Tissue characterization of progressive cardiac allograft vasculopathy in patients with everolimus therapy compared with donor-transmitted atherosclerosis assessed using serial intravascular imaging: a case report.

Using serial intravascular ultrasound (IVUS), integrated-backscatter IVUS, and optical coherence tomography, we observed rapidly progressive cardiac allograft vasculopathy (CAV) and donor-transmitted plaque in the left anterior descending artery. Late-phase everolimus-resistant CAV had a rapidly progressive course (maximal intimal thickness [MIT] increased by 0.5 mm between years 3 and 4 after cardiac transplantation, from MIT growth<0.5 mm at year 1). Conversely, the donor-transmitted plaque grew slowly (0.1 mm increase during the same period). Tissue characteristics in the 2 segments were also different; CAV had eccentric, noncalcified, and lipid-rich components and was associated with macrophage accumulation, whereas donor-transmitted atherosclerosis presented with typical features of atherosclerosis (ie, fibrocalcific plaque). CAV with late-phase progression involves everolimus resistance and features of vulnerable plaques seen in nontransplantation patients and is independent of donor-transmitted atherosclerosis.

The Parker Flex-Tip tube for nasotracheal intubation: the influence on nasal mucosal trauma.

We tested our hypothesis that use of the Parker Flex-Tip tracheal tube could reduce the incidence of nasal mucosal trauma during nasotracheal intubation when compared with a conventional tip tracheal tube. One hundred and two patients, who were scheduled for elective oral surgery in which nasotracheal intubation was indicated to optimise the surgical approach, were recruited into this study. Either a Flex-Tip tracheal tube or a conventional tip tracheal tube was chosen randomly for each nasotracheal intubation. The incidence of epistaxis using the Flex-Tip tracheal tube (6 (11.8%)) was significantly lower than that with the conventional tip tracheal tube (18 (35.3%); p = 0.009). Nasal pain due to intubation, rated on a 100-mm visual analogue scale, was less intense with the Flex-Tip tracheal tube (median, (10th-90th percentile) 19 (12-28) mm compared with the conventional tip tracheal tube (30 (22-35) mm; p < 0.001). The Flex-Tip tracheal tube thus appeared to reduce the incidence of nasal mucosal trauma during nasotracheal intubation and the incidence of post-intubation nasal pain, compared with the conventional tip tracheal tube.

Excitation of toroidicity-induced Alfvén eigenmodes by the electrodes inserted in a heliotron/torsatron plasma.

A novel method of exciting shear Alfvén waves using electrodes inserted in a plasma was developed for basic study of Alfvén eigenmodes in a heliotron/torsatron plasma. The electrodes can induce excitation current along the confinement field line, and generate magnetic perturbations perpendicular to the confinement field. By sweeping the frequency of the current in a cold plasma, the toroidicity-induced Alfvén eigenmode was resonantly excited at the predicted frequency and radial location. Plasma response to the applied magnetic perturbations indicates a fairly large damping rate caused by continuum damping.

Abnormal myocardial free fatty acid utilization deteriorates with morphological changes in the hypertensive heart.

The left ventricle's morphological adaptation to high blood pressure is classified into 4 patterns based on mass and wall thickness. The geometric changes caused by maladaptation to pressure overload possibly relate to progression of contractile dysfunction with abnormal energy metabolism. The present study assessed whether the geometric adaptation of the left ventricle (LV) to high blood pressure relates to changes in myocardial energy metabolism, especially free fatty acid (FFA) utilization. Thirty-five patients with essential hypertension underwent echocardiography and dual isotopes myocardial scintigraphy using iodine-123 labeled 15-p-iodophenyl-3-(R,S)-methylpentadecanoic acid (BMIPP, an analogue of a FFA) and thallium-201 (Tl-201). Systolic (endocardial fractional shortening; %FS) and diastolic indices (the ratio of early to atrial filling waves; E/A) of LV function were also assessed. Quantitative myocardial BMIPP uptake was evaluated by the BMIPP/TI-201 myocardial uptake ratio (B/T). The subjects were divided into 4 groups based on LV mass and wall thickness: (1) concentric hypertrophy (CH), (2) eccentric hypertrophy (EH), (3) concentric remodeling (CR), and (4) normal geometry (N). The %FS was lower in the EH group than in the other groups. The mitral E/A ratio in the CH group was lowest. B/T was significantly decreased in the EH group compared with the N group (p < 0.05). B/T correlated with the mitral E/A ratio significantly (p < 0.05, r = 0.42), whereas there was no relationship between %FS and B/T. These results indicate that the geometric changes occurring in hypertensive hearts strongly correlate with alternations in cardiac function and with abnormal myocardial FFA metabolism, and that the latter is associated with diastolic abnormality, but not with systolic function.

