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Microvascular Injury (microvascular + injury)
Selected AbstractsEarly Hepatic Microvascular Injury in Response to Acetaminophen ToxicityMICROCIRCULATION, Issue 5 2003YOSHIYA ITO ABSTRACT Objective: The hepatic toxic response to acetaminophen (APAP) is characterized by centrilobular (CL) necrosis preceded by hepatic microvascular injury and congestion. The present study was conducted to examine changes in liver microcirculation after APAP dosing. Methods: Male C57Bl/6 mice were treated with APAP (600 mg/kg body weight) by oral gavage. The livers of anesthetized mice were examined using established in vivo microscopic methods at 0, 0.5, 1, 2, 4, 6, 12 hours after APAP. Results: The levels of hepatic transaminases (i.e., alanine aminotransferase [ALT] and aspartate transaminase) increased minimally for up to 2 hours. Thereafter, their levels were significantly and progressively increased. The numbers of swollen sinusoidal endothelial cells (SECs) in periportal regions were increased (3.5-fold) from 0.5 to 6 hours, and those in CL regions were increased (4.0-fold) at 0.5 and 1 hour. The intensity of in vivo staining for formaldehyde-treated serum albumin, which is a specific ligand for SECs, was reduced from 2 to 12 hours. Erythrocytes infiltrated into the space of Disse as early as 2 hours, and the area occupied by these cells was markedly increased at 6 hours. Sinusoidal perfusion was reduced from 1 through 12 hours, with a nadir (35% decrease) at 4 and 6 hours. Phagocytic Kupffer cell activity was significantly elevated from 0.5 through 12 hours. Although gadolinium chloride minimized the changes in sinusoidal blood flow and reduced ALT levels 6 hours after APAP, it failed to inhibit endothelial swelling, extravasation of erythrocytes, and CL parenchymal necrosis. Conclusions: These results confirm that APAP-induced SEC injury precedes hepatocellular injury, supporting the hypothesis that SECs are an early and direct target for APAP toxicity. These findings also suggest that reduced sinusoidal perfusion and increased Kupffer cell activity contribute to the development of APAP-induced liver injury. [source] Blood Pressure and Brain Injury in Older Adults: Findings from a Community-Based Autopsy StudyJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 11 2009Lucy Y. Wang MD OBJECTIVES: To examine correlations between blood pressure (BP) and dementia-related pathological brain changes in a community-based autopsy sample. DESIGN: Prospective cohort study. SETTING: A large health maintenance organization in Seattle, Washington. PARTICIPANTS: A cohort of 250 participants aged 65 and older and cognitively normal at time of enrollment in the Adult Changes in Thought (ACT) Study and who underwent autopsy. MEASUREMENTS: BP and history of antihypertensive treatment were taken at enrollment. A linear regression model was used to examine the relationship between BP (systolic (SBP) and diastolic (DBP)) at enrollment and pathological changes in the cerebrum (cystic macroscopic infarcts, microinfarcts, neuritic plaques, neurofibrillary tangles, and cortical Lewy bodies). RESULTS: The presence of more than 2 microinfarcts, but not any other pathological change, was independently associated with SBP in younger participants (65,80, n=137) but not in older participants (>80, n=91). The relative risk (RR) for more than two microinfarcts with each 10-mmHg increase in SBP was 1.15 (95% confidence interval (CI)=1.00,1.33) in the younger participants, adjusted for age at entry, sex, and time to death. This RR was particularly strong in younger participants not taking antihypertensive medications (RR=1.48, 95% CI=1.21, 1.81); significant associations were not observed in participants treated for hypertension. Findings for DBP were negative. CONCLUSION: The association between high SBP and cerebrovascular damage in untreated older adults (65,80) suggests that adequate hypertension treatment may reduce dementia risk by minimizing microvascular injury to cerebrum. [source] Chondrodermatitis nodularis helicis as a marker of internal syndromes associated with microvascular injuryJOURNAL OF CUTANEOUS PATHOLOGY, Issue 5 2005Cynthia M. Magro Chondrodermatitis typically occurs in elderly men where associations with underlying trauma and sun exposure have been postulated as potential inciting