76 research outputs found
Effects of adenosine on pressure-flow relationships in an in vitro model of compartment syndrome
No full text Shrier, Ian, Ari Baratz, and Sheldon Magder. Effects of adenosine on pressure-flow relationships in an in vitro model of compartment syndrome. J. Appl. Physiol. 82(3): 755–759, 1997.—Blood flow through skeletal muscle is best modeled with a vascular waterfall at the arteriolar level. Under these conditions, flow is determined by the difference between perfusion pressure (Pper) and the waterfall pressure (Pcrit), divided by the arterial resistance (Ra). By pump perfusing an isolated canine gastrocnemius muscle ( n = 6) after it was placed within an airtight box, with and without adenosine infusion, we observed an interaction between the pressure surrounding a muscle (as occurs in compartment syndrome) and baseline vascular tone. We titrated adenosine concentration to double baseline flow. We measured Pcrit and Ra at box pressures (Pbox), which resulted in 100 (Pbox = 0), 90, 75, and 50% flow without adenosine; and 200, 180, 150, 100, and 50% flow with adenosine. Without adenosine, each 10% decline in flow was associated with a 5.7 mmHg increase in Pcrit ( P < 0.01). With adenosine, the same decrease in flow was associated with a 2.6-mmHg increase in Pcrit ( P < 0.01). Values of Pcrit at 50% of flow were almost identical. Each 10% decrease in flow was also associated with 2.2% increase in Ra with or without adenosine ( P < 0.001). Ra decreased with adenosine infusion ( P < 0.05), and there was no interaction between adenosine and flow ( P > 0.9). We conclude that increases in pressure surrounding a muscle limit flow primarily through changes in Pcrit with and without adenosine-induced vasodilation. The interaction between Pbox and adenosine with respect to Pcrit but not Ra suggests that Pbox affects the tone of the vessels responsible for Pcrit but not Ra. </jats:p
Critical closing pressures, vascular waterfalls, and the control of blood flow to the hindlimb
No full textNote:Pressure- flow relations in the hindlimb are best explained by a model which incorporates a vascular waterfall at the level of the arterioles. The mechanisms controlling the critical pressure at the waterfall (P crit) and arterial resistance (~) were examined in the canine hindlimb. Lowering carotid sinus pressure (Pear) caused both P crit and Ra to increase (neural response). Increases in local perfusion pressure (P per) caused P crit to increase (predominantly a myogenic response), but Ra to decrease (predominately a passive or flow-mediated response). When tone was increased by blocking the synthesis of endothelium-derived relaxing factor or through a1 - activation, the myogenic response of P crit increased and the decrease in Ra with increasing P per was abolished. The myogenic response of P crit was not eliminated with a calcium-channel blocker, nor when reactive hyperemia was abolished with maximal vasodilation. However, maximal vasodilation lowered P crit below the downstream pressure, thereby eliminating waterfall behaviour during normal flow. These findings suggest that P crit and Ra are dependent on the interaction of several different control systems.C'est le modelé intégrant une cascade de réactions vasculaires au niveau des artérioles qui peut le mieux rendre compte des relations entre la pression et le débit dans les membres antérieurs. Les mécanismes qui contrôlent la pression critique au point de cascade P crit et la résistance arterielle (Ra ) ont été étudies dans les membres antérieurs de chiens. L'abaissement de la pression du sinus carotidien (P car) a entrainé une augmentation de P crit et de Ra (réponse neurale). L'augmentation de la pression locale a provoqué l'augmentation de P Crit (réponse avant tout myogénique), mais un abaissement de Ra (réponse avant tout passive ou à médiation par le débit). L'augmentation de tonus par blocage de la synthèse du facteur de relaxation dérive de l'endothélium ou par activation a1 a provoqué l'augmentation de la réaction myogénique de P Crit et l'abaissement de Ra , qui est fonction de l'augmentation de P per, a été supprimé. L'administration d'un inhibiteur des voies du calcium n'a pas supprime la réaction myogénique de P Crit non plus que la vasodilatation maximale n'a fait disparaitre l'hyperémie réactive. Toutefois, la vasodilatation maximale a abaisse P crit sous la pression en aval, supprimant ainsi le phénomène de cascade pendant le débit normal. Ces résultats semblent indiquer que P crit et RA dépendent de 1 'interaction de plusieurs systèmes de contrôle distincts
Endothelial dependent dilation by estrogen through the AKTPKB pathway
No full textAcute administration of estrogen results in the vasodilatation and in the release of nitric oxide (NO) that occurs through activation of the serine-threonine kinase Akt/protein-kinase-B (PKB), which is known to increase the eNOS activity. 10-8 M of 17-beta-estradiol resulted in a left shift of the vasodilatory response to Ach in preconstricted aortic rings from oophorectomized rats (EC50 = 0.7 x 10-8 M with 17-beta-estradiol and 0.15 x 10-7 M of Ach without 17-beta-estradiol, P < 0.05). The effect was blocked by pre-treatment with Wortmannin, a PI(3)K inhibitor. AKT/PKB was phosphorylated in endothelial cells (EC) as early as 1-minute after estradiol-stimulation. Phosphorylation of eNOS and NO release in EC treated with 17-beta-estradiol were also increased. We conclude that the AKT/PKB pathway is involved in the acute release of NO by estrogen
Role of nitric oxide and its interaction with superoxide in porcine model of septic shock
