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)

Insulin accelerates the entry of glucose and amino acids into muscle cells by acting upon the 'carrier-facilitated' transport mechanism. For glucose this process is passive and leads to equilibration of intracellular and extracellular concentrations. In heart muscle, glucose transport is a rate-limiting step for glucose uptake. During hypoxia and ischemia the heart turns to anaerobic glycolysis for energy production and therefore, maximal glucose transport becomes important. Insulin is necessary to insure proper protein synthesis, probably at the level of membrane-bound polyribosomes. However, during myocardial hypoxia, insulin alone cannot restore the associated depression in protein synthesis. Although insulin hyperpolarizes the cell, a change in the ratio of intracellular to extracellular activities of potassium is not its primary mode of action. An insulin-induced configurational change in the plasma membrane could simultaneously account for the effects of insulin on sodium and potassium permeability and the action on facilitated transport. Intracellular levels of cyclic adenylate may be reduced by insulin in adipose tissue because of inhibition of adenyl cyclase or stimulation of phosphodiesterase. However, at this time there is little evidence that insulin alters cyclic AMP levels in the heart. Insulin secretion is depressed in patients with heart disease in proportion to the reduction of cardiac index sustained. Since the ischemic heart is dependent upon glucose as the major fuel, insulin lack may deprive the heart of adequate substrate.
 ...
PMID:Insulin: fundamental mechanism of action and the heart. 18 67

In 30 experiments in isolated canine hearts perfused with whole donor blood disorders in myocardial contractions were studied following the termination of paired stimulation. It was concluded that the cause of depression of cardiac contractions following paired stimulation is not myocardial hypoxia and energy reserve exhaustion during enhanced mechanical activity of the heart, but a dissociation of the electric and mechanical processes in the myocardium; switching off the second (stand-by) action potential together with the termination of the paired stimulation caused disorders in the regimen of coupling processes that have established themselves under this form of electric stimulation. This suggestion is supported by the fact that repeated paired stimulation during depression is capable of producing the same stimulating effect upon the cardiac contractions as the initial one. The depression was eliminated by the administration of potassium ions and catecholamines.
 ...
PMID:[Analysis of depression of contractions of the isolated dog heart following paired stimulation]. 101 51

Patients with prolapsing mitral leaflet syndrome (PML) frequently have chest pain of undetermined etiology. Twenty-three patients with PML underwent cardiac hemodynamic, angiographic, and metabolic studies. The latter were performed during control spontaneous heart rate and tachycardia by right atrial pacing. Myocardial supply-demand ratio (DPTI:SPTI) was estimated from the planimetric integration of the diastolic area (diastolic pressure time index = DPTI) and systolic area (systolic pressure time index = SPTI) of the central aortic pressure. Chest pain during pacing occurred in five patients. In two patients, it was associated with ST depression typical of ischemia on the electrocardiogram. Myocardial lactate abnormalities (lactate production or less than 10% extraction) occurred in seven patients during pacing tachycardia and was present in two patients during control state. DPTI:SPTI ratio during control state was 1.22 (+/- 0.07 SE) and decreased to 0.85 (+/- 0.05 SE) during pacing tachycardia. It is concluded that the myocardial lactate abnormalities in PML, which were present in approximately 30% of the patients in the present series, are most likely due to myocardial hypoxia. Whether or not the hypoxia is secondary to "small vessel disease" is not elucidated by this study.
 ...
PMID:Myocardial metabolic studies in prolapsing mitral leaflet syndrome. 118 56

Previous studies have demonstrated that catecholamines produce massiive disseminated cardiac necrosis closely resembling experimental myocardial infarction. Since catecholamine-induced lipolysis increases myocardial oxygen demand and increased levels of FFA are associated with a depression of myocardial function during myocardial hypoxia, the effect of inhibition of lipolysis on myocardial necrosis induced by isoproterenol was studied. Measurements of creatine phosphokinase (CPK) activity in extracts of whole heart homogenates provide a sensitive and relatively specific index of cellular necrosis. Accordingly, CPK activity was measured in rat hearts 48 hours after the animals had received either isoproterenol, given s.c., 3 times at hourly intervals, or isoproterenol after prior administration of nicotinic acid. Control animals were given saline. With increasing doses of isoproterenol, CPK activity in whole heart homogenates was depressed from 21.7 +/- 0.40 in untreated animals (N = 36) to 14.9 +/- 0.46 in animals given the highest dose of isoproterenol (N = 47). In animals in which isoproterenol-induced lipolysis was inhibited by nicotinic acid, CPK was less depressed (16.3 +/- 0.36, N = 47) than with isoproterenol alone (p less 0.02). Nicotinic acid given alone did not interfere with CPK activity. This study suggests that part of the necrosis induced by isoproterenol is due to increased release and oxidation of FFA in the rat heart.
 ...
PMID:Role of free fatty acids in catecholamine-induced cardiac necrosis. 119 80

