Employment of color Doppler echocardiographic video clips in a cardiac auscultation class with a cardiology patient simulator: discrepancy between students' satisfaction and learning.

BACKGROUND: We have provided fourth-year medical students with a three-hour cardiac auscultation class using a cardiology patient simulator since 2010. The test results of 2010-2012 revealed that as compared with aortic stenosis murmur, students correctly identified murmurs of other valvular diseases less often. We investigated whether employment of color Doppler echocardiographic video clips would improve proficiency in identifying murmurs of aortic regurgitation and mitral regurgitation, and whether students' favorable responses to a questionnaire were associated with improved proficiency. METHODS: A total of 250 fourth-year medical students were divided into groups of 7-9 students in 2014 and 2015. Each group attended a three-hour cardiac auscultation class comprising a mini-lecture, facilitated training, two different auscultation tests (the second test being closer to clinical setting than the first) and a questionnaire. We provided each student with color Doppler echocardiographic videos of aortic regurgitation and mitral regurgitation using a tablet computer, which they freely referred to before and after listening to corresponding murmurs. The test results were compared with those in 2010-2012. The students had already completed the course of cardiovascular medicine, comprising lectures including those of physical examination, echocardiography, and valvular heart diseases, before participating in this auscultation training class. RESULTS: Most students indicated that the videos were useful or somewhat useful regarding aortic regurgitation (86.3%) and mitral regurgitation (85.7%). The accuracy rates were 78.4% (81.2% in 2010-2012) in aortic regurgitation and 76.0% (77.8%) in mitral regurgitation in the first test, and 83.3% (71.4%) in aortic regurgitation and 77.1% (77.6%) in mitral regurgitation in the second test, showing no significant differences as compared to 2010-2012. Overall accuracy rate of all heart sounds and murmurs in the first test and that of second/third/fourth sounds in the first and second tests were significantly lower in 2014-2015 than in 2010-2012. CONCLUSIONS: Referring to color Doppler echocardiographic video clips in the way employed in the present study, which most students regarded as useful, did not improve their proficiency in identifying the two important regurgitant murmurs, revealing a discrepancy between students' satisfaction and learning. Video clips synchronized with their corresponding murmurs may contribute toward improving students' proficiency.

Cardiac Resynchronization Therapy for Improving Non-Uniform Thickening of Left Ventricular Wall: Assessment by Quantitative Gated Myocardial Perfusion SPECT.

Cardiac resynchronization therapy (CRT) improves cardiac dyssynchrony in heart failure patients with a wide QRS electrocardiogram (ECG). Assessment of left ventricular (LV) dyssynchrony using echocardiography or other imaging modalities is important to predict CRT effectiveness. In this study, we retrospectively evaluated cardiac nuclear imaging of ECG-gated myocardial perfusion single-photon emission computed tomography (SPECT) with 99mTc-sestamibi for CRT candidate (n = 120) with severe heart failure and wide QRS (> 120 msec) in ECG. To analyze LV non-uniformity, we used the quantitative gated SPECT (QGS) software to calculate changes in regional LV wall thickness during a cardiac cycle (i.e., wall thickening scores). Cardiac events (heart failure, ventricular arrhythmias and cardiac death) after CRT during 38 ± 22 (SD) months were also evaluated. In 97 of 120 patients who underwent QGS before and 6 months after CRT, CRT homogenized non-uniform wall thickening between septal and lateral of the LV especially in CRT responders. This observation was indicated as increase in the lateral deflection (XWT) of wall thickening scores before CRT and its decrease after CRT. In 120 patients with QGS before CRT, the larger XWT before CRT (≥ 16.5) predicted better prognoses after CRT. This finding was similarly observed even in patients with narrower baseline QRS (≤ 140 msec; n = 41 of 120), who usually have less benefits from CRT. In conclusion, CRT improved non-uniformity of wall thickening between the LV septal and lateral regions evaluated using QGS, which is predictive of better prognosis in the chronic phase after CRT.

A Medical Record Peer-Review System to Evaluate Residents' Clinical Competence: Criterion Validity Analysis.

