Transient Fall Research Articles

Design and application of germanium based complementary TFET devices with step tunneling paths

Expanding tunneling has consistently been one of the approaches to enhance the on-state current (Ion) and performance of Tunnel Field-Effect Transistor (TFET). This paper proposes a novel structure for TFET called Step Tunneling Path TFET (STP TFET). The stepped tunneling path is achieved by preparing majority carrier channel and introducing pocket doping layers and lightly doped channel extension regions in the channel. Taking Germanium TFET as an example, the complementary structures, electrical parameters, DC and analog characteristics of STP TFET are investigated. Simulation results demonstrate that, compared to normal TFET, STP TFET exhibits significant improvements in Ion (n-TFET∼18/p-TFET∼45 times), cut-off frequency (n-TFET∼6/p-TFET∼16 times), Gain Bandwidth Product enhancement (n-TFET∼22/p-TFET∼16 times), and Transconductance Frequency Product enhancement (n-TFET∼3/p-TFET∼15 times). Furthermore, in the C-TFET inverter, the transient rise and fall times have decreased by 149 and 199 ns, respectively, while the voltage gain has increased by 6.7 times. The proposed device shows promising potential for applications in high-speed and low-power circuit designs.

Anaesthetic implications of intra-operative Indocyanine Green use in pediatric surgery

IntroductionThe use of Indocyanine Green (ICG) dye for fluorescent guided surgery is increasing in children. In many cases, ICG is injected intravenously peri-operatively and is known to falsely alter peripheral oxygenation readings because of interference with the measured red/infrared absorbance ratio of pulsatile blood. MethodsThe study occurred at a single centre tertiary children's hospital. ICG was delivered peri-operatively. SpO2 was monitored real-time in all patients. Blood pressure, heart rate, expired carbon dioxide and electrocardiographic data were collected from anaesthetic records. Data is median (interquartile range) ResultsTwenty-five patients(13 F;12 M) age 60(77)months and weight 17(18.7)kg were included between 01/April/2021 and 31/Nov/2022.Fifteen patients received 0.5(0.38) mg/kg ICG at induction of anesthesia with ΔSpO2 of 6(2) %. Median time to ΔSpO2 fall was 25(6) s with recovery taking 74(68) s. Time to recovery and ΔSpO2 were proportional to ICG dose/kg with r2 of 0.7993 and 0.597 and p of 0.0008 and 0.001 respectively on linear regression. Five patients had intralesional ICG and one had an enteral dose with no effect on SpO2.Eight patients had a total of 20 intraoperative bolus doses of ICG with no effect on SpO2 in 11. In 9, time to SpO2 fall was 26(12) s with ΔSpO2 of 4(1) % and recovery at 24(50) s.No corrective anaesthetic manoeuvres were required. ConclusionUnderstanding the timings of the transient artefactual fall and recovery in SpO2 following ICG injection is essential for safe anesthesia. This is the first study to evaluate this effect in children prospectively.

1564-P: Impaired Insulin Secretion Increases Glucagon Action on the Liver

The transition from prediabetes to diabetes is characterized by defects in insulin secretion and glucagon suppression in response to glucose. However, simultaneous estimation of both hormones actions on endogenous glucose production (EGP) remains a challenge. To address this, we studied 36 nondiabetic subjects on 2 occasions when endogenous hormone secretion was inhibited by somatostatin. Glucagon was infused at 0.65 ng/kg/min, at 0 min to prevent a fall in its concentration (non-suppressed - NS) or at 120 min to create a transient fall (suppressed - S). [3-3H]-glucose was infused to mimic an oral glucose challenge together with a prandial insulin infusion - one group received the full dose (100%), another 80% and another 60%. We tested models describing EGP as a function of glucose, insulin and glucagon concentrations. The optimal model assumes that EGP is suppressed by the actions of glucose, its rate of change and insulin in a remote compartment, while plasma glucagon stimulated EGP (through parameter SGn), with an effect that is evanescent. With 60% replacement (corresponding to severely impaired insulin secretion), SGn was significantly higher than with 80% (moderately impaired) and 100% replacement (p=0.02, Fig.1). This demonstrates that glucagon action on EGP is modulated by insulin concentrations, emphasizing the need to quantify secretion and action of both hormones when measuring postprandial islet function. Disclosure A. Tonello: None. M.C. Laurenti: None. C. Cobelli: None. A. Vella: Other Relationship; Novo Nordisk. Advisory Panel; Rezolute, Inc. Consultant; Crinetics Pharmaceuticals, Inc., Hanmi Pharm. Co., Ltd., Zealand Pharma A/S. C. Dalla Man: Research Support; Sanofi-Aventis Deutschland GmbH, Becton, Dickinson and Company. Funding Italian Minister for Education; National Institutes of Health (DK116723)

