Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of insulin on contractile and energy metabolic dysfunctions during hypoperfusion (2 ml/min/g heart wt., 60 min) with 10(-6) M norepinephrine were studied in paced hearts isolated from streptozotocin-diabetic rats. Insulin (2 mU/min/g heart wt.) was infused 20 min before and during hypoperfusion (pre-treated group) or 30 min after the onset of hypoperfusion (post-treated group). Hearts in the non-treated group were hypoperfused without insulin and other hearts in the control group were not hypoperfused. In the non-treated group, resting contractile force (CF) and resting left ventricular pressure (LVP) were significantly elevated to maximum levels within 30 min after hypoperfusion and these elevations were restored in the pre-treated group but not in the post-treated group. Developed CF was depressed in the non-treated group and improved significantly in the pretreated group but not in the post-treated group. Developed LVP was depressed in the non-treated group, and depression was slightly larger in the pre-treated group. In the non-treated group, ATP and creatine phosphate contents in the left ventricle significantly decreased. Decreases in ATP and creatine phosphate contents in the inner layer were partially restored in the pre-treated group but not in the post-treated group. Lactate significantly increased in the non-treated group and increased even further in the insulin treated groups. These results indicate that contractile dysfunction during hypoperfusion with norepinephrine is improved by pre-treated insulin, as is partial recovery of energy metabolism.
 ...
PMID:Improvement of hypoperfusion with norepinephrine injury by ex vivo insulin in isolated diabetic rat hearts. 209 Aug 38

Following transient ischemia of the brain, the coupling between somatosensory activation and the hemodynamic-metabolic response is abolished for a certain period despite the partial recovery of somatosensory evoked responses. To determine whether this disturbance is due to alterations of the stimulus-induced neuronal excitation or to a breakdown of the coupling mechanisms, cortical spreading depression was used as a metabolic stimulus in rats before and after ischemia. Adult rats were subjected to 30 min of global forebrain ischemia and 3-6 h of recirculation. EEG, cortical direct current (DC) potential, and laser-Doppler flow were continuously recorded. Local CBF (LCBF), local CMRglc (LCMRglc), regional tissue contents of ATP, glucose, and lactate, and regional pH were determined by quantitative autoradiography, substrate-induced bioluminescence, and fluorometry. Amplitude and frequency of the DC shifts did not differ between groups. In control animals, spreading depression induced a 77% rise in cortical glucose consumption, a 66% rise in lactate content, and a drop in tissue pH of 0.3 unit. ATP and glucose contents were not depleted. During the passage of DC shifts, transient increases (less than 2 min) in laser-Doppler flow were observed, followed by a post-spreading depression hypoperfusion. A comparable although less expressed pattern of hemodynamic and metabolic changes was observed in the postischemic rats. Although baseline LCMRglc was depressed after ischemia, it was activated 47% during spreading depression. Lactate increased by 26%, pH decreased by 0.3 unit, and ATP and glucose remained unchanged. The extent of the transient increase in laser-Doppler flow did not differ from that of the control group, and a post-spreading depression hypoperfusion was also found.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Metabolic and hemodynamic activation of postischemic rat brain by cortical spreading depression. 211 36

Numerous studies report controversial results about the occurrence and role of cardiodepressant substances in various forms of circulatory shock. We investigated the net inotropic effect of the low molecular weight fraction (mol wt less than or equal to 1,000) of plasma in prolonged canine hypovolemic traumatic shock using an in vitro guinea pig papillary muscle assay (isotonic mode). The shock plasma fractions (ultrafiltrates) after 4 hr of hypotension (mean arterial blood pressure 40-50 mm Hg) and immediately post-reinfusion significantly depressed papillary muscle function (P less than .02). The extent of papillary muscle shortening was decreased by 49.5 +/- 9.9% in pre- and 50.6 +/- 10.0% in post-reinfusion plasma ultrafiltrates (mean values +/- standard error of the mean; n = 6 shock experiments). In contrast, both the plasma ultrafiltrates from ten non-anesthetized healthy dogs and the control ultrafiltrates obtained prior to onset of shock in the experiments (-6.4 +/- 2.6; n = 6) induced no significant change of the in vitro performance of papillary muscle contraction. These results were achieved with plasma fractions in which ionized calcium and pH were adjusted to concentrations equivalent to the bioassay solution. Lactate acidosis and severe hypoglycemia (1.97 +/- 0.43 mM post-reinfusion) occurred in the shock experiments. Lack of energy substrate (glucose) was not responsible for the in vitro depression. Four depressive shock ultrafiltrates with glucose concentrations adjusted to control ultrafiltrate levels induced a 66.6 +/- 8.8% decrease in the extent of papillary muscle shortening. These results suggest that the possible occurrence of high net negative inotropic activity in plasma, especially just post-reinfusion, may play a role in the pathogenesis of irreversible circulatory shock.
 ...
PMID:Net inotropic plasma activity in canine hypovolemic traumatic shock: low molecular weight plasma fraction after prolonged hypotension depresses cardiac muscle performance in vitro. 231 Dec 3

