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Peter Jarzem - One of the best experts on this subject based on the ideXlab platform.
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mitigating spinal cord distraction injuries the effect of durotomy in decreasing cord Interstitial Pressure in vitro
European Journal of Orthopaedic Surgery and Traumatology, 2014Co-Authors: Waleed Awwad, Mahdi Bassi, Ian Shrier, Abdulaziz Alahaideb, Russell Steele, Peter JarzemAbstract:Study design The present study involved an in vitro examination of spinal cord Interstitial Pressure (CIP) during distraction before and after durotomy in three spinal cord segments obtained from five pigs.
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Mitigating spinal cord distraction injuries: the effect of durotomy in decreasing cord Interstitial Pressure in vitro.
European journal of orthopaedic surgery & traumatology : orthopedie traumatologie, 2014Co-Authors: Waleed Awwad, Mahdi Bassi, Ian Shrier, Abdulaziz Al-ahaideb, Russell J Steele, Peter JarzemAbstract:The present study involved an in vitro examination of spinal cord Interstitial Pressure (CIP) during distraction before and after durotomy in three spinal cord segments obtained from five pigs. To determine whether durotomy can be used to decrease the elevated CIP associated with spinal cord distraction. Spinal cord distraction is a known cause of spinal cord injury. Several articles describing the pathophysiology of cord distraction injuries suggest that the underlying mechanism of injury is a microvascular ischemic event. The authors have previously described an increase in CIP with spinal cord distraction, with average Pressures of 23 mmHg at loads of 1,000 g. To date, there are no published studies that have evaluated the efficacy of intentional durotomies as a treatment for elevated CIP. A total of 15 spinal cord sections were harvested from pigs and distracted while immersed in saline, using a fixed 1,000 g distraction force. The CIP decay was then measured at 30-s intervals for 10 min. The distraction/relaxation maneuver was performed six times with continuous CIP monitoring and was subsequently followed by durotomy. The Pressure-decay curves were similar for each specimen, but varied according to individual pigs and anatomical levels. CIP decayed over the first 4 min of distraction and remained constant for the final 6 min. Longitudinal durotomy led to a dramatic drop in CIP toward baseline and appeared to be as effective as transverse durotomy with regard to the normalization of Pressure. Spinal cord distraction causes elevations in CIP. Durotomy lowers elevated CIP in vitro and may be effective at lowering CIP in vivo. Further study is required to evaluate the usefulness of durotomy in vivo.
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An in vitro study on the effects of freezing, spine segment, repeat measurement, and individual cord properties on cord Interstitial Pressure.
Spine, 2009Co-Authors: Bassi, Peter Jarzem, Matthew Steibel, Peter Barriga, Jean Ouellet, Rudy ReindlAbstract:STUDY DESIGN: In vitro study of the spinal cord tension and Pressure relationships before and after thawing in 6 different spinal cord segment from 2 individual pigs. OBJECTIVES: To determine if frozen and thawed spinal cord segments had different tension/cord Interstitial Pressure(CIP) relationships to fresh spinal cord segments. In addition, we will determine if the cord level, individual cord properties, and repeated CIP measurements affect the tension/CIP relationships. SUMMARY OF BACKGROUND DATA: Spinal cord distraction is a known cause of spinal cord injury. Several articles published on the pathophysiology of the cord distraction injury suggest that the underlying mechanism of injury is a microvascular ischemic event. We have previously described an increase in CIP with spinal cord distraction, Pressures average 23 mmHg at 1 kg loads. METHODS: Six cord segments harvested from 2 pigs contained cervical, thoracic, and lumbar segments, and underwent distraction using a series of 7 calibrated weights from 0 to 1000 g weight. The cords were measured at each level of distraction. The cords were then frozen at -20 degrees C for a period of 2 weeks, and then thawed and retested. Multiple linear regression was then performed. RESULTS: There was no difference between the fresh and the frozen-thawed cords; there was statistical difference between the 2 pigs (18 mmHg) (P < 0.001). There are differences between the cervical and the thoracic cord segments (P < 0.001), and between cervical and lumbar cord segments (P = 0.056). There is a significant relation between the tension applied and CIP. Repeated trials showed no drift with repeated measures. CONCLUSION: Freezing and thawing spinal cords has no effect on the CIP/tension curves. Cord Interstitial Pressure developed is dependant on cord tension, cord level, individual cord properties, but not on the number of repetitions carried out while testing the spinal cord.
