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Background Cribriform glands, regardless of their morphology and size, are categorized with Gleason pattern (GP) 4. However, recent studies indicate that the size and percentage of cribriform patterns in GP 4 are associated with risk of biochemical recurrence (BCR). Thus, we aimed to examine the prognostic value of the area and percentage of cribriform patterns in patients with Gleason score (GS) 4 + 4 prostate cancer who underwent robot-assisted radical prostatectomy (RARP). Methods We investigated 108 patients with GS 4 + 4 prostate cancer who underwent RARP. After digitally scanning the slides, we measured the area of the entire cancer and cribriform patterns. Predictive factors for BCR were explored using the log-rank test and Cox proportional hazard model analyses. Results Sixty-seven (62.0%) patients had a cribriform architecture in RARP specimens, and thirty-two (29.6%) experienced BCR. Median total cancer area (mm2), cribriform pattern area (mm2), and percentage of cribriform pattern area (% cribriform) were 427.70 (interquartile range [IQR], 171.65–688.53), 8.85 (IQR, 0–98.83), and 2.44 % (IQR, 0–33.70), respectively. In the univariate analyses, higher preoperative serum prostate-specific antigen levels, positive resection margin (RM), advanced pathological T stage, extraprostatic extension, larger total cancer area, larger cribriform morphology area, and higher % cribriform were significantly associated with BCR. Multivariate analysis demonstrated that PSA and % cribriform were independent predictors of BCR. Conclusions Higher % cribriform was associated with BCR in GS 4 + 4 prostate cancer following RARP.

Background Fibrinogen concentration is an important indicator of the treatment for obstetric disseminated intravascular coagulation (DIC). We present how using the fibrinogen measuring device could solve problems in the treatment of postpartum hemorrhage with complicated DIC. Case presentation A 32-year-old woman with monochorionic diamniotic twins at 22 weeks of pregnancy was diagnosed with placental abruption and underwent emergent cesarean section. The estimated blood loss was 8375 g. She was transferred to our hospital for further treatment. Compressive uterine sutures and balloon tamponade were performed. We transfused fibrinogen and fresh frozen plasma actively during the operation to maintain plasma fibrinogen above 200 mg/dL by using a point-of-care fibrinogen measuring device. In spite of massive hemorrhage exceeding 10 L, she was extubated at the end of the operation and discharged on the 7th day after the operation. Conclusion The portable fibrinogen measuring device was useful for point-of-care assessment of obstetric DIC.

Background Opioids are widely used as effective analgesics, but opioid sensitivity varies widely among individuals. The underlying genetic and nongenetic factors are not fully understood. Based on the results of our previous genome‐wide association study, we investigated the effects of single nucleotide polymorphisms (SNPs) of the astrotactin 2 (ASTN2) gene on pain‐related phenotypes in surgical patients. Methods We investigated the effects of two SNPs, rs958804 T/C and rs7858836 C/T, of the ASTN2 gene on eight and seven pain‐related phenotypes in 350 patients who underwent laparoscopic colectomy (LAC) and 358 patients who underwent mandibular sagittal split ramus osteotomy (SSRO), respectively. In both surgical groups, intravenous fentanyl patient‐controlled analgesia (PCA) was used for postoperative analgesia, and 24‐hour postoperative PCA fentanyl use was the primary endpoint. Results The association analyses among the two SNPs and pain‐related traits showed that 24‐hour fentanyl use was significantly associated with the two SNP genotypes in both surgical groups. The Mann‐Whitney test showed that 24‐hour fentanyl use was lower in patients with the C allele than in patients with the TT genotype of the rs958804 T/C SNP (P = .0019 and .0200 in LAC and SSRO patients, respectively), and it was lower in patients with the T allele than in patients with the CC genotype of the rs7858836 C/T SNP (P = .0017 and .0098 in LAC and SSRO patients, respectively). Conclusion The two SNPs of the ASTN2 gene were consistently associated with fentanyl requirements after two different types of surgery. These findings may contribute to personalized pain control., We investigated the effects of two SNPs, rs958804 T/C and rs7858836 C/T, which are located in the same LD block of the ASTN2 gene, on pain‐related phenotypes in two groups of patients who underwent laparoscopic colectomy and mandibular sagittal split ramus osteotomy. We found that these SNPs consistently reduced fentanyl requirements for postoperative analgesia, possibly by enhancing the analgesic effect of fentanyl.

