Efficacy and safety of tolvaptan in acute heart failure patients during long-distance transportation.

AIMS: Treating patients with acute heart failure is difficult at the local hospitals in medically depopulated areas where cardiologists are generally absent. These patients require long-distance and time-consuming transportation to the intensive care units. It is well known that tolvaptan is effective for the treatment of congestive heart failure, but the effect of prehospital tolvaptan use in patients is not well evaluated. The aim of this study was to evaluate the efficacy and safety of prehospital tolvaptan use in patients with acute congestive heart failure who require long-distance and time-consuming transportation. METHODS: This retrospective study included 30 patients who were newly diagnosed with acute heart failure at Wakkanai City Hospital and transported to Nayoro City General Hospital between January 2013 and May 2020. The patients were classified into those who received tolvaptan (tolvaptan group, n = 18) and did not receive tolvaptan (control group, n = 12). RESULTS: The percentage of patient survival at discharge did not show a statistically significant difference between the groups (100% [tolvaptan] vs. 91% [control], p = 0.414). During transportation, the percentage of patients in the tolvaptan group who required increased oxygen doses was statistically significantly lower than that in the control group (0% vs. 36%, p = 0.0181). Patients in the tolvaptan group had statistically significantly shorter intensive care unit stays (median: 2 days vs. 6 days, p = 0.0376), less days to discontinuation of oxygen (median: 2.8 days vs. 6.9 days, p < 0.00125), and less days to ambulation (median: 1.5 days vs. 7.5 days, p = 0.0362) compared with the control group. In the tolvaptan group, blood pressure was not different; however, heart rate was statistically significantly reduced (99 ± 21 vs. 88 ± 21 beats per minute, p = 0.016) during transportation. CONCLUSION: The use of tolvaptan in patients with acute heart failure requiring long-distance transport is safe and may show better clinical course compared with conventional therapies.

Acute Myocardial Infarction in a 17-year-old High-school Girl.

We report an unusual case of acute myocardial infarction in a high school girl. The patient was 17 years of age and had multiple coronary risk factors, including marked obesity with a body mass index (BMI) of 42.7 kg/m2, dyslipidemia and glucose intolerance. She had been an on and off smoker since she was 13 years of age. Due to the recent Westernization of the lifestyle, the prevalence of metabolic syndrome in the young generation has been increasing in Japan. Cardiovascular disease based on lifestyle-related diseases may become more common in young people.

Computed tomography findings of complications resulting from cardiopulmonary resuscitation.

INTRODUCTION: This retrospective study was conducted to evaluate injuries related to cardiopulmonary resuscitation (CPR) and their associated factors using postmortem computed tomography (PMCT) and whole body CT after successful resuscitation. METHODS: The inclusion criteria were adult, non-traumatic, out-of-hospital cardiac arrest patients who were transported to our emergency room between April 1, 2008 and March 31, 2013. Following CPR, PMCT was performed in patients who died without return of spontaneous circulation (ROSC). Similarly, CT scans were performed in patients who were successfully resuscitated within 72h after ROSC. The injuries associated with CPR were analysed retrospectively on CT images. RESULTS: During the study period, 309 patients who suffered out-of hospital cardiac arrest were transported to our emergency room and received CPR; 223 were enrolled in the study. The CT images showed that 156 patients (70.0%) had rib fractures, and 18 patients (8.1%) had sternal fractures. Rib fractures were associated with older age (78.0 years vs. 66.0 years, p<0.01), longer duration of CPR (41min vs. 33min, p<0.01), and lower rate of ROSC (26.3% vs. 55.3%, p<0.01). All sternal fractures occurred with rib fractures and were associated with a greater number of rib fractures, higher age, and a lower rate of ROSC than rib fractures only cases. Bilateral pneumothorax was observed in two patients with rib fractures. CONCLUSIONS: PMCT is useful for evaluating complications related to chest compression. Further investigations with PMCT are needed to reduce complications and improve the quality of CPR.

Zinc is released by cultured astrocytes as a gliotransmitter under hypoosmotic stress-loaded conditions and regulates microglial activity.

AIM: Astrocytes contribute to the maintenance of brain homeostasis via the release of gliotransmitters such as ATP and glutamate. Here we examined whether zinc was released from astrocytes under stress-loaded conditions, and was involved in the regulation of microglial activity as a gliotransmitter. MAIN METHODS: Hypoosmotic stress was loaded to astrocytes using balanced salt solution prepared to 214-314 mOsmol/L, and then intra- and extra-cellular zinc levels were assessed using Newport Green DCF diacetate (NG) and ICP-MS, respectively. Microglial activation by the astrocytic supernatant was assessed by their morphological changes and poly(ADP-ribose) (PAR) polymer accumulation. KEY FINDINGS: Exposure of astrocytes to hypoosmotic buffer, increased the extracellular ATP level in osmolarity-dependent manners, indicating a load of hypoosmotic stress. In hypoosmotic stress-loaded astrocytes, there were apparent increases in the intra- and extra-cellular zinc levels. Incubation of microglia in the astrocytic conditioned medium transformed them into the activated "amoeboid" form and induced PAR formation. Administration of an extracellular zinc chelator, CaEDTA, to the astrocytic conditioned medium almost completely prevented the microglial activation. Treatment of astrocytes with an intracellular zinc chelator, TPEN, suppressed the hypoosmotic stress-increased intracellular, but not the extracellular, zinc level, and the increase in the intracellular zinc level was blocked partially by a nitric oxide synthase inhibitor, but not by CaEDTA, indicating that the mechanisms underlying the increases in the intra- and extra-cellular zinc levels might be different. SIGNIFICANCE: These findings suggest that under hypoosmotic stress-loaded conditions, zinc is released from astrocytes and then plays a primary role in microglial activation as a gliotransmitter.