To investigate the mechanism of precordial ST segment depression during right coronary artery occlusion, precordial ST segment shifts and myocardial lactate metabolism were evaluated during coronary angioplasty in 10 patients with (group A) and 7 patients without (group B) precordial ST segment depression during balloon occlusion of the right coronary artery, and in 17 patients with precordial ST segment depression during balloon occlusion of the left anterior descending artery (group C). A 12 lead electrocardiogram was continuously recorded in each patient. Blood lactate in the aorta and great cardiac vein was measured during the procedure, and the lactate extraction ratio in the anterior wall was determined both before and during balloon occlusion. Eight of the 10 patients in group A and 1 of the 7 patients in group B had a dominant large right coronary artery. There were no significant differences in summed ST segment elevation in leads II, III and a VF between group A (0.56 +/- 0.26 mV) and group B (0.46 +/- 0.19 mV) during balloon occlusion of the right coronary artery, and no significant differences in summed ST segment depression in leads V1 to V6 during balloon occlusion between group A (0.44 +/- 0.26 mV) and group C (0.38 +/- 0.14 mV). Lactate extraction ratio before balloon occlusion was similar among the three groups. Patients in group A had a higher lactate extraction ratio during (38 +/- 11%) compared with before (30 +/- 11%) (p less than 0.05) balloon occlusion despite precordial ST segment depression.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Right coronary artery occlusion: its role in the mechanism of precordial ST segment depression. 252 31

The effect of leucine enkephalin (LNK) on spontaneous locomotor activity was studied in mice of both sexes. The effect of a depressant dose of ethanol (ET) on LNK-mediated response on motility was also studied. In addition, the determination of specific activities of the hepatic enzymes primarily involved in the metabolism of ET and acetaldehyde was studied. Lactate dehydrogenase (LDH) isoenzymes were also assayed in both plasma and heart tissues. Intraperitoneal injection of LNK, 100 mg/kg, exerted behavioral depression in the male but not female mouse compared to controls. This effect was apparent for the initial 30 min posttreatment. Injection of two smaller doses of LNK, which were devoid of effect on mouse motility, prior to a depressant dose of ET counteracted ET-caused depression of motility only in the female mouse. This became apparent 30 min postdrug injection and lasted for 60 min thereafter. The LNK and ET treatment inhibited only male mouse liver aldehyde dehydrogenase in both cytoplasmic and mitochondrial preparations concomitant with reduction of plasma but not heart LDH1 isoenzyme from corresponding controls. The results suggest that LNK and ET affect different systems involved in behavioral depression tested and show a potential for LNK in antagonizing the ET effect studied. The data also indicate a sex-dependent effect of LNK on motility and of its interaction with ethanol on the enzymes studied.
 ...
PMID:Effect of leucine enkephalin on ethanol produced behavioral depression in the mouse. 281 53

Control of glycolysis during anoxia was investigated in five organs (heart, brain, liver, and red and white skeletal muscles) of the freshwater turtle, Pseudemys scripta, after 1 or 5 h of submergence in N2-bubbled water. Lactate was produced as the metabolic end product, with distinct organ differences in the amount (net lactate accumulation was 2.4-fold higher in brain than white muscle) and rate (lactate production in liver dropped 16-fold after the 1st h) of lactate accumulation. ATP and total adenylate contents of all organs were reduced (by 15-32%) after 1 h of submergence, but energy charge was maintained; after 5 h, adenylate contents had fully recovered. Changes in the levels of hexose and triose phosphate intermediates of glycolysis indicated an activation of glycolysis within the 1st h of anoxia exposure in brain, heart, and skeletal muscles. By 5 h, however, these were reversed, and a glycolytic rate depression was indicated, consistent with the overall metabolic rate depression accompanying long-term anaerobiosis in the turtle. Crossover analysis indicated glycolytic control at the pyruvate kinase reaction in all organs during both glycolytic activation and metabolic depression; regulatory control at the phosphofructokinase locus was primarily important only during glycolytic activation in heart and red muscle. The same analysis indicated a very rapid glycolytic inhibition in liver occurring within the 1st h of anoxia exposure; this allows glycogenolysis to be directed toward glucose export yielding the fermentative fuel used by other organs during anoxia.
 ...
PMID:Organ-specific control of glycolysis in anoxic turtles. 297 50

