-dimensional echocardiograpy demonstrated a large irregular mass in the right atrium floating freely, prolapsing through the tricuspid valve into the right ventricle during diastole, and leading to inflow and outflow obstruction. An emergency operation was performed and the thromboembolic material was successfully extracted from the right atrium without using cardiopulmonary bypass. This exemplary case highlights the benefit of surgical intervention rather than more conservative approaches such as anticoagulation and/or thrombolysis.

Protective effects of trimetazidine in transient spinal cord ischemia.

The neuroprotective effect of trimetazidine (TMZ) was tested prospectively in a rabbit spinal cord ischemia model. Ischemia was induced by clamping the aorta just distal to the left renal artery and proximal aortic bifurcation for 20 min. Twenty-five male New Zealand white rabbits were randomized as follows: TMZ group (n=100) receiving 3 mg/kg trimetazidine intravenously before the occlusion of the aorta; control group undergoing occlusion but receiving no pharmacologic intervention (n=10); sham-operation group (n=5) subjected to operative dissections without aortic occlusion. Physiological parameters and somatosensory evoked potentials (SEP) were monitored in animals before the ischemia, during the ischemia and in the 1st, 15th and 60th min of reperfusion. Neurologic status was assessed 24 and 48 h after the operation. The spinal cord, abdominal aorta, and its branches were processed for histopathologic examinations 48 h after the operation. At the end of the ischemic period, the average N1-P1 amplitude was reduced to 22% of the baseline in all ischemic animals. This was followed by a gradual return to 90+/-2% of the initial amplitude in the TMZ group and 81+/-2% in the control group (P<0.05) after 60 min of reperfusion. The average motor function score was significantly higher in the TMZ group than the control group (3.7+/-0.5 vs 3.1+/-0.6 at 24 and 3.5+/-0.7 vs 2.9+/-0.6 at 48 h; P<0.05). Histologic observations were clearly correlated with the neurologic findings. The results suggest that trimetazidine reduces spinal cord injury during thoracoabdominal aortic operations and may have therapeutic utility during high risk operations.

Neuroprotective effects of preischemia subcutaneous magnesium sulfate in transient cerebral ischemia.

OBJECTIVE: Neurological injury due to transient cerebral ischemia is a potential complication of cardiovascular surgery. The neuroprotective effect of magnesium, when given subcutaneously before the ischemia, was assessed in a rat model of transient global cerebral ischemia. METHODS: Thirty-six male Wistar albino rats were included to this randomized, controlled, prospective study. In 24 animals, ischemia was induced with four-vessel occlusion technique with the duration of 15 min. MgSO4 was given 600 mg/kg subcutaneously 48 h before the procedure in group 1 (n = 12). Similar volume of saline solution was used in animals of control group (group 2, n = 12). The animals in group 3 (sham group, n = 12) were anesthetized and subjected to operative dissections without vascular occlusion. Physiological parameters and somatosensory evoked-potentials (SEP) were monitored in animals before ischemia, during ischemia and in the first 30 min of reperfusion. Their neurological outcome had been clinically evaluated and scored up to 4 days postischemia. The intergroup differences were compared. Then the animals were sacrificed and their brains were processed for histopathological examination. RESULTS: In group 3, SEP amplitudes did not change during the procedures, and all animals recovered without neurologic deficits. At the end of ischemic period, the average amplitude was reduced to 5 +/- 3% of the baseline in all ischemic animals. This was followed by a gradual return to 87 +/- 10% and 83 +/- 8% of the initial amplitude after 30 min of reperfusion in group 1 and group 2, respectively (P > 0.05). The average neurological score was significantly higher in group 1 than in group 2 at 48, 72 and 96 h after the ischemic insult (P < 0.05). Histological observations were clearly correlated with the neurological findings. CONCLUSION: The results suggest that subcutaneous MgSO4 reduces cerebral injury and preserves neurologic function when given two days before the transient global ischemia in rats.

