Role of protein kinase D1 in vasoconstriction and haemodynamics in rats.

AIMS: Protein kinase D (PKD), once considered an effector of protein kinase C (PKC), now plays many pathophysiological roles in various tissues. However, little is known about role of PKD in vascular function. We investigated the role of PKD in contraction of rat aorta and human aortic smooth muscle cells (HASMCs) and in haemodynamics in rats. METHODS AND RESULTS: Isometric tension of rat aortic was measured to examine norepinephrine-induced contraction in the presence of PKD, PKC and Rho-kinase inhibitors. Phosphorylation of PKD1, myosin targeting subunit-1 (MYPT1), myosin light chain (MLC), CPI-17 and heat-shock protein 27 (HSP27), and actin polymerization were measured in the aorta. Phosphorylation of MYPT1 and MLC was also measured in HASMCs knocked down with specific siRNAs of PKD 1, 2 and 3. Intracellular calcium concentrations and cell shortening were measured in HASMCs. Norepinephrine-induced aortic contraction was accompanied by increased phosphorylation of PKD1, MYPT1 and MLC and actin polymerization, all of which were attenuated with PKD inhibitor CRT0066101. PKD1 phosphorylation was not inhibited by PKC inhibitor, chelerythrine or Rho kinase inhibitor, fasudil. In HASMCs, the phosphorylation of MYPT1 and MLC was attenuated by PKD1, but not PKD2, 3 knockdown. In HASMCs, CRT0066101 inhibited norepinephrine-induced cell shortening without affecting calcium concentration. Administration of CRT0066101 decreased systemic vascular resistance and blood pressure without affecting cardiac output in rats. CONCLUSIONS: PKD1 may play roles in aorta contraction and haemodynamics via phosphorylation of MYPT1 and actin polymerization in a calcium-independent manner.

Ultrasound-Guided Placement of a Hemodialysis Catheter into the Distal Femoral Vein in a Patient with Multiple Catheters: A Case Report.

Cardiac surgery-associated acute kidney injury may require postoperative renal replacement therapy. Although the right internal jugular vein and femoral veins are generally the preferred insertion sites for the hemodialysis catheter for continuous renal replacement therapy, the presence of other indwelling catheters or prior thrombotic events from previous catheters may preclude use of these sites. We present a case in which the hemodialysis catheter was inserted into the distal femoral vein using point-of-care ultrasound in a patient with multiple catheter insertions after coronary artery bypass grafting. Although the tip of the dialysis catheter was more distal than the classic femoral approach, renal replacement therapy was performed without problems. Moreover, it was easier for the nurses to keep the insertion site clean and to change the patient's position.

Anesthetic Care During Tracheostomy in a Patient with Generalized Tetanus: A Case Report.

Tetanus is a potentially fatal infectious disease caused by the toxins produced by the anaerobic bacterium, Clostridium tetani. Of major concern during the perioperative care of these patients is control of muscle spasms, skeletal rigidity, and autonomic dysfunction. Several of the modern sedative and opioid agents including remifentanil have not been fully evaluated in managing tetanus. We present the intraoperative use of remifentanil in a 75-year-old woman with generalized tetanus who required anesthetic care during placement of a tracheostomy. The end-organ involvement of tetanus is presented, previous reports of anesthetic care reviewed, and the potential utility of remifentanil explored.

Combined Spinal-Epidural Anesthesia for Subtotal Colectomy in a Patient With Hamman Syndrome and Epidural Pneumatosis: A Case Report.

It remains unclear how epidural pneumatosis affects the efficacy of neuraxial anesthesia. Spontaneous pneumomediastinum (Hamman syndrome) with epidural pneumatosis is rare. Regardless of its etiology, general anesthesia with positive pressure ventilation in patients with pneumomediastinum carries the risk of pneumothorax. We present a 19-year-old patient with Hamman syndrome and epidural pneumatosis who required emergency laparotomy. Effective analgesia was obtained using neuraxial anesthesia with a combined spinal-epidural anesthesia technique.

The U-shaped association of serum iron level with disease severity in adult hospitalized patients with COVID-19.

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that leads to severe respiratory failure (RF). It is known that host exposure to viral infection triggers an iron-lowering response to mitigate pathogenic load and tissue damage. However, the association between host iron-lowering response and COVID-19 severity is not clear. This two-center observational study of 136 adult hospitalized COVID-19 patients analyzed the association between disease severity and initial serum iron, total iron-binding capacity (TIBC), and transferrin saturation (TSAT) levels. Serum iron levels were significantly lower in patients with mild RF than in the non-RF group; however, there were no significant differences in iron levels between the non-RF and severe RF groups, depicting a U-shaped association between serum iron levels and disease severity. TIBC levels decreased significantly with increasing severity; consequently, TSAT was significantly higher in patients with severe RF than in other patients. Multivariate analysis including only patients with RF adjusted for age and sex demonstrated that higher serum iron and TSAT levels were independently associated with the development of severe RF, indicating that inadequate response to lower serum iron might be an exacerbating factor for COVID-19.

