Discrete Infarction Research Articles

Abstract TP208: A Novel Rat Model Of Vascular Parkinsonism Using The Vasoconstrictor Endothelin-1

Background: Vascular parkinsonism (VP) results from one or more small strokes in the basal ganglia. Patients with vascular parkinsonism usually are unaware of the individual strokes that occur, until progressive motor symptoms gradually appear. While Parkinson’s Disease (PD) and VP share some common symptoms, patients with VP show clear evidence of cerebrovascular disease, are likely to be older, more likely to present with gait difficulty rather than tremor, and less likely to respond to the use of levodopa compared with patients with PD. There is currently no clinically effective treatment for this condition and no rodent model established in the field to study VP. Methods: To stimulate the onset of VP, male Sprague Dawley rats (10-12 mos) were injected with the vasoconstrictor endothelin-1 (ET-1) into the dorsolateral striatum (DLS) or sham operation. Adhesive-tape removal test (ART) was used to test sensory-motor function at 2- and 5- days post DLS stroke and brains were removed and stained with TTC to assess the location of the infarct. In another set, animals were tested for apomorphine-induced rotational behavior at 21-28 days, in conjunction with immunohistochemistry to assess dopamine loss in the substantia nigra pars compacta. Results: We observed a discrete infarct localized to the DLS in animals injected with ET-1. There was no difference in latency to remove the tape in ART outcomes of ET-1 injected animals at 2- and 5- day post ischemia when compared to sham, consistent the fact that these coordinates resulted in a discrete striatal infarction, rather than a cortico-striatal infarction, which is seen in the ET1-induced middle cerebral artery stroke model in rats. At 21- and 28- days post, there was minimal rotational behavior and minimal loss of tyrosine hydroxylase (TH)-positive cells in the lesioned hemisphere, unlike that of the 6-OHDA model of PD, where rapid changes are seen in rotational behavior and loss of TH-positive cells. Conclusions: These data suggest that ET-1-mediated ischemia into the DLS is a promising model for the slow progression of dopaminergic loss and motor deficits reminiscent to that seen in VP patients. Apomorphine induced rotations and TH immunohistochemistry will be evaluated at 30-, 60- and 90- day timepoints.

Vascular Cognitive Impairment and the Gut Microbiota.

Vascular cognitive impairment (VCI), the second most common cause of dementia in elderly people, is a term that refers to all forms of cognitive disorders that can be attributed to cerebrovascular disease such as manifestations of discrete infarctions, brain hemorrhages, and white matter lesions. The gut microbiota (GM) has emerged recently as an essential player in the development of VCI. The GM may affect the brain's physiological, behavioral, and cognitive functions through the brain-gut axis via neural, immune, endocrine, and metabolic pathways. Therefore, microbiota dysbiosis may mediate or affect atherosclerosis, cerebrovascular disease, and endothelial dysfunction, which are the predominant risk factors for VCI. Moreover, the composition of the GM includes the bacterial component lipopolysaccharides and their metabolic products including trimethylamine-N-oxide and short-chain fatty acids. These products may increase the permeability of the intestinal epithelium, leading to systemic immune responses, low-grade inflammation, and altered signaling pathways that are associated with the pathogenesis of VCI. In this review, we discuss the proposed mechanisms of the GM in the maintenance of VCI and how it is implicated in acquired metabolic diseases, particularly in VCI regulation.

Lack of Association of CNS Lesion Number with Cognitive Performance and Cerebral Blood Flow in Sickle Cell Disease

