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Rhabdomyolysis and Myoglobinuric Nephrosis (CaptureMyopathy) in a Striped Dolphin

Authors: Herráez, P., Sierra, E., Arbelo, M., Jaber, J. R., de losMonteros, A. Espinosa, et al.

Source: Journal of Wildlife Diseases, 43(4) : 770-774

Published By: Wildlife Disease Association

URL: https://doi.org/10.7589/0090-3558-43.4.770

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Journal of Wildlife Diseases, 43(4), 2007, pp. 770–774# Wildlife Disease Association 2007

Rhabdomyolysis and Myoglobinuric Nephrosis (Capture Myopathy) in

a Striped Dolphin

P. Herraez,1,2 E. Sierra,1 M. Arbelo,1 J. R. Jaber,1 A. Espinosa de los Monteros,1 and A. Fernandez1

1Department of Comparative Pathology, Institute of Animal Health, Veterinary College, University of Las Palmasde Gran Canaria, Trasmontana s/n 35413, Arucas Las Palmas, Spain; 2Corresponding author (email: [email protected])

ABSTRACT: This report describes delayed myo-globinuric capture myopathy in a striped dol-phin (Stenella coeruleoalba) found strandedalive on the coast of Fuerteventura (CanaryIslands, Spain). The animal was transported toGran Canaria where it died 48 hr after strand-ing. The main lesions consisted of acuterhabdomyolysis affecting both cardiac andskeletal muscles, and myoglobinuric nephrosis.Using immunohistochemistry, degenerate myo-fibers with depletion of myoglobin, and anintracytoplasmatic immunoreaction for fibrino-gen were observed. Orange-red pigmentedcasts in renal tubular lumens were stronglyimmunolabeled for myoglobin. To our knowl-edge, this is the first pathologic description ofcapture myopathy with myoglobinuric nephro-sis in stranded cetaceans. Stress, exertion,trauma, and crush injury caused during thestranding, restraint, and transportation werethe main causes of rhabdomyolysis in this case.

Key words: Capture myopathy, cetaceans,dolphin, fibrinogen, myoglobin, myoglobinuricnephrosis, rhabdomyolysis, Stenella coeru-leoalba.

Capture myopathy (CM) is a metabolicmuscle disease described in wild mammalsassociated with stress of capture, restraint,and transportation. Four clinical syn-dromes are associated with CM: captureshock, ruptured muscle, ataxic myoglobi-nuric, and delayed peracute (Spraker,1993). Ataxic myoglobinuric and delayedperacute syndromes occur most common-ly, and pathologic findings include mild tomoderate rhabdomyolysis affecting thecardiac and skeletal muscle. Moreover, inataxic myoglobinuric syndrome, renal le-sions have been described consisting ofmoderate to severe tubular necrosis withintratubular protein casts; the urinarybladder usually contains a small amountof brownish urine (Spraker, 1993).

Stress, exertion, and crush injury arewell-documented causes of rhabdomyoly-

sis, but other causes, such as proceduresthat involve long periods of restraint,struggling from unnatural positioning, orlengthy pursuit during capture, are alsomajor factors in the development of CM inwildlife (Williams and Thorne, 1996).

Capture myopathy has been documen-ted in ungulates, carnivores, rodents,primates, marsupials, pinnipeds, andbirds. Previous studies in cetaceans havedemonstrated hematologic changes indic-ative of activation of the hypothalamic-pituitary-adrenal axis and muscle damagein response to capture stress (St. Aubinand Geraci, 1989). In 1978, Colgrove(1978) reported a suspected transporta-tion-associated myopathy in a bottle-noseddolphin based on increased serum enzymeactivities. However, descriptions of thepathologic features of myoglobinuric CMin stranded dolphins appear to be lacking.

We describe the gross and histopatho-logic features of CM in an active strandedstriped dolphin (Stenella coeruleoalba).Acute rhabdomyolysis affecting both car-diac and skeletal muscles and myoglobi-nuric nephrosis were the distinctive le-sions. Stress, trauma, and excessive activityas well as prolonged muscle compressionduring the stranding, restraint, and trans-portation are considered to be the mostprobable causes of muscular damage.

On 20 November 2004, a live adult malestriped dolphin was found stranded on thecoast of Fuerteventura (Canary Islands,Spain, 28u449N, 13u529W). The animalwas in good body condition and kept ina private swimming pool until transportedby car and helicopter to the WildlifeRescue Center facilities in Gran Canaria.The animal died 48 hr later, without

770


specific clinical signs; a complete necropsywas done within 2 hr of death at theVeterinary College in Gran Canaria.

At necropsy, the heart had multiple,locally extensive, pale, whitish subendo-cardial areas in the ventricular myocardi-um. Kidneys were deeply dark, whereasthe urinary bladder was empty. No grosslesions were detected in skeletal muscles.Other gross lesions included a rostralmandibular fracture with loss of soft tissuefrom the nose caused during the strand-ing, mild multifocal granulomatous ver-minous pneumonia, moderate peritonealparasitism (Monorigma grimaldi), smallintestine catharral enteritis, and multifocalparasitic cholangitis (Campula sp).