In contrast to input evaluation (education delivered at school) and output evaluation (students' capability at graduation), the methods of outcome evaluation (performance after graduation) of medical education have not been sufficiently established. To establish a method to measure the quality of patient care and conduct outcome evaluation, we have been developing a peer review system of medical records. Here, we undertook a pilot study to evaluate the criterion validity of our system by using "evaluation by program directors (supervisors in the hospitals)" as a criterion standard. We selected 13 senior residents from three teaching hospitals. Five reviewers (general internists working in other hospitals) visited the hospitals independently and evaluated five patients' records for each resident based on the previously established sheet comprising 15 items. Independently, program directors of the senior residents evaluated their clinical performance using an evaluation sheet comprising ten items. Pearson's analysis revealed statistically significant correlation coefficients in three pairs of assessments including clinical reasoning (r = 0.5848, P = 0.0358). Bootstrap analysis revealed statistically significant correlation coefficients in additional 5 pairs including history taking (r = 0.509, 95% confidence interval: 0.034-0.847). In contrast, the correlation coefficients were low in some items: r = 0.132 (-0.393-0.639) for physical examination and r = 0.089 (-0.847-0.472) for attitude toward patients. To the best of our knowledge, this is the first study, albeit a pilot one, that investigates the criterion validity of medical record evaluations conducted by comparing the assessments of medical records with those by program directors.

The role of integrative medicine and Kampo treatment in an aging society: experience with Kampo treatment during a natural disaster.

BACKGROUND AND OBJECTIVES: After the Great East Japan Earthquake, elderly individuals, who are particularly vulnerable during natural disasters, experienced difficulty while evacuating the area. This report discusses the Kampo treatments provided to elderly individuals in the disaster areas, and the role of integrative medicine and Kampo treatment. METHODS: The changes in symptoms and Kampo treatment contents were summarized using the medical records of treatments provided in the evacuation centers until 10 weeks after the earthquake. RESULTS: Infectious diseases, the common cold and hypothermia were frequently observed in most patients for first two weeks after the disaster. Allergies increased two weeks later, and mental distress was commonly observed six weeks later. We prescribed several Kampo formulas to treat the individual symptoms. DISCUSSION: Many elderly individuals were treated using Western medications, but the symptoms persisted; however, after Kampo formulas were included in the treatment, the symptoms of many patients improved. Unlike Western medications, Kampo formulas warmed the bodies of elderly individuals who often had a reduced basal metabolism and low body temperatures due to exposure to the cold tsunami waters. Therefore, the Kampo formulas may have improved the immunity of those who were under psychological and physical stress because they had spent several days in the evacuation centers. CONCLUSION: Many studies have reported the effectiveness of Kampo formulas. Therefore, the combined usage of both Western and Kampo medicine may be used in a mutually complementary manner, and these combination treatments may play an important role in preserving the victims overall health after natural disasters.

Interactive training with a novel simulation model for upper gastrointestinal endoscopic hemostasis improves trainee technique and confidence.

Background and study aims Endoscopic hemostasis is a life-saving procedure for gastrointestinal bleeding; however, training for it is often performed on real patients and during urgent situations that put patients at risk. Reports of simulation-based training models for endoscopic hemostasis are scarce. Herein, we developed a novel simulator called "Medical Rising STAR-Ulcer type" to practice endoscopic hemostasis with hemoclips and coagulation graspers. This study aimed to evaluate the reproducibility of the clinical difficulty of this model and the effectiveness of simulation-based training for clipping hemostasis. Patients and methods This was a prospective educational study. Fifty gastroenterology residents from Japan and Canada were recruited to participate in a simulation-based training program. The primary outcome was the success rate for clipping hemostasis. We measured differences in trainee subjective assessment scores and evaluated the co-occurrence network based on comments after training. Results The hemostasis success rate of the trainees significantly increased after instruction (64% vs. 86%, P < 0.05). The success rate for ulcers in the upper body of the stomach (59%), a high-difficulty site, was significantly lower than that for ulcers in the antrum, even after feedback and instruction. Trainee self-perceived proficiency and confidence significantly improved after simulation-based training ( P < 0.05). Co-occurrence network analysis showed that trainees valued a structured learning approach, acknowledged simulator limitations, and recognized the need for continuous skill refinement. Conclusions Our study demonstrates the potential of our simulation-based training model as a valuable tool for improving technical skills and confidence in trainees learning to perform endoscopic hemostasis.

