Bronchial Circulation

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Lillian D. Traber - One of the best experts on this subject based on the ideXlab platform.

  • Effect of reduced Bronchial Circulation on lung fluid flux after smoke inhalation in sheep
    2016
    Co-Authors: Lillian D. Traber, Daniel L. Traber, Richard Johnigan, Yuji Kikuchi, Mikihiko Harada, Daniel L
    Abstract:

    Traber. Effect of reduced Bronchial Circulation on lung fluid flux after smoke inhalation in sheep. J. Appl. Physiol. 84(3): 980–986, 1998.—We determined the effect of reduced bron-chial blood flow on lung fluid flux through changes in lung lymph flow, lung wet weight-to-dry weight (wet/dry) ratios, and pulmonary microvascular reflection coefficient (s). In the first of two surgical procedures, Merino ewes (n 5 21) were surgically prepared for chronic study. Five to seven days later, in a second operation, the Bronchial artery of the injection group (n 5 7) was ligated, and 4 ml of 70 % ethanol were injected into the Bronchial artery to cause sclerosis of the airway Circulation. In the ligation group (n 5 7), only the Bronchial artery was ligated. In the sham group (n 5 7), the Bronchial artery was surgically exposed but left intact with-out ligation or ethanol injection. One day after these opera

  • Bronchial vasculature of sheep Distribution of blood flow and neutrophil kinetics in
    2015
    Co-Authors: E. M. Baile, Lillian D. Traber, Richard Johnigan, Yuji Kikuchi, Mikihiko Harada, Hiroyuki Sakurai, David Ernest, Peter Dodek, David B. Pearse
    Abstract:

    Effect of reduced Bronchial Circulation on lung fluid flux after smoke inhalation in sheep [PDF] [Full Text]

  • Impact of Bronchial Circulation on Bronchial exudates following combined burn and smoke inhalation injury in sheep.
    Burns : journal of the International Society for Burn Injuries, 2010
    Co-Authors: Naoki Morita, Perenlei Enkhbaatar, Martin Westphal, Marc O. Maybauer, Dirk M. Maybauer, Lillian D. Traber, Kazunori Murakami, Hal K. Hawkins, Robert A. Cox, Daniel L. Traber
    Abstract:

    Abstract We previously reported Bronchial Circulation contributes to pulmonary edema and increases shunt fraction following smoke inhalation, and Bronchial blood flow significantly increases in inhalation injury. We hypothesized reduction of Bronchial blood flow reduces exudation to the airway and ameliorates lung injury from combined burn and smoke insults (BS (2) Bronchial artery left intact and injured (injury + no ligation group); (3) Bronchial artery ligated but not injured (no injury + ligation group) were subjected to a flame burn and inhalation injury under halothane anesthesia. Parameters were analyzed using Scheffe's post hoc test ( P Results Pulmonary gas exchange (PaO 2 /FiO 2 ) improved in injury + ligation group. Further, obstruction score, an index of airway cast formation, significantly changed between injury + no ligation group compared to both ligation groups. Conclusion Bronchial Circulation plays a significant role in lung injury after B&S injury, and reduction of Bronchial blood flow by Bronchial artery ligation reduces Bronchial exudates, resulting in improved gas exchange.

  • Effect of ablated airway blood flow on systemic and pulmonary microvascular permeability after smoke inhalation in sheep
    Burns : journal of the International Society for Burn Injuries, 2007
    Co-Authors: Hiroyuki Sakurai, Lillian D. Traber, Kazutaka Soejima, Motohiro Nozaki, Daniel L. Traber
    Abstract:

    The Bronchial Circulation plays a significant role in the pathogenesis of smoke inhalation. We investigated the physiological manifestations in both the systemic and the pulmonary Circulation after smoke inhalation injury, and determined whether ablation of the Bronchial Circulation had any effect on these changes. We used a chronically instrumented ovine model with lung and prefemoral lymph fistulae to determine the changes in pulmonary and systemic microvascular permeability. Fourteen animals were divided into two groups. The injection group had Bronchial Circulation ablation with an ethanol injection into the Bronchial artery, whereas it was left intact in the sham group. The sham group showed a four-fold increase in lung lymph flow (l-QL) and a two-fold increase in prefemoral lymph flow (s-QL) 24 h after injury. The increase in s-QL was associated with a decrease in lymph oncotic pressure. Therefore, systemic colloid clearance (s-CC), an indicator of systemic microvascular permeability to protein, was unchanged. The ablated Bronchial Circulation reversed the pulmonary but not the systemic manifestations after smoke inhalation. In conclusion, the pathophysiological events occurring after smoke inhalation were confined to the lung with increased Bronchial blood flow delivering inflammatory mediators directly to the lung parenchyma.

