Biomedical subjects

I Cernak

Publications and source records attributed to I Cernak.

At least 19 recordsLinked to original sources

PubMed2001

An overview of new and novel pharmacotherapies for use in traumatic brain injury.

1. Although a number of interventional pharmacotherapies have undergone clinical trial in traumatic brain injury (TBI), none has shown considerable promise. The present short review will examine some of the more novel compounds that have been proposed recently as potential therapeutic agents for use in TBI. 2. Previous experimental studies have demonstrated that brain intracellular free magnesium significantly declines following TBI and that the administration of magnesium salts attenuates the post-traumatic neurological deficits. More recent studies have established that magnesium salts administered after trauma enter the brain intracellular space and reduce the size of the lesion volume. Such protection could be afforded through attenuation of both necrotic and apoptotic cell death. Magnesium salts are currently on clinical trial in TBI. 3. Cyclosporine A is known to inhibit opening of the mitochondrial permeability transition pore. Administration of cyclosporine A after TBI has been shown to attenuate axonal injury and decrease the resultant lesion volume. Therefore, inhibitors of mitochondrial transition pore opening and resultant attenuation of apoptosis show some promise as neuroprotective agents. 4. Recent evidence has shown that substance P antagonists may decrease lesion volume and improve neurological outcome after ischaemia. Similar findings have recently been reported in TBI. The fact that substance P antagonists are known to reduce neurogenic inflammation, oedema formation and are clinically being trialed as both antidepressants and antinociceptive agents suggests that these agents warrant further investigation as therapeutic agents following TBI. 5. There are numerous contradictions in the literature regarding the potential neuroprotective effects of the hormones oestrogen and progesterone. Recent studies suggest that both hormones are protective in TBI and further studies are required to ascertain the mechanisms associated with this protection and any potential for clinical application.

Brain Injuries↗

PubMed2001

Activation of cyclo-oxygenase-2 contributes to motor and cognitive dysfunction following diffuse traumatic brain injury in rats.

1. Post-traumatic inflammation may play a significant role in the development of delayed secondary brain damage following traumatic brain injury. 2. During post-traumatic inflammation, metabolic products of arachidonic acid, known as prostanoids (prostaglandins and thromboxanes) are released and aggravate the injury process. Prostanoid synthesis is regulated by the enzyme cyclo-oxygenase (COX), which is present in at least two isoforms, COX-1 (the constitutive form) and COX-2 (the inducible form). 3. In the present study, we examine the temporal and spatial profiles of COX-2 expression and the effects of the COX-2 inhibitor nimesulide on motor and cognitive outcome following diffuse traumatic brain injury in rats. 4. Adult male Sprague-Dawley rats were injured using the 2 m impact acceleration model of diffuse traumatic brain injury. At preselected time points after injury, animals were killed and the expression of COX-2 was measured in the cortex and hippocampus by western blotting techniques. 5. Increased expression of COX-2 was found in the cortex at 3 days and in the hippocampus as early as 3 h postinjury and this persisted for at least 12 days. 6. Administration of nimesulide (6 mg/kg, i.p.) at 30 min after injury and daily over a 10 day post-traumatic neurological assessment period resulted in a significant improvement compared with vehicle (2% dimethylsulphoxide diluted in isotonic saline)-treated controls in cognitive deficits, as assessed by the Barnes circular maze. There was also a significant improvement in motor dysfunction as assessed by the rotarod test on days 1 and 2 post-trauma compared with vehicle-treated controls. 7. These results implicate the involvement of COX-2 in cognitive and motor dysfunction following diffuse traumatic brain injury.

Animals↗

PubMed2001

Cognitive deficits following blast injury-induced neurotrauma: possible involvement of nitric oxide.

