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In JoVE (1)
Other Publications (13)
- Academic Radiology
- Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
- Advances in Experimental Medicine and Biology
- Methods in Molecular Medicine
- Methods in Enzymology
- Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society
- Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society
- Antioxidants & Redox Signaling
- Anesthesia and Analgesia
- Anesthesiology
- Plastic and Reconstructive Surgery
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine
Articles by Mark D. Rollins in JoVE
JoVE General
Murine Model of Hindlimb Ischemia
1Division of Cardiovascular Medicine, Stanford University, 2Department of Anesthesiology, University of California, San Francisco
The surgical procedure for induction of unilateral hindlimb ischemia is demonstrated, with confirmation of ischemia by laser Doppler perfusion imaging.
Other articles by Mark D. Rollins on PubMed
Correlation of a Simple Direct Measurement of Muscle PO(2) to a Clinical Ischemia Index and Histology in a Rat Model of Chronic Severe Hindlimb Ischemia
The lack of suitable experimental models of chronic severe limb ischemia and deficiencies in the available methods that allow for direct intermittent measurement of regional limb perfusion are obstacles to the evaluation of recently developed molecular strategies to reverse severe limb ischemia. Our aim was to develop a model of clinically relevant severe limb ischemia and correlate a simple direct measurement of muscle pO(2) to a clinical ischemia index, muscle mass, and capillary density.
Hyperoxia Improves Microvascular Perfusion in a Murine Wound Model
There is a need for a noninvasive method that measures wound angiogenesis. Hyperoxia is known to increase the appearance of new blood vessels in wounds, yet no study has confirmed increases in wound bed perfusion with periodic hyperbaric oxygen (HBO) exposure. This study investigates whether laser Doppler imaging is able to detect and quantify the enhancement of wound angiogenesis that is known to occur with intermittent HBO treatments. Full-thickness dorsal dermal wounds were created on mice randomized to hyperoxic (n = 14) and control (n = 15) groups. Hyperbaric oxygen was administered twice daily for 90 minutes each at 2.1 atmospheres for 7 days. Wound bed perfusion was measured by laser Doppler imaging on days 0, 7, and 10 postwounding. Wound blood flow increased significantly over baseline on day 7 and 10 in the hyperoxic group, but only on day 10 in the control group. Comparison between groups showed a 20% statistically significant increase in wound perfusion in HBO-treated animals compared to control on day 10 (p = 0.05). Laser Doppler imaging was able to detect and quantify the increase in wound bed perfusion resulting from intermittent HBO treatments and shows promise as a noninvasive measure of angiogenesis and wound healing.
Hyperoxia and Angiogenesis
We hypothesized that tissue hyperoxia would enhance and hypoxia inhibit neovascularization in a wound model. Therefore, we used female Swiss-Webster mice to examine the influence of differential oxygen treatment on angiogenesis. One milliliter plugs of Matrigel, a mixture of matrix proteins that supports but does not itself elicit angiogenesis, were injected subcutaneously into the mice. Matrigel was used without additive or with added vascular endothelial growth factor (VEGF) or anti-VEGF antibody. Animals were maintained in hypoxic, normoxic, or one of four hyperoxic environments: hypoxia -- 13 percent oxygen at 1 atmosphere absolute (ATA); normoxia -- 21 percent oxygen at 1 ATA; hyperoxia -- (groups a-d) 100 percent oxygen for 90 minutes twice daily at the following pressures: Group a, 1 ATA; Group b, 2 ATA; Group c, 2.5 ATA; Group d, 3.0 ATA. Subcutaneous oxygen tension was measured in all groups. The Matrigel was removed 7 days after implantation. Sections were graded microscopically for the extent of neovascularization. Angiogenesis was significantly greater in all hyperoxic groups and significantly less in the hypoxic group compared with room air-exposed controls. Anti-VEGF antibody abrogated the angiogenic effect of both VEGF and increased oxygen tension. We conclude that angiogenesis is proportional to ambient pO(2) over a wide range. This confirms the clinical impression that angiogenesis requires oxygen. Intermittent oxygen exposure can satisfy the need for oxygen in ischemic tissue.
Wounds: an Overview of the Role of Oxygen
We sought to review the role of oxygen in wound healing, with an emphasis on the role tissue oximetry has played in clinical advances in the care of patients with wounds. Oxygen is required for wound healing. Hypoxia sufficient to impair healing is common in wounds, frequently resulting from sympathetically induced vasoconstriction. Correction or prevention of vasoconstriction, as well as provision of increased inspired oxygen in well-perfused patients, has been shown in randomized, controlled clinical trials to improve wound outcomes. Our understanding of the role of oxygen in wound healing has been fueled by tissue oximetry. Advances in technology will lead to further advances in the management of patients with wounds.
Thromboemboli, Acute Right Heart Failure and Disseminated Intravascular Coagulation After Intraoperative Application of a Topical Hemostatic Matrix
Topical hemostatic agents are frequently used in spine surgeries to control or reduce bleeding. Although there are a number of commercially available products, at our institution, an absorbable gelatin powder (Surgifoam) is mixed with bovine thrombin and used for this purpose. We report the case of a patient undergoing a posterior spinal fusion for scoliosis who developed acute right heart failure, cardiac arrest, and disseminated intravascular coagulation after probable intravascular hemostatic agent-induced emboli. Clinicians need to be aware of this potentially deadly complication associated with topical hemostatic agents.
Monitoring Partial and Full Venous Outflow Compromise in a Rabbit Skin Flap Model
Free flap failure often results from venous thrombosis. The authors developed a rabbit flap model of partial venous obstruction and evaluated four monitoring devices in detecting partial and full venous compromise.
Embryonic Stem Cell-derived Endothelial Cells Engraft into the Ischemic Hindlimb and Restore Perfusion
We examined the effect of delivery modality on the survival, localization, and functional effects of exogenously administered embryonic stem cells (ESCs) or endothelial cells derived from them (ESC-ECs) in the ischemic hindlimb.
Quantitative Tissue Oxygen Measurement in Multiple Organs Using 19F MRI in a Rat Model
Measurement of individual organ tissue oxygen levels can provide information to help evaluate and optimize medical interventions in many areas including wound healing, resuscitation strategies, and cancer therapeutics. Echo planar (19) F MRI has previously focused on tumor oxygen measurement at low oxygen levels (pO(2)) <30 mmHg. It uses the linear relationship between spin-lattice relaxation rate (R(1)) of hexafluorobenzene (HFB) and pO(2). The feasibility of this technique for a wider range of pO(2) values and individual organ tissue pO(2) measurement was investigated in a rat model. Spin-lattice relaxation times (T(1) = 1/R(1)) of hexafluorobenzene were measured using (19) F saturation recovery echo planar imaging. Initial in vitro studies validated the linear relationship between R(1) and pO(2) from 0 to 760 mmHg oxygen partial pressure at 25, 37, and 41°C at 7 Tesla for hexafluorobenzene. In vivo experiments measured rat tissue oxygen (ptO2) levels of brain, kidney, liver, gut, muscle, and skin during inhalation of both 30 and 100% oxygen. All organ ptO(2) values significantly increased with hyperoxia (P < 0.001). This study demonstrates that (19) F MRI of hexafluorobenzene offers a feasible tool to measure regional ptO2 in vivo, and that hyperoxia significantly increases ptO2 of multiple organs in a rat model.
