Doxorubicin induces cardiomyocyte death owing to the accumulation of dysfunctional mitochondria by inhibiting the autophagy fusion process.

Doxorubicin (Dox), an anthracycline antibiotic, is an anticancer drug that inhibits DNA replication and cellular metabolic processes in cancer cells with high proliferative potential. However, Dox causes severe side effects, including myocardial damage and heart failure, but the molecular mechanism underlying Dox-induced myocardial injury remains uncertain. In the present study, we evaluated the effects of Dox on the mitochondrial quality control system and regulation of mitochondrial respiration and autophagy in an in vitro rat myoblast H9c2 cell culture model using western blotting, immunohistochemistry, the Seahorse XF24 system, and flow cytometry. Our results showed that Dox did not impair the initiation of autophagic flux or the functions of lysosomes; however, Dox affected the mitochondrial quality control system, leading to a fission-dominant morphology and impaired regulation of mitochondrial respiration, thereby increasing oxidative stress and inhibited progression of autophagy, particularly the fusion of autophagosomes with lysosomes. This inhibition caused a significant decrease in the formation of autolysosomes and was responsible for the accumulation of dysfunctional mitochondria and subsequent increase in oxidative stress, eventually leading to increased myocardial cell death.

Comparison of Clinical Efficacy and Anatomical Investigation between Retrolaminar Block and Erector Spinae Plane Block.

Retrolaminar block (RLB) and erector spinae plane block (ESPB) are alternative approaches to paravertebral block (PVB) and are advantageous in that they are easier and safer techniques compared with the traditional PVB. Many clinical reports of these blocks have described their efficacy for ipsilateral thoracic analgesia. The local anesthetic injection points of RLB and ESPB are the lamina and transverse process, respectively. Despite the similarity of the puncture sites, there have been no clinical studies comparing RLB and ESPB. In addition, the underlying mechanism of these blocks has not been clarified. Recent anatomical investigations indicated that the injectate was distributed in the paravertebral space and spread laterally into the intercostal spaces. The limited distribution into the paravertebral space indicated that compared to PVB, RLB and ESPB exert their effects via a different mechanism. In this review, we describe the features of and differences between RLB and ESPB based on current clinical and anatomical reports. We also propose the clinical indication and discuss the differences, clinical outcomes, and anatomical mechanisms of the techniques.

Perioperative anesthetic management for cesarean delivery of severe Wilson's disease with liver failure: a case report.

BACKGROUND: Wilson's disease is a rare autosomal recessive disorder affecting copper metabolism, which presents liver and brain dysfunction caused by abnormal copper accumulation. We report a patient who showed exacerbation of liver failure during pregnancy. CASE PRESENTATION: A 24-year-old woman with Wilson's disease was scheduled for emergency cesarean delivery at 30 weeks of gestation. The patient exhibited severe coagulopathy and prominent body weight gain (+ 30 kg) caused by systemic edema and ascites. We decided to perform emergency cesarean delivery under general anesthesia. We used platelet concentrates, cryoprecipitate, and fibrinogen concentrate. Intraoperative hemorrhage was well controlled. On the 15th postpartum day, weight was reduced by 20 kg and liver function had improved. She and her baby were discharged without complications. CONCLUSIONS: The appropriate continued treatment of Wilson's disease and supplementation of coagulation factors and/or platelets when indicated greatly increase the likelihood of a successful pregnancy, even in patients with liver failure exacerbation.

Effects of intraoperative nutrients administration on energy expenditure during general anesthesia.

OBJECTIVES: Recent reports have shown that intraoperative infusions of glucose and amino acids exert anticatabolic effects. The appropriate dosages of these amino acids and glucose during general anesthesia remain unknown. METHODS: Patients who underwent esophagectomy for thoracic esophageal cancer were infused with acetated Ringer's solution that contained glucose and amino acids (B1 group [10 patients]: glucose, 3 g/h; amino acids, 1.2 g/h; B2 group [12 patients]: glucose, 4.5 g/h; amino acids, 1.8 g/h) or did not contain glucose and amino acids (C group, 10 patients). The measured energy expenditure was measured by indirect calorimetry. Nitrogen balance was measured during the anesthesia, and the lengths of the hospital stay were recorded. RESULTS: Resting energy expenditure (B1: 1230 ± 228; B2: 1317 ± 282; C: 1012 ± 153 kcal/h; B2 vs C, P < 0.05) and nitrogen balance (B1: -1.78 ± 0.78 g; B2: -0.85 ± 0.98 g; C: -2.94 ± 2.4 g; B2 vs C, P < 0.05) differed significantly between the B2 and C groups. The lengths of the hospital stay differed between the B2 and C groups (B1: 29 ± 15 d; B2: 18 ± 6 d; C: 37 ± 27 d; B2 vs C, P = 0.06). CONCLUSIONS: The administration of amino acids and glucose increased measured energy expenditure, alleviated nitrogen balance, and may decrease the length of the hospital stay.