High-Dose Intravenous Steroid Treatment Seems to Have No Long-Term Negative Effect on Bone Mineral Density of Young and Newly Diagnosed Multiple Sclerosis Patients: A Pilot Study.

High-dose intravenous steroid treatment (HDIST) represents the first choice of treatment for multiple sclerosis (MS) relapses. Chronic oral glucocorticoid (GC) administration correlates with bone loss whereas data regarding HDIST in MS are still conflicting. Twenty-five newly diagnosed MS patients (NDMSP) (median age: 37 years) were prospectively studied for the effects of HDIST on bone mineral density (BMD) and bone metabolism. Patients received 1000 mg methylprednisolone intravenously every day for 5 days followed by oral prednisolone tapering over 21 days. Bone metabolism indices were determined prior to GC, on days 2, 4, 6, and 90, and at months 6, 12, 18, and 24 post GC therapy. Femoral, lumbar-spine BMD, and whole-body measurement of adipose/lean tissue were assessed prior to GC-administration and then every six months. Ten patients completed the study. N-terminal-propeptide-procollagen-type-1 and bone-specific alkaline phosphatase showed a significant increase at day-90 (p < 0.05). A transient non-significant fall of BMD was observed at 6 months after GC-administration, which subsequently appeared to be restored. We conclude that HDIST seems not to have long-term negative effects on BMD, while the observed transient increase of bone formation markers probably indicates a high bone turnover phase to GC-administration. Additional prospective studies with larger sample size are needed.

The effect of daily UVA phototherapy for 2 weeks on clinic and 24-h blood pressure in individuals with mild hypertension

Latitude and season determine exposure to ultraviolet radiation and correlate with population blood pressure. Evidence for Vitamin D causing this relationship is inconsistent, and temperature changes are only partly responsible for BP variation. In healthy individuals, a single irradiation with 20 J/cm2 UVA mobilises NO from cutaneous stores to the circulation, causes arterial vasodilatation, and elicits a transient fall in BP. We, therefore, tested whether low-dose daily UVA phototherapy might be an effective treatment for mild hypertension. 13 patients with untreated high-normal or stage 1 hypertension (BP 130-159/85-99 mm Hg), confirmed by 24-h ambulatory blood pressure (ABP), were recruited. Using home phototherapy lamps they were either exposed to 5 J/cm2 full body UVA (320–410 nm) radiation each day for 14 days, or sham-irradiated with lamps filtered to exclude wavelengths <500 nm. After a washout period of 3 ± 1 week, the alternate irradiation was delivered. 24-h ABP was measured on day 0 before either irradiation sequence and on day 14. Clinic BP was recorded on day 0, and within 90 min of irradiation on day 14. There was no effect on 24-h ABP following UVA irradiation. Clinic BP shortly after irradiation fell with UVA (−8.0 ± 2.9/−3.8 ± 1.1 mm Hg p = 0.034/0.029) but not sham irradiation (1.1 ± 3.0/0.9 ± 1.5 mm Hg). Once daily low-dose UVA does not control mildly elevated BP although it produces a transient fall shortly after irradiation. More frequent exposure to UVA might be effective. Alternatively, UVB, which photo-releases more NO from skin, could be tried.

