Periprocedural hypotension after conscious sedation versus local anesthesia during defibrillator implantation for left ventricular dysfunction: analysis of a national inpatient database in Japan.

The association between periprocedural hypotension and conscious sedation (CS) during defibrillator implantation remains to be elucidated. The aim of the present study was to compare the occurrence of periprocedural hypotension after CS or local anesthesia (LA) during defibrillator implantation in a retrospective cohort study using a national inpatient database. Using the Japanese Diagnosis Procedure Combination database, we retrospectively collected data for adult inpatients who underwent implantation of a cardioverter defibrillator or cardiac resynchronization therapy device from July 2010 to March 2016. Multivariable logistic regression analyses were performed to compare the occurrence of periprocedural hypotension between the CS and LA groups with adjustment for patient background characteristics and hospital factors. Additional analysis was performed after dividing the CS group into each specific anesthetic use. We identified 4842 patients, comprising 1533 patients with CS and 3309 with LA. The CS group had a significantly higher proportion of periprocedural hypotension than the LA group (13.4% versus 9.7%; adjusted odds ratio, 1.56; 95% confidence interval, 1.19-2.04; p = 0.001). Body mass index < 18.5 kg/m2, New York Heart Association Class IV, and use of cardiac resynchronization therapy device were independently associated with occurrence of periprocedural hypotension. Additionally, ketamine and dexmedetomidine were significantly associated with higher incidence of hypotension than the LA group (adjusted odds ratio, 2.64; 95% confidence interval, 1.32-5.26; p = 0.006; adjusted odds ratio, 1.86; 95% confidence interval, 1.11-3.12; p = 0.019, respectively). Periprocedural hypotension was significantly more likely to occur in the CS group than the LA group, and was associated with CS.

Nitric oxide production contributes to Bacillus anthracis edema toxin-associated arterial hypotension and lethality: ex vivo and in vivo studies in the rat.

We showed previously that Bacillus anthracis edema toxin (ET), comprised of protective antigen (PA) and edema factor (EF), inhibits phenylephrine (PE)-induced contraction in rat aortic rings and these effects are diminished in endothelial-denuded rings. Therefore, employing rat aortic ring and in vivo models, we tested the hypothesis that nitric oxide (NO) contributes to ET's arterial effects. Compared with rings challenged with PA alone, ET (PA + EF) reduced PE-stimulated maximal contractile force (MCF) and increased the PE concentration producing 50% MCF (EC50) (P < 0.0001). Compared with placebo, l-nitro-arginine methyl-ester (l-NAME), an NO synthase (NOS) inhibitor, reduced ET's effects on MCF and EC50 in patterns that approached or were significant (P = 0.06 and 0.03, respectively). In animals challenged with 24-h ET infusions, l-NAME (0.5 or 1.0 mg·kg(-1)·h(-1)) coadministration increased survival to 17 of 28 animals (60.7%) compared with 4 of 27 (14.8%) given placebo (P = 0.01). Animals receiving l-NAME but no ET all survived. Compared with PBS challenge, ET increased NO levels at 24 h and l-NAME decreased these increases (P < 0.0001). ET infusion decreased mean arterial blood pressure (MAP) in placebo and l-NAME-treated animals (P < 0.0001) but l-NAME reduced decreases in MAP with ET from 9 to 24 h (P = 0.03 for the time interaction). S-methyl-l-thiocitrulline, a selective neuronal NOS inhibitor, had effects in rings and, at a high dose in vivo models, comparable to l-NAME, whereas N'-[3-(aminomethyl)benzyl]-acetimidamide, a selective inducible NOS inhibitor, did not. NO production contributes to ET's arterial relaxant, hypotensive, and lethal effects in the rat.

Maternal hypotension during fetoscopic surgery: incidence and its impact on fetal survival outcomes.

In this retrospective cohort study, we aimed to determine the incidence of intraoperative maternal hypotension during fetoscopic surgery for twin-twin transfusion syndrome (TTTS) and to evaluate the impact of intraoperative hypotension on fetal survival. A total of 328 TTTS patients with recipient twin cardiomyopathy who underwent fetoscopic surgery under epidural anesthesia were included. The exposure of interest was maternal medical therapy with nifedipine for the treatment of fetal cardiomyopathy. We found that intraoperative hypotension occurred in 53.4% (175/328 patients). There was no statistically significant difference in incidence of hypotension between nifedipine exposure and nonexposure groups (54.8% versus 50.8%, P = 0.479). However, the nifedipine exposure group received a statistically significant higher dose of phenylephrine (7.04 ± 6.38 mcg/kg versus 4.70 ± 4.14 mcg/kg, P = 0.018) and higher doses of other vasopressor, as counted by number of treatments (6.06 ± 4.58 versus 4.96 ± 3.42, P = 0.022). There were no statistically significant differences in acute fetal survival rate (within 5 days) and fetal survival rate at birth between hypotensive and nonhypotensive patients. We concluded that preoperative exposure to nifedipine resulted in increased intraoperative maternal vasopressor requirement during fetoscopic surgery under epidural anesthesia. In patients who had intraoperative maternal hypotension, there was no correlation between the presence of maternal hypotension and postoperative fetal survival.