Synthesis, spectral, and electrochemical characterization of the first arsenic(V)-phthalocyanines.

The first arsenic(V)-phthalocyanines, [As(tbpc)X(2)](+), where tbpc denotes tetra(tert-butyl)phthalocyaninate, C(48)H(48)N(8)(2-) and X = F, Cl, and Br) have been prepared through an appropriate oxidative addition process to a highly soluble arsenic(III) derivative, [As(tbpc)](+). Among them, [As(tbpc)F(2)](+) has been isolated as PF(6)(-) salt. Unlike conventional metal derivatives of phthalocyanines, they show a significantly red-shifted (by >1000 cm(-1)) Q-band and facile reduction of the macrocyclic ligand (redox potentials for [As(tbpc)F(2)](+) have been determined by cyclic voltammetry; 1.13 V vs ferricinium(+)/ferrocene (tbpc(-/2-)), -0.45 V (tbpc(2-/3-)), and -0.90 V (tbpc(3-/4-)), of which the values are anodically shifted by about 1 V) as compared to those of conventional phthalocyanines. Although the anomaly in their spectral and electrochemical properties is similar to that of the known antimony analogues, the arsenic-phthalocyanines have been found less stable.

Current perspectives on protective roles of erythropoietin in cardiovascular system: erythropoietin receptor as a novel therapeutic target.

Erythropoietin (EPO) is a principal regulator that promotes proliferation and terminal differentiation of erythroid progenitor cells. EPO receptors are expressed not only in hematopoietic lineage cells but also in the cardiovascular system. We performed animal experiments using transgene-rescued EPO receptor null mutant mice (EpoR-/- rescued) that express the EPO receptor exclusively in the hematopoietic cells. The results of these experiments suggest that endogenous EPO/EPO receptor system in the heart exerts cardioprotective effects against myocardial injury induced by ischemia followed by reperfusion and pressure-overload induced left ventricular dysfunction. Many animal experiments have shown that the administration of recombinant human EPO also elicits cardioprotective effects against myocardial injury induced by ischemia and reperfusion. In contrast to the promising results of these animal experiments, recent clinical trials failed to demonstrate the reduction in infarct size or improvement of cardiac function by the administration of recombinant human EPO in patients with acute myocardial infarction who underwent primary percutaneous coronary intervention. It should be tested in future clinical studies whether a relatively low dose of recombinant human EPO or its derivatives that have no erythropoietic action reduces infarct size and ameliorates cardiac dysfunction in patients with acute myocardial infarction. In this article, we review implications of anemia associated with chronic heart failure, roles of the endogenous EPO/EPO receptor system, and the effects of the administration of erythropoiesis-stimulating agents in pathologic conditions of the heart by focusing on the EPO receptor as a potential candidate of novel therapeutic targets in cardiovascular diseases.

Feasibility and effectiveness of cardiac auscultation training with a cardiology patient simulator for first-year medical students.

BACKGROUND: The effectiveness of cardiac auscultation training with a cardiology patient simulator for medical students is still unclear. Starting such training earlier may help students improve their proficiency. We investigated whether cardiac auscultation training using a simulator for first-year students is feasible and effective. METHODS: A total of 43 first-year medical students (5-12 in each year, 2015-2019) participated in three 1.5-hour extra-curricular classes comprising mini-lectures, facilitated training, two different auscultation tests (the second test closer to clinical setting than the first), and a questionnaire. The test results were compared with those of 556 fourth-year medical students who participated in a compulsory 3-hour cardiac auscultation class in 2016-2019. RESULTS: The accuracy rate of all heart sounds and murmurs was higher in the first-year students than in the fourth-year students in both the first (85.8 vs. 79.4 %, p = 0.001) and second (71.3 vs. 61.2 %, p = 0.02) tests. That of second/third/fourth sounds was also higher in the first-year students than in the fourth-year students in both the first (86.0 vs. 79.7 %, p = 0.01) and second (70.9 vs. 53.9 %, p = 0.002) tests. The accuracy rate of murmurs was higher in the first-year students than in the fourth-year students in the first test (85.5 vs. 78.9 %, p = 0.04), but not in the second test (72.1 vs. 75.7 %, p = 0.58). All the first-year students and 65 % of them agreed that they had received sufficient knowledge and built sufficient skills, respectively. All the first-year students and 93 % of them agreed that they were satisfied with the program, and that the program was suitable for first-year students, respectively. CONCLUSIONS: Although training time was different between the two groups and it is possible that only motivated first-year students participated in the program, these results suggest that our cardiac auscultation training is feasible and effective for first-year medical students.