Blast injuries, that is injuries caused by the complex pressure wave generated by some explosions, show increasing frequency throughout the world. However, whether blast injury is capable of inducing memory dysfunction has not been previously investigated. The present study examines the effects of blast injury-induced neurotrauma on memory deficit in rats. Furthermore, it is hypothesized that blast injury, stimulating nitric oxide production in the medial mesodiencephalic reticular formation and the dorsal hippocampus, both structures being involved in memory processing, may induce memory deficits. Prior to blast injury, Wistar rats were trained for an active avoidance task for 6 days. On day 6, rats that had acquired the avoidance response were subjected to whole-body blast injury, using a BT-I shock tube. Neurotrauma was confirmed by electron microscopical examination. At the completion of cognitive testing, rats were sacrificed at 3, 24 hours and 5 days after injury. The nitric oxide production in the brain structures was determined by the total nitrite/nitrate concentration, and by the expression of inducible nitric oxide synthase mRNA. The rats with blast injury revealed significant deficits in performance of the active avoidance task that persisted up to 5 days post-injury. Electron microscopical findings in both brain structures showed swellings of neurons, glial reaction, myelin debris, and increased pinocytotic activity on the fifth day following trauma. In blast injured rats, there was a significant elevation in total nitrite/nitrate levels 3 and 24 hours following injury which was comparable with the changes in the expression of inducible nitric oxide synthase mRNA. The results indicate that blast injury-induced neurotrauma is able to cause cognitive deficits.

Animals↗

PubMed2001

Increased expression of neuronal glucose transporter 3 but not glial glucose transporter 1 following severe diffuse traumatic brain injury in rats.

Traumatic brain injury results in an increased brain energy demand that is associated with profound changes in brain glycolysis and energy metabolism. Increased glycolysis must be met by increasing glucose supply that, in brain, is primarily mediated by two members of the facilitative glucose transporter family, Glut1 and Glut3. Glut1 is expressed in endothelial cells of the blood-brain barrier (BBB) and also in glia, while Glut3 is the primary glucose transporter expressed in neurons. However, few studies have investigated the changes in glucose transporter expression following traumatic brain injury, and in particular, the neuronal and glial glucose transporter responses to injury. This study has therefore focussed on investigating the expression of the glial specific 45-kDa isoform of Glut1 and neuronal specific Glut3 following severe diffuse traumatic brain injury in rats. Following impact-acceleration injury, Glut3 expression was found to increase by at least 300% as early as 4 h after induction of injury and remained elevated for at least 48 h postinjury. The increase in Glut3 expression was clearly evident in both the cerebral cortex and cerebellum. In contrast, expression of the glial specific 45-kDa isoform of Glut1 did not significantly change in either the cerebral cortex or cerebellum following traumatic injury. We conclude that increased glucose uptake after traumatic brain injury is primarily accounted for by increased neuronal Glut 3 glucose transporter expression and that this increased expression after trauma is part of a neuronal stress response that may be involved in increasing neuronal glycolysis and associated energy metabolism to fuel repair processes.

Animals↗

PubMed2001

Ultrastructural and functional characteristics of blast injury-induced neurotrauma.

OBJECTIVE: The present study investigates whether whole-body or local (chest) exposure to blast overpressure can induce ultrastructural, biochemical, and cognitive impairments in the brain. METHODS: Male Wistar rats were trained for an active avoidance task for 6 days. On day 6, rats that had acquired the avoidance response were subjected to whole-body blast injury (WBBI), generated by large-scale shock tube (n = 40); or local (chest) blast injury (LBI), induced by blast overpressure focused on the right middle thoracic region and generated by small-scale shock tube (n = 40) while the heads of animals were protected. At the completion of cognitive testing, rats were killed at 3 hours, 24 hours, and 5 days after injury. Ultrastructural changes in the hippocampus were analyzed electron microscopically. Parameters of oxidative stress (malondialdehyde and superoxide anion generation) and antioxidant enzyme defense (superoxide dismutase and glutathione peroxidase activity) were measured in the hippocampus to assess biochemical changes in the brain after blast. RESULTS: Ultrastructural findings in animals subjected to WBBI or LBI demonstrated swellings of neurons, glial reaction, and myelin debris in the hippocampus. All rats revealed significant deficits in performance of the active avoidance task 3 hours after injury, but deficits persisted up to day 5 after injury only in rats subjected to WBBI. Oxidative stress development and altered antioxidant enzyme defense was observed in animals in both groups. Cognitive impairment and biochemical changes in the hippocampus were significantly correlated with blast injury severity in both WBBI and LBI groups. CONCLUSION: These results confirm that exposure to blast overpressure induces ultrastructural and biochemical impairments in the brain hippocampus, with associated development of cognitive deficits.

Animals↗

PubMed2000

Regulation of intracellular free magnesium in central nervous system injury.

