Fructose Administration Increases Intraoperative Core Temperature by Augmenting Both Metabolic Rate and the Vasoconstriction Threshold

Mer om hvordan fruktose øker kroppvarme (termogenese). I denne er det snakk om å bruke det intravenøst for å unngå at pasienter blir kalde etter operasjoner. Det øker restitusjonsevnen etter operasjonen.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1473168/

Abstract

Background

We tested the hypothesis that intravenous fructose ameliorates intraoperative hypothermia both by increasing metabolic rate and the vasoconstriction threshold (triggering core temperature)

Methods

40 patients scheduled for open abdominal surgery were divided into two equal groups and randomly assigned to intravenous fructose infusion (0.5 g·kg−1·h−1 for 4 h, starting 3 h before induction of anesthesia and continuing for 4 hours) or an equal volume of saline. Each treatment group was subdivided: esophageal core temperature, thermoregulatory vasoconstriction, and plasma concentrations were determined in half, and oxygen consumption was determined in the remainder. Patients were monitored for 3 h after induction of anesthesia.

Results

Patient characteristics, anesthetic management, and circulatory data were similar in the four groups. Mean final core temperature (3 h after induction of anesthesia) was 35.7±0.4°C (mean ± SD) in the fructose group and 35.1±0.4°C in the saline group (P=0.001). The vasoconstriction threshold was greater in the fructose (36.2±0.3°C) than in the saline group (35.6±0.3°C; P<0.001). Oxygen consumption immediately before anesthesia induction in the fructose group (214±18 ml/min) was significantly greater than in the saline group (181±8 ml/min, P<0.001). Oxygen consumption was 4.0 L greater in the fructose patients during 3 hours of anesthesia; the predicted difference in mean-body temperature based only on the difference in metabolic rates was thus only 0.4°C. Epinephrine, norepinephrine, and angiotensin II concentrations, and plasma renin activity were similar in each treatment group.

Conclusions

Preoperative fructose infusion helped maintain normothermia by augmenting both metabolic heat production and increasing the vasoconstriction threshold.

Fructose is known to provoke the greatest thermogenesis among various carbohydrates.19,20 Fructose also provokes dietary-induced thermogenesis in awake healthy volunteers, and does so far better than glucose.15 We thus tested the hypothesis that intravenous fructose increases metabolic heat production in anesthetized humans. We also tested the hypothesis that fructose, like amino acids, increases the vasoconstriction threshold and thus has a thermoregulatory as well as metabolic contribution to maintaining perioperative normothermia.

CO2 production before infusion showed no significant difference between saline group (147+19 ml min−1) and fructose group (142+16 ml min−1) but increased significantly in the fructose group (201+26 ml min−1) just before induction of anesthesia, compared with the saline group (146+19 ml min−1)(p<0.001). This increased level was maintained for 135 min after induction of anesthesia.

HIF-1α and HIF-2α induce angiogenesis and improve muscle energy recovery.

HIF er et signalmolekyl som aktiverer angiogenese, altså produksjonen av nye blodkar. Ved lave oksygennivåer økes HIF. Dette kan komme fra trening, men også fra øvelser med å holde pusten.

http://www.ncbi.nlm.nih.gov/pubmed/25208310

Abstract

BACKGROUND:

Cardiovascular patients suffer from reduced blood flow leading to ischemia and impaired tissue metabolism. Unfortunately, an increasing group of elderly patients cannot be treated with current revascularization methods. Thus, new treatment strategies are urgently needed. Hypoxia inducible factors (HIFs) upregulate the expression of angiogenic mediators together with genes involved in energy metabolism and recovery of ischemic tissues. Especially, HIF-2α is a novel factor and only limited information is available about its therapeutic potential.

METHODS:

Gene transfers with adenoviral HIF-1α and HIF-2α were done into the mouse heart and rabbit ischemic hindlimbs. Angiogenesis was evaluated by histology. Left ventricle function was analysed with echocardiography. Perfusion in rabbit skeletal muscles and energy recovery after electrical stimulation-induced exercise were measured with ultrasound and 31 P-magnetic resonance spectroscopy (31 P-MRS), respectively.