Rakesh K. Jain - One of the best experts on this subject based on the ideXlab platform.
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pharmacologic modification of tumor blood flow and Interstitial fluid Pressure in a human tumor xenograft network analysis and mechanistic interpretation
Microvascular Research, 1995Co-Authors: Robert A Zlotecki, Laurence T. Baxter, Yves Boucher, Rakesh K. JainAbstract:Abstract Various vasoactive agents have been used to modify tumor blood flow with the ultimate goal of improving cancer detection and treatment, with widely disparate results. Furthermore, the lack of mechanistic interpretations has hindered understanding of how these agents affect the different physiological parameters involved in perfusion. Thus, there is a need to develop a unified framework for understanding the interrelated physiological effects of pharmacological and physical agents, The goals of this study were (1) to develop a mathematical model which helps determine the location and magnitude of changes in the vascular resistance of tumor and normal tissues and (2) to test the model with our own experimental studies and by comparison with results from the literature. The systemic and Interstitial Pressures and relative tumor blood flow were measured before and after administration of angiotensin II, epinephrine, norepinephrine, nitroglycerin, and hydralazine in SCID mice bearing LS174T human colon adenocarcinoma xenografts. A mathematical model was developed in analogy to electrical circuits which examined the Pressure, flow, and resistance relationships for arterial and venous segments of the vasculature of a tumor and surrounding normal tissue. Vasoconstrictor-induced increases in the mean arterial blood Pressure led to increases in tumor blood flow and Interstitial Pressure with the magnitude of change dependent on the agent (percentage change in blood flow: angiotensin > epinephrine > norepinephrine). The vasodilating agents induced decreases in tumor blood flow in parallel to the induced decreases in the systemic Pressure, but only the long-acting arterial vasodilator hydralazine was capable of effecting a decrease in tumor Interstitial Pressure. The model was also found to be consistent with other data available in the literature on norepinephrine, pentoxifylline, nicotinamide, and hemodilution, and was useful in providing input as to the location and degree of the physiological effects of these agents. The results of the data and model show that the steal phenomenon is the dominant mechanism for redistribution of host blood flow to the tumor. However, some degree of arterial control was found to be present in the tumors. Moreover, the parallel increases in tumor Interstitial Pressure and blood flow contradict any hypothesis suggesting that elevated Interstitial fluid Pressure precipitates chronic vascular collapse, thus decreasing blood flow.
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Interstitial Pressure Gradients in Tissue-isolated and Subcutaneous Tumors: Implications for Therapy
Cancer Research, 1990Co-Authors: Y. Boucher, Laurence T. Baxter, Rakesh K. JainAbstract:High Interstitial fluid Pressure (IFP) in solid tumors is associated with reduced blood flow as well as inadequate delivery of therapeutic agents such as monoclonal antibodies. In the present study, IFP was measured as a function of radial position within two rat tissue-isolated tumors (mammary adenocarcinoma R3230AC, 0.4-1.9 g, n = 9, and Walker 256 carcinoma, 0.5-5.0 g, n = 6) and a s.c. tumor (mammary adenocarcinoma R3230AC, 0.6-20.0 g, n = 7). Micropipettes (tip diameters 2 to 4 microns) connected to a servo-null Pressure-monitoring system were introduced to depths of 2.5 to 3.5 mm from the tumor surface and IFP was measured while the micropipettes were retrieved to the surface. The majority (86%) of the Pressure profiles demonstrated a large gradient in the periphery leading to a plateau of almost uniform Pressure in the deeper layers of the tumors. Within isolated tumors, Pressures reached plateau values at a distance of 0.2 to 1.1 mm from the surface. In s.c. tumors the sharp increase began in skin and levelled off at the skin-tumor interface. These results demonstrate for the first time that the IFP is elevated throughout the tumor and drops precipitously to normal values in the tumor's periphery or in the immediately surrounding tissue. These results confirm the predictions of our recently published mathematical model of Interstitial fluid transport in tumors (Jain and Baxter, Cancer Res., 48: 7022-7032, 1988), offer novel insight into the etiology of Interstitial hypertension, and suggest possible strategies for improved delivery of therapeutic agents.