  • The role of the Bronchial Circulation in the acute lung injury resulting from burn and smoke inhalation
    Pulmonary pharmacology & therapeutics, 2006
    Co-Authors: Daniel L. Traber, Perenlei Enkhbaatar, Frank C. Schmalstieg, Hal K. Hawkins, Robert A. Cox, Joseph B. Zwischenberger, Lillian D. Traber
    Abstract:

    Smoke inhalation in burn patients is a serious medical problem around the world. Inhalation injury increases mortality in addition to increasing infections, ventilator-days, and hospital stays. There are also large numbers of patients subjected to smoke inhalation without burns from cooking fires, burning crops and forest fires. The injury results in a fall in arterial oxygenation as a result of airway blockade, increased pulmonary transvascular fluid flux and loss of hypoxic pulmonary vasoconstriction. The changes in cardiopulmonary function are mediated at least in part by reactive oxygen and nitrogen species. Nitric oxide (NO) is generated by both inducible and constitutive isoforms of nitric oxide synthase (NOS). NO combines with superoxide to form reactive nitrogen species such as peroxynitrite. These reactive nitrogen species can be detected by measuring their reaction products such as 3-nitrotyrosine. The latter is elevated in the airway following smoke/burn injury. The control of NO formation involves poly (ADP ribose) polymerase (PARP) and its ability to up-regulate the activity of nuclear transcription factors through ribosylation. Present data also support a major role for the Bronchial Circulation in the injury since blockade of Bronchial blood flow will also minimize the pulmonary injury. The data suggest that cytotoxins or activated cells are formed in the airway and carried to the parenchyma. These materials cause the formation of oedema and a reduction of PaO(2).

Daniel L. Traber - One of the best experts on this subject based on the ideXlab platform.

  • Effect of reduced Bronchial Circulation on lung fluid flux after smoke inhalation in sheep
    2016
    Co-Authors: Lillian D. Traber, Daniel L. Traber, Richard Johnigan, Yuji Kikuchi, Mikihiko Harada, Daniel L
    Abstract:

    Traber. Effect of reduced Bronchial Circulation on lung fluid flux after smoke inhalation in sheep. J. Appl. Physiol. 84(3): 980–986, 1998.—We determined the effect of reduced bron-chial blood flow on lung fluid flux through changes in lung lymph flow, lung wet weight-to-dry weight (wet/dry) ratios, and pulmonary microvascular reflection coefficient (s). In the first of two surgical procedures, Merino ewes (n 5 21) were surgically prepared for chronic study. Five to seven days later, in a second operation, the Bronchial artery of the injection group (n 5 7) was ligated, and 4 ml of 70 % ethanol were injected into the Bronchial artery to cause sclerosis of the airway Circulation. In the ligation group (n 5 7), only the Bronchial artery was ligated. In the sham group (n 5 7), the Bronchial artery was surgically exposed but left intact with-out ligation or ethanol injection. One day after these opera

  • Impact of Bronchial Circulation on Bronchial exudates following combined burn and smoke inhalation injury in sheep.
    Burns : journal of the International Society for Burn Injuries, 2010
    Co-Authors: Naoki Morita, Perenlei Enkhbaatar, Martin Westphal, Marc O. Maybauer, Dirk M. Maybauer, Lillian D. Traber, Kazunori Murakami, Hal K. Hawkins, Robert A. Cox, Daniel L. Traber
    Abstract:

    Abstract We previously reported Bronchial Circulation contributes to pulmonary edema and increases shunt fraction following smoke inhalation, and Bronchial blood flow significantly increases in inhalation injury. We hypothesized reduction of Bronchial blood flow reduces exudation to the airway and ameliorates lung injury from combined burn and smoke insults (BS (2) Bronchial artery left intact and injured (injury + no ligation group); (3) Bronchial artery ligated but not injured (no injury + ligation group) were subjected to a flame burn and inhalation injury under halothane anesthesia. Parameters were analyzed using Scheffe's post hoc test ( P Results Pulmonary gas exchange (PaO 2 /FiO 2 ) improved in injury + ligation group. Further, obstruction score, an index of airway cast formation, significantly changed between injury + no ligation group compared to both ligation groups. Conclusion Bronchial Circulation plays a significant role in lung injury after B&S injury, and reduction of Bronchial blood flow by Bronchial artery ligation reduces Bronchial exudates, resulting in improved gas exchange.