Emergence of the erythropoietin/erythropoietin receptor system as a novel cardiovascular therapeutic target.

Although hypoxia and ischemia are known to be involved in the pathogenesis of cardiovascular disease, specific therapeutic targets still remain elusive. To address this important issue, we have performed 2 series of experimental studies, aiming at erythropoietin (Epo)/Epo receptor (EpoR) based on the following backgrounds. Epo has long been regarded as a hematopoietic hormone that acts exclusively in the proliferation and differentiation of erythroid progenitors. Although recent studies have demonstrated that EpoR is expressed in the cardiovascular system, the potential protective role of the vascular Epo/EpoR system in vivo remains to be examined. We hypothesized that the vascular Epo/EpoR system plays an important protective role against the development of cardiovascular disease. Using vascular EpoR-deficient mouse, we demonstrated that the vascular Epo/EpoR system plays a crucial role for endothelial function and vascular homeostasis. The vascular Epo/EpoR system is important for the activation of the vascular endothelial growth factor/vascular endothelial growth factor receptor-2 system, inhibits hypoxia-induced pulmonary endothelial damage and promotes ischemia-induced angiogenesis in vivo. These results indicate that the vascular Epo/EpoR system plays an important protective role against hypoxia/ischemia, demonstrating that this system is a novel therapeutic target in cardiovascular medicine.

Protective effects of recombinant human erythropoietin against pressure overload-induced left ventricular remodeling and premature death in mice.

Chronic left ventricular (LV) pressure overload induced by hypertension is one of the most common causes of heart failure. Earlier reports have shown the cardioprotective effects of erythropoietin (EPO). In the present study, we tested the hypothesis that recombinant human EPO exerts a protective effect against pressure-overload induced LV remodeling. Mice subjected to transverse aortic constriction (TAC) (n = 70) were randomly assigned to the treatment with phosphate buffer solution (PBS) (TAC-PBS) or EPO (2,000 U/kg twice a week) (TAC-EPO). At 8 weeks after TAC, LV weight was comparably increased in both TAC groups compared with sham-operated mice (Sham) (both P < 0.001). The treatment with EPO improved the survival of TAC mice as compared with treatment with PBS (80 vs. 47%, P < 0.01), which was associated with reductions in the extent of myocardial fibrosis and the number of TUNEL positive cardiomyocytes (both P < 0.05). Echocardiography revealed that TAC increased LV chamber diameter and decreased LV fractional shortening compared with Sham (P < 0.05), which was ameliorated by the treatment with EPO (P < 0.05). In TAC-EPO as compared to TAC-PBS, phosphorylation of STAT3, Akt and eNOS was all increased, while phosphorylation of p38 was decreased (all P < 0.05). Importantly, the expression level of VEGF and the capillary density in LV myocardium were similar among the 3 groups. These results suggest that recombinant human EPO ameliorates the cardiac remodeling and the premature death associated with chronic LV pressure overload through the mechanisms independent of angiogenesis.

Protein-losing gastroenteropathy with severe hypoalbuminemia associated with Sjögren's syndrome: A case report and review of the literature.

