Complete atrio-ventricular block with coronary artery spasm due to direct laryngoscopy in a pediatric patient with laryngeal papillomatosis: a case report.

BACKGROUND: Coronary artery spasm has rarely been reported in pediatric patients. Previous studies have reported comorbidities and risk factors for coronary artery spasms. We present the case of a complete atrio-ventricular (AV) block that occurred in the absence of other risk factors immediately after direct laryngoscopy. CASE PRESENTATION: A 2-year-old girl developed severe coronary artery spasm after direct laryngoscopy for elective laryngeal papillomatosis resection. Immediately after the initiation of laryngoscopy, complete AV block and ST elevation on lead II of the electrocardiogram were observed. These findings indicated that the complete AV block was caused by a right coronary artery spasm. CONCLUSION: Coronary artery spasm resulting in lethal arrhythmia rarely occurs in healthy pediatric patients. To the best of our knowledge, this is the first pediatric case of a severe coronary artery spasm resulting in a complete AV block due to direct laryngoscopy in a healthy patient.

Association between ionized magnesium and postoperative shivering.

PURPOSE: Ionized magnesium (iMg) is considered to be the biologically active fraction of circulating total serum Mg (tMg). However, only the relationship between tMg and postoperative shivering has been studied. To our knowledge, hitherto no clinical studies have investigated the association between serum ionized magnesium concentration ([iMg]) and postoperative shivering. Therefore, we aimed to retrospectively examine this association, focusing on hypomagnesemia and depletion of [iMg]. METHODS: This retrospective study involved 421 patients who underwent pancreaticoduodenectomy under general anesthesia at our center from December 2012 to September 2019. Logistic regression analysis was performed to estimate the odds ratio (OR) for the incidence of postoperative shivering. RESULTS: Postoperative shivering developed in 111 out of 421 patients. The post-surgical concentration of [iMg] was significantly associated with postoperative shivering in the non-adjusted model, but not in the multivariable-adjusted model. In multivariable-adjusted analysis, progressive decrease of [iMg] by 0.1 mmol/L significantly increased the risk of postoperative shivering (OR: 1.64, 95% CI 1.02-2.64, p = 0.04). The multivariable-adjusted OR for postoperative shivering was 3.65 (95% CI 1.25-13.55, p = 0.02) in subjects with post-surgical [iMg] less than 0.6 mmol/L and decrease in [iMg] during surgery compared with those with post-surgical [iMg] more than 0.6 mmol/L and constant or increased of [iMg] during surgery. CONCLUSION: A decrease in the [iMg] during surgery was significantly associated with postoperative shivering. Subjects who had an [iMg] lower than 0.6 mmol/L post-surgery and decreased [iMg] during surgery had a significantly higher risk of postoperative shivering. Intraoperative depletion of [iMg] was significantly associated with shivering.

Surgical treatment for breast cancer in a patient with erythropoietic protoporphyria and photosensitivity: a case report.

BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare disorder of heme synthesis. Patients with EPP mainly show symptoms of photosensitivity, but approximately 20% of EPPs are associated with the liver-related complications. We report a case of breast cancer in a 48-year-old female patient with EPP in whom meticulous perioperative management was required in order to avoid complications resulting from this disease. CASE PRESENTATION: The patient was diagnosed with EPP at the age of 33 and had a rich family history of the disease. For right breast cancer initially considered as TisN0M0 (Stage 0), the right mastectomy and sentinel lymph node biopsy were performed, while the final stage was pT1bN0M0, pStage I. In the perioperative period, we limited the drug use and monitored light wavelength measurements. Besides, we covered surgical lights, headlights, and laryngoscope's light with a special polyimide film that filtered the wavelength of light causing dermal photosensitivity. After the surgery, any emerging complications were closely monitored. CONCLUSIONS: The surgery, internal medicine, anesthesiology, and operation departments undertook all possible measures through close cooperation to ensure a safe surgery for the patient with a rare condition.

Incidence of Venous Air Embolism During Endoscopic Retrograde Cholangiopancreatography.

BACKGROUND: Known complications of endoscopic retrograde cholangiopancreatography (ERCP) include pancreatitis, bleeding, duodenal perforation, and venous air embolism (VAE). The aim of this study was to determine the incidence of VAE during ERCP and be able to differentiate high-risk versus low-risk ERCP procedures. METHODS: This is a prospective cohort study consisting of patients who underwent ERCP and were monitored with a precordial Doppler ultrasound (PDU) for VAE. PDU monitoring was digitally recorded and analyzed to confirm the suspected VAE. Demographic and clinical data related to the anesthetic care, endoscopic procedure, and intraoperative hemodynamics were analyzed. RESULTS: A total of 843 ERCP procedures were performed over a 15-month period. The incidence of VAE was 2.4% (20 patients). All VAE's occurred during procedures in which stent placement, sphincterotomy, biopsy, duct dilation, gallstone retrieval, cholangioscopy, or necrosectomy occurred. Ten of 20 (50%) of VAEs were associated with hemodynamic alterations. None occurred if the procedure was only diagnostic or for stent removal. Subanalysis for the type of procedure showed that VAE was statistically more frequent when stents were removed and then replaced or if a cholangioscopy was performed. CONCLUSIONS: The high incidence of VAE highlights the need for practitioners to be aware of this potentially serious event. Use of PDU can aid in the detection of VAE during ERCP and should be considered especially during high-risk therapeutic procedures. Detection may allow appropriate interventions before serious adverse events such as cardiovascular collapse occur.

