Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Early changes in lysosomal enzymes must occur if their role is significant in irreversible myocardial injury. Therefore, we ligated the anterior descending coronary artery in 14 dogs and after 60 min excised epicardial and endocardial samples from the ischemic and adjacent normal heart. The collateral flow measured with radioactive microspheres in the endocardial samples averaged 19% of control. The muscle was disrupted and fractionated by ultracentrifugation into nuclear pellet (NP), heavy lysosomal pellet (HL), light lysosomal pellet (LL), microsomal pellet (M) and supernate (S). Electron microscopy demonstrated changes characteristic of sichemia in whole tissues and sedimented fractions. Acid phosphatase reaction product was present in residual bodies in the HL fraction and membrane-bound vesicles in the LL fraction and in the intact tissue. Significant decreases in the specific activity of N-acetyl-beta-glucosaminidase and beta-glucuronidase occurred in the endocardial LL fraction, while significant increases in both were found in the ts fraction (P less than 0.05). Losses of acid phosphatase occurred in both LL and S fractions. Moreover, decreases of total N-acetyl-beta-glucosaminidase in the HL fraction and of total beta-glucuronidase and acid phosphatase in the LL fraction were positively correlated (P less than 0.01) with the degree of ischemia measured with radioactive microspheres. Only insignificant enzymatic changes were found when the collateral flow was greater than 40%, and the differences were less significant in epicardial samples where the flow averaged 29%. The early loss of enzymes from the lysosomal fractions in severe ischemia suggests a role for lysosomal hydrolases in the necrosis that follows coronary occlusion.
 ...
PMID:Effect of collateral flow on epicardial and endocardial lysosomal hydrolases in acute myocardial ischemia. 115 94

Abnormalities of myocardial metabolism during acute rejection may be due to ischemia to primary metabolic changes related to rejection. An experimental study of heterotopic cardiac transplantation in the rat was undertaken to study myocardial mitochondrial oxidation during acute rejection. The receivers were Lewis rats and the donors Fischer (FL: allograft) or Lewis (LL: isograft) rats. The oxygen consumption of the mitochondria (VO2m) isolated from the transplanted and native hearts was measured by oxygraphy six days after transplantation. Using maleate and glutamate substrates, the VO2m of transplanted hearts was significantly lower than that of native hearts in the two groups of rats (FL, p less than 0.01; LL, p less than 0.01). In addition, the VO2m of FL allograft transplanted hearts was significantly lower than in the LL rats (30 +/- 9 vs 100 +/- 15 nanoatoms of oxygen/min.mg/prot, p less than 0.01) as was the VO2m of the native hearts (FL: 106 +/- 23 vs LL: 164 +/- 26, p less than 0.02). The respiratory control ratio (RCR) was significantly lower in the transplanted than in the native hearts in both the FL and LL groups (p less than 0.05 and p less than 0.01 respectively). The comparison of the RCR in the two groups (FL vs LL) showed no significant difference for transplanted or native hearts. Electron microscopy of transplanted (rejected or not) and native hearts showed no morphological abnormality of the mitochondria. The lower VO2m of the allograft group indicates a disturbance in the mitochondrial respiratory pathway during acute rejection.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Demonstration of abnormalities of myocardial mitochondrial oxygenation in cardiac graft rejection]. 189 20

To acquire cost-benefit analysis data for limb salvage a prospective study was performed between 1. January 1988 und 30. Juni 1988, including 128 admissions for AOD Stage IV or acute complete ischemia. After dividing the patients into three groups--limb salvage (LS), limb loss (LL) and primary amputation (PA)--the average total costs per admission were calculated. In the LS group these costs amounted to DM 14,652 for all cases and DM 14,069 for the survivors, in the LS group to DM 25,364 and DM 27,583 and in the PA group to DM 22,946 and DM 28,186. Therefore in light of the total costs alone every effort should be made to salvage threatened limbs.
 ...
PMID:[Cost-benefit analysis of saving the leg]. 257 6

