Glycemia and the cardioprotective effects of insulin pre-conditioning in the isolated rat heart

Abstract Background While acute hyperglycemia has been shown to mitigate the beneficial effects of ischemic preconditioning, its effect on insulin-induced preconditioning remains unclear. Methods The study was designed to test the hypothesis that acute hyperglycemia diminishes the cardioprotective effects following a 20-min pre-ischemic pre-conditioning with insulin in the isolated rat heart using the Langendorff system. Forty hearts were assigned to receive modified Krebs–Henseleit (KH) buffer containing 0.5 U/L insulin and 100 mg/dL glucose (InsG100, n = 10), KH buffer with 100 mg/dL glucose (G100, n = 10), KH buffer supplemented with 0.5 U/L insulin and 600 mg/dL glucose (InsG600, n = 10), or with 600 mg/dL glucose (G600, n = 10). To match the osmotic pressure of the InsG600 group, 27.5 mmol/L of mannitol was added to KH solution in the InsG100 and G100 group. The four groups were perfused with each solution for 20 min prior to 15 min of no-flow ischemia, and during 20 min of reperfusion. Only during the ischemic period the heart was paced at 222 beats/min. Measurements of heart rate, coronary flow and maximum of LV derivative of pressure development (dP/dt max) were recorded. Myocardial phospho-protein kinase B (p-Akt) and tumor necrosis factor-α (TNF-α) levels were assayed by enzyme-linked immunosorbent assay and sandwich ELISA, respectively following reperfusion. Results After reperfusion, LV dP/dt max and heart rate in the InsG100 group was significantly higher than that in the other three groups. The myocardial p-Akt level in the InsG100 group was significantly elevated when compared to the InsG600 group at the end of reperfusion. The p-Akt levels in the InsG600 and InsG100 group were significantly higher than in the corresponding non-insulin groups. Conclusions Acute hyperglycemia diminishes the cardioprotective effects of insulin preconditioning in the isolated rat heart, possibly mediated through the suppression of myocardial Akt phosphorylation

Safety of intranasal insulin administration in patients undergoing cardiovascular surgery: An open-label, nonrandomized, dose-escalation studyCentral MessagePerspective

Objective: This study aimed to determine the maximum safe dose of intranasal insulin administration during cardiac surgery. Methods: This open-label, Phase 1, single-center, dose-escalation clinical trial recruited patients scheduled to undergo elective cardiac surgery or major vascular surgery requiring cardiopulmonary bypass between February and September 2021. They were grouped into 5 dose-escalation cohorts and administered 0, 40, 80, 160, and 240 IU insulin (n = 6 in each group) via a metered nasal dispenser after the induction of general anesthesia. Blood samples were collected at 10-minute intervals for the first 60 minutes and at 30-minute intervals thereafter. Hypoglycemia was defined as a blood glucose level <70 mg/dL. Patient recruitment was terminated after hypoglycemia was observed in 2 patients in any of the groups. Results: In total, 27 of 29 enrolled patients were administered intranasal insulin or saline. Hypoglycemia was not observed after the administration of intranasal insulin in the 0, 40, 80, or 160 IU groups; however, it was observed in 2 of 3 patients in the 240 IU group. The serum insulin concentration was elevated in the 160-IU group, but the C-peptide concentration was not elevated in any of the groups. Conclusions: The administration of up to 160 IU intranasal insulin did not induce clinically significant hypoglycemia. However, 160 IU intranasal insulin should be administered cautiously because insulin can enter the systemic circulation in a dose-dependent manner

The Bess-Polar II Long Duration Flight Above Antarctica

The Balloon-borne Experiment with a Superconducting Spectrometer, BESS, has been developed to study elementary particle phenomena in the early universe through measurements of low energy antiprotons to investigate their origin and through a search for antihelium. The BESS collaboration carried out nine northern latitude flights between 1993 and 2002. BESS-Polar is an advanced program of the BESS collaboration to study these topics with much greater precision using long duration flights above Antarctica. The BESS-Polar spectrometer was successfully developed to accumulate much larger numbers of events during long duration flights around the South Pole. Approximately a factor of four reductions in the amount of material in the particle beam enables measurement of much lower energy antiprotons down to 100 MeV (at top of atmosphere). The first BESS-Polar flight (BESS-Polar I) of 8.5 days was carried out above Antarctica in December 2004. recording 900 million cosmic-ray events. The second BESS-Polar flight (BESS-Polar 11) was successfully carried out in the austral summer season of 2007-2008. Based on experience with BESS-Polar I, the spectrometer was improved in performance and achieved long term stability during the flight. A newly constructed magnet with a larger liquid He capacity and improved thermal insulation and an upgraded data storage system with larger capacity of hard disk drives (HDDs) enabled longer observation time. BESS-Polar II was launched on December 22, 2007 from Williams Field, McMurdo Station, in Antarctica. The spectrometer worked properly and observed cosmic rays for about 24.5 days at float altitude, recording 4.6 billion events on the HDDs until the limit of the magnet operation was reached on January 16, 2008. The flight was terminated and the spectrometer was safely landed on the West Antarctic ice sheet (1000 km from the South Pole) on January 21, 2008. Here, the BESS-Polar instrument is discussed, highlighting improvements made for BESS-Polar II, and overviews of the flight and performance are reported

The Bess Investigation of the Origin of Cosmic-ray Antiprotons and Search for Cosmological Antimatter

The Balloon-borne Experiment with a Superconducting Spectrometer (BESS) collaboration has made precise measurements of the spectra of cosmic ray antiprotons and light nuclei and conducted a sensitive search for antinuclei. Ten BESS high-latitude flights, eight from Canada and two from Antarctica, span more than a Solar cycle between 1993 and 2007/2008. BESS measurements of low-energy antiprotons constrain candidate models for dark matter including the possible signature of primordial black hole evaporation. The stringent BESS measurements of antiprotons and the elemental and isotopic spectra of H and He provide strong constraints on models of cosmic-ray transport in the Galaxy and Solar System. BESS has also reported the first antideuterium upper limit. BESS employs a superconducting magnetic-rigity spectrometer with time-of-flight and aerogel Cherenkov detectors to identify incident particles by charge, charge sign, mass, and energy. The BESS-Polar long-duration instrument has reduced lower energy limit of 100 MeV (top of the atmosphere) to increase its sensitivity to possible primary antiproton sources. BESS-Polar II was rebuilt with extended magnet lifetime, improved detector and electronic performance, and greater data storage capacity. It was flown fro Antarctica December 2007-January 2008, recording about 4.6 bission events during 24.5 days at float altitude with the magnet on. During the flight the influence of a high-speed stream in the Solar wind was observed. Details of the BESS-Polar II instrument and flight performance are reported elsewhere at this conference. The successful BESS-Polar II flight at Solar minimum is especially important. Most cosmic-ray antiprotons are secondary products of nuclear interactions of primary cosmic-ray nuclei with the interstellar gas, giving a spectrum that peaks at about 2 GeV and falls rapidly to higher and lower energies. However, BESS data taken in the previous Solar minimum show a small excess over secondary expectations at low energies, possibly suggesting the presence of an additional component that may be masked at higher levels of Solar modulation. The high-statistics Solar minimum data obtained by BESS-Polar II will provide a difinitive test of this component. We will review the BESS program and report the latest results including the antiproton and proton spectra measured in the BESS-Polar I flight, the search for cosmic antinuclei, and the status of the BESS-Polar II analysis