Giant cell carcinoma of the lung is a rare tumor with poor prognosis. A 70-year-old male was referred to our hospital because of chest pain and abnormal shadow on the chest X-ray. He had a lung tumor invading the chest wall. The tumor was surgically removed, and since the diagnosis of giant cell carcinoma with p-N2 was obtained pathologically, adjuvant chemotherapy was performed. However, the local recurrence was found at eight months after surgery and was treated with radiotherapy( total 70 Gy/28 Fr). The patient has been well for over 10 years with no clinically evident recurrence after treatment.

Background We report a case in which a list of high-risk pregnant women on cloud-based business communication tools was useful in formulating an anesthetic plan for unscheduled cesarean section. Case presentation A 37-year-old woman, who had been prescribed icosapentate for hypertriglyceridemia, received an antenatal anesthetic evaluation for possible cesarean delivery, and it was agreed that the anesthetic method for emergency cesarean section was general anesthesia if the surgery would take place within 7 days after the discontinuation of the drug, and regional anesthesia if it would take place any time later. Then this agreement was uploaded on the cloud-based business communication tools, and updated until she delivered her baby via unscheduled cesarean section. Conclusions A cloud-based business communication tools was useful in formulating an anesthesia plan for a patient undergoing a cesarean delivery. However, more discussion would be needed to utilize it in security.

The development process of recurrence in prostate cancer patients with pathologically organ-confined (pT2) disease and negative surgical margins is unclear. The aim of the present study was to determine factors associated with the development of biochemical recurrence following robot-assisted radical prostatectomy among those prostate cancer patients. We retrospectively reviewed the data of patients who underwent robot-assisted radical prostatectomy without neoadjuvant endocrine therapy. We evaluated prognostic factors in 1096 prostate cancer patients with pT2 disease and negative surgical margins. Univariate and multivariate Cox proportional hazards regression analyses were used to identify independent predictors for biochemical recurrence. Of the 1096 patients, 55 experienced biochemical recurrence during the follow-up period. The 5-year biochemical recurrence-free survival rate for patients with pT2 and negative surgical margins was 91.8%. On univariate analysis, clinical stage, biopsy Gleason score, percent of positive core, pathological Gleason score, and the presence of micro-lymphatic invasion were significantly associated with biochemical recurrence. On a multivariate analysis, the presence of micro-lymphatic invasion and a pathological Gleason score ≥ 4 + 3 were significant prognostic factors for biochemical recurrence. Based on these factors, we developed a risk stratification model. The biochemical recurrence-free survival rate differed significantly among the risk groups. The prognosis of prostate cancer patients with pT2 disease and negative surgical margins is favorable. However, patients with the presence of micro-lymphatic invasion and a pathological Gleason score ≥ 4 + 3 tend to experience biochemical recurrence more often after surgery. Therefore, careful follow-up might be necessary for those patients.

A 72-year-old man with ileocecal lymphadenopathy was found to have Epstein-Barr virus-positive diffuse large B-cell lymphoma using open biopsy, and an ileostoma was created. R-CHOP-like chemotherapy was initiated, but his malnutrition did not improve. After 3 cycles of chemotherapy, a 2-m-long Cestoda was removed from the stoma and was identified as Diphyllobothrium nihonkaiense using mitochondria cytochrome c oxidase subunit 1 targeted polymerase chain reaction analysis. Although D. nihonkaiense infections are asymptomatic, the ileostomy was thought to have exacerbated the malabsorption in this patient. Parasitic infections are rare; however, they should be added to the differential diagnosis of malnutrition of unknown cause during chemotherapy for hematological malignancies.

