Heart is the first organ to form and function during development. At blastula stage, cells that contribute to the cardiogensis are found in the posterior region of the epiblast, and they are specified to the mesoderm fate during gastrulation. At gastrula to neurula stages, heart-forming mesoderm in the anterior lateral plate is specified and differentiates to beating primitive heart tube. Subsequently, primitive heart tube establishes an S-shaped heart (d-loop heart). Endocardial cushion tissue, a primordium of valves and septa, is established in atrioventricular canal and outflow tract regions. Thereafter, outflow septum, muscular septum, atrioventricular septum and atrial septum develop individually and align each other, resulting in the formation of four-chambered heart at late embryonic stage. Several genes are identified to regulate these complicated heart forming processes, and candidate genes for human congenital malformation syndromes associated with congenital heart defects are identified, Tbx5 for Holt-Oram syndrome and Tbx1 for del22q11 syndrome. Recently, different types of stem cell, which can trans-differentiate to beating cardiomyocytes, are found in adult bone marrow and heart. Understanding the molecular mechanisms of heart development facilitates the stem cell technology that has potential ability to restore heart diseases including congenital heart defects and degenerated heart diseases.

View full abstract

Modern neuroimaging detects more frequently cerebral white matter lesions. These lesions, which are highly observed in old people and/or patients with cerebrovasucular diseases, are caused by chronic cerebral hypoperfusion and associated with cognitive disturbance. In addition, it has been recognized that preventing white matter damage is quite important to ameliorate ischemic neuronal damage. But the mechanisms of white matter damage and the drug sensitivity of white matter are quite different from those of grey matter. We investigated effects of hypocapnia induced by hyperventilation on white matter lesions using a rat model of chronic cerebral hypoperfusion. Hypocapnia exclusively aggravated white matter lesions in the caudoputamen, which is associated with cognition and working memory. The lesions were significantly alleviated by ketamine, an N-methyl-D-aspartate receptor antagonist. Our results may imply postoperative brain dysfunction, such as delirium, in old people or patients with cerebrovascular diseases may be due, at least partly, to the aggravation of white matter lesions in the caudoputamen.

View full abstract

The demographics of clinical populations can predict the demand for critical care services. Both Japan and the United States forecast a substantial expansion of the aged population. The inevitable consequence is a sharp increase in the number of patients who may wish to be admitted to an intensive care unit. No economy can meet the predicted demand. As a consequence, some rationing of critical care services is inevitable. Such rationing cannot be done by rules, but rather must reflect a system of values that is clearly stated and compassionately applied. Each critical care physician must undertake introspection to understand his or her own values and ensure that those values are transparent in any rationing process. Values such as integrity, honesty and respect for the personal views of patients and families can enlighten difficult decisions regarding the goals and duration of critical care services.

View full abstract

Background: Considerable parts of the myocardium fall into myocardial stunning just after reperfusion therapy for acute myocardial infarction (AMI). In the present study, the prediction of recovery from myocardial stunning by the change in the stroke volume (SV) with a Swan-Ganz catheter (Stroke Volume with Swan-Ganz, SGSV) just after reperfusion therapy was attempted. Methods: The study consisted of 35 consecutive patients transferred to the Emergency Center of Kitasato University Hospital with a first uncomplicated anteroseptal AMI. Primary percutaneus transluminal coronary angioplasty (primary PTCA) for left anterior descending artery (LAD) was performed in 32 patients. They were divided into a stroke volume-increasing group (SGSV-UP group) or decreasing group (SGSV-DOWN group) according to their SGSV change during the CCU stay. The ejection fraction (EF) and SV on left ventriculography (LVG) (EF on LVG, LVGEF; SV on LVG, LVGSV) in the acute and chronic phase (about 6-8 months later) were compared between the two groups. Results: Twenty four patients were classified into the SGSV-UP group and 8 patients into the SGSV-DOWN group. LVGEF increased significantly in the SGSV-UP group but not in the SGSV-DOWN group (from 40.8±8.5% to 54.1±9.1%, P=0.0022 vs. from 42.2±10.6% to 43.6±7.7%, N. S.). LVGSV changed similar to LVGEF. In the SGSV-UP group, the relationship between the change in LVGEF (Δ LVGEF) and SGSV (Δ SGSV) was revealed to be Δ LVGEF (%)=1.4+0.5 Δ SGSV (ml) (P=0.0082). Regional asvnergy was significantly reduced in the SGSV-UP group (P=0.034). Conclusion: The increase in SGSV just after reperfusion therapy for AMI was related to the recovery of LVGEF and LVGSV in the chronic-phase. This suggests that recovery from myocardial stunning begins just after reperfusion therapy for AMI.

