Ischemic Neuropathy Research Articles

An atypical case of acute ischaemic monomelic neuropathy post vascular access surgery in a patient with Type 1 diabetes mellitus

An atypical case of acute ischaemic monomelic neuropathy post vascular access surgery in a patient with Type 1 diabetes mellitus

Antiangiogenesis Mediates Cisplatin-Induced Peripheral Neuropathy

Toxic neuropathies induced by cisplatin and other chemotherapeutic agents are important clinical problems because of their high incidence, their lack of effective treatment, and the fact that neuropathy represents a dose-limiting factor for these therapies. The pathogenic basis for toxic neuropathies induced by chemotherapeutic agents has not been completely elucidated. We investigated the hypothesis that experimental toxic neuropathy results from an antiangiogenic effect of these drugs, resulting in destruction of the vasa nervorum, and accordingly that the neuropathy could be prevented or reversed by locally administered VEGF gene transfer without augmenting tumor growth. In an animal model of cisplatin-induced neuropathy, nerve blood flow was markedly attenuated, and there was a profound reduction in the number of vasa nervorum associated with marked endothelial cell apoptosis, resulting in a severe peripheral neuropathy with focal axonal degeneration characteristic of ischemic neuropathy. After intramuscular gene transfer of naked plasmid DNA encoding VEGF-1 in animals with an established neuropathy, vascularity and blood flow returned to levels similar to those of control rats, peripheral nerve function was restored, and histological nerve architecture was normalized. Gene therapy administered in parallel with cisplatin chemotherapy completely attenuated endothelial cell apoptosis and inhibited destruction of nerve vasculature, deterioration of nerve function, and axonal degeneration. In a rat tumor model, VEGF gene transfer administered locally did not alter tumor growth or vascularity. These findings implicate microvascular damage as the basis for toxic neuropathy induced by cisplatin and suggest that local angiogenic gene therapy may constitute a novel prevention or treatment for this disorder without augmenting tumor growth or vascularization.

Efficacy of levodopa and carbidopa on visual function in patients with non-arteritic anterior ischaemic optic neuropathy

The benefit of levodopa and carbidopa therapy in improving visual function in patients with non-arteritic anterior ischaemic neuropathy (NAION) was evaluated. Twenty-four subjects with NAION were randomly selected to receive either levodopa-carbidopa or a placebo. Visual functions of neither the study nor the placebo groups showed improvement. Side effects of levodopa such as dizziness, orthostatic hypotension, vomiting and cardiac arrhythmia were seen. Levodopa and carbidopa had no therapeutic effect on visual recovery in our patients with NAION.

Episodic third nerve palsy with cryptococcal meningitis

Azran et al. have postulated transient ischemic neuropathy associated with mycotic vasculitis as the mechanism for this rare presentation of episodic third nerve palsy. However, a closer examination of the photomicrograph shows scanty small capillaries with no evidence of vasculitis.1 What may be seen is a conglomerate of inflammatory cells …

Aortic occlusion causing ischemic neuropathy and paraparesis

Acute aortic occlusion can present with leg weakness.1 Occlusion of the aorta above the renal arteries could cause spinal cord ischemia by flow obstruction to the Adamkiewicz artery, whereas occlusion of the aorta below the renal arteries could cause ischemic neuropathy (by flow obstruction to the external iliac or femoral arteries). Paraparesis caused by ischemic neuropathy is uncommon. We present a case of ischemic neuropathy from aortic occlusion. A 64-year-old woman sought treatment for acute onset of severe bilateral gluteal, thigh, and lower leg pain and weakness of ankle dorsiflexion and plantar flexion. There was numbness in both feet, preservation of patellar and ankle reflexes, and absent Babinski sign. Medical history included coronary artery disease, atrial fibrillation, rheumatic heart disease, porcine mitral valve replacement, pacemaker placement, and right middle cerebral artery territory stroke with residual mild left-sided weakness. She had no history of peripheral neuropathy or diabetes mellitus. …

VEGF: once regarded as a specific angiogenic factor, now implicated in neuroprotection.

