Serum paraoxonase activity in patients with ischaemic and nonischaemic dilated cardiomyopathy.

BACKGROUND: This study examined whether the serum PON1 activity is different in patients with ischaemic dilated cardiomyopathy (IDCM) and nonischaemic dilated cardiomyopathy (NDCM) and the relation between the serum PON1 activity and serum pro-BNP levels. METHODS AND RESULTS: In this study, we enrolled 60 patients with left ventricular systolic failure (New York Heart Association [NYHA] class III-IV) and a left ventricular ejection fraction (EF) < 40% as determined by echocardiography and 30 healthy subjects. The patients with systolic heart failure were divided into two groups: patients with IDCM and patients with NDCM. Blood samples were obtained to measure the serum PON1 activity and the serum pro-BNP levels. The median serum PON1 activities were lower among the patients with IDCM or with NDCM compared with the control subjects (p < .001, p = .043, respectively). Compared with the control subjects, the patients with IDCM or with NDCM had higher serum pro-BNP levels (p < .001, p < .001, respectively). The serum PON1 activity was negatively correlated with the serum pro-BNP levels in patients with IDCM (r = -0.548, p < .001). The area under the ROC curve of the serum PON1 activity was 0.798. Using a serum PON1 activity of 201.3 U/L as a cut-off value, the sensitivity was 86.84% and specificity was 66.67% for the diagnosis of IDCM. CONCLUSIONS: In this study, the serum PON1 activity was significantly reduced in the patients with IDCM or with NDCM compared with the control subjects. The serum PON1 activity of the patients with IDCM was negatively correlated with the serum pro-BNP levels.

Cardiac pauses in competitive athletes: a systematic review examining the basis of current practice recommendations.

AIMS: It is generally recommended that individuals aspiring to competitive sports should undergo pre-participation cardiovascular assessment, particularly including arrhythmia risk evaluation. In regard to bradyarrhythmias, the 36th Bethesda Conference suggested that asymptomatic cardiac pauses ≤3 s are 'probably of no significance', whereas longer 'symptomatic' pauses may be abnormal. This study focused on assessing the evidence for the '3 s' threshold. METHODS: A systematic literature search was undertaken including Embase (1980-) and Ovid Medline (1950-). The following MeSH terms were used in the database searches: Cardiac.mp & pause.mp. Additionally, pertinent publications found by review of citation lists of identified publications were examined. Individuals with reversible causes of bradyarrhythmia (e.g. drugs) were excluded. RESULTS: The study population comprised 194 individuals with cardiac pauses of 1.35-30 s. In 120 athletes, specific records for pause durations were provided, but it was not always clear whether pauses occurred at rest. Among these 120 athletes, 106 had pauses ≤3 s, of whom 92 were asymptomatic and 14 were symptomatic. Fourteen athletes had pauses >3 s, of whom nine were asymptomatic and five were symptomatic. There were no deaths during follow-up (7.46 ± 5.1 years). With respect to symptoms, the ≤3 s threshold had a low-positive predictive value (35.7%) and low sensitivity (26.3%), but good negative predictive value (86.7%) and specificity (91%). CONCLUSION: While the evidence is not incontrovertible, the 3 s pause threshold does not adequately discriminate between potentially asymptomatic and symptomatic competitive athletes, and alone should not be used to exclude potential competitors.

Syncope: Assessment of risk and an approach to evaluation in the emergency department and urgent care clinic.

Syncope is among the most frequent forms of transient loss of consciousness (TLOC), and is characterized by a relatively brief and self-limited loss of consciousness that by definition is triggered by transient cerebral hypoperfusion. Most often, syncope is caused by a temporary drop of systemic arterial pressure below that required to maintain cerebral function, but brief enough not to cause permanent structural brain injury. Currently, approximately one-third of syncope/collapse patients seen in the emergency department (ED) or urgent care clinic are admitted to hospital for evaluation. The primary objective of developing syncope/TLOC risk stratification schemes is to provide guidance regarding the immediate prognostic risk of syncope patients presenting to the ED or clinic; thereafter, based on that risk assessment physicians may be better equipped to determine which patients can be safely evaluated as outpatients, and which require hospital care. In general, the need for hospitalization is determined by several key issues: i) the patient's immediate (usually considered 1 week to 1 month) mortality risk and risk for physical injury (e.g., falls risk), ii) the patient's ability to care for him/herself, and iii) whether certain treatments inherently require in-hospital initiation (e.g., pacemaker implantation). However, at present no single risk assessment protocol appears to be satisfactory for universal application, and development of a consensus recommendation is an essential next step.

