Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to investigate the angiogenic response to exogenously administered basic fibroblast growth factor (FGF-2) in normal and ischemic skin, using the hairless mouse ear microcirculatory model. The hairless mouse ear is a well-established model for in vivo studies of skin microcirculation. Using this model, angiogenesis- and angiogenesis-associated changes in the microcirculation can be directly and continuously viewed and quantified in a variety of different experimental settings. To create ischemia in the mouse ear, all but one of the three to four feeding vessels nourishing the ear were ligated 3 days prior to a local subdermal injection of FGF-2 (9.3 + 1-0.5 mm/mm2) or saline into the dorsum of the ears. Angiogenesis was quantified by direct observation, at high magnification, of the injection site where increases in total vessel length (TVL) were measured repeatedly over 18 days following injection. We found a significant (P < 0.01) increase in TVL in normal and ischemic ears injected with FGF-2. Saline injection also induced a significant increase in TVL in ischemic ears. However, the angiogenic response to FGF-2 in ischemic ears was significantly stronger than saline alone in ischemic ears or saline or FGF-2 in normal ears. This response could be used clinically to accelerate angiogenesis and thus increase perfusion in ischemic tissue.
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PMID:Ischemia increases the angiogenic potency of basic fibroblast growth factor (FGF-2). 939 66

Distal muscle flap ischemia and necrosis is a recognized complication of acute elevation of large skeletal muscle flaps. The aim of this study was to investigate whether the angiogenic properties of platelet derived growth factor (PDGF) could be used to augment skeletal muscle flap survival through the induction of new blood vessel formation before flap elevation. We compared this form of flap augmentation with that achieved by subjecting the muscle to a bipedicled vascular delay procedure. The animal model used was the latissimus dorsi muscle of the male homozygous (hr/hr) hairless mouse. Four groups of animals were investigated in this study (n = 10 per group). Group 1 was the control group in which the entire muscle was elevated as a thoracodorsally based island flap. In group 2, the muscle was subjected to a bipedicled vascular delay procedure. In group 3, the muscle was treated with 500 microg of recombinant human platelet derived growth factor BB. In group 4, the muscle was treated with placebo. Ten days later the entire latissimus dorsi muscle was elevated as a thoracodorsally based island flap in groups 2, 3, and 4. Percentage muscle flap survival was quantitated in all groups 5 days after elevation of the entire muscle. Angiogenesis was then quantitated by analyzing capillary to muscle fiber ratios after alkaline phosphatase staining of representative latissimus dorsi muscle samples from the proximal, middle, and distal flap segments. Percentage muscle flap survival was significantly better in PDGF treated muscles when compared with the vascularly delayed muscles (p < 0.001). Histologic analysis of latissimus dorsi muscle flaps demonstrated a significantly greater number of capillaries in the middle (p < 0.001) and distal (p < 0.001) flap segments of PDGF-treated flaps when compared with the vascularly delayed flaps. Treatment of skeletal muscle with PDGF before flap creation resulted in survival of the entire muscle flap. Our results suggest that this survival may be secondary to PDGF-induced angiogenesis.
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PMID:Augmentation of skeletal muscle flap survival using platelet derived growth factor. 970 77

Using intravital fluorescence microscopy in the ears of hairless mice, we determined skin microvascular adaptations during the process of aging from juvenile to adult and senescent life (6-78 wk). Despite an increase of ear area within the first 36 wk, the number and branching pattern of both arteriolar and venular microvessels remained constant during the whole life period. Both arterioles and venules exhibited an increase in length, diameter, and intervascular distance up to the age of 36 wk. With the increase of the size of the ears, the observation that cutaneous capillary density remained unchanged implied new capillary formation. During aging to 78 wk, capillary density in the ears was reduced to approximately 40%. Functional analysis revealed an appropriate hyperemic response to a 2-min period of ischemia during late juvenile and adult life, which, however, was markedly reduced during senescence. Thus, except for capillaries, there is no indication for age-related new vessel formation. The process of aging from adult to senescent life does not cause any significant remodeling but is associated with a decrease of nutritive perfusion and a functional impairment to respond to stimuli such as ischemia.
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PMID:Skin microvascular adaptations during maturation and aging of hairless mice. 1100 45

Induction of the "delay phenomenon" by chronic ischemia is an established clinical procedure, but the mechanisms conferring tissue protection are still incompletely understood. To elucidate the role of heme oxygenase-1 [HO-1 or heat shock protein-32 (HSP-32)] in delay, we examined in the skin-flap model of the ear of the hairless mouse, 1) whether chronic ischemia (delay) is capable to induce expression of HO-1, and 2) whether delay-induced HO-1 affects skin-flap microcirculation and survival by either its carbon monoxide-associated vasodilatory action or its biliverdin-associated anti-oxidative mechanism. Chronic ischemia was induced by transsection of the central feeding vessel of the ear 7 days before flap creation. The flap was finally raised by an incision through four-fifths of the base of the ear. Microcirculatory dysfunction and tissue necrosis were studied with the use of laser Doppler fluxmetry and intravital fluorescence microscopy. HO-1 protein expression was determined with Western blot analysis. Seven days of chronic ischemia (delay) induced a marked expression of HO-1. This was paralleled by a significant improvement (P <0.05) of microvascular perfusion and a reduction (P <0.05) of flap necrosis when compared with nondelayed controls. Importantly, blockade of HO-1 activity by tin protoporhyrin-IX completely blunted the protection of microcirculation and the improvement of tissue survival. Additional administration of the vitamin E analog trolox after blockade of HO-1 to mimic exclusively the anti-oxidative action of the heat shock protein did not restore the HO-1-associated microcirculatory improvement and only transiently attenuated the manifestation of flap necrosis. Thus our data indicate that the delay-induced protection from tissue necrosis is mediated by HO-1, predominantly through its carbon monoxide-associated action of adequately maintaining nutritive capillary perfusion.
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PMID:Mechanism of the delay phenomenon: tissue protection is mediated by heme oxygenase-1. 1521 2

The nerve agent VX has a variable and delayed absorption through the skin, which may have implications for treatment regimens. In the present study, central and peripheral effects of percutaneous VX intoxication were investigated in hairless guinea pigs. Although onset times of clinical signs varied considerably, the relative onset times of signs of poisoning were shown to have a predictive value for survival time. All animals showed elevation of brain choline (Ch) levels. Only two of six animals demonstrated seizure activity on EEG, which was accompanied by acetylcholine (ACh) accumulation. The non-seizing animals displayed only marginal increases of ACh levels, but significant changes in all EEG bands. Acetylcholinesterase activity was highly inhibited in brain and diaphragm. The increases in Ch levels and EEG effects observed in non-seizing animals probably reflected those of ischemia induced by peripheral effects leading to cardiorespiratory compromise. In conclusion, clinical signs will mainly serve as indicators for the onset and maintenance of treatment in subsequent studies.
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PMID:Percutaneous exposure to VX: clinical signs, effects on brain acetylcholine levels and EEG. 1794 Aug 80


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