Pentoxifylline reduces injury of the brain in transient ischaemia.

OBJECTIVE: The beneficial effect of pentoxifylline (PTX) on ischaemic-reperfusion injury was assessed in a rat model of transient global cerebral ischaemia. DESIGN: Randomized, controlled, prospective study. SETTING: University research laboratory. SUBJECTS: Thirty-six male Wistar albino rats. INTERVENTIONS: Ischaemia was induced with a four-vessel occlusion technique in 24 animals with the duration of 15 minutes. Group 1 animals (n = 12) received PTX treatment started 20 minutes before the occlusion of carotid arteries (60 mg/kg bolus followed by infusion at 0.1 mg/kg/min). A similar volume of saline solution was used in animals of the control group (group 2, n = 12). The animals in group 3 (sham group, n = 12) were anaesthetized and subjected to operative dissections without vascular occlusion. MEASUREMENTS: Physiological parameters and somatosensory evoked potentials (SEP) were monitored in animals before ischaemia, during ischaemia and in the first 30 minutes of reperfusion. Their neurological outcome had been clinically evaluated and scored up to 4 days post ischaemia. The intergroup differences were compared. Then the animals were sacrificed and their brains were processed for histopathological examination. MAIN RESULTS: In group 3, SEP amplitudes did not change during the procedures, and all animals recovered without neurologic deficits. At the end of the ischaemic period, the average amplitude was reduced to 4 +/- 3% of the baseline in all ischaemic animals. This was followed by a gradual return to 92 +/- 9% and 82 +/- 8% of the initial amplitude after 30 minutes of reperfusion in group 1 and group 2, respectively (p < 0.05). The average neurological score was significantly higher in group 1 than in group 2 in the post-ischaemia period (p < 0.05). Histological observations were clearly correlated with the neurological findings. CONCLUSION: The results suggest that PTX reduces cerebral injury and preserves neurologic function in transient global ischaemia in rats.

Aprotinin reduces injury of the spinal cord in transient ischemia.

OBJECTIVE: The protective effect of aprotinin, which is a protease inhibitor, was assessed in a rabbit spinal cord ischemia model. DESIGN: Randomized, controlled, prospective study. SETTING: University research laboratory. SUBJECTS: New Zealand white rabbits (36) of both sexes. METHODS: In 24 animals, ischemia was induced with midline laparotomy and clamping the aorta just distal to left renal artery and proximal to aortic bifurcation for 20 min. Aprotinin was given 30000 KIU as a short intravenous injection after anesthesia, and was followed by 10000 KIU/h by continuous infusion in group 1 (n = 12). Similar volume of saline solution was used in control group of animals (group 2, n = 12). Group 3 of animals (sham group, n = 12) were anesthetized and subjected to laparotomy without aortic occlusion. Physiological parameters and somatosensory evoked-potentials (SEP) were monitored in animals before ischemia, during ischemia and in the first 60 min of reperfusion. Their neurological outcome was clinically evaluated up to 48 h postischemia. Their motor function was scored, and the intergroup differences were compared. The animals were sacrificed after two days of postischemia. Their spinal cord, abdominal aorta, and its branches were processed for histopathological examination. RESULTS: In group 3, SEP amplitudes did not change during the procedures, and all animals recovered without neurologic deficits. At the end of ischemic period, the average amplitude was reduced to 53+/-7% of the baseline in all ischemic animals. This was followed by a gradual return to 89+/-8 and 81+/-13% of the initial amplitude after 60 min of reperfusion in group 1 and group 2 correspondingly (P > 0.05). The average motor function score was significantly higher in group 1 than group 2 at 24 and 48 h after the ischemic insult (P < 0.05). Histological observations were clearly correlated with the neurological findings. CONCLUSION: The results suggest that aprotinin reduces spinal cord injury and preserves neurologic function in transient spinal cord ischemia in rabbits.