The mysterious light of dark chocolate.

A healthy diet plays a key role in the prevention and management of cardiovascular diseases. Dark chocolate in particular has been shown to improve endothelial functions and lipid profile and to have cardiovascular protective effects via an inhibitory action on platelet functions. Recently, several studies have demonstrated the beneficial effects of chocolate, primarily on hypertension and other conditions such as coronary artery disease and hyperlipidemia. The present review provides a summary of the ingredients, bioavailability and cardiovascular protective effects of chocolate / cocoa and the published effects of chocolate on a number of cardiovascular diseases.

Effects of off-pump versus on-pump coronary artery bypass grafting: apoptosis, inflammation, and oxidative stress.

BACKGROUND: It has been suggested that off-pump coronary artery bypass grafting (CABG) surgery reduces myocardial ischemia-reperfusion injury, postoperative systemic inflammatory response, and oxidative stress. The aim of this study was to measure serum malondialdehyde (MDA), high-sensitivity C-reactive protein (hs-CRP), M30, and M65 levels and to investigate the relationship between M30 levels and oxidative stress and inflammation in patients undergoing on-and off-pump CABG surgery. METHODS: Fifty patients were randomly assigned to on-pump or off-pump CABG surgery (25 patients off-pump and 25 on-pump CABG surgery), and blood samples were collected prior to surgery, and 30 minutes, 60 minutes, 6 hours, and 24 hours after CABG surgery. RESULTS: Compared to the on-pump group, serum MDA levels at 30 minutes, 60 minutes, 6 hours, and 24 hours after the CABG surgery were significantly lower in the off-pump group (P=.001, P=.001, P=.001, and P=.001, respectively). Serum M30 levels were found to be elevated in both groups, returning to baseline at 24 hours. When compared to baseline, the hs-CRP level reached its peak at 24 hours at 13.28±5.32 mg/dL in the on-pump group, and 15.44±4.02 mg/dL in the off-pump group. CONCLUSION: CABG surgery is associated with an increase in inflammatory markers and serum M30 levels, indicating epithelial/endothelial apoptosis in the early period.

Heart Failure Awareness Survey in a Turkish Population: HFAS-TR.

OBJECTIVE: Heart failure is a leading cause of death and the most common diagnosis leading to hospitalization. Its awareness is lower than that of other cardiovascular diseases, both in the general population and among patients with heart failure (HF). This study aimed to establish the current level of knowledge about HF in patients with HF with reduced ejection fraction (HFrEF) and mildly reduced ejection fraction (HFmrEF) in Türkiye. METHODS: This questionnaire-based survey study is multicenter, conducted across 34 centers from December 2021 to July 2022. We performed a survey consisting of two sets of questions focusing on individual characteristics of the patients and HF-related knowledge. RESULTS: The study included a total of 2,307 outpatient HF patients, comprising 70.5% males and 29.5% females with a mean age of 64.58 ± 13 (56-74) years and a mean body mass index value of 32.5 ± 10 kg/m2. HFrEF and HFmrEF were determined in 74.7% and 25.3% of patients, respectively. Thirty percent of the patients were unaware that they had HF. While 28.7% of the patients thought that they had sufficient information about HF, 71.3% believed they lacked adequate knowledge. In the study, 25.2% of the participants identified dyspnea, 22% identified tiredness, and 25.4% identified leg edema as the most common symptoms of HF. Only 27.4% of patients recognized all three typical symptoms of HF. CONCLUSION: We found that the study population's knowledge about HF symptoms and the nature of the disease was poor. Educational and awareness activities are necessary to optimize outcomes and benefits.

Dislodgement of a sirolimus-eluting stent in the circumflex artery and its successful deployment with a small-balloon technique.