Differential effects of volatile anesthetics on M3 muscarinic receptor coupling to the Galphaq heterotrimeric G protein.

BACKGROUND: Halothane inhibits airway smooth muscle contraction in part by inhibiting the functional coupling between muscarinic receptors and one of its cognate heterotrimeric G proteins, Galphaq. Based on previous studies indicating a more potent effect of halothane and sevoflurane on airway smooth muscle contraction compared with isoflurane, the current study hypothesized that at anesthetic concentrations of 2 minimum alveolar concentration (MAC) or less, halothane and sevoflurane but not isoflurane inhibit acetylcholine-promoted Galphaq guanosine nucleotide exchange. METHODS: Galphaq guanosine nucleotide exchange was measured in crude membranes prepared from COS-7 cells transiently coexpressing the human M3 muscarinic receptor and human Galphaq. A radioactive, nonhydrolyzable analog of guanosine-5'-triphosphate, [35S]GTPgammaS, was used as a reporter for nucleotide exchange at Galphaq. RESULTS: Acetylcholine caused a concentration-dependent increase in Galphaq [35S]GTPgammaS-GDP exchange. Neither anesthetic affected constitutive Galphaq [35S]GTPgammaS-GDP exchange in the absence of acetylcholine. Conversely, each anesthetic caused a concentration-dependent and reversible inhibition of Galphaq [35S]GTPgammaS-GDP exchange when promoted by acetylcholine. At concentrations of 3 MAC or less, the effect of halothane and sevoflurane were significantly greater than that of isoflurane, with only a minimal inhibition by isoflurane observed at 2 MAC. CONCLUSION: The differential effects of volatile anesthetics on acetylcholine-promoted guanosine nucleotide exchange at Galphaq are consistent with the apparent more potent direct effect of halothane and sevoflurane compared with isoflurane on muscarinic receptor-mediated contraction of isolated airway smooth muscle. These differential effects also suggest a mode of anesthetic action that could be due to anesthetic-protein interactions and not simply anesthetic accumulation in the lipid membrane.

Halothane does not inhibit the functional coupling between the beta2-adrenergic receptor and the Galphas heterotrimeric G protein.

BACKGROUND: This study investigated whether halothane affects the functional coupling between the beta2 adrenergic receptor and the alpha subunit of its cognate stimulatory heterotrimeric guanosine-5'-triphosphate (GTP)-binding protein (Galphas). The authors hypothesized that halothane does not affect isoproterenol-promoted guanosine nucleotide exchange at Galphas and hence would not affect isoproterenol-induced relaxation of airway smooth muscle. METHODS: Halothane effects on isoproterenol-induced inhibition of calcium sensitivity were measured in permeabilized porcine airway smooth muscle. Galphas nucleotide exchange was measured in crude membranes prepared from COS-7 cells transfected to transiently coexpress the human beta1 or beta2 receptor each with human short Galphas. A radioactive, nonhydrolyzable analog of GTP, [S]GTPgammaS, was used as the reporter for nucleotide exchange at Galphas. RESULTS: Halothane (0.75 mm, approximately 2.8 minimum alveolar concentration [MAC] in pigs) did not affect isoproterenol-induced inhibition of calcium sensitivity. Isoproterenol caused a time- and concentration-dependent increase in Galphas nucleotide exchange. Halothane, even at concentrations of 1.5 mm (approximately 5.6 MAC), had no effect on basal Galphas nucleotide exchange in the absence of isoproterenol, whereas halothane inhibited isoproterenol-promoted Galphas nucleotide exchange in both the beta1-Galphas and beta2-Galphas expressing membranes. However, the effect was significantly greater on beta1-Galphas coupling compared with beta2-Galphas coupling, with no effect on beta2-Galphas coupling at 2.8 MAC halothane. CONCLUSION: Halothane does not inhibit the biochemical coupling between the beta2 receptor and Galphas and hence does not affect the inhibition of calcium sensitivity induced by isoproterenol. Therefore, halothane should not affect the efficacy of beta2 agonists, as suggested by studies of in vivo animal models of asthma.

Anesthetics inhibit membrane receptor coupling to the Gq/11 heterotrimeric G protein in airway smooth muscle.

