scholarly journals Aging is associated with an increased susceptibility to ischaemic necrosis due to microvascular perfusion failure but not a reduction in ischaemic tolerance

2007 ◽  
Vol 112 (8) ◽  
pp. 429-440 ◽  
Author(s):  
Yves Harder ◽  
Michaela Amon ◽  
Mirko Georgi ◽  
Claudia Scheuer ◽  
Rene Schramm ◽  
...  

In the present study in a murine model of chronic ischaemia, we analysed: (i) whether aging was associated with an increased susceptibility to ischaemic necrosis, and (ii) whether this was based on microvascular dysfunction or reduced ischaemic tolerance. An ischaemic pedicled skin flap was created in the ear of homozygous hairless mice. The animals were assigned to three age groups, including adolescent (2±1 months), adult (10±2 months) and senescent (19±3 months). Microvascular perfusion of the ischaemic flap was assessed over 5 days by intravital microscopy, evaluating FCD (functional capillary density), capillary dilation response and the area of tissue necrosis. Expression of the stress-protein HO (haem oxygenase)-1 was determined by immunohistochemistry and Western blotting. Induction of chronic ischaemia stimulated a significant expression of HO-1 without a significant difference between the three age groups. This was associated with capillary dilation, which, however, was more pronounced in adolescent (10.5±2.8 μm compared with 3.95±0.79 μm at baseline) and adult (12.1±3.1 μm compared with 3.36±0.45 μm at baseline) animals compared with senescent animals (8.5±1.7 μm compared with 3.28±0.69 μm at baseline; P value not significant). In senescent animals, flap creation further resulted in complete cessation of capillary flow in the distal area of the flap (FCD, 0±0 cm/cm2), whereas adult (11.9±13.5 cm/cm2) and, in particular, adolescent animals (58.4±33.6 cm/cm2; P<0.05) were capable of maintaining residual capillary perfusion. The age-associated microcirculatory dysfunction resulted in a significantly increased flap necrosis of 49±8% (P<0.05) and 42±8% (P<0.05) in senescent and adult animals respectively, compared with 31±6% in adolescent mice. Of interest, functional inhibition of HO-1 by SnPP-IX (tin protoporphyrin-IX) in adolescent mice abrogated capillary dilation, decreased functional capillary density and aggravated tissue necrosis comparably with that observed in senescent mice. Thus aging is associated with an increased susceptibility to tissue necrosis, which is due to a loss of vascular reactivity to endogenous HO-1 expression, rather than a reduction in ischaemic tolerance.


2006 ◽  
Vol 291 (5) ◽  
pp. H2445-H2452 ◽  
Author(s):  
Pedro Cabrales ◽  
Amy G. Tsai

The hamster window chamber model was used to study systemic and microvascular hemodynamic responses to extreme hemodilution with low- and high-viscosity plasma expanders (LVPE and HVPE, respectively) to determine whether plasma viscosity is a factor in homeostasis during extreme anemic conditions. Moderated hemodilution was induced by two isovolemic steps performed with 6% 70-kDa dextran until systemic hematocrit (Hct) was reduced to 18% ( level 2). In a third isovolemic step, hemodilution with LVPE (6% 70-kDa dextran, 2.8 cP) or HVPE (6% 500-kDa dextran, 5.9 cP) reduced Hct to 11%. Systemic parameters, cardiac output (CO), organ flow distribution, microhemodynamics, and functional capillary density, were measured after each exchange dilution. Fluorescent-labeled microspheres were used to measure organ (brain, heart, kidney, liver, lung, and spleen) and window chamber blood flow. Final blood and plasma viscosities after the entire protocol were 2.1 and 1.4 cP, respectively, for LVPE and 2.8 and 2.2 cP, respectively, for HVPE (baseline = 4.2 and 1.2 cP, respectively). HVPE significantly elevated mean arterial pressure and CO compared with LVPE but did not increase vascular resistance. Functional capillary density was significantly higher for HVPE [87% (SD 7) of baseline] than for LVPE [42% (SD 11) of baseline]. Increases in mean arterial blood pressure, CO, and shear stress-mediated factors could be responsible for maintaining organ and microvascular perfusion after exchange with HVPE compared with LVPE. Microhemodynamic data corresponded to microsphere-measured perfusion data in vital organs.