[Six Cases of Anesthetic Management of Adult Patients Undergoing Coarctation of Aorta Repair].

BACKGROUND: In Japan, every year more than 9,000 patients with congenital heart disease reach adulthood due to improved medical treatments. Adult coarctation of aorta (CoA) patient is likely to need surgery for re- CoA, progressive CoA and/or aortic aneurysm. There- fore, it is necessary to consider anesthetic management of complicated aortic surgery of CoA patient Methods: This is a retrospective study of six pa- tients with CoA who underwent the CoA repair sur- gery in adulthood from 2005 to 2013. RESULTS: Pre-operative CoA diameter was 7.8?2.5 mm and pressure gradient was 37±13 mmHg. Four patients had aortic aneurysm. Three patients received lateral thoracotomy and one-lung ventilation; five patients underwent selective cerebral perfusion. As perioperative complications, all two patients with re-CoA surgery had pneumothorax; two of five patients with arch repair surgery had recurrent nerve paralysis; a patient with left subclavian artery ischemia/reperfu- sion, and elevation and flexion of left upper extremity position had left upper extremity paralysis. CONCLUSIONS: In anesthetic management of adult CoA repair, it is important to understand various surgical approach and corresponding ventilation and extracorporeal circulation methods and possible complications.

Comparison of the effects of long-term pimobendan and benazepril administration in normal cats.

Pimobendan (PIMO) can cause adverse effects, such as mitral valve degeneration, in dogs; however, it is unclear whether these effects occur in cats. Therefore, we aimed to determine whether PIMO or benazepril produces adverse cardiac effects in healthy cats. This was a blinded, randomized, prospective parallel study. Twelve cats were randomly divided into two groups of six cats, namely, an angiotensin-converting-enzyme inhibitor group that received benazepril and a PIMO group. Cats were administered their respective treatments for 506 days, and we evaluated cardiac parameters, blood biochemistry and glomerular filtration rates during that time. At the end of the trial, the cats were euthanized, and histopathological examinations were performed by a pathologist who was blinded to the treatment groups. No significant changes were observed in any of the parameters measured in either of the groups. In particular, no significant cardiac lesions were observed in either of the groups. In healthy cats, neither PIMO nor benazepril appears to cause cardiac lesions, but future studies are needed to examine the effects of PIMO in cats with heart disease.

Predictive model for the detection of pulmonary hypertension in dogs with myxomatous mitral valve disease.

Pulmonary hypertension (PH) often occurs due to a left heart disease, such as myxomatous mitral valve disease (MMVD), in dogs and is diagnosed using Doppler echocardiography and estimated pulmonary arterial pressure. Diagnosis of PH in dogs requires expertise in echocardiography: however, the examination for PH is difficult to perform in a clinical setting. Thus, simple and reliable methods are required for the diagnosis of PH in dogs. The purpose of this study was to develop models using multiple logistic regression analysis to detect PH due to left heart disease in dogs with MMVD without echocardiography. The medical records of dogs with MMVD were retrospectively reviewed, and 81 dogs were included in this study and classified into PH and non-PH groups. Bivariate analysis was performed to compare all parameters between the groups, and variables with P values of <0.25 in bivariate analysis were included in multiple logistic regression analysis to develop models for the detection of PH. In multiple logistic regression analysis, the model included a vertebral heart scale short axis of >5.2 v, and a length of sternal contact of >3.3 v was considered suitable for the detection of PH. The predictive accuracy of this model (85.9%) was judged statistically adequate, and therefore, this model may be useful to screen for PH due to left heart disease in dogs with MMVD without echocardiography.

The diagnostic significance of the plasma N-terminal pro-B-type natriuretic Peptide concentration in asymptomatic cats with cardiac enlargement.

We evaluated the diagnostic significance of the N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration in asymptomatic cats with cardiac enlargement. The plasma NT-proBNP concentration was measured in 21 clinically healthy control cats, and 67 asymptomatic cats with cardiac enlargement defined as end-diastolic interventricular septum thickness (IVSd) and/or diastolic left ventricular posterior wall thickness (LVPWd) >0.6 cm, vertebla heart scale (VHS) >7.8, and/or left atria/aorta ratio (LA/Ao) >1.5. The plasma NT-proBNP concentration in the asymptomatic cats with cardiac enlargement (median: 662.0, range: 24.0-2,449.0 pmol/l) was significantly higher than that in the controls (24.0, 24.0-95.0 pmol/l, P<0.001). The plasma NT-proBNP concentration was significantly correlated with the VHS, LA/Ao, IVSd and LVPWd (r=0.578, P<0.001; r=0.462, P<0.001; r=0.563, P<0.001; and r=0.764, P<0.001, respectively). Receiver operating characteristic analysis showed a cut-off value of 95.0 pmol/l for the detection of asymptomatic cats with cardiac enlargement, sensitivity and specificity of 88.1 and 100%, respectively, and an area under the curve of 0.971. These results suggest that the determination of the plasma NT-proBNP concentration can be a useful screening test for asymptomatic cats with cardiac enlargement.

