Human Amnion Membrane Proteins Prevent Doxorubicin-Induced Oxidative Stress Injury and Apoptosis in Rat H9c2 Cardiomyocytes.

Doxorubicin (DOX) is widely used as an effective chemotherapy agent in cancer treatment. Cardiac toxicity in cancer treatment with DOX demand urgent attention and no effective treatment has been established for DOX-induced cardiomyopathy. It has been well documented that human amniotic membrane proteins (AMPs), extracted from amnion membrane (AM), have antioxidant, anti-apoptotic, and cytoprotective properties. Therefore, in this study, we aimed to investigate the protective effects of AMPs against cardiotoxicity induced by DOX in cultured rat cardiomyocyte cells (H9c2). DOX-induced cell injury was evaluated using multi-parametric assay including thiazolyl blue tetrazolium bromide (MTT), the release of lactic dehydrogenase (LDH), intracellular Ca2+ , reactive oxygen species (ROS) levels, cellular antioxidant status, mitochondrial membrane potential (ΔΨm), malondialdehyde (MDA), and NF-κB p65 DNA-binding activity. Moreover, expression profiling of apoptosis-related genes (P53, Bcl-2, and Bax) and Annexin V by flow cytometry were used for cell apoptosis detection. It was shown that AMPs pretreatment inhibited the cell toxicity induced by DOX. AMPs effectively attenuated the increased levels of LDH, Ca2+ , ROS, and MDA and also simultaneously elevated the ΔΨm and antioxidant status such as superoxide dismutase (SOD) and Catalase (CAT) in pretreated H9c2 cardiomyocytes. Besides, the activity of NF-kB p65 was reduced and the p53 and Bax protein levels were inhibited in these myocardial cells subjected to DOX. These findings provide the first evidence that AMPs potently suppressed DOX-induced toxicity in cardiomyocytes through inhibition of oxidative stress and apoptosis. Thus, AMPs can be a potential therapeutic agent against DOX cardiotoxicity.

The role of sphingosine 1 phosphate in coronary artery disease and ischemia reperfusion injury.

Coronary artery disease (CAD) is a common cause of morbidity and mortality worldwide. Atherosclerotic plaques, as a hallmark of CAD, cause chronic narrowing of coronary arteries over time and could also result in acute myocardial infarction (AMI). The standard treatments for ameliorating AMI are reperfusion strategies, which paradoxically result in ischemic reperfusion (I/R) injury. Sphingosine 1 phosphate (S1P), as a potent lysophospholipid, plays an important role in various organs, including immune and cardiovascular systems. In addition, high-density lipoprotein, as a negative predictor of atherosclerosis and CAD, is a major carrier of S1P in blood circulation. S1P mediates its effects through binding to specific G protein-coupled receptors, and its signaling contributes to a variety of responses, including cardiac inflammation, dysfunction, and I/R injury protection. In this review, we will focus on the role of S1P in CAD and I/R injury as a potential therapeutic target.

SIRT3-mediated cardiac remodeling/repair following myocardial infarction.

The recent investigations have extensively focused on the importance of sirtuins, as a highly conserved family of gene products, particularly SIRT3 in various biological and pathological processes. SIRT3, the mitochondrial NAD+-dependent deacetylase has been demonstrated to target a broad range of proteins involved in the oxidative stress, ischemia-reperfusion injury, mitochondrial metabolism homeostasis and cellular death. The critical function of SIRT3 in myocardial infarction (MI), which is one of the complex phenotype of coronary artery disease and a result of interaction between various genetic and environmental factors, as well as in cardiac repair and remodeling post-MI have attracted more attention in the recent years. Therefore, in this review, we will summarize important literature about the involvement of SIRT3 in cardiac remodeling/repair following MI and its potential underlying mechanisms.

The role of cholesterol-enriched diet and paraoxonase 1 inhibition in atherosclerosis progression.