The incremental torque resisting rotation of the foot about the ankle joint was studied in normal seated subjects. Prior to each rotation, subjects were required to activate triceps surae (TS) muscles and maintain a constant plantar flexion torque (range 6-14 N X m) on a platform whose position was controlled by a torque motor. Subjects were instructed to increase torque as rapidly as possible once rotation commenced. Rotations ranged from 0.5 to 14 degrees amplitude and from 20 to 300 degrees/s maximum velocity. The torque in response to rotations stretching TS muscles and releasing tibialis anterior (TA) muscles increased steeply and then rapidly decreased with stretch velocity. At approximately 60 ms from stretch onset, the torque reduction terminated, torque then increased again until it began to level off at approximately 120 ms. A further large increase in torque occurred at 180 ms. A burst of short-latency (SL) electromyographic (EMG) activity in soleus (SOL) commenced at 40 ms, and was followed by a second burst at approximately 68 ms, provided that stretch deceleration started later than 20 ms after stretch onset. A period of sustained EMG activity in SOL commenced at approximately 130 ms (long-latency (LL) activity). Incremental torque in response to stretch of TA and release of TS muscles initially showed a step decrease followed by a reversal of the torque trajectory back toward base line. This change was arrested at 60 ms and torque then remained approximately constant until a large increase in torque at 180 ms. Ischemia was used to reduce SL EMG reflexes without significantly modifying the background EMG activity. A comparison between torque curves under control and ischemic conditions indicated that SL EMG activity in TS muscles recruited the force responsible for terminating the torque reduction coincident with decreasing stretch velocity. The torque response prior to the onset of force recruited by SL activity was attributed to the intrinsic properties of active muscle fibers. Thereafter, until the onset of LL activity, the torque response was attributed to intrinsic and reflex-recruited force. Torque in these two time periods was compared under a variety of stretch conditions in order to test the hypothesis that force recruited by segmental reflexes compensates for the non-linear stretch properties of active TS muscles. The relationships of SL EMG amplitudes and areas to stretch velocity and acceleration were also examined.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Compensation for intrinsic muscle stiffness by short-latency reflexes in human triceps surae muscles. 651 89

We devised a nine-lead Holter monitor system with a lead-switching technique to record electrocardiograms from multiple sites in the anterior and the posterior or lateral chest. Leads CM1 to CM6, high lateral (HL), low lateral (LL), and low posterior chest (LB) were used. The sensitivity, specificity, and predictive accuracy of this system for identifying specific regions of myocardial ischemia and coronary artery disease were investigated in 130 patients with coronary artery disease. Anterolateral leads (CM4 to CM6, HL, and LL) showed high sensitivity for detecting anterior and lateral ischemia (69% to 100%) but low specificity (4% to 44%) compared with tomographic results. The specificity of these leads for identifying single-vessel disease was low (6% to 47%) although some leads showed high sensitivity (69% to 100%). In contrast, the LB lead exhibited high sensitivity and specificity for detecting inferior ischemia (70% and 95%, respectively) and right coronary artery (RCA) disease (74% and 93%, respectively). Consequently, ST depressions in the LB lead (anode) are specific for identifying inferior ischemia and RCA disease, whereas those in the anterior and lateral chest leads do not identify the ischemic region or the obstructed coronary artery.
 ...
PMID:Evaluation of a nine-lead Holter monitor for identifying and localizing ischemia and coronary artery disease detected by quantitative thallium-201 tomography. 794 90

A 9-lead Holter monitoring apparatus was devised using a commercially-available 3-lead Holter recorder. The CM5 lead was monitored continuously on channel 1, and our apparatus was applied to channels 2 and 3. Channel 2 was switched serially to V1-like (CM1), V4-like (CM4), V2-like (CM2) and V3-like (CM3) leads every 20 sec. Channel 3 was switched serially to V6-like (CM6), low-back (LB), high lateral (HL) and low-lateral (LL) leads every 20 sec. The study subjects included 98 patients with coronary artery disease. Myocardial ischemia was evaluated by exercise thallium-201 (Tl-201) scintigrams. Functional maps of myocardial perfusion were made from Tl-201 myocardial SPECT studies, and the extent and severity scores were calculated from these maps. The CM5 lead had a high sensitivity for detecting anterior, inferior and lateral wall ischemia, however, its specificity was very low. In contrast, the LB lead had very high sensitivity and high specificity for detecting inferior ischemia (79%, 76%, respectively). The percent extent score and percent severity score determined by the bull's eye method were compared between patients with ST depression of 0.5-1.0 mm and those with that greater than 1.0 mm detected by the LB lead. Both the percent extent score and percent severity score in the latter group were significantly higher than those in the former group (p < 0.001, p < 0.01, respectively), suggesting that the degree of ST depression in the LB lead reflects the degree of myocardial ischemia. The HL and LL leads had high sensitivity and specificity for detecting lateral ischemia. It was concluded that the CM5 lead is necessary for screening global myocardial ischemia and that leads LB and HL (or LL) are mainly useful for detecting inferior and lateral ischemia.
 ...
PMID:[A newly-devised nine-lead Holter system for diagnosing myocardial ischemia evaluated using Tl-201 exercise scintigraphy]. 816 32