The Effect of Diabetes-Associated Variation in TCF7L2 on Postprandial Glucose Metabolism When Glucagon and Insulin Concentrations Are Matched.

Background: The rs7903146 variant in the TCF7L2 gene is associated with defects in postprandial insulin and glucagon secretion and increased risk of type 2 diabetes. However, it is unclear if this variant has effects on glucose metabolism that are independent of islet function. Methods: We studied 54 nondiabetic subjects on two occasions where endogenous hormone secretion was inhibited by somatostatin. Twenty-nine subjects were homozygous for the diabetes-associated allele (TT) and 25 for the diabetes-protective allele (CC) at rs7903146, but otherwise matched for anthropometric characteristics. On 1 day, glucagon infused at a rate of 0.65 ng/kg/min, and at 0 min prevented a fall in glucagon (nonsuppressed day). On the contrary, infusion commenced at 120 min to create a transient fall in glucagon (suppressed day). Subjects received glucose (labeled with [3-3H]-glucose) infused to mimic the systemic appearance of oral glucose. Insulin was infused to mimic a prandial insulin response. Endogenous glucose production (EGP) was measured using the tracer dilution technique. Results: Lack of glucagon suppression increased postchallenge glucose concentrations and impaired EGP suppression. However, in the presence of matched insulin and glucagon concentrations, genetic variation in TCF7L2 did not alter glucose metabolism. Conclusion: These data suggest that genetic variation in TCF7L2 alters glucose metabolism through changes in islet hormone secretion.

The continuing impacts of the COVID‐19 pandemic on diagnosis and surgical prostate cancer management: a population‐based analysis

The continuing impacts of the <scp>COVID</scp>‐19 pandemic on diagnosis and surgical prostate cancer management: a population‐based analysis

Bradykinin-induced nociceptive responses are more potent than capsaicin-induced responses in rat models

Background: Peripheral blood vessels are concerned with sensing the perivascular nociceptive information and signaling it to the higher centers through ipsilateral somatic nerves, thereby regulating the cardiorespiratory parameters by means of vasosensory reflex responses. Aims and Objectives: The present study was conducted to compare the potency of nociceptive responses elicited by bradykinin (BK) with the capsaicin-induced responses. Materials and Methods: Charles-Foster rats were anesthetized with urethane and injected intraperitoneally. After tracheostomy, the right femoral artery was cannulated with a 24G, double ported cannula for administering the chemicals/saline through vertical port and to record the blood pressure (BP) through horizontal port. BP, Electrocardiogram, and respiratory movements were recorded. Results: Injection of capsaicin into a segment of femoral artery evoked instantaneous transient tachypnoeic, hyperventilatory, and hypotensive responses. BK also produced similar pattern of nociceptive responses along with a transient fall in heart rate. In addition, the vasosensory responses produced by BK are of greater magnitude as compared to the capsaicin. Conclusions: BK is more potent in eliciting reflex nociceptive responses as compared to capsaicin. Further, BK has an additional cardioprotective role by slowing the heart, in the events of acute inflammation.

Insulin secretion and action and the response of endogenous glucose production to a lack of glucagon suppression in nondiabetic subjects.

