The Regulation of Skeletal and Cardiac Muscle Blood Flow in Humans. Studies by positron emission tomography with special reference to exercise, adenosine and nitric oxide

Virtually every cell and organ in the human body is dependent on a proper oxygen supply. This is taken care of by the cardiovascular system that supplies tissues with oxygen precisely according to their metabolic needs. Physical exercise is one of the most demanding challenges the human circulatory system can face. During exercise skeletal muscle blood flow can easily increase some 20-fold and its proper distribution to and within muscles is of importance for optimal oxygen delivery. The local regulation of skeletal muscle blood flow during exercise remains little understood, but adenosine and nitric oxide may take part in this process. In addition to acute exercise, long-term vigorous physical conditioning also induces changes in the cardiovasculature, which leads to improved maximal physical performance. The changes are largely central, such as structural and functional changes in the heart. The function and reserve of the heart’s own vasculature can be studied by adenosine infusion, which according to animal studies evokes vasodilation via it’s a2A receptors. This has, however, never been addressed in humans in vivo and also studies in endurance athletes have shown inconsistent results regarding the effects of sport training on myocardial blood flow. This study was performed on healthy young adults and endurance athletes and local skeletal and cardiac muscle blod flow was measured by positron emission tomography. In the heart, myocardial blood flow reserve and adenosine A2A receptor density, and in skeletal muscle, oxygen extraction and consumption was also measured. The role of adenosine in the control of skeletal muscle blood flow during exercise, and its vasodilator effects, were addressed by infusing competitive inhibitors and adenosine into the femoral artery. The formation of skeletal muscle nitric oxide was also inhibited by a drug, with and without prostanoid blockade. As a result and conclusion, it can be said that skeletal muscle blood flow heterogeneity decreases with increasing exercise intensity most likely due to increased vascular unit recruitment, but exercise hyperemia is a very complex phenomenon that cannot be mimicked by pharmacological infusions, and no single regulator factor (e.g. adenosine or nitric oxide) accounts for a significant part of exercise-induced muscle hyperemia. However, in the present study it was observed for the first time in humans that nitric oxide is not only important regulator of the basal level of muscle blood flow, but also oxygen consumption, and together with prostanoids affects muscle blood flow and oxygen consumption during exercise. Finally, even vigorous endurance training does not seem to lead to supranormal myocardial blood flow reserve, and also other receptors than A2A mediate the vasodilator effects of adenosine. In respect to cardiac work, atheletes heart seems to be luxuriously perfused at rest, which may result from reduced oxygen extraction or impaired efficiency due to pronouncedly enhanced myocardial mass developed to excel in strenuous exercise.Siirretty Doriast

Existence and non-existence of minimal graphic and p-harmonic functions

To appearWe prove that every entire solution of the minimal graph equation that is bounded from below and has at most linear growth must be constant on a complete Riemannian manifold M with only one end if M has asymptotically non-negative sectional curvature. On the other hand, we prove the existence of bounded non-constant minimal graphic and p-harmonic functions on rotationally symmetric Cartan-Hadamard manifolds under optimal assumptions on the sectional curvatures.Peer reviewe

Solvability of Minimal Graph Equation Under Pointwise Pinching Condition for Sectional Curvatures

We study the asymptotic Dirichlet problem for the minimal graph equation on a Cartan-Hadamard manifold M whose radial sectional curvatures outside a compact set satisfy an upper bound K(P) and a pointwise pinching condition |K(P)| for some constants phi > 1 and C-K >= 1, where P and P ' a re any 2-dimensional subspaces of TxM containing the (radial) vector del(x) and r (x) = d(o,x) is the distance to a fixed point o. M. We solve the asymptotic Dirichlet problem with any continuous boundary data for dimensions n = dim M > 4/phi+ 1.Peer reviewe

Relationships of leisure-time physical activity and work ability between different occupational physical demands in adult working men

Purpose Leisure-time physical activity (LTPA) is known to be associated with positive health benefits, but the role of occupational physical demands remains inconsistent. The purpose of the current study was to assess the relationship between LTPA and work ability in different occupational physical activity (OPA) levels between young adult men. Methods We performed physical activity measurements in work and leisure time with the long version of International Physical Activity Questionnaire (IPAQ) and work ability with the Work Ability Index (WAI) in 921 Finnish employed male volunteer participants. The participants were divided into LTPA tertiles I ( 28 MET-h/week) and OPA tertiles I (0 MET-h/week), II (= 64 MET-h/week). Results There was a significant relationship between LTPA and WAI in OPA tertiles (adjusted for age, alcohol consumption, working class status, BMI, and employment years). Moreover, each LTPA tertile showed significant linear associations with WAI (P <0.001). Conclusion LTPA is positively associated with work ability among young adult men. More specifically, the relationships between LTPA and WAI were significantly greater in physically demanding jobs than in more passive jobs. Our results indicate the importance of LTPA, particularly with individuals under higher work-related physical strain.Peer reviewe