Introduction: Atherosclerosis could be deemed as a chronic, progressive, and inflammatory disease. It has been well-documented that high-density lipoprotein (HDL) can reduce the risk of the atherosclerosis occurrence through exerting some anti-atherogenic mechanisms. In recent years, the strong evidence has suggested that paraoxonase 1 (PON1) may contribute to antioxidant properties of HDL. In the present study, the impact of a diet enriched with cholesterol and also the PON1 inhibition on atheroma formation and lipid profile has been investigated. Methods: In this study, 24 New Zealand rabbits were randomly assigned to three groups receiving standard diet, atherogenic diet, and atherogenic diet plus once daily intramuscular injection of nandrolone decanoate as the PON1 inhibitor. Triglyceride, cholesterol, HDL, and low-density lipoprotein (LDL) were determined and both cholesterol accumulation in aorta and fatty streak formation were evaluated. Results: The comparison of the results in three groups reveals that cholesterol level in the group received cholesterol-enriched diet plus once daily injection of PON1 inhibitor was higher than the groups received standard diet or atherogenic diet without PON1 inhibitor (P < 0.05). Furthermore, the percentage of atheroma with type-I lesions was equal to 75% compared with the group received atherogenic diet plus nandrolone at 30%. Additionally, the differences in fatty streak formation in aorta, as well as the right and left coronary arteries in three groups given show that the difference between groups receiving atherogenic diet and standard diet was significantly lower (P < 0.05) than the difference between groups receiving atherogenic diet plus PON1 inhibitor and standard diet. Conclusion: It can be concluded that lack of paraoxanase1 or even reduced the activity of this enzyme could accelerate the progression of fatty streak lesions toward advanced atherosclerotic lesions.

Perventricular Muscular Ventricular Septal Defect (VSD) Closure under Epicardial Echocardiography Guidance: A Case Report.

Ventricular septal defects (VSDs) are among the most common congenital cardiac lesions. Large defects at apicomuscular regions, especially in young patients, are far from accessible to surgeons for conventional surgery. Moreover, the transcatheter closure of VSDs in these patients is difficult and carries a high risk of complications because of the large sheath size relative to the patient's size. The periventricular approach simplifies VSD closure and, thus, eliminates the potential complications of cardiac catheterization and fluoroscopy as it is performed under echocardiographic guidance. A 3-year-old girl with a body weight of 11 kg (failure to thrive) was referred to us. She had multiple adjacent apicomuscular VSDs, the largest one being about 19 mm in diameter, and subsystemic pulmonary artery pressure (PAP). The patient underwent periventricular apicomuscular VSD closure with a Lifetech muscular VSD occluder (size 22 mm) under epicardial echocardiography guidance without cardiopulmonary bypass. Post procedure, the PAP was decreased to mild level. The residual shunt was mild across the adjacent small defects. She was discharged after 7 days without complications. At 2 years' follow-up, the patient was hemodynamically stable and had a normal PAP (PAP = about 16 mmHg) by transthoracic echocardiographic assessment.

Dispersive liquid-liquid microextraction based on solidification of floating organic droplet followed by spectrofluorimetry for determination of carvedilol in human plasma.

BACKGROUND: Simple, chip and rapid analytical methods are required in biomedical analysis laboratories to support therapeutic drug monitoring units in hospitals. The present work aimed to provide such a method for quantitative determination of carvedilol in plasma samples. RESULTS: A new, simple, precise and efficient method was developed for the determination of carvedilol in human plasma using a dispersive liquid-liquid microextraction based on solidification of floating organic droplet, followed by spectrofluorimetry method. Some important parameters such as types and volumes of extraction and disperser solvents, pH, salt effect and sample volume were optimized. Under the optimized experimental conditions, the method provided a linear range of 40 to 300 ng ml(-1), with a correlation coefficient of 0.996. The limit of detection, lower limit of quantification and upper limit of quantification were 18, 40 and 300 ng ml(-1), respectively. The found recovery was from 98.2 to 102.2%, the mean intra- and inter-day precisions were 8.3 and 6.4%, respectively. The relative error for accuracy varied from 0.4 to 2.2%. The short-term temperature and freeze-thaw stability studies showed that carvedilol in human plasma was stable for sample preparation and analysis after storage. CONCLUSION: The proposed method provided reasonable acceptable results and could be used for therapeutic monitoring of carvedilol.

Atherosclerotic changes in common carotid artery, common femoral artery, and ascending aorta/aortic arch in candidates for coronary artery bypass graft surgery.

