Distinguishable DNA methylation defines a cardiac-specific epigenetic clock.

BACKGROUND: The present study investigates whether epigenetic differences emerge in the heart of patients undergoing cardiac surgery for an aortic valvular replacement (AVR) or coronary artery bypass graft (CABG). An algorithm is also established to determine how the pathophysiological condition might influence the human biological cardiac age. RESULTS: Blood samples and cardiac auricles were collected from patients who underwent cardiac procedures: 94 AVR and 289 CABG. The CpGs from three independent blood-derived biological clocks were selected to design a new blood- and the first cardiac-specific clocks. Specifically, 31 CpGs from six age-related genes, ELOVL2, EDARADD, ITGA2B, ASPA, PDE4C, and FHL2, were used to construct the tissue-tailored clocks. The best-fitting variables were combined to define new cardiac- and blood-tailored clocks validated through neural network analysis and elastic regression. In addition, telomere length (TL) was measured by qPCR. These new methods revealed a similarity between chronological and biological age in the blood and heart; the average TL was significantly higher in the heart than in the blood. In addition, the cardiac clock discriminated well between AVR and CABG and was sensitive to cardiovascular risk factors such as obesity and smoking. Moreover, the cardiac-specific clock identified an AVR patient's subgroup whose accelerated bioage correlated with the altered ventricular parameters, including left ventricular diastolic and systolic volume. CONCLUSION: This study reports on applying a method to evaluate the cardiac biological age revealing epigenetic features that separate subgroups of AVR and CABG.

Ozone effect on the inflammatory and proteomic profile of human macrophages and airway epithelial cells.

Ozone (O3) is one of the most harmful urban pollutants, but its biological mechanisms have not been fully elucidated yet. Human bronchial epithelial cells (HBEpC) and human macrophage cells (differentiated human monocytic cell line) were exposed to O3 at the concentration of 240 µg/m3 (120 ppb), corresponding to the European Union alert threshold. Cell viability, reactive oxygen species (ROS) production, and pro-inflammatory cytokines release (IL-8 and TNF-α) were evaluated. Results indicated that O3 exposure increases ROS production in both cell types and enhances cytokines release in macrophages. O3 stimulated IL-8 and TNF-α in HBEpC when the cells were pretreated with Lipopolysaccharide, used to mimic a pre-existing inflammatory condition. Proteomics analysis revealed that, in HBEpC, O3 caused the up-regulation of aldo-keto reductase family 1 member B10, a recognized critical protein in lung carcinogenesis. In conclusion, our results show that 120 ppb O3 can lead to potential damage to human health suggesting the need for a revision of the actual alert levels.

Cigarette smoke is associated with up-regulation of inducible NOS and COX-2 protein expression and activity in granulosa cells of women undergoing in vitro fertilization.

Cigarette smoke exposure represents a well-established ovotoxic exogenous stress, but the molecular mechanisms underlying of this effect are still unclear. Cigarette smoke upregulates inflammatory genes in the female reproductive organs, therefore an abnormal inflammation response may contribute to the impairment of female fertility. In this study we investigated for the first time the effect of cigarette smoke exposure on NOS and COX expression and activity and on their transcription factors (CREB and NF-kB) in human GCs and on the release of NO and PGE2 in the FF in smoking and non-smoking patients undergoing IVF treatment. In addition, correlation analysis between AMH serum levels, an index of ovarian reserve, and smoking exposure or iNOS and COX-2 protein expression levels were performed using a Pearson correlation method. Cigarette smoke exposure resulted in a significant increase of iNOS and COX-2 protein expression together with an increase of iNOS activity and PGE2 levels. pNF-kB and pCREB protein expression were upregulated in the GCs of smokers compared to non-smokers. The habit of smoking was negatively correlated with serum AMH levels, and positively correlated with iNOS and COX-2 protein expression levels. The data presented in the current study revealed a novel molecular mechanism underlying the toxic effects of cigarette smoke on fertility. Additional pathways mediating the effects of cigarette smoke exposure in human GCs cannot be excluded and should be investigated in future studies.

Robotic versus laparoscopic approach to treat symptomatic achalasia: systematic review with meta-analysis.