No full textAlthough nitric oxide (NO) from inducible nitric oxide synthase (NOSII) is proposed to be the major factor in the vascular abnormalities of sepsis in rats, its role in higher order species is not well established. This thesis thus, addresses the role of NO in septic pigs.I first hypothesized that induction of NOSII in pigs is the cause of sepsis-induced hypotension as occurs in rodents. To test this, I treated pigs with lipopolysaccharide (LPS) to simulate sepsis. In contrast to what is observed in rats and mice, plasma nitrite did not change during the 4 hours of the LPS infusion and there was no increase in calcium (Ca)-independent nitric oxide synthase (NOS) activity in lung tissue from endotoxemic pigs compared to control animals. Furthermore, there was only minimal induction of NOSII mRNA.My second hypothesis was that NOS (NOSIII) is not down regulated in septic pigs, and NO from NOSIII, could contribute to peroxynitrite formation. In support of this, western blot analysis of samples from aorta and vena cava showed no down regulation of NOSIII. There also was an increase in Ca ++-dependent NOS activity of aorta and vena cava after 2-hour of endotoxemia, which indicates increased constitutive NOS activity. Moreover, there was an increase in NOSI in the vena cava. LPS produced a leftward shift in the dose-response curves of SVR and RVR in response to the NOS inhibitor, L-NAME (NG -nitro-L-arginine-methyl-ester).Peroxynitrite is formed from NO and superoxide (O2 -). Since NO was not increased in endotoxemic pigs, I next hypothesized that O2- is increased in endotoxemic pigs and this reacts with NO from constitutive NOS to form peroxynitrite. To test this hypothesis, I first studied rats to confirm that O2 - is increased in arterial vessels of endotoxic rats. There was a small increase in basal O2- in endotoxic rats. Stimulation of NAD(P)H oxidase by giving the substrate, NADH, did not result in different O2- production in control and endotoxic rats. However, inhibition of NOS increased O2 - in endotoxic rats.I demonstrated by immunohistochemistry and western blot analysis, that the components of NAD(P)H oxidase, gp91phox, p22phox , and p47phox are present in skeletal muscle and it has similar behavior to other non-phagocytic NADPH oxidases. The addition of L-NAME to NADH-treated diaphragm strips of endotoxic rats, increased O 2- production in endotoxic rats indicating that O2- production counters the increased NO formation as we observed in rat aorta. These observations indicate that O2 - generation from NADPH oxidase in skeletal muscles can play a role in the pathophysiology of sepsis. (Abstract shortened by UMI.
Peripheral vs central control of cardiac output
No full textNeural, humoral and mechanical factors affecting cardiac function and the peripheral vasculature were examined to assess the relative importance of peripheral vs cardiac factors in the control of cardiac output during exercise. First, I examined neural vs local regulation of humoral vasoconstrictors endothelin-1 (ET) and NPY, in anesthetized dogs, and showed that plasma ET levels, in contrast to NPY, increase in response to systemic hypotension but not carotid sinus baroreceptor activation. This did not occur with intact vagi suggesting an interaction of neural and humoral factors. In the next two studies I separated peripheral vascular and cardiac neural influences on cardiac output (CO) and right atrial pressure (Pra) responses during graded exercise by comparing cardiac denervated heart transplant patients (HT) with normally innervated subjects. The increase in Pra was higher in HT than normals but stabilized as the CO increased at peak effort. Stimulation of the heart with dobutamine in 2 patients did not increase exercise capacity, suggesting that peripheral not cardiac factors limit exercise in HT patients. The rise in central venous pressure at exercise onset was similar in both groups which demonstrates the importance of the mechanical effect of muscle contraction vs reflex changes in mobilizing blood from the peripheral vasculature at exercise onset. In the fourth study I assessed whether large changes in human body mass, induced by isolated gastric bypass surgery, would affect the heart rate (HR)/oxygen consumption (VO2) relationship during exercise. Peak absolute VO2 was significantly lower in the previously obese group vs obese and control groups despite similar normalized 24-hour energy expenditure. HR was higher in the previously obese at a given submaximal VO2 due to the higher relative VO2, suggesting a significant loss of muscle mass and supporting the idea that HR is a function of the relative VO2. In the fifth study I assessed the influence o
Intracellular pH Regulation and the Acid Delusion
No full textThe concentration H+ ([H+]) in intracellular fluid (ICF) must be maintained in a narrow range in all species for normal protein functions. Thus, mechanisms regulating ICF are of fundamental biological importance. Studies on the regulation of ICF [H+] have been hampered by use of pH notation,failure to consider the roles played by differences in the concentration of strong ions ( SID), the conservation of mass, the principle of electrical neutrality and that [H+] and [HCO3-] are dependent variables. This argument is based on the late Peter Stewart’s physical- chemical analysis of [H+] regulation reported in this journal nearly forty years ago. We start by outlining the principles of Stewart’s analysis and then provide a general understanding of its significance for regulation of ICF [H+]. The system may initially appear complex, but it becomes evident that changes in SID dominanate regulation of [H+]. The primary strong ions are Na+, K+ and Cl-, and a few organic strong anions. The second independent variable, PCO2, can easily be assessed. The third independent variable, the activity of intracellular weak acids ([Atot]), is much more complex but largely plays a modifying role. Attention to these principles potentially will provide new insights into ICF pH regulation.The presentation of the authors' names and (or) special characters in the title of the pdf file of the accepted manuscript may differ slightly from what is displayed on the item page. The information in the pdf file of the accepted manuscript reflects the original submission by the author
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