Background: Neurocognitive studies demonstrate a deficit in performance for sickle cell anemia (SCA) patients as compared to age-matched peers. The underlying mechanism for this deficit is not yet understood, but possible contributors include CNS lesion load, perfusion deficits, oxygen deprivation and cerebrovascular autoregulatory impairment. We hypothesized that the number of white matter hyperintensities and the cerebral blood flow (CBF) might contribute to cerebral dysfunction in SCA patients. We sought to examine the relationship between cognition, laboratory parameters and brain perfusion in sickle cell patients as compared to non-sickle cell (AA) controls.Methods: SCA (HbSS/HbSβ0) and AA subjects, ages 18-55 years old, with no evidence of TIA/Stroke, no clotting/bleeding disorders, and not on anticoagulation were recruited. Hydroxyurea use was noted but was neither an inclusion nor exclusion criterion. Evaluation included a routine questionnaire for basic social, educational and health information. Steady state laboratory evaluation was obtained within one week of imaging. Neurocognitive performance was evaluated by the Cogstate battery at the time of the MRI. Cogstate analysis included tests of executive function, recall, social and emotional cognition and learning. Lesion number and CBF were determined using 3T MRI, which included T1w 3D, T2 FLAIR, pseudo-continuous arterial spin labeling, diffusion tensor imaging, and blood oxygen level depending imaging before and during a brief period of hyperoxia. Oxygen saturation and blood pressure were monitored throughout the procedure at 5-minute intervals.Results: To date, we have recruited 15 SCA and 7 AA subjects who answered a tailored questionnaire and underwent 3T MRI, routine laboratory testing and neurocognitive testing. Of the 15 SCA subjects, 6 had no lesions on 3T MRI and 9 had multiple lesions with 8 persons having more than 5. Lesion number correlated only with age (p=0.02). Of the 7 AA patients, 3 had no lesions, 2 had 1, 1 had 4 and 1 patient had >20 lesions. SCA patients fared worse on only one of the cognitive tests, the Groton Maze Learning Test for executive function (GMLT), in which a higher GMLT demonstrates decreased ability (p=0.02). Amongst the SCA subjects, a worse score on GMLT correlated positively with age (p=0.03), ferritin (p=0.02), mean arterial pressure (p=.02) and %HbF (p=0.03) while GMLT correlated negatively with %S (p=0.007), indirect bilirubin (p=0.02) and absolute reticulocyte count (p=0.005). There did not appear to be a relationship of GMLT with LDH, Hb, MCV, MCHC, platelet count, white cell parameters, number of crisis, oxygen saturation, CBF or lesion load. Gray matter CBF in SCA patients was significantly greater than that in AA subjects (164 ml/100g/min vs 113 ml/100g/min in AA, p < 0.007) as was white matter CBF (93 ml/100g/min vs 71 ml/100g/min, p=0.03). Both gray matter and white matter CBF correlated negatively with Hb/Hct levels in SCA patients (p=0.004). SCA patients also had a significantly lower average DP and MAP than the AA patients (p-0.004 and 0.015 respectively).Discussion: This study was undertaken to assess the role of a variety of clinical parameters against neurocognitive performance in SCA patients who had not been diagnosed with prior CVA or stroke. None-the-less, with the use of more powerful 3T MRI technology, there is an increase in the measurement and prevalence of white matter lesions in both SCA and AA subjects and a significant proportion of subjects were found to have evidence of white matter lesions. While white matter hyperintensities have been associated with cognitive outcomes, better detection of these lesions questions these assumptions and the prevailing theory that white matter hyperintensities are a marker of cerebral health and predict cognitive performance. Lesion number did not demonstrate an association with CBF or the GMLT; CBF correlated only with Hb levels and did not correlate with GMLT. There was an association of age with both cognition, as measured by the GMLT, and with lesion number.Conclusion: We suggest that diffuse cerebral dysfunction, rather than discrete infarct quantity, may be the more important mechanism of decreased cognition. We are currently assessing the functional assessments by fMRI to better delineate the nature of this cerebral dysfunction. DisclosuresNo relevant conflicts of interest to declare.

Neuropsychiatric Symptoms as a Putative Crescendo Warning of a Striatocapsular Infarct?

Neuropsychiatric Symptoms as a Putative Crescendo Warning of a Striatocapsular Infarct?

Targeted transendocardial therapeutic delivery guided by mri—x‐ray image fusion

To validate a multi-modality image fusion approach to guide catheter-based, targeted transendocardial therapeutic delivery in a swine myocardial infarction (MI) model. Biologic agents such as stem cells may curb post MI adverse ventricular remodeling if delivered by a transendocardial catheter directly into the infarct border. 3D visualization of the infarct and other cardiac surfaces is required to perform this task. We propose registering and overlaying magnetic resonance imaging (MRI) roadmaps onto live x-ray fluoroscopy (XRF) to guide targeted transendocardial delivery. Custom software was used to register and overlay MRI models of the endocardium and infarct on live XRF by aligning common endocardial border features. In a swine MI model, transendocardial injections of co-localizing imaging labels were performed, targeting a 20 mm perimeter around the infarct. Directed targeting error (DTE) was defined as the difference between the predicted injection site-to-infarct distance calculated by the image fusion system, to the actual distance determined by postprocedure in vivo MRI. The mobile image fusion system was designed to be vendor-independent for imaging systems and transendocardial catheters. Transendocardial injections were performed in all animals without complications. Mean DTE was 0.9 ± 5.0 mm (n = 8 swine). Time to register the images and establish a high quality roadmap was less than 12 min in all animals. Custom imaging tools to display injection sites and distribution were useful adjuncts during targeted injection procedures. Multi-modality image fusion is a feasible and accurate platform technology to guide transendocardial injections precisely to the discrete infarct border.