triggers. Its association as a marker of systemic disease is not well established. We describe 24 patients with CNH, in whom there were also significant underlying diseases largely associated with vascular injury including those of immune-based etiology and/or conditions which have been previously linked with granuloma annulare, another necrobiotic process of collagen. These patients with concomitant systemic disease were characteristically younger compared to the classic demographics described for CNH. In some cases, chondrodermatitis may represent an ischemic necrobiotic disorder of collagen, potentially defining an important sign of underlying systemic disease in younger patients. [source] Ischemia,reperfusion injury pathophysiology, part IJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 4 2004DACVECC, Maureen McMichael DVM Abstract Objective: To review the current scientific literature on ischemia,reperfusion (IR) injury in both human and veterinary medicine. To describe the normal antioxidant defense mechanisms, the pathophysiology of IR injury, and the role of neutrophils in IR injury. Data sources: Data sources include scientific reviews and original research publications in both human and veterinary medicine. Summary: IR injury is a complex pathophysiological process involving numerous pathways and body systems. Normal antioxidant defense mechanisms function to limit oxidative injury during times of health. Ischemia is the period that occurs before oxygenated blood is re-introduced and the severity of injury has been shown to correlate with the magnitude and length of ischemia in dogs. During ischemia, there is a buildup of substances (i.e., xanthine oxidase, hypoxanthine, etc.) that, upon re-introduction of oxygen, form reactive oxygen species (ROS). ROS, produced in large part upon reperfusion, can cause extensive damage to DNA, proteins, carbohydrates, and lipids. Although mammalian systems are endowed with abundant antioxidant defenses, the generation of large amounts of ROS can overwhelm these mechanisms leading to cell dysfunction and death. Neutrophils play a critical role in IR injury and may mediate the majority of mucosal and microvascular injury that occurs by releasing ROS and proteolytic enzymes. Although experimental studies have been carried out on cats, dogs, and horses there are few clinical studies on companion animals. Conclusions: The pathophysiology of IR injury is complex and involves damage by ROS to all biological membranes. Neutrophils play a major role in IR injury and initiate and propogate much of the damage. This article is intended as a review of the pathophysiology of IR injury. [source] Microvascular Thrombosis Models in Venules and Arterioles In VivoMICROCIRCULATION, Issue 3 2005ROLANDO E. RUMBAUT MD ABSTRACT Platelets are intimately involved in hemostasis and thrombosis. Under physiological conditions, circulating platelets do not interact with microvascular walls. However, in response to microvascular injury, platelet adhesion and subsequent thrombus formation may be observed in venules and arterioles in vivo. Numerous intravital video microscopy techniques have been described to induce and monitor the formation of microvascular thrombi. The mechanisms of microvascular injury vary widely among different models. Some models induce platelet activation with minimal effects on endothelium, others induce endothelial inflammation or injury, while other models lead to thrombus formation associated with endothelial denudation. The molecular mechanisms mediating platelet,vessel wall adhesive interactions differ among various models. In some instances, differences in responses between venules and arterioles are described that cannot be explained solely by hemodynamic factors. Several models for induction of microvascular thrombosis in vivo are outlined in this review, with a focus on the mechanisms of injury and thrombus formation, as well as on differences in responses between venules and arterioles. Recognizing these characteristics should help investigators select an appropriate model for studying microvascular thrombosis in vivo. [source] Early Hepatic Microvascular Injury in Response to Acetaminophen ToxicityMICROCIRCULATION, Issue 5 2003YOSHIYA ITO ABSTRACT Objective: The hepatic toxic response to acetaminophen (APAP) is characterized by centrilobular (CL) necrosis