Protective effects of activated protein C (APC) on free groin flaps after secondary venous stasis in the rat model.

BACKGROUND: The goal of this study was to determine whether the focused delivery of APC by rinsing of free adipocutaneous groin flaps shows protective effects on flap survival following a fatal secondary venous stasis in a rat model. METHODS: 36 Sprague Dawley rats were randomized to three groups and free microvascular groin flaps were transplanted to the neck in each animal. 20 hours postoperatively the flap pedicle was re-explored and the distal stump of the flap artery was catheterised. Animals in group I (n = 12) remained untreated, whereas animals of group II were treated with 1 ml of Ringer's solution. Those in group III received 1 ml of APC (2 mg/kg). Afterwards the flap vein was clamped for 35 minutes. The skin of the flaps and the native contralateral groin was examined by intravital video microscopy using FITC-Dextran and CFDA-SE-labelled thrombocytes. RESULTS: APC-pretreatment significantly increased the functional capillary density (FCD) of the flaps. Flap viability was 8% in group I (n = 1/12), 9% in group II (n = 1/11) and 60% in group III (n = 6/10), respectively. No partial flap loss was detected. CONCLUSIONS: The focused delivery of APC resulted in significantly improved flap salvage.

Protective effects of antithrombin on free groin flaps after secondary venous stasis in the rat model.

BACKGROUND: The anticoagulant activity of heparin is well established and led to its widespread clinical use for the prophylaxis and treatment of venous thrombosis in microsurgery. Heparin accelerates antithrombin (AT)-mediated inhibition of clotting and fibrinolytic proteinases. AIM: The aim of the study is to determine whether the focussed delivery of AT by rinsing of free adipocutaneous groin flaps shows protective effects on flap survival, following a fatal secondary venous stasis in the rat model. Further, intravital video microscopy (IVM) is used to detect substance-specific alterations in microvascular perfusion with special focus on regional differences between central and peripheral flap regions. METHODS: Free microvascular groin flaps (n = 22) were transplanted to the neck in adult Sprague-Dawley rats. The flap pedicle was re-explored and the distal stump of the flap artery was catheterised 20 h later. Animals in group I (n = 11) were treated with 1 ml of Ringer's solution administered over 10 min via intraarterial infusion. Those in group II (n = 11) received 1 ml of AT (50 IU/kg). Afterwards, the flap vein was clamped for 35 min. The skin of the flaps and the native contralateral groin was examined by IVM using the plasma-marker fluorescein isothiocyanate (FITC)-dextran and carboxyfluorescein diacetate succinimidyl ester (CFDA-SE)-labelled thrombocytes. After 14 days, the viability of the flaps was evaluated. RESULTS: The treatment with AT significantly increased the functional capillary density (FCD) of the flaps. After 14 days, flap necrosis occurred in nine animals of group I and three animals of group II, respectively. No partial flap loss was detected. CONCLUSIONS: The focussed delivery of AT resulted in significantly improved flap salvage. The results may reinforce the clinical custom of AT substitution in the setting of major surgical procedures such as elaborate microsurgical reconstructions, at least in cases with diminished AT levels.

Somatotopic organization of human somatosensory cortices for pain: a single trial fMRI study.

The ability to locate pain plays a pivotal role in immediate defense and withdrawal behavior. However, how the brain localizes nociceptive information without additional information from somatotopically organized mechano-receptive pathways is not well understood. To investigate the somatotopic organization of the nociceptive system, we applied Thulium-YAG-laser evoked pain stimuli, which have no concomitant tactile component, to the dorsum of the left hand and foot in randomized order. We used single-trial functional magnetic resonance imaging (fMRI) to assess differential hemodynamic responses to hand and foot stimulation for the group and in a single subject approach. The primary somatosensory cortex (SI) shows a clear somatotopic organization ipsi- and contralaterally to painful stimulation. Furthermore, a differential representation of hand and foot stimulation appeared within the contralateral opercular--insular region of the secondary somatosensory cortex (SII). This result provides evidence that both SI and SII encode spatial information of nociceptive stimuli without additional information from the tactile system and highlights the concept of a redundant representation of basic discriminative stimulus features in human somatosensory cortices, which seems adequate in view of the evolutionary importance of pain perception.

Single trial fMRI reveals significant contralateral bias in responses to laser pain within thalamus and somatosensory cortices.

Pain is processed in multiple brain areas, indicating the complexity of pain perception. The ability to locate pain plays a pivotal role in immediate defense and withdrawal behavior. However, how the brain localizes nociceptive information without additional information from somatotopically organized mechano-receptive pathways is not well understood. We used single-trial functional magnetic resonance imaging (fMRI) to assess hemodynamic responses to right and left painful stimulation. Thulium-YAG-(yttrium-aluminium-granate)-laser-evoked pain stimuli, without concomitant tactile component, were applied to either hand in a randomized order. A contralateral bias of the BOLD response was investigated to determine areas involved in the coding of the side of stimulation, which we observed in primary (SI) and secondary (SII) somatosensory cortex, insula, and the thalamus. This suggests that these structures provide spatial information of selective nociceptive stimuli. More importantly, this contralateral bias of activation allowed functionally segregated activations within the SII complex, the insula, and the thalamus. Only distinct subregions of the SII complex, the posterior insula and the lateral thalamus, but not the remaining SII complex, the anterior insula and the medial thalamus, showed a contralaterally biased representation of painful stimuli. This result supports the hypothesis that sensory-discriminative attributes of painful stimuli, such as those related to body side, are topospecifically represented within the forebrain projections of the nociceptive system and highlights the concept of functional segregation and specialization within these structures.

