Histone modification of pain-related gene expression in spinal cord neurons under a persistent postsurgical pain-like state by electrocautery.

Chronic postsurgical pain (CPSP) is a serious problem. We developed a mouse model of CPSP induced by electrocautery and examined the mechanism of CPSP. In this mouse model, while both incision and electrocautery each produced acute allodynia, persistent allodynia was only observed after electrocautery. Under these conditions, we found that the mRNA levels of Small proline rich protein 1A (Sprr1a) and Annexin A10 (Anxa10), which are the key modulators of neuropathic pain, in the spinal cord were more potently and persistently increased by electrocautery than by incision. Furthermore, these genes were overexpressed almost exclusively in chronic postsurgical pain-activated neurons. This event was associated with decreased levels of tri-methylated histone H3 at Lys27 and increased levels of acetylated histone H3 at Lys27 at their promoter regions. On the other hand, persistent allodynia and overexpression of Sprr1a and Anxa10 after electrocautery were dramatically suppressed by systemic administration of GSK-J4, which is a selective H3K27 demethylase inhibitor. These results suggest that the effects of electrocautery contribute to CPSP along with synaptic plasticity and epigenetic modification.

Perioperative management of patients with atrial fibrillation receiving anticoagulant therapy.

The number of patients with atrial fibrillation (AF) and the number of patients indicated for anticoagulant therapy have been increasing because AF would affect patient survival due to thromboembolism. Once AF develops, following the disappearance of pulsation, the circumstances within the atrium become prothrombotic and thrombus formation within the left atrium occurs in patients with AF. In recent years, not only warfarin but also new oral anticoagulants were introduced clinically and have become used as oral anticoagulants. In the perioperative period, the risk of major hemorrhage needs to be reduced. On the other hand, the suspension of anticoagulant therapy and neutralization of anticoagulant effects elevate the risk of thrombosis. The perioperative management of patients receiving anticoagulant therapy is different from that of scheduled surgery and emergency surgery. In addition, knowledge of the characteristics of each oral anticoagulant is required at drug cessation and resumption. Unlike warfarin, which has been used in the past five decades, direct oral anticoagulants (DOACs) do not have sensitive indicators such as prothrombin time-international normalized ratio. To avoid major hemorrhages and thromboembolism, quantitative assays can be implemented for DOAC monitoring and for reversal therapies in perioperative settings.

Fixation of intracapsular fracture of the femoral neck using combined peripheral nerve blocks and transthoracic echocardiography in a patient with severe obstructive hypertrophic cardiomyopathy: a case report.

BACKGROUND: Hypertrophic obstructive cardiomyopathy (HOCM) is a type of hypertrophic cardiomyopathy associated with left ventricular outflow tract stenosis. The increased pressure gradients across the left ventricular outflow tract in patients with HOCM could lead to circulatory collapse. We describe our experience with perioperative management under femoral nerve block (FNB), lateral femoral cutaneous nerve block (LFCNB), and transthoracic echocardiography (TTE) monitoring during open reduction and internal fixation of a femoral neck fracture in a patient with severe HOCM. CASE PRESENTATION: A 72-year-old man, who was indicated to undergo open reduction and internal fixation of an intracapsular femoral neck fracture, had a history of treatment for hypertension and HOCM. He had heart failure for 4 years and was hospitalized several times. He was resuscitated after ventricular fibrillation and received an implantable cardioverter-defibrillator at that time. He also had severe physical limitations (New York Heart Association class III). We selected FNB and LFCNB as the methods for anesthesia and injected 0.25% levobupivacaine (20 mL) around the femoral nerve and 0.25% levobupivacaine (10 mL) into the lateral femoral nerve region. He underwent TTE during the perioperative period, which enabled us to perform hemodynamic and morphological evaluations of the heart. The intraoperative TTE findings remained stable from before the induction of anesthesia to the patient's exit from the operating room. Postoperatively, his hemodynamic parameters continued to remain stable. CONCLUSIONS: In this case, FNB and LFCNB contributed to hemodynamic stability during non-cardiac surgery. Additionally, TTE was useful for the perioperative evaluation of cardiac hemodynamics and morphology in our patient with severe HOCM.

Angiogenesis and vasculogenesis are impaired in the precocious-aging klotho mouse.

BACKGROUND: The effects of aging on angiogenesis (vascular sprouting) and vasculogenesis (endothelial precursor cell [EPC] incorporation into vessels) are not well known. We examined whether ischemia-induced angiogenesis/vasculogenesis is altered in klotho (kl) mutant mice, an animal model of typical aging. METHODS AND RESULTS: After unilateral hindlimb ischemia, laser Doppler blood-flow (LDBF) analysis revealed a decreased ischemic-normal LDBF ratio in kl mice. Tissue capillary density was also suppressed in kl mice (+/+>+/kl>kl/kl). Aortic-ring culture assay showed impaired angiogenesis in kl/kl mice, accompanied by reduced endothelium-derived nitric oxide release. Moreover, the rate of transplanted homologous bone marrow cells incorporated into capillaries in ischemic tissues (vasculogenesis) was lower in kl/kl mice than in wild-type (+/+) mice, which was associated with a decrease in the number of c-Kit+CD31+ EPC-like mononuclear cells in bone marrow and in peripheral blood. Finally, the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor cerivastatin restored the impaired neovascularization in kl/kl mice, accompanied by an increase in c-Kit+CD31+ cells in bone marrow and peripheral blood, and enhanced angiogenesis in the aortic-ring culture. CONCLUSIONS: Angiogenesis and vasculogenesis are impaired in kl mutant mice, a model of typical aging. Moreover, the age-associated impairment of neovascularization might be a new target of statin therapy.