A 30-year-old man with severe hypoalbuminemia (serum albumin: 0.9 g/dL) was admitted with severe bilateral leg edema and unilateral pleural effusion. Serum anti-SS-A and SS-B antibody levels were abnormally elevated, and his symptoms fulfilled the diagnostic criteria for Sjögren's syndrome. Technetium-99m albumin scintigraphy revealed protein leakage from a large area of the small intestine. Immunohistochemistry revealed perivascular deposition of C1q, C3d, and immunoglobulin G in the duodenal mucosa. The patient was diagnosed with protein-losing gastroenteropathy associated with Sjögren's syndrome. Within 2 months of treatment with oral prednisolone and mycophenolate mofetil, the clinical symptoms of hypoalbuminemia and Sjögren's syndrome disappeared completely.

Sarcomere mechanics in uniform and non-uniform cardiac muscle: a link between pump function and arrhythmias.

Starling's Law and the well-known end-systolic pressure-volume relationship (ESPVR) of the left ventricle reflect the effect of sarcomere length (SL) on stress (sigma) development and shortening by myocytes in the uniform ventricle. We show here that tetanic contractions of rat cardiac trabeculae exhibit a sigma-SL relationship at saturating [Ca2+] that depends on sarcomere geometry in a manner similar to skeletal sarcomeres and the existence of opposing forces in cardiac muscle shortened below slack length. The sigma-SL-[Ca2+]free relationships (sigma-SL-CaR) at submaximal [Ca2+] in intact and skinned trabeculae were similar, albeit that the sensitivity for Ca2+ of intact muscle was higher. We analyzed the mechanisms underlying the sigma-SL-CaR using a kinetic model where we assumed that the rates of Ca2+ binding by Troponin-C (Tn-C) and/or cross-bridge (XB) cycling are determined by SL, [Ca2+] or stress. We analyzed the correlation between the model results and steady state stress measurements at varied SL and [Ca2+] from skinned rat cardiac trabeculae to test the hypotheses that: (i) the dominant feedback mechanism is SL, stress or [Ca2+]-dependent; and (ii) the feedback mechanism regulates: Tn-C-Ca2+ affinity, XB kinetics or, unitary XB-force. The analysis strongly suggests that feedback of the number of strong XBs to cardiac Tn-C-Ca2+ affinity is the dominant mechanism that regulates XB recruitment. Application of this concept in a mathematical model of twitch-stress accurately reproduced the sigma-SL-CaR and the time course of twitch-stress as well as the time course of intracellular [Ca2+]i. Modeling of the response of the cardiac twitch to rapid stress changes using the above feedback model uniquely predicted the occurrence of [Ca2+]i transients as a result of accelerated Ca2+ dissociation from Tn-C. The above concept has important repercussions for the non-uniformly contracting heart in which arrhythmogenic Ca2+ waves arise from weakened areas in cardiac muscle. These Ca2+ waves can reversibly be induced in muscle with non-uniform excitation contraction coupling (ECC) by the cycle of stretch and release in the border zone between the damaged and intact regions. Stimulus trains induced propagating Ca2+ waves and reversibly induced arrhythmias. We hypothesize that rapid force loss by sarcomeres in the border zone during relaxation causes Ca2+ release from Tn-C and initiates Ca2+ waves propagated by the sarcoplasmic reticulum (SR). These observations suggest the unifying hypothesis that force feedback to Ca2+ binding by Tn-C is responsible for Starling's Law and the ESPVR in uniform myocardium and leads in non-uniform myocardium to a surge of Ca2+ released by the myofilaments during relaxation, which initiates arrhythmogenic propagating Ca2+ release by the SR.

Important role of erythropoietin receptor to promote VEGF expression and angiogenesis in peripheral ischemia in mice.

