Jun Hwi Cho

Changes of aortic dimensions as evidence of cardiac pump mechanism during cardiopulmonary resuscitation in humans

The mechanism of forward blood flow during cardiopulmonary resuscitation (CPR) remains controversial. We hypothesized that, if the heart acts as a pump, the proximal descending thoracic aorta would be distended during compression by forward blood flow, and would be constricted or remained unchanged if blood flow is generated by increased intrathoracic pressure. Fourteen patients with nontraumatic cardiac arrest underwent transesophageal echocardiography to verify changes in the descending thoracic aorta during standard manual CPR. The aortic dimensions, including cross-sectional area and diameter at the end of compression and relaxation, were measured proximal to, and at the maximal compression site of the descending thoracic aorta. At the maximal compression site, deformation of the descending thoracic aorta was observed during compression in all patients and the ratio of maximal to minimal diameter of the aorta (deformation ratio) decreased during compression compared with relaxation (0.58+/-0.15 vs. 0.81+/-0.11, P=0.001). This suggests eccentric compression of the descending thoracic aorta by external chest compression. The deformation ratio of the descending thoracic aorta proximal to the maximal compression site remained unchanged during compression and relaxation (1.0+/-0.88 vs. 1.0+/-0.9, P=0.345). The cross-sectional area of the descending thoracic aorta proximal to the maximal compression site increased 15% on average during compression compared with relaxation in 12 of 14 patients. In conclusion, deformation of the aorta at the maximal compression site and increase in the cross-sectional area of the proximal aorta suggests that cardiac pumping is the dominant mechanism in generating forward blood flow during CPR in humans.

Melatonin Improves Cognitive Deficits via Restoration of Cholinergic Dysfunction in a Mouse Model of Scopolamine-Induced Amnesia

Melatonin is known to improve cognitive deficits, and its functions have been studied in various disease models, including Alzheimers disease. In this study, we investigated effects of melatonin on cognition and the cholinergic system of the septum and hippocampus in a mouse model of scopolamine-induced amnesia. Scopolamine (1 mg/kg) and melatonin (10 mg/kg) were administered intraperitoneally to mice for 2 and 4 weeks. The Morris water maze and passive avoidance tests revealed that both treatments of scopolamine significantly impaired spatial learning and memory; however, 2- and 4-week melatonin treatments significantly improved spatial learning and memory. In addition, scopolamine treatments significantly decreased protein levels and immunoreactivities of choline acetyltransferase (ChAT), high-affinity choline transporter (CHT), vesicular acetylcholine transporter (VAChT), and muscarinic acetylcholine receptor M1 (M1R) in the septum and hippocampus. However, the treatments with melatonin resulted in increased ChAT-, CHT-, VAChT-, and M1R-immunoreactivities and their protein levels in the septum and hippocampus. Our results demonstrate that melatonin treatment is effective in improving the cognitive deficits via restoration of the cholinergic system in the septum and hippocampus of a mouse model of scopolamine-induced amnesia.

Changes in histopathology and tumor necrosis factor-α levels in the hearts of rats following asphyxial cardiac arrest

Objective Post cardiac arrest (CA) syndrome is associated with a low survival rate in patients who initially have return of spontaneous circulation (ROSC) after CA. The aim of this study was to examine the histopathology and inflammatory response in the heart during the post CA syndrome. Methods We induced asphyxial CA in male Sprague-Dawley rats and determined the survival rate of these rats during the post resuscitation phase. Results Survival of the rats decreased after CA: 66.7% at 6 hours, 36.7% at 1 day, and 6.7% at 2 days after ROSC following CA. The rats were sacrificed at 6 hours, 12 hours, 1 day, and 2 days after ROSC, and their heart tissues were examined. Histopathological scores increased at 12 hours post CA and afterwards, histopathological changes were not significant. In addition, levels of tumor necrosis factor-α immunoreactivity gradually increased after CA. Conclusion The survival rate of rats 2 days post CA was very low, even though histopathological and inflammatory changes in the heart were not pronounced in the early stage following CA.

Cardiac physiologic regulation of sub-type specific adrenergic receptors in transgenic mice overexpressing β 1 - and β 2 -adrenergic receptors

Objective Combination of β1-adrenergic receptor (AR) blockade and β2-AR activation might be a potential novel therapy for treating heart failure. However, use of β-AR agonists and/or antagonists in the clinical setting is controversial because of the lack of information on cardiac inotropic or chronotropic regulation by AR signaling. Methods In this study, we performed hemodynamic evaluation by examining force frequency response (FFR), Frank-Starling relationship, and response to a non-selective β-AR agonist (isoproterenol) in hearts isolated from 6-month-old transgenic (TG) mice overexpressing β1- and β2-ARs (β1- and β2-AR TG mice, respectively). Results Cardiac physiologic consequences of β1- and β2-AR overexpression resulted in similar maximal response to isoproterenol and faster temporary decline of positive inotropic response in β2-AR TG mice. β1-AR TG mice showed a pronounced negative limb of FFR, whereas β2-AR TG mice showed high stimulation frequencies with low contractile depression during FFR. In contrast, Frank-Starling relationship was equally enhanced in both β1- and β2-AR TG mice. Conclusion Hemodynamic evaluation performed in the present showed a difference in β1- and β2-AR signaling, which may be due to the difference in the desensitization of β1- and β2-ARs.

Age‑dependent decreases in insulin‑like growth factor‑I and its receptor expressions in the gerbil olfactory bulb

Insulin-like growth factor-I (IGF-I) is a multifunctional protein present in the central nervous system. A number of previous studies have revealed alterations in IGF-I and its receptor (IGF-IR) expression in various regions of the brain. However, there are few reports on age-dependent alterations in IGF-I and IGF-IR expressions in the olfactory bulb, which contains the secondary neurons of the olfactory system. The present study examined the cellular morphology in the olfactory bulb by using cresyl violet (CV) staining at postnatal month (PM) 3 in the young group, PM 6 in the adult group and PM 24 in the aged group in gerbils. In addition, detailed examinations were performed of the protein levels and immunoreactivities of IGF-I and IGF-IR in the olfactory bulb in each group. There were no significant changes in the cellular morphology between the three groups. The protein levels and immunoreactivities of the IGF-I and IGF-IR were the highest in the young group and they decreased with age. He protein levels and immunoreactivities of the IGF-I and IGF-IR were the lowest in the aged group. In brief, our results indicate that IGF-I and IGF-IR expressions are strong in young olfactory bulbs and significantly reduced in aged olfactory bulbs. In conclusion, subsequent decreases in IGF-I and IGF-IR expression with age may be associated with olfactory decline. Further studies are required to investigate the roles of IFG-I and IGF-IR in disorders of the olfactory system.