Subcortical structures involved in pain processing: evidence from single-trial fMRI.

Pain is processed in multiple cortical and subcortical brain areas. Subcortical structures are substantially involved in different processes that are closely linked to pain processing, e.g. motor preparation, autonomic responses, affective components and learning. However, it is unclear to which extent nociceptive information is relayed to and processed in subcortical structures. We used single-trial functional magnetic resonance imaging (fMRI) to identify subcortical regions displaying hemodynamic responses to painful stimulation. Thulium-YAG (yttrium-aluminum-granate) laser evoked pain stimuli, which have no concomitant tactile component, were applied to either hand of healthy volunteers in a randomized order. This procedure allowed identification of areas displaying differential fMRI responses to right- and left-sided stimuli. Hippocampal complex, amygdala, red nucleus, brainstem and cerebellum were activated in response to painful stimuli. Structures related to the affective processing of pain showed bilateral activation, whereas structures involved in the generation of withdrawal behavior, namely red nucleus, putamen and cerebellum displayed differential (i.e. asymmetric) responses according to the side of stimulation. This suggests that spatial information about the nociceptive stimulus is made available in these structures for the guidance of defensive and withdrawal behavior.

Apparent diffusion coefficient decreases and magnetic resonance imaging perfusion parameters are associated in ischemic tissue of acute stroke patients.

Perfusion-and diffusion-weighted magnetic resonance imaging scans are thought to allow the characterization of tissue at risk of infarction. The authors tested the hypothesis that the apparent diffusion coefficient (ADC) decrease should be associated with the severity of the perfusion deficit in ischemic tissue of acute stroke patients. Perfusion-and diffusion-weighted scans were performed in 11 patients with sudden onset of neurologic deficits within the last 6 hours and T2-weighted magnetic resonance imaging scans were obtained after 6 days. Parameter images of the maximum of the contrast agent concentration, time to peak, relative cerebral blood volume, relative cerebral blood flow, and relative mean transit time were computed from the perfusion-weighted data. A threshold function was used to identify tissue volumes with stepwise ADC decreases. An onionlike distribution of successively decreasing ADC values was found, with the lowest ADC in the center of the ischemic region. Correspondingly, tissue perfusion decreased progressively from the periphery toward the ischemic core. This effect was most pronounced in the time-to-peak maps, with a linear association between ADC decrease and time-to-peak increase. Apparent diffusion coefficient values decreased from the periphery toward the ischemic core, and this distribution of ADC values was strongly associated with the severity of the perfusion deficit.

Surface orientation discrimination activates caudal and anterior intraparietal sulcus in humans: an event-related fMRI study.

Perception of surface orientation is an essential step for the reconstruction of the three-dimensional (3D) structure of an object. Human lesion and functional neuroimaging studies have demonstrated the importance of the parietal lobe in this task. In primate single-unit studies, neurons in the caudal part of the intraparietal sulcus (CIP) were found to be active during the extraction of surface orientation through monocular (two-dimensional) cues such as texture gradients and linear perspective as well as binocular (3D) cues such as disparity gradient and orientation disparity. We used event-related fMRI to study the functional neuroanatomy of surface orientation discrimination using stimuli with monocular depth cues in six volunteers. Both posterior (CIP) and anterior (AIP) areas within the intraparietal sulcus showed a stronger activation during surface orientation as compared with a control (color discrimination) task using identical stimuli. Furthermore, the signal changes in CIP showed a greater performance effect than those in AIP, suggesting that CIP is tightly linked to the discrimination task.

fMRI during word processing in dyslexic and normal reading children.

The present study addresses phonological processing in children with developmental dyslexia. Following the hypothesis of a core deficit of assembled phonology in dyslexia a set of hierarchically structured tasks was applied that specifically control for different kinds of phonological coding (assembled versus addressed phonological strategies). Seventeen developmental dyslexics and 17 normal reading children were scanned during four different tasks: (1) passive viewing of letter strings (control condition), (2) passive reading of non-words, (3) passive reading of legal words, and (4) a task requiring phonological transformation. Statistical analysis of the data was performed using statistical parametric mapping (SPM96). Comparison of patterns of activation in dyslexic and normal reading children revealed significant differences in Broca's area and the left inferior temporal region for both, non-word reading and the phonological transformation task. The present data provide new evidence for alteration of the phonological system in dyslexic children, and in particular, the system that mediates assembled phonological coding.