Traumatic injury to the central nervous system (CNS) initiates an autodestructive cascade of biochemical and pathophysiological changes that ultimately results in irreversible tissue damage. Known as secondary injury, this delayed injury process is multifactorial in nature and it is generally thought that the simultaneous attenuation of a number of the secondary injury factors will be required for interventional therapies to have a significant beneficial effect on outcome. This review summarizes the growing body of evidence that suggests that magnesium plays a pivotal role in the secondary injury process following CNS trauma, affecting a number of secondary injury factors including neurotransmitter release and activity, ion changes, oxidative stress, protein synthesis, and energy metabolism. By having effects on such a range of secondary injury factors following trauma, pharmacological studies have shown that magnesium may be an effective therapy following neurotrauma, improving survival, motor outcome and alleviating cognitive deficits.

Animals↗

PubMed2000

Pulmonary blast injury increases nitric oxide production, disturbs arginine metabolism, and alters the plasma free amino acid pool in rabbits during the early posttraumatic period.

Plasma nitrate + nitrite (nitrates), as final NO products, and free amino acid pool (FAAP) characteristics, as indicators of protein/amino acid metabolism, were analyzed in the early (30 min) period following blast injury. The experiments were performed on 27 rabbits subjected to pulmonary blast injury (experimental group) or not exposed to overpressure (controls). We report that pulmonary blast injury (PBI) induces prompt NO overproduction within a very early period. Increased arginine utilization via NO synthase, presumably associated with its cleavage by arginase, leads to the depletion of the arginine level in arterial plasma 30 min following PBI. Impaired balance between arginine utilization and release/resynthesis from endogenous sources causes disturbed nutritional status and urea cycle activity. Early identification and appropriate management of the changes in amino acid metabolism should be included in the evaluation of patients with blast injury. Furthermore, the results suggest that depleted arterial levels of arginine and NO overproduction may be helpful in diagnosis and prognosis of blast injury.

Amino Acids↗

PubMed2000

Characterization of plasma magnesium concentration and oxidative stress following graded traumatic brain injury in humans.

Plasma magnesium, calcium, and oxidative status were investigated in 31 male casualties with traumatic brain injury (TBI) during a 7-day posttraumatic period. The study group consisted of eight patients with mild closed head injury (Glasgow Coma Scale score [GCS] of 13-15), 10 patients with extensive penetrating head injury (GCS 4-6), and 13 patients with blast injuries but without direct head trauma. The latter group was included since previous experimental and clinical data have confirmed the development of indirect brain trauma in patients with blast injuries. Patients with multiple injuries were not included. Significant declines in plasma divalent cations were found in GCS 4-6 patients immediately after TBI and persisting for the entire 7-day study period. Similar changes in magnesium, but not calcium, were present in the GCS 13-15 and the blast injury groups, but only up until day 3 after injury. Alterations in lipid peroxidation products and superoxide anions were also observed following TBI. Increased lipid peroxidation was noted in all three groups over the entire posttraumatic period while increases in superoxide anion generation occurred transiently immediately following TBI. Thereafter, in the GCS 13-15 and blast injury groups, superoxide anions subsequently normalized, whereas in extensive head injury (GCS 4-6), superoxide anion generation significantly declined. A negative correlation between magnesium balance and oxidative stress was observed in all patients immediately after injury persisting in GCS 4-6 patients to the end of the observation period. Our findings suggest an interrelationship between magnesium changes and blood oxidants/antioxidants after TBI, which could be of both diagnostic and prognostic value in patients with neurotrauma.

Adolescent↗

PubMed2000

Alterations in magnesium and oxidative status during chronic emotional stress.

Magnesium and oxidative status were investigated in young volunteers exposed to chronic stress (political intolerance, awareness of potential military attacks, permanent stand-by duty and reduced holidays more than 10 years) or subchronic stress consisting of everyday mortal danger in military actions lasting more than 3 months. Significant decreases in plasma ionized Mg2+, total Mg and ionized Ca2+ concentrations were found in both groups. Similarly, both study groups exhibited oxidative stress as assessed by increased plasma superoxide anions and malondialdehyde and modified antioxidant defense. There were no significant differences between the two stress groups. A negative correlation between magnesium balance and oxidative stress was observed suggesting that the same etiological factor (chronic stress) initiate decreases in both free and total magnesium concentrations and simultaneously increase oxidative stress intensity. These findings support the need for magnesium supplementation with antioxidant vitamins for people living in conditions of chronic stress.

Adolescent↗

PubMed1999

Recognizing, scoring, and predicting blast injuries.