Waleed Awwad - One of the best experts on this subject based on the ideXlab platform.
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mitigating spinal cord distraction injuries the effect of durotomy in decreasing cord Interstitial Pressure in vitro
European Journal of Orthopaedic Surgery and Traumatology, 2014Co-Authors: Waleed Awwad, Mahdi Bassi, Ian Shrier, Abdulaziz Alahaideb, Russell Steele, Peter JarzemAbstract:Study design The present study involved an in vitro examination of spinal cord Interstitial Pressure (CIP) during distraction before and after durotomy in three spinal cord segments obtained from five pigs.
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Mitigating spinal cord distraction injuries: the effect of durotomy in decreasing cord Interstitial Pressure in vitro.
European journal of orthopaedic surgery & traumatology : orthopedie traumatologie, 2014Co-Authors: Waleed Awwad, Mahdi Bassi, Ian Shrier, Abdulaziz Al-ahaideb, Russell J Steele, Peter JarzemAbstract:The present study involved an in vitro examination of spinal cord Interstitial Pressure (CIP) during distraction before and after durotomy in three spinal cord segments obtained from five pigs. To determine whether durotomy can be used to decrease the elevated CIP associated with spinal cord distraction. Spinal cord distraction is a known cause of spinal cord injury. Several articles describing the pathophysiology of cord distraction injuries suggest that the underlying mechanism of injury is a microvascular ischemic event. The authors have previously described an increase in CIP with spinal cord distraction, with average Pressures of 23 mmHg at loads of 1,000 g. To date, there are no published studies that have evaluated the efficacy of intentional durotomies as a treatment for elevated CIP. A total of 15 spinal cord sections were harvested from pigs and distracted while immersed in saline, using a fixed 1,000 g distraction force. The CIP decay was then measured at 30-s intervals for 10 min. The distraction/relaxation maneuver was performed six times with continuous CIP monitoring and was subsequently followed by durotomy. The Pressure-decay curves were similar for each specimen, but varied according to individual pigs and anatomical levels. CIP decayed over the first 4 min of distraction and remained constant for the final 6 min. Longitudinal durotomy led to a dramatic drop in CIP toward baseline and appeared to be as effective as transverse durotomy with regard to the normalization of Pressure. Spinal cord distraction causes elevations in CIP. Durotomy lowers elevated CIP in vitro and may be effective at lowering CIP in vivo. Further study is required to evaluate the usefulness of durotomy in vivo.
Giuseppe Miserocchi - One of the best experts on this subject based on the ideXlab platform.
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Lung Interstitial Pressure and structure in acute hypoxia.