  • Recombinant human activated protein C in acute lung injury: what is the role of Bronchial Circulation?
    Critical care (London England), 2009
    Co-Authors: Marc O. Maybauer, Daniel L. Traber, Dirk M. Maybauer
    Abstract:

    Impairment of the protein C pathway plays a central role in the pathogenesis of sepsis. Treatment with recombinant human activated protein C (rhAPC) has been reported to increase survival from severe sepsis. Protein C levels also decrease markedly in acute lung injury, of both septic and nonseptic origin. Low levels of protein C in acute lung injury are associated with poor clinical outcome. The present article discusses the beneficial effects of rhAPC in oleic acid-induced lung injury as well as the controversies between different animal models and the timing of drug administration. The unique Bronchial Circulation in ovine models seems to be responsible for the beneficial effects of rhAPC when given simultaneously to the injury.

  • Effect of ablated airway blood flow on systemic and pulmonary microvascular permeability after smoke inhalation in sheep
    Burns : journal of the International Society for Burn Injuries, 2007
    Co-Authors: Hiroyuki Sakurai, Lillian D. Traber, Kazutaka Soejima, Motohiro Nozaki, Daniel L. Traber
    Abstract:

    The Bronchial Circulation plays a significant role in the pathogenesis of smoke inhalation. We investigated the physiological manifestations in both the systemic and the pulmonary Circulation after smoke inhalation injury, and determined whether ablation of the Bronchial Circulation had any effect on these changes. We used a chronically instrumented ovine model with lung and prefemoral lymph fistulae to determine the changes in pulmonary and systemic microvascular permeability. Fourteen animals were divided into two groups. The injection group had Bronchial Circulation ablation with an ethanol injection into the Bronchial artery, whereas it was left intact in the sham group. The sham group showed a four-fold increase in lung lymph flow (l-QL) and a two-fold increase in prefemoral lymph flow (s-QL) 24 h after injury. The increase in s-QL was associated with a decrease in lymph oncotic pressure. Therefore, systemic colloid clearance (s-CC), an indicator of systemic microvascular permeability to protein, was unchanged. The ablated Bronchial Circulation reversed the pulmonary but not the systemic manifestations after smoke inhalation. In conclusion, the pathophysiological events occurring after smoke inhalation were confined to the lung with increased Bronchial blood flow delivering inflammatory mediators directly to the lung parenchyma.

  • The role of the Bronchial Circulation in the acute lung injury resulting from burn and smoke inhalation
    Pulmonary pharmacology & therapeutics, 2006
    Co-Authors: Daniel L. Traber, Perenlei Enkhbaatar, Frank C. Schmalstieg, Hal K. Hawkins, Robert A. Cox, Joseph B. Zwischenberger, Lillian D. Traber
    Abstract:

    Smoke inhalation in burn patients is a serious medical problem around the world. Inhalation injury increases mortality in addition to increasing infections, ventilator-days, and hospital stays. There are also large numbers of patients subjected to smoke inhalation without burns from cooking fires, burning crops and forest fires. The injury results in a fall in arterial oxygenation as a result of airway blockade, increased pulmonary transvascular fluid flux and loss of hypoxic pulmonary vasoconstriction. The changes in cardiopulmonary function are mediated at least in part by reactive oxygen and nitrogen species. Nitric oxide (NO) is generated by both inducible and constitutive isoforms of nitric oxide synthase (NOS). NO combines with superoxide to form reactive nitrogen species such as peroxynitrite. These reactive nitrogen species can be detected by measuring their reaction products such as 3-nitrotyrosine. The latter is elevated in the airway following smoke/burn injury. The control of NO formation involves poly (ADP ribose) polymerase (PARP) and its ability to up-regulate the activity of nuclear transcription factors through ribosylation. Present data also support a major role for the Bronchial Circulation in the injury since blockade of Bronchial blood flow will also minimize the pulmonary injury. The data suggest that cytotoxins or activated cells are formed in the airway and carried to the parenchyma. These materials cause the formation of oedema and a reduction of PaO(2).