Development of Carotid Intraplaque Hemorrhage Demonstrated by Serial Magnetic Resonance Imaging

68-year-old man presented with a sudden onset of weakness and paresthesia of the left arm. He had a history of myocardial infarction 4 years earlier and a known renal artery stenosis. A nonenhanced computed tomographic scan of the brain showed no signs of hemorrhage or infarction. The patient underwent intravenous thrombolysis with alteplase (0.9 mg/kg body wt, 10% initial bolus dose over 1 minute, followed by infusion of the remaining 90% of the dose over 60 minutes). Soon after, the symptoms completely disappeared except for the persistence of a slight paresthesia of the left arm. Doppler ultrasonography revealed a hypoechoic plaque proximally in the right internal carotid artery causing a 50% to 69% stenosis. ECG showed sinus rhythm with complete right bundle-branch block without ST-segment or T-wave abnormalities. Transcranial Doppler imaging revealed no stenosis of the right middle cerebral artery. Serum lipid profile was within normal limits. In addition to the aspirin (100 mg once per day) and atorvastatin (40 mg once per day) he was already using, the patient was prescribed dipyridamole (200 mg twice per day) for secondary stroke prevention. Fifteen days after the initial onset of symptoms, the patient was enrolled in a clinical study investigating the natural history of carotid artery plaques. Magnetic resonance imaging scans of the brain and right carotid artery plaque were obtained, which revealed a recent discrete infarction of the right sensory region (Figure 1A and 1B) and a plaque with a large lipid-rich necrotic core with no or little hemorrhage (Figure 2A through 2D), respectively. Three months after the initial event, the patient once more presented with sudden onset of weakness and a numb feeling of the left arm. The patient again underwent intravenous thrombolysis with alteplase. However, the symptoms persisted. A nonenhanced computed tomographic scan, performed 24 hours after thrombolysis, revealed a hypodense area in the right motor region. Repeated Doppler ultrasonography showed no change in carotid plaque echogenicity and degree of luminal narrowing of the right internal carotid artery. Ten days after the onset of the second event, the patient underwent repeated magnetic resonance imaging scans of the brain and right internal carotid artery plaque. These scans confirmed recent infarction in the right motor region (Figure 1C and 1D) and revealed recent intraplaque hemorrhage (Figure 2E through 2H). Because of recurrent symptoms, the patient underwent carotid endarterectomy 20 days after the onset of the second event. Histological analysis of the excised plaque demonstrated large intraplaque hemorrhage (Figure 3A and 3B), confirming the magnetic resonance imaging findings. According to the American Heart Association, it was a type VI plaque (complex plaque with possible surface defect, hemorrhage, or thrombus). 1

Doin vivoExperimental Models Reflect Human Cerebral Small Vessel Disease? a Systematic Review

Cerebral small vessel disease (SVD) is a major cause of stroke and dementia. Pathologically, three lesions are seen: small vessel arteriopathy, lacunar infarction, and diffuse white matter injury (leukoaraiosis). Appropriate experimental models would aid in understanding these pathologic states and also in preclinical testing of therapies. The objective was to perform a systematic review of animal models of SVD and determine whether these resemble four key clinicopathologic features: (1) small, discrete infarcts; (2) small vessel arteriopathy; (3) diffuse white matter damage; (4) cognitive impairment. Fifteen different models were included, under four categories: (1) embolic injuries (injected blood clot, photochemical, detergent-evoked); (2) hypoperfusion/ischaemic injury (bilateral common carotid occlusion/stenosis, striatal endothelin-1 injection, striatal mitotoxin 3-NPA); (3) hypertension-based injuries (surgical narrowing of the aorta, or genetic mutations, usually in the renin-angiotensin system); (4) blood vessel damage (injected proteases, endothelium-targeting viral infection, or genetic mutations affecting vessel walls). Chronic hypertensive models resembled most key features of SVD, and shared the major risk factors of hypertension and age with human SVD. The most-used model was the stroke-prone spontaneously hypertensive rat (SHR-SP). No model described all features of the human disease. The optimal choice of model depends on the aspect of pathophysiology being studied.