The aim of this study was to find relevant signs and readily available parameters for the recognition of blast injuries and estimation of their severity. The injury severity, estimated by the Injury Severity Score (ISS), Red Cross Wound Classification (RCWC), and experimentally defined Pathology Scoring System for Blast Injuries (PSS/IS) according to Yelverton and modified for use in humans, was compared with a great number of subjective sensations, clinical signs, parameters of hemodynamic, metabolic, neuroendocrine and immune conditions. On the basis of these data, the confidence of the above-mentioned methods was analyzed in the evaluation of blast injuries. This study included 1303 casualties, wounded by explosive devices and with suspected blast injuries, treated at the Military Medical Academy in Belgrade (MMA) from 1991 to 1994. The patients were examined on admission at the MMA (<18 hours) and during hospitalization (1, 2, 5, and 7 days after wounding). The casualties with confirmed blast injury (n = 665, 51%) had an ISS ranging from 0 to 34 (mean 13) had wounds ranging from G1ST (soft tissue wounds caused by low energy transfer) to G3VF (massive wounds with fractures and injury of vital structures) according to the RCWC, with PSS/IS scores from 2 to 105 (mean 60). Statistically significant correlation was found between ISS and PSS/IS as well as RCWC and PSS/IS. Cytokines (IL-1, TNF|ga) and amino acids responded to a blast injury in similar manner as to gunshot wounds with a greater ISS or more severe RCWC injury type. The subjective sensations in blasted patients (deafness, thoracic pain, vertigo) and mediators, confirmed in previous experimental investigations as important factors in the pathogenesis of blast injuries (TxA2, sulfidopeptide leukotrienes) were relationed only to the PSS/IS.

Adult↗

PubMed1999

Neuroendocrine responses following graded traumatic brain injury in male adults.

In an effort to characterize thyroid, gonadal and adrenal function following neurotrauma, the present study determined serum concentrations of thyroid-stimulating hormone (TSH), total triiodothyronine (T3), thyroxine (T4), testosterone and cortisol over a 7 day period in 31 patients with traumatic brain injury. The study group consisted of eight patients with mild closed head injury (Glasgow Coma Scale--GCS 13-15), 10 patients with extensive penetrating head injury (GCS 4-6) and 13 patients with blast injuries but without direct head trauma. The latter group was included in the study because the development of indirect brain trauma has previously been implicated in blast injuries. Patients with multiple injuries were not included. Following mild injury (GCS 13-15), TSH was increased up until day 3 after injury. T3 levels were elevated on days 1, 5 and 7 after injury while T4 remained unchanged throughout. While testosterone was decreased over only the first 2 days post-trauma, cortisol was increased over these first 2 days after injury. In contrast, following severe penetrating injury (GCS 4-6), there were significant declines in TSH, T3 and testosterone over the 7 day observation period post-trauma. Serum cortisol also declined in these patients between 1-3 days after injury, before increasing again on days 5 and 7 after injury. Following indirect neurotrauma, TSH was slightly decreased immediately after trauma but increased to above normal levels on days 5 and 7 post-trauma. Similarly, T3 initially declined after injury, but then increased to above normal levels between 5 and 7 days after injury. T4 and testosterone remained unchanged over the entire post-traumatic period. Serum cortisol was significantly increased after indirect neurotrauma but only up to day 2 post-trauma. In summary, patients with both direct and indirect traumatic brain injury demonstrated endocrine alterations after trauma, the dynamics of which may be a reflection of the severity of brain damage.

Adolescent↗

PubMed1999

Blast injury from explosive munitions.

OBJECTIVE: To evaluate the effect of blast in common war injuries. METHODS: One thousand three hundred and three patients injured by explosive munitions and demonstrating extremity wounds without other penetrating injuries were admitted to the Military Medical Academy in Belgrade between 1991 and 1994. Of these, 665 patients (51%) had symptoms and physical signs that were compatible with the clinical diagnosis of primary blast injury, whereas the remaining 658 patients did not. RESULTS: Random sampling of 65 patients in the blast group during the early posttraumatic period showed statistically significant elevations in blood thromboxane A2 (TxA2), prostacyclin (PGI2), and sulfidopeptide leukotrienes compared with the random sample of 62 patients in the nonblast group. This difference could not be accounted for by differing injury severity between the groups, because the severity of wounds as measured by both the Injury Severity Score and the Red Cross Wound Classification was similar in both groups. Amongst blast patients, 200 patients (30%) had long-term (1 year) symptoms and signs reflecting central nervous system disorders. These symptoms and signs were only sporadically found in 4% of the nonblast patients. These findings indicate that primary blast injury is more common in war injuries than previously thought and that of those affected by blast, a surprisingly high proportion retain long-term neurologic disability. The elevation in eicosanoids could be used to confirm and monitor blast injury. CONCLUSION: In relation to the immediate management of patients injured by explosive weapons, it follows that particular attention should be paid to the presence and/or development of blast injury. Our findings indicate that blast is more common in war injuries than previously thought. Eicosanoid changes after blast injury suggest that blast injury causes a major physiologic stress. A variety of effects on the central nervous system suggest that blast injury could be responsible for some aspects of what is now considered to be the posttraumatic stress disorder.