Role of Raf-1 conserved region 2 in regulation of Ras-dependent Raf-1 activation.

Full activation of Raf-1 requires the interaction of its CRD with Ras. The serine/threonine-rich region, CR2, of Raf-1 was implicated in Raf-1 regulation, but the underlying mechanism was unclear. Here we show that CRD loses its Ras-binding activity when expressed in connection with CR2, suggesting that CR2 masks CRD. This masking effect is abolished by substitution of Asp or Ala for Ser-259, a growth factor- and TPA-induced phosphorylation site in CR2. Treatment of COS-7 cells expressing Ha-Ras(Val-12) and Raf-1 with TPA enhances the Ha-Ras(Val-12)-dependent Raf-1 kinase activity. In contrast, the Ha-Ras(Val-12)-dependent activities of the Raf-1(S259D) and Raf-1(S259A) mutants are comparable to that of wild-type Raf-1 stimulated by both Ha-Ras(Val-12) and TPA and cannot be further stimulated by TPA treatment. These results suggest that the in vivo phosphorylation of Ser-259 may comprise a crucial step for Ras-dependent Raf-1 activation by unmasking CRD and promoting its association with Ras.

Enteral nutrition prevents bacterial translocation but does not improve survival during acute pancreatitis.

OBJECTIVE: To evaluate the effect of enteral nutrition (EN) in attenuating bacterial and/or endotoxin translocation, maintaining immune responsiveness, and improving outcome in early acute pancreatitis (AP) in Wistar male rats. DESIGN: Acute pancreatitis was induced in rats receiving total parenteral nutrition (TPN) (AP/TPN group) (n=34) and EN (AP/EN group) (n=35) by pressure injection of 1% deoxycholate into the biliopancreatic duct (0.6 mg/kg of body weight). Rats in the sham/TPN and sham/EN groups (n=10 each) underwent laparotomy without induction of AP. Catheters for TPN and EN were placed into the external jugular vein and jejunum, respectively. Rats were infused with Ringer lactate solution for 48 hours followed by TPN in the AP/TPN and sham/TPN groups, and EN in the AP/EN and sham/EN groups until day 7. The fluid volume and energy (calories) intake were similar in all groups. SETTING: Medical school research laboratory. MAIN OUTCOME MEASURES: Survival, blood endotoxin level, villus height, 5-bromo-2'-deoxyuridine (BrdU) uptake in the jejunum and ileum, bacterial culture of mesenteric lymph nodes, and CD4/CD8 ratio of T cells in mesenteric lymph nodes, spleen, and peripheral blood. RESULTS: There was no difference in survival and pancreatic healing between the AP/TPN and AP/EN groups. Colony-forming units of the mesenteric lymph nodes and the endotoxin level were significantly lower in the AP/EN group than in the AP/TPN group (P<.05). Villus height and BrdU intake was significantly higher in the AP/EN group than in the AP/TPN group (P<.05). The CD4/CD8 ratio of T cells in spleen and peripheral blood was higher in the AP/EN group than in the AP/TPN group (P<.05), whereas there was no difference in mesenteric lymph nodes. CONCLUSIONS: Jejunal administration of EN is well tolerated in early AP, maintains immune responsiveness and gut integrity, and reduces bacterial and/or endotoxin translocation. However, compared with TPN, EN does not improve outcome. These results suggest that factors other than bacterial and/or endotoxin translocation may be responsible for mortality in this rat model of early AP. However, additional studies of both early bacterial and/or endotoxin translocation and late assessment of outcome are indicated.