Selected tissue samples were collected,fixed in 10% neutral buffered formalin,and embedded in paraffin wax, andsections (4 mm) were stained with hema-toxylin and eosin, PTAH, and Masson’strichrome techniques. In addition, immu-nohistochemical examination was per-formed on cardiac, skeletal muscle, andrenal tissue sections using the avidin-biotin-peroxidase method (Vector Labora-tories, Burlingame, California, USA). Pri-mary antibodies consisted of rabbit anti-human myoglobin diluted to 1:2,000,rabbit antihuman fibrinogen diluted to1:200, and rabbit antihuman Heat ShockProtein 70 (HSP70) diluted to 1:100(Dako, Glostrup, Denmark). Tissue sec-tions in which the primary antibodies werereplaced by phosphate-buffered saline ornonimmune serum (rabbit or mouse) wereused as negative controls. Kidney andskeletal and cardiac muscle tissue sectionsfrom horses with exertional rhabdomyoly-sis were used as positive controls.

Histopathologic examination of themyocardium revealed multiple, locallyextensive areas of acute myocyte degener-ation. Myocyte changes consisted of cyto-plasmic eosinophilia, loss of cross striations,cytoplasmic fragmentation, myocytolysis,and nuclear condensation (Fig. 1). Limitedto the immediate subendocardial regions,scattered myocytes had dense, hypereosi-

nophilic bands running transversely acrossthe cytoplasm (Fig. 1, inset), which wereindicative of contraction band necrosis.Immunohistochemically, degenerate myo-cytes had depletion of myoglobin (Fig. 2a)and an intense cytoplasmic immunoreac-tion with antifibrinogen antibody (Fig. 2b).A strong, homogeneous immunoreactionwith antimyoglobin antibody was detectedin the intravascular plasma of medium- tosmall-size vessels in the affected areas.Similar degenerative changes were de-

FIGURE 1. Heart: Myocytes have acute degener-ative changes characterized by cytoplasmic fragmen-tation and myocytolysis (hematoxylin and eosinmethod). Inset: Subendocardial myocytes with con-traction band necrosis (Masson’s trichrome method).

FIGURE 2. Heart: (a) Depletion of myoglobin indegenerate myocytes is demonstrated by decreasedimmunoreaction for myoglobin. (b) Strong intracy-toplasmatic immunoreaction for fibrinogen in affect-ed myocytes (avidin-biotin-peroxidase complexmethod with 3-amino-9 ethylcabazole as chromagen).

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tected in skeletal muscles including de-pletion of myoglobin and a cytoplasmicimmunoreaction for fibrinogen. Renal le-sions consisted of extensive swelling ofrenal tubular cells and pigmented orange-red, homogeneous intratubular casts(Fig. 3). Granules, droplets, and casts inBowman’s space, tubular lumens, andcytoplasm of degenerate tubular cells werestrongly labeled by the antimyoglobinantibody (Fig. 4a). In addition, some ofthese degenerate cells had a granularcytoplasmic immunoreaction for HSP70(Fig. 4b). No other lesions were observed.

Capture myopathy is an acute diseasecharacterized by rhabdomyolysis and renaltubular necrosis that occurs in wildanimals hours or days following a chase,a struggle, or transport. No specificclinical signs indicative of rhabdomyolysiswere detected in this case, and the animaldied 48 hr after the stranding. AlthoughCM can cause depression, hyperthermia,ataxia, torticollis, and myoglobinuria, inmany cases, the disease is asymptomaticand only laboratory abnormalities aredetected (Spraker, 1993). Myoglobinuriais the central element in the developmentof rhabdomyolysis-induced acute renalfailure, and it is frequently considered tobe the first clinical sign indicator ofmyoglobinuric nephrosis. However, thegross diagnosis of CM in cetaceans can

be complicated because the urinary blad-der of cetaceans usually is devoid of urineat necropsy, they urinate in the aquaticenvironment, making visualization of theurine difficult, and the kidneys usually aredeeply dark secondary to vascular com-promise.

Myocardial lesions consisted of multifo-cal degenerative changes and subendocar-dial areas of contraction band necrosis.Contraction band necrosis develops aftertransient ischemia and reperfusion, and itis the characteristic myocardial lesionassociated with elevated concentrationsof endogenous catecholamines (Jiang andDowning, 1990). This lesion is recognizedin wide clinical circumstances, includingstress and trauma, and it has beenimplicated as a mechanism of suddendeath in these situations. Similar cardiaclesions described in stranded cetaceanshave been attributed to physiologic orpsychologic stress related to stranding,injury, or disease (Turnbull and Cowan,1998). In addition, the immunohistochem-ical study revealed depletion of myoglobinand cytoplasmic immunoreaction for fi-brinogen, which could indicate hypoxiccellular injury. Fibrinogen and myoglobin

FIGURE 3. Kidney: Intratubular pigmented castsassociated with tubular epithelial cells swelling(hematoxylin and eosin method).