Adult↗

PubMed1996

Involvement of the central nervous system in the general response to pulmonary blast injury.

The local, general, and cerebral responses of rabbits exposed to pulmonary blasts were examined to define the role of vagal afferentation in cardiorespiratory as well as metabolic control after a blast injury. Two series of experiments were conducted on rabbits to analyze the general, local, and cerebral responses to pulmonary injury caused by blast overpressure, and to evaluate the effects of bilateral vagotomy on the general, local, and cerebral responses to local (pulmonary) blast injury. The blast wave was generated in laboratory conditions using an air-driven shock tube that was able to cause moderate pulmonary blast injury, i.e., four pulmonary contusions characterized as confluent ecchymoses involving 30 to 60% of the lungs. One group of animals was subjected to pulmonary deafferentation, performed by bilateral transections of the vagus, glossopharyngeal, and hypoglossal nerves. Numerous hemodynamic as well as biochemical parameters were observed in systemic circulation and in lung and brain (medulla oblongata) tissues. After observation during the early posttraumatic period, rabbits were sacrificed by decapitation 30 minutes after the blast injury. On the basis of obtained results, it was concluded that vagal afferents have an important role in the modification of general and local responses to a pulmonary blast injury. Furthermore, it was suggested that functional changes in medulla oblongata may be the consequences of afferent neural impulses from the injured region (lungs) rather than consequences of ischemia, energy transfer to the brain, or both.

Afferent Pathways↗

PubMed1996

Glucose as an adjunct triage tool to the Red Cross Wound Classification.

The plasma concentrations of glucose, adrenaline, noradrenaline, insulin, and cortisol were measured in 59 patients within 18 hours of military gunshot/missile (MG/M) wound. The wounds were categorized by the Red Cross Wound Classification (RCWC) and assessed by the Injury Severity Score (ISS) method. The majority of the measured biochemical parameters, except insulin, were significantly increased after MG/M wounds, compared with control values. Plasma glucose concentration in wounded patients was positively related to ISS over the whole severity range. Plasma insulin concentration increased with glucose. Noradrenaline and cortisol were positively related to glucose. Because hemorrhage is the most common cause of general response to MG/M wound, we concluded that glucose measurement could be a useful adjunct tool to the RCWC in rapid and accurate assessment of severely wounded patients, especially those with occult thoraco-abdominal wounds.

Adolescent↗

PubMed1996

Leukotrienes in the pathogenesis of pulmonary blast injury.

Our previous studies demonstrate a significant increase of sulfidopeptide leukotriene concentrations in animals exposed to a free air blast. The aim of this study was to analyze the role of leukotrienes in the local response of lung tissue as well as in the general response of organisms to blast overpressure. The study was conducted on adult rabbits exposed to moderate blast overpressure (four pulmonary contusions characterized as confluent ecchymoses involving 30 to 60% of the lungs), generated in laboratory conditions. One group of experimental animals was treated with 5-lipoxygenase (5-LO) inhibitor, diethylcarbamazine (DEC, Sigma, St. Louis, Missouri) (50 mg/kg, i.v.), immediately before blast. The early posttraumatic period was observed (30 minutes after blast). Hemodynamic parameters (mean arterial pressure, heart rate, blood gases) as well as arterial plasma levels of conjugated dienes were observed. The myeloperoxidase activity, lipid peroxidation products levels, and water contents were measured in the lung tissue of injured rabbits. We observed that 5-LO inhibition reduced edema formation, accumulation of neutrophils, and generation of lipid peroxidation products in injured lungs. In this study, we demonstrated that treatment with DEC inhibits the increased systemic generation of conjugated dienes after blast injury. Although DEC exerts local antioxidant activity with beneficial effects on lung tissue, this 5-LO inhibitor intensifies the blast overpressure caused hemodynamic insufficiency.