Background The aim of this study was to study the prognostic significance of tertiary Gleason grade (TGG) 5 in patients with clinically localized prostate cancer treated with robot-assisted radical prostatectomy (RARP). Methods A total of 600 Japanese patients who underwent RARP for clinical stage T1-3N0M0 prostate cancer were evaluated. TGG5 was evaluated according to the International Society of Urological Pathology criterion. Cox hazard regression was used to evaluate the prognostic significance of prostate-specific antigen and pathological features in RARP specimens. Results Of the 600 RARP specimens, 92 (15%) had TGG5. TGG5 component was found in 30 (10%) of 287 cases with Gleason score (GS) 3 + 4, 55 (37%) of 149 cases with GS 4 + 3 and 7 (17%) of 40 cases with GS 4 + 4. There were no significant differences in pathological stage and surgical margin status between GS 3 + 4 with and without TGG5, as well as between GS 4 + 4 with and without TGG5. Of the 600 patients, 92 (15%) patients had biochemical recurrence (BCR) after surgery, with a median follow-up period of 42 (3-104) months. There were no differences in 5-year BCR-free survival rates between patients with GS 3 + 4 with and without TGG5 (92 vs. 100%, P = 0.16), as well as between patients with GS 4 + 3 with and without TGG5 (79 vs. 71%, P = 0.30). Similarly, there were no differences in 3-year BCRFS rates between patients with GS 4 + 4 with and without TGG5 (80 vs. 71%, P = 0.38). Conclusions In our population, the presence of TGG5 in RARP specimens had no strong impact on pathological and prognostic outcomes.

Objective We used real-ear insertion gain (REIG), with the international speech test signal (ISTS), to evaluate the amplifying characteristics of hearing aids, set for patients who have been wearing such aids for a long time in a stable manner. We further compared this to the target values of the DSLv5 and NAL-NL2 methods. Methods The subjects were adults with moderate sensorineural hearing loss. We examined 40 ears in 25 individuals (15 people wearing hearing aids in both ears and ten people wearing aid in only one ear). Fit assessments were performed based on the speech performance-intensity functions and tolerance of environmental noise, and the ears studied were categorized as either ears with sufficient benefit or ears with insufficient benefit. Additionally, we evaluated the REIG for international speech test signals at 65-dB and 80-dB sound pressure level (SPL). We compared the REIG and target values for voice input at 65-dB and 80-dB SPL, calculated from the DSLv5 and NAL-NL2 methods. Results Among the 40 ears, 34 received sufficient benefit and six received an insufficient benefit from hearing aids. The REIG for ISTS at 65-dB in the sufficient benefit ears, at frequencies of 1,000 Hz and 2,000 Hz, were similar to the target values of NAL-NL2 and DSLv5 but were significantly lower at 250 Hz, 500 Hz, and 4,000 Hz frequencies. The compression ratio of REIG for sufficient benefit ears was similar to that of DSLv5. The REIG for ISTS at 65-dB in the insufficient benefit ears was smaller than that in the sufficient benefit ears at frequencies of 2,000 Hz and 4,000 Hz. Conclusion This study suggested that the target values of NAL-NL2 and DSLv5 are appropriate, even for Japanese-speaking individuals, at mid-pitch sounds. Although it is necessary to investigate the necessity for low-pitch and high-pitch gains further in the future, this study provides meaningful data regarding the amplifying characteristics in Japanese-speaking individuals who have been wearing hearing aids in a stable manner.

The importance of fibrinogen replacement therapy in obstetric disseminated intravascular coagulation is well recognized. However, fibrinogen measurement in conventional laboratories has been a time-consuming task. Recently, a Japanese manufacturer developed a portable device that enables immediate fibrinogen measurement at the point of care. This report describes a case in which this device was used for the successful management of obstetric disseminated intravascular coagulation.