Both blood vessels and nerves are guided to their target. Vascular endothelial growth factor (VEGF)A is a key signal in the induction of vessel growth (a process termed angiogenesis). Though initial studies, now a decade ago, indicated that VEGF is an endothelial cell-specific factor, more recent findings revealed that VEGF also has direct effects on neural cells. Genetic studies showed that mice with reduced VEGF levels develop adult-onset motor neuron degeneration, reminiscent of the human neurodegenerative disorder amyotrophic lateral sclerosis (ALS). Additional genetic studies confirmed that VEGF is a modifier of motor neuron degeneration in humans and in SOD1(G93A) mice--a model of ALS. Reduced VEGF levels may promote motor neuron degeneration by limiting neural tissue perfusion and VEGF-dependent neuroprotection. VEGF also affects neuron death after acute spinal cord or cerebral ischemia, and has also been implicated in other neurological disorders such as diabetic and ischemic neuropathy, nerve regeneration, Parkinson's disease, Alzheimer's disease and multiple sclerosis. These findings have raised growing interest in assessing the therapeutic potential of VEGF for neurodegenerative disorders.

Complications des blépharoplasties

Blepharoplasty complications are infrequent, most often minor and transitory, rarely major and permanent with functional or esthetic consequences. Treatment is above all preventive: screening at risk patients with a history of ophthalmic problems, but also general illnesses that would contraindicate blepharoplasty. Patients must be informed of possible risks through informative booklets with the most important points underlined. Complications can be purely ophthalmological, the more serious sequelae being partial or complete visual loss due to ischemic optical neuropathy, with very poor prognosis, or more rarely compression of the ocular globe by intraorbital hemorrhage, which has a better prognosis provided the origins are quickly recognized and treated immediately. Other visual complications include oculomotor problems, keratoconjunctivitis sicca, epiphora, and chemosis of lymphatic origin. Eyelid complications are more frequent: ptosis on the upper eyelid or lagophthalmia caused by incorrect resection of the skin, scarring and eyelid fold anomalies. The most serious esthetic complication is the malposition of the lower eyelid, which can manifest as retraction, lagophthalmia, ectropion, deformation of the external canthus, or lower eyelid tissue relaxation. These malpositions are quite often minor, sometimes reversible, but at times major, with psychological, esthetic and functional consequences that are difficult for the patient. Other local complications also arise: enophthalmia with a sunken lid, as well as under- and overcorrection. General complications can include scarring related to pigmentation problems and residual hematomas, and exceptionally infections going as far as the orbital fat tissue. Finally, other complications are related to new laser surgical techniques that are responsible for ectropion of the lower eyelid and even burns or residual redness, or complications related to periocular injections of filling material. A comprehensive review of prevention, diagnosis, and management of complications after blepharoplasty is presented.

Permanent Neurologic Symptoms after Prolonged Epidural Analgesia

Although transient neurologic symptoms may occur after neuraxial anesthetics with lidocaine, permanent neurologic symptoms (PNS) are unusual after uncomplicated continuous epidural analgesia (CEA). This report demonstrates that PNS may follow CEA uncomplicated by paresthesias, dural puncture, spinal hemorrhage, or intravascular local anesthetic injection; and performed with bupivacaine alone administered at high dosages with vasoconstrictors over a prolonged time period. An obstetrical patient developed fixed left L5-S1 sensorimotor radiculopathy following L5-S1 level CEA with bupivacaine alone administered at high doses (270 mg) with a vasoconstrictor (epinephrine, 225 mg) over a prolonged time period (62 hours). CEA should be administered at higher lumbar levels for labor analgesia rather than at lumbosacral levels that may require higher volumes and concentrations of local anesthetics with greater potential for local anesthetic neurotoxicity. Local anesthetics with vasoconstrictors should only be used as sentinel markers of unrecognized intravascular entry, rather than as primary local anesthetics during CEA to avoid any potential for ischemic neuropathy.

This Issue of Acta

This Issue of Acta

Ischemic optic neuropathies.

To review recent clinical data on ischemic optic neuropathies, which are some of the most frequently encountered optic neuropathies. These disorders include nonarteritic anterior ischemic optic neuropathy, arteritic anterior ischemic optic neuropathy, and posterior ischemic optic neuropathy. Recent studies have facilitated our understanding of the natural history of visual loss, recovery, and recurrence in these disorders. Additionally, the value of various diagnostic techniques and treatment options, particularly for arteritic anterior ischemic neuropathy, has been clarified. Application of the studies described in this paper should allow the clinician to more accurately diagnose ischemic optic neuropathies and counsel the patient with regard to appropriate management, prognosis for visual recovery and future risk of recurrence.