2005 ◽  
Vol 288 (3) ◽  
pp. H1224-H1232 ◽  
Author(s):  
Yves Harder ◽  
Michaela Amon ◽  
Mirko Georgi ◽  
Andrej Banic ◽  
Dominique Erni ◽  
...  

Using intravital microscopy in a chronic in vivo mouse model, we studied the demarcation of myocutaneous flaps and evaluated microvascular determinants for tissue survival and necrosis. Chronic ischemia resulted in a transition zone, characterized by a red fringe and a distally adjacent white falx, which defined the demarcation by dividing the proximally normal from the distally necrotic tissue. Tissue survival in the red zone was determined by hyperemia, as indicated by recovery of the transiently reduced functional capillary density, and capillary remodeling, including dilation, hyperperfusion, and increased tortuosity. Angiogenesis and neovascularization were not observed over the 10-day observation period. The white rim distal to the red zone, appearing as “falx lunatica,” showed a progressive decrease of functional capillary density similar to that of the necrotic distal area but without desiccation, and thus transparency, of the tissue. Development of the distinct zones of the critically ischemic tissue could be predicted by partial tissue oxygen tension (Pt[Formula: see text]) analysis by the time of flap elevation. The falx lunatica evolved at a Pt[Formula: see text] between 6.2 ± 1.3 and 3.8 ± 0.7 mmHg, whereas tissue necrosis developed at <3.8 ± 0.7 mmHg. Histological analysis within the falx lunatica revealed interstitial edema formation and muscle fiber nuclear rarefaction but an absence of necrosis. We have thus demonstrated that ischemia-induced necrosis does not demarcate sharply from normal tissue but develops beside a fringe of tissue with capillary remodeling an adjacent falx lunatica that survives despite nutritive capillary perfusion failure, probably by direct oxygen diffusion.



1996 ◽  
Vol 271 (6) ◽  
pp. H2388-H2398 ◽  
Author(s):  
A. G. Harris ◽  
R. Leiderer ◽  
F. Peer ◽  
K. Messmer

The purpose of this study was to examine the effect of varying durations of ischemia on several microvascular parameters in the awake hamster chamber model. The goal was to characterize the microvascular damage that occurs in skeletal muscle as a result of ischemia and reperfusion. The chamber tissues were subjected to 1-5 h of ischemia, and then the following parameters were measured: vessel diameter, endothelial thickness, macromolecular leakage, red blood cell velocity, adherent leukocytes, rolling leukocytes, freely flowing leukocytes, functional capillary density, and propidium iodide-positive cell nuclei. In control animals there was no significant difference in any parameters over the entire observation period. After 1 or 2 h of ischemia an increase in rolling and adherent leukocytes was measured. After 3 h of ischemia there was a significant increase in the mean endothelial thickness and in the number of nonviable cells. After 4 h of ischemia a significant difference in the extent of macromolecular leakage and the functional capillary density was additionally observed. After 5 h of ischemia this damage was more pronounced and often so severe that approximately 50% of the vessels demonstrated no reflow.



1995 ◽  
Vol 15 (5) ◽  
pp. 238-243 ◽  
Author(s):  
Amy G. Tsai ◽  
Barbara Friesenecker ◽  
M. Intaglietta


2007 ◽  
Vol 107 (6) ◽  
pp. 939-945 ◽  
Author(s):  
Andreas Bauer ◽  
Sieglinde Kofler ◽  
Manfred Thiel ◽  
Sandra Eifert ◽  
Frank Christ