FIGURE 4. Kidney: (a) Immunoreaction for myo-globin in the granules and casts in the Bowman spaceand tubular lumen. The apical cytoplasm of de-generate tubular cells shows immunoreaction formyoglobin. (b) Some of damaged tubular cells showimmunoreaction for anti-HSP70 antibody (avidin-biotin-peroxidase complex method with XXXas chromagen).

772 JOURNAL OF WILDLIFE DISEASES, VOL. 43, NO. 4, OCTOBER 2007


have been used as morphologic parame-ters of early myocardial ischemia. Exper-imental studies have demonstrated thatacute ischemia produces early myocardialcell membrane rupture, causing depletionof cytoplasmic myoglobin and depositionof plasma proteins such as fibrinogen inmyocytes (Xiaohong et al., 2002).

No gross lesions were observed inskeletal muscles, and tissue samples wereroutinely obtained from superficial por-tions of the mulitifindus and longissimusmuscles just caudal to the dorsal fin.Previous studies have not described path-ologic changes in locomotory muscles indolphins that died during fishing opera-tions (Cowan and Walker, 1979), whichhas been interpreted as the usual absenceof muscle lesions in the delayed-peracutecapture myopathy syndrome (Curry,1999). However, histologic and immuno-histochemical examination of skeletal mus-cles in our study revealed similar lesions tothose described in the myocardium, in-dicating ischemic damage. Exertion, trau-ma, and crush muscular injury during thestranding and transportation are consid-ered to be the main causes of skeletalmuscular lysis in our case. The mech-anisms underlying exercise-induced rhab-domyolysis remain unclear, but hypokale-mia and ischemia appear to be involved(Guis et al., 2005). In traumatic and crush-induced rhabdomyolysis, the muscles areinitially compressed and ischemic, andmuscle dysfunction starts to develop onlywhen the animals are evacuated, causingreperfusion of the damaged muscles(reperfusion injury) (Odeh, 1991). Acomparable situation could have hap-pened in our case when the animal wasreintroduced into an aquatic medium afterthe active stranding and transportation.

Regardless of the initiating mechanism,rhabdomyolysis results in the release ofmuscular cell components into circulation,mainly myoglobin. Myoglobin is an im-portant storage site for oxygen in themuscles of diving marine mammals, andtheir high muscular concentration is con-

sidered to be one of their most importantadaptations. However, myoglobin in thelocomotory muscles is not homogeneouslydistributed. Myoglobin is found in greaterconcentrations in the epaxial than in thehypaxial muscles, with the highest con-centrations located in deeper portionsclose to vertebrae and in the most caudalregion closest to the flukes, which producethrust during swimming (Dolar et al.,1999). In addition, the rectus abdominismuscle, which is a nonaxial muscle thatoriginates at the pubic symphysis andinserts into the sternum and costal carti-lages, has a myoglobin concentrationcomparable to the epaxial locomotorymuscle (Dolar et al., 1999), and it couldhave suffered traumatic and compressiveinjury during the stranding and posteriortransportation, contributing to the devel-opment of the myoglobinemia in our case.Data related to myoglobin distribution incetaceans probably should be used totarget those groups of muscles likely tobe most susceptible to exertional rhabdo-myolysis and its consequences for exami-nation.

Rhabdomyolysis can cause the death viaseveral mechanisms, including heart fail-ure, volumen depletion, metabolic acido-sis, hypocalcemia, hyperphosphatemia,and disseminated intravascular coagula-tion. Acute renal failure (ARF) is the mostimportant and frequent complication inrhabdomyolysis, mainly in animals withlarge muscle masses (Guis et al., 2005).Renal lesions in this case were similar tothose described in other mammalianmyoglobinuric nephrosis. Cowan and Cur-ry (2002) reported on a series of dolphinswith lesions related to capture and chaseduring fishery operations; all animalsstudied had acute necrosis of renal tubulesattributed to ischemia but none hadintratubular myoglobinuric casts. In thiscase, immunohistochemistry was usefulfor demonstrating myoglobin as the originof the intratubular casts and identifyingmyoglobinuric-related tubular degenera-tion. The main pathophysiologic mech-

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anisms of myoglobinuric ARF includerenal vasoconstriction, intraluminal castformation, and direct heme protein–in-duced cytotoxicity (Zager, 1996). In ourstudy, some of the degenerate epithelialtubular cells were immunohistochemicallyreactive for HSP70. Previous studies haveindicated that the immunohistochemicalstaining of myoglobin and oxidative injury-related markers, including HSP70, offersimportant information for the diagnosis ofmyoglobinuric-related ARF (Ishigami etal., 2003).

In conclusion, this study showed thatCM should be included in the differentialdiagnostic of delayed death in activestranded cetaceans, the importance of anexhaustive examination of skeletal musclein order to find degenerative changes, andthe usefulness of the inmunohistochemicaldemonstration of fibrinogen, myoglobin,and HSP70 as markers of early ischemicmuscle damage and myoglobinuric ne-phrosis in dolphins.

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Received for publication 20 July 2006.

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