RESULTS:

HIF-1α and HIF-2α gene transfers increased capillary size up to 5-fold in myocardium and ischemic skeletal muscles. Perfusion in skeletal muscles was increased by 4-fold without edema. Especially AdHIF-1α enhanced the recovery of ischemic muscles from electrical stimulation-induced energy depletion. Special characteristic of HIF-2α gene transfer was a strong capillary growth in muscle connective tissue and that HIF-2α gene transfer maintained left ventricle function.

CONCLUSIONS:

We conclude that both AdHIF-1α and AdHIF-2α gene transfers induced beneficial angiogenesis in vivo. Transient moderate increases in angiogesis improved energy recovery after exercise in ischemic muscles. This study shows for the first time that a moderate increase in angiogenesis is enough to improve tissue energy metabolism which is potentially a very useful feature for cardiovascular gene therapy.

Inflammatory Cytokine Concentrations Are Acutely Increased by Hyperglycemia in Humans

Denne viser hvordan selv de uten diabetes får økt cytokinverdi (betennelse) i blodet i 1-2 timer etter blodsukkerstigning. I denne studien var det snakk om blodsukker over 15 mmol/L. De sier at blodsukker økninger påvirker cytokinnivået mer enn et stabilt høyt blodsukker.

http://circ.ahajournals.org/content/106/16/2067.full

Control Subjects:

Plasma IL-6 levels rose from a basal value of 2.0±0.7 pg/mL to a peak of 3.1±0.9 pg/mL at 1 hour (P<0.01) and returned to basal level at 3 hours (Figure 2).

Fasting plasma TNF-α levels were 3.3±1.2 pg/mL; they peaked at 1 hour (4.9±1.4 pg/mL, P<0.01), and returned to baseline at 3 hours.

Plasma IL-18 levels rose from a basal value of 116±28 pg/mL to a peak of 140±31 pg/mL at 2 hours (P<0.01) and returned to basal levels at 3 hours (110±26 pg/mL).

The novel findings of the present study were that (1) acute hyperglycemia in control and in IGT subjects induces an increase in plasma IL-6, TNF-α, and IL-18 concentrations; (2) the effect of sustained hyperglycemia is reproduced by transient oscillations in plasma glucose and is amplified by the IGT status; and (3) the antioxidant glutathione completely prevents the rise in plasma cytokines induced by hyperglycemia. These results indicate that hyperglycemic spikes affect cytokine concentrations more than continuous hyperglycemia, at least in the short term, and suggest that an oxidative mechanism mediates the effect of hyperglycemia.

Another finding of the present study was that glutathione, a powerful antioxidant, completely prevented cytokine increase induced by oscillatory hyperglycemia in healthy humans. Hyperglycemia-induced oxidative stress, 32 along with soluble advanced glycation end products and products of lipid peroxidation, possibly serves as a key activator of upstream kinases, leading to induction of inflammatory gene expression.33

The evolutionary origin of form and function

Spennende studie som nevner at gener har lite med utvikling av organismer å gjøre. Det er heller «the second law of thermodynamics» som styrer det.

In summary, we propose that the life process is based not on genetic variation, but on the second law of thermodynamics (hereinafter the second law) and the principle of least action, as proposed for thermodynamically open systems by De Maupertuis (Ville et al2008), which at the most fundamental level say the same thing.

Det som avgjør om en organisme er levedyktig eller ikke er dens evne til å hente energi fra omgivelsene. For oss kan dette peke på jo mer effektiv blodsirkulasjonens distribusjon av oksygen til cellene er, jo mer fri energi har vi tilgjengelig.

In this reformulation form and function, extant and extinct, are the consequence of natural selection acting primarily upon the ability of organisms to extract energy (nutrient) from their environment, as pointed out in 1835, prior to the publication of Origin, by Edward Blyth (Blyth, 1835).

De reformulerer også definisjonen på entropi, som vanligvis er sett på som kaos. Her sier de at det egentlig bør oppfattes som en organisert kompleksitet fordi den bundede energien i lavere livsformer er tilgjengelig som fri energi for høyere livsformer. Det er fullt mulig dette kan forståes i sammenheng med mitokondrias funksjon for oss. Energien som mitokondria skaper blir tilgjengelig som fri energi for oss.

Energy, in the form of nutrient, is consumed, thereby producing entropy, according to the second law in the most efficient way (least action) possible given the conditions. Under these circumstances, explicitly thermodynamically open systems, entropy is maximised in the form of organisation or complexity (Sharma & Annila, 2007) and not, as proposed by Boltzmann, disorder (Sharma & Annila2007). In terms of the food chain, the entropy (bound energy) of lower forms is available as free energy (nutrient) for higher forms.