Impaired ventricular repolarization dynamics in patients with early repolarization syndrome.

INTRODUCTION: Almost all current investigations on early repolarization syndrome (ERS) have focused on the J-wave characteristics and ST-segment configuration; however, few have reported on ventricular repolarization indexes in ERS. METHODS AND RESULTS: A total of 145 subjects were enrolled: 10 ERS patients, 45 uneventful ER pattern (ERP) subjects, and 90 healthy controls without J waves or ST-segment elevation. Ambulatory ECG-derived parameters (QT, QTc(B), QTc(F), T peak-Tend(Tpe), and QT/RR slope) were measured and statistically compared. Among the groups, there was no significant difference in the average QT and QTc(B); however, ERS patients had the shortest QTc(F) and longest Tpe (QTc(F): 396.2 ± 19 vs 410.4 ± 20 vs 419.2 ± 19 milliseconds, P = 0.036, Tpe: 84.9 ± 12 vs 70.4 ± 11 vs 66.9 ± 15 milliseconds, P < 0.001, for the ERS, ERP, and control groups, respectively). Importantly, the 24-hour QT/RR slope was significantly smaller in the ERS than ERP and control groups (QT/RR: 0.105 ± 0.01 vs 0.154 ± 0.02 vs 0.161 ± 0.03, respectively; P < 0.001). When analyzing the diurnal and nocturnal QT/RR slopes, ERS patients had small diurnal and nocturnal QT/RR slopes while the ERP and control groups had large diurnal and small nocturnal QT/RR slopes (diurnal QT/RR: 0. 077 ± 0.01 vs 0.132 ± 0.03 vs 0.143 ± 0.03, P < 0.001; nocturnal QT/RR: 0.093 ± 0.02 vs 0.129 ± 0.03 vs 0.130 ± 0.04, P = 0.02 in the ERS, ERP, and control groups, respectively). CONCLUSION: ERS patients had a continuously depressed diurnal and nocturnal adaptation of the QT interval to the heart rate. Such abnormal repolarization dynamics might provide a substrate for reentry and be an important element for developing ventricular fibrillation in the ERS cohort.

Acute myocardial infarction with a left main trunk lesion and documented lambda-like J waves.

We herein describe a case of a myocardial infarction, in which Lambda-like J waves were documented. The patient was referred to our hospital due to ventricular fibrillation. The twelve-lead electrocardiogram (ECG) on admission showed prominent J waves in the lateral and precordial leads. Coronary angiography revealed 99% stenosis with a delay in the left anterior descending artery, 75% stenosis in the left main trunk, and possible ischemia in the conus branch. Our report addresses the possibility that ischemic J waves can be used as an important marker for lethal arrhythmias in patients with acute myocardial infarction.

Peroxynitrite treatment reduces adenosine uptake via the equilibrative nucleoside transporter in rat astrocytes.

In the oxidative stress-loaded brain, extracellular adenosine levels are elevated and thereby neuronal damage is attenuated, but mechanisms underlying alteration of the extracellular kinetics of adenosine remain unclear. Here we investigated whether oxidative stress might alter functional expression of nucleoside transporters (NTs), a predominant regulatory system for nucleoside kinetics, in cultured rat astrocytes. Treatment of astrocytes with 0.5mM SIN-1 for 3h caused apparent cellular accumulation of nitrotyrosine, but had no effect on their viability, indicating load of oxidative stress to astrocytes without any change in their viability. Under the condition, [(3)H]adenosine uptake was significantly less than that by control cells. This decreased uptake was due to decrease in adenosine uptake mediated by an equilibrative NT (ENT) 1 which was inhibited by low concentrations (≤0.1 µM) of nitrobenzylthioinosine (NBMPR), but not by sodium-dependent or high concentrations (≥1 µM) of NBMPR-inhibitable nucleoside transporters. The expression level of ENT1 was not altered, while the Michaelis constant, but not the maximum rate, of adenosine uptake was increased. These findings suggest that under oxidative stress-loaded conditions, decreased adenosine clearance via astrocytic ENT1 might involve, at least in part, in an elevated extracellular adenosine level in the brain.

Possible contribution of ischemia of the conus branch to induction or augmentation of Brugada type electrocardiographic changes in patients with coronary artery disease.

Recent evidence suggests an association between vasospastic angina and Brugada syndrome. Here we present two cases of coronary artery disease who presented with ECG abnormalities which might have been provoked or enhanced by ischemia of the conus branch of the right coronary artery. The 12-lead ECGs demonstrated normal sinus rhythm in these two cases. Interestingly, a saddle back or coved type ST segment elevation in leads V1-V3 was documented either in the percutaneous transluminal angioplasty procedure of the proximal right coronary artery or with an intracoronary acetylcholine (Ach) administration into the right coronary artery. These Brugada type ECG changes were restored to the baseline ECG waveform after improvement in the ischemia. In the second case, vasospasms of the conus branch of the right coronary artery were associated with a coved type ST segment elevation in leads V1 to V2. We discuss the possible interaction between ischemia caused by conus branch lesions and Brugada type electrocardiographic changes.