The impact of ischemic intervals on neuromuscular recovery in a porcine (Sus scrofa) survival model of extremity vascular injury.
BACKGROUND
Despite advances in revascularization following extremity vascular injury, the relationship between time to restoration of flow and functional limb salvage is unknown. The objectives of this study are to describe a large animal survival model of hind limb ischemia/reperfusion and define neuromuscular recovery following increasing ischemic periods.


METHODS
Sus scrofa swine (N = 38; weight, 87 ± 6.2 kg) were randomized to iliac artery occlusion for 0 (Control), 1 (1HR), 3 (3HR), or 6 (6HR) hours, followed by vessel repair and 14 days of recovery. Additionally, one group underwent iliac artery division with no restoration of flow (Ligation), and one group underwent iliac artery exposure only without intervention (Sham). A composite physiologic measure of recovery (PMR) was generated to assess group differences over 14 days of survival. PMR included limb function (Tarlov score) and electrophysiologic measures (compound muscle action potential amplitude, sensory nerve action potential amplitude, and nerve conduction velocity). Using the PMR and extrapolating the point at which recovery following ligation crosses the slope connecting recovery after 3 and 6 hours of ischemia, an estimate of the ischemic threshold for the hind limb is made. These results were correlated with peroneus muscle and peroneal nerve histology.


RESULTS
Baseline physiologic characteristics were similar between groups. Neuromuscular recovery in groups with early restoration of flow (Control, 1HR, 3HR) was similar and nearly complete (92%, 98%, and 88%, respectively; P > .45). While recovery was diminished in both 6HR and Ligation, Ligation, rather than repair, exhibited greater recovery (68% vs 53%; P < .05). These relationships correlated with the pathologic grade of degeneration, necrosis, and fibrosis (P < .05). The PMR model predicts minimal and similar persistent loss of function in groups undergoing early surgical restoration of flow (Control 8%, 1HR 1%, 3HR 12%; P > .45). In contrast, the Ligation group exhibited the greatest degree of injury early in the reperfusion period, followed by more complete recovery and at a faster rate than 6HR. Extrapolating from the PMR the point at which Ligation (68% recovery) crosses the slope connecting 3 hours (84% recovery) and 6 hours (53% recovery) of ischemia estimates the ischemic threshold to be 4.7 hours. Restoration of flow at ischemic intervals exceeding this are associated with less physiologic recovery than ligation.


CONCLUSIONS
In this model, surgical and therapeutic adjuncts to restore extremity perfusion early (1-3 hours) after extremity vascular injury are most likely to provide outcomes benefit compared with delayed restoration of flow or ligation. Furthermore, the ischemic threshold of the extremity after which neuromuscular recovery is significantly diminished is less than 5 hours. Additional studies are necessary to determine the effect of other factors such as shock or therapeutic measures on this ischemic threshold.
San Antonio Military Medicine Center Consortium, Wilford Hall United States Air Force Medical Center, the 59th Clinical Research Squadron, and Genesis Concepts & Consultants (under USAF Contract No: FA7014-09-D-0008), Lackland Air Force Base, San Antonio, TX, USA.
Gabriel E
GE
Burkhardt
Shaun M
SM
Gifford
Brandon
B
Propper
Jerry R
JR
Spencer
Ken
K
Williams
Lyell
L
Jones
Nathan
N
Sumner
Jerry
J
Cowart
Todd E
TE
Rasmussen
D000200:Action Potentials; D000818:Animals; D006614:Hindlimb / Q000098:blood supply* / Q000294:innervation; D007083:Iliac Artery / Q000293:injuries* / Q000503:physiopathology / Q000601:surgery; D007511:Ischemia / Q000503:physiopathology*; D008026:Ligation; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000098:blood supply / Q000294:innervation; D009431:Neural Conduction; D010543:Peroneal Nerve / Q000503:physiopathology; D020127:Recovery of Function / Q000502:physiology; D015424:Reperfusion; D034421:Sus scrofa; D014855:Wallerian Degeneration