Direct numerical simulation of infusion and flow-front tracking in materials with heterogeneous permeability using a pressure mapping sensor

This paper explores the use of thin film piezoresistive pressure mapping sensors as a means to improve resin transfer moulding processes. The pressure mapping sensor was located between the preform and mould, giving information regarding the permeability map prior to infusion. The permeability map is used as an input to a direct numerical simulation of the infusion step of a highly variable reclaimed carbon fibre preform. The pressure sensor was also used to track the flow front position in-situ, due to a change in load sharing between the preform and liquid during the infusion experiment. Flow front tracking with the pressure mapping sensor was validated against conventional camera images taken through a transparent mould. The direct numerical simulation was able to account for local permeability variation in the preform, providing improved flow-front prediction than homogeneous permeability only, and could be part of a wider strategy to improve resin transfer moulding process robustness.

The Effect of Dexmedetomidine on Oral Mucosal Blood Flow and the Absorption of Lidocaine

Dexmedetomidine (DEX) is a sedative and analgesic agent that acts via the alpha-2 adrenoreceptor and is associated with reduced anesthetic requirements, as well as attenuated blood pressure and heart rate in response to stressful events. A previous study reported that cat gingival blood flow was controlled via sympathetic alpha-adrenergic fibers involved in vasoconstriction. In the present study, experiment 1 focused on the relationship between the effects of DEX on alpha adrenoreceptors and vasoconstriction in the tissues of the oral cavity and compared the palatal mucosal blood flow (PMBF) in rabbits between general anesthesia with sevoflurane and sedation with DEX. We found that the PMBF was decreased by DEX presumably because of the vasoconstriction of oral mucosal vessels following alpha-2 adrenoreceptor stimulation by DEX. To assess if this vasoconstriction would allow decreased use of locally administered epinephrine during DEX infusion, experiment 2 in the present study monitored the serum lidocaine concentration in rabbits to compare the absorption of lidocaine without epinephrine during general anesthesia with sevoflurane and sedation with DEX. The depression of PMBF by DEX did not affect the absorption of lidocaine. We hypothesize that this is because lidocaine dilates the blood vessels, counteracting the effects of DEX. In conclusion, despite decreased palatal blood flow with DEX infusion, local anesthetics with vasoconstrictors should be used in implant and oral surgery even with administered DEX.

Physiologic hyperleptinemia in obesity does not affect vasopressin secretion in acute hypo- or hyperosmolality

Purpose. Abnormal water excretion after ingestion of a water load has been described in obesity. We hypothesized that AVP secretion is abnormal in obese subjects in acute hypo- and hyperosmolality and that the hormone leptin is partly responsible for this. Methods. We studied the relation between leptin, AVP and serum osmolality in two separate tests: (1) after ingestion of a water load (20 ml/kg lean body mass plus 5 ml /kg of adipose tissue) and (2) after iv hypertonic saline (5% NaCl) at a rate of 0.1 ml/kg lean body mass/minute for 120 min in ten subjects of normal weight (BMI > 20 and < 25 kg/m2; controls) and ten obese females (BMI > 30 kg/m2). Obese subjects were tested before (98.6 ± 9.3 kg) and after weight loss (90.2 ± 8.5 kg). Results. In the water load experiment, obese subjects excreted a smaller percentage of the water load than controls. Weight loss restored the ability to excrete the water load in the obese. In the water load and hypertonic saline infusion experiment, plasma AVP concentrations and the area under the curve (AUC) for AVP concentration were not different in obese from normal weight women. Baseline leptin concentration was not correlated with baseline AVP or the change in AVP during the experiment in any of the groups. Weight loss did not change AVP responses in obese subjects. Conclusion. AVP secretion in response to acute hypo- and hyperosmolality is not different in normal weight and obese subjects. There is no correlation between leptin and AVP in normal weight or obese subjects.

Disodium cromoglycate stabilizes mast cell degranulation while reducing the number of hemoglobin-induced microvascular leaks in rat mesentery

