Estimated Functional Diameter of Alveolar Septal Microvessels at the Zone I-II Border

Objective : To measure the functional diameter of alveolar septal microvessels under conditions in which the pulmonary arterial pressure and the lung inflation pressure are equal, at 25 cm H₂O (zone I-II border), and to compare these results with those obtained when inflation pressure exceeded arterial pressure by 5 or 10 cm H₂O (zone I). Methods : We perfused isolated rat lungs (P_A 25, P_PA 25, P_LA 0 cm H₂O) with fluorescent latex particles of specific diameters (0.49, 1.05, 2.0, 4.0, or 10 μm) and then prepared samples for histology. Using a confocal, laser-scanning fluorescence microscope, we measured latex particle densities within the septal plane of individual alveoli. We compared these particle densities with those in arterioles supplying the septa and calculated the density ratio. We fit curves produced by the Verniory equation to these ratios to estimate the septal microvessel functional diameter. Results : Particle densities in septa ranged from 0.06 ± 0.02 particles per μm² ‘for 0.49-μm-diameter particles to 0.007 ± 0.004 particles per μm² for 4.0-μm-diameter particles. The 10-μm particles did not enter septa. Calculations based on these data suggest a septal microvessel functional diameter of 6–8 μm. Conclusions : In a previous study, conducted at the same value of P_inflat, but with P_PA set at 15 or 20 (5 or 10 cm H₂O into zone I), we estimated the capillary diameter to be 1.7 μm. Thus, the septal capillary diameter seems to increase by three- to fourfold as P_PA is raised to equal P_inflat.     

A Correlation Between the Permeability Characteristics of a Series of Peptides Using an in Vitro Cell Culture Model (Caco-2) and Those Using an in Situ Perfused Rat Ileum Model of the Intestinal Mucosa

In an attempt to establish an in vitro/in situ correlation of intestinal permeability data, the permeability coefficients (P _app) for a series of model peptides, which were determined using an in situ perfused rat ileum model, were compared to the permeability coefficients (P _mono) determined using an in vitro cell culture model (Caco-2). The model peptides, which were all blocked on the N-terminal (acetyl, Ac) and the C-terminal (amide, NH2) ends, consisted of D-phenylalanine (F) residues (e.g., AcFNH₂, AcFFNH₂, AcFFFNH₂). To alter the degree of hydrogen bonding potential, the nitrogens of the amide bonds were sequentially methylated [e.g., AcFF(Me)FNH₂, AcF(Me)F(Me)FNH₂, Ac(Me)F(Me)F(Me)FNH₂, Ac-(Me)F(Me)F(Me)FNH(Me)]. These peptides were shown not to be metabolized in the in situ perfused rat ileum system. The results of the transport experiments showed that there were poor correlations between the apparent permeability coefficients (P _app) determined in an in situ perfused rat ileum model and the octanol–water partition coefficients (r = 0.60) or the hydrogen bonding numbers (r = 0.63) of these peptides. However, good correlations were observed between the in situ P _app values for these peptides and their partition coefficients in heptane–ethylene glycol (r = 0.96) and the differences in their partition coefficients between octanol–water and isooctane–water (r = 0.86). These results suggest that lipophilicity may not be the major factor in determining the intestinal permeability of these peptides and that hydrogen bonding potential may be a major contributing factor. A good correlation (r = 0.94) was also observed between the P _app values determined for these peptides in the in situ perfused ileum model and those P _mono values determined in the in vitro cell culture model (Caco-2) (Conradi et al., Pharm. Res. 8:1453–1460, 1991). These results suggest that the permeability values determined in the Caco-2 cell culture model may be a good predictor of the intestinal permeability of peptides.     

Laser Doppler flowmetry of blood perfusion in mucoperiosteal flaps covering membranes in bone augmentation and implant procedures. A pilot study in dogs.