Effect of hyperbaric oxygen therapy on nerve regeneration in early diabetes

Nerve regeneration in diabetes is essential for reversal of neuropathy as well as the recovery of nerves from injury due to acute nerve compression and entrapment. Endoneural hypoxia due to hyperglycemia-induced blood flow reductions is observed early in the course of diabetes, and the resultant ischemia plays a role in the diminished neural regeneration. Hyperbaric oxygen therapy is capable of producing tissue hyperoxia by raising oxygen tensions in ischemic tissues, and was shown to be beneficial in the reversal of experimental ischemic neuropathy. In this study, an experimental diabetes model was used to evaluate the functional and histomorphological effects of hyperbaric oxygen therapy on early diabetic nerve regeneration. Our results indicate that there is significant histomorphological impairment of nerve regeneration, even in very early stages of diabetes. However, no beneficial effects of hyperbaric oxygen therapy could be demonstrated at this stage.

Paracrine control of vascularization and neurogenesis by neurotrophins.

The neuronal system plays a fundamental role in the maturation of primitive embryonic vascular network by providing a paracrine template for blood vessel branching and arterial differentiation. Furthermore, postnatal vascular and neural regeneration cooperate in the healing of damaged tissue. Neurogenesis continues in adulthood although confined to specific brain regions. Following ischaemic insult, neural staminal cells contribute towards the healing process through the stimulation of neurogenesis and vasculogenesis. Evidence indicates that nerves and blood vessels exert a reciprocal control of their own growth by paracrine mechanisms. For instance, guidance factors, including vascular endothelial growth factor A (VEGF-A) and semaphorins, which share the ability of binding neuropilin receptors, play a pivotal role in the tridimensional growth pattern of arterial vessels and nerves. Animal models and clinical studies have demonstrated a role of VEGF-A in the pathogenesis of ischaemic and diabetic neuropathies. Further, supplementation with VEGF-A ameliorates neuronal recovery by exerting protective effects on nerves and stimulating reparative neovascularization. Human tissue kallikrein, a recently discovered angiogenic and arteriogenic factor, accelerates neuronal recovery by stimulating the growth of vasa nervorum. Conversely, the neurotrophin nerve growth factor, known to regulate neuronal survival and differentiation, is now regarded as a stimulator of angiogenesis and arteriogenesis. These results indicate that angiogenesis and neurogenesis are paracrinally regulated by growth factors released by endothelial cells and neurons. Supplementation of these growth factors, alone or in combination, could benefit the treatment of ischaemic diseases and neuropathies.

Aortic dissection: new frontiers in diagnosis and management: Part I: from etiology to diagnostic strategies.

Cardiovascular disease is the leading cause of death in most Western societies and is increasing steadily in many developing countries. Aortic diseases constitute an emerging share of the burden. New diagnostic imaging modalities, longer life expectancy in general, longer exposure to elevated blood pressure, and the proliferation of modern noninvasive imaging modalities have all contributed to the growing awareness of acute and chronic aortic syndromes. Despite recent progress in recognition of both the epidemiological problem and diagnostic and therapeutic advances, the cardiology community and the medical community in general are far from comfortable in understanding the spectrum of aortic syndromes and defining an optimal pathway to manage aortic diseases.1–13 This comprehensive review is organized in two parts, with a focus on the etiology, natural history, and classification (with vascular staging) of aortic wall disease in Part I and emphasis on therapeutic management and follow-up in Part II. Both parts may help to better integrate the complexities of acute aortic syndromes.

Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 39

A 40‐year‐old smoker complained of pain, deep and burning in character, constant, and persistent, associated with paresthesias in his feet for a period of two years. Furthermore, he developed aching non‐traumatic foot ulcers. There was no history of diabetes and systemic illness. Neurological examination revealed loss of all modalities of sensation and hyperhidrosis in the limbs with a prominent distal‐to‐proximal gradient. The following laboratory tests were normal: blood count; test for liver, kidney, and thyroid function; cryoglobulins; anti‐HCV antibodies and HIV. Neurophysiological investigation revealed an axonal neuropathy with a distal‐to‐proximal distribution in the limbs. Sural nerve biopsy showed a severe chronic axonal neuropathy. Prominent thickening of endoneurial microvessel endothelial cells was present with narrowing of lumen. Congo Red staining was negative. He initiated treatment with alprostadil alfa‐ciclodestrina and stopped smoking. The patient reported prompt improvement of neurologic symptoms as well as skin abnormalities few months after the begin of therapy. Ischemic neuropathy in which nerve damage occurs in the more distal portion of the limbs has been reported. In our patient, clinical presentation, neurophysiological and neuropathological findings suggest the diagnosis of a Lower Extremity Ischemic Neuropathy probably triggered by smoke.