Blood substitutes, such as diaspirin cross-linked Hb (DBBF-Hb), have been considered for use during blood transfusions. Unfortunately, bolus injection of modified Hb has been shown to rapidly increase the leakage of microvessels to plasma albumin. This effect may result from production of excess reactive oxygen species (ROS) and could be linked to the observed increase in degranulated mast cells (DMC). Disodium cromoglycate (cromolyn) stabilizes mast cells and therefore might minimize the venular permeability in the rat mesentery. In 10 anesthetized Sprague-Dawley rats, the mesenteric preparation was continuously suffused with cromolyn while the microvasculature was filled with DBBF-Hb solution (10 mg/ml) for 10 min. Six animals received cromolyn pretreatment [two intravascular injections over 30 min ( experiment A)] and four animals received pretreatment with 2% HEPES-buffered saline (HBS)-BSA ( experiment B). Two more animals were pretreated with HBS-BSA without DBBF-Hb infusion but with cromolyn suffusion ( experiment C). Another set of experiments was performed on five animals without cromolyn suffusion or any pretreatment but with DBBF-Hb infusion ( experiment D). All groups then received a 1-min perfusion of FITC-albumin, fixation for 60 min, and microscopic examination. Experiments A and B demonstrated a significant reduction in the number of venular leaks and DMC compared with experiment D, but not in the area of venular leaks. These results suggest mast cell degranulation is not a major contributor to microvascular leakage induced by DBBF-Hb.

Increased cerebral blood flow but no reversal or prevention of vasospasm in response to l-arginine infusion after subarachnoid hemorrhage

Object. The reduction in the level of nitric oxide (NO) is a purported mechanism of delayed vasospasm after subarachnoid hemorrhage (SAH). Evidence in support of a causative role for NO includes the disappearance of nitric oxide synthase (NOS) from the adventitia of vessels in spasm, the destruction of NO by hemoglobin released from the clot into the subarachnoid space, and reversal of vasospasm by intracarotid NO. The authors sought to establish whether administration of l-arginine, the substrate of the NO-producing enzyme NOS, would reverse and/or prevent vasospasm in a primate model of SAH.Methods. The study was composed of two sets of experiments: one in which l-arginine was infused over a brief period into the carotid artery of monkeys with vasospasm, and the other in which l-arginine was intravenously infused into monkeys over a longer period of time starting at onset of SAH. In the short-term infusion experiment, the effect of a 3-minute intracarotid infusion of l-arginine (intracarotid concentration 10−6 M) on the degree of vasospasm of the right middle cerebral artery (MCA) and on regional cerebral blood flow (rCBF) was examined in five cynomolgus monkeys. In the long-term infusion experiment, the effect of a 14-day intravenous infusion of saline (control group, five animals) or l-arginine (10−3 M; six animals) on the occurrence and degree of cerebral vasospasm was examined in monkeys. The degree of vasospasm in all experiments was assessed by cerebral arteriography, which was performed preoperatively and on postoperative Days 7 (short and long-term infusion experiments) and 14 (long-term infusion experiment). In the long-term infusion experiment, plasma levels of l-arginine were measured at these times in the monkeys to confirm l-arginine availability.Vasospasm was not affected by the intracarotid infusion of l-arginine (shown by the reduction in the right MCA area on an anteroposterior arteriogram compared with preoperative values). However, intracarotid l-arginine infusion increased rCBF by 21% (p < 0.015; PCO2 38–42 mm Hg) in all vasospastic monkeys compared with rCBF measured during the saline infusions. In the long-term infusion experiment, vasospasm of the right MCA occurred with similar intensity with or without continuous intravenous administration of l-arginine on Day 7 and had resolved by Day 14. The mean plasma l-arginine level increased during infusion from 12.7 ± 4 µg/ml on Day 0 to 21.9 ± 13.1 µg/ml on Day 7 and was 18.5 ± 3.1 µg/ml on Day 14 (p < 0.05).Conclusions. Brief intracarotid and continuous intravenous infusion of l-arginine did not influence the incidence or degree of cerebral vasospasm. After SAH, intracarotid infusion of l-arginine markedly increased rCBF in a primate model of SAH. These findings discourage the use of l-arginine as a treatment for vasospasm after SAH.

Reversal and prevention of cerebral vasospasm by intracarotid infusions of nitric oxide donors in a primate model of subarachnoid hemorrhage

