A large animal survival model (Sus scrofa) of extremity ischemia/reperfusion and neuromuscular outcomes assessment: A pilot study

Gabriel E. Burkhardt, Jerry R. Spencer, Shaun M. Gifford, Brandon Propper, Lyell Jones, Nathan Sumner, Jerry Cowart, Todd E. Rasmussen

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background: Extremity ischemia/reperfusion has been studied mostly in small-animal models with limited characterization of neuromuscular or functional outcome. The objective of this experiment was to report a large-animal survival model of extremity ischemia/reperfusion using circulating, electromyographic (EMG), gate, and histologic measures of injury and limb recovery. Methods: Sus scrofa swine (n = 6; mean, 83 kg) were randomized to iliac artery occlusion for 0 (control), 1 (1 HR), 3 (3 HR), or 6 (6 HR) hours. Restoration of flow after a standard large-vessel reconstructive technique (thrombectomy, heparin irrigation, and patch angioplasty) was performed in each of the control, 1HR, 3HR, and 6HR animals, whereas one animal had iliac artery segment excision with no restoration (NR) of axial flow. One animal had operative exposure but no intervention on the iliac artery (sham). Animals were recovered and closely monitored for 2 weeks. Indicators of ischemia/reperfusion and functional recovery, including circulating markers, EMG measures (complex motor action potential), and Tarlov gate scoring (0-4; 0, insensate/paralyzed to 4, normal posture and no gait abnormality) were measured at 24 hours and 72 hours and 7 days and 14 days. Muscle (peroneus) and nerve (peroneal) were collected during necropsy at 14 days to assess gross and histologic changes. Duplex ultrasound was performed serially during the recovery period to confirm patency of vascular reconstruction. Results: There were no deaths or failures of vascular reconstruction. Control had a Tarlov score of 4 and normal EMG measures at each point during recovery (same as sham). Tarlov scores at 1, 3, and 14 days recovery in each of the animals were as follows: 1HR: 3, 3, and 4; 3HR: 1, 2, and 4; 6HR: 1, 2, and 3; and NR: 1, 2, and 4. Complex motor action potential as a percentage of baseline at 1, 2, and 14 days recovery was as follows: 1HR: 56%, 55%, and 84%; 3HR: 9%, 8%, and 57%; 6HR: 5%, 5%, and 16%; and NR: 22%, 28%, and 33%. Muscle and nerve histology was the same in sham, control, and 1HR animals. Moderate degeneration and necrosis was observed in peroneus muscle of the 3HR animals. The peroneal nerve in 3HR demonstrated minimal Wallerian degeneration. Severe necrosis was present, as was minimal regeneration, and peroneal nerve demonstrated moderate Wallerian degeneration in 6HR. Conclusions: This study reports a new large-animal survival model of extremity ischemia/reperfusion using circulating, functional, and histologic markers of neuromuscular recovery. Findings provide insight into an extremity ischemic threshold after which functional neuromuscular recovery is lost. Additional study is necessary to define this threshold and factors that may move it to a more or less favorable position in the setting of extremity injury.

Original languageEnglish (US)
JournalJournal of Trauma - Injury, Infection and Critical Care
Volume69
Issue numberSUPPL. 1
DOIs
StatePublished - Jul 1 2010
Externally publishedYes

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Sus scrofa
Reperfusion
Ischemia
Extremities
Animal Models
Outcome Assessment (Health Care)
Peroneal Nerve
Iliac Artery
Wallerian Degeneration
Muscles
Action Potentials
Necrosis
Vascular Patency
Thrombectomy
Wounds and Injuries
Posture
Gait
Angioplasty
Blood Vessels
Heparin

Keywords

  • Extremity
  • Ischemia
  • Large-animal model
  • Neuromuscular recovery
  • Reperfusion

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine

Cite this

A large animal survival model (Sus scrofa) of extremity ischemia/reperfusion and neuromuscular outcomes assessment : A pilot study. / Burkhardt, Gabriel E.; Spencer, Jerry R.; Gifford, Shaun M.; Propper, Brandon; Jones, Lyell; Sumner, Nathan; Cowart, Jerry; Rasmussen, Todd E.

In: Journal of Trauma - Injury, Infection and Critical Care, Vol. 69, No. SUPPL. 1, 01.07.2010.

Research output: Contribution to journalArticle

Burkhardt, Gabriel E. ; Spencer, Jerry R. ; Gifford, Shaun M. ; Propper, Brandon ; Jones, Lyell ; Sumner, Nathan ; Cowart, Jerry ; Rasmussen, Todd E. / A large animal survival model (Sus scrofa) of extremity ischemia/reperfusion and neuromuscular outcomes assessment : A pilot study. In: Journal of Trauma - Injury, Infection and Critical Care. 2010 ; Vol. 69, No. SUPPL. 1.
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keywords = "Extremity, Ischemia, Large-animal model, Neuromuscular recovery, Reperfusion",
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TY - JOUR

T1 - A large animal survival model (Sus scrofa) of extremity ischemia/reperfusion and neuromuscular outcomes assessment

T2 - A pilot study

AU - Burkhardt, Gabriel E.

AU - Spencer, Jerry R.

AU - Gifford, Shaun M.

AU - Propper, Brandon

AU - Jones, Lyell

AU - Sumner, Nathan

AU - Cowart, Jerry

AU - Rasmussen, Todd E.