Urgosedin inhibits hypotension, hypoglycemia, and pro-inflammatory mediators induced by lipopolysaccharide.

Urgosedin is a newly synthesized compound especially with serotonergic and alpha-adrenergic blocking actions. In rat isolated thoracic aorta, urgosedin competitively antagonized norepinephrine-, clonidine-, and serotonin-induced vasocontractions in a concentration-dependent manner. In radioligand binding experiments, urgosedin had significant binding affinities on alpha1/alpha2, 5-HT1A, 5-HT1B and 5-HT2A receptors. Intravenous injection of lipopolysaccharide (LPS) produced a biphasic hypotension in normotensive rats. Although intravenous injection of urgosedin caused minor depressor actions in the normotensive Wistar rat, urgosedin significantly attenuated the secondary prolonged hypotension produced by LPS. The plasma levels of cytokines (IL-1beta, IL-6, TNF-alpha, and IFN-gamma) and hypoglycemia induced by LPS were also reduced by urgosedin. Moreover, the acute survival rates (350 minutes) of endotoxic shock increased from 0% (LPS group) to 100% in the groups pretreated with urgosedin. In RAW264.7 cells, urgosedin inhibited LPS-induced inducible nitric oxide synthase (iNOS) expression. In conclusion, our data suggest that urgosedin was a newly potent serotonergic and mild alpha-adrenergic blocking agent. Its prevention of LPS-induced hypotension and hypoglycemia might partially mediate through its inhibition activities on the iNOS expression and cytokines formation. Urgosedin might be an effective pharmacological agent against LPS-induced hypotension, hypoglycemia, and the formation of pro-inflammatory mediators.

Acute and subacute toxicity and efficacy of S-nitrosylated captopril, an ACE inhibitor possessing nitric oxide activities.

The toxicity and efficacy of S-nitrosocaptopril (CapNO), a novel vasodilator possessing the capacities of both a nitric oxide donor and an angiotensin converting enzyme (ACE) inhibitor, were examined in rodents. In single-dose acute toxicity studies in ICR mice, the median lethal dose (LD(50)) for CapNO was 674+/-94 mg/kg (iv) and 2078+/-100 mg/kg (po), whereas for oral captopril was 4286+/-173 mg/kg. S-nitrosoglutathione, containing the same S-nitroso moiety as CapNO, showed an LD(50) equal to CapNO when the values were expressed by the mol/kg. The cause of acute death by the high doses of CapNO was lethal hypotension. In the subacute toxicity studies, oral CapNO was well tolerated in normotensive and hypertensive rats at doses up to 500 mg/kg/day for 3 months, except for considerable reductions in food consumption and growth rate observed in the 500 mg/kg/day group. Serum chemistry and hematology tests performed in the subacute toxicity studies revealed no adverse effects of oral CapNO except for a significant decrease in cholesterol levels in hypertensive SHR rat. At autopsy, no histopathological changes in major organs were observed over the subacute period. Administration of a therapeutic dose of CapNO (iv, 250 microg/kg which produced 25% decreases in blood pressure) revealed no changes in the hematological parameters. Subchronic treatment of SHR and SS/Jr rats with oral CapNO (50 mg/kg/day) significantly reduced mean arterial pressure to the normotensive level. Considering the absence of adverse effects of CapNO in the subchronic toxicity study, CapNO appears to be a safe drug for further clinical trials, but particular caution must be taken because it can cause hypotension when overdosed.

Deferoxamine induces hypotension in experimental gram-negative septicemia.

Multiple organ system failure may result from tissue damage caused by activated neutrophils or endotoxin. A significant part of this tissue damage is due to peroxidation induced by oxygen-free radicals and requires iron as a co-factor. Iron chelation has been shown to prevent tissue damage in some models. This experiment was carried out to determine whether iron chelation with deferoxamine (DFO) would prevent lung damage in a swine model of Gram-negative septicemia. Fifteen animals were randomized to control, Pseudomonas aeruginosa infusion at a rate of 2 x 10(7) colony forming units/20 kg/min (septic group), or Pseudomonas infusion combined with DFO pretreatment at a dose of 80 mg/kg/h (septic-treated group). Three of six septic-treated animals became severely hypotensive and died during the course of the experiment as opposed to none of six septic animals. Surviving septic-treated animals were significantly hypotensive (60 +/- 24 mmHg mean arterial pressure) compared to septic (122 +/- 9 mmHg) and control (109 +/- 8 mmHg) animals. DFO did not improve respiratory function (e.g., pO2) or morphology in septic animals. We conclude that iron-chelation therapy with DFO at the above dosage results in a significant deterioration in cardiovascular function in septic swine. Lung damage was not prevented.