Minimally invasive Heller myotomy is considered the gold standard surgical approach for symptomatic achalasia because it is a safe and effective procedure. Over the last years, several studies comparing the laparoscopic and robotic approach for Heller myotomy have been published. Although the robotic approach appears to have some advantages over standard laparoscopy, data on this topic are still controversial and no definite conclusions have been drawn. This metanalysis has been designed to systematically evaluate and compare the effectiveness and safety of the robot-assisted Heller myotomy as compared to the standard laparoscopic approach. According to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, a systematic search on both laparoscopic and robotic Heller myotomy was performed in all the major electronic databases (PubMed, Web of Science, Scopus, EMBASE), using the following search string: (achalasia OR Dor) AND robotic. Six articles were included in the final analysis. A metaregression analysis was performed to assess the possible effects of demographic variables (age, gender, body mass indes (BMI)) and previous abdominal surgery or endoscopic intervention on the analyzed outcomes. No statistical difference was observed in operative times (mean difference (MD) = 20.79, P = 0.19, 95% confidence interval (CI) -10.05,51,62), estimated blood loss (MD = -17.10, P = 0.13, 95% CI -40.48,5.08), conversion rate to open surgery (risk difference (RD) = -0.01, P = 0.33, 95% CI -0.05,0.02), length of hospital stay (MD = -0.73, P = 0.15, 95% CI -1.71,0.25) and long-term recurrence (odds ratio (OR) = 0.59, P = 0.45, 95% CI 0.15,2.33). On the contrary, the robotic approach was found to be associated with a significantly significant lower rate of intraoperative esophageal perforations (OR = 0.13, P < 0.001, 95% CI 0.04, 0.45). Our results suggest that the robotic approach is safer than the laparoscopic Heller myotomy, encouraging the use of robot-assisted surgery. However, our analysis is limited because of the exiguous number of comparative studies and because most of the included studies were statistically underpowered, given the small sample size. Moreover, a high degree of heterogeneity was observed in most of published studies. Taking in consideration the additional costs of robot-assisted procedures, larger Randomized Controlled Trials (RCTs) are advocated to confirm the safety and effectiveness of the robotic approach, and its advantages over standard laparoscopic surgery. In conclusion, well-designed prospective trials and RCTs with homogeneous parameters are needed to draw definitive conclusions about the best surgical approach to pursue in treating symptomatic achalasia.

The treatment of achalasia patients with esophageal varices: an international study.

Background: Treatment options for achalasia include endoscopic and surgical techniques that carry the risk of esophageal bleeding and perforation. The rare coexistence of esophageal varices has only been anecdotally described and treatment is presumed to carry additional risk. Methods: Experience from physicians/surgeons treating this rare combination of disorders was sought through the International Manometry Working Group. Results: Fourteen patients with achalasia and varices from seven international centers were collected (mean age 61 ± 9 years). Five patients were treated with botulinum toxin injections (BTI), four had dilation, three received peroral endoscopic myotomy (POEM), one had POEM then dilation, and one patient underwent BTI followed by Heller's myotomy. Variceal eradication preceded achalasia treatment in three patients. All patients experienced a significant symptomatic improvement (median Eckardt score 7 vs 1; p < 0.0001) at 6 months follow-up, with treatment outcomes resembling those of 20 non-cirrhotic achalasia patients who underwent similar therapy. No patients had recorded complications of bleeding or perforation. Conclusion: This study shows an excellent short-term symptomatic response in patients with esophageal achalasia and varices and demonstrates that the therapeutic outcomes and complications, other than transient encephalopathy in both patients who had a portosystemic shunt, did not differ to disease-matched patients without varices.

The plasmatic and salivary levels of IL-1ß, IL-18 and IL-6 are associated to emotional difference during stress in young male.

Saliva collection is considered a non-invasive method to detect inflammatory markers in response to emotional states within natural social contexts. Numerous studies have prompted an important role of cytokines in modulating distinct aspects of social and emotional behavior. The aim of this study was to investigate the reliability of plasma and saliva as investigative tools for measure some inflammatory marker levels (CRP, IL-1ß, IL-18, and IL-6). At the same time, the relationships between these markers and emotional states in response to a socio-cognitive stress (Academic Exam, AE), were considered. It was demonstrated that the plasma and saliva concentrations of all immune-mediators analyzed were significantly related across the socio-cognitive stress. In addition, when there was a close correlation to AE, the anger state, the IL-1ß, the IL-18 salivary and plasmatic concentrations were significantly higher, while they decreased during the AE. On the other hand, the anxiety state and the IL-6 levels significantly increased throughout the AE. The IL-1ß and IL-6 were positively associated to the anger and the anxiety state, respectively. In conclusion, our data highlight that different immune markers are similarly detectable in plasma and saliva during socio-cognitive stress. Also, they could be related to different emotional responses.