PY - 2010/7/1

Y1 - 2010/7/1

N2 - Background: Extremity ischemia/reperfusion has been studied mostly in small-animal models with limited characterization of neuromuscular or functional outcome. The objective of this experiment was to report a large-animal survival model of extremity ischemia/reperfusion using circulating, electromyographic (EMG), gate, and histologic measures of injury and limb recovery. Methods: Sus scrofa swine (n = 6; mean, 83 kg) were randomized to iliac artery occlusion for 0 (control), 1 (1 HR), 3 (3 HR), or 6 (6 HR) hours. Restoration of flow after a standard large-vessel reconstructive technique (thrombectomy, heparin irrigation, and patch angioplasty) was performed in each of the control, 1HR, 3HR, and 6HR animals, whereas one animal had iliac artery segment excision with no restoration (NR) of axial flow. One animal had operative exposure but no intervention on the iliac artery (sham). Animals were recovered and closely monitored for 2 weeks. Indicators of ischemia/reperfusion and functional recovery, including circulating markers, EMG measures (complex motor action potential), and Tarlov gate scoring (0-4; 0, insensate/paralyzed to 4, normal posture and no gait abnormality) were measured at 24 hours and 72 hours and 7 days and 14 days. Muscle (peroneus) and nerve (peroneal) were collected during necropsy at 14 days to assess gross and histologic changes. Duplex ultrasound was performed serially during the recovery period to confirm patency of vascular reconstruction. Results: There were no deaths or failures of vascular reconstruction. Control had a Tarlov score of 4 and normal EMG measures at each point during recovery (same as sham). Tarlov scores at 1, 3, and 14 days recovery in each of the animals were as follows: 1HR: 3, 3, and 4; 3HR: 1, 2, and 4; 6HR: 1, 2, and 3; and NR: 1, 2, and 4. Complex motor action potential as a percentage of baseline at 1, 2, and 14 days recovery was as follows: 1HR: 56%, 55%, and 84%; 3HR: 9%, 8%, and 57%; 6HR: 5%, 5%, and 16%; and NR: 22%, 28%, and 33%. Muscle and nerve histology was the same in sham, control, and 1HR animals. Moderate degeneration and necrosis was observed in peroneus muscle of the 3HR animals. The peroneal nerve in 3HR demonstrated minimal Wallerian degeneration. Severe necrosis was present, as was minimal regeneration, and peroneal nerve demonstrated moderate Wallerian degeneration in 6HR. Conclusions: This study reports a new large-animal survival model of extremity ischemia/reperfusion using circulating, functional, and histologic markers of neuromuscular recovery. Findings provide insight into an extremity ischemic threshold after which functional neuromuscular recovery is lost. Additional study is necessary to define this threshold and factors that may move it to a more or less favorable position in the setting of extremity injury.

AB - Background: Extremity ischemia/reperfusion has been studied mostly in small-animal models with limited characterization of neuromuscular or functional outcome. The objective of this experiment was to report a large-animal survival model of extremity ischemia/reperfusion using circulating, electromyographic (EMG), gate, and histologic measures of injury and limb recovery. Methods: Sus scrofa swine (n = 6; mean, 83 kg) were randomized to iliac artery occlusion for 0 (control), 1 (1 HR), 3 (3 HR), or 6 (6 HR) hours. Restoration of flow after a standard large-vessel reconstructive technique (thrombectomy, heparin irrigation, and patch angioplasty) was performed in each of the control, 1HR, 3HR, and 6HR animals, whereas one animal had iliac artery segment excision with no restoration (NR) of axial flow. One animal had operative exposure but no intervention on the iliac artery (sham). Animals were recovered and closely monitored for 2 weeks. Indicators of ischemia/reperfusion and functional recovery, including circulating markers, EMG measures (complex motor action potential), and Tarlov gate scoring (0-4; 0, insensate/paralyzed to 4, normal posture and no gait abnormality) were measured at 24 hours and 72 hours and 7 days and 14 days. Muscle (peroneus) and nerve (peroneal) were collected during necropsy at 14 days to assess gross and histologic changes. Duplex ultrasound was performed serially during the recovery period to confirm patency of vascular reconstruction. Results: There were no deaths or failures of vascular reconstruction. Control had a Tarlov score of 4 and normal EMG measures at each point during recovery (same as sham). Tarlov scores at 1, 3, and 14 days recovery in each of the animals were as follows: 1HR: 3, 3, and 4; 3HR: 1, 2, and 4; 6HR: 1, 2, and 3; and NR: 1, 2, and 4. Complex motor action potential as a percentage of baseline at 1, 2, and 14 days recovery was as follows: 1HR: 56%, 55%, and 84%; 3HR: 9%, 8%, and 57%; 6HR: 5%, 5%, and 16%; and NR: 22%, 28%, and 33%. Muscle and nerve histology was the same in sham, control, and 1HR animals. Moderate degeneration and necrosis was observed in peroneus muscle of the 3HR animals. The peroneal nerve in 3HR demonstrated minimal Wallerian degeneration. Severe necrosis was present, as was minimal regeneration, and peroneal nerve demonstrated moderate Wallerian degeneration in 6HR. Conclusions: This study reports a new large-animal survival model of extremity ischemia/reperfusion using circulating, functional, and histologic markers of neuromuscular recovery. Findings provide insight into an extremity ischemic threshold after which functional neuromuscular recovery is lost. Additional study is necessary to define this threshold and factors that may move it to a more or less favorable position in the setting of extremity injury.

KW - Extremity

KW - Ischemia

KW - Large-animal model

KW - Neuromuscular recovery

KW - Reperfusion

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