Maintenance oral pantoprazole therapy is effective for patients with Zollinger-Ellison syndrome and idiopathic hypersecretion

Objective Maintenance proton pump inhibitor (PPI) therapy is effective for gastric acid hypersecretory states, although data with pantoprazole are limited. The aim of this study was to evaluate the safety and efficacy of long term p.o. pantoprazole in individuals with hypersecretion. Methods All subjects had Zollinger-Ellison syndrome or idiopathic hypersecretion. Baseline acid output was measured in the presence of prior maintenance antisecretory therapy before pantoprazole exposure. The starting dose was 40 mg b.i.d. in most cases, and the dose was adjusted to document control within the first 2 wk of therapy. The maximal allowable dose was 240 mg daily. Acid output was measured on day 28 and then quarterly from month 3. The primary efficacy endpoint was documented control of acid secretion at 6 months, i.e., acid output in the last 1 h before the next dose of therapy of <10 mEq/h (<5 mEq/h in subjects with prior acid-reducing surgery). Results A total of 26 subjects had Zollinger-Ellison syndrome (six with multiple endocrine neoplasia syndrome type 1) and nine had idiopathic hypersecretion. Pre-enrollment therapy included omeprazole in 27 subjects and lansoprazole in eight, and 82.4% of subjects were controlled on their prior regimens. With upward dose titration, acid output was controlled in all subjects by day 10 and in all but two (6%) at the 6-month time point. Median acid secretion on therapy at 6 months was <2 mEq/h (mean 2.2 mEq/h; range 0–10.5 mEq/h) at a dose of 40 mg b.i.d. for 24 subjects, 80 mg b.i.d. for seven subjects, and 120 mg b.i.d. for two subjects. During the course of the study, five subjects required doses of 240 mg daily. Pantoprazole was generally well tolerated. No cases of anterior optic ischemic neuropathy occurred. Five subjects died during follow-up, all because of events unrelated to the study drug. Conclusions Maintenance p.o. pantoprazole therapy at a dose of 80–240 mg/day in divided doses was both effective and generally well tolerated for patients with Zollinger-Ellison syndrome and idiopathic hypersecretion.

Maintenance oral pantoprazole therapy is effective for patients with Zollinger-Ellison syndrome and idiopathic hypersecretion

Maintenance proton pump inhibitor (PPI) therapy is effective for gastric acid hypersecretory states, although data with pantoprazole are limited. The aim of this study was to evaluate the safety and efficacy of long term p.o. pantoprazole in individuals with hypersecretion. All subjects had Zollinger-Ellison syndrome or idiopathic hypersecretion. Baseline acid output was measured in the presence of prior maintenance antisecretory therapy before pantoprazole exposure. The starting dose was 40 mg b.i.d. in most cases, and the dose was adjusted to document control within the first 2 wk of therapy. The maximal allowable dose was 240 mg daily. Acid output was measured on day 28 and then quarterly from month 3. The primary efficacy endpoint was documented control of acid secretion at 6 months, i.e., acid output in the last 1 h before the next dose of therapy of <10 mEq/h (<5 mEq/h in subjects with prior acid-reducing surgery). A total of 26 subjects had Zollinger-Ellison syndrome (six with multiple endocrine neoplasia syndrome type 1) and nine had idiopathic hypersecretion. Pre-enrollment therapy included omeprazole in 27 subjects and lansoprazole in eight, and 82.4% of subjects were controlled on their prior regimens. With upward dose titration, acid output was controlled in all subjects by day 10 and in all but two (6%) at the 6-month time point. Median acid secretion on therapy at 6 months was <2 mEq/h (mean 2.2 mEq/h; range 0-10.5 mEq/h) at a dose of 40 mg b.i.d. for 24 subjects, 80 mg b.i.d. for seven subjects, and 120 mg b.i.d. for two subjects. During the course of the study, five subjects required doses of 240 mg daily. Pantoprazole was generally well tolerated. No cases of anterior optic ischemic neuropathy occurred. Five subjects died during follow-up, all because of events unrelated to the study drug. Maintenance p.o. pantoprazole therapy at a dose of 80-240 mg/day in divided doses was both effective and generally well tolerated for patients with Zollinger-Ellison syndrome and idiopathic hypersecretion.