Repair of Postinfarction Ventricular Septal Defect Through the Right Atrium

Repair of post infarction posterior ventricular septal defect has generally been performed with a ventriculotomy through the infarcted zone. This approach has a significant mortality and morbidity due to haemorrhage, extension of infarction or further compromise of ventricular function secondary to suture placement. We present a case with delayed repair of a post infarction posterior septal defect using a right atrial approach, where no discrete infarct or other abnormality of the free ventricular wall was found.

Thalamic infarct presenting with thalamic astasia

Astasia, inability to stand unsupported despite good strength, resembles the marked balance impairment of patients with vestibulocerebellar disease. We describe a patient with unilateral thalamic infarct that presented with astasia. A 76-year-old hypertensive woman was admitted to our hospital because of marked unsteadiness. On neurological examination, she could not stand unsupported and the woman's body swayed back and forth markedly. The swaying was not compensated for by her taking a step forward or backward, and she frequently collapsed when support was withdrawn. Diffusion-weighted magnetic resonance image revealed a discrete infarct within the right posterolateral thalamus. Brain single photon emission computerized tomography revealed markedly decreased regional cerebral blood flow within in the right thalamus with concomitant left superior cerebellar region. We discuss the possible pathomechanisms of thalamic astasia.

Strain Rate Imaging for Assessment of Regional Myocardial Function

Regional myocardial function assessment is essential in the management of coronary artery disease (CAD). Tissue Doppler imaging (TDI) by depicting local myocardial motion can potentially quantify regional myocardial function. Strain rate imaging (SRI) that depicts regional deformation is less susceptible to cardiac translation and tethering and may be superior to TDI for regional function analysis. We examined regional myocardial function using TDI and SRI in a unique clinical model of a small, discrete myocardial infarction. Ten patients with severely symptomatic septal hypertrophy underwent basal septal ablation via intracoronary alcohol injection and had TDI and SRI pre- and postablation. Invasive hemodynamics showed no appreciable change in global function. Peak systolic strain rate was significantly lower postablation versus preablation (-0.5 versus -1.2 s(-1), P<0.001) and when comparing infarct and noninfarct areas (-0.5 versus -1.5 s(-1), P<0.001). In contrast, peak systolic tissue velocities were similar pre- and postablation (3.9 versus 2.9 cm/s, P=0.16) and between infarct and noninfarct areas (2.9 versus 2.2 cm/s, P=0.13). SRI analysis demonstrated reduced systolic function in the peri-infarct zone and preserved systolic function in the remote nonischemic zone. In the clinical setting of a small, discrete infarct unaccompanied by changes in global function, SRI accurately depicted changes in regional function. These data suggest that SRI may be the optimal method for objective, quantitative assessment of regional myocardial dysfunction.

A murine photochemical stroke model with histologic correlates of apoptotic and nonapoptotic mechanisms

Introduction: The neuronal cell death that occurs after ischemia-induced cerebral infarction (stroke) contains elements of apoptosis and necrosis, an intermediary form of the two, and a distinct excitotoxic process. We previously developed a photochemical model of stroke in the rat. We have now adapted this model for use in the mouse. The present manuscript describes the mouse model. Methods: Minimal beam intensity (0.1 W/cm 2) cold white light (8 min exposure) was used to evoke discrete infarcts in the parietal lobes of 11 mice sensitized by the administration of fresh Rose Bengal (10 mg/kg by rapid iv infusion). Results: At 2 h, five out of five mice and at 6 h, six out of six mice demonstrated light microscopic histologic features like those in the rat model. These included a superior ischemic zone with shrunken and pyknotic nuclei, a middle transition zone of edematous vacuolated neuropil but normal neurons with open chromatin and retained Nissl granules, and an inferior zone with normal neurons. There was widespread nuclear terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL) in the superior infarct zone in 11/11 mice. However, in the edematous vacuolated transition zone, 11/11 mice had TUNEL positive and negative nuclei randomly mixed. Light microscopic analysis of that same transition zone showed no pyknosis or chromatin bodies in the TUNEL positive or negative cells. Discussion: In mice, photoactivation of Rose Bengal evoked similar infarct and transition zone patterns found previously in rats, with TUNEL evidence of apoptotic and nonapoptotic events. Thus, it will be possible to use this model for further quantitative study of apoptotic and excitotoxic events in wild and transgenic mice.

