The American journal of physiology
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The relationships among cerebral blood flow, cerebral blood volume, intracranial pressure (ICP), and the action of cerebrovascular regulatory mechanisms (autoregulation and CO2 reactivity) were investigated by means of a mathematical model. The model incorporates the cerebrospinal fluid (CSF) circulation, the intracranial pressure-volume relationship, and cerebral hemodynamics. The latter is based on the following main assumptions: the middle cerebral arteries behave passively following transmural pressure changes; the pial arterial circulation includes two segments (large and small pial arteries) subject to different autoregulation mechanisms; and the venous cerebrovascular bed behaves as a Starling resistor. ⋯ Simulations performed in dynamic conditions with varying ICP underline the existence of a significant correlation between ICP dynamics and cerebral hemodynamics in response to CO2 changes. This correlation may significantly increase in pathological subjects with poor intracranial compliance and reduced CSF outflow. In perspective, the model can be used to study ICP and blood velocity time patterns in neurosurgical patients in order to gain a deeper insight into the pathophysiological mechanisms leading to intracranial hypertension and secondary brain damage.
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Baroreflex regulation of cardiac output is determined by the performance of the heart as well as the available blood flow returning to the heart (i.e., venous return). We hypothesized that a decrease in arterial compliance (C(a)) would affect carotid baroreflex control of cardiac output by altering the slope of the venous return curve (VR curve). Baroreflex control of systemic arterial pressure (Pa), central venous pressure (Pv), heart rate, cardiac output (CO), and peripheral vascular resistance (R) were determined during bilateral carotid occlusion (BCO) in spontaneously hypertensive (hypertensive, HT) and Sprague-Dawley (normotensive, NT) rats. ⋯ However, BCO significantly decreased CO in NT but not HT (delta CO, -24 +/- 5 vs. -4 +/- 6 ml.kg-1.min-1, P < 0.05). In NT, RVR was increased 39 +/- 9% during BCO (P < 0.05), whereas RVR increased 8 +/- 3% in HT (P = NS). From these findings, we conclude that the difference in baroreflex control of CO is mediated, in part, by the reduction in C(a), which minimized the baroreflex-evoked increase in RVR.
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We measured, the bioelectric properties of 14 cystic fibrosis (CF) and 33 non-CF human fetal tracheal xenografts in severe combined immunodeficiency (SCID) mice. All xenografts exhibited a mature airway-type epithelium irrespective of their gestational age, duration of engraftment, and genotype. The in vivo potential difference and the in vitro baseline short-circuit current (Isc) were significantly higher in non-CF than in CF xenografts. ⋯ In CF xenografts, forskolin had no significant effect on Isc, whereas amiloride- and ATP-induced changes in Isc were proportionally higher than in non-CF xenografts (-60.0 and +68.8%, respectively). These results indicate that the bioelectric properties of non-CF xenografts are similar to those of postnatal airways and that CF xenografts exhibit lower baseline electrogenic activity than non-CF xenografts but similar regulation of ion transport processes to postnatal CF airways. This model of mature human fetal tracheal mucosa may help gain insight into early CF airway pathogenesis.
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Using infant piglets, we studied the effects of nonspecific inhibition of nitric oxide (NO) synthase by NG-nitro-L-arginine methyl ester (L-NAME; 3 mg/kg) on vascular pressures, regional blood flow, and cerebral metabolism before 8 min of cardiac arrest, during 6 min of cardiopulmonary resuscitation (CPR), and at 10 and 60 min of reperfusion. We tested the hypotheses that nonspecific NO synthase inhibition 1) will attenuate early postreperfusion hyperemia while still allowing for successful resuscitation after cardiac arrest, 2) will allow for normalization of blood flow to the kidneys and intestines after cardiac arrest, and 3) will maintain cerebral metabolism in the face of altered cerebral blood flow after reperfusion. Before cardiac arrest, L-NAME increased vascular pressures and cardiac output and decreased blood flow to brain (by 18%), heart (by 36%), kidney (by 46%), and intestine (by 52%) compared with placebo. ⋯ Thus nonspecific inhibition of NO synthase did not adversely affect the rate of resuscitation from cardiac arrest while attenuating cerebral and myocardial hyperemia. Even though CMRGluc and CMRLac early after resuscitation were decreased, they were maintained at baseline levels. This may be clinically advantageous in protecting the brain and heart from the damaging effects of hyperemia, such as blood-brain barrier disruption.