Coronary stent dislodgement or embolization before deployment is a rare but serious complication in interventional cardiology. A 60-year-old male presented with unstable angina five years after coronary artery bypass surgery. There was a stenosis (70%) in the obtuse marginal branch of the circumflex artery. During percutaneous coronary intervention, a sirolimus-eluting stent was stripped from its balloon mainly because of significant proximal angulation and incarcerated within the proximal circumflex artery. A smaller balloon dilatation catheter was advanced and pushed through the inside of the slipped stent. Using this technique, the stent could be advanced into the lesion and was successfully deployed. To our knowledge, this is the first case report on sirolimus-eluting stent dislodgement.

Factors Affecting Hypertension in the Adult Population of the Marmara Region, Turkey: A Descriptive Field Study.

INTRODUCTION: Hypertension is an increasingly prevalent global public health problem. Nutritional culture and lifestyle are among the factors related to hypertension. The aim of this study was to evaluate the prevalence and influential factors of hypertension in the adult population of the Marmara region, Turkey. METHODS: The study was conducted in 10 provinces in the Marmara region between June 01, 2018, and November 30, 2018. Participants included 2353 patients over 18 years of age diagnosed with hypertension by any of the 30 family physicians working in the Family Health Centers in these provinces. After the participants provided written consent, a survey consisting of 25 questions was administered by their family physicians. SPSS 25.0 (IBM Corporation, Armonk, New York, United States) was used for all statistical analysis calculations. RESULTS: The patients included 1449 females (61.6%) and 904 males (38.4%). Among the respondents, 1555 (73.1%) had primary hypertension etiology and 572 (26.9%) had secondary etiology. While 1614 patients (68.6%) did not exercise at all, 739 patients (31.4%) reported exercising; 1026 patients (43.9%) did not restrict salt in their diet; and 1134 patients (48.2%) had a family history of hypertension. CONCLUSION: Since individual and environmental factors affect the etiology of hypertension, it is recommended that family physicians address these factors first as part of a holistic approach for hypertension prevention, diagnosis, treatment, and follow-up.

A rare combination of left main coronary artery fistula to main pulmonary artery with severe left main coronary artery disease in a 69-year-old man.

A 69-year-old man was referred to our hospital with a diagnosis of non-ST elevation myocardial infarction. A selective left coronary angiography revealed a fistula connecting the left main coronary artery with the pulmonary artery in addition to severe left main coronary artery disease. The patient subsequently underwent ligation of fistulae and coronary bypass grafting. The combination of a fistula and severe artery disease seen in this patient is unusual because fistulas originating from the left main coronary artery drain into the pulmonary artery in patients with severe left main coronary artery disease.

Serum arylesterase activity is negatively correlated with inflammatory markers in patients with acute coronary syndromes.

OBJECTIVES: To examined whether serum paraoxonase (PON1) and arylesterase (ARE) activities are correlated with inflammatory biomarkers (procalcitonin and high sensitivity C-reactive protein (hs-CRP) in patients with acute coronary syndrome (ACS). METHODS: This cross-sectional study was conducted at the Departments of Cardiology and Biochemistry, Uludag University School of Medicine, Bursa, Turkey, from April 2007 to December 2007. Seventy-eight consecutive patients with ACS and 39 healthy controls were investigated. Acute coronary syndrome patients were divided into 3 groups according to their clinical presentation: unstable angina pectoris (UAP) (Braunwald III-B, n=25), non-ST elevation myocardial infarction (NSTEMI) (n=18), and ST-elevation myocardial infarction (STEMI) (n=35). Serum PON1/ARE activities were measured spectrophotometrically. Levels of procalcitonin and hs-CRP were measured by immunoassay. RESULTS: Paraoxonase/ARE activities were significantly lower in all patient groups compared to controls. No correlation between PON1/ARE activities and high-density-cholesterol levels was seen. Among ACS patients, serum ARE activity correlated inversely with baseline and 48-hour procalcitonin (r=-0.577, p=0.009, and r=-0.642, p=0.019) and hs-CRP levels (r=-0.614, p=0.03, and r=-0.719, p=0.044). CONCLUSION: Serum ARE activity is reduced in ACS patients and inversely correlated with inflammatory markers.

The relationship between cardiac autonomic neuropathy and Tei index in patients with type II diabetes mellitus.