The circulatory and metabolic responses to hypoxia in humans - with special reference to adipose tissue physiology and obesity

Adipose tissue metabolism and circulation play an important role in human health. It is well-known that adipose tissue mass is increased in response to excess caloric intake leading to obesity and further to local hypoxia and inflammatory signaling. Acute exercise increases blood supply to adipose tissue and mobilization of fat stores for energy. However, acute exercise during systemic hypoxia reduces subcutaneous blood flow in healthy young subjects, but the response in overweight or obese subjects remains to be investigated. Emerging evidence also indicates that exercise training during hypoxic exposure may provide additive benefits with respect to many traditional cardiovascular risk factors as compared to exercise performed in normoxia, but unfavorable effects of hypoxia have also been documented. These topics will be covered in this brief review dealing with hypoxia and adipose tissue physiology

Translating solitons over Cartan-Hadamard manifolds

We prove existence results for entire graphical translators of the mean curvature flow (the so-called bowl solitons) on Cartan-Hadamard manifolds. We show that the asymptotic behaviour of entire solitons depends heavily on the curvature of the manifold, and that there exist also bounded solutions if the curvature goes to minus infinity fast enough. Moreover, it is even possible to solve the asymptotic Dirichlet problem under certain conditions.Comment: This replaces the first version. We have deleted the whole Section 3 from the previous version due to a gap in a proof. We are grateful to Dr. Hengyu Zhou for pointing out the gap in the proof of Lemma 3.3 in the previous versio

Non-parametric mean curvature flow with prescribed contact angle in Riemannian products

Assuming that there exists a translating soliton u(infinity) with speed C in a domain Omega and with prescribed contact angle on partial derivative Omega, we prove that a graphical solution to the mean curvature flow with the same prescribed contact angle converges to u(infinity) + Ct as t -> infinity. We also generalize the recent existence result of Gao, Ma, Wang and Weng to non-Euclidean settings under suitable bounds on convexity of Omega and Ricci curvature in Omega.Peer reviewe

Busy day effect on the use of obstetrical interventions and epidural analgesia during labour : a cross-sectional register study of 601 247 deliveries

Background Daily delivery volume might affect the quality of obstetric care. We explored the busy day effect on selected obstetrical interventions and epidural analgesia performed during labour in different sized delivery hospitals and on the Finnish obstetric ecosystem. Methods We conducted a cross-sectional study on Finnish Medical Birth Register data of singleton pregnancies (N = 601,247) from 26 delivery hospitals from 2006 to 2016. Delivery hospitals were stratified by annual delivery volume: C (category) 1: = 3000, and C5: university hospitals. The exposure variables were defined as quiet, optimal, and busy days determined based on daily delivery volume distribution in each hospital category. Quiet and busy days included approximately 10% of the lowest and highest delivery volume days, while the rest were defined as optimal. Outcome measures were unplanned caesarean section (CS), instrumental delivery, induction of labour, and epidural analgesia. We compared the incidence of outcomes in quiet vs. optimal, busy vs. optimal, and busy vs. quiet days using logistic regression. The statistical significance level was set at 99% to reduce the likelihood of significant spurious findings. Results In the total population, the incidence of instrumental delivery was 8% (99% CI 2-15%) lower on quiet than on optimal days. In smaller hospitals (C1 and C2), unplanned caesarean sections were performed up to one-third less frequently on busy than optimal and quiet days. More (27%, 99% CI 12-44%) instrumental deliveries were performed in higher delivery volume hospitals (C4) on busy than quiet days. In C1-C3, deliveries were induced (12-35%) less often and in C5 (37%, 99% CI 28-45%) more often on busy than optimal delivery days. More (59-61%) epidural analgesia was performed on busy than optimal and quiet days in C4 and 8% less in C2 hospitals. Conclusions Pooled analysis showed that busyness had no effect on outcomes at the obstetric ecosystem level, but 10% fewer instrumental deliveries were performed in quiet than on busy days overall. Furthermore, dissecting the data shows that small hospitals perform less, and large non-tertiary hospitals perform more interventions during busy days.Peer reviewe

Animal models of heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) constitutes a clinical syndrome in which the diagnostic criteria of heart failure are not accompanied by gross disturbances of systolic function, as assessed by ejection fraction. In turn, under most circumstances, diastolic function is impaired. Although it now represents over 50% of all patients with heart failure, the mechanisms of HFpEF remain understood, precluding effective therapy. Understanding the pathophysiology of HFpEF has been restricted by both limited access to human myocardial biopsies and by the lack of animal models that fully mimic human pathology. Animal models are valuable research tools to clarify subcellular and molecular mechanisms under conditions where the comorbidities and other confounding factors can be precisely controlled. Although most of the heart failure animal models currently available represent heart failure with reduced ejection fraction, several HFpEF animal models have been proposed. However, few of these fulfil all the features present in human disease. In this review we will provide an overview of the currently available models to study HFpEF from rodents to large animals as well as present advantages and disadvantages of these models