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)

Ischemia-induced myocardial potassium loss and post-ischemic potassium reuptake was quantitated in 8 open chest pigs during control conditions and during hemodynamic alterations which have been shown to increase steady state sarcolemmal potassium fluxes. Myocardial K+ balance was continuously computed before, during and after a 90 s occlusion of a branch of the circumflex artery during control (CTR), during pacing tachycardia (PACE: 34% increase in heart rate), during proximal aortic constriction (AC; 28% increase in LVSP), and during isoprenaline infusion (ISO; 135% increase in LVdP/dt and 35% increase in heart rate). Ischemia-induced potassium loss increased significantly (40%) during ISO only. Higher basal metabolic rate, increased sarcolemmal K+ conductance, or ischemia-induced depression of a more active Na/K-pump during ISO are possible explanations to why increased K+ loss appeared in this situation. The maximal rate of post-ischemic potassium reuptake was not different from CTR during PACE and ISO, but it was reduced during AC, which might be due to persisting subendocardial ischemia in early reperfusion when ventricular wall stress is high. The extent of potassium restoration was not different from CTR during AC, PACE and ISO.
 ...
PMID:Effects of hemodynamic variables on myocardial K+ balance during and after shortlasting ischemia. 263 10

Heart transplantation is the best option for surgical treatment of end-stage congestive heart failure. However, when heart transplantation is not possible, other surgical options are available, and one of them is cardiomyoplasty. Below is a new multi-step approach for improving cardiomyoplasty results according to our clinical and experimental data. In order to decrease the length of time and damage of cardiomyoplasty operation one can use a lateral approach to mobilize the latissimus dorsi muscle and wrap the heart. In order to receive long-term fatigue resistance in the latissimus dorsi muscle of older patients one can increase the length of time of the pre-assist training of the latissimus dorsi muscle using a more cautious regimen. In order to improve hemodynamic results after muscle conditioning the cardiosynchronization regimen can be changed from 1:2 to 1:4. In order to prolong the period of effective latissimus dorsi muscle performance the electrical stimulation may be switched off at night or changed to a rate of 1:8. New cardiomyostimulator LD-PACE II may be used to change day/night regimen. In order to prevent sudden cardiac death in the patient with severe cardiac arrhythmia it is possible to combine cardiomyoplasty with implantable cardioverter defibrillator (ICD) implantation. In order to implement cardiac assist immediately after cardiomyoplasty it is possible to start with cautious electrical stimulation regimen just after cardiomyoplasty or use cardiac assist in work-rest regimen several hours daily. In order to prevent ischemia-reperfusion damage of latissimus dorsi muscle after subtotal mobilization, the latissimus dorsi muscle can be treated with an application of fibrin sealant with added aprotinin, pyrrolostatin, or deferoxamine. In order to accelerate angiogenesis and indirect myocardial revascularization, fibrin sealant with own endothelial cells can be administrated between the latissimus dorsi muscle and the myocardium.
 ...
PMID:Current status of cardiomyoplasty as surgical alternative for end-stage heart failure. 1451 42

Long-term memory impairment is reported in more than 50% of cardiac arrest survivors. Monosialoganglioside (GM1) provided neuroprotection in experimental models of stroke but failed to replicate its promise clinically for unknown reasons. GM1 stimulates the release of nerve growth factor (NGF), which is synthesized as a precursor protein (pro-NGF) that either mediates apoptosis through the p75 neurotrophin receptor (p75NTR) or is cleaved by the protease furin (FUR) to yield mature NGF, the latter supporting survival through tropomyosin kinase receptor (Trk). The flavanol epicatechin (EPI) inhibits p75NTR-mediated signaling and apoptosis by pro-NGF. The aim of the current work is to test whether these two drugs affect, or communicate with, each other in the setting of CNS injuries. Using the two-vessel occlusion model of global ischemia/reperfusion (I/R), we tested if pharmacological modulation of Trk, p75NTR, and NGF balance with GM1, EPI, and their combination, can correct the memory deficit that follows this insult. Finally, we tested if FUR insufficiency and/or p75NTR-mediated apoptosis negatively affect the neurotherapeutic effect of GM1. Key proteins for Trk and p75NTR, FUR, and both forms of NGF were assessed. All treatment regiments successfully improved spatial memory retention and acquisition. A week after the insult, most Trk and p75NTR proteins were normal, but pro/mature NGF ratio remained sharply elevated and was associated with the poorest memory performance. Pharmacological correction of this balance was achieved by reinforcing Trk and p75NTR signaling. GM1 increased FUR levels, while concomitant administration of EPI weakened GM1 effect on pro-survival Trk and p75NTR mediators. GM1 neuroprotection is therefore not limited by FUR but could be dependent on p75NTR. Graphical Abstract "."
 ...
PMID:Pharmacological Manipulation of Trk, p75NTR, and NGF Balance Restores Memory Deficit in Global Ischemia/Reperfusion Model in Rats. 3086 91

Elevated soluble (pro)renin receptor (s(P)RR) concentration in maternal blood is associated with gestational hypertension and preeclampsia. Placenta has abundant expression of (P)RR, and the binding of (P)RR with pyruvate dehydrogenase E1 beta subunit (PDHB) is reported to maintain oxidative metabolism. Thus, we hypothesized that placental hypoxia may increase (P)RR, and the increased (P)RR may preserve PDHB expression. Expression and functional analyses were performed using human placental trophoblast cells, mainly JAR cells. (P)RR co-immunoprecipitated and showed co-immunofluorescence with PDHB mainly in the mitochondria. Hypoxia treatment significantly increased intracellular s(P)RR protein expression, but secreted s(P)RR in the culture medium was decreased by hypoxia. Hypoxia treatment did not alter PDHB expression or activity in the basal condition, but when (P)RR was knocked down by siRNA, PDHB protein and activity were reduced by hypoxia. Acetyl-CoA, the product of PDH activity, was significantly reduced by hypoxia treatment with (P)RR siRNA. S(P)RR is generated from full-length PRR when cleaved by specific proteases. Protease inhibitor experiments suggested furin and site 1 protease as the enzymes generating s(P)RR in JAR cells, and only when treated by site 1 protease inhibitor, PF429242, PDHB protein showed a significant trend to decrease with hypoxia. In JAR cells, hypoxia increased intracellular s(P)RR, and (P)RR preserved the expression and function of PDHB during hypoxia. (P)RR may help maintain oxidative metabolism and efficient energy production during placental ischemia in hypertensive disorders of pregnancy.
 ...
PMID:Soluble (pro)renin receptor increased by hypoxia maintains oxidative metabolism in trophoblasts. 3195 19