To clarify the mechanism of stress-induced ST segment elevation in patients with previous anterior myocardial infarction, we examined myocardial lactate metabolism during atrial pacing in 32 patients with previous anterior myocardial infarction (MI group) and 11 control subjects (control group). In the MI group, atrial pacing resulted in new or additional ST segment elevation in leads with Q waves in 15 patients (ST elevation group), ST segment depression in 7 (ST depression group), but induced no appreciable ST segment changes in the remaining 10 patients (ST unchanged group). In all patients, the ST segment changes were identical to the results of exercise stress testing which was carried out prior to the atrial pacing. Lactate extraction ratio increased moderately during the atrial pacing in the control group (p less than 0.01). Although marked reduction of the myocardial lactate extraction ratio was noted in the ST depression group (p less than 0.05), no significant change in the ratio was evoked in the ST elevation group or the ST unchanged group during atrial pacing. Left ventricular end-diastolic pressure (LVEDP) increased markedly in the ST depression group during atrial pacing, but the elevation was less evident in the other groups. The ST elevation group demonstrated the lowest left ventricular ejection fraction and the severest degree of left ventricular asynergy. Thus, the present study indicates that aggravated left ventricular asynergy in the infarcted area and associated left ventricular dysfunction, rather than peri-infarction zone ischemia is a possible mechanism of stress-induced ST segment elevation in leads with Q waves following previous anterior myocardial infarction.
 ...
PMID:Clinical significance of stress-induced ST segment elevation in patients with previous anterior myocardial infarction. Analysis of lactate metabolism with atrial pacing. 317 72

To study the cardiac effects of progressive hypoxemia, we measured the left ventricular end-systolic pressure-volume relation (ESPVR), myocardial oxygen consumption (MVO2), and myocardial oxygen delivery (MQO2) in eight thoracotomized dogs anesthetized with fentanyl and droperidol. We specifically looked for evidence of oxygen supply limitation of MVO2 and depressed contractility (altered ESPVR) during stepwise decreases in inspired oxygen fraction. We hypothesized that the reported relation between MVO2 and left ventricular pressure-volume area (PVA) may hold when inadequate MQO2 determines MVO2, which then may limit PVA, manifested partly as a change in the ESPVR. Initially, as arterial oxygen saturation was decreased from 95 +/- 3% to 64 +/- 14%, coronary blood flow increased so that MQO2 was maintained with no change in myocardial extraction ratio (ERm = MVO2/MQO2). During this first phase, lactate utilization, PVA, and ESPVR did not change. When oxygen saturation was further reduced, coronary blood flow rose no higher and ERm increased, but not enough to maintain MVO2. Lactate consumption decreased and ST segments rose, signaling a change from aerobic metabolism. MVO2 decrease was associated with a fall in PVA, which was due to a fall in blood pressure and a significant depression of the ESPVR. Specifically, the volume intercept of the ESPVR increased in all dogs (6.5-20.1 ml, p less than 0.0001), accounting for two thirds of the increase in end-systolic volume. The slope of the ESPVR decreased during hypoxia (13.3-6.1 mm Hg/ml, p less than 0.02), accounting for only one third of the observed increase in end-systolic volume. We believe that the evidence of anaerobic metabolism, the decrease in PVA, and the depression of the ESPVR demonstrates onset of oxygen supply limitation of MVO2. Our data are consistent with the hypothesis that limited MVO2 may limit PVA. The hypoxic volume intercept alteration of the ESPVR is different from changes in the slope of ESPVR seen with other interventions. This may be analogous to recent observations in isolated muscle that show hypoxic depression in contractility to be different from other interventions.
 ...
PMID:Progressive hypoxemia limits left ventricular oxygen consumption and contractility. 318 Mar 52

Forty-seven nonmelancholic depressed outpatients were infused with sodium lactate to explore the relationship between history of panic attacks and lactate-induced panic. Lactate panic was rated without knowledge of history of panic. Fifteen of 29 patients (52%) with a history of spontaneous panic experienced panic attacks in response to lactate. Only 1 of 18 patients (6%) without a history of spontaneous panic experienced a lactate-induced panic attack--a highly significant difference. The likelihood of lactate panic was related to frequency of spontaneous panic attacks. The implications of these findings for understanding the relationship of panic attacks and depression are discussed.
 ...
PMID:Lactate provocation of panic attacks in depressed outpatients. 321 65

The contribution of research with lactate infusion to an understanding of agoraphobia, generalized anxiety disorder, and panic disorder (PD) was reviewed. Lactate-induced panic seems to differentiate panic disorder from generalized anxiety disorder. Panic disorder seems to have important links to depression; both respond to tricyclic antidepressant drugs and neither responds well to the benzodiazepine antianxiety drugs. Response to pharmacotherapy, epidemiological surveys, and familial studies support the distinction between panic disorder and generalized anxiety disorder and the overlap between major depression and panic disorder. Understanding the mechanism of lactate-induced attacks may provide a better understanding of the pathophysiology of naturally occurring panic.
 ...
PMID:Psychopharmacological investigation of panic disorder by means of lactate infusion. 361 9


<< Previous 1 2 3 4 5 6 7 Next >>