Keisuke Kohama

Hydrogen inhalation protects against acute lung injury induced by hemorrhagic shock and resuscitation

INTRODUCTION Hemorrhagic shock followed by fluid resuscitation (HS/R) triggers an inflammatory response and causes pulmonary inflammation that can lead to acute lung injury (ALI). Hydrogen, a therapeutic gas, has potent cytoprotective, antiinflammatory, and antioxidant effects. This study examined the effects of inhaled hydrogen on ALI caused by HS/R. METHODS Rats were subjected to hemorrhagic shock by withdrawing blood to lower blood pressure followed by resuscitation with shed blood and saline to restore blood pressure. After HS/R, the rats were maintained in a control gas of similar composition to room air or exposed to 1.3% hydrogen. RESULTS HS/R induced ALI, as demonstrated by significantly impaired gas exchange, congestion, edema, cellular infiltration, and hemorrhage in the lungs. Hydrogen inhalation mitigated lung injury after HS/R, as indicated by significantly improved gas exchange and reduced cellular infiltration and hemorrhage. Hydrogen inhalation did not affect hemodynamic status during HS/R. Exposure to 1.3% hydrogen significantly attenuated the upregulation of the messenger RNAs for several proinflammatory mediators induced by HS/R. Lipid peroxidation was reduced significantly in the presence of hydrogen, indicating antioxidant effects. CONCLUSION Hydrogen, administered through inhalation, may exert potent therapeutic effects against ALI induced by HS/R and attenuate the activation of inflammatory cascades.

Can carbon monoxide-poisoned victims be organ donors?

The increasing demand for organ allografts to treat end-stage organ failure has driven changes in traditional donor criteria. Patients who have succumbed to carbon monoxide (CO) poisoning, a common cause of toxicological mortality, are usually rejected as organ donors. To fulfill the increasing demand, selection criteria must be expanded to include CO-poisoned donors. However, the use of allografts exposed to high CO concentrations is still under debate. Basic research and literature review data suggest that patients with brain death caused by CO poisoning should be considered appropriate organ donors. Accepting organs from CO-poisoned victims could increase the number of potential donors and lower the death rate of patients on the waiting lists. This review and reported cases may increase awareness among emergency department physicians, as well as transplant teams, that patients dying of CO exposure may be acceptable organ donors.

Supplementation of parenteral nutrition with fish oil attenuates acute lung injury in a rat model

Fish oil rich in n-3 polyunsaturated fatty acids has diverse immunomodulatory properties and attenuates acute lung injury when administered in enternal nutrition. However, enteral nutrition is not always feasible. Therefore, we investigated the ability of parenteral nutrition supplemented with fish oil to ameliorate acute lung injury. Rats were infused with parenteral nutrition solutions (without lipids, with soybean oil, or with soybean oil and fish oil) for three days. Lipopolysaccharide (15 mg/kg) was then administered intratracheally to induce acute lung injury, characterized by impaired lung function, polymorphonuclear leukocyte recruitment, parenchymal tissue damage, and upregulation of mRNAs for inflammatory mediators. Administration of parenteral nutrition supplemented with fish oil prior to lung insult improved gas exchange and inhibited neutrophil recruitment and upregulation of mRNAs for inflammatory mediators. Parenteral nutrition supplemented with fish oil also prolonged survival. To investigate the underlying mechanisms, leukotriene B4 and leukotriene B5 secretion was measured in neutrophils from the peritoneal cavity. The neutrophils from rats treated with fish oil-rich parenteral nutrition released significantly more leukotriene B5, an anti-inflammatory eicosanoid, than neutrophils isolated from rats given standard parenteral nutrition. Parenteral nutrition with fish oil significantly reduced lipopolysaccharide-induced lung injury in rats in part by promoting the synthesis of anti-inflammatory eicosanoids.

Application of carbon monoxide for treatment of acute kidney injury

Acute kidney injury in critically ill patients is common and associated with a substantial increase in morbidity and mortality. Even with aggressive medical care and renal replacement therapy, acute kidney injury remains a significant health care concern. Recent published reports offer new strategies for the prevention and amelioration of acute kidney injury using carbon monoxide. Although considered a toxic environmental gas, carbon monoxide has recently aroused scientific and clinical interest, as its beneficial effects and mechanisms of action have been substantially defined in various in vitro and in vivo experiments. The exogenous application of carbon monoxide can confer cytoprotection by modulating intracellular signaling pathways through its anti‐inflammatory, anti‐apoptotic, vasodilative, antithrombotic and antiproliferative properties. Thus, evidence is accumulating to support the notion of carbon monoxide treatment for acute kidney disease. In this review, we focus on the extensively analyzed advantageous value of treatment with inhaled/soluble carbon monoxide in the context of kidney injury. Mechanisms such as signaling pathways, as well as an expanded view regarding toxicity and side‐effects, are described broadly. In addition, we discuss the clinical applicability of carbon monoxide as a promising therapeutic strategy for the treatment of patients with acute kidney disease based on translating basic experimental findings into clinical application.