We assessed the association between common carotid and common femoral artery intima-media thickness (ccIMT and cfIMT, respectively), histopathologic severity of atherosclerosis in the ascending aorta/aortic arch, and the extent of coronary artery disease (CAD) in 150 candidates for elective coronary artery bypass grafting (CABG). One-, 2-, and 3-vessel diseases were present in 20%, 25.9%, and 54.1%, respectively. Although no significant relationship was present between the ccIMT and the number of occluded coronary vessels (P = .41), both the cfIMT and severity of atherosclerosis in the ascending aorta/aortic arch were predictive of more extensive CAD (P = .03 and .01, respectively). Neither the ccIMT nor the cfIMT was correlated with the severity of aortic atherosclerosis (P = .81 and .63, respectively). In conclusion, both cfIMT and atherosclerosis of ascending aorta/aortic arch are independent predictors of CAD extent. However, interrelationships between these 2 variables as well as the ccIMT are complex in CABG candidates.

Scoliosis after thoracotomy/sternotomy in children with congenital heart disease.

CONTEXT: Congenital heart disease (CHD) patients bear a higher risk of scoliosis during their lifetime compared to their normal counterparts. On the other hand, operation on chest wall has been shown to increase the risk of scoliosis. However, the data are inconclusive. The present retrospective analysis is undertaken to determine the frequency of post-thoracotomy/sternotomy scoliosis in children with CHD. MATERIALS AND METHODS: One hundred and eighty children with CHD who underwent thoracotomy/sternotomy and had a minimum followup of 3 years in a teaching center from 1997 to 2010 were recruited. After operation, all the patients were regularly examined for the development of scoliosis. 102 patients underwent thoracotomy and 78 sternotomy. Student's t test, Chi-square test, Fisher's exact test were used for statistical analyses. RESULTS: Eighty-eight males and 92 females with a mean age of 9.95 ± 2.31 (range: 5-15) years were enrolled. The mean age at operation was 2.59 ± 1.66 (range: 0-9) years and the mean follow-up period was 7.36 ± 2.12 (range: 5-13) years. Scoliosis was confirmed in two patients (1.1%): 1 (1%) in the thoracotomy group (a 12-year-old female operated 2 years earlier with a spinal 22° convexity to the right and 78° kyphosis) and another (1.1%) in the sternotomy group (an 8-year-old female operated during her neonatal period with a spinal 23° convexity to the left). CONCLUSION: Scoliosis is not a common finding among the operated children with CHD in our center.

Influence of anterior periaortic fat pad excision on incidence of postoperative atrial fibrillation.

OBJECTIVE: In humans, the existence of an anterior periaortic fat pad (AFP) containing parasympathetic ganglia has been described in the aortopulmonary window. Changes in the autonomic nervous system (ANS) tone can lead to postoperative atrial fibrillation (POAF). The AFP is usually removed during coronary bypass grafting (CABG) to fully expose the aortic root. The purpose of this study was to evaluate the influence of AFP removal during CABG on the ANS tone, incidence of POAF, hospital stay, and in-hospital morbidity and mortality. METHODS: A total of 215 patients were randomized in this prospective, double-blind trial to either removal (n=107) or maintenance (n=108) of the AFP during their first CABG. All patients underwent continuous telemetry monitoring after surgery. They underwent at least 1-h Holter monitoring on the second postoperative day. Heart rate variability measurements of both time-domain and frequency-domain analysis were included. POAF was defined as AF for more than 5min or causing hemodynamic instability. RESULTS: The mean age was nearly 58 years, and 76% were male. There was no difference in the incidence of POAF between the retained and removed AFP groups (19.3% vs 17%, respectively; P=0.664, odds ratio=1.16). Mean heart rate and heart rate variability parameters, in-hospital stay, and postoperative morbidity and mortality were similar in both groups. CONCLUSIONS: Removal of the AFP during CABG has no significant effect on the incidence of POAF, ANS tone, and postoperative morbidity or mortality.

Aortocaval tunnel to the superior vena cava: a case report.

A 20-year old female with a rare anomaly of aortocaval tunnel to superior vena cava is presented. Rare cases of congenital communications between aorta and right sided of the heart has been reported previously. The patient underwent surgical repair and had uneventful recovery.