In guided tissue regeneration (GTR) procedures, flap recession or sloughing may occur as an unwanted sequel to the placement of a membrane. This study was designed to assess the applicability of laser Doppler flowmetry (LDF) in the evaluation of blood perfusion in the mucoperiosteal flap covering the membrane. Five Labrador dogs were initially used inthe study, but one animal was later excluded due to post‐operative problems. Maxillary premolar teeth were extracted and full thickness mucoperiosteal flaps were raised. Following removal of the buccal bone plate, 4 titanium implants were placed on each side. An experimental biodegradable polylactic‐acid membrane was placed over the fixtures on one side to allow for GTR. The mucoperiosteal flap was repositioned and secured with sutures. The contralateral side served as control with no membrane. Blood perfusion was measured in the flaps before surgery, immediately after suturing and at 24, 48 and 72 h postoperatively. A laser Doppler flowmeter was used to assess the blood perfusion. In 3 animals the membrane was exposed within 2 weeks post‐operatively, and in these 3 animals the LDF values were lower on the membrane side than on the control side. The mean LDF value was lower on the membrane side for each of the 4 periods studied. The tindings suggest that LDF can be a valuable method to study blood perfusion of oral mucosal flaps and that there may be a relationship between a reduced relative LDF value and subsequent exposure of the membrane to the oral environment.     

Cerebral perfusion assessment by bolus tracking using hyperpolarized 13C.

Cerebral perfusion was assessed with 13C MRI in a rat model after intravenous injections of the 13C-labeled compound bis-1,1-(hydroxymethyl)-1-13C-cyclopropane-D8 in aqueous solutions hyperpolarized by dynamic nuclear polarization (DNP). Since the tracer acted as a direct signal source, several of the problems associated with techniques based on traditional dynamic susceptibility contrast (DSC) MRI contrast agents were avoided. Maps of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were calculated. The MTT was determined to be 2.8 +/- 0.8 sec. However, arterial partial-volume effects in the animal model prevented accurate absolute quantification of CBF and CBV. It was demonstrated that depolarization of the hyperpolarized 13C tracer via relaxation and the imaging sequence had little influence on CBF assessment when the time resolution of the imaging sequence was short compared to the MTT. However, CBV and MTT were increasingly underestimated as MTT or the depolarization rate increased if depolarization was not taken into account. With a modified bolus-tracking theory depolarization could be compensated for, assuming that the depolarization rate was known. Three separate compensation methods were investigated experimentally and by numerical simulations.     

温血高钾间断灌注心肌保护的临床应用

目的　探讨浅低温体外循环 (CPB)温血间断灌注心肌保护的临床效果。方法　全组随机分为对照组 (A组 )6 8例 ,采用浅低温CPB温血高钾持续灌注心肌保护。实验组 (B组 ) 91例 ,采用浅低温CPB温血高钾间断灌注心肌保护。观察两组术中心肌保护效果的差别。结果　CPB时间、主动脉阻断时间B组明显小于A组 (P <0 .0 5 ) ;库血用量和 2 4h胸腔引流量B组明显少于A组 (P <0 .0 5 ) ;主动脉开放前血钾浓度B组明显低于A组 (P <0 .0 5 ) ;主动脉开放后心脏自动复跳率B组明显高于A组 (P <0 .0 5 ) ;术后心功能临床观察两组无显著差异。结论　浅低温CPB温血高钾间断灌注保护心肌效果良好。     

Ocular perfusion pressures in different types of glaucoma

Summary It is widely accepted that a disturbed blood supply of the optic disc may cause (in addition with an increased intraocular pressure) optic nerve fibre damage. Therefore we measured ocular perfusion pressures in 79 healthy subjects. In 18 patients with low tension glaucoma, in 27 patients suffering from ocular hypertension and in 49 glaucoma (OAG) patients. For measuring perfusion pressures we used the technique of oculooscillo-dynamography (OODG) as described by Ulrich. Additionally we measured intraocular pressure and systemic blood pressure. In OODG the IOP is simultaneously increased in both eyes by application of a suction cup. After increase of the IOP the negative pressure in the suction cup is slowly and linearly decreased. During this decrease the pulse-depending oscillations of each eye are recorded on a strip-chart-recorder. By means of this method retinal and ciliary perfusion pressures can be separated. As a result we could show that mean arterial blood pressure and systolic retinal perfusion pressure were comparable and not statistically significantly different between the groups examined. The systolic ocular perfusion pressures in patients with low tension glaucoma showed a highly statistically significant reduction compared with the other groups. Between healthy subjects, OAG-patients and patients suffering from ocular hypertension there was no difference in systolic ciliary perfusion pressure detectable.     