A question is "what are the optimal targets for anticoagulant therapies?"

A high mortality rate is found among septic patients with disseminated intravascular coagulation (DIC). Anticoagulants have been used for treating septic DIC especially in Japanese clinical settings; however, their effectiveness is quite controversial across studies. According to several randomized controlled trials and meta-analyses, antithrombin and recombinant thrombomodulin had no therapeutic benefit in the treatment of sepsis. However, the majority of the previous research did not discuss "septic DIC" but simply "sepsis", and some reviews showed that anticoagulants were benefit only in septic DIC. Although immunothrombosis plays an important role in early host defense, it can lead to DIC and organ failure if dysregulated. Therefore, we advocate anticoagulant therapies might have beneficial effects, but research on optimal patient selection is currently lacking.

Effects of vasopressin during a pulmonary hypertensive crisis induced by acute hypoxia in a rat model of pulmonary hypertension.

BACKGROUND: A pulmonary hypertensive crisis (PHC) can be a life-threatening condition. We established a PHC model by exposing rats with monocrotaline (MCT)-induced pulmonary hypertension to acute hypoxia, and investigated the effects of vasopressin, phenylephrine, and norepinephrine on the PHC. METHODS: Four weeks after MCT 60 mg kg-1 administration i.v., right ventricular systolic pressure (RVSP), systolic BP (SBP), mean BP (MBP), cardiac index (CI), and pulmonary vascular resistance index (PVRI) were measured. PHC defined as an RVSP exceeding or equal to SBP was induced by changing the fraction of inspiratory oxygen to 0.1. Rats were subsequently treated by vasopressin, phenylephrine, or norepinephrine, followed by assessment of systemic haemodynamics, isometric tension of femoral and pulmonary arteries, cardiac function, blood gas composition, and survival. RESULTS: PHC was associated with increased RV dilatation and paradoxical septal motion. Vasopressin increased MBP [mean (standard error)] from 52.6 (3.8) to 125.0 (8.9) mm Hg and CI from 25.4 (2.3) to 40.6 (1.8) ml min-1 100 g-1 while decreasing PVRI. Vasopressin also improved RV dilatation, oxygenation, and survival in PHC. In contrast, phenylephrine increased MBP from 54.8 (2.3) to 96.8 (3.2) mm Hg without improving cardiac pump function. Norepinephrine did not alter MBP. Vasopressin contracted femoral but not pulmonary arteries, whereas phenylephrine contracted both arterial beds. Hence, improvements with vasopressin in PHC might be associated with decreased PVRI and selective systemic vasoconstriction. CONCLUSIONS: In this rat model of a PHC, vasopressin, but not phenylephrine or norepinephrine, resulted in better haemodynamic and vascular recovery.

Comparison between High- and Low-Cost Transmission of Tele-Anesthesia in Japan.

Background: We previously reported a tele-anesthesia system that connected Sado General Hospital (SGH) to Yokohama City University Hospital (YCUH) using a dedicated virtual private network (VPN) that guaranteed the quality of service. The study indicated certain unresolved problems, such as the high cost of constantly using a dedicated VPN for tele-anesthesia. In this study, we assessed whether use of a best-effort system affects the safety and cost of tele-anesthesia in a clinical setting. Methods: One hundred patients were enrolled in this study. We provided tele-anesthesia for 65 patients using a guaranteed transmission system (20 Mbit/s; guaranteed, 372,000 JPY per month: 1 JPY = US$0.01) and for 35 patients using a best-effort system (100 Mbit/s; not guaranteed, 25,000 JPY per month). We measured transmission speed and number of commands completed from YCUH to SGH during tele-anesthesia with both transmission systems. Results: In the guaranteed system, anesthesia duration was 5780 min (88.9 min/case) and surgical duration was 3513 min (54.0 min/case). In the best-effort system, anesthesia duration was 3725 min (106.4 min/case) and surgical duration was 2105 min (60.1 min/case). The average transmission speed in the best-effort system was 17.3 ± 3.8 Mbit/s. The system provided an acceptable delay time and frame rate in clinical use. All commands were completed, and no adverse events occurred with both systems. Discussion: In the field of tele-anesthesia, using a best-effort internet VPN system provided equivalent safety and efficacy at a better price as compared to using a guaranteed internet VPN system.