Extremely low-frequency electromagnetic fields accelerates wound healing modulating MMP-9 and inflammatory cytokines.

OBJECTIVES: In our previous reports, we have demonstrated that extremely low-frequency electromagnetic fields (ELF-EMF) exposure enhances the proliferation of keratinocyte. The present study aimed to clarify effects of ELF-EMF on wound healing and molecular mechanisms involved, using a scratch in vitro model. MATERIALS AND METHODS: The wounded monolayer cultures of human immortalized keratinocytes (HaCaT), at different ELF-EMF and Sham exposure times were monitored under an inverted microscope. The production and expression of IL-1ß, TNF-α, IL-18 and IL-18BP were measured by enzyme-linked immunosorbent assay and quantitative real-time PCR. The activity and the expression of matrix metalloproteinases (MMP)-2/9 was evaluated by zymography and Western blot analysis, respectively. Signal transduction proteins expression (Akt and ERK) was measured by Western blot. RESULTS: The results of wound healing in vitro assay revealed a significant reduction of cell-free area time-dependent in ELF-EMF-exposed cells compared to Sham condition. Gene expression and release of cytokines analysed were significantly increased in ELF-EMF-exposed cells. Our results further showed that ELF-EMF exposure induced the activity and expressions of MMP-9. Molecular data showed that effects of ELF-EMF might be mediated via Akt and ERK signal pathway, as demonstrated using their specific inhibitors. CONCLUSIONS: Our results highlight ability of ELF-EMF to modulate inflammation mediators and keratinocyte proliferation/migration, playing an important role in wound repair. The ELF-EMF accelerates wound healing modulating expression of the MMP-9 via Akt/ERK pathway.

Oncoplastic breast surgery: comprehensive review.

Breast cancer is the most common female cancer in Western populations, affecting 12.5% of women, with 1.38 million patients per year. Breast-conserving surgery followed by postoperative radiotherapy replaced the radical and modified-radical procedures of Halsted and Patey as the standard of care for early-stage breast cancer once the overall and disease-free survival rates of breast-conserving surgery were demonstrated to be equivalent to those of mastectomy. However, excision of >20% of breast tissue, low or centrally located cancer, and large-sized breasts with various grades of breast ptosis, result a in unacceptable cosmetic outcomes. Oncoplastic breast surgery evolved from the breast-conserving surgery by broadening its general indication to achieve wider excision margins without compromising on the cosmetic outcomes. Thus, oncoplastic breast surgery can be defined as a tumor-specific immediate breast reconstruction method that applies aesthetically derived breast reduction techniques to the field of breast cancer surgery and allows for higher volume excision with no aesthetic compromise. However, contralateral breast symmetrization should be regarded as an intrinsic component of the oncoplastic surgery. The main procedures involved are volume-displacement or volume-replacement techniques, which depend on breast size and cancer size/location. Volume-displacement or reshaping procedures apply the plastic surgery principles to transpose a dermo-glandular flap of breast tissue into the defect site, while volume-replacement techniques use autologous tissues to replace the volume loss that follows tumor resection. Furthermore, these procedures are more complex and time-consuming than those involved in breast-conserving surgery. Based on current literature, the authors analyze the different techniques and indications of the oncoplastic breast surgery, determining its complication rate, in order to help both surgeons and their patients in the decision-making stage of breast reconstruction.

A single-puncture arthrocentesis technique, using a peripheral intravenous catheter.

Arthrocentesis is a technique used for lavage of the inflammatory content of the supradiscal space and lysis of the fibrous strands attaching the articular disc to the superior compartment of the temporomandibular joint (TMJ). The most widely accepted and classical manner in which this technique is performed is through two-needle access to the superior joint space. Nevertheless, it has been reported in the literature that this technique is challenging and has several limitations. Thus, the use of a single-puncture approach has been proposed, which represents a less traumatic and easier to perform technique. The single-puncture approach may have several advantages over the classical two-needle approach in regard to completion time, tolerability, stabilization of the needle, and retention of the intra-articular medication. A single-puncture technique is described herein, which uses an intravenous catheter to provide simultaneous inflow/outflow for low or high volume irrigation of the TMJ. The feasibility and low cost of this technique are primary advantages; peripheral intravenous catheters are one of the most widely used devices for vascular access in the primary and hospital healthcare settings.