Donor pretreatment with carbon monoxide prevents ischemia/reperfusion injury following heart transplantation in rats

Because inhaled carbon monoxide (CO) provides potent anti-inflammatory and antioxidant effects against ischemia reperfusion injury, we hypothesized that treatment of organ donors with inhaled CO would decrease graft injury after heart transplantation. Hearts were heterotopically transplanted into syngeneic Lewis rats after 8 hours of cold preservation in University of Wisconsin solution. Donor rats were exposed to CO at a concentration of 250 parts per million for 24 hours via a gas-exposure chamber. Severity of myocardial injury was determined by total serum creatine phosphokinase and troponin I levels at three hours after reperfusion. In addition, Affymetrix gene array analysis of mRNA transcripts was performed on the heart graft tissue prior to implantation. Recipients of grafts from CO-exposed donors had lower levels of serum troponin I and creatine phosphokinase; less upregulation of mRNA for interleukin-6, intercellular adhesion molecule-1, and tumor necrosis factor-α; and fewer infiltrating cells. Although donor pretreatment with CO altered the expression of 49 genes expressly represented on the array, we could not obtain meaningful data to explain the mechanisms by which CO potentiated the protective effects.Pretreatment with CO gas before organ procurement effectively protected cardiac grafts from ischemia reperfusion-induced injury in a rat heterotopic cardiac transplant model. A clinical report review indicated that CO-poisoned organ donors may be comparable to non-poisoned donors.

Hemorrhagic shock due to ruptured left and right gastric artery aneurysm

We report a case of hemorrhagic shock due to a ruptured gastric artery aneurysm successfully treated with transarterial embolization. A 72‐year‐old woman with cholangitis presented with hemoperitoneum following a ruptured aneurysm of the gastric artery.

Inhaled hydrogen ameliorates endotoxin-induced bowel dysfunction

Gastrointestinal dysmotility frequently occurs during sepsis and multiple organ failure, remaining a major cause of morbidity and mortality in critically ill patients. Previous studies have shown that hydrogen, a new therapeutic gas, can improve various organ damage associated with sepsis. In this study, we investigated the protective efficacies of inhaled hydrogen against lipopolysaccharide (LPS)‐induced ileus.

Successfully treated life-threatening upper gastrointestinal bleeding from fistula between gastroduodenal artery pseudoaneurysm and duodenum

An 85‐year‐old man was admitted to the hospital, underwent laparotomy, and was diagnosed with diffuse peritonitis due to perforation of gastric ulcer. Omental patch repair was carried out. After surgery, he suddenly vomited blood and manifested hypovolemic shock. An emergency upper gastrointestinal endoscopy was carried out immediately. However, the bleeding source was not visible. Dynamic‐enhanced abdominal computed tomography showed a pseudoaneurysm of the gastroduodenal artery‐communicating duodenal lumen with extravasation. Next, the patient underwent angiography for embolization. However, selective arterial embolization was not successful.

Duodenal perforation due to infection caused by pledget 29 months after blunt liver injury suture

Dear Editor, In liver trauma care, operative management is still necessary for hemodynamically unstable patients. Although liver suture using pledgets is considered a standard procedure, complications related to pledgets have not yet been described. Here, we present a case in which pledgets used for an operation in blunt liver injury caused delayed perihepatic abscess infection, leading to gastrointestinal perforation. A 34-year-old woman was referred to our emergency department after falling from the fifth floor of a building. As the patient’s hemodynamics were unstable, we decided to perform surgery and transferred her to the operating room. A median laparotomy revealed a laceration of segments V, VII, and VIII, and the falciform ligament of the liver. We performed gauze packing as a damage control surgery, and open abdominal management was selected. The second generation cephalosporin antibiotic cefmetazole (Daiichi Sankyo, Tokyo, Japan) was given prophylactically. A second operation was carried out 48 h after the first, which involved removal of packing gauze and additional sutures with a pledget on the oozing point of the liver. We confirmed complete hemostasis and washed the abdominal cavity, and then closed the wall. The patient was discharged on day 74 with a remaining fistula and abscess and she received follow-up care as an outpatient. During follow-up, food residue outflow from the fistula was seen 27 months after initial surgery. Abdominal computed tomography showed a perihepatic abscess containing foreign matter, which was most likely a floating pledget that was used for liver suture (Fig. 1). Fistulography showed traffic with a fistula and the duodenum. The diagnosis was perihepatic abscess and duodenal perforation secondary to infection caused by a felt pledget. The patient had surgery to remove the pledget 29 months after the injury, for abscess infection control. The fistula was closed and the patient shortly resumed her normal life. It is important to choose a surgical strategy that does not involve using the device or removing the device early. However, in trauma surgery, the best strategy should be followed, depending on the situation. The surgeon can use one or more of the following hemostatic maneuvers for severe parenchymal injury: packing, direct suture, finger fracture, omental packing, fibrin sealants, hemostatic devices, and resection. Application of double sutures or wall reinforcement with felt strips are widely used methods to prevent laceration of the liver parenchyma by suture. Procedures using absorbable, minimal foreign sheets instead of pledgets may be possible, but cases in which bleeding is stanched solely with such sheets have been reported only in animal experiments. Although liver suture with felt pledgets is an effective approach for liver trauma, trauma surgeons should keep in mind the possibility of secondary infection to foreign body, even over a long-term period. At this stage, there are no alternatives to pledgets. It is important to find replacements that could avoid complications such as those described here. Our case may be helpful to describe to trauma surgeons the surgical technique and the pledget material, as well as indications for pledget utilization.