We have recently demonstrated that endogenous erythropoietin (Epo)/Epo receptor (EpoR) system plays an important protective role in hypoxia-induced pulmonary hypertension. However, it remains to be examined whether vascular EpoR system contributes to angiogenesis in response to ischemia. We examined angiogenesis in EpoR(-/-)-rescued mice that lack EpoR in most organs including cardiovascular system except erythroid-lineage cells. Two weeks after femoral artery ligation, blood flow recovery, activation of VEGF/VEGF receptor system, and mobilization of endothelial progenitor cells were all impaired in EpoR(-/-)-rescued mice as compared with wild-type (WT) mice. Bone marrow (BM) transplantation with WT-BM cells in EpoR(-/-)-rescued mice partially but significantly improved blood flow recovery after hindlimb ischemia. The extent of VEGF upregulation and the number of BM-derived cells in ischemic tissue were significantly less in EpoR(-/-)-rescued mice compared with WT mice even after BM reconstitution with WT-BM cells. Similarly, the recovery of blood flow was significantly impaired in recipient EpoR(-/-)-rescued mice that had been transplanted with WT-BM or EpoR(-/-)-rescued-BM as compared with recipient WT mice. Furthermore, the Matrigel implantation assay and aortic ring assay showed that microvessel growth in vitro was significantly reduced in EpoR(-/-)-rescued mice as compared with WT mice. These results indicate that vascular EpoR system also plays an important role in angiogenesis in response to hindlimb ischemia through upregulation of VEGF/VEGF receptor system, both directly by enhancing neovascularization and indirectly by recruiting endothelial progenitor cells and BM-derived proangiogenic cells.

Protective role of endogenous erythropoietin system in nonhematopoietic cells against pressure overload-induced left ventricular dysfunction in mice.

BACKGROUND: Erythropoietin (Epo) receptors (EpoRs) are expressed in the heart. We have recently demonstrated that the endogenous Epo-EpoR system plays an important protective role in myocardial ischemia in mice and humans. In the present study, we tested our hypothesis that the endogenous Epo-EpoR system in nonhematopoietic cells also plays a protective role against pressure overload-induced cardiac dysfunction in vivo. METHODS AND RESULTS: Transgene-rescued EpoR-null mutant mice (EpoR-/-(rescued)) that express EpoR exclusively in the hematopoietic cells were subjected to transverse aortic constriction (TAC). At 1 week after TAC, left ventricular weight and lung weight were significantly increased in EpoR-/-(rescued) mice compared with wild-type mice, although the fibrotic area was comparably increased after TAC in the 2 genotypes. In the EpoR-/-(rescued) mice with TAC, left ventricular end-diastolic diameter was significantly increased, left ventricular fractional shortening was significantly decreased, and survival rate was significantly decreased compared with wild-type mice with TAC. Phosphorylation of STAT3 at 5 hours and 1 week after TAC and that of p38 at 5 hours after TAC were significantly increased in wild-type mice but not in EpoR-/-(rescued) mice. Vascular endothelial growth factor protein expression and capillary density in left ventricular myocardium were significantly decreased in EpoR-/-(rescued) mice with TAC compared with wild-type mice with TAC. CONCLUSIONS: These results suggest that the endogenous Epo-EpoR system in the nonhematopoietic cells plays an important protective role against pressure overload-induced cardiac dysfunction in vivo.

Sarcomere mechanics in uniform and nonuniform cardiac muscle: a link between pump function and arrhythmias.