Advanced MRI techniques, such as MR spectroscopy, diffusion and perfusion MR imaging can give important in vivo physiological and metabolic information, complementing morphologic findings from conventional MRI in the clinical setting. Combining perfusion MRI and MR spectroscopy can help in patients with brain masses in who the pre-operative differential diagnosis is unclear. This review demonstrates the use of dynamic, susceptibility weighted, contrast-enhanced MR imaging (DSC MRI) and magnetic resonance spectroscopic imaging (MRSI) to distinguish surgical from non-surgical lesions in the brain. There is overlap in the MRI appearance of many enhancing and ring-enhancing lesions such as gliomas, metastases, inflammatory lesions, demyelinating lesions, subacute ischemia, abscess and some AIDS related lesions. We review examples of histopathologically confirmed high-grade glioma, a middle cerebral artery territory infarct, a tumefactive demyelinating lesion and a metastasis for which conventional MR imaging (MRI) was non-specific and potentially misleading and demonstrate how DSC MRI and MRSI features were used to increase the specificity of neurodiagnosis. At several institutions, many patients routinely undergo MRI as well as MRSI and DSC MRI. Cerebral blood flow (CBF), mean transit time (MTT), and relative cerebral blood volume (rCBV) measurements are obtained from regions of maximal perfusion as determined from perfusion color overlay maps. Metabolite levels and ratios are determined for Choline (Cho), N-Acetyl Aspartate (NAA), Lactate and Lipids (LL). Metabolite levels are obtained by measuring the peak heights of each metabolite and the ratios are obtained from these measurements for Cho/Cr, Cho/NAA and NAA/Cr. Neurosurgical intervention carries substantial morbidity, mortality, financial and potential emotional cost to the patient and family. Making a pre-operative diagnosis allows the neurosurgeon to be confident in the choice of treatment plan for the patient and allays considerable patient anxiety. The utility of combining clinical findings with multi-parametric information from perfusion and spectroscopic MR imaging in differentiating surgical lesions from those which do not require surgical intervention is discussed.
 ...
PMID:Differentiating surgical from non-surgical lesions using perfusion MR imaging and proton MR spectroscopic imaging. 1556 Jul 13

Nitric oxide (NO) and arachidonic acid (AA) and also its metabolites are very important inter- and intracellular second messengers. They are involved in mechanisms of learning and memory. However, liberated in excessive amount in brain ischemia, Parkinson and Alzheimer diseases they are responsible for cell degeneration and death. Previously, we could show that Alzheimer disease's amyloid-beta protein enhanced nitric oxide liberation. The role of NO in AA metabolism is till now not well understood. Therefore, the aim of the present study was to investigate the mechanisms of NO-evoked activation of AA release and inhibition of AA incorporation into phospholipids of cortical rat brain synaptoneurosomes. The studies were carried out using NO donors, butyryl-cGMP (b-cGMP) and H2O2. All these compounds enhanced AA liberation from phosphatydilinositol (PI) and phosphatidylcholine (PC). Protein kinase ERK1/2, protein kinase C (PKC), cGMP-dependent protein kinase G (PKG) were involved in basal and NO-induced cytosolic phospholipase A2 (cPLA2) activation. Moreover, NO donors, b-cGMP and hydrogen peroxide (H2O2) exerted inhibitory effect on AA incorporation into PI and PC influencing arachidonyl-CoA transferase (AA-CoA-T) activity. AA-CoA synthase (AA-CoA-S) activity did not change. Specific inhibitors of protein kinase ERK1/2 (UO126), PKC (GF109203X), PKG (KT5823) had no effect on NO-mediated lowering of AA incorporation into PI and PC but inhibited the basal AA-CoA-S activity. Our data indicated that AA (10 microM) itself markedly decreased AA incorporation by about 50% into phospholipids of synaptoneurosomes membranes. Increasing release of AA and its metabolites causes the lowering of AA incorporation evoked by NO, b-cGMP and H2O2. Antioxidant, Resveratrol (100 microM) prevented NO- and cGMP-evoked inhibition of AA incorporation. These results suggest that NO affects the intracellular level of AA through alteration of cPLA2 and AA-CoA acyltransferase activities and may have an important implication in alterations of nerve endings properties and function.
 ...
PMID:Nitric oxide alters arachidonic acid turnover in brain cortex synaptoneurosomes. 1621 87