The effects of exogenous epinephrine on a convulsive dose of lidocaine: relationship with cerebral circulation.

In order to understand why exogenous epinephrine decreases the convulsive dose of lidocaine, the authors investigated cerebral circulation and plasma lidocaine concentrations in Wistar rats under general anesthesia. In the first experiment, baseline evaluations of each rat's electroencephalogram (EEG), mean arterial pressure (MAP), regional cerebral blood flow (r-CBF), cerebrospinal fluid (CSF) pressure, and cerebral perfusion pressure (CPP) were made. The rats were then assigned to one of three groups: Group L (n=6) received intravenous lidocaine (5 mg/kg/min); Group LE (n=6) received intravenous lidocaine (5 mg/kg/min) and epinephrine (2.5 kg/kg/min); and Group E (n=5) received intravenous epinephrine (2.5 microg/kg/min). Cumulative doses of lidocaine at the onset of EEG spike activity in Groups L and LE were compared. Blood-brain barrier (BBB) permeability was evaluated by observing extravasation of Evans blue (EB) dye. In the second experiment, additional rats were allocated to two treatment groups: Group L' (n=6) received intravenous lidocaine (5 mg/kg/min); Group LE' (n=6) received intravenous lidocaine (5 mg/kg/min) and epinephrine (2.5 microg/kg/min). Brain tissue oxygen partial pressure (PtO2) was monitored during infusion, and arterial and sagittal sinus blood samples were obtained immediately after the onset of EEG spike activity to determine plasma lidocaine concentration. The convulsive dose of lidocaine was significantly decreased when lidocaine was administered with epinephrine (Group L: 61.5+/-5.3 mg/kg (mean+/-SD); Group LE: 30.1+/-4.0 mg/kg) (p < 0.05), but there were no significant differences in plasma lidocaine concentration among these groups. R-CBF, CSF pressure, and CPP immediately before EEG spike activity were higher in Group LE than in Group L. Neither decreased PtO2 nor extravasation of EB was observed in rats treated with epinephrine and lidocaine, excluding cerebral ischemia and BBB breakdown from possible mechanisms by which epinephrine decreased the convulsive dose of lidocaine. None of the rats in Group E exhibited EEG findings suggestive of a preconvulsive state, ruling out a convulsive effect of epinephrine itself. The results suggest that an increase in lidocaine supply to the brain caused by increased CBF causes the low cumulative dose of lidocaine at the onset of convulsion in rats given lidocaine plus epinephrine.

Nutritional modulation of immunity and the inflammatory response.

The metabolic derangements of the injured or stressed patient are governed by multiple factors that partially include the severity of insult, preexisting illnesses, available energy reserves, and appropriateness of intervention. The normal response to injury is further characterized by the release of proinflammatory and antiinflammatory mediators that exert potent effects on cellular and organ function. Although brief periods of starvation and catabolism are tolerable in otherwise healthy individuals, protracted nutritional deprivation can manifest as immunocompromise, irreversible organ injury, and late mortality. Moreover, patients with severe injuries or preexisting illnesses who exhibit exaggerated inflammatory responses may be further predisposed to such deleterious consequences following the insult. The optimal supply of appropriate nutrients and substrates in such circumstances has often been championed as a necessary means of restoring proper cellular metabolism, wound healing, immune competence, and proper organ function. However, much debate surrounds the present efficacy of nutritional therapy in modulating the immune response associated with injury and stress. This article seeks to assess the merits of nutritional therapeutics in the injured patient through available biological and clinical evidence.

[The role of haptoglobin in asphyxia mechanism (II)--Acute drowning and hanging].

