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The impact of islet neuronal nitric oxide synthase (nNOS) on glucose-stimulated insulin secretion (GSIS) is less understood. We investigated this issue by performing simultaneous measurements of the activity of nNOS versus inducible NOS (iNOS) in GSIS using isolated murine islets. Additionally, the significance of extracellular NO on GSIS was studied. Islets incubated at basal glucose showed modest nNOS but no iNOS activity. Glucose-induced concentration-response studies revealed an increase in both NOS activities in relation to secreted insulin. Culturing at high glucose increased both nNOS and iNOS activities inducing a marked decrease in GSIS in a following short-term incubation at high glucose. Culturing at half-maximal glucose showed strong iNOS expression revealed by fluorescence microscopy also in human islets. Experiments with nNOS-inhibitors revealed that GSIS was inversely related to nNOS activity, the effect of iNOS activity being negligible. The increased GSIS after blockade of nNOS was reversed by the intracellular NO-donor hydroxylamine. The enhancing effect on GSIS by nNOS inhibition was independent of membrane depolarization and most likely exerted in the pentose phosphate pathway (PPP). GSIS was markedly reduced, 50%, by glucose-6-phosphate dehydrogenase (G-6-PD) inhibition both in the absence and presence of nNOS inhibition. NO gas stimulated GSIS at low and inhibited at high NO concentrations. The stimulatory action was dependent on membrane thiol groups. In comparison, carbon monoxide (CO) exclusively potentiated GSIS. CO rather than NO stimulated islet cyclic GMP during GSIS. It is suggested that increased nNOS activity restrains GSIS, and that the alternative pathway along the PPP initially might involve as much as 50% of total GSIS. In the PPP, the acute insulin response is downregulated by a negative feedback effect executed by a marked upregulation of nNOS activity elicited from secreted insulin exciting insulin receptors at exocytotic sites of an nNOS-associated population of secretory granules.

Background. Patients undergoing breast surgery are at risk of severe postoperative pain. Several opioid-sparing strategies exist to alleviate this condition. Regional anesthesia has long been a part of perioperative pain management for these patients. Aim. This randomized study examined the benefits of interpectoral and pectoserratus plane block (IPP/PSP), also known as pectoralis nerve plain block, compared with advanced local anesthetic infiltration. Methods. We analyzed 57 patients undergoing partial mastectomy with sentinel node dissection. They received either an ultrasound-guided IPP/PSP block performed preoperatively by an anesthetist or local anesthetic infiltration performed by the surgeon before and during the surgery. Results. Pain measured with the numerical rating scale (NRS) indicated no statistically significant difference between the groups (IPP/PSP 1.67 vs. infiltration 1.97; p value 0.578). Intraoperative use of fentanyl was significantly lower in the IPP/PSP group (0.18 mg vs 0.21 mg; p value 0.041). There was no statistically significant difference in the length of stay in the PACU (166 min vs 175 min; p value 0.51). There were no differences in reported postoperative nausea and vomiting (PONV) between the groups. The difference in postoperative use of oxycodone in the PACU (p value 0.7) and the use of oxycodone within 24 hours postoperatively (p value 0.87) was not statistically significant. Conclusions. Our study showed decreased intraoperative opioid use in the IPP/PSP group and no difference in postoperative pain scores up to 24 hours. Both groups reported low postoperative pain scores. This trial is registered with NCT04824599.

BackgroundBalanced transfusions, including platelets, are critical for bleeding patients to maintain hemostasis. Many rural hospitals have no or limited platelet inventory, with several hours of transport time from larger hospitals. This study aimed to evaluate the feasibility of using cryopreserved platelets that can be stored for years, in remote hospitals with no or limited platelet inventory.Material and methodsThree remote hospitals participated in a prospective study including adult bleeding patients where platelet transfusions were indicated. Cryopreserved platelets were prepared in a university hospital, concentrated in 10 ml, transported on dry ice, and stored at −80°C at the receiving hospital. At request, the concentrated platelet units were thawed and diluted in fresh frozen plasma. The indications, blood transfusion needs, and laboratory parameters pre- and post-transfusion, as well as logistics, such as time from request to transfusion and work efforts in preparing cryopreserved platelets, were evaluated.ResultsTwenty-three bleeding patients were included. Nine patients (39%) were treated for gastrointestinal bleeding, five (22%) for perioperative bleeding, and four (17%) for trauma bleeding. The transfusion needs were 4.9 ± 3.3 red blood cell units, 3.2 ± 2.3 plasma units, and 1.9 ± 2.2 platelet units, whereof cryopreserved were 1.5 ± 1.1 (mean ± SD). One patient had a mild allergic reaction. We could not show the difference in laboratory results between pre- and post-transfusion of the cryopreserved units in the bleeding patients. The mean time from the order of cryopreserved platelets to transfusion was 64 min, with a range from 25 to 180 min.ConclusionCryopreserved platelets in remote hospitals are logistically feasible in the treatment of bleeding. The ability to have platelets in stock reduces the time to platelet transfusion in bleeding patients where the alternative often is many hours delay. Clinical effectiveness and safety previously shown in other studies are supported in this small feasibility study.