preceded by hepatic microvascular injury and congestion. The present study was conducted to examine changes in liver microcirculation after APAP dosing. Methods: Male C57Bl/6 mice were treated with APAP (600 mg/kg body weight) by oral gavage. The livers of anesthetized mice were examined using established in vivo microscopic methods at 0, 0.5, 1, 2, 4, 6, 12 hours after APAP. Results: The levels of hepatic transaminases (i.e., alanine aminotransferase [ALT] and aspartate transaminase) increased minimally for up to 2 hours. Thereafter, their levels were significantly and progressively increased. The numbers of swollen sinusoidal endothelial cells (SECs) in periportal regions were increased (3.5-fold) from 0.5 to 6 hours, and those in CL regions were increased (4.0-fold) at 0.5 and 1 hour. The intensity of in vivo staining for formaldehyde-treated serum albumin, which is a specific ligand for SECs, was reduced from 2 to 12 hours. Erythrocytes infiltrated into the space of Disse as early as 2 hours, and the area occupied by these cells was markedly increased at 6 hours. Sinusoidal perfusion was reduced from 1 through 12 hours, with a nadir (35% decrease) at 4 and 6 hours. Phagocytic Kupffer cell activity was significantly elevated from 0.5 through 12 hours. Although gadolinium chloride minimized the changes in sinusoidal blood flow and reduced ALT levels 6 hours after APAP, it failed to inhibit endothelial swelling, extravasation of erythrocytes, and CL parenchymal necrosis. Conclusions: These results confirm that APAP-induced SEC injury precedes hepatocellular injury, supporting the hypothesis that SECs are an early and direct target for APAP toxicity. These findings also suggest that reduced sinusoidal perfusion and increased Kupffer cell activity contribute to the development of APAP-induced liver injury. [source] IMPACT OF BLOOD FLOW OCCLUSION ON LIVER NECROSIS FOLLOWING THERMAL ABLATIONANZ JOURNAL OF SURGERY, Issue 1-2 2006Mehrdad Nikfarjam Background: Laser, radiofrequency and microwave are common techniques for local destruction of liver tumours by thermal ablation. The main limitation of thermal ablation treatment is the volume of necrosis that can be achieved. Blood flow occlusion is commonly advocated as an adjunct to thermal ablation to increase the volume of tissue necrosis based on macroscopic and histological assessment of immediate or direct thermal injury. This study examines the impact of blood flow occlusion on direct and indirect laser induced thermal liver injury in a murine model using histochemical methods to assess tissue vitality. Methods: Thermal ablation produced by neodymium yttrium-aluminium-garnet laser (wavelength 1064 nm) was applied to the liver of inbred male CBA strain mice at 2 W for 50 s (100 J). Treatment was performed with and without temporary portal vein and hepatic artery blood flow occlusion. Animals were killed upon completion of the procedure to assess direct thermal injury or at 24, 48 and 72 h to assess the progression of tissue damage. The maximum diameter of necrosis was assessed by vital staining for nicotinamide adenine dinucleotide (NADH) diaphorase. Microvascular changes were assessed by laser Doppler flowmetry, confocal in vivo microscopy and scanning electron microscopy. Results: The direct thermal injury (mean SE) assessed by NADH diaphorase staining was significantly greater following thermal ablation treatment without blood flow occlusion than with blood flow occlusion (3.3 (0.4) mm vs 2.9 (0.3) mm; P = 0.005). Tissue disruption, cracking and vacuolization was more pronounced adjacent to the fibre insertion site in the group treated with thermal ablation combined with blood flow occlusion. There was an equivalent increase in the extent of injury following therapy in both groups that reached a peak at 48 h. The maximum diameter of necrosis in the thermal ablation alone group at 48 h was significantly greater than the thermal ablation combined with blood flow occlusion group (5.8 (0.4) mm vs 5.3 (0.3) mm; P = 0.011). The patterns of microvascular injury were similar in both groups, varying in extent. Conclusion: Temporary blood flow inflow occlusion appears to decrease the extent of initial injury measured by vital staining techniques and does not alter the time sequence of progressive tissue injury following thermal ablation therapy. [source] | ||||||||||