Neurocognitive impairment after off-pump and on-pump coronary artery bypass graft surgery - an Iranian experience.

BACKGROUND: Coronary artery bypass graft (CABG) surgery is one of the most commonly performed surgical procedures worldwide, and it may be accompanied by postoperative neurocognitive impairment. Although this complication has been attributed to the use of cardiopulmonary bypass, it is still a matter of debate whether the switch from on-pump to off-pump technique affects the cognitive function. OBJECTIVE: The aim of this study was to compare the impact of the on-pump and off-pump techniques on neurocognitive impairment in low-risk CABG surgery groups. METHODS: In a descriptive and analytic study, 201 CABG patients with left-ventricular ejection fraction >30%, and without cardiac arrhythmia were enrolled. Before the elective operation, all patients underwent neurological examination and neurocognitive test, Mini-Mental State Examination (MMSE). Two months following the operation, both on- and off-pump, the patients were re-examined by MMSE to detect any neurocognitive impairment. RESULTS: Out of 154 patients included in the study, 95 (61.6%) and 59 (38.3%) patients were in off-pump and on-pump groups, respectively. Mean age of the patients was 57.17 ± 9.82 years. A 2-month postoperative neurocognitive impairment was detected among 17 patients of on-pump group (28.8%) and in 28 cases of off-pump group (29.4%) (P = 0.54). The mean postoperative MMSE scores were not comparable between groups (25.01 ± 4.49 in off-pump group versus 23.73 ± 4.88 in on-pump group, P = 0.09). CONCLUSION: The present study revealed that in low-risk patients undergoing CABG surgery, either the techniques of on-pump or off-pump did not differ regarding the neurocognitive outcome 2 months after the procedure.

Isolated cardiac hydatidosis--a case report.

Cardiac hydatidosis is rarely encountered. A case of isolated cardiac hydatid cyst of the left ventricle in a young woman is described. The diagnosis was suggested by echocardiography and was confirmed later by pathological evaluation. Serological tests were negative. The patient underwent a successful operation for cyst resection.

Valved patch for ventricular septal defect with pulmonary arterial hypertension.

From March 1998 to December 2004, 16 acyanotic patients aged 2 to 22 years (mean, 7 +/- 5.7 years) with a large ventricular septal defect and elevated pulmonary vascular resistance (9.6 +/- 3.8 Wood units) underwent surgery. A Gore-Tex patch with a 5-8 mm longitudinal slit in the center was used. A piece of pericardium was sewn around the slit on one side of the patch, except for the upper quarter. In all patients, the defect was closed with a trimmed patch and the pericardial aspect was placed on the left ventricular side to allow right-to-left shunting. Echocardiography on the day of operation revealed a right-to-left shunt in 6 cases. Two patients (12.5%) died in the early postoperative period due to frequent episodes of pulmonary hypertensive crisis and persistent severe pulmonary hypertension. In 3 years of follow-up, pulmonary vascular resistance gradually decreased in all but one patient in whom it increased with a right-to-left shunt and cyanosis. Insertion of a valved patch seems to be a promising technique to decrease morbidity and mortality in severe pulmonary arterial hypertension.

Transcranial and carotid Doppler study in coronary artery bypass graft patients.