Starling's law and the end-systolic pressure-volume relationship (ESPVR) reflect the effect of sarcomere length (SL) on the development of stress (sigma) and shortening by myocytes in the uniform ventricle. We show here that tetanic contractions of rat cardiac trabeculae exhibit a sigma-SL relationship at saturating [Ca2+] that depends on sarcomere geometry in a manner similar to that of skeletal sarcomeres and the existence of opposing forces in cardiac muscle shortened below slack length. The sigma-SL -[Ca2+](free) relationships (sigma-SL-Ca relationships) at submaximal [Ca2+] in intact and skinned trabeculae were similar, although the sensitivity for Ca2+ of intact muscle was higher. We analyzed the mechanisms underlying the sigma-SL-Ca relationship by using a kinetic model assuming that the rates of Tn-C Ca2+ binding and/or cross-bridge (XB) cycling are determined by either the SL, [Ca2+], or sigma. We analyzed the correlation between the model results and steady-state sigma measurements at varied SL at [Ca2+] from skinned rat cardiac trabeculae to test the hypotheses that the dominant feedback mechanism is SL-, sigma-, or [Ca2+]-dependent, and that the feedback mechanism regulates Tn-C Ca2+ affinity, XB kinetics, or the unitary XB force. The analysis strongly suggests that the feedback of the number of strong XBs to cardiac Tn-C Ca2+ affinity is the dominant mechanism regulating XB recruitment. Using this concept in a model of twitch-sigma accurately reproduced the sigma-SL-Ca relationship and the time courses of twitch sigma and the intracellular [Ca2+]i. The foregoing concept has equally important repercussions for the nonuniformly contracting heart, in which arrhythmogenic Ca2+ waves arise from weakened areas in the cardiac muscle. These Ca2+ waves can reversibly be induced with nonuniform excitation-contraction coupling (ECC) by the cycle of stretch and release in the border zone between the damaged and intact regions. Stimulus trains induced propagating Ca2+ waves and reversibly induced arrhythmias. We hypothesize that rapid force loss by the sarcomeres in the border zone during relaxation causes Ca2+ release from Tn-C and initiates Ca2+ waves propagated by the sarcoplasmic reticulum (SR). Modeling of the response of the cardiac twitch to rapid force changes using the feedback concept uniquely predicts the occurrence of [Ca2+]i transients as a result of accelerated Ca2+ dissociation from Tn-C. These results are consistent with the hypothesis that a force feedback to Ca2+ binding by Tn-C is responsible for Starling's law and the ESPVR in the uniform myocardium and leads to a surge of Ca2+ released by the myofilaments during relaxation in the nonuniform myocardium, which initiates arrhythmogenic propagating Ca2+ release by the SR.

Important role of endogenous erythropoietin system in recruitment of endothelial progenitor cells in hypoxia-induced pulmonary hypertension in mice.

BACKGROUND: Recent studies have suggested that endogenous erythropoietin (Epo) plays an important role in the mobilization of bone marrow-derived endothelial progenitor cells (EPCs). However, it remains to be elucidated whether the Epo system exerts protective effects on pulmonary hypertension (PH), a fatal disorder encountered in cardiovascular medicine. METHODS AND RESULTS: A mouse model of hypoxia-induced PH was used for study. We evaluated right ventricular systolic pressure, right ventricular hypertrophy, and pulmonary vascular remodeling in mice lacking the Epo receptor (EpoR) in nonerythroid lineages (EpoR(-/-) rescued mice) after 3 weeks of exposure to hypoxia. Those mice lack EpoR in the cardiovascular system but not in the hematopoietic system. The development of PH and pulmonary vascular remodeling were accelerated in EpoR(-/-) rescued mice compared with wild-type mice. The mobilization of EPCs and their recruitment to the pulmonary endothelium were significantly impaired in EpoR(-/-) rescued mice. By contrast, reconstitution of the bone marrow with wild-type bone marrow cells ameliorated PH in the EpoR(-/-) rescued mice. Hypoxia enhanced the expression of EpoR on pulmonary endothelial cells in wild-type but not EpoR(-/-) rescued mice. Finally, hypoxia activated endothelial nitric oxide synthase in the lungs in wild-type mice but not in EpoR(-/-) rescued mice. CONCLUSIONS: These results indicate that the endogenous Epo/EpoR system plays an important role in the recruitment of EPCs and prevents the development of PH during chronic hypoxia in mice in vivo, suggesting the therapeutic importance of the system for the treatment of PH.

Total entrance skin dose: an effective indicator of maximum radiation dose to the skin during percutaneous coronary intervention.

OBJECTIVE: A number of cases of radiation-associated patient skin injury during percutaneous coronary intervention (PCI) have been reported. To protect against this complication, maximum skin dose to the patient should be monitored in real time. Unfortunately, in most cardiac intervention procedures, real-time monitoring of maximum skin dose is not possible. Angiographic X-ray units, however, display the patient's total entrance skin dose in real time. We therefore investigated the relation between maximum skin dose and total entrance skin dose to determine whether total entrance skin dose can be used to estimate maximum skin dose during PCI. MATERIALS AND METHODS: The dose-area product was measured, and maximum skin dose and total entrance skin dose were calculated with a skin-dose-mapping software program. The target vessels of 194 PCI procedures were divided into four groups according to the American Heart Association (AHA) segment system. RESULTS: The maximum skin dose constituted 48%, 52%, 50%, and 52% of the total entrance skin dose during PCI on AHA segments 1-3, 4, 5-10, and 11-15, respectively. There were significant correlations between maximum skin dose and total entrance skin dose during PCI (r = 0.894, 0.935, 0.859, and 0.898 for segments 1-3, 4, 5-10, and 11-15, respectively; p < 0.001). CONCLUSION: Maximum skin dose during PCI is approximately 50% of the total entrance skin dose for each target vessel. Correlation between the two doses was very good. Total entrance skin dose is an effective predictor of maximum skin dose during PCI when the formula used is maximum skin dose = 0.5 x total entrance skin dose. Our results provide useful information for avoiding deterministic radiation skin injury to patients undergoing PCI.