The SHP-1 expression is associated with cytokines and psychopathological status in unmedicated first episode schizophrenia patients.

BACKGROUND: Recent lines of research have boosted awareness of the immunological facets of schizophrenia. However, associations with protein tyrosine phosphatase regulators have never been reported. The aim of our study was to investigate the expression and promoter status methylation of phosphatase SHP-1, a key negative regulator of the inflammatory process, in Peripheral blood mononuclear cells (PBMCs) of Schizophrenic patients. METHODS: We enrolled fifty-four (28 men and 26 women) unmedicated first episode subjects (SC) who met DSM-IV and thirty-eight (22 men and 16 women) healthy controls (HC). The SC psychopathological status was assessed using the Positive and Negative Syndrome Scale. We evaluated SHP-1 expression by Quantitative Real-time PCR (qPCR) and Western blotting (WB) methods and promoter status methylation through PCR bisulfate. IKK/NFkB signaling was detected by WB, and medium and plasma levels of pro-inflammatory cytokines (IL-1ß, IL-2, and TNF-α) by the ELISA method. SHP-1 was silenced by treating cells with specific siRNA. RESULTS: We found a significantly lower level of SHP-1 gene expression in PBMCs from SC vs. HC, consistently with which the promoter region analyzed presented significant hypermethylation. Silencing of SHP-1 expression induced higher activation of IKK/NF-kB signaling and pro-inflammatory cytokine production in ex vivo PBMCs from both SC and HC. Linear regression among patients generated a model in which SHP-1 expression explained 30% of the clinical negative symptom variance (adjusted R(2)=0.30, ANOVA p<0.001). CONCLUSIONS: Our findings are the first to suggest that impairment of SHP-1 expression is involved in the physiopathology of schizophrenia, opening fruitful new avenues for ameliorating treatment at least of negative symptoms.

Impact of long-term exposure to cigarette smoking on skin microvascular function.

In order to evaluate the impact of cigarettes smoking and smokers' clinical characteristics on skin microvascular function, we measured the skin forearm blood flux, basally and during post-occlusive reactive hyperaemia, in 100 current smokers (mean age 51±11 years; range: 18 to 86 years) and in 66 healthy never-smokers matched for age and sex, by using laser Doppler fluximetry (LDF). Basal and post-ischemic LDF tracings were analyzed in the frequency domain within 0.009-0.02 Hz, 0.021-0.06 Hz and 0.061-0.2 Hz ranges, related to endothelial-dependent, sympathetic-dependent and myogenic-dependent vasomotion, respectively, using an adapted version of the Fourier analysis. The post-ischemic percentage change from baseline of the area under the LDF curve (AUC%) was significantly lower in smokers than in never-smokers [162.5% (139.3-183.0) vs 190.1% (156.3-216.8); p=0.00016]. Compared to controls, smokers also showed a reduced basal power spectral density (PSD) in the myogenic-dependent vasomotion (p=0.0034) and a reduced post-ischemic percentage increase in PSD of the endothelial-dependent vasomotion (p=0.0010) and sympathetic-dependent vasomotion (p=0.0016). An inverse relationship was observed in smokers between AUC% and smoking exposure duration (r=0.23, p=0.018), pack-years (r=0.33, p=0.0007), age (r=0.26, p=0.008) and body mass index (r=0.21, p=0.037). In the multiple linear regression model, pack-years was the only variable independently associated with AUC% (r=0.21, p=0.03). This study confirms that smoking is associated with cutaneous microvascular dysfunction and shows that the severity of this impairment is independently related to the duration and intensity of the exposure to smoking.

Kinetic study on the effects of extremely low frequency electromagnetic field on catalase, cytochrome P450 and inducible nitric oxide synthase in human HaCaT and THP-1 cell lines.