Elizabeth M Wagner - One of the best experts on this subject based on the ideXlab platform.

  • Bronchial Artery Angiogenesis Drives Lung Tumor Growth.
    Cancer research, 2016
    Co-Authors: Lindsey Eldridge, Wayne Mitzner, Aigul Moldobaeva, Qiong Zhong, John Jenkins, Michael Snyder, Robert H. Brown, Elizabeth M Wagner
    Abstract:

    Angiogenesis is vital for tumor growth but in well-vascularized organs such as the lung its importance is unclear. This situation is complicated by the fact that the lung has two separate Circulations, the pulmonary and the systemic Bronchial Circulation. There are few relevant animal models of non-small cell lung cancer, which can be used to study the lung's complex Circulations, and mice, lacking a systemic Bronchial Circulation cannot be used. We report here a novel orthotopic model of non-small cell lung cancer in rats, where we have studied the separate contributions of each of the two Circulations for lung tumor growth. Results show that Bronchial artery perfusion, quantified by fluorescent microspheres (206% increase in large tumors) or high-resolution computed tomography scans (276% increase in large tumors), parallels the growth in tumor volume, whereas pulmonary artery perfusion remained unchanged. Ablation of the Bronchial artery after the initiation of tumor growth resulted in a decrease in tumor volume over a subsequent course of 4 weeks. These results demonstrate that although the existing pulmonary Circulation can supply the metabolic needs for tumor initiation, further growth of the tumor requires angiogenesis from the highly proliferative Bronchial Circulation. This model may be useful to investigate new therapeutic approaches that target specifically the Bronchial Circulation. Cancer Res; 76(20); 5962-9. ©2016 AACR.

  • Angiogenesis in the Mouse Lung
    The American journal of pathology, 2000
    Co-Authors: Wayne Mitzner, Won Jae Lee, Dimitrios Georgakopoulos, Elizabeth M Wagner
    Abstract:

    When pulmonary arterial blood flow is obstructed in all mammals studied, there is a compensatory growth of the Bronchial vasculature. This angiogenesis normally occurs through a proliferation of the systemic Circulation to the intraparenchymal airways. It is an important pathophysiological process, not only in pulmonary vascular disease, but also in lung cancer, because the blood flow that supplies primary lung tumors arises from the systemic Circulation. In the mouse, however, the systemic blood vessels that supply the trachea and mainstem bronchi do not penetrate into the intraparenchymal airways, as they do in all other larger species. In this study, we attempted to generate a new functional Bronchial Circulation in the mouse by permanently obstructing 40% of the pulmonary Circulation. We quantified the systemic blood flow to the lung with fluorescent microspheres for 3 months after left pulmonary artery ligation. Results demonstrated that a substantial systemic blood flow to the lung that can eventually supply up to 15% of the normal pulmonary flow can be generated beginning 5–6 days after ligation. These new angiogenic vessels do not arise from the extraparenchymal Bronchial Circulation. Rather they enter the lung directly via a totally new vasculature that develops between the visceral and parietal pleuras, supplied by several intercostal arteries. This unique model of angiogenesis occurs in the absence of any hypoxic stimulus and mimics the vascular source of many lung tumors.

  • Site of functional bronchopulmonary anastomoses in sheep.
    The Anatomical record, 1999
    Co-Authors: Elizabeth M Wagner, Wayne Mitzner, Robert H. Brown
    Abstract:

    The location of bronchopulmonary anastomoses has long been a topic of discussion, and pre-, post-, and capillary sites have all been demonstrated in postmortem examinations. However, there have been few studies that have provided insight into the patency and function of these anastomoses in the intact lung. To identify these functional sites where the Bronchial Circulation anastomoses with the pulmonary Circulation, we studied sheep lungs in situ serial sectioned with high-resolution computed tomography (CT). Differences in radiodensities of blood, air, and nonionic contrast medium were used to differentiate and localize airways and vessels and to identify the effluent from the Bronchial Circulation. After an initial series of scans to identify the pulmonary arteries and veins adjacent to airways 2-12 mm in diameter, contrast material was infused into the Bronchial artery. In three sheep, the major accumulation of contrast medium was found in pulmonary veins. In one of the sheep, a comparable number of pulmonary arteries and veins contained contrast medium. Serial histologic sections were able to identify small Bronchial venules lying within subepithelial Bronchial folds that drain directly into pulmonary veins. These results using serial CT and histologic images suggest that drainage from the intraparenchymal Bronchial vasculature is predominantly into postcapillary pulmonary vessels.

