Bioassays of Humoral Cardioprotective Factors Released by Remote Ischemic Conditioning in Patients Undergoing Coronary Artery Bypass Surgery.

Remote ischemic conditioning (RIC) induces the release of circulating cardioprotective factors and attenuates myocardial ischemia/reperfusion injury. Evidence for such humoral cardioprotective factor(s) is derived from transfer with plasma (derivatives) from one individual undergoing RIC to another individual's heart, even across species. With transfer into an isolated perfused heart, only a single plasma (derivative) sample can be studied with infarct size as endpoint, and therefore the comparison of samples before and after RIC or between RIC and placebo is hampered by the inter-individual variation of infarct sizes in isolated perfused hearts. We therefore developed a preparation of cardiomyocytes from a single mouse heart, where aliquots of the same heart can undergo hypoxia/reoxygenation (H/R) with exposure to buffer, RIC, or placebo samples without or with pharmacological blockade. To validate this approach, we used plasma dialysates taken before and after RIC from patients undergoing coronary bypass grafting who had experienced protection by RIC (troponin release ↓ by 28% vs placebo). The cardiomyocyte bioassay had little variation after H/R with buffer (mean ± standard deviation; 7% ± 2% viable cells) and demonstrated preserved viability after RIC (15% ± 5% vs 6% ± 3% before). For comparison, infarct size in isolated mouse hearts after global ischemia and reperfusion was 22% ± 14% of left ventricular mass after versus 42% ± 14% before RIC. Stattic, an inhibitor of signal transducer and activator of transcription (STAT)3 protein, abrogated protection in the cardiomyocytes. We have thus established a cardiomyocyte bioassay to analyze RIC's protection which minimizes inter-individual variation and the use of animals.

Mitochondrial and Contractile Function of Human Right Atrial Tissue in Response to Remote Ischemic Conditioning.

Background Remote ischemic preconditioning ( RIPC ) by repeated brief cycles of limb ischemia/reperfusion attenuates myocardial ischemia/reperfusion injury. We aimed to identify a functional parameter reflecting the RIPC -induced protection in human. Therefore, we measured mitochondrial function in right atrial tissue and contractile function of isolated right atrial trabeculae before and during hypoxia/reoxygenation from patients undergoing coronary artery bypass grafting with RIPC or placebo, respectively. Methods and Results One hundred thirty-seven patients under isoflurane anesthesia underwent RIPC (3×5 minutes blood pressure cuff inflation on the left upper arm/5 minutes deflation, n=67) or placebo (cuff uninflated, n=70), and right atrial appendages were harvested before ischemic cardioplegic arrest. Myocardial protection by RIPC was assessed from serum troponin I/T concentrations over 72 hours after surgery. Atrial tissue was obtained for isolation of mitochondria ( RIPC /placebo: n=10/10). Trabeculae were dissected for contractile function measurements at baseline and after hypoxia/reoxygenation (60 min/30 min) and for western blot analysis after hypoxia/reoxygenation ( RIPC /placebo, n=57/60). Associated with cardioprotection by RIPC (26% decrease in the area under the curve of troponin I/T), mitochondrial adenosine diphosphate-stimulated complex I respiration (+10%), adenosine triphosphate production (+46%), and calcium retention capacity (+37%) were greater, whereas reactive oxygen species production (-24%) was less with RIPC than placebo. Contractile function was improved by RIPC (baseline, +7%; reoxygenation, +24%). Expression and phosphorylation of proteins, which have previously been associated with cardioprotection, were not different between RIPC and placebo. Conclusions Cardioprotection by RIPC goes along with improved mitochondrial and contractile function of human right atrial tissue. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT 01406678.

Acute Stent Migration into the Right Ventricle in a Patient with Iliac Vein Stenting.

Endovascular stent placement for chronic postthrombotic iliofemoral venous obstructive lesions is an effective therapeutic option and might be complicated by stent migration. We report a case of a venous stent that was lost from the iliac vein into the right ventricle rescued by emergent open-heart surgery.

Development and Validation of Attitude toward Gestational Surrogacy Scale in Iranian Infertile Couples.

BACKGROUND: Surrogacy is one of the most challenging infertility treatments engaging ethical, psychological and social issues. Attitudes survey plays an important role to disclosure variant aspects of surrogacy, to help meeting legislative gaps and ambiguities, and to convert controversial dimensions surrounding surrogacy to a normative concept that eliminates stigma. The aim of this study is to develop a comprehensive scale for gestational surrogacy attitudes. MATERIALS AND METHODS: Development process of gestational surrogacy attitudes scale (GSAS) performed based on a descriptive cross-sectional study and included a rich data pool gathered from literature reviews, a qualitative pilot study on 15 infertile couples (n=30), use of expert advisory panel (EAP) consisting of 20 members, as well as use of content validity through qualitative and quantitative study by the means of content validity ratio (CVR) and content validity index (CVI). Also internal consistence using Cronbach's alpha and test-retest reliability using intracalss correlation coefficient (ICC) were evaluated. Application of GSAS was tested in a cross-sectional study that was conducted on 200 infertile couples (n=400) at Royan Institute, Tehran, Iran, during 2014. RESULTS: Final version of GSAS had 30 items within five subscales including "acceptance of surrogacy", "Surrogacy and public attitudes", "Child born through surrogacy", "Surrogate mother", and "Intentional attitude and surrogacy future attempt". Content validity was represented with values of CVR=0.73 and CVI =0.98. Cronbach's alpha value was 0.91 for the overall scale, while ICC value due to test-retest responses was 0.89. CONCLUSION: Acceptable level of competency and capability of GSAS is significantly indicated; therefore, it seems to be an appropriate tool for the evaluation of gestational surrogacy attitudes in Iranian infertile couples.