✓ Decreased endothelium-derived relaxing factor, nitric oxide (NO), in the arterial wall has been hypothesized to be a potential cause of cerebral vasospasm following subarachnoid hemorrhage (SAH). The authors sought to determine whether intracarotid infusions of newly developed NO-donating compounds (NONOates) could reverse vasospasm or prevent the occurrence of cerebral vasospasm in a primate model of SAH. Twenty-one cynomolgus monkeys were studied in two experimental settings. In an acute infusion experiment, saline or NONOate was infused intracarotidly in four normal monkeys and in four monkeys after onset of SAH. During the infusions regional cerebral blood flow (rCBF) was measured in eight animals and CBF velocity in two. In a chronic infusion experiment, saline (four animals) or NONOate (diethylamine-NO [three animals] or proli-NO [six animals]) was infused intracarotidly in monkeys for 7 days after SAH. In acute infusion experiments, 3-minute intracarotid diethylamine-NO infusions reversed arteriographically confirmed vasospasm of the right middle cerebral artery (MCA) (as viewed on anteroposterior projection, the decrease in area was 8.4 ± 4.3% in the treatment group compared with 35 ± 12% in the control group; p < 0.004), increased rCBF by 31 ± 1.9% (p < 0.002), and decreased the mean systolic CBF velocity in the right MCA. In a long-term infusion experiment, the area of the right MCA in control animals decreased by 63 ± 5%. In animals undergoing a 7-day continuous glucantime-NO intracarotid infusion, the area of the right MCA decreased by 15 ± 6.2%, and in animals undergoing a 7-day proli-NO infusion, the area of the right MCA decreased by 11 ± 2.9% (p < 0.05). The mean arterial blood pressure decreased in the glucantime-NO group from 75 ± 12 mm Hg (during saline infusion) to 57 ± 10 mm Hg (during glucantime-NO infusion; p < 0.05), but it was unchanged in animals undergoing proli-NO infusion (76 ± 12 mm Hg vs. 78 ± 12 mm Hg). Results of these experiments show that cerebral vasospasm is both reversed and completely prevented by NO replacement. However, only the use of regional infusion of the NONOate with an extremely short half-life avoided a concomitant decrease in arterial blood pressure, which could produce cerebral ischemia in patients with impaired autoregulation of CBF after the rupture of an intracranial aneurysm.

Effects of a V1-vasopressin antagonist on ACTH release following vasopressin infusion or insulin-induced hypoglycemia in normal men

Experimental evidence indicates that arginine vasopressin contributes to the release of adrenocorticotropic hormone under certain conditions. We studied for the first time the AVP antagonist [d(CH2)5 Tyr(Me)AVP] in 6 normal men in order to evaluate the possible role of AVP as an ACTH-releasing hormone during insulin-induced hypoglycemia. To test the agent's capacity to inhibit an ACTH release by exogenous AVP, we compared the ACTH response to an infusion of 300 ng AVP/min a. 30 min after injection of 5 μg/kg of the antagonist, b. after injection of placebo (0.9% NaCl). Plasma ACTH levels during AVP infusion rose from 17.2±1.6 ng/l (3.8±0.35 pmol/l) to 31.7±4.2 ng/l (7.0±0.92 pmol/l) at 40 min after injection of the antagonist, the difference to the control-group (increment from 16.5±1.2 ng/l (3.6±0.26 pmol/l) to 41.8±3.5 ng/l) (9.2±0.77 pmol/l) being significant (p<0.05). Peak plasma cortisol levels were 323±42 and 529±52 nmol/l, respectively (p<0.05). We then tested the compound in the same subjects during an insulin-induced hypoglycemia; 30 min after administration of 10 μg/kg of the AVP antagonist or placebo, all subjects received 0.12 IU/kg of normal insulin, thus inducing a fall of blood glucose levels below 2 mmol/l. The AVP antagonist caused a moderate but insignificant reduction of the rise in plasma ACTH and a slightly greater, significant reduction of the increment in plasma cortisol (350±19 nmol/l with antagonist and 469±90 nmol/l with placebo, p<0.05) during insulininduced hypoglycemia. The results indicate that a. the AVP antagonist partly inhibits the stimulatory effect of infused AVP on ACTH release in normal men; b. a slightly higher dose of this competitive AVP antagonist inhibits ACTH and cortisol stimulation by hypoglycemia only very little. The importance of AVP as an ACTH-releasing factor in the latter condition may have been underestimated by our experiment, since AVP concentrations in hypophyseal portal blood during hypoglycemia probably were higher than during the AVP infusion experiment.

Simulation of calcium homeostasis: modeling and parameter estimation

The system that regulates plasma calcium in the bird has been formalized into a model based on a series of differential equations and solved by computer simulation. Bone, kidney, and intestine have been considered as the control subsystems, with parathyroid hormone and 1,25-dihydroxycholecalciferol as the regulating hormones. The parameters used in the simulation model have been computed either from published results or by specifically designed experiments described here. For the estimation of parameters, an iterative procedure has been developed that was designed to minimize the sum of square errors between observed and system-simulated values. Parameters of 1,25-dihydroxycholecalciferol metabolism were experimentally obtained from the kinetic behavior of the 3H-labeled hormone in rachitic birds after a single dose. Model parameters have been adjusted using the results of in vivo calcium loading and validated by an EDTA infusion experiment. The simulation model has been used to study the hierarchy of the activities of the three control subsystems and of the regulating hormones, at different calcium intakes. Positive or negative errors in plasma calcium resulted in an asymmetry in the activities of the controlling systems, bone and kidney, whereas the intestine is characterized by its relatively long response time.