Background The recent introduction of orthogonal polarization spectral imaging enables the direct visualization of the microcirculation of man without imaging enhancing dyes. The authors studied the changes in microvascular perfusion of sublingual mucosa during cardiac surgery with the use of cardiopulmonary bypass (CPB) using this optical method. Method Orthogonal polarization spectral images were recorded in 47 patients after skin incision (T1), after the start of CPB (T2), in the late phase of CPB (T3), and 1 h after the discontinuation of CPB (T4). The images were analyzed for microvascular diameter, erythrocyte velocity, and functional capillary density using an established analysis routine for intravital microscopy studies. In a subpopulation (n = 8), the expression of the adhesion molecules CD18 on circulation leukocytes was compared with the number of visualized rolling leukocytes. Results Preoperatively, no significant changes of the microvascular diameter and erythrocyte velocity were seen. The functional capillary density was significantly reduced at T3 to 90% of the values observed before CPB but recovered at T4 and showed a weak but significant correlation with body temperature (r = 0.38, P &lt; 0.01) and hemoglobin concentration (r = 0.20, P &lt; 0.05). Expression of CD18 was significantly increased in the late phase of CPB (T3) only, whereas the numbers of rolling leukocytes increased during CPB and revealed a significant threefold increase 1 h after termination of CPB. Conclusions Orthogonal polarization spectral imaging revealed no major changes of microvascular perfusion during uncomplicated hypothermic CPB. The slightly reduced functional capillary density during CPB may be caused by several factors all present during CPB, including hypothermia, the artificial extracorporeal perfusion, surgical trauma, hemodilution, and inflammatory reaction. The current data do not allow differentiation between the effects of those possible causes.



2000 ◽  
Vol 279 (2) ◽  
pp. H550-H558 ◽  
Author(s):  
M. Rücker ◽  
O. Strobel ◽  
B. Vollmar ◽  
F. Roesken ◽  
M. D. Menger

We analyzed the incidence and interaction of arteriolar vasomotion and capillary flow motion during critical perfusion conditions in neighboring peripheral tissues using intravital fluorescence microscopy. The gracilis and semitendinosus muscles and adjacent periosteum, subcutis, and skin of the left hindlimb of Sprague-Dawley rats were isolated at the femoral vessels. Critical perfusion conditions, achieved by stepwise reduction of femoral artery blood flow, induced capillary flow motion in muscle, but not in the periosteum, subcutis, and skin. Strikingly, blood flow within individual capillaries was decreased ( P < 0.05) in muscle but was not affected in the periosteum, subcutis, and skin. However, despite the flow motion-induced reduction of muscle capillary blood flow during the critical perfusion conditions, functional capillary density remained preserved in all tissues analyzed, including the skeletal muscle. Abrogation of vasomotion in the muscle arterioles by the calcium channel blocker felodipine resulted in a redistribution of blood flow within individual capillaries from cutaneous, subcutaneous, and periosteal tissues toward skeletal muscle. As a consequence, shutdown of perfusion of individual capillaries was observed that resulted in a significant reduction ( P < 0.05) of capillary density not only in the neighboring tissues but also in the muscle itself. We conclude that during critical perfusion conditions, vasomotion and flow motion in skeletal muscle preserve nutritive perfusion (functional capillary density) not only in the muscle itself but also in the neighboring tissues, which are not capable of developing this protective regulatory mechanism by themselves.



2004 ◽  
Vol 286 (1) ◽  
pp. H340-H345 ◽  
Author(s):  
Barbara Tribl ◽  
Ryon M. Bateman ◽  
Stephanie Milkovich ◽  
William J. Sibbald ◽  
Christopher G. Ellis

Sepsis-induced nitric oxide (NO) overproduction has been implicated in a redistribution of flow from the pancreas making it vulnerable to ischemic injury in septic shock. To test this hypothesis in a remote injury model of normotensive sepsis, we induced Pseudomonas pneumonia in the rat and used intravital video microscopy (IVVM) of the pancreas to measure functional capillary density, capillary hemodynamics [red blood cell (RBC) velocity, lineal density, and supply rate], and lethal cellular damage (propidium iodine staining) at 6 and 24 h after the induction of pneumonia. With pneumonia, plasma nitrite/nitrate [[Formula: see text]] levels were doubled by 21 h ( P < 0.05). To assess the effect of NO overproduction on microvascular perfusion, N6-(1-iminoethyl)-l-lysine (l-NIL) was administered to maintain [Formula: see text] levels at baseline. Pneumonia did cause a decrease in RBC velocity of 23% by 6 h, but by 24 h RBC velocity and supply rate had increased relative to sham by 22 and 38%, respectively ( P < 0.05). l-NIL treatment demonstrated that this increase was due to NO overproduction. With pneumonia, there was no change in functional capillary density and only modest increases in cellular damage. We conclude that, in this normotensive pneumonia model of sepsis, NO overproduction was protective of microvascular perfusion in the pancreas.