Type 2 diabetes is a disease characterized by impaired insulin secretion and defective glucagon suppression in the postprandial period. We examined the effect of impaired glucagon suppression on glucose concentrations and endogenous glucose production (EGP) at different degrees of insulin secretory impairment. The contribution of anthropometric characteristics, peripheral, and hepatic insulin action to this variability was also examined. To do so, we studied 54 nondiabetic subjects on two occasions in which endogenous hormone secretion was inhibited by somatostatin, with glucagon infused at a rate of 0.65 ng/kg/min, at 0 min to prevent a fall in glucagon (nonsuppressed day) or at 120 min to create a transient fall in glucagon (suppressed day). Subjects received glucose (labeled with [3-3H]-glucose) infused to mimic the systemic appearance of 50-g oral glucose. Insulin was infused to mimic a prandial insulin response in 18 subjects, another 18 received 80% of the dose, and the remaining 18 received 60%. EGP was measured using the tracer-dilution technique. Decreased prandial insulin resulted in greater % increase in peak glucose but not in integrated glucose concentrations attributable to nonsuppressed glucagon. The % change in integrated EGP was unaffected by insulin dose. Multivariate regression analysis, adjusted for age, sex, weight, and insulin dose, did not show a relationship between the EGP response to impaired suppression of glucagon and insulin action as measured at the time of screening by oral glucose tolerance. A similar analysis for hepatic insulin action also did not show a relationship with the EGP response. These data indicate that the effect of impaired glucagon suppression on EGP is independent of anthropometric characteristics and insulin action.NEW & NOTEWORTHY In prediabetes, anthropometric characteristics as well as insulin action do not alter the hepatic response to glucagon. The postprandial suppression or lack of suppression of glucagon secretion is an important factor governing postprandial glucose tolerance independent of insulin secretion.

Geodynamic significance of a buried transient Carboniferous landscape

Abstract It is increasingly clear that present-day dynamic topography on Earth, which is generated and maintained by mantle convective processes, varies on timescales and length scales on the order of 1–10 m.y. and 103 km, respectively. A significant implication of this behavior is that Phanerozoic stratigraphic records should contain indirect evidence of these processes. Here, we describe and analyze a well-exposed example of an ancient landscape from the Grand Canyon region of western North America that appears to preserve a transient response to mantle processes. The Surprise Canyon Formation lies close to the Mississippian-Pennsylvanian boundary and crops out as a series of discontinuous lenses and patches that are interpreted as remnants of a westward-draining network of paleovalleys and paleochannels within a coastal embayment. This drainage network is incised into the marine Redwall Limestone whose irregular and karstified upper surface contains many caves and collapse structures. The Surprise Canyon Formation itself consists of coarse imbricated conglomerates, terrestrial plant impressions including Lepidodendron, and marine invertebrate fossils. It is overlain by marine, fluvial, and aeolian deposits of the Supai Group. These stratal relationships are indicative of a transient base-level fall whose amplitude and regional extent are recognized as being inconsistent with glacio-eustatic sea-level variation. We propose that this transient event is caused by emplacement and decay of a temperature anomaly within an asthenospheric channel located beneath the lithospheric plate. An analytical model is developed that accounts for the average regional uplift associated with landscape development and its rapid tectonic subsidence. This model suggests that emplacement and decay of a ~50 °C temperature anomaly within a channel that is 150 ± 50 km thick can account for the observed vertical displacements. Our results are corroborated by detrital zircon studies that support wholesale drainage reorganization at this time and by stratigraphic evidence for spatially variable regional epeirogeny. They are also consistent with an emerging understanding of the temporal and spatial evolution of the lithosphere-asthenosphere boundary.

Naturally occurring hypothermia promotes survival in severe anaphylaxis

Although hypothermia has received substantial attention as an indicator of severity in anaphylaxis, it has been neglected from the perspective of whether it could act as a disease-modifying factor in this condition. Here, the impact of naturally occurring (spontaneous) hypothermia on anaphylaxis was evaluated in a murine model of ovalbumin (OVA)-induced allergy. Nonextreme changes in the ambient temperature (Ta) were used to modulate the magnitude of spontaneous hypothermia. At a Ta of 24°C, challenge with OVA intraperitoneally or intravenously resulted in a rapid, transient fall in body core temperature, which reached its nadir 4-6°C below baseline in 30 min. This hypothermic response was largely attenuated when the mice were kept at a Ta of 34°C. The Ta-dependent attenuation of hypothermia resulted in a survival rate of only 30%, as opposed to survival of 100% in the condition that favored the development of hypothermia. The protective effect of hypothermia did not involve changes in the rate of mast cell degranulation, as assessed by the concentration of mast cell protease-1 in bodily fluids. On the other hand, hypothermia improved oxygenation of the brain and kidneys, as indicated by higher NAD+/NADH ratios. Therefore, it is plausible to propose that naturally occurring hypothermia makes organs more resistant to the anaphylactic insult.