OBJECTIVE: We have investigated the relationship between silent cardiac autonomic neuropathy (CAN), one of the most important causes of mortality in diabetic patients, and the Tei index, which is an indicator of global ventricular function. METHODS: Among the patients with type 2 diabetes mellitus, 15 without autonomic neuropathy (Ewing score < 1) were accepted as CAN (-) and 18 with autonomic neuropathy (Ewing score > or =1) were accepted as CAN (+).Twelve healthy individuals were included in the control group. Diastolic dysfunction and Tei index were evaluated by means of 2-D and Doppler echocardiographic examination. RESULTS: Not only Doppler mitral, but also tricuspid inflow parameters showed a significant decrease in E/A ratio, an increase in A wave amplitude and deceleration time with CAN (+) patients. Left ventricular Tei index and Ewing score were found to be positively correlated (P < 0.001, r = 0.55). Likewise to the correlation in the left ventricle, a positive correlation was also detected between right ventricular Tei index and Ewing score (P = 0.004, r = 0.43). CONCLUSIONS: We have shown that in patients with type II diabetes, CAN is related with left and right ventricular diastolic dysfunction.We also have determined that the Tei index is in correlation with CAN (Ewing score), which is a complication of diabetes.

Association between paraoxonase 1 activity and severity of coronary artery disease in patients with acute coronary syndromes.

OBJECTIVE: We sought to investigate serum paraoxonase/arylesterase activities in patients with acute coronary syndromes (ACS) and their correlations with the severity and extent of coronary artery disease (CAD). METHODS AND RESULTS: Three groups of patients were investigated: 89 patients with ACS, 54 patients with normal coronary angiograms (no-CAD group), and 27 healthy comparison subjects. ACS patients were divided into three groups according to their clinical presentation: unstable angina pectoris (UAP, Braunwald III-B, n = 31), non-ST elevation myocardial infarction (NSTEMI) (n = 27), and ST-elevation myocardial infarction (STEMI) (n = 31). Serum paraoxonase/arylesterase activities were measured spectrophotometrically. Angiographic CAD extent was expressed both by the number of vessels diseased and by the Gensini scoring system. Results showed that serum paraoxonase/ arylesterase activities and the paraoxonase/high density lipoprotein-cholesterol (HDL-C) ratio were significantly lower in the STEMI, NSTEMI, UAP groups than in no-CAD and control groups. Serum paraoxonase/arylesterase activities and paraoxonase/HDL-C ratio were reduced in patients with 2-vessel disease (VD) and 3-VD compared to the I-VD and no-CAD group (P < 0.001). In patients with ACS, the Gensini score correlated inversely with serum paraoxonase (r = -0.419, P < 0.001), arylesterase (r = -0.492, P < 0.0001), and the paraoxonase/HDL-C ratio (r = -0.377, P < 0.001). Serum arylesterase (r = 0.161, P = 0.03) and paraoxonase (r = 0.135, P = 0.002) activities were positively correlated with HDL-C levels. Serum arylesterase activity (P < 0.0001), gender (P = 0.0037), diabetes mellitus (P = 0.005) and LDL-C levels (P = 0.03) were independent predictors of CAD presence. CONCLUSIONS: Serum paraoxonase/arylesterase activities are reduced in ACS patients and inversely correlated with the severity of CAD.

Procalcitonin in patients with acute coronary syndrome: correlation with high-sensitive C-reactive protein, prognosis and severity of coronary artery disease.

OBJECTIVES: The aim of this study is to determine the relation of high-sensitive serum C-reactive protein (hsCRP) and procalcitonin with presence and severity of coronary artery disease and early prognosis in patients with acute coronary syndrome (ACS). METHODS AND RESULTS: Procalcitonin and hsCRP levels were measured at admission and after 48 hours in 50 patients (41 men, 9 women) with ACS. The patients were assigned to three groups according to their clinical diagnosis: unstable angina pectoris (UAP) (Braunwald III-B), non-ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI). Incidences of adverse cardiac events were recorded in a 3-month follow-up. Coronary angiography was performed to evaluate presence and severity of coronary artery disease. In the groups of STEMI, NSTEMI and UAP, procalcitonin (P = 0.01 3, P = 0.045 and P = 0.000 1, respectively) and hsCRP (P = 0.000 1, P = 0.01 and P = 0.00 1, respectively) levels were significantly increased. No significant correlation was found between these markers and the presence and severity of coronary artery disease. There was no correlation between procalcitonin and hsCRP levels at admission and after 48 hours and primary end points after 3 months except in the group of UAP with revascularization procedure. In the group of UAP, hsCRP levels at 48 hours were found higher in the patients with a revascularization procedure (P = 0.04). CONCLUSIONS: In conclusion, levels of hsCRP and procalcitonin are increased in patients with ACS but failed to correlate with severity of coronary disease and early prognosis.