We examined changes in plasma during drowning and hanging to determine the mechanism of acute asphyxia. Rabbits were used for the acute drowning and hanging experiments (using artificial sea water or fresh water for the former and complete or incomplete hanging for the latter). The plasma was examined for changes in haptoglobin and total protein contents. For acute drowning, the haptoglobin level reduced dramatically after one minute of inhalation of artificial sea and fresh water by about 46.0% and about 61.0%, respectively. Total protein content showed the same pattern of reduction. Afterward, haptoglobin remained generally unchanged but the total protein content returned to the original level 3 minutes after inhalation. For the handing, the haptoglobin level reduced within 1 minute. When respiratory arrest was near, both haptoglobin and total protein contents rose gradually. The changes in the haptoglobin level caused by hanging were similar to those that occur in acute asphxia when the air passage is completely obstructed and in subacute asphxia when the air passage is strangulated. Totally different and unique patterns were seen in association with drowning in comparison with obstructive asphyxia. These results suggested that the pathological physiology of acute drowning is different from that of fatal neck compression or other types of acute asphyxia.

Effect of cerebral venous congestion on the pressure-volume index in the evaluation of intracranial pressure dynamics.

Translocation of cerebrospinal fluid (CSF) between the intracranial and spinal subarachnoid space was blocked by ligating the cervical spinal core in eight cats under pentobarbital and nitrous oxide anesthesia, and the effects of cerebral venous congestion on the pressure-volume index (PVI), a measure relating the change in intracranial volume, and the logarithm of intracranial pressure (ICP) were evaluated. The changes in the volume-pressure response (VPR), a measure of intracranial elastance, were calculated simultaneously. Cerebral venous congestion was induced by lowering the head relative to the level of the heart by tilting the trunk of the animals to 20 degrees below horizontal. The presence of venous congestion was confirmed by an increase in the sagittal sinus pressure (SSP). The body position was shifted from horizontal prone (H1 group) to head-down tilt (D1 group) in four animals (group 1) and from head-down tilt (D2 group) to horizontal prone (H2 group) in the other four animals (group 2), and PVI and VPR were determined in each group. The changes in ICP and SSP with change of body position in group 1 were not significantly different from those in group 2, with both pressures changing by 7-8 mm Hg. PVI showed no significant differences between the H1 group and H2 group or between the D1 group and D2 group. The mean (+/- SEM) PVI for all measurements in the head-down tilt position (D1 and D2 groups) was significantly higher (0.50 +/- 0.02 ml; p < 0.01) than in the horizontal position (H1 and H2 groups; 0.35 +/- 0.02 ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Re-evaluation of death by asphyxia based on cerebral blood flow (VII)--on the information on electric potentials obtained from deep electroencephalographic electrodes.

The author presents electroencephalographic patterns (a physiological parameter of the brain function observed at rapid and fatal drowning of rabbits), cerebral blood flow (CBF) which support the physiological activities of the brain, and the relationship between systemic respiration and circulation with special reference to changes in the electrical potentials detected by deep electroencephalographic electrodes. The possibility of diagnosis of fatal drowning is examined, based on the results.

[Mathematical simulation of intracranial condition--Part 1. Linear model stimulation].

We developed a linear mathematical model of the intracranial vessels, which reflects changes of the pulse wave (pulse pressure) of intracranial pressure after ligation of the internal jugular vein. The model composed of eight major variables: 1. resistance of arteries, 2. resistance of small arteries and capillary vessels, 3. resistance of veins, 4. resistance of internal jugular and vertebral veins, 5. compliance of arteries, 6. compliance of small arteries and capillary vessels, 7. compliance of veins and 8. intracranial compliance. All variables are presumed to have linear elements and replaced with electrical elements. The model of neck dissection is expressed as the change of resistance of the internal jugular and vertebral veins. Intracranial condition is expressed as the pulse wave (pulse pressure) of intracranial pressure and driving pressure. After unilateral ligation of the internal jugular vein, the pulse wave of intracranial pressure increased 24% and, after bilateral ligation of the internal jugular vein, it increased 55%. After unilateral ligation of the internal jugular vein, the pulse wave of intracranial pressure increased 27%, and, after bilateral ligation, it increased 79%. When intracranial compliance is normal, the respective ratios of pulse wave of intracranial pressure and driving pressure to cross-sectional area decreased, whereas those after increase of intracranial compliance increased.

Effect of sevoflurane on intracranial pressure, sagittal sinus pressure, and the intracranial volume-pressure relation in cats.