BACKGROUND: Some anesthetics relax airway smooth muscle in part by inhibiting acetylcholine-induced increases in Ca2+ sensitivity, an effect associated with inhibition of guanosine nucleotide exchange at the alpha subunit of the Gq/11 (Galphaq/11) heterotrimeric G protein. This study tested the hypothesis that these anesthetic effects are not unique to the muscarinic receptor but are a general property of the heptahelical receptors that increase Ca2+ sensitivity in airway smooth muscle. METHODS: Anesthetic effects on agonist-induced increases in Ca2+ sensitivity were measured in porcine airway smooth muscle strips permeabilized with S. aureus alpha-toxin. Anesthetic effects on basal (without agonist stimulation) and agonist-promoted Galphaq/11 guanosine nucleotide exchange were determined in crude membranes prepared from porcine airway smooth muscle. The nonhydrolyzable, radioactive form of guanosine 5'-triphosphate was used as the reporter for nucleotide exchange at Galphaq/11. RESULTS: Acetylcholine, endothelin-1, and histamine caused a concentration-dependent increase in Ca2+ sensitivity. Halothane (0.67 +/- 0.07 mM) and hexanol (10 mM) significantly inhibited the increase in Ca2+ sensitivity induced by each agonist. Each agonist also caused a time- and concentration-dependent increase in Galphaq/11 nucleotide exchange. Neither anesthetic had an effect on basal Galphaq/11 nucleotide exchange, whereas halothane and hexanol significantly inhibited the increase in Galphaq/11 nucleotide exchange promoted by each agonist. CONCLUSION: These data suggest that inhibition of agonist-promoted guanosine nucleotide exchange at Galphaq/11 by some anesthetics may be a general property of heptahelical receptors involved cellular processes mediated by Galphaq/11, including muscarinic, endothelin-1, and histamine receptor activation of Ca2+ sensitivity.

Inactivation of protease-activated receptor-1 by proteolytic removal of the ligand region in vascular endothelial cells.

Proteolysis plays an important role in inactivating protease-activated receptor-1 (PAR1). We aimed to determine the cleavage site(s) responsive for the proteolytic inactivation of PAR1 in human umbilical vein endothelial cells. Fura-2 fluorometry revealed that the preceding stimulation with trypsin abolished the subsequent [Ca(2+)](i) response to thrombin, while the responses to PAR1-activating peptides remained intact. On the other hand, thrombin had no effect on the subsequent response to trypsin. The immunostaining with antibodies against the residues 35-46 (SPAN12) and 51-64 (WEDE15) revealed the broad boundaries of cleavage. Trypsin removed both epitopes from the cell surface within 3 min, while thrombin removed the epitope of SPAN12. The longer incubation with thrombin removed the epitope of WEDE15. However, PAR1-activating peptides thereafter induced an attenuated but significant elevation of [Ca(2+)](i). Not only the receptor internalization as observed with a confocal microscope, but also an additional cleavage was thus suggested to contribute to the thrombin-induced removal of the epitope of WEDE15. The analyses of the PAR1 mutants identified three cleavage sites for trypsin; residues 41-42, 70-71 and 82-83. The cleavage at the latter two sites was suggested to dominate that at the former, and thus remove the ligand region (residues 42-47). The inactivation of PAR1 due to proteolytic removal of the ligand region may contribute not only to the inactivation of PAR1 by proteases such as trypsin, but also to the termination of the intracellular signaling initiated by thrombin in the vascular endothelial cells.

Unproductive cleavage and the inactivation of protease-activated receptor-1 by trypsin in vascular endothelial cells.

1 Using fura-2 fluorometry of [Ca(2+)](i) in response to thrombin, trypsin and protease-activated receptor activating peptides (PAR-APs), we determined whether trypsin cleaves protease-activated receptor 1 (PAR1) and activates it in the endothelial cells of the porcine aortic valves and human umbilical vein. 2 Once stimulated with thrombin, the subsequent application of trypsin induced a [Ca(2+)](i) elevation similar to that obtained without the preceding stimulation with thrombin in the valvular endothelial cells. However, the preceding stimulation with trypsin abolished the subsequent response to thrombin, but not to bradykinin or substance P. 3 The response to PAR1-AP (SFLLRNP) was significantly (P<0.05) reduced by the preceding stimulation with thrombin and PAR1-AP in the valvular endothelial cells, while, importantly, it remained unaffected by the preceding stimulation with either trypsin or PAR2-AP (SLIGRL). The response to PAR2-AP was reduced by the preceding stimulation with trypsin and PAP2-AP. PAR1-AP attenuated the subsequent responses not only to thrombin and PAR1-AP but also to trypsin and PAR2-AP, while PAR2-AP specifically attenuated the subsequent responses to trypsin and PAR2-AP. 4 In human umbilical vein endothelial cells, a higher affinity PAR1-AP (haPAR1-AP) (Ala-pF-Arg-Cha-HArg-Tyr-NH(2)) specifically attenuated the responses to thrombin but not trypsin. On the other hand, the response to haPAR1-AP was significantly (P<0.05) attenuated by the preceding stimulation with thrombin but not trypsin. 5 In conclusion, trypsin cleaved PAR1 but did not activate it in the endothelial cells. Moreover, the trypsin-cleaved PAR1 was no longer responsive to thrombin.