Post-discharge heart failure monitoring program in Turkey: Hit-PoinT.

OBJECTIVE: The aim of this study was to assess the efficacy and feasibility of an enhanced heart failure (HF) education with a 6-month telephone follow- up program in post-discharge ambulatory HF patients. METHODS: The Hit-Point trial was a multicenter, randomized, controlled trial of enhanced HF education with a 6-month telephone follow-up program (EHFP) vs routine care (RC) in patients with HF and reduced ejection fraction. A total of 248 patients from 10 centers in various geographical areas were randomized: 125 to EHFP and 123 to RC. Education included information on adherence to treatment, symptom recognition, diet and fluid intake, weight monitoring, activity and exercise training. Patients were contacted by telephone after 1, 3, and 6 months. The primary study endpoint was cardiovascular death. RESULTS: Although all-cause mortality didn't differ between the EHFP and RC groups (p=NS), the percentage of cardiovascular deaths in the EHFP group was significantly lower than in the RC group at the 6-month follow up (5.6% vs. 8.9%, p=0.04). The median number of emergency room visits was one and the median number of all cause hospitalizations and heart failure hospitalizations were zero. Twenty-tree percent of the EHFP group and 35% of the RC group had more than a median number of emergency room visits (p=0.05). There was no significant difference regarding the median number of all-cause or heart failure hospitalizations. At baseline, 60% of patients in EHFP and 61% in RC were in NYHA Class III or IV, while at the 6-month follow up only 12% in EHFP and 32% in RC were in NYHA Class III or IV (p=0.001). CONCLUSION: These results demonstrate the potential clinical benefits of an enhanced HF education and follow up program led by a cardiologist in reducing cardiovascular deaths and number of emergency room visits with an improvement in functional capacity at 6 months in post-discharge ambulatory HF patients.

Acute effect of hemodialysis on arterial elasticity.

BACKGROUND/AIM: Reduced arterial elasticity is an independent predictor of cardiovascular mortality in patients with end-stage renal disease (ESRD). Hemodialysis (HD) treatment per se can bring additional risk factors for vascular disease. Our study was designed to determine whether a single hemodialysis session leads to an acute alteration in parameters of arterial elasticity in ESRD. MATERIALS AND METHODS: In this study, 58 patients undergoing chronic hemodialysis and 29 healthy controls were enrolled. Large artery elasticity index (LAEI) and the small artery elasticity index (SAEI) were measured by applanation tonometry. The acute effect of a hemodialysis session on arterial elasticity indices was assessed by comparison of prehemodialysis and posthemodialysis determinations. RESULTS: At baseline, LAEI did not differ significantly in patients compared with controls. In contrast, the SAEI was significantly lower in patients (4.1 ± 2.6 mL/mmHg x 100) than in healthy individuals (8.9 ± 3.4 mL/mmHg x 100, P < 0.05). In patients with ESRD, no significant changes in LAEI was observed after HD, but SAEI deteriorated significantly (from 4.1 ± 2.6 mL/mmHg x 100 to 3.4 ± 2.3, P < 0.05). CONCLUSION: We conclude that ESRD patients face a significant reduction in SAEI, which is exacerbated by a dialysis procedure.

Myocardial performance is impaired in patients with branch retinal vein occlusion.

OBJECTIVE: To investigate whether the Tei index, which is an indicator of global myocardial function and an independent predictor of cardiac death, is increased in patients with branch retinal vein occlusion (BRVO). METHODS: The Tei index was used to evaluate myocardial performance, in addition to conventional echocardiographic evaluation of myocardial structural and functional changes, in patients with BRVO, patients with hypertension and healthy controls. RESULTS: Out of 36 patients with BRVO (18 female, 18 male; 17 hypertensive, 19 normotensive), 29 patients with hypertension (15 female, 14 male) and 28 healthy controls (15 female, 13 male), there were no significant between-group differences in age and sex. The mitral A wave was higher and mitral E/A ratio, mitral E wave and ejection time were lower, in patients with BRVO than in healthy controls. Mean Tei index was significantly higher in the BRVO group than in patients with hypertension or healthy controls. Compared with healthy controls, the Tei index was significantly higher in hypertensive and normotensive patients with BRVO. CONCLUSION: Myocardial performance is decreased in patients with BRVO, independent of whether or not they have hypertension.

