The challenge of translating ischemic conditioning from animal models to humans: the role of comorbidities
Following a period of ischemia (local restriction of blood supply to a tissue), the restoration of blood supply to the affected area causes significant tissue damage. This is known as ischemia-reperfusion injury (IRI) and is a central pathological mechanism contributing to many common disease states...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2014-12-01
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| Series: | Disease Models & Mechanisms |
| Subjects: | |
| Online Access: | http://dmm.biologists.org/content/7/12/1321 |
| _version_ | 1818313323724144640 |
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| author | Kieran McCafferty Suzanne Forbes Christoph Thiemermann Muhammad M. Yaqoob |
| author_facet | Kieran McCafferty Suzanne Forbes Christoph Thiemermann Muhammad M. Yaqoob |
| author_sort | Kieran McCafferty |
| collection | DOAJ |
| description | Following a period of ischemia (local restriction of blood supply to a tissue), the restoration of blood supply to the affected area causes significant tissue damage. This is known as ischemia-reperfusion injury (IRI) and is a central pathological mechanism contributing to many common disease states. The medical complications caused by IRI in individuals with cerebrovascular or heart disease are a leading cause of death in developed countries. IRI is also of crucial importance in fields as diverse as solid organ transplantation, acute kidney injury and following major surgery, where post-operative organ dysfunction is a major cause of morbidity and mortality. Given its clinical impact, novel interventions are urgently needed to minimize the effects of IRI, not least to save lives but also to reduce healthcare costs. In this Review, we examine the experimental technique of ischemic conditioning, which entails exposing organs or tissues to brief sub-lethal episodes of ischemia and reperfusion, before, during or after a lethal ischemic insult. This approach has been found to confer profound tissue protection against IRI. We discuss the translation of ischemic conditioning strategies from bench to bedside, and highlight where transition into human clinical studies has been less successful than in animal models, reviewing potential reasons for this. We explore the challenges that preclude more extensive clinical translation of these strategies and emphasize the role that underlying comorbidities have in altering the efficacy of these strategies in improving patient outcomes. |
| first_indexed | 2024-12-13T08:31:55Z |
| format | Article |
| id | doaj.art-eb196efc4823414f9cdc87dc0729e6be |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-12-13T08:31:55Z |
| publishDate | 2014-12-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-eb196efc4823414f9cdc87dc0729e6be2022-12-21T23:53:44ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112014-12-017121321133310.1242/dmm.016741016741The challenge of translating ischemic conditioning from animal models to humans: the role of comorbiditiesKieran McCaffertySuzanne ForbesChristoph ThiemermannMuhammad M. YaqoobFollowing a period of ischemia (local restriction of blood supply to a tissue), the restoration of blood supply to the affected area causes significant tissue damage. This is known as ischemia-reperfusion injury (IRI) and is a central pathological mechanism contributing to many common disease states. The medical complications caused by IRI in individuals with cerebrovascular or heart disease are a leading cause of death in developed countries. IRI is also of crucial importance in fields as diverse as solid organ transplantation, acute kidney injury and following major surgery, where post-operative organ dysfunction is a major cause of morbidity and mortality. Given its clinical impact, novel interventions are urgently needed to minimize the effects of IRI, not least to save lives but also to reduce healthcare costs. In this Review, we examine the experimental technique of ischemic conditioning, which entails exposing organs or tissues to brief sub-lethal episodes of ischemia and reperfusion, before, during or after a lethal ischemic insult. This approach has been found to confer profound tissue protection against IRI. We discuss the translation of ischemic conditioning strategies from bench to bedside, and highlight where transition into human clinical studies has been less successful than in animal models, reviewing potential reasons for this. We explore the challenges that preclude more extensive clinical translation of these strategies and emphasize the role that underlying comorbidities have in altering the efficacy of these strategies in improving patient outcomes.http://dmm.biologists.org/content/7/12/1321ComorbiditiesIschemic postconditioningIschemic preconditioningRemote ischemic preconditioning |
| spellingShingle | Kieran McCafferty Suzanne Forbes Christoph Thiemermann Muhammad M. Yaqoob The challenge of translating ischemic conditioning from animal models to humans: the role of comorbidities Disease Models & Mechanisms Comorbidities Ischemic postconditioning Ischemic preconditioning Remote ischemic preconditioning |
| title | The challenge of translating ischemic conditioning from animal models to humans: the role of comorbidities |
| title_full | The challenge of translating ischemic conditioning from animal models to humans: the role of comorbidities |
| title_fullStr | The challenge of translating ischemic conditioning from animal models to humans: the role of comorbidities |
| title_full_unstemmed | The challenge of translating ischemic conditioning from animal models to humans: the role of comorbidities |
| title_short | The challenge of translating ischemic conditioning from animal models to humans: the role of comorbidities |
| title_sort | challenge of translating ischemic conditioning from animal models to humans the role of comorbidities |
| topic | Comorbidities Ischemic postconditioning Ischemic preconditioning Remote ischemic preconditioning |
| url | http://dmm.biologists.org/content/7/12/1321 |
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