Development of correction formulas for canine and feline urine specific gravity measured using a Japanese refractometer.

One of the most important functions of the kidney is to concentrate urine through the reabsorption of water. Urine specific gravity (USG) is used in routine tests of urine concentration and can be estimated using a refractometer. However, as the scale of Japanese refractometer is based on experimental data from healthy Japanese people, and human USG obtained by Japanese refractometers show higher values than that by refractometer produced in Europe or the U.S.A. The purpose of this study was to establish correction formulas for the USG of dogs and cats measured using Japanese refractometers. In this study, we found that Japanese refractometers overestimated USG in both dogs and cats. This study shows that the correlation formulas described in this study are useful for the accurate evaluation of USG.

Evaluation of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations in dogs with mitral valve insufficiency.

The diagnostic significance of the plasma concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP) was evaluated in 72 dogs with mitral valve insufficiency and 36 control dogs. In the controls, the plasma NT-proBNP concentration was 163.9 +/- 114.7 (SD) pmol/l. The values in those with International Small Animal Cardiac Health Council (ISACHC) functional classification of heart failure class Ia, Ib, II and IIIa mitral valve insufficiency were 302.8 +/- 257.1 (n=21), 634.2 +/- 642.5 (n=23), 1,277.9 +/- 756.2 (n=18) and 1,908.9 +/- 538.8 (n=10) pmol/l, respectively; those in the class Ib or severer groups were significantly higher than that in the controls. In dogs in which the intensity of cardiac murmurs was Levine 3, 4, 5 and 6, plasma NT-proBNP concentrations were 647.6 +/- 577.3 (n=27), 1,184.7 +/- 841.0 (n=18), 1,532.4 +/- 784.2 (n=10) and 1,461.8 +/- 932.2 (n=4) pmol/l, respectively, and were significantly higher than that in the controls. The plasma NT-proBNP concentration was significantly correlated with the cardiac size (VHS) and LA/Ao (r=0.611, n=89, p<0.01; and r=0.705, n=91, p<0.01, respectively). When dogs with ISACHC class II or IIIa were regarded as heart failure, the cut-off value was 713.5 pmol/l, and the sensitivity and specificity were 0.913 and 0.857, respectively. These findings could indicate that plasma NT-proBNP concentration was significantly associated with the severity of heart failure due to mitral valve insufficiency in dogs. Further investigation is required to determine factors other than heart failure affecting plasma NT-proBNP concentration.

[Pharmacodynamics and pharmacokinetics of remifentanil: overview and comparison with other opioids].

In this review, the authors tried to summarize the characteristics and main differences of remifentanil with other opioids, and to overview its pharmacodynamics and pharmacokinetics. Clearance and volume of distribution of remifentnail are extremely different from other conventional opioids. In addition, the context-sensitive half time of remifentanil is almost stable (about 3 minutes) even if the continuous infusion of remifentanil lasts for longer than 10 hours. As remifentanil is metabolized by a non-specific esterase, excretion of remifentnil is predictable in basically all patients undergoing general anesthesia and surgery. Therefore, remifentanil is considered to be an optimal opioid as an analgesic combined either with inhalational anesthetics or intravenous hypnotics in balanced general anesthesia.

[Anesthetic management in two infants undergoing hemilaminectomy for giant mediastinal neuroblastoma].

We report the anesthetic management in two infants who were a three-month-old boy (case 1) and a two- month-old girl (case 2), undergoing hemilaminectomy for giant mediastinal neuroblastoma. Neuroblastoma invades into the intrathecal space in a rare occasion, resulting in paraplegia, which requires emergent operation to save the spinal cord. Mediastinal neuroblastoma also possesses significant respiratory and cardiovascular risks due to the close anatomic relationship with vital organs. In the present report, we show that preoperative computed tomography (CT) scan and/or echocardiography revealed tracheal deviation in case 1 and mass compression of the left atrium in case 2. Therefore, the patients with mediastinal masses should be carefully evaluated before subjecting them to anesthesia. Especially, there is a possibility that the masses which do not appear to compress the airway and cardiovascular systems develop the airway obstruction and cardiovascular collapse after induction of general anesthesia. In fact, before induction of general anesthesia in the case 2, trial of the prone positioning which was scheduled for the hemilaminectomy, resulted in bradycardia and hypotension, presumably due to the compression of the left atrium. In summary, the authors here discussed the preoperative evaluation and anesthetic management for giant mediastinal neuroblastoma in infants.

Isolation of nitrophenols from diesel exhaust particles (DEP) as vasodilatation compounds.

The compounds in diesel exhaust particles (DEP) that are responsible for vasodilatation were isolated and characterized for the first time. From benzene extract of DEP, 2-methyl-4-nitrophenol, 3-methyl-4-nitrophenl and 4-nitrophenol were isolated, and their vasodilatation activities were confirmed. 3-methyl-4-nitrophenol caused dilatation of rat thoracic artery, and the other two nitrophenols, also showed vasodilatation activities.