  • Aerosol clearance by the Bronchial Circulation.
    Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine, 1996
    Co-Authors: Elizabeth M Wagner
    Abstract:

    The importance of the tracheoBronchial Circulation in supporting mucociliary clearance is unclear. In anesthetized, ventilated sheep (n = 8), mucociliary transport of 99mTc-labeled sulfur colloid particles (2.1 microns) was measured during control perfusion of the cannulated Bronchial branch of the bronchoesophageal artery or when perfusion through this artery was stopped. Particle retention 60 min after aerosol delivery of particles averaged 55% during control Bronchial blood flow conditions. When perfusion was stopped, average retention was significantly increased to 76% (p < 0.05). These results indicate that the Bronchial vasculature exerts an important modulating influence on mucociliary transport.

  • aerosol clearance by the Bronchial Circulation
    Journal of Aerosol Medicine-deposition Clearance and Effects in The Lung, 1996
    Co-Authors: Elizabeth M Wagner
    Abstract:

    ABSTRACT The importance of the tracheoBronchial Circulation in supporting mucociliary clearance is unclear. In anesthetized, ventilated sheep (n = 8), mucociliary transport of 99mTc-labeled sulfur ...

E K Potter - One of the best experts on this subject based on the ideXlab platform.

  • Inhibition of vagal vasodilatation by a selective neuropeptide Y Y2 receptor agonist in the Bronchial Circulation of anaesthetised dogs.
    Journal of the autonomic nervous system, 1998
    Co-Authors: D A Mahns, J S Lacroix, E K Potter
    Abstract:

    Neuropeptide Y (NPY) is both co-stored and co-released with noradrenaline from sympathetic nerve terminals. In the cardiovascular system, NPY acts on two main receptor subtypes. At postjunctional, or Y1 receptors, NPY can cause both direct vasoconstriction and the potentiation of various constrictor agents. NPY acting at the presynaptic, or Y2 receptor, inhibits the release of neurotransmitter from autonomic nerves. In the present paper, we have used both sympathetic stimulation and the selective NPY Y2 receptor agonist, N-acetyl [Leu28,Leu31] NPY24-36, to examine the role of NPY in the inhibition of vagally mediated vasodilatation in the Bronchial Circulation of the anaesthetised dog. Stimulation of the cardiac end of the cervical vagus nerve at 1 Hz for 15 s (1 ms, 70 V) increased Bronchial vascular conductance by 45%. This increase in flow was abolished by atropine. Sympathetic stimulation for 2.5 min at 16 Hz (1 ms, 20 V) produced a significant (P < 0.05) and prolonged (9 min) inhibition of the subsequent parasympathetically evoked vasodilatation. Similarly, the NPY Y2 receptor agonist, N-acetyl [Leu28,Leu31] NPY24-36, produced a significant (P < 0.05) and prolonged (15 min) inhibition of parasympathetically evoked vasodilatation. When vagus was stimulated at 2.5 Hz for 30 s (1 ms, 70 V), an atropine-resistant, but capsaicin-sensitive vasodilatation was observed. Neither sympathetic stimulation nor the NPY Y2 receptor agonist could be demonstrated to inhibit this vasodilatation. These results suggest that NPY can inhibit cholinergic parasympathetic vasodilatation in the Bronchial Circulation by an action on NPY Y2 receptors.