Acute Haemodialysis-induced Changes in Tissue Doppler Echocardiography Parameters.

BACKGROUND: Tissue Doppler imaging (TDI) is a method that determines the tissue motion and velocity within the myocardium. AIMS: To characterize acute haemodialysis (HD)-induced changes in TDI-derived indices for patients that have end-stage renal disease (ESRD). STUDY DESIGN: Cross sectional study. METHODS: Conventional echocardiography and TDI methods were applied to study ESRD patients (n=58) before and after HD. Pulmonary venous flow, mitral inflow, and TDI signals of the lateral and septal mitral annulus were examined for the determination of altered left-ventricular diastolic filling parameters. Flow velocities from early- (E) and late-atrial (A) peak transmitral; peak pulmonary vein systolic (S) and diastolic (D); and myocardial peak systolic (Sm) and peak early (Em) and late (Am) diastolic mitral annular velocities were also assessed for changes. RESULTS: Transmitral E and A velocities and the E/A ratio decreased significantly after HD (p<0.001). Pulmonary vein S (p<0.001) and D (p<0.001) velocities decreased, and S/D ratios increased significantly (p=0.027). HD led to a reduction in septal Em (p<0.001), lateral Em (p=0.006), and Am (p<0.001) velocities. Contrary to the decreases in Em and Am, the Em/Am ratio remained unchanged. CONCLUSION: A single HD session was associated with an acute deterioration in the diastolic parameters. Since the Em/Am ratio remained unchanged, we conclude that this index is a relatively load-independent measure of diastolic function in HD patients.

Effective inhibition of cardiomyocyte apoptosis through the combination of trimetazidine and N-acetylcysteine in a rat model of myocardial ischemia and reperfusion injury.

OBJECTIVE: Apoptosis is the early and predominant form of cell death in infarcted myocardia. The aim of the study was to investigate the effects of trimetazidine (TMZ) and N-acetylcysteine (NAC), used alone or in combination, on oxidative stress, infarct size, and ischemia-reperfusion (IR)-induced cardiomyocyte apoptosis in a rat model of myocardial IR. METHODS AND RESULTS: Myocardial IR was established by ligating an area under the left main coronary artery for 30 min followed by 3 h of reperfusion. Saline (1 ml/kg), NAC (50, 150 mg/kg), or TMZ (3, 5 mg/kg) was intravenously injected during the middle of the ischemic period. At the end of the reperfusion, blood samples were collected from the animals to measure serum M30 and M65 levels, which are markers of cell death, the S100b level, which is a marker of inflammation, and the malondialdehyde (MDA) level, which is a marker of oxidative stress. The infarct size was evaluated as the ratio of the infarct area to the risk area. Apoptotic activation was assessed by caspase-3 immunostaining and a TUNEL assay. TMZ and NAC, either alone or in combination, significantly reduced serum MDA levels, infarct area and apoptotic activity compared to those observed in saline group. Interestingly, the infarct area was more smaller in TMZ (3 and 5 mg/kg) injected groups (9.72 ± 1.3% and 9.96 ± 2.3%) than those observed in NAC (50 and 150 mg/kg) (16.1 ± 2.5% and 19.1 ± 2.14%) or TMZ (5 mg/kg)- NAC (150 mg/kg) combination groups (16.9 ± 1.6%). However, the apoptotic activity was reduced more significantly in the combination of TMZ (5 mg/kg)-NAC (50 mg/kg) compared to TMZ-only group. Neither TMZ or NAC treatments nor the combination of the drugs significantly affected serum M30, M65 and S100B levels. CONCLUSION: Intravenous NAC and TMZ administration decreased oxidative stress, infarct area and apoptotic activity in a rat model of IR. Although the combination treatment was more effective in reducing the apoptotic activity than either treatment groups alone, TMZ treatment was more successful in reducing the infarct area than NAC or combination treatments. Present results suggest that, in addition to mechanical attempts to secure myocardial reperfusion, the use of TMZ and NAC may help to reduce IR injury.