259-OR: The Effect of Impaired Glucagon Suppression on Endogenous Glucose Production Is Independent of Insulin Action

Type 2 diabetes is a disease characterized by impaired insulin secretion and defective glucagon suppression in the postprandial period. We examined the effect of impaired glucagon suppression on glucose concentrations and Endogenous Glucose Production (EGP) at different degrees of insulin secretory impairment. The contribution of anthropometric characteristics, peripheral, and hepatic, insulin action to this variability was also examined. To do so, we studied 54 nondiabetic subjects on two occasions in which endogenous hormone secretion was inhibited by somatostatin, with glucagon infused at a rate of 0.65 ng/kg/min, at 0 min to prevent a fall in glucagon (non-suppressed day) or at 120 min to create a transient fall in glucagon (suppressed day). Subjects received glucose (labeled with [3-3H]-glucose) infused to mimic the systemic appearance of 50g oral glucose. Insulin was infused to mimic a prandial insulin response in 18 subjects, another 18 received 80% of the dose and the remaining 18 received 60%. EGP was measured using the tracer-dilution technique. Decreased prandial insulin resulted in greater % increase in peak glucose (56±5 vs. 44±6 vs. 31±6 %, p=0.01 - 0.6, 0.8 and 1.0 dose respectively) but not in integrated (area above basal - AAB) glucose (39±4 vs. 43±9 vs. 36±9 %, p=0.82) caused by non-suppressed glucagon. The % change in integrated EGP was unaffected by insulin dose (51±20 vs. 27±19 vs. 22±18 %, p=0.53). Multivariate regression analysis, adjusted for age, sex, weight and insulin dose, did not show a relationship (R2=0.04, p=0.21) between the EGP response to impaired suppression of glucagon and insulin action as measured at the time of screening by oral glucose tolerance. A similar analysis for hepatic insulin action did not show a relationship (R2=0.06, p=0.06) with the EGP response to non-suppressed glucagon. These data indicate that the change in EGP produced by impaired glucagon suppression is independent of anthropometric characteristics and insulin action. Disclosure M. C. Laurenti: None. A. M. Egan: None. D. Schembri wismayer: None. C. Cobelli: None. C. Dalla man: Research Support; Self; Becton, Dickinson and Company, Sanofi-Aventis Deutschland GmbH. A. Vella: Research Support; Self; Novo Nordisk. Funding National Institutes of Health (DK116231, DK78646)

SARS-CoV-2 vaccination of people living with human T leukaemia virus type 1

<b>Hardarson, T., Ziady, G. M., and Khattri, H. N. (1974).</b><i>Thorax</i>, <b>29</b>, 359-365. <b>Assessment of left ventricular function following coronary bypass surgery: a non-invasive study.</b> In a series of 15 patients...

High-dose spironolactone lacks effectiveness in treatment of fibromyalgia (RCT).

Spironolactone (SPL) is a reversible mineralocorticoid receptor (MR) and androgen receptor (AR) antagonist which attracts pharmacotherapeutic interest not only because of its beneficial effects in heart failure but also because of the pathogenetic roles of MR and AR activities in neuropsychiatric diseases. Recently, beneficial and rapid-onset effects of SPL have been documented in a case series of women with fibromyalgia syndrome (FMS). To reaffirm this observation, we performed a double-blind placebo-controlled randomized clinical trial (RCT). A total of 69 patients were screened, 56 patients were eligible and randomized to SPL or placebo (each n=28). Forty-three patients completed the clinical trial to the last visit (n=21 and n=22). After a run-in phase of 50 and 100mg/day, 200mg/day SPL or placebo were applied between days 7 and 28. Primary outcome was the change in the FIQ-G score (Fibromyalgia Impact Questionnaire, German version). Secondary outcome parameters were the changes in pain (numeric rating scale, NRS), mood (ADS), quality of life (SF-36) and change in FIQ scores 14days after the end of the medication. SPL of 200mg/day did not change significantly either the primary or the secondary end points. SPL evoked a transient rise in serum potassium and a transient fall in GFR maximal after 2weeks, but without clinical relevance. SPL at 200mg/day does not improve symptoms in women with FMS, but was considered not to cause harm. The mineralocorticoid receptor and androgen receptor antagonist spironolactone is repeatedly tested for its therapeutic effectivity against neuropsychiatric disorders. The present RCT demonstrated that 200mg spironolactone does not change the symptoms of the fibromyalgia syndrome (FMS) in adult women. Between 2 and 4weeks, spironolactone evokes a transient decrease in GFR and increase in serum potassium. Spironolactone cannot be recommended for the treatment of FMS.