Internal iliac occlusion without coil embolization during endovascular abdominal aortic aneurysm repair.

When abdominal aortic aneurysms and common iliac artery (CIA) aneurysms undergo concomitant endovascular repair, endograft limb extension into the external iliac artery is often necessary. Usually, the internal iliac artery (IIA) is coil embolized in such a case to prevent endoleak. It has been our practice to coil embolize the IIA only in cases where there is not adequate stent graft seal in the CIA immediately proximal to the IIA origin (effectively sealing the entire IIA origin). In this study, we evaluated the outcomes of this approach. We retrospectively reviewed 204 consecutive endovascular abdominal aortic aneurysm repairs at Dartmouth-Hitchcock Medical Center from 1996 to 2001. Computed tomographic angiography with three-dimensional reconstruction was the primary preoperative imaging modality, and the decision to cover the IIA without concomitant coil embolization was based before surgery on the presence of adequate graft oversizing (> or =10% to 15%) in the most distal 5 mm of CIA and 15 mm of proximal external iliac artery, respectively. The IIA was occluded 33 times in 31 patients. In 22 cases (67%), the IIA was covered without coil embolization (COVER group). The remaining 11 patients (33%) with inadequate graft oversizing in the CIA underwent IIA coil embolization (COIL group). The follow-up periods for the COVER and COIL groups were 19 +/- 2 months and 10 +/- 3 months, respectively. All operations in both groups were technically successful without evidence of endoleak at completion angiography. No endoleaks, graft migrations, or aneurysm enlargements were associated with the covered or coiled IIAs during the follow-up period. No clinical sequelae were seen in the COVER group, with the exception of buttock claudication in six patients (27%) that resolved completely in five patients. In the COIL group, five patients (45%) had buttock claudication. In addition, one case of buttock necrosis and one case of ischemic neuropathy occurred in the COIL group. Covering the IIA without coiling effectively excluded the CIA aneurysm in every case and was associated with a low incidence rate of complications compared with coil embolization. With detailed preoperative imaging and patient selection, IIA coil embolization may not be necessary in as many as two thirds of patients who need IIA occlusion.

The initial management of scapulothoracic dissociation: A challenging task for the vascular surgeon

The medical records of nine patients who had sustained a STD secondary to a blunt trauma during the last decade (1990±2000) were reviewed in the University of Crete Vascular Surgery Unit. Patients with penetrating or open trauma, and those with musculoskeletal or vascular or neurologic injury alone, were excluded from the study. The diagnosis of STD was made initially from the patients' history and the clinical presentation. All patients ± males with a median age of 30 years (range from 21 to 54 years) ± were victims of decelerating, high speed motorcycle or automobile accidents (Table 1) and presented with a pulseless and severely ischaemic upper limb, absence of motor and sensory function below the shoulder or arm, and a shoulder girdle or chest wall swelling or haematoma and ecchymoses with intact skin. On subsequent plain X-rays or CTs all patients were found to have disruption of the acromioclavicular or sternoclavicular joints and/or clavicular fracture (Table 1). Surgical exploration in three patients and an urgent arteriogram or CT scan in the remaining patients demonstrated the vascular injury in the thoracic outlet region. Innominate artery or aorta rupture was not found in our patient population. Active bleeding from the damaged subclavian arteries was recognised in five patients and from several perforator arteries and veins of the chest wall in all patients. Concomitant injuries of the trunks of the brachial plexus were identified in all patients. In all patients, head injury, hypovolaemic shock and upper extremity fractures or ischaemic neuropathy made detailed preoparative assessment of the neurological status of the upper extremity ipsilaterally to the injured shoulder girdle unreliable, if not impossible. The specific injuries of neurovascular structures identified during the operative intervention are outlined in Table 1. Additionally, all patients experienced multiple other moderate or severe local and remote injuries. After initial stabilisation of the patients' vital signs and general condition all patients were operated upon urgently. The surgical exploration was performed via a supraclavicular incision in five patients, a combined supraclavicular incision and sternotomy in three patients (Table 1: cases 1, 4 and 8), and a combined supraclavicular incision and left thoracotomy in one patient (Table 1: case 5). After controlling the actively bleeding sites and detailed investigation and identification of the injured trunks of the brachial plexus and other structures, our effort was directed to reestablishing arterial flow to the ischaemic arm. Arterial reconstruction was performed in eight patients, using the autologous great saphenous vein as an interposition arterial graft connecting the proximal Please address all correspondence to: N. Katsamouris, Vascular Surgical Unit, University of Crete Medical School, University Hospital of Heraklion, Crete, Greece. Tel.: ‡30 81 392 379 or ‡30 932 277 357; Fax: ‡30 81 542 063; E-mail: asterios@med.uoc.gr Eur J Vasc Endovasc Surg 24, 547±549 (2002) doi:doi:10.1053/ejvs.2002.1722, available online at http://www.idealibrary.com on