  • Inhibition of vagal vasodilatation by a selective neuropeptide Y Y2 receptor agonist in the Bronchial Circulation of anaesthetised dogs
    Journal of The Autonomic Nervous System, 1998
    Co-Authors: D A Mahns, J S Lacroix, E K Potter
    Abstract:

    Abstract Neuropeptide Y (NPY) is both co-stored and co-released with noradrenaline from sympathetic nerve terminals. In the cardiovascular system, NPY acts on two main receptor subtypes. At postjunctional, or Y1 receptors, NPY can cause both direct vasoconstriction and the potentiation of various constrictor agents. NPY acting at the presynaptic, or Y2 receptor, inhibits the release of neurotransmitter from autonomic nerves. In the present paper, we have used both sympathetic stimulation and the selective NPY Y2 receptor agonist, N-acetyl [Leu28,Leu31] NPY24-36, to examine the role of NPY in the inhibition of vagally mediated vasodilatation in the Bronchial Circulation of the anaesthetised dog. Stimulation of the cardiac end of the cervical vagus nerve at 1 Hz for 15 s (1 ms, 70 V) increased Bronchial vascular conductance by 45%. This increase in flow was abolished by atropine. Sympathetic stimulation for 2.5 min at 16 Hz (1 ms, 20 V) produced a significant (P

Anne V Clough - One of the best experts on this subject based on the ideXlab platform.

  • Bronchial Circulation angiogenesis in the rat quantified with SPECT and micro-CT.
    European journal of nuclear medicine and molecular imaging, 2008
    Co-Authors: Christian Wietholt, Robert C Molthen, Steven T Haworth, David L Roerig, John B. Gordon, Anne V Clough
    Abstract:

    Introduction As pulmonary artery obstruction results in proliferation of the Bronchial Circulation in a variety of species, we investigated this angiogenic response using single photon emission computed tomography (SPECT) and micro-CT.

  • quantification of Bronchial Circulation perfusion in rats
    Medical Imaging 2004: Physiology Function and Structure from Medical Images, 2004
    Co-Authors: Christian Wietholt, Robert C Molthen, Steven T Haworth, David L Roerig, C A Dawson, Anne V Clough
    Abstract:

    The Bronchial Circulation is thought to be the primary blood supply for pulmonary carcinomas. Thus, we have developed a method for imaging and quantifying changes in perfusion in the rat lung due to development of the Bronchial Circulation. A dual-modality micro-CT/SPECT system was used to detect change in perfusion in two groups of rats: controls and those with a surgically occluded left pulmonary artery. Both groups were imaged following injections on separate days i) 2mCi of Tc99m labeled macroaggregated albumin (MAA) into the left carotid artery (IA) and ii) a similar injection into the femoral vein (IV). The IA injection resulted in Tc99m accumulation in capillaries of the systemic Circulation including the Bronchial Circulation, whereas the IV resulted in Tc99m accumulation in the pulmonary capillaries. Ordered subset expectation maximization (OSEM) was used to reconstruct the SPECT image volumes and a Feldkamp algorithm was used to reconstruct the micro-CT image volumes. The micro-CT and SPECT volumes were registered, the SPECT image volume was segmented using the right and left lung boundaries defined from the micro-CT volume, and the ratio of IA radioactivity accumulation in the left lung to IV radioactivity accumulation in both lungs was used as a measure of left lung flow via the Bronchial Circulation. This ratio was ~0.02 for the untreated rats compared to the treated animals that had an increased flow ratio of ~0.21 40 days after left pulmonary artery occlusion. This increase in flow to the occluded left lung via the Bronchial Circulation suggests this will be a useful model for further investigating antiangiogenic treatments.

  • SPECT/Micro-CT Imaging of Bronchial Angiogenesis in a Rat
    Small-Animal Spect Imaging, 1
    Co-Authors: Anne V Clough, Christian Wietholt, Robert C Molthen, John C. Gordon, David L Roerig
    Abstract:

    The Bronchial Circulation provides the lung with an oxygenated blood supply, derived from the aorta, whose primary purpose under normal conditions is thought to be nourishment of the airway walls +Guyton, 1996-. However,the study of the Bronchial Circulation and its development is particularly important with regard to lung tumors whose blood supply is via the Bronchial Circulation rather than the pulmonary Circulation +Hirsch, 2001, Ohta, 2002-. Thus, we have developed a rat model of Bronchial Circulation angiogenesis,induced by complete occlusion of the left pulmonary artery. We have been observing the resulting perfusion changes in the left lung using dual-modality SPECT/micro-CT imaging. The initial objective of this study is to develop the necessary imaging system, protocol, and analysis methods for determining the time course of this angiogenesis, with the subsequent goal of using this approach to study the particular angiogenic mechanisms that might be involved.