We hypothesized that the ischemic reperfused (I/R) lung expresses and liberates tumor necrosis factor-alpha (TNF-alpha) to injure the nonischemic lung, and that a TNF-alpha-converting enzyme inhibitor (TACEI) prevents injury of the nonischemic lung by blocking TNF-alpha liberation from the I/R lung. In isolated ventilated rat lungs in which differential perfusion to the right (RL) or left (LL) lung was feasible, LLs were selectively made ischemic (60 min) while maintaining perfusion to RLs, then reperfused (30 min) in a nonrecirculating manner with buffer solution (non-R; n = 18) or in a recirculating manner with buffer containing TACEI (TACEI[+]; n = 18) or without TACEI (TACEI[-]; n = 18). Ischemia reperfusion induced TNF-alpha messenger RNA expression in the ischemic LLs; the expression was highest in TACEI(+) group (P < 0.01). The expression of TNF-alpha, which was detected as immunofluorescence signals on CD34-positive endothelial cells, was observed in ischemic LLs; the highest expression being that in the TACEI(+) group. Wet/dry ratio and protein content in bronchoalveolar lavage fluid were higher in LLs than in RLs, and among the RLs, these 2 parameters were significantly increased in the TACEI(-) group (P < 0.01) in which the RLs were exposed to the TNF-alpha-rich perfusate. On the other hand, protein content in bronchoalveolar lavage fluid of the TACEI(+) group in which RLs were exposed to recirculating perfusate containing little TNF-alpha was decreased to a level close to but still higher than that in the non-R group (P < 0.05). The unilateral I/R lung affected the permeability of the nonischemic lung by liberating mainly TNF-alpha and induced TNF-alpha, interleukin (IL)-1beta, IL-6, and IL-10 messenger RNA expression in the nonischemic lung. These findings support the idea of organ-organ interaction in which an injured organ affects a remote organ by liberating humoral mediators.
 ...
PMID:Nonischemic lung injury by mediators from unilateral ischemic reperfused lung: ameliorating effect of tumor necrosis factor-alpha-converting enzyme inhibitor. 1717 85

Ischemia reperfusion (I/R) injury of the lung affects the function of the nonischemic lung. Our objective is to determine how apocynin, which is a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, protects the nonischemic control right lung (RL) from injury by the unilateral ischemic left lung (LL). In isolated ventilated (by air containing 5% CO(2)) rat lungs, in which differential perfusion of the RL or LL was feasible, the LL was selectively made ischemic (60 min) and reperfused (30 min) in a nonrecirculating or recirculating manner with buffer (Krebs-Henseleit) solution, or in a recirculating manner with buffer that contained apocynin (10 mmol/L) or apocynin + TACEI (tumor necrosis factor)-alpha converting enzyme inhibitor; 10 microg/mL) (each group: n = 12) or with buffer that contained SOD (superoxide dismutase, 3000 U before ischemia and at reperfusion) or SOD + TACEI (each group: n = 5). The permeability of pulmonary endothelium/epithelium (wet/dry ratio and protein content of bronchoalveolar lavage fluid of each lung), perfusion pressure, and cytokine messenger RNA (mRNA) expression was increased not only in the LL (compared with nonischemic control RL, P < 0.01 with paired-samples T) but also in the RL in recirculating groups (compared with RL in the nonrecirculating group). Apocynin + TACEI as well as SOD + TACEI prevented those permeability increases in the RL by the ischemic LL. However, apocynin with or without TACEI as well as SOD with or without TACEI could only partially ameliorate I/R injury in the LL (P < 0.01 by 1-way analysis of variance (ANOVA)). TNF-alpha and possibly reactive oxygen species produced and released from the ischemic lung may synergistically induce control RL (remote organ) damage.
 ...
PMID:Salvage of nonischemic control lung from injury by unilateral ischemic lung with apocynin, a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, in isolated perfused rat lung. 1905 62


1 2 Next >>