Gener fungerer bare som en blueprint for de erfaringene molekyler og celler gjør seg med omgivelsene. Genene er notisblokken.

We predicate the current proposal on a metabolism-first origin of life (Baverstock, 2013), in which proteins, free of DNA, were a form of proto-life. Life appeared when these proto-life forms recruited nucleic acids in the form of DNA to act as a template for replication and to code for essential peptides (Annila & Baverstock, 2014) through the process of reverse translation making it possible for true replication to occur.

Sett i lys av dette kan vi innse at gen-mutasjon har lite å gjøre med evolusjon.

In other words mutation of existing coding sequences is unnecessary for evolution to have taken place – that is not to say that evolution has not taken advantage of mutational events, but that genetic variation is not rate limiting.

De forklarer også hvorfor f.eks. en mus og et menneske har nesten helt samme genuttykk, men helt forskjellig form og funksjon.

Thus, for example, mouse and man are phenotypically distinct organisms with closely similar genotypes (Baverstock, 2011), that is, a near identical complement of peptides, which give rise through dissipative information generating processes within the cell, to two distinct information outputs (phenotypes).

De konkluderer med at utvikling skjer ved at en organisme utvikler bedre måter å tilegne seg energi fra omgivelsene på. F.eks. kan mitokontria, respirasjonssystemet, sirkulasjonssystemet og nervesystemet være funksjoner som gir bedre tilegning og utnyttelse av energi i en organisme slik vi er. 

The evolution of multicellular organisms with complex forms and functional abilities can be accounted for based on a fundamental tenet underpinned by the second law of thermodynamics, with natural selection acting on the ability of the organism to transduct energy (nutrient) most efficiently from its ecosystem by deploying that form and those functions.

http://onlinelibrary.wiley.com/enhanced/doi/10.1113/jphysiol.2014.271775/

RR interval-respiratory signal waveform modeling in human slow paced and spontaneous breathing.

Enda en bekreftelse på at pusten påvirker vagusnerven, og vagusnerven påvirker betennelser. Og at 0,1Hz (6 pust i minuttet) gir sterkest påvirkning på vagusnerven.

http://www.ncbi.nlm.nih.gov/pubmed/25139803/

Denne studien var en datamodell av hvordan forskjellige elementer av pusten (dybde og hastighet i dette tilfellet) påvirker hjerterytmen, som uttrykker vagusnerven. De fant at pustefrekvensen påvirket mest, altså hastigheten i dette tilfellet. 

The model’s results depended on breathing frequency with the least error occurring during slow paced breathing.

Deres forklaring på hvorfor pusten påvirker hjerterytmen er at strekk-reseptorer i lungene sier ifra om lungevolum som hjernen så bruker til å vurdere kardiovagale (vagusnervens påvirkning på hjertet) signaler.

Assuming that a0 represents slowly adapting pulmonary stretch receptors (SARs) and a1 SARs in coordination with other stretch receptors and central integrative coupling; then pulmonary stretch receptors relaying the instantaneous lung volume are the major factor determining cardiovagal output during inspiration.

De sier at ved forskjellige sykdommer blir det dårligere forbindelse mellom blodstrømning, blodtrykk, hjerterytme og pust, som gir ustabil kardivagal styring.

The role of vagal afferent neurons in cardiorespiratory coupling may relate to neurocardiovascular diseases in which weakened coupling among venous return, arterial pressure, heart rate and respiration produces cardiovagal instability.

Dette kan bidra til saktere, eller manglende, helbredelse av sykdom. Når man lærer å bruke pusten til å styrke vagusnerven er man i det minste én faktor nærmere helbredelse.

 

Sukker + inflammasjon = sant?

Veldig bra artikkel om norsk forskning som gjøres på forholdet mellom mat og betennelser. Beskriver hvordan urinsyrekrystaller, som kommer fra leverens omdanning av sukker til fett, aktiverer immunceller i blodårene og skaper betennelser. Nevner også at kolesterolkrystaller, som kommer fra kolesteroloppsamling på blodkarveggene, kan gi samme aktivering av immunsystemets betennelsesmekanisme.

http://blog.medisin.ntnu.no/sukker-inflammasjon-sant/

Inflammasjon må reguleres nøye, for dersom immunforsvaret overreagerer kan responsen i seg selv gi mer skade enn selve årsaken. Kronisk inflammasjon kobles blant annet til sykdommer som aterosklerose (åreforkalkning), overvekt, kreft, diabetes (sukkersyke) og demens.