The effect of sevoflurane on intracranial pressure (ICP), sagittal sinus pressure (SSP), and the intracranial volume-pressure (V-P) relation was examined in cats. In experiment 1, on nine cats, changes in ICP and SSP were studied for 180 min during anesthesia with 1 MAC sevoflurane (2.6%, inspired) and 50% nitrous oxide (N2O) in oxygen (O2). ICP significantly (p <0.01) increased from 8.4 +/- 3.8 cm H2O (mean +/- SD), the control level to 10.6 +/- 5.1 cm H2O immediately after the administration of sevoflurane. ICP was unchanged for the subsequent 120 min but then increased significantly (p <0.05) 140 min after administration, being 15.5 +/- 9.0 cm H2O at 180 min. There were no changes in SSP or blood gases. In experiment 2, the rapid injection technique of mock cerebrospinal fluid was used to determine the intracranial V-P relation in ten cats. Measures of V-P relationships included (a) ICP before volume injection (Po), (b) peak ICP caused by volume injection (Pp), (c) intracranial compliance (C) calculated as the ratio of change of intracranial volume Delta V) to change of ICP (Delta P), and (d) the pressure volume index (PVI) calculated as the ratio of Delta V to log Pp/Po. The subjects were divided into two groups, one administered 2.6% sevoflurane and 50% N2O in O2 (n = 6) and the other 50% N2O in O2 (n = 4). Each cat in both groups was given two bolus injections into the lateral ventricle at 180 min after the start of anesthesia. Then, C and PVI were calculated. C and PVI in the group treated with sevoflurane were significantly (p <0.05) lower than in the other group. These findings suggest that prolonged use of sevoflurane increases the intracranial elastance.

Effects of bilateral jugular vein ligation on intracranial pressure and cerebrospinal fluid outflow resistance in cats.

In order to study the effect of jugular venous outflow obstruction on intracranial pressure and cerebrospinal fluid (CSF) reabsorption capability, changes in epidural pressure (EDP) and CSF outflow resistance (Ro) were examined following bilateral jugular vein ligation in cats. EDP increased significantly (P less than 0.01) immediately after ligation from the control value of 4.9 +/- 0.5 mmHg (mean +/- SEM) to 15.9 +/- 0.9 mmHg. Thereafter, EDP gradually decreased back toward the control value. The pressure level had decreased to 6.7 +/- 0.5 mmHg by 20 minutes after ligation. The mean Ro was significantly (P less than 0.01) higher in the ligation group (200.4 +/- 9.7 mmHg/ml/min) that in the non-ligation group (120.0 +/- 9.9 mmHg/ml/min). These results suggest that bilateral jugular vein ligation impairs CSF reabsorption.

Effect of head-down tilt on intracranial pressure and sagittal sinus pressure during general anesthesia in cats.

The effect of head-down tilt during general anesthesia on intracranial pressure (ICP) dynamics was examined in eight cats. Changes in lateral ventricular pressure (LVP), sagittal sinus pressure (SSP), and effective CSF pressure (ECSFP), which is the driving pressure of cerebrospinal fluid (CSF) absorption, were studied in association with a shift from the horizontal prone position to the 20 degrees head-down tilt position. Both LVP and SSP values were significantly (P < 0.01) increased at 10 min in the head-down tilt position as compared with the control position, remained elevated during the next 110 min, and returned to baseline when the horizontal position was restored. However, ECSFP (expressed by LVP - SSP) was not significantly different from the control value, because changes in LVP and SSP were similar. These results suggest that head-down tilt does not impair CSF absorption.

[Influence of location for jugular venous blood sampling to cerebral circulatory index (CCI)].

When cerebral circulatory index (CCI) expressed as inverse of arterial-jugular venous oxygen content difference is measured, venous sampling at the internal jugular bulb needs to be done in order to avoid mixture with extra-cerebral perfusion blood. To estimate the validity of this point, difference of values calculated with blood obtained simultaneously at the jugular superior bulb, the inferior region and the cerebral sinus were examined in monkeys. As a result, no significant differences were found to result from location of the sampling, and significant correlation between PaCO2 and CCI was recognized. These findings supported the idea that CCI reflects the cerebral blood flow due to PaCO2 changes.