Animals↗

PubMed1995

Experimental magnesium depletion in adult rabbits caused by blast overpressure.

The complex pressure wave (blast) generated by some explosions causes pulmonary pathological changes which resemble the histological findings of the adult respiratory distress syndrome (ARDS). The development of indirect neurotrauma following experimental pulmonary blast injury has been shown previously. The purpose of this study was to evaluate lung and brainstem total tissue magnesium concentrations in adult rabbits following pulmonary blast injury. In order to assess the interrelationship between magnesium and other secondary injury factors, total calcium and high energy phosphate (phosphocreatine, PCr; adenosine triphosphate, ATP) contents were simultaneously measured. Twenty adult male rabbits were divided into two groups. Group C (n = 10) served as control, while group B (n = 10) was subjected to a focused blast wave, generated in laboratory conditions using an air-driven shock tube. Moderate pulmonary blast injury was verified by histological examination in group B. Total tissue magnesium and calcium contents were measured by atomic absorption spectrophotometry in the lungs and brainstem of adult rabbits 30 min following blast overpressure and in their uninjured controls. Simultaneously, PCr and ATP contents were measured by fluorimetric enzymatic analyses in same structures. Lung and brainstem water contents were determined by wet weight to dry weight ratio. Blast overpressure to the lungs induced significant magnesium depletion, increased calcium and decreased the Mg/Ca ratio in lung tissue of injured animals. Increases in water content and PCr/ATP ratio were also observed. Significant correlations between these Mg/Ca and PCr/ATP and between Mg and ATP parameters confirmed the functional relationship between magnesium depletion and impaired bioenergetic state in indirect neurotrauma in adult rabbits through blast overpressure.

Animals↗

PubMedDate not supplied

Relations among plasma prolactin, testosterone, and injury severity in war casualties.

Tissue trauma leads to a complex hormonal response of pituitary end-organ axis. This response can be recorded by determining parameters that represent the functional integrity of these systems. The concentrations of serum prolactin (PRL), serum testosterone, and plasma adrenocorticotropin (ACTH) were measured in 62 adult male casualties from the recent war in former Yugoslavia. Patients with brain injury were not included. Venous blood samples were taken as soon as possible (2-18 hours) after admission and at 1, 2, 5, and 14 days after injury. The severity of gunshot/missile wounds was assessed by the Injury Severity Score (ISS). The control group consisted of healthy blood donors. Uninjured subjects who had undergone great stress on the battlefield (explosion in the vicinity without injury) served as the sham-control group. Tissue trauma leads to a severity-dependent decrease in serum testosterone concentrations during the first 5 days following injury. Significant correlations were observed between ACTH, prolactin, and ISS during the first 18 hours after injury. A strong negative correlation between testosterone and prolactin serum concentrations was found during the first 18 hours. In patients with additional complications or unsatisfactory outcome, the prolactin concentrations remained elevated, whereas testosterone concentrations were reduced. Our results support the usefulness of recording hormonal changes for determining trauma severity and monitoring the clinical course. Such monitoring also helps assess the efficacy of therapeutic strategies. The relation between testosterone and prolactin might be helpful for predicting the clinical course and trauma outcome.

Adrenocorticotropic Hormone↗

PubMedDate not supplied

[Experimental study of the pathogenesis of frostbite. Part I. Pathohistologic and ultrastructural changes in tissues immediately after thawing].

Histopathologic and ultrastructural changes in the tissues of frozen extremities of Wistar rats were investigated immediately after thawing. Three experimental groups were formed: two were exposed to cryoinjuries of different intensity, while the third was the control one. Cryoinjury was caused by experimental model of local, controlled freezing of hind, right extremities. Immediately after thawing the tissue samples were taken from frozen right and unfrozen left extremities, in which histopathologic and ultrastructural changes were compared mutually and with control group, respectively. It was observed that the freezing directly caused ultrastructural and histopathologic damage of the tissues that were manifested immediately after thawing and were proportional to the intensity of freezing. Simultaneously, in the tissues existed complex circulatory disorders manifested in open arteriovenous shunts, venous congestion and microcirculatory insufficiency caused by evident spasm of arteriolae that could be considered to be very significant pathogenetic factor in ischemic damage of unfreezed tissues.

Animals↗