Keiichi Hagiya

Significant reversal of cardiac upregulated endothelin-1 system in a rat model of sepsis by landiolol hydrochloride.

AIMS Landiolol hydrochloride, an ultra-short-acting highly cardio-selective β-1 blocker, has become useful for various medical problems. Recent studies have demonstrated that co-treatment with landiolol protects against acute lung injury and cardiac dysfunction in rats of lipopolysaccharide (LPS)-induced systemic inflammation, and was also associated with a significant reduction in serum levels of the inflammation mediator HMGB-1 and histological lung damage. Endothelin (ET)-1, a potent vasoconstrictor, has been implicated in pathogenesis of sepsis and sepsis-induced multiple organ dysfunction syndrome. Here, we investigated whether landiolol hydrochloride can play important roles in ameliorating LPS-induced alterations in cardiac ET system of septic rats. MAIN METHODS Eight-week-old male Wistar rats were administered LPS only for 3 h and the rest were treated with LPS as well as with landiolol non-stop for 3 h. KEY FINDINGS At 3 h after LPS (only) administration, circulatory tumor necrosis factor (TNF)-α level, blood lactate concentration and percentage of fractional shortening of heart were significantly increased. In addition, LPS induced a significant expression of various components of cardiac ET-1 system compared to control. Finally, treatment of LPS-administered rats with landiolol for 3 h normalized LPS-induced blood lactate levels and cardiac functional compensatory events, without altering levels of plasma TNF-α and ET-1. Most strikingly, landiolol treatment significantly normalized various components of cardiac ET-1 signaling system in septic rat. SIGNIFICANCE Taken together, these data led us to conclude that landiolol may be cardio-protective in septic rats by normalizing the expression of cardiac vasoactive peptide such as ET, without altering the circulatory levels of inflammatory cytokines.

Potential amelioration of upregulated renal HIF-1alpha–endothelin-1 system by landiolol hydrochloride in a rat model of endotoxemia

AIMS Endothelin (ET)-1 is the best known potent vasoconstrictor and has been implicated in pathogenesis of sepsis-associated acute kidney injury (AKI) in human or lipopolysaccharide (LPS)-induced AKI in animal models. We have previously shown that ET-1 is highly up-regulated in renal tissues and in plasma after LPS administration. Here, we investigated whether landiolol hydrochloride, an ultra-short-acting beta-blocker, can play an important role in ameliorating levels of LPS-induced up-regulation of renal HIF-1α-ET-1 system and inflammatory cytokines in a rat model of endotoxemia. MAIN METHODS Male Wistar rats at 8 weeks of age were either administered with: a) lipopolysaccharide (LPS) only for three hours (3 h) or b) LPS, followed by continuous administration of landiolol for 3 h; c) third group was only treated with vehicle. KEY FINDINGS At 3 h after LPS administration there was: a) minimal injury in kidney tissues; b) circulatory levels of creatinine, blood urea nitrogen and NGAL increased and c) expression of inflammatory cytokines, such as TNF-α, IL-6 and iNOS increased at the level of both circulatory and renal tissues. In addition, LPS significantly induced renal expression of ET-1 and HIF-1α compared to control. Finally, treatment of LPS-administered rats with landiolol for 3 h normalized elevated serum markers of renal injury and up-regulated levels of renal HIF-1α-ET-1 system with normalization of TNF-α. SIGNIFICANCE Taken together, these data led us to conclude that landiolol ameliorates the up-regulation of HIF-1α-ET-1 system in minimally morphologically-injured kidney and normalizes biomarkers of renal injury in early hours of endotoxemia of a rat model.

Endotracheal Tube Extubation Force: Adhesive Tape Versus Endotracheal Tube Holder

BACKGROUND: Adhesive tape is commonly used to secure the endotracheal tube (ETT) in anesthesia and intensive-care settings. OBJECTIVE: To determine the force required to extubate when the ETT is secured with adhesive tape or commercially available ETT holders. METHODS: We orally intubated a simulation manikin with a standard 8.0-mm inner-diameter ETT, inflated the cuff to 20 cm H2O, and measured the force required to extubate with the ETT secured in several ways. We tested 3 brands of tape (Durapore, Multipore Dry, and Wardel) with 6 methods, and 2 commercially available ETT holders (LockTite and Thomas) with one method. We also tested a bite block (Universal Bite Block) with 2 methods. We used a releasable cable tie with the bite block and/or ETT holder. We connected the ETT to a digital force gauge and pulled perpendicular to the oral cavity, until the entire cuff was removed from the trachea. In each trial we considered the largest force recorded the extubation force. RESULTS: One of the conventional tape methods (with wider tape and longer tape strips) required the largest force to extubate. CONCLUSIONS: With tape strips of sufficient length and width, a conventional tape method was superior to the 2 tested commercial ETT holders in holding the ETT in place in the manikin.