Comparison of Single-Event Transients in an Epitaxial Silicon Diode Resulting From Heavy-Ion-, Focused X-Ray-, and Pulsed Laser-Induced Charge Generation

Heavy-ion, focused X-ray, and pulsed laser single-event transient (SET) experiments are performed on a silicon epitaxial diode. Collected charge, transient rise times, and transient fall times are calculated and compared between different sources. The transient shape characteristics depend on the source (ion, X-ray, or laser), even when similar amounts of charge are generated. The observed differences are examined and explained in terms of basic charge collection mechanisms.

The Calculation Method of PV Direct Current Energy Based on Modulated Broadband Mode Decomposition and Compound Simpson Integral Algorithm

The application of photovoltaic power is becoming more and more extensive presently, when the existing time-frequency analysis methods are used to analyze photovoltaic mutation signals such as transient rise and transient fall, the cornered signal will produce Gibbs phenomenon and leads to errors. Thus, the Broadband Mode Decomposition (BMD) method is proposed. The main idea of BMD is to search in the associated dictionary that contains the wideband and narrowband signals. However, the BMD algorithm may treat the wideband signal as several narrowband components, when applied to a wideband signal interfered by strong noise, because the relative bandwidth is not sufficiently small. Therefore, a modulated broadband modal decomposition (MBMD) based on the modulation differential operator is proposed. By multiplying a high-frequency single-frequency signal, the relative bandwidth of the effective wideband signal is much smaller than 1, and the wideband signal is processed as an approximate wideband signal. Meanwhile, because the errors of the traditional dot product sum algorithm in DC energy measurement cannot be positive and negative offset, while the compound Simpson integral algorithm has small error and high calculation accuracy. Therefore, a photovoltaic DC power calculation method based on the MBMD and compound Simpson integration is proposed.

Relation of Endothelin-1 to Abnormal Umbilical Doppler Waveform Studies in Pregnancies Complicated by IDDM and its Relation to the Neonatal Outcome

Introduction Endothelin-1 (ET-1) seems to act as a local paracrine signal rather than a circulating hormone. Its effects are mediated by specific, membrane- bound receptors, which are detectable in high concentrations in the fetoplacental tissue. ET-1 causes an initial transient fall in blood pre

Paneth Cell Alterations During Ischemia-reperfusion, Follow-up, and Graft Rejection After Intestinal Transplantation.

Ischemia-reperfusion injury is inevitable during intestinal transplantation (ITx) and executes a key role in the evolution towards rejection. Paneth cells (PCs) are crucial for epithelial immune defense and highly vulnerable to ischemia-reperfusion injury. We investigated the effect of ITx on PC after reperfusion (T0), during follow-up, and rejection. Moreover, we investigated whether PC loss was associated with impaired graft homeostasis. Endoscopic biopsies, collected according to center protocol and at rejection episodes, were retrospectively included (n = 28 ITx, n = 119 biopsies) Biopsies were immunohistochemically co-stained for PC (lysozyme) and apoptosis, and PC/crypt and lysozyme intensity were scored. We observed a decrease in PC/crypt and lysozyme intensity in the first week after ITx (W1) compared with T0. There was a tendency towards a larger decline in PC/crypt (P = 0.08) and lysozyme intensity (P = 0.08) in W1 in patients who later developed rejection compared with patients without rejection. Follow-up biopsies showed that the PC number recovered, whereas lysozyme intensity remained reduced. This persisting innate immune defect may contribute to the well-known vulnerability of the intestine to infection. There was no clear evidence that PCs were affected throughout rejection. This study revealed a transient fall in PC numbers in the early post-ITx period but a permanent reduction in lysozyme intensity following ITx. Further research is needed to determine the potential clinical impact of PC impairment after ITx.