Aim This study aimed to investigate the rate of labor-onset hypertension (LOH) under neuraxial labor analgesia and the effect of neuraxial labor analgesia on LOH. Methods A retrospective study was conducted in a tertiary university hospital from 2015 to 2016. Patients who were admitted to the hospital for vaginal delivery under combined spinal and epidural anesthesia were selected. LOH was defined as the elevation of systolic blood pressure (BP) to ≥140 mmHg or diastolic BP to ≥90 mmHg for the first time after the onset of labor. Cases of LOH that persisted after neuraxial labor analgesia (prolonged LOH) were further analyzed to determine the hypertension severity and therapeutic intervention rate. Results Among 775 patients, 213 (28.4%) developed LOH. Prolonged LOH was observed in 30 patients (3.9%). LOH severity and the likelihood of prolonged LOH were positively correlated. Therapeutic intervention was administered only to the patients with prolonged LOH, that is, to 100% of those with emergent hypertension, to 21.1% of those with severe hypertension during labor, and to 36.8% of those with severe hypertension, to 55.6% of those with mild hypertension in the post-partum period. Conclusion The rate of LOH was reduced significantly after neuraxial labor analgesia. Patients with prolonged LOH should be carefully followed up during labor and in the post-partum period because such patients often require antihypertensive therapy.

Background: The purpose of this study was to validate the treatment strategy for a cohort of Japanese patients with very low-risk (VLR) and low-risk (LR) prostate cancer according to the National Comprehensive Cancer Network (NCCN) guidelines. Methods: We studied 751 patients with T1- 3N0M0 prostate cancer treated with radical prostatectomy at our institution between 2000 and 2012. Patients with neoadjuvant treatments were excluded. We retrospectively reviewed the clinical and pathological outcomes for patients with VLR or LR prostate cancers that were classified by NCCN guidelines. Results: We identified 45 patients with VLR and 137 with LR prostate cancer. Non-biochemical recurrence rate at 5-year for 45 patients with VLR was 86.9% and 81.2% for 137 patients with LR (p = 0.56). However, none of the 19 patients >65 years old with VLR progressed, while 19% of 26 patients ≤65 years old with VLR cancer, 14% of patients >65 years old with LR cancer, and 17% of patients ≤65 years old with LR cancer progressed during the follow-up period (p = 0.04, p = 0.04 and p = 0.05, respectively). In analyses of prostatectomy specimens, both VLR and LR had similarly favorable outcomes, but patients >65 years old with VLR had the smallest tumors, with a mean of 5 mm in diameter. Conclusions: Our results support the treatment strategy of the NCCN that patients with VLR cancer and age >65 years old are good candidates for active surveillance, and that other treatment options—including active surveillance and aggressive treatments—can be applied to the remaining patients with VLR or LR cancers.

Objective To develop a nomogram based on postoperative factors and prostate-specific antigen levels to predict the non-biochemical recurrence rate after radical prostatectomy in a Japanese cohort. Methods A total of 606 Japanese patients with T1-3N0M0 prostate cancer who underwent radical prostatectomy and pelvic lymph node dissection at Tokyo Medical University hospital from 2000 to 2010 were studied. A nomogram was constructed based on Cox hazard regression analysis evaluating the prognostic significance of serum prostate-specific antigen and pathological factors in the radical prostatectomy specimens. The discriminating ability of the nomogram was assessed by the concordance index (C-index), and the predicted and actual outcomes were compared with a bootstrapped calibration plot. Results With a mean follow up of 60.0 months, a total of 187 patients (30.9%) experienced biochemical recurrence, with a 5-year non-biochemical recurrence rate of 72.3%. Based on a Cox hazard regression model, a nomogram was constructed to predict non-biochemical recurrence using serum prostate-specific antigen level and pathological features in radical prostatectomy specimens. The concordance index was 0.77, and the calibration plots appeared to be accurate. Conclusions The postoperative nomogram described here can provide valuable information regarding the need for adjuvant/salvage radiation or hormonal therapy in patients after radical prostatectomy.

To evaluate the relationship between our proposed sonographic classification of testicular tumors by tissue harmonic imaging and histological type. We retrospectively analyzed 58 testicular tumors and tumor-like lesions [seminomatous germ cell tumor (SGCT): 28; non-seminomatous germ cell tumor (NSGCT): 16; lymphoid and hematopoietic tumor (LHT): 7; Leydig cell tumor: 1; epidermal cyst: 2; and tumor of paratesticular structure (TPS): 4]. We divided a sonographic image into six types for morphological criteria and three types for color Doppler criteria. We examined the relationship between the sonographic classification and histological type. For morphological criteria, there were 21 cases of Type I (36%), 15 Type II (26%), 9 Type III (15%), five Type IV (9%), five Type V (9%), and three Type VI (5%). For color Doppler criteria, there were 47 cases classified as hypervascular (81%), eight as hypovascular (14%), and three as avascular (5%). Most of the SGCTs were divided into types I and II; the NSGCTs into types III, IV, and V; the LHTs into only type II; and the TPSs into type VI. We established a sonographic classification of testicular tumors with various histological types. This sonographic classification is potentially useful for estimating the histological type of testicular tumors.