Extensive metabolic and neuropsychological abnormalities associated with discrete infarction of the genu of the internal capsule

OBJECTIVEThe clinical presentation of capsular genu infarct varies. Prominent faciolingual weakness and subcortical dementia are the rule, but symptoms depend on the precise location and extension of the lesion beyond...

Cerebral polyopia, neuroimaging localization

Objective: To report neuroimaging correlation in two patients with cerebral polyopia. Methods: Record review of the evaluation by a referral neuro-ophthalmology consultation service and neuroimaging of two patients who experienced monocular diplopia while hospitalized. Results: Magnetic resonance imaging and computed tomography of the brain demonstrated discrete occipital infarcts in the dominant hemisphere which corresponded to the visual field loss. At least in one case, the extrastriate cortex appeared spare. The cerebral polyopia was transient, while the field defects were permanent. Conclusions: Cerebral polyopia can be caused by an occipital lesion that does not necessarily extend to the associational areas and can be located in the dominant hemisphere.

Impairment of memory following discrete thalamic infarction

Impairment of memory following discrete thalamic infarction

Immunohistochemical patterns of selective cellular vulnerability in human cerebral ischemia

Although specific patterns of cellular vulnerability have been identified in experimental models of cerebral ischemia, there is little data on the occurrence of similar abnormalities in human ischemia. We therefore used a variety of histochemical methods to define changes affecting specific classes of cells in post-mortem specimens from seven patients with hippocampal and neocortical ischemic lesions. In acute lesions, staining with SMI-32, an antibody directed against nonphosphorylated neurofilaments that labels pyramidal projection neurons, was prominently depleted even when conventional Nissl staining revealed only mild pyknosis. In contrast, staining for other markers such as microtubule-associated protein 2 (MAP-2), another cytoskeletal protein, or parvalbumin, a calcium-binding protein found in γ-aminobutyric acid (GABA)-ergic interneurons, were relatively preserved. SMI-32 antibody also labeled dystrophic axons and axonal retraction balls in and around acute ischemic lesions. The pattern of differential changes in immunoreactivity was essentially the same in all acute ischemic injuries, including both diffuse lesions in the CA1 field (Sommer's sector) and discrete infarcts in CA1 and neocortex. In addition, immunoreactivity for the immediate early gene product c- fos was enhanced in and around the acute ischemic lesions that we studied. In some very acute lesions, immunoreactivity for glial fibrillary acidic protein (GFAP) was depleted in areas of severe ischemia and necrosis, but, as expected, GFAP immunoreactivity was increased in lesions more than a few days old. In contrast, the loss of SMI-32 immunoreactivity persisted in chronic lesions. These findings are consistent with those of experimental ischemia in animals and confirm the relevance of these studies for human cerebral ischemia. The pattern of selective changes also resembles that of injuries induced directly by excitatory amino acids, which may play a significant role in the pathogenesis of ischemic damage.

Selective Paralysis of Voluntary but Not Limbically Influenced Automatic Respiration

We describe a patient in whom a discrete infarction of the ventral basis pontis caused a complete loss of voluntary respiration, while automatic respiration remained intact. Respiratory excursions, quantified title volumes, and ventilatory response to carbon dioxide were normal, but the patient could not volitionally modify any respiratory parameters. Emotional stimuli producing laughter, crying, or anxiety appropriately modulated automatic respiration. This case established that pathways subserving limbic modulation of automatic respiration descend in the pontine tegmentum and/or lateral portion of the basis pontis spared by this lesion. Furthermore, descending limbic influences on automatic respiration are anatomically and functionally independent of the voluntary respiratory system.

Claude's syndrome: Clinical and computed tomography correlations

A patient with Claude's syndrome (ipsilateral fascicular third nerve palsy with contralateral ataxia) in whom computed tomography demonstrated a discrete infarct in the paramedian rostral mesencephalic tegmentum is reported. The vascular supply of the rostral mesencephalon is discussed.