Extremely low frequency electromagnetic fields (ELF-EMF) have been found to produce a variety of biological effects. These effects of ELF-EMF depend upon frequency, amplitude, and length of exposure, and are also related to intrinsic susceptibility and responsiveness of different cell types. Although the mechanism of this interaction is still obscure, ELF-EMF can influence cell proliferation, differentiation, cell cycle, apoptosis, DNA replication and protein expression. The aim of this study was to estimate various kinetic constants of catalase, cytochrome P450 and inducible nitric oxide synthase in response to ELF-EMF exposure in human HaCaT and THP-1 cell lines. In order to evaluate the effect of ELF-EMF on the modulation of cellular responses to an inflammatory stimulus, both cell lines were treated with lipopolysaccharide. To the best of our knowledge there is no available report on such type of kinetic study of selected enzymes in response to ELF-EMF in these cell lines. Therefore, the current study may reveal novel mechanism of ELFEMF biological interaction with the enzymological and hormonal systems of living organisms. These new insights may be important for ELF-EMF application particularly for wound healing, tissue regeneration, Parkinson's and Alzheimer's diseases.

Extremely low frequency electromagnetic fields modulate expression of inducible nitric oxide synthase, endothelial nitric oxide synthase and cyclooxygenase-2 in the human keratinocyte cell line HaCat: potential therapeutic effects in wound healing.

BACKGROUND: Extremely low frequency (ELF) electromagnetic fields (EMF) are known to produce a variety of biological effects. Clinical studies are ongoing using EMF in healing of bone fractures and skin wounds. However, little is known about the mechanisms of action of ELF-EMF. Several studies have demonstrated that expression and regulation of nitric oxide synthase (NOS) and cyclooxygenase-2 (COX-2) are vital for wound healing; however, no reports have demonstrated a direct action of ELF-EMF in the modulation of these inflammatory molecules in human keratinocytes. OBJECTIVES: The present study analysed the effect of ELF-EMF on the human keratinocyte cell line HaCaT in order to assess the mechanisms of action of ELF-EMF and to provide further support for their therapeutic use in wound healing. METHODS: Exposed HaCaT cells were compared with unexposed control cells. At different exposure times, expression of inducible NOS (iNOS), endothelial NOS (eNOS) and COX-2 was evaluated by Western blot analysis. Modulation of iNOS and eNOS was monitored by evaluation of NOS activities, production of nitric oxide (NO) and O(2)(-) and expression of activator protein 1 (AP-1). In addition, catalase activity and prostaglandin (PG) E(2) production were determined. Effects of ELF-EMF on cell growth and viability were monitored. RESULTS: The exposure of HaCaT cells to ELF-EMF increased iNOS and eNOS expression levels. These ELF-EMF-dependent increased expression levels were paralled by increased NOS activities, and increased NO production. In addition, higher levels of AP-1 expression as well as a higher cell proliferation rate were associated with ELF-EMF exposure. In contrast, ELF-EMF decreased COX-2 expression, PGE(2) production, catalase activity and O(2)(-) production. CONCLUSIONS: Mediators of inflammation, such as reactive nitrogen and PGE(2), and keratinocyte proliferation are critical for the tissue regenerative processes. The ability of ELF-EMF to upmodulate NOS activities, thus nitrogen intermediates, as well as cell proliferation, and to downregulate COX-2 expression and the downstream intermediate PGE(2), highlights the potential therapeutic role of ELF-EMF in wound healing processes.

Anti-inflammatory properties of the plant Verbascum mallophorum.

Verbascum mallophorum is part of a large family of Scrophulariaceae consisting of more than 360 species. Verbascum mallophorums contains diverse polysaccharides, iroid glycosides, flavonoids, saponins, volatile oils and phenylentanoids. Verbascum has been used in popular medicine for treating wounds, chilblains, respiratory ailments, acne and arthritic disturbances. Inducible nitric oxide synthase (iNOS) represents one of the three isoforms that produce nitric oxide using L-arginine as a substrate in response to an increase in superoxide anion activated by NF-kappaB. It is implicated in different pathophysiological events and its expression increases greatly during an inflammatory process due to oxidative stress. In our study we reproduced an inflammatory state by treating THP-1 cells (human myelomonocytic leukaemia) with pro-inflammatory stimuli, such as LPS and IFN-gamma, obtaining an up-regulation both in the expression and in the activity of iNOS. The aim of our work is to investigate the possible antiinflammatory action of verbascoside extract from Verbascum mallophorum using a concentration of 100 muM. Our results show a significant decrease in the expression and activity of iNOS and extracellular O2- when cells were treated with verbascoside. Based on these results we hypothesize that verbascoside extract from Verbascum mallophorum has anti-inflammatory properties since it reduces the production of superoxide radicals and consequently reduces the activity of iNOS.