Author(s):  
Anders Batman Mjelle ◽  
Anesa Mulabecirovic ◽  
Roald Flesland Havre ◽  
Edda Jonina Olafsdottir ◽  
Odd Helge Gilja ◽  
...  

Abstract Purpose Liver elastography is increasingly being applied in screening for and follow-up of pediatric liver disease, and has been shown to correlate well with fibrosis staging through liver biopsy. Because time is of the essence when examining children, we wanted to evaluate if a reliable result can be achieved with fewer acquisitions. Materials and Methods 243 healthy children aged 4–17 years were examined after three hours of fasting. Participants were divided into four age groups: 4–7 years; 8–11 years; 12–14 years and 15–17 years. Both two-dimensional shear wave elastography (2D-SWE; GE Logiq E9) and point shear wave elastography (pSWE; Samsung RS80A with Prestige) were performed in all participants, while transient elastography (TE, Fibroscan) was performed in a subset of 87 children aged 8–17 years. Median liver stiffness measurement (LSM) values of 3, 4, 5, 6, 7, and 8 acquisitions were compared with the median value of 10 acquisitions (reference standard). Comparison was performed for all participants together as well as within every specific age group. We investigated both the intraclass correlation coefficient (ICC) with absolute agreement and all outliers more than 10 %, 20 % or ≥ 0.5 or 1.0 kPa from the median of 10 acquisitions. Results For all three systems there was no significant difference between three and ten acquisitions, with ICCs ≥ 0.97. All systems needed 4 acquisitions to achieve no LSM deviating ≥ 1.0 kPa of a median of ten. To achieve no LSM deviating ≥ 20 % of a median of ten acquisitions, pSWE and TE needed 4 acquisitions, while 2D-SWE required 6 acquisitions. Conclusion Our results contradict recommendations of 10 acquisitions for pSWE and TE and only 3 for 2D-SWE.



Author(s):  
A. E. Chernikova ◽  
Yu. P. Potekhina

Introduction. An osteopathic examination determines the rate, the amplitude and the strength of the main rhythms (cardiac, respiratory and cranial). However, there are relatively few studies in the available literature dedicated to the influence of osteopathic correction (OC) on the characteristics of these rhythms.Goal of research — to study the influence of OC on the rate characteristics of various rhythms of the human body.Materials and methods. 88 adult osteopathic patients aged from 18 to 81 years were examined, among them 30 men and 58 women. All patients received general osteopathic examination. The rate of the cranial rhythm (RCR), respiratory rate (RR) heart rate (HR), the mobility of the nervous processes (MNP) and the connective tissue mobility (CTM) were assessed before and after the OC session.Results. Since age varied greatly in the examined group, a correlation analysis of age-related changes of the assessed rhythms was carried out. Only the CTM correlated with age (r=–0,28; p<0,05) in a statistically significant way. The rank dispersion analysis of Kruskal–Wallis also showed statistically significant difference in this indicator in different age groups (p=0,043). With the increase of years, the CTM decreases gradually. After the OC, the CTM, increased in a statistically significant way (p<0,0001). The RCR varied from 5 to 12 cycles/min in the examined group, which corresponded to the norm. After the OC, the RCR has increased in a statistically significant way (p<0,0001), the MNP has also increased (p<0,0001). The initial heart rate in the subjects varied from 56 to 94 beats/min, and in 15 % it exceeded the norm. After the OC the heart rate corresponded to the norm in all patients. The heart rate and the respiratory rate significantly decreased after the OC (р<0,0001).Conclusion. The described biorhythm changes after the OC session may be indicative of the improvement of the nervous regulation, of the normalization of the autonomic balance, of the improvement of the biomechanical properties of body tissues and of the increase of their mobility. The assessed parameters can be measured quickly without any additional equipment and can be used in order to study the results of the OC.



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