Advances in Experimental Medicine and Biology, 2020Co-Authors: Giuseppe MiserocchiAbstract:The air blood barrier is a gas exchanger and is well designed to fulfill this task as its main feature is its minimum thickness that in turn reflects a minimum amount of extravascular water. The maintenance of a minimum water volume is due to mechanisms able to control Interstitial fluid turnover and to offset transient conditions of increase in this volume. The hydraulic Pressure in the lung interstitium is ~ -10 cmH2O and reflects the equilibrium between the lymphatic absorption Pressure and the microvascular filtration through the basement membrane whose hydraulic permeability is kept very low due to the macromolecular organization of heparansulphate proteoglycans (HS-PGs). When microvascular filtration is increased, the increase in extravascular water is minimal in face of a considerable increase in Interstitial Pressure (up to ~ 5 cmH2O) because of the high elastance of the extracellular matrix thanks to the mechanical role of matrix chondroitin sulphate proteoglycans (CS-PGs). This increase in Pressure buffers microvascular filtration. Hypoxia causes fragmentation of CS-PGs of the extracellular matrix and of HS-PGs of the basement membrane: the result is a decrease in tissue elastance and an increase in permeability of the endothelial and epithelial barriers. When the overall PGs fragmentation overcomes a critical threshold, severe lung edema develops. Recovery from severe lung edema requires that extracellular integrity is restored. We provide evidence for a prompt lung cellular response to Interstitial edema. We interpret this response as a fine mechanism to detect minor increases in extravascular water and to promote the reparative process.
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Interstitial Pressure and lung oedema in chronic hypoxia
European Respiratory Journal, 2010Co-Authors: Ilaria Rivolta, V. Lucchini, Marcella Rocchetti, F. Kolar, F. Palazzo, Antonio Zaza, Giuseppe MiserocchiAbstract:We evaluated how the increase in lung Interstitial Pressure correlates with the pulmonary vascular response to chronic hypoxia. In control and hypoxic (30 days; 10% O 2 ) Wistar male rats, we measured: pulmonary Interstitial Pressure ( P ip ), cardiac and haemodynamic parameters by echocardiography, and performed lung morphometry on tissue specimens fixed in situ . In control animals, mean±sd P ip , air/tissue volume ratio and capillary vascularity index in the air–blood barrier were -12±2.03 cmH 2 O, 3.9 and 0.43, respectively. After hypoxia exposure, the corresponding values of these indices in apparently normal lung regions were 2.6±1.7 cmH 2 O, 3.6, and 0.5, respectively. In oedematous regions, the corresponding values were 12±4 cmH 2 O, 0.4 and 0.3, respectively. Furthermore, in normal regions, the density of pre-capillary vessels (diameter ∼50–200 μm) increased and their thickness/internal diameter ratio decreased, while opposite results were found in oedematous regions. Pulmonary artery Pressure increased in chronic hypoxia relative to the control (39.8±5.9 versus 26.2±2.2 mmHg). Heterogeneity in local lung vascular response contributes to developing pulmonary hypertension in chronic hypoxia. In oedematous regions, the decrease in capillary vascularity correlated with the remarkable increase in Interstitial Pressure and morphometry of the pre-capillary vessels suggested an increase in vascular resistance; the opposite was true in apparently normal regions.
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pulmonary Interstitial Pressure and tissue matrix structure in acute hypoxia
American Journal of Physiology-lung Cellular and Molecular Physiology, 2001Co-Authors: Giuseppe Miserocchi, D. Negrini, Alberto Passi, Massimo Del Fabbro, G. De LucaAbstract:Pulmonary Interstitial Pressure was measured via micropuncture in anesthetized rabbits in normoxia and after breathing 12% O2. In normoxia [arterial Po 2 = 88 ± 2 (SD) mmHg], pulmonary arterial pre...
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Pulmonary Interstitial Pressure and proteoglycans during development of pulmonary edema
American Journal of Physiology-heart and Circulatory Physiology, 1996Co-Authors: D. Negrini, Alberto Passi, G. De Luca, Giuseppe MiserocchiAbstract:In anesthetized adult rabbits, pulmonary perivascular Interstitial Pressure (P(ip)), measured by micropuncture technique with intact pleural space, averaged -10.5 +/- 1.9 (SD) cmH2O in control cond...