Salivary gland tumors are relatively uncommon and there exists a considerable diagnostic difficulty owing to their diverse histological features in individual lesions and the presence of a number of types and variants, in addition to overlapping histological patterns similar to those observed in different tumor entities. The classification is complex, but is closely relevant to the prognostic and therapeutic aspects. Although hematoxylin-eosin staining is still the gold standard method used for the diagnosis, immunohistochemistry (IHC) can enhance the accuracy and be a helpful tool when in cases to investigate the subjects that cannot be assessed by histological examination, such as the cell nature and differentiation status, cell proliferation, and tumor protein expression. This review depicts on the practical diagnostic utility of IHC in salivary gland tumor pathology under the following issues: assessment of cell differentiation, focusing on neoplastic myoepithelial cells; discrimination of histologically mimic tumor groups; diagnosis of specific tumor types, e.g., pleomorphic adenoma, adenoid cystic carcinoma, and salivary duct carcinoma; and evaluation of malignancy and prognostic factors. IHC plays a limited, even though important, role in the diagnosis of salivary gland tumors, but is often useful to support the histological assessment. However, unfortunately few tumor type-specific markers are still currently available. For these reasons, IHC should be considered a method that can be used to assist the final diagnosis, and its results themselves do not directly indicate a definitive diagnosis.

語音明瞭度検査による補聴器の適合判定の目安を得ることを目的として, 補聴器外来で実施した589例の検査結果について, 音場における65dBSPL (会話レベル) の語音明瞭度の補聴による改善と, これに関与する被検者と補聴器の要因について調査した。また, 望ましい補聴器装用状態では語音了解度指数と語音明瞭度の関係が裸耳と補聴時で変わらないと仮定して語音明瞭度改善の目標値を求め, 実際の症例の検査結果と比較した。会話レベルの語音明瞭度は, 平均聴力レベルが65dB付近の症例で最も改善量が大きく, 平均聴力レベルが40～90dBであった症例の語音明瞭度は平均31.7%改善した。重回帰分析の結果, 裸耳の語音了解度指数, 裸耳の最高語音明瞭度, 補聴による語音了解度指数の増加量を説明変数としたときに, 語音明瞭度の改善量との重相関係数が最大となった。裸耳に比べて補聴器装用時に最高語音明瞭度の低下が認められなかった症例では, 会話レベルの語音明瞭度の改善の平均は目標値と等しかったのに対して, 補聴時に最高語音明瞭度が低下した症例では, 目標値に届かない場合が多かった。

補聴器適合中の80症例を対象に, 試聴中の補聴器を用いて5周波数における実耳挿入利得 (REIG) とファンクショナルゲイン (FG) を測定し比較した。非線形増幅補聴器では, 補聴閾値と等しい入力音圧レベルにおけるREIGを比較に用いた。その結果, 高利得のCIC補聴器を装用する1症例でのみ, ハウリングのためREIGの測定が行えなかった。これ以外の症例においては, 250 Hzから2 kHzの周波数では, 2つの測定値は比較的よく一致した。4 kHzでは, REIGはFGより平均約5 dB小さくなり, 差の標準偏差も他の周波数より大きかった。REIG測定における補聴器挿入時のプローブチューブ位置のずれが, この不一致の一因である可能性が示唆された。いくつかの特殊な場合にはFGの測定が必須であるものの, REIGの測定結果から補聴閾値 (FG) を推定することはノンリニア補聴器でも可能であり, 通常の補聴器の利得評価においては, REIGはFGに比べ利点が多いことが確かめられた。

