The American journal of physiology
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Hepatic tissue perfusion and O2 supply after ischemia are indispensable for recovery of cellular functions, but few studies have been performed regarding the recovery of tissue blood flow and O2 transport. After 5, 15, and 30 min of ischemia of rat livers, hepatic tissue perfusion, hepatic arterial and portal blood flow, plasma PO2, and O2 transport parameters were measured. Hepatic tissue blood flow and erythrocyte velocity in the sinusoids showed biphasic recoveries after temporal ischemia for 5, 15, and 30 min. ⋯ Livers that had been subjected to a prior hepatic artery ligation only showed the first peak at approximately 4 min. The first increase in hepatic blood flow corresponded to the peak in the portal venous flow, and the second increase corresponded to that of the hepatic artery. These results suggested that hepatic microcirculation after temporary hepatic ischemia showed biphasic recoveries because of different restoration patterns of the portal vein and hepatic artery.
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In humans, adenine phosphoribosyltransferase (APRT, EC 2.4.2.7) deficiency can manifest as nephrolithiasis, interstitial nephritis, and chronic renal failure. APRT catalyzes synthesis of AMP from adenine and 5-phosphoribosyl-1-pyrophosphate. In the absence of APRT, 2,8-dihydroxyadenine (DHA) is produced from adenine by xanthine dehydrogenase (XDH) and can precipitate in the renal interstitium, resulting in kidney disease. ⋯ Throughout their lifespans, homozygous null female mice manifested significantly less renal damage than homozygous null males of the same age. APRT-deficient females showed no significant impairment of GFR at age 12 wk. Consequences of APRT deficiency in male mice are more pronounced than in females, possibly due to differences in rates of adenine or DHA synthesis or to sex-determined responses of the kidneys.
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Although it is generally believed that circulating exogenous pyrogens [e.g., lipopolysaccharides (LPS)] induce fever via the mediation of endogenous pyrogens (EP) such as cytokines, the first of these, tumor necrosis factor-alpha, is usually not detectable in blood until at least 30 min after intravenous administration of LPS, whereas the febrile rise begins within 15 min after its administration. Moreover, although abundant evidence indicates that circulating LPS is cleared primarily by liver macrophages [Kupffer cells (KC)], these do not secrete EP in immediate response. This would imply that other factors, presumably evoked earlier than EP, may mediate the onset of the febrile response to intravenous LPS. ⋯ To test this postulated mechanism, we measured directly the levels of prostaglandin E2 (PGE2) in the interstitial fluid of the preoptic anterior hypothalamus (POA), the presumptive site of the fever-producing controller, of conscious guinea pigs over their entire febrile course, before and after C depletion by cobra venom factor (CVF) and before and after elimination of KC by gadolinium chloride (GdCl3). CVF and GdCl3 pretreatment each individually attenuated the first of the biphasic core temperature (Tc) rises after intravenous LPS, inverted the second into a Tc fall, and greatly reduced the usual fever-associated increase in POA PGE2. We conclude, therefore, that C activation may indeed be pivotal in the induction of fever by intravenous LPS and that substance(s) generated presumably by KC in almost immediate reaction to the presence of LPS and/or C may transmit pyrogenic signals via hepatic vagal afferents to the POA, where they rapidly induce the production of PGE2 and, hence, fever.
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We investigated the contribution of perivascular nerves and neurotransmitters to cortical spreading depression (CSD)-associated hyperperfusion in the rat. Chronic transection of the nasociliary nerve (NCN, 2 wk before) decreased ipsilateral CSD-associated hyperperfusion by 23 +/- 13% (mean +/- SD; n = 5, P < 0.05), whereas acute transection of the NCN or sham surgery had no effect (n = 8). When the NCN and parasympathetic nerve fibers (PSN) were both chronically transected, CSD hyperperfusion was attenuated by 55 +/- 19% (n = 5, P < 0.05). ⋯ Atropine (10(-4) M) afforded a decrease by 17 +/- 6% (n = 3). These reductions were not statistically significant. We conclude that CSD-associated hyperperfusion is mediated in part by a depolarization of trigeminal sensory and parasympathetic nerve fibers, resulting in a release of vasoactive trigeminal and parasympathetic neurotransmitters.
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The mathematical model presented in a previous work is used to simulate the time pattern of intracranial pressure (ICP) and of blood velocity in the middle cerebral artery (VMCA) in response to maneuvers simultaneously affecting mean systemic arterial pressure (SAP) and end-tidal CO2 pressure. In the first stage of this study, a sensitivity analysis was performed to clarify the role of some important model parameters [cerebrospinal fluid (CSF) outflow resistance, intracranial elastance coefficient, autoregulation gain, and the position of the regulation curve] during CO2 alteration maneuvers performed at different SAP levels. The results suggest that the dynamic "ICP-VMCA" relationship obtained during changes in CO2 pressure may contain important information on the main factors affecting intracranial dynamics. ⋯ Best fitting between model and clinical curves was achieved by minimizing a least-squares criterion function and adjusting certain parameters that characterize CSF circulation, intracranial compliance, and the strength of the regulation mechanisms. A satisfactory reproduction was achieved in all cases, with parameter numerical values in the ranges reported in clinical literature. It is concluded that the model may be used to give reliable estimations of the main factors affecting intracranial dynamics in individual patients, starting from routine measurements performed in neurosurgical intensive care units.