OBJECTIVE: Atherosclerosis is a pathogenesis which is common in both coronary and intracranial arterial diseases. Therefore, we designed a group of coronary artery bypass graft (CABG) surgery patients for transcranial Doppler (TCD) to assess intracranial artery diseases and carotid duplex studies to assess carotid artery diseases. METHODS: In a prospective randomized study, 129 elective CABG patients with proven coronary artery disease by angiography, were examined by TCD and 45 patients by carotid duplex preoperatively. Neurologic examination was carried out pre- and post- operatively. This study was carried out from April 2001 to August 2002 at Imam Hospital of Tabriz Medical Science University, Iran. RESULTS: Out of the 129 CABG patients, there were 105 males and 24 females, with an average age of 57+\-9.9 years. Risk factors were as follows: smoking in 44.8%, hypertension in 38%, hypercholesterolemia in 29%, and diabetes mellitus in 18.6%. The TCD findings of 30 patients (23.2%, 11 female and 19 male) revealed the following abnormalities: stenosis of basilar artery in 7 patients (5.4%), carotid siphon in 3 (2.3%), intracranial internal carotid in 5 (3.9%), middle cerebral artery in 3 (2.3%) and vertebral artery in one patient (0.8%). Multiple vessel abnormality was detected in 11 patients (8.5%). There was a significant correlation between severity of coronary artery disease in angiography and abnormality in TCD (p=0.008). The TCD abnormality was detected more in females (p=0.008) or hypertensive patients (p=0.004). In the carotid duplex study of the randomized 45 patients, 23 (51.1%) had abnormal results as follows: stenosis <50% in 17 (38%) cases, stenosis between 50-70% in 5 (11%), and hemodynamically significant stenosis (>70%) only in one (2%) patient. There was also significant correlation between severity of coronary involvement and carotid involvement (p<0.01). No stroke occurred in the first postoperative week following CABG surgery. CONCLUSION: Stenosis of intracranial and carotid arteries was more common in CABG patients with more than 2-coronary vessel involvement or hypertensive or female patients. We recommend TCD and carotid duplex studies in these patients for prevention of probable cerebrovascular accidents.

Effects of low fat and low calorie diet on plasma lipid levels in the fasting month of Ramadan.

OBJECTIVE: In Ramadan, which is one month of the Hijra year, Muslims change their eating habits from 3 times to 2 times daily. The aim of this study was to evaluate the effects of fasting with low fat and low calorie diet on anthropometric parameters and plasma lipid profiles in hyperlipidemic men during the month of Ramadan. METHODS: This study was carried out at the Madani Heart Hospital, Tabriz University of Medical Sciences, Tabriz, Iran during the year of 1997. Twenty-eight hyperlipidemic healthy men in a fasting group and 10 healthy men with top normal lipid levels in a non-fasting group were voluntarily enrolled for study. They were encouraged to use low fat and low calorie diet. The study started 20 days before and lasted one month after Ramadan. Laboratory tests including plasma total cholesterol, cholesterol-low density lipoprotein, cholesterol-high density lipoprotein and triglyceride were measured 4 times; 20 days before Ramadan, first day of Ramadan, on the last day of Ramadan and 30 days after Ramadan. RESULTS: Data analysis in fasting group revealed a significant reduction in energy intake and nutrient materials during Ramadan month (P<0.05) and plasma total cholesterol, cholesterol low density lipoprotein and triglyceride levels decreasing towards the end of Ramadan (P<0.01). In the non-fasting group, there were no significant changes in the above-mentioned parameters. CONCLUSION: It seems that Islamic fasting in Ramadan with low fat and low calorie diet leads to plasma lipids reduction in hyperlipidemic men.

Effects of Ramadan fasting on serum lipid profiles on 2 hyperlipidemic groups with or without diet pattern.

OBJECTIVE: The effects of Ramadan fasting, with low fat and low calorie diet, on blood lipid and lipoprotein levels were studied. Results revealed reduction of plasma lipid levels and anthropometric parameters in the hyperlipidemic cases. To find out whether such reductions were due to nutritional diet or Ramadan fasting, we conducted a study to evaluate effects of Ramadan fasting on 2 separate hyperlipidemic groups with or without nutritional diet regimen. METHODS: This study was carried out at Madani Heart Hospital, Tabriz, Iran, during the year 1998. Thirty-eight hyperlipidemic healthy men voluntarily enrolled into 2 groups, group I, 22 men on low fat and low calorie diet and group II, 16 men without any special diet interference. The blood lipid profile tests were measured 4 times (3 weeks before, first week, last week and one month after Ramadan). To evaluate nutritional composition, 12 times in non-successive days, 24 hour nutrition recalls were obtained from all individuals during the study. RESULTS: Analysis of data revealed that only triglyceride in both groups reduced in the beginning of Ramadan compared to 3 weeks before. During Ramadan, with a reduction of 300 Kcal/day in comparison to before Ramadan, no changes were seen concerning anthropometric parameters and serum lipids levels. CONCLUSION: It seems that the effect of Ramadan fasting on serum lipid levels may be closely related to the nutritional diet. For reduction of plasma lipid levels, it would be necessary to omit at least one term meal or reduce energy by 500 Kcal or more per day.