本研究は軽度発達障害の中でもアスペルガー症候群に焦点をあて、K市内にある1小学校において該当児童が在籍する通常学級において授業を実施し、授業分析を行うことを通して養護教諭として特別支援を必要とする児童への保健学習・保健指導を行う際、養護教諭の専門性を活かすためにはどのような視点を持ち、どのように指導や支援をすればよいかについて検討した。

北里大学病院補聴外来における補聴器適合とその評価法について概説した。適応は耳科診察と聴力検査によって決定される。適合の評価は補聴器の器械的評価, 聴力検査の評価, および自覚的評価に分けられる。補聴器の器械的評価では調整された補聴器の最大出力と利得を測定する。実耳挿入利得は短時間で施行でき, 客観的かつ実用的情報を得ることができる。聴力検査では純音聴力検査, 語音弁別検査, 補充現象検査は必須である。不快閾値測定も有用である。装用耳と裸耳との比較によって評価する。器械的評価と聴力評価が一致すれば適合がうまく行っていることを示す。自覚的評価にはきこえについての質問紙2002を使用した。質問紙は外来での適合の問題点の把握と対処に有用で, 補聴効果の評価にも有用であった。

INTRODUCTION AND OBJECTIVES: It is one of our major concerns to investigate the clinical implication of lymphovascular invasion (LVI) in transurethral resection of bladder tumor (TURBT) specimens (TUR-LVI) in clinical decision making in patients with bladder cancer. Immunohistochemistry (IHC) may improve LVI detection in small TUR specimens. We aimed to investigate the clinical significance of TUR-LVI for bladder cancer staging and compare the clinical values of IHC-detected LVI (IHC-LVI) with HE-detected LVI (HE-LVI). METHODS: This study included 157 non-metastatic bladder cancer patients treated with radical cystectomy (RC) at our institution. A single pathologist with expertise in genitourinary malignancies evaluated all TURBT specimens and assessed the venous, lymphatic and lymphovascular invasions in HE and IHC stained specimens. Two IHC markers for lymphatic channels (D2-40) and endothelial cells (CD31) were used to clarify lymphatic (ly) and venous (v) invasions in IHC studies. The univariate and multivariate logistic regression analyses were used to identify preoperative factors correlated with extra-vesical disease ( pT3) at RC., RESULTS: Sixty-nine patients (44%) were diagnosed with pT3 disease on RC specimens. HE-LVI was detected in 38 (24%) patients while IHC-LVI in 57 (36%). Twenty-six (46%) of the 57 patients with positive IHC-LVI was determined negative for HE-LVI, while 7 (18%) of the 38 patients with positive HE-LVI was determined negative by IHC. In univariate analyses, clinical T (cT) stage, tumor multifocality, hydronephrosis, and HE-LVI were significantly associated with pT3 disease, but v and ly by both HE and IHC staining and IHC-LVI were not. In multivariate analyses, cT stage (p

Objectives The aim of this study was to investigate the effect of positive surgical margin (PSM) without extraprostatic extension after robot-assisted radical prostatectomy (RARP). Materials and methods We retrospectively reviewed 837 patients who underwent RARP for clinically localized prostate cancer without neoadjuvant endocrine therapy. The pT2+category lesions were defined according to World Health Organization classification. The actuarial probabilities of biochemical recurrence-free survival (BCR-FS) were determined using Kaplan-Meier analysis. Univariate and multivariate Cox proportional hazards regression analyses were also used to identify independent predictors for BCR. Results Of the 837 patients, 102 (12.2%) experienced BCR during the follow-up period. The BCR-FS rate was significantly higher in patients with pT2+category tumors than in those with pT3a category tumors, and significantly lower in patients with pT2+category tumors than that in those with pT2 category tumors without PSM. The BCR-FS rate of patients with pT2+category tumors was significantly higher than that with pT3a category tumors with PSM but not significantly different from that with pT3a category tumors without PSM. In a multivariate analysis, the pathological T category considering pT2+category was one of independent predictive factors for BCR. Conclusions This study support the hypothesis that the pT2+category disease is associated with a significantly increased risk of BCR in patients with organ-confined prostate cancer after RARP. As PSM can be avoided in some cases, urologists should continually seek to improve their operative skills and to reduce the rate of PSM, especially in patients with organ-confined prostate cancer.