Ischemic neurophysiological changes of rat sciatic nerve in vitro

Purpose: Patients with ischemic neuropathy always have a progressive reduction in nerve conduction resulting in a transient increase in sensation, such as pain or hyperesthesia. We examined the effect of acute complete ischemia on neurophysiological functions in rat and related electrophysiological changes in ischemic nerve with adenosine 5′-triphosphate (ATP) administration. Methods: The sciatic nerve of rat was placed directly on 16 parallel 0.5 mm diameter platinum electrodes (5 mm interelectrode distance) in a Perspex chamber bathed in Ringer's solution. The stimulus was applied through the electrode at the rostral end of the nerve, and the action potential recorded along different recording electrodes towards the caudal end of the nerve. Measurements were recorded immediately upon initial nerve placing and then 5, 10, 15, 30, 60, 90 and 120 min after nerve placing. Results: We observed two major components in the monophasic compound action potential of the sciatic nerve of rats (A and B waves). Nerve conduction and amplitude of A and B waves underwent an initial increase followed by a reduction and after ATP administration, the transient augmentation of conduction velocity and amplitude in A and B waves disappeared. The median survival time of peripheral nerve was 60 min. Conclusion: At the onset of ischemia, the membrane Na–K pump does not work resulting in an increase of threshold potential in nerve membrane. When ATP levels further decrease, nerve function progressively fails.

Morphological, histochemical, and interstitial pressure changes in the tibialis anterior muscle before and after aortofemoral bypass in patients with peripheral arterial occlusive disease.

BackgroundMorphological and electrophysiological studies of ischemic muscles in peripheral arterial disease disclosed evidence of denervation and fibre atrophy. The purpose of the present study is to describe morphological changes in ischemic muscles before and after reperfusion surgery in patients with peripheral occlusive arterial disease, and to provide an insight into the effect of reperfusion on the histochemistry of the reperfused muscle.MethodsMuscle biopsies were obtained from the tibialis anterior of 9 patients with chronic peripheral arterial occlusive disease of the lower extremities, before and after aortofemoral bypass, in order to evaluate the extent and type of muscle fibre changes during ischemia and after revascularization. Fibre type content and muscle fibre areas were quantified using standard histological and histochemical methods and morphometric analysis. Each patient underwent concentric needle electromyography, nerve conduction velocity studies, and interstitial pressure measurements.ResultsPreoperatively all patients showed muscle fibre atrophy of both types, type II fibre area being more affected. The mean fibre cross sectional area of type I was 3,745 μm2 and of type II 4,654 μm2 . Fibre-type grouping, great variation in fibre size and angular fibres were indicative of chronic dennervation-reinnervation, in the absence of any clinical evidence of a neuropathic process. Seven days after the reperfusion the areas of both fibre types were even more reduced, being 3,086 μm2 for type I and 4,009 μm2 for type II, the proportion of type I fibres, and the interstitial pressure of tibialis anterior were increased.ConclusionsThe findings suggest that chronic ischemia of the leg muscles causes compensatory histochemical changes in muscle fibres resulting from muscle hypoxia, and chronic dennervation-reinnervation changes, resulting possibly from ischemic neuropathy. Reperfusion seems to bring the oxidative capacity of the previously ischemic muscle closer to normal.