Diffuse Axonal Injury (DAI) is not Associated with Elevated Intracranial Pressure (ICP)

Summary Objective. Traditionally, intracranial pressure (ICP) monitoring has been utilized in all patients with severe head injury (Glasgow coma score of 3–8). Ventriculostomy placement, however, does carry a 4 to 10 percent complication rate consisting mostly of hematoma and infection. The authors propose that a subgroup of patients presenting with severe head trauma and diffuse axonal injury without associated mass lesion, do not need ICP monitoring. Additionally, the monitoring data from ICP, MAP, and CPP for a comparison severe head injury group, and subgroups of DAI would be presented. Materials and methods. Thirty-six patients sustaining blunt head trauma and fitting our strict clinical and radiographic diagnosis of DAI were enrolled in our study. Inclusion criteria were severe head injury patients who did not regain consciousness after the initial impact, and whose CT scan demonstrated characteristic punctate hemorrhages of <10 mm diameter at the greywhite junction, basal ganglia, corpus callosum, upper brainstem, or a combination of the above. Patients with significant mass lesions and documented anoxia were excluded. Their intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were compared to a control group of 36 consecutive patients with severe non-penetrating non-operative head injury, using the Analysis for Variance method. Results. Eighteen (50.0%), six (16.7%), and twelve (33.3%) patients had types I, II, and III DAI, respectively. The admission Glasgow Coma Score (GCS) was higher for types I and II than for type III DAI. ICP was monitored from 23 to 165 hours, with a mean ICP for 36 patients of 11.70 mmHg (SEM=75) and a range from 4.3 to 17.3 mmHg. Of all ICP recordings, of which 89.7% (2421/2698) were ≤20 mmHg. Average mean arterial pressure (MAP) was 96.08 mmHg (SEM=1.69), and 94.6% (2038/2154) of all MAP readings were greater than 80 mmHg. Average cerebral perfusion pressure (CPP) was 85.16 mmHg (SEM=1.68), and 90.1% (1941/2154) of all CPP readings were greater than 70 mmHg. This is compared to the control group mean ICP, MAP, and CPP of 16.84 mmHg (p=0.000021), 92.80 mmHg (p=0.18), and 76.49 mmHg (p=0.0012). No treatment for sustained elevated ICP>20 mmHg was needed for DAI patients except in two; one with extensive intraventricular and subarachnoid hemorrhage who developed communicating hydrocephalus, and another with ventriculitis requiring intrathecal and intravenous antibiotic treatments. Two complications, one from a catheter tract hematoma, and another with Staph epidermidis ventriculitis, were encountered. All patients, except type III DAI, generally demonstrated marked clinical improvement with time. The outcome, as measured by Glasgow Coma Score (GCS) and Glasgow Outcome Score (GOS) was similarly better with types I and II than type III DAI. Conclusion. The authors conclude that ICP elevation in DAI patients without associated mass lesions is not as prevalent as other severe head injured patients, therefore ICP monitoring may not be as critical. The presence of an ICP monitoring device may contribute to increased morbidity. Of key importance, however, is an accurate clinical history and interpretation of the CT scan.     