Endogenous erythropoietin system in non-hematopoietic lineage cells plays a protective role in myocardial ischemia/reperfusion.

OBJECTIVE: Recent studies suggested that erythropoietin (Epo) receptors (EpoR) are expressed not only in the hematopoietic lineage cells but also in the heart and that the administration of recombinant human Epo elicits protective effects in myocardial ischemia and reperfusion (I/R). We tested our hypothesis that endogenous Epo signals mediated by EpoR expressed in the non-hematopoietic lineage cells play a protective role against myocardial I/R injury. METHODS: Transgene-rescued EpoR null mutant mice (RES), which express EpoR exclusively in the hematopoietic lineage cells, were subjected to 30 min left coronary artery occlusion followed by reperfusion. RESULTS: Hematocrit, heart rate, blood pressure, heart weight, and echocardiographic parameters were comparable between wild-type mice (WT) and RES under the baseline condition. After 24 h of reperfusion, the infarct size in RES with I/R (RES/MI) was larger than that in WT/MI. Caspase-3 activity and number of TUNEL-positive cardiomyocytes in the ischemic area were increased in RES/MI compared with WT/MI. The extents of p38 and JNK phosphorylations in the ischemic area were significantly increased in WT/MI, but not in RES/MI as compared with corresponding sham-operated mice. Plasma Epo concentration in RES/MI did not differ from that in sham-operated RES, while that in WT/MI was peaked at 24 h post I/R. Additionally, left ventricular (LV) end-diastolic diameter was increased and LV fractional shortening tended to be reduced in the RES/MI compared with WT/MI at 21 days after I/R. CONCLUSIONS: These results suggest that the endogenous Epo-EpoR system in the non-hematopoietic lineage cells plays an important protective role against myocardial I/R injury.

Long-term efficacy of an extracorporeal membrane oxygenation simulation with a novel, low-cost vascular model "Endo-Circuit".

AIMS: This study investigated the long-term efficacy of a half-day extracorporeal membrane oxygenation simulation and low-cost vascular model for practitioner knowledge, skills, and attitudes in clinical settings and also assessed the usefulness of the vascular model. METHODS: We included participants who attended a half-day extracorporeal membrane oxygenation simulation focused on the veno-arterial method between April 2013 and January 2016 at Tohoku University Simulation Center (Sendai, Japan). A survey questionnaire form was sent to each participant in March 2016. Ninety-six survey respondents engaged in real extracorporeal membrane oxygenation practice after the simulation were eligible for this study, and their answers were analyzed for differences between doctors and nurses. The survey asked questions regarding occupation, workplace, course date, years of experience, extracorporeal membrane oxygenation practice before simulation, problems and fears before the simulation, usefulness of reference materials, long-term efficacy of the simulation for practice, usefulness of the vascular model, and intensive care data review. RESULTS: Among all eligible answers, every average self-reported score (ranging from 0 to 10) of the long-term efficacy for extracorporeal membrane oxygenation practice was above 4. Nurses reported experiencing fears more frequently than doctors before the simulation. The usefulness of an original low-cost vascular model was evaluated at a median score of 7. CONCLUSION: A half-day extracorporeal membrane oxygenation simulation with an original low-cost vascular model had long-term positive efficacy for knowledge, skills, and attitudes of practitioners who engaged in real practice after the simulation, and the practitioners considered the model to be useful for them.