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Pulmonary Interstitial Pressure in premature rabbits
Respiration Physiology, 1995Co-Authors: Giuseppe Miserocchi, Massimo Del Fabbro, Besa Haxhiu Poskurica, Beatrice CrisafulliAbstract:Abstract By micropuncture technique we measured pulmonary Interstitial pressuure (P ip ) from birth up to 6 h postnatal age in anesthetized and paralyzed cesarian delivered term (31 days gestation) and premature (27 to 30 days gestation) rabbits. In term cesarian delivered rabbits P ip followed the time course of vaginally delivered rabbits, namely, it increased from about zero at birth up to about 5 cmH 2 O at 2 h, as a result of alveolar fluid reabsorption, subsequently it decreased becoming subatmospheric due to progressive Interstitial fluid drainage. In ventilated lung regions of premature rabbits, P ip also peaked to about 5 cmH 2 O at 2 h but its subsequent decrease was markedly slowed down while in atelectatic regions of premature rabbits P ip remained slightly subatmospheric. Up to 6 h, the wet/dry weight ratio of the lung was higher in premature relative to vaginally and cesarian delivered term rabbits (at birth 8.4 ± 0.9 vs. 7.5 ± 0.8). In 29–31 days rabbits, plasma protein concentration at birth was 3.6 ± 0.5 g/dl (within 95% confidence limits for vaginally delivered rabbits, considered as control) while in 27–28 days rabbit it was 3.1 ± 0.4 g/dl (at the lower edge of control confidence limits). In the first postnatal hours, the increase in P ip favoured fluid reabsorption into pulmonary microcirculation in term cesarian delivered rabbits and in ventilated regions of premature rabbits. Conversely, in the atelectatic regions of premature rabbits the unchanged P ip value in the postnatal hours favours fluid filtration from microcirculation into lung interstitium.
John Lowengrub - One of the best experts on this subject based on the ideXlab platform.
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the effect of Interstitial Pressure on tumor growth coupling with the blood and lymphatic vascular systems
Journal of Theoretical Biology, 2013Co-Authors: Min Wu, Hermann B Frieboes, Steven Robert Mcdougall, Mark A J Chaplain, Vittorio Cristini, John LowengrubAbstract:The flow of Interstitial fluid and the associated Interstitial fluid Pressure (IFP) in solid tumors and surrounding host tissues have been identified as critical elements in cancer growth and vascularization. Both experimental and theoretical studies have shown that tumors may present elevated IFP, which can be a formidable physical barrier for delivery of cell nutrients and small molecules into the tumor. Elevated IFP may also exacerbate gradients of biochemical signals such as angiogenic factors released by tumors into the surrounding tissues. These studies have helped to understand both biochemical signaling and treatment prognosis. Building upon previous work, here we develop a vascular tumor growth model by coupling a continuous growth model with a discrete angiogenesis model. We include fluid/oxygen extravasation as well as a continuous lymphatic field, and study the micro-environmental fluid dynamics and their effect on tumor growth by accounting for blood flow, transcapillary fluid flux, Interstitial fluid flow, and lymphatic drainage. We thus elucidate further the non-trivial relationship between the key elements contributing to the effects of Interstitial Pressure in solid tumors. In particular, we study the effect of IFP on oxygen extravasation and show that small blood/lymphatic vessel resistance and collapse may contribute to lower transcapillary fluid/oxygen flux, thus decreasing the rate of tumor growth. We also investigate the effect of tumor vascular pathologies, including elevated vascular and Interstitial hydraulic conductivities inside the tumor as well as diminished osmotic Pressure differences, on the fluid flow across the tumor capillary bed, the lymphatic drainage, and the IFP. Our results reveal that elevated Interstitial hydraulic conductivity together with poor lymphatic function is the root cause of the development of plateau profiles of the IFP in the tumor, which have been observed in experiments, and contributes to a more uniform distribution of oxygen, solid tumor Pressure and a broad-based collapse of the tumor lymphatics. We also find that the rate that IFF is fluxed into the lymphatics and host tissue is largely controlled by an elevated vascular hydraulic conductivity in the tumor. We discuss the implications of these results on microenvironmental transport barriers, and the tumor invasive and metastatic potential. Our results suggest the possibility of developing strategies of targeting tumor cells based on the cues in the Interstitial fluid.