 

Cellene sender da ut et kraftig rop om hjelp, som aktiverer immunforsvaret ytterligere. Dette nødsignalet er tett regulert, for om det skyter over mål får vi en kronisk inflammasjon. Om dette manifesterer seg i et ledd får vi rødme, varme, smerte, og hevelse, kanskje bedre kjent som sykdommen urinsyregikt.

Vi fullfører for tiden et prosjekt hvor vi har sett på om kolesterolkrystaller aktiverer immunforsvaret på samme måte. Også her overreagerer nemlig immunforsvaret, og konsekvensen kan være at selve åreveggen, og ikke krystallene brytes ned. Dette kan gi et sår, som igjen kan gi en blodpropp

 

Vibration Therapy in Management of Delayed Onset Muscle Soreness (DOMS).

Svært interessant studie på hvordan vibrasjon (percussor) hjelper mot smerte og stølhet. Den snakker mest om whole-body-vibration, som f.eks. på en Vibroplate. Men de fleste fysiologiske effektene gjelder også for lokal vibrasjon som gis av en Percussor. 

http://www.ncbi.nlm.nih.gov/pubmed/25121012

Hele studien her: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4127040/

Abstract

Both athletic and nonathletic population when subjected to any unaccustomed or unfamiliar exercise will experience pain 24-72 hours postexercise. This exercise especially eccentric in nature caused primarily by muscle damage is known as delayed-onset muscle soreness (DOMS). This damage is characterized by muscular pain, decreased muscle force production, reduce range of motion and discomfort experienced. DOMS is due to microscopic muscle fiber tears. The presence of DOMS increases risk of injury. A reduced range of motion may lead to the incapability to efficiently absorb the shock that affect physical activity. Alterations to mechanical motion may increase strain placed on soft tissue structures. Reduced force output may signal compensatory recruitment of muscles, thus leading to unaccustomed stress on musculature. Differences in strength ratios may also cause excessive strain on unaccustomed musculature. A range of interventions aimed at decreasing symptoms of DOMS have been proposed. Although voluminous research has been done in this regard, there is little consensus among the practitioners regarding the most effective way of treating DOMS. Mechanical oscillatory motion provided by vibration therapy. Vibration could represent an effective exercise intervention for enhancing neuromuscular performance in athletes. Vibration has shown effectiveness in flexibility and explosive power. Vibration can apply either local area or whole body vibration. Vibration therapy improves muscular strength, power development, kinesthetic awareness, decreased muscle sore, increased range of motion, and increased blood flow under the skin. VT was effective for reduction of DOMS and regaining full ROM. Application of whole body vibration therapy in postexercise demonstrates less pressure pain threshold, muscle soreness along with less reduction maximal isometric and isokinetic voluntary strength and lower creatine kinase levels in the blood.

 

Cutaneous Receptors Responses: The sensation of pressure and touch is masked during vibration [20], and also postvibration [21]. Some cutaneous mechanoreceptor afferents get aroused for many minutes postvibration [21] and this may be the physiological reason for the tingling sensation often experienced postvibration. On the basis of gate control hypothesis [22] we can infer that vibration strongly impacts affrents discharge from fast adapting mechanoreceptors and muscle spindles and hence become an effective pain reliever.

Pain Perception Responses: Vibration can be used as transcutaneous electrical nerve stimulation (TENS) [23] to reduce the perception of pain [7]. Passive vibration has reduced pain in 70% of patients with acute and chronic musculoskeletal pain [24] and passive 80 Hz vibration has been shown to reduce pain caused by muscle pressure [25]. More recent evidence suggests that pain perception in DOMS depends partly on fast myelinated afferent fibres, which are distinct from those that convey most other types of pain [26].

Lundeberg et al., concluded that vibration relieved pain by activating the large diameter fibres while suppressing the transmission activity in small diameter fibres [24,28].

Vibration therapy leads to increase of skin temperature and blood flow [30].