Endogenous brain-sparing responses in brain pH and PO2 in a rodent model of birth asphyxia.

To study brain-sparing physiological responses in a rodent model of birth asphyxia which reproduces the asphyxia-defining systemic hypoxia and hypercapnia. Steady or intermittent asphyxia was induced for 15-45minutes in anaesthetized 6- and 11-days old rats and neonatal guinea pigs using gases containing 5% or 9% O2 plus 20% CO2 (in N2 ). Hypoxia and hypercapnia were induced with low O2 and high CO2 respectively. Oxygen partial pressure (PO2 ) and pH were measured with microsensors within the brain and subcutaneous ("body") tissue. Blood lactate was measured after asphyxia. Brain and body PO2 fell to apparent zero with little recovery during 5% O2 asphyxia and 5% or 9% O2 hypoxia, and increased more than twofold during 20% CO2 hypercapnia. Unlike body PO2 , brain PO2 recovered rapidly to control after a transient fall (rat), or was slightly higher than control (guinea pig) during 9% O2 asphyxia. Asphyxia (5% O2 ) induced a respiratory acidosis paralleled by a progressive metabolic (lact)acidosis that was much smaller within than outside the brain. Hypoxia (5% O2 ) produced a brain-confined alkalosis. Hypercapnia outlasting asphyxia suppressed pH recovery and prolonged the post-asphyxia PO2 overshoot. All pH changes were accompanied by consistent shifts in the blood-brain barrier potential. Regardless of brain maturation stage, hypercapnia can restore brain PO2 and protect the brain against metabolic acidosis despite compromised oxygen availability during asphyxia. This effect extends to the recovery phase if normocapnia is restored slowly, and it is absent during hypoxia, demonstrating that exposure to hypoxia does not mimic asphyxia.

Smart Baroreceptor Activation Therapy Strikingly Attenuates Blood Pressure Variability in Hypertensive Rats With Impaired Baroreceptor.

Increased blood pressure (BP) variability (BPV) is an independent risk factor of cardiovascular events among hypertensive patients. The arterial baroreceptor reflex is a powerful regulator of BP and attenuates BPV via a sympathetic negative feedback control. Conventional baroreceptor activation therapy (cBAT) electrically stimulates the carotid baroreceptors with constant stimulation parameters. While cBAT lowers BP, it does not mount a pressure feedback mechanism. We hypothesized that baroreceptor activation therapy with a pressure feedback system (smart BAT [sBAT]) is able to reduce BPV as well as lower BP. We developed sBAT that electrically stimulated baroreceptors at a frequency proportional to the difference between instantaneous BP and a preset reference pressure, and compared its performance with cBAT. In 14-week-old spontaneously hypertensive rats (n=6), we implanted BP telemeter and created impaired arterial baroreceptors by modified sino-aortic denervation. One week after surgical preparation, we administered sBAT, cBAT or no stimulation (sham) for 15 minutes and compared BP and BPV under freely moving condition. Both cBAT and sBAT significantly lowered mean BP (sham, 141.3±12.8; cBAT, 114.3±11.4; and sBAT, 112.0±7.3 mm Hg). Conventional BAT did not affect BPV at all, while sBAT significantly reduced BPV (sham, 15.4±2.6; cBAT, 16.0±5.2; and sBAT, 9.7±3.3 mm Hg). sBAT also prevented transient excessive BP rise and fall. In conclusion, sBAT was capable of reducing BP and attenuating BPV in hypertensive rats with impaired baroreceptor. sBAT is a novel treatment option for hypertensive patients with increased BPV.