View full abstract

A 48 year-old deep coma female was transfered to our emergency room by her commonlaw marriage husband by his car. Her pupils were miotic and reacted sluggish on a light stimulation. There were some bruises on her face and breast. Firstly, we suspected the cause of coma as a brain injury. But there were no abnormal findings in a head CT scan, nor chest, abdominal X-ray images. We unexpectedly observed high density substance in her stomach on a CT scan. This finding reminded us a radiopaque drug intoxication. Bromovaleryl urea is a wellknown radiopaque hypnotic drug. Later, four empty boxes of drug packages printed “Wutt^TM”, which contains bromovareryl urea, were discovered in her house. After she became awake, she confirmed an overdose use of this drug and had a suicidal ideation. We found 4.5mg·dl^-1 of bromine in her blood taken just after her admission. We diagnosed the cause of unconsciousness as acute bromovaleryl urea intoxication by a CT image which is more sensitive than a plain abdominal X-ray image in this case.

View full abstract

An 82-year-old man who had advanced gastrointestinal stromal tumor (GIST) received chemotherapy with imatinib mesylate. CT scan showed remarkable tumor shrinkage after 2 weeks of the treatment and the treatment was continued. He developed, however, exertional dyspnea and cough after 35 days of the therapy with the agent. Three days after the onset of those symptoms, marked hypoxemia and bilateral interstitial filtrate on chest CT examination appeared and he was hospitalized. The diagnosis of drug-induced pneumonitis was strongly suggested, so that the agent was discontinued. He received mechanical ventilation for 6 days and corticosteroid therapy consisting of methylprednisolone (1g·day^-1) for 3 days, followed by administration of prednisolone. These treatments were effective for respiratory failure and they achieved almost complete recovery from the respiratory failure symptomatically and radiographically. These findings suggested that the patient had drug-induced interstitial pneumonitis caused by imatinib mesylate. Imatinib mesylate was restarted with steroid subsequently and he is now in good health. Although there are several reported cases of interstitial pneumonitis by imatinib mesylate as far as we know, careful attention must be taken for the early identification of such adverse effect during imatinib mesylate therapy.

View full abstract

At 4 years old, a male infant was diagnosed with progressive muscular dystrophy. His heart functions, however, were not examined. Although he had general fatigue and limb weakness at the time of entry to a junior high school, there were no major problems in daily life. At 12 years old nine months, liver dysfunction became evident, which led to diagnosis of dilated cardiomyopathy complicated by liver dysfunction. He was transferred to the ICU of our hospital due to deteriorating heart failure. Because the heart failure was intractable to medication after ICU admission, we implanted ventricular assist devices. However, subsequent to infection, the patient died from multiple organ failure 33 days after ICU admission. To enable the earliest detection and treatment of cardiomyopathy, for patients who present symptoms of myopathy, it is important to specify the type of myopathy and to periodically evaluate cardiac function. As long as there are no apparent contraindications, such as respiratory muscle paralysis, it is possible to apply ventricular assist devices or cardiac transplantation to these patients.

View full abstract

Objectives: Previous studies demonstrated that a class III antiarrhythmic agent amiodaraone inhibits K⁺ channels on cardiac myocytes, resulting in antiarrhythmic properties. However, it has not been determined that this agent may induce the inhibition of K⁺ channel activity in blood vessels. Therefore, the present study was designed to evaluate whether amiodarone modulates vasorelaxation mediated by adenosine triphosphate (ATP)-sensitive K⁺ channels in arteries from humans as well as rats. Methods: The ethical committee of our institute approved this study. Human omental arteries were obtained from surgical patients without hypertension, cardiac diseases, diabetes mellitus, hypercholesterolemia and smoking habit, under written informed consent. Aortas were taken from Wister rats under halothane anesthesia. Isometric force recordings were performed using human omental arterial or rat aortic rings without endothelium, under contraction with U46619 (3×10^-8M) or phenylephrine (3×10^-7M), respectively. Results: An ATP-sensitive K⁺ channel opener levcromakalim (10^-8-10^-5M) induced vasorelaxation in both human omental arterial and rat aortic rings in a concentration-dependent fashion, which is completely abolished by the treatment with a selective ATP-sensitive K⁺ channel antagonist glibenclamide (5×10^-6M). Pretreatment with amiodarone (10^-6-3×10^-6M) did not alter the relaxation. Conclusions: These results suggest that clinically relevant concentrations of amiodarone do not affect vasodilation mediated by ATP-sensitive K⁺ channels in the vascular smooth muscle cells including those from humans.

View full abstract