新生児聴覚スクリーニングで要精査となり北里大学病院耳鼻咽喉科を受診し, ABRで閾値上昇が見られ, 言語聴覚士に依頼された乳児20例の精密検査の過程を分析し, 診断に至るまでに配慮すべき点を検討した。NICU児で well born 児と比べ, 確定診断までに長期間を要した。5例でABRや乳幼児聴力検査の閾値が改善し, 両者の結果が一致しない症例も認められた。スクリーニング後の精査において, ABR検査とともに乳幼児聴力検査を継続して実施することの重要性が示唆された。発達障害を合併し精査が長期化する場合は, 聴力検査と並行して発達支援を行った。発達支援は, 家族の適切な養育を支え不安を軽減するとともに, 乳幼児聴力検査で明確な反応を早期に得るためにも有効であることが示唆された。

Possible mechanisms underlying sodium overload-induced ischemia/reperfusion injury in perfused rat hearts were examined. Massive accumulation of myocardial Na(+) occurred during ischemia, suggesting cytosolic sodium overload in cardiac cells. Treatment of the pre-ischemic heart with 0.3 micromol/l tetrodotoxin or 3 micromol/l ethyl-isopropyl amiloride enhanced post-ischemic contractile recovery (72 or 82% of initial vs 24% for untreated group), which was associated with suppression of tissue Na(+) accumulation (138 or 141% of initial vs 270% for untreated group), restoration of tissue high-energy phosphates, and preservation of the ability of mitochondria to produce ATP in the ischemic/reperfused heart. The release of cytochrome c from the ischemic heart was observed, which was blocked by treatment of the pre-ischemic heart with these agents. The improvement of post-ischemic contractile recovery by these agents was closely correlated with the ability of mitochondria to produce ATP during ischemia. To examine the effects of sodium overload on mitochondrial function, isolated mitochondria were incubated in the presence of various concentrations of Na(+). Na(+) induced mitochondrial membrane perturbations such as depolarization of the membrane potential, mitochondrial swelling, cytochrome c release from isolated mitochondria, and a reduction in oxidative phosphorylation. These events in the isolated mitochondria were not blocked by the presence of the above agents. The results suggest that cytosolic sodium overload in cardiac cells may induce deterioration of the mitochondrial function during ischemia and that this mitochondrial damage may determine post-ischemic contractile dysfunction in perfused rat hearts.

1. The present study was aimed to determine whether propranolol improves contractile function of the ischaemic/reperfused heart through protection of the mitochondrial function during ischaemia. 2. Isolated perfused rat hearts were subjected to 35-min ischaemia followed by 60-min reperfusion. Pre-treatment with propranolol at the concentrations of 10 to 100 microM for the final 3 min of pre-ischaemia resulted in the improvement of ischaemia/reperfusion-induced contractile dysfunction, release of creatine kinase (CK) into perfusate, and decrease in myocardial high-energy phosphates. Propranolol also attenuated ischaemia-induced accumulation in Na+, suggesting that cytosolic sodium overload during ischaemia was prevented by propranolol. 3. The mitochondrial oxygen consumption rate of skinned bundles from the perfused heart decreased at the end of ischaemia and it further decreased at the end of reperfusion. These decreases were cancelled by treatment with propranolol. A release of cytochrome c from the perfused heart was observed during ischaemia, and this release was suppressed by treatment with propranolol. 4. To elucidate the direct effect of propranolol on mitochondria, the mitochondria were isolated from normal hearts and their activities were determined in the presence of various concentrations of Na+ and propranolol. The addition of sodium lactate, which mimicked sodium overload in the ischaemic heart, reduced the state 3 respiration, whereas this reduction was not attenuated by the presence of propranolol. 5. These results suggest that cardioprotection of propranolol may be exerted via attenuating Na+ influx into cardiac cells followed by prevention of the mitochondrial dysfunction in the ischaemic heart, leading to improvement of energy production of the heart during reperfusion.