Visual scoring and laser Doppler perfusion imaging of skin irritancy induced by different nicotine patches

Background/aims: Local skin reactions are the most common reason for discontinuation of transdermal nicotine replacement therapy in smoking cessation programs. The aims of the present study were (1) to quantify the intensity of skin reactions induced by different types of nicotine patches and (2) to compare the clinical evaluation of skin erythema using visual scores with independently performed quantitative estimates of skin perfusion.
Methods: Thirty-three subjects were included in the study, each receiving 2 different types of nicotine patches (Nicotinell and Nicorette) and 1 type of placebo patch (Nicorette), placed ventrally on the upper arms according to a randomized protocol. Patches were removed after 24 h (Nicotinell) and 16 h (Nicorette), respectively, according to recommended application times. Visual scoring and laser Doppler perfusion imaging were performed 45 min after removal of patches, in a randomized order.
Results: Nicotinell patches induced the highest cumulative clinical score for skin irritancy. All 3 investigated patches gave rise to a slight but significant skin perfusion increase and individual visual scores and perfusion data correlated.
Conclusion The degree of skin irritancy and underlying perfusion increase induced by 1 daily maintenance dose of transdermal nicotine via a patch is low, but differs between patch types.     

Increased sensitivity through use of overlapping 180° orbits in clinical myocardial perfusion imaging

Clinical cardiac imaging is hindered by noise due to limited activity and imaging time. Use of 90° dual-detector systems with 90° gantry rotation may provide the best sensitivity/resolution for cardiac imaging, but this option is not readily available to those using a triple-detector system with detectors at 120° intervals. This study utilizes a cardiac/chest phantom to compare several triple-detector orbits, with assessment of sensitivity and resolution. A 180° rotation with reconstruction of two of the three heads was evaluated, resulting in overlapping 180° orbits; use of a starting angle of 165° for the first head placed the overlapping portion of the orbits over the LAO myocardial region, where camera-cardiac distance is most favorable. Use of this overlapping orbit yielded resolution equivalent to a conventional (single-head) 180° rotation. Sensitivity was 87%–90% of that of a 90° dual-detector system, and 16%–20% better than the common practice of using a 120° orbit with reconstruction of 1 /12 heads to achieve 180° of data. Use of 360° acquisition with reconstruction of all three heads provided the greatest sensitivity, though at the expense of some loss in image quality. Thus, for those centers performing cardiac imaging using a triple-detector system, use of overlapping 180° orbits is the preferred acquisition choice.     

Analysis of Intestinal Perfusion Data for Highly Permeable Drugs Using a Numerical Aqueous Resistance—Nonlinear Regression Method

Purpose. To develop, validate and apply a method for analyzing the intestinal perfusion data of highly permeable compounds using the Numerical Aqueous Resistance (NAR) theory and nonlinear regression (NAR-NLR) and to compare the results with the well-established Modified Boundary Layer (MBL) Analysis. Methods. The NAR-NLR method was validated and the results were compared to the MBL analysis results using previously reported cephradine jejunal perfusion data. Using the Single Pass Intestinal Perfusion (SPIP) method, the concentration dependence of intestinal permeability was investigated for formycin B, proline, and thymidine, three compounds reported to be absorbed by carrier-mediated transport processes. The MBL and NAR-NLR analyses were then applied to the three sets of SPIP data. Results. The results demonstrate that the intrinsic MBL transport parameters were highly variable and, in one case, the analyses failed to give a statistically significant Michaelis constant. The MBL mean dimensionless wall permeabilities (P*_w) were greater than the NAR-NLR P*_w and were also highly variable. In all cases, the NAR-NLR variability was significantly lower than the MBL variability. The extreme variability in the MBL-calculated P*_w is due to the sensitivity of P*_w when the fraction of unabsorbed drug (C_m/C_o) is low or, alternatively, when P*_w approached the aqueous permeability, P*_aq. Conclusions. The NAR-NLR method facilitates the analysis of intestinal perfusion data for highly permeable compounds such as those absorbed by carrier-mediated processes at concentrations below their K_m. The method also allows for the use of a wider range of flow conditions than the MBL analysis resulting in more reliable and less variable estimates of intestinal transport parameters as well as intestinal wall permeabilities.