Regional reduction in ventricular norepinephrine after healing of experimental myocardial infarction in cats

Regional ventricular norepinephrine and myosin heavy chain concentrations were measured in two models of healed left ventricular myocardial infarction in cats. One model was characterized by a well-defined dense transmural scar (discrete myocardial infarction), while the other demonstrated a pattern of nontransmural diffuse patchy fibrosis in the infarct area (diffuse myocardial infarction). Norepinephrine and myosin heavy chain concentrations were measured in the scarred area, the non-infarcted zone surrounding the scar(s), and in sites remote from the scar. Corresponding tissue sites from unoperated animals and sham operated animals served as controls. Myosin heavy chain concentration was used as an index of surviving muscle mass to express norepinephrine concentration. Norepinephrine concentration, as a function of crude tissue mass, was significantly reduced in both the scarred tissues and the non-scarred tissues surrounding the scar in the discrete infarction model but was significantly reduced only in non-scarred tissues adjacent to the dense scar when expressed as a function of myosin heavy chain. The heavily scarred area of the discrete preparation approached normal values when corrected for myosin heavy chain content. The diffuse infarct preparation demonstrated normal norepinephrine concentration at all three sites studied, whether expressed as a function of tissue mass or myosin heavy chain. These data indicate a long-term regional reduction in norepinephrine concentration specific to non-infarcted tissues adjacent to a dense transmural myocardial infarction scar. This regional reduction in norepinephrine concentration corresponds to reported regions of increased sensitivity to sympathetic nerve stimulation in the discrete myocardial infarction model.

Left ventricular outflow obstruction caused by a Starr-Edwards mitral prosthesis

ranged from 400,000 to 800,000/mm3. The final hospital admission at age 22 years was necessitated by severe CHF and ischemia of the distal left fourth finger. Cardiac output and blood pressure diminished progressively and the patient died 10.5 months after the acute MI. At necropsy (Medical College of Ohio #A-82-2), the heart weighed 450 g. The apical half of the anterior LV free wall was replaced by dense scar at and adjacent to the LV aneurysectomy incision (Fig. I). The posterior LV wall was also scarred. The LV apex contained mural thrombus adherent to underlying endocardial fibrous tissue. Fresh and organized mural thrombus also covered the LV outflow tract (Fig. 2). The R and LAD were totally occluded proximally; the length of the LAD occlusion was approximately 2 cm and that of the R 4 cm. The other portions of the LAD and R and the entire left circumflex artery were normal. Branches of the major epicardial coronary contained discrete focal severe narrowings with normal intervening areas. Histologic examination of the narrowed coronary arterial segments showed fibrocellular intimal profileration without foam cells, cholesterol clefts, pultaceous debris or calcific deposits (Fig. 3). In some segments, the lumen contained several small channels, and a platelet-fibrin thrombus was present in the LAD (Fig. 3). The intima of the narrowed coronary arteries was similar histologically to the thickened fibrous tissue on the LV mural endocardium (Fig. 4). Histologic examination of LV myocardium disclosed necrosis adjacent to the healed MI and multiple small intramural coronary vessels with plateletfibrin thromboemboli (Fig. 4). Both the spleen and lung contained discrete infarcts. The aorta was free of atherosclerotic plaques. The bone marrow, specifically the megakaryocytes, was normals The kidneys contained focal hyaline sclerosis of glomerular capillary tufts consistent with organized microthrombi, but no other abnormalities to explain the hematuria and proteinuria throughout childhood. (Sections of kidney were examined by John M. Kissane, MD, a recognized renal expert, who agreed with our renal diagnosis.)

Creatine phosphokinase MB isoenzyme in hypothermia: Case reports and experimental studies

Six patients with severe medical disorders and profound hypothermia are presented who had elevated total serum creatine phosphokinase (CPK) and CPK-MB isoenzyme activity without clinical 3 or postmortem 3 evidence of acute myocardial infarction. Experiments in dogs indicate that hypothermia reduces total CPK activity in both striated and myocardial muscle resulting in increased serum enzyme activity. These data suggest that profound hypothermia may result in diffuse striated and cardiac muscle cellular injury without evidence of discrete infarction with consequent release of CPK-MB isoenzyme into serum.