Nicotine poisoning due to intravenous injection of cigarette soakage

A 27-year-old female nurse intravenously injected 5 mL of cigarette soakage solution that contained approximately 5.7 mg nicotine, in a suicidal attempt. Clinical manifestations consisted of nausea, palpitation, abdominal pain, repeated vomiting, and diarrhea. She remained fully conscious during this episode. About 7 hours later, she visited emergency department on foot and received fluid infusion for dehydration. She fully recovered at night of the day. This is the first documented report of acute nicotine poisoning due to intravenous injection of cigarette soakage in humans. Signs and symptoms appeared immediately after the injection, but this case seemed to be relatively mild in terms of clinical manifestation. The elimination half-life of nicotine seems to be short, that is, less than 1 hour. Therefore, if initial treatment is appropriate and the patient can survive acute phase of nicotine poisoning, prognosis is good.

Influence of Acidosis on Cardiotonic Effects of Colforsin and Epinephrine: A Dose-Response Study

OBJECTIVE Acidosis produces a negative inotropic effect on cardiac muscle against which catecholamines and phosphodiesterase III inhibitors have limited therapeutic effects. This study evaluated the effects of colforsin, which directly activates adenylate cyclase without β-adrenergic receptor activation, in isolated Langendorff rat hearts in a pH- and concentration-dependent manner. DESIGN Experimental animal study. SETTING A university laboratory. PARTICIPANTS Sprague-Dawley rats. INTERVENTIONS Hearts were isolated and perfused with 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid/Tyrode solution (pH 7.4) in the Langendorff preparation. The hearts were assigned randomly to the control (pH 7.4), mild acidosis (pH 7.0), or severe acidosis (pH 6.6) group (n = 8 per group) and were perfused continuously with colforsin 10(-7), 10(-6), and 10(-5) mol/L. MEASUREMENTS AND MAIN RESULTS Maximum dP/dt was determined, and the concentration-response relation was evaluated at each pH. Colforsin at 10(-6) mol/L increased the maximum dP/dt from 2,592 ± 557 to 5,189 ± 721 mmHg/s (p < 0.001) and from 1,942 ± 325 to 3,399 ± 608 mmHg/s (p < 0.001) in the control and mild acidosis groups, respectively; whereas colforsin, 10(-5) mol/L, significantly increased the maximum dP/dt even in the severe acidosis group. No significant difference was seen in maximum dP/dt among the 3 groups after infusion with colforsin 10(-5) mol/L. CONCLUSIONS In contrast to catecholamines and other inodilators, colforsin at a high concentration restores decreased cardiac contractility against severe acidosis to an extent similar to physiologic pH.

Improving the neurological prognosis following OHCA using real-time evaluation of cerebral tissue oxygenation: a case report

Background The neurological prognosis is poor for patients suffering from out‐of‐hospital cardiac arrest (OHCA), in the absence of bystander cardio pulmonary resuscitation (CPR), and showing asystole as the initial waveform. However, such patients have the potential of resuming social activity if cerebral tissue oxygen saturation can be preserved. Case presentation We recently encountered a 60‐year‐old man who had suffered an OHCA in the absence of bystander CPR, and who successfully resumed complete social activity despite initial asystole and requiring at least 75 min of chest compressions before return of spontaneous circulation (ROSC). In this case, chest compression was appropriately performed concurrently with real‐time evaluation of cerebral tissue oxygenation using near‐infrared spectroscopy (NIRS). As a result, the cerebral tissue oxygenation was well maintained, leading to resumption of social activity. Conclusions Improved neurological prognoses can be expected if OHCA patients with the potential for social activity resumption are identified, using NIRS, and effective cardiopulmonary and cerebral resuscitation is performed while visually checking CPR quality.