Direct minimally invasive intramyocardial injection of bone marrow-derived AC133+ stem cells in patients with refractory ischemia: preliminary results.

BACKGROUND: Bone marrow-derived stem cells (BMSC) may represent a viable option for patients with myocardial ischemia refractory to conventional treatments. MATERIAL AND METHODS: In 5 patients (4 males and 1 female, mean age 64 +/- 8 years) with untreatable angina pectoris (Canadian Cardiovascular Society Class III/IV), myocardial segments with stress-induced ischemia as assessed by gated single-photon emission computed tomography were injected with 4 to 12 million CD133+ BMSC. Cells were injected into the myocardium (2 anterior, 2 lateral, 1 inferior wall) through minimally invasive approaches (left minithoracotomy [n = 4] and subdiaphragmatic approach [n = 1]). At baseline, at 6 months and at 1 year of follow-up, an exercise test, gated single-photon emission computed tomography (SPECT), 2-D echocardiography and coronary angiography were performed to assess exercise capacity, myocardial perfusion, LV function and coronary anatomy. RESULTS: Intramyocardial injection of autologous CD133+ BMSC cells was safe. No early or long-term complications were observed. After an average of 3.8 weeks from cell inoculation, all patients experienced a significant improvement of CCS class (from 3.8 to 1.8 at 6 months) and serial SPECT documented improvements of rest and stress perfusion in the injected territories at 6 months from operation. In 3 cases, coronary angiography showed an increase in the collateral score of the target areas. Clinical improvements still persist unchanged in 4 out of 5 cases at a mean of 36.5 months postoperatively. CONCLUSIONS: After stand-alone BMSC transplantation for refractory myocardial ischemia, we observed long-term clinical and perfusion improvements in the absence of adverse events.

Long-lasting improvement of myocardial perfusion and chronic refractory angina after autologous intramyocardial PBSC transplantation.

We report the case of a 60-year-old man with patent coronary by-pass grafts on the left anterior descending and circumflex coronary arteries, who experienced recurrent Canadian class IV angina refractory to medical and interventional treatments for a dominant right coronary artery occlusion. He underwent autologous PBSC transplant into the inferior ventricular wall through a minimally invasive approach as a stand-alone therapy, in an attempt to induce therapeutic angiogenesis. Six months after the operation, angina significantly ameliorated; scintigraphy and coronary angiography showed a marked improvement in perfusion of the target injection area. These benefits had persisted at 25 months after stem cell transplant.

Sex-based differences in serum cardiac troponin I, a specific marker for myocardial injury, after cardiac surgery.

BACKGROUND: Prevalence and causes of sex-based differences in morbidity and mortality secondary to cardiovascular disease remain controversial. Cardiac troponin I (cTnI) is a sensitive and specific marker for myocardial injury. Serial cTnI measurements have been used to identify perioperative myocardial cell injury. OBJECTIVE: To determine whether sex influences the extent of myocardial injury during cardiac surgery, we measured perioperative cTnI in male and female patients. DESIGN: A total of 17 male and 17 female patients were prospectively studied in an age- and case-matched manner. Arterial cTnI were obtained preinduction, 30 mins after the application of the aortic cross-clamp, at arrival to the intensive care unit, and on postoperative day 1. SETTING: Tertiary cardiac surgery center at a major teaching hospital. RESULTS: There was no difference between men and women in body mass index (kg/m2), duration of cardiopulmonary bypass, and aortic cross-clamp times. Preoperative cTnI measurements were similar in men (0.24 +/- 0.15 ng/mL) and women (0.25 +/- 0.13 ng/mL, mean +/- sem). The maximum serum cTnI occurred on postoperative day 1 in all patients, and it was 3-fold higher in men (18.5 +/- 5.7 ng/mL) compared with women (6.4 +/- 1.0 ng/mL). CONCLUSIONS: Men had markedly higher serum cTnI compared with women, although they were case matched with respect to age and cardiac risk factors. Our results may suggest there may be sex-related differences in the myocardial response to ischemia and reperfusion injury or intrinsic differences between the male and female myocardium.