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Updated: Jul 13, 2026

Assessing Therapeutic Angiogenesis in a Murine Model of Hindlimb Ischemia
Published on: June 8, 2019
[Pathophysiology, diagnosis, and laboratoy examination in critical limb ischemia]
Norihide Sugano1, Takehisa Iwai
1Division of Vascular Surgery, Department of Surgery, Tokyo Medical and Dental University Guraduate School of Medicine, Tokyo, Japan.
Insights
Critical limb ischemia (CLI) occurs when arterial disease severely reduces blood flow, causing pain, ulcers, or gangrene. Evaluating microcirculation is key to understanding and managing CLI.
Area of Science:
- Vascular Medicine
- Peripheral Artery Disease
- Ischemia Research
Context:
- Critical limb ischemia (CLI) is characterized by chronic ischemic pain, ulcers, or gangrene due to confirmed occlusive arterial disease.
- Specific ankle pressure (AP) and toe pressure (TP) thresholds define CLI severity, with lower pressures indicating poorer outcomes.
- Healing of CLI-related wounds necessitates higher perfusion pressures than those causing ischemic pain at rest.
Purpose:
- To define critical limb ischemia (CLI) and its diagnostic pressure thresholds.
- To explain the pathophysiological basis of CLI, involving macrovascular and microvascular factors.
- To highlight the importance of microcirculation assessment in CLI.
Summary:
- CLI is defined by chronic ischemic symptoms (pain, ulcers, gangrene) linked to arterial disease, with diagnostic pressure cutoffs for AP and TP.
- CLI results from reduced blood flow due to arterial lesions and local tissue perfusion imbalances.
- Assessing microcirculation using transcutaneous oxygen tension and skin perfusion pressure is crucial for understanding CLI pathophysiology.
Impact:
- Provides clear diagnostic criteria for critical limb ischemia based on objective pressure measurements.
- Emphasizes the dual role of macrovascular and microvascular dysfunction in CLI development.
- Underscores the clinical utility of microcirculation assessment techniques in managing CLI patients.
Abstract:
The term critical limb ischemia (CLI) is defined as chronic ischemic pain at rest, ulcers, or gangrene lasting more than 2 weeks attributable to objectively confirmed occlusive arterial disease. Patients with ischemic pain at rest generally have ankle pressure (AP) of less than 50 mmHg or toe pressure (TP) of less than 30 mmHg, while patients with ulcers or gangrene usually have AP of less than 70 mmHg or TP of less than 50 mmHg. Healing requires an inflammatory response and additional perfusion above that required for supporting intact skin and underlying tissues. The AP and TP levels needed for healing are, therefore, higher than the pressures found in ischemic pain at rest. A combination of blood-flow reduction due to multisegmental lesions of the proximal artery and blood-flow imbalance in the local tissue lead to CLI. It is important to evaluate not only the macroscopic blood flow but also the microcirculation to understand the pathophysiology of CLI. Transcutaneous oxygen tension measurement (critical level <30 mmHg) and skin perfusion pressure measurement (critical level < 30 mmHg) are useful methods to evaluate the microcirculation.
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