Changes in somatosensory evoked potentials following an experimental focal ischaemic lesion in thalamus

Experiments have been performed to produce localized thalamic ischaemia in baboons anaesthetised with alpha-chloralose. Somatosensory evoked potentials to median nerve stimulation were recorded in the medial lemniscus. VPL of thalamus and the primary somatosensory cortex. Local blood flow was also recorded by the hydrogen clearance technique in these regions. The early potential recorded in thalamus has been shown to be generated from 3 sources: (i) a positivity generated outside the VPL, (ii) local wavelets, most likely from synaptic activity close to the recording electrode, and (iii) a local overall negativity. The first of these potentials alone remains after thalamic ischaemia. It arises below the level of the thalamus, being very likely generated by the afferent volley in the medial lemniscus, and is seen in the surface-recorded response as the early component P8 (corresponding to P15 in the human).     

Antioxidant defenses in rat intestine and mesenteric lymph

Abstract

Dietary oxysterols can reach the circulation and this may contribute to atherosclerosis, where lipid oxidation is thought to be important. There is also evidence that, in rats,peroxidized lipids are absorbed and transported into lymph [Aw TY, Williams MW, Gray L. Absorption and lymphatic transport of peroxidized lipids by rat small intestine in vivo: role of mucosal GSH. Am J Physiol 1992; 262: G99–G106], although the method used to detect lipid peroxides lacked specificity. We tested whether intragastric administration of vegetable oils containing triglyceride hydroperoxides (TG-OOH) to rats resulted in detectable lipid hydroperoxides in mesenteric lymph. Using sensitive HPLC with postcolumn chemiluminescence detection, we were unable to detect hydroperoxides of triglycerides, cholesterylesters or phospholipids during the course of lipid absorption, and lymph levels of ascorbate, urate, α-tocopherol and ubiquinol-9 did not change significantly. By contrast, we observed a striking reducing activity judged by the efficient reduction of administered ubiquinones-9 and -10 to the corresponding ubiquinols. Exposure of rat lymph and isolated chylomicrons to aqueous peroxyl radicals revealed patterns of antioxidant consumption and lipid hydroperoxide formation similar to those described previously for human extravascular fluids and isolated lipoproteins, respectively. In particular, rates of TG-OOH formation in lymph and chylomicrons were very low to undetectable as long as ascorbate and/or ubiquinols were present, but subsequently proceeded in a chain reaction despite the presence of α-tocopherol. These studies demonstrate that rat intestine and mesenteric lymph possess efficient antioxidant defenses against preformed lipid hydroperoxides and (peroxyl) radical mediated lipid oxidation. We conclude that dietary lipid hydroperoxides or postprandial oxidation of lipids are not likely to contribute to these particular forms of oxidized lipids in circulation and aortic tissue.     

Liposome accumulation in chronic ischaemia is dependent on tissue necrosis

Liposomes accumulate in ischaemic rat intestine 24 h after mesenteric occlusion. The accumulation of liposomal components is shown to depend on necrotic or allied alterations in cell integrity/function associated with chronic ischaemia. Moreover) not all liposomai components accumulate at sites of infarction. It is concluded therefore that liposomes are likely to be of little value in the diagnosis and management of ischaemic disorders.     

The development of anoxia following occlusion

Following arteriolar occlusion, tissue oxygen concentration decreases and anoxic tissue eventually develops. Although anoxia first appears in the region most distal to the capillary at the venous end, it eventually spreads throughout the entire region of supply. In this paper the changing oxygen concentration, from the time of occlusion until the tissue is entirely anoxic, is examined mathematically. The equations governing oxygen transport to tissue are solved by iterating a nonlinear integral equation. This solution is valid until anoxia first appears. After anoxia develops it is necessary to solve a moving boundary problem. This is done using the method of matched asymptotic expansions, and accurate solutions are obtained for a wide range of physiological conditions.     

Selective antagonism of peptidoleukotriene response does not reduce myocardial damage opr neutrophil accumulation following coronary artery occlusion with reperfusion

This study was designed to assess the effect of a peptidol eukotriene receptor antagonist. SK&F 104353, for limiting myocardial damage and neutrophil accumulation in rats subjected to myocardial reperfusion injury (MI/R). In conscious rats, SK&F 104353 (25 mg/kg, i.v.) antagonized LTD₄-induced vasopressor responses by 90% and 60% at 1 and 4 hr, respectively, indicating effective blockade of peptidol eukotriene responses. In another group of animals subjected to 30 min of coronary artery occlusion with reperfusion for 24 hr, myocardial injury and neutrophil infiltration were determined by measuring creatine phosphokinase (CPK) specific activity and myeloperoxidase (MPO) activity, respectively, in the left ventricular free wall (LVFW). Myocardial CPK levels were 8.1 ± 0.2 U/mg protein in Sham-MI/R vehicle-treated animals, and were significantly decreased to 6.4 ± 0.6 U/mg protein in MI/R-vehicle animals. Myocardial MPO values were 1.5 ± 0.5 U/g LVFW in Sham-MI/R vehicle-treated animals, and significantly increased to 4.3 ± 0.6 U/g LVFW in MI/R-vehicle animals. Administration of SK&F 105353 (25 mg/kg, i.v.) 1 min prior to coronary occlusion and 3.5 hr post reperfusion and no effect on the loss of myocardial CPK specific activity or the increase in MPO levels (p > 0.05, compared to the MI/R-vehicle group). Thus, at a dose that antagonized LTD₄-induced vasopressor responses, SK&F 104353 did not attenuate either the extent of myocardial injury or inflammatory cell accumulation associated with myocardial ischemia/ reperfusion. These results suggest that peptidoleukotrienes do not contribute to the progression of myocardial ischemic/reperfusion injury.     

Selective antagonism of peptidoleukotriene responses does not reduce myocardial damage or neutrophil accumulation following coronary artery occlusion with reperfusion

This study was designed to assess the effect of a peptidoleukotriene receptor antagonist, SK&F 104353, for limiting myocardial damage and neutrophil accumulation in rats subjected to myocardial reperfusion injury (MI/R). In conscious rats, SK&F 10,4353 (25 mg/kg, i.v.) antagonized LTD4-induced vasopressor responses by 90% and 60% at 1 and 4 hr, respectively, indicating effective blockade of peptido-leukotriene responses. In another group of animals subjected to 30 min of coronary artery occlusion with reperfusion for 24 hr, myocardial injury and neutrophil infiltration were determined by measuring creatine phosphokinase (CPK) specific activity and myeloperoxidase (MPO) activity, respectively, in the left ventricular free wall (LVFW). Myocardial CPK levels were 8.1 +/- 0.2 U/mg protein in Sham-MI/R vehicle-treated animals, and were significantly decreased to 6.4 +/- 0.6 U/mg protein in MI/R-vehicle animals. Myocardial MPO values were 1.5 +/- 0.5 U/g LVFW in Sham-MI/R vehicle-treated animals, and significantly increased to 4.3 +/- 0.6 U/g LVFW in MI/R-vehicle animals. Administration of SK&F 10,4353 (25 mg/kg, i.v.) 1 min prior to coronary occlusion and 3.5 hr post reperfusion had no effect on the loss of myocardial CPK specific activity or the increase in MPO levels (p greater than 0.05, compared to the MI/R-vehicle group). Thus, at a dose that antagonized LTD4-induced vasopressor responses, SK&F 104353 did not attenuate either the extent of myocardial injury or inflammatory cell accumulation associated with myocardial ischemia/reperfusion. These results suggest that peptidoleukotrienes do not contribute to the progression of myocardial ischemic/reperfusion injury.