The present experiments were carried out to investigate the cardiovascular effects of endothelin 1 (ET) in pithed spontaneously hypertensive (SH) rats and to evaluate its mechanism of action. The results show that ET (0.1-3 nmol/kg i.v.) is a powerful vasoconstrictor agent in the pithed rat. However, at a dose of 3 nmol/kg i.v. all the pithed animals "died" following a gradual decrease in mean arterial blood pressure and pulse pressure and changes in the form of the electrocardiogram (ECG). The predominant feature of the change in the ECG was a progressive decrease in the amplitude of the T wave resulting in a depression of the curve representing repolarization. Investigations in isolated perfused SH rat hearts showed that ET powerfully reduces coronary flow concentration-dependently (IC50 2.1 +/- 0.3 nM) an effect associated with sinus bradycardia and a decrease in coronary pressure amplitude. No overt ECG changes were seen. Control experiments with mechanical flow restriction suggest that bradycardia is a consequence of reduced coronary flow and that the ECG changes observed in vivo can be explained on the basis of coronary insufficiency and resulting myocardial hypoxia. Vasoconstrictor responses to angiotensin II (0.4 microgram/kg i.v.), phenylephrine (8 micrograms/kg i.v.) and ET (0.5 nmol/kg i.v.) were antagonised by around 70% by isradipine (0.03 mg/kg i.a.). The results suggest that endothelin-induced vasoconstriction may involve receptor operated channel activation and opening of voltage sensitive Ca2+ channels.
 ...
PMID:Cardiovascular effects of endothelin 1 in pithed spontaneously hypertensive rats: evaluation of its mechanism(s) of action. 253 Dec 95

We studied the effects of urapidil on bronchospasm, myocardial hypoxia and postural hypotension in experimental animals. Urapidil dose-dependently inhibited bronchospasm induced by histamine in anaesthetized guinea pigs and the contraction of isolated trachea induced by noradrenaline or phenylephrine. Urapidil markedly delayed the appearance of severe dyspnoea induced by histamine aerosol in guinea pigs. Further, urapidil inhibited isoproterenol-induced ST depression in rats and inhibited histamine-induced ST depression in rabbits. The postural hypotension induced by prazosin was greater than that induced by urapidil in equihypotensive doses in conscious rabbits. Urapidil induced a lesser alpha-blockade in the vein than in the artery compared with prazosin. These combined properties of urapidil suggest that the drug is worth investigation in hypertensive patients with bronchial asthma or ischaemic heart disease.
 ...
PMID:Pharmacological effects of urapidil on bronchospasm, myocardial hypoxia and postural hypotension in experimental animals. 323 Apr 72

[(5Z,13E,9 alpha,11 alpha,15S)-2,3,4-Trinor - 1,5 - inter-m - phenylene - 6,9 - epoxy - 11,5 - dihydroxy - 15 - cyclohexyl - 16,17,18,19,20-pentanor]- prosta-5,13-dienoic acid (sodium salt) (CG 4203) is a new stable epoprostenol (prostacyclin) analogue with a relative platelet antiaggregatory potency of 0.46 (ADP aggregation in vitro) and a hypotensive potency of 0.14 (anaesthetized rat i.v.) as compared to epoprostenol. In isolated perfused rat hearts, CG 4203 (4.64 X 10(-9) mol/l) significantly attenuated arrhythmias and loss of left ventricular creatine kinase (CK) activity observed in control hearts after 30 min perfusion with hypoxic and 30 min reperfusion with oxygenated Krebs-Ringer solution. In anaesthetized rats, CG 4203 (1.0 microgram X kg-1 X min-1 i.v.) significantly reduced incidence of ventricular fibrillation and increase in plasma CK activity after ligation of the left coronary artery. Infusion of 1.0 and 2.15 micrograms X kg-1 X min-1 CG 4203 i.v. in anaesthetized rats dose-dependently inhibited electrocardiographic changes, i.e. ST depression observed after i.v. injection of 1.0 IU X kg-1 vasopressin. In rat models of sustained myocardial hypoxia, myocardial infarction, and transient cardiac ischemia, CG 4203 thus exerts cardioprotective effects which, depending on the model considered, may be ascribed to either its vasodilatory, coronary dilatory, antiaggregatory or epoprostenol-like cytoprotective activity.
 ...
PMID:Cardioprotective action of the new stable epoprostenol analogue CG 4203 in rat models of cardiac hypoxia and ischemia. 644 79

Brief myocardial hypoxia causes both systolic and diastolic dysfunction, the latter often persisting during re-oxygenation. The underlying mechanisms may involve cytosolic Ca2+ overload as well as altered myofilament properties. Recent studies show that nitric oxide enhances myocardial relaxation via a cGMP-induced reduction in myofilament response to Ca2+. We studied the effects of pretreatment with a nitric oxide donor, sodium nitroprusside (0.1-1 microM) on the response to 5 min hypoxia in isovolumic rat hearts perfused at constant coronary flow. Left ventricular relaxation was assessed by an exponential time constant of pressure fall. Sodium nitroprusside reduced the depression of peak left ventricular pressure and peak dP/dt during hypoxia, and improved left ventricular relaxation both during hypoxia and re-oxygenation. Similar results were observed with a Ca2+ antagonist, nicardipine (10 nM). However, adenosine (400 nM), which reduced coronary perfusion pressure to a similar extent as the other two drugs, failed to improve left ventricular function. Addition of sodium nitroprusside or nicardipine at re-oxygenation did not improve relaxation, but instead impaired recovery of peak left ventricular pressure. These results suggest that exogenous nitric oxide improves LV contractile function, in particular relaxation, during brief hypoxia-re-oxygenation independent of changes in coronary flow or coronary perfusion pressure. Its failure to be protective if administered only during re-oxygenation suggests that its action does not involve an anti-oxidant effect.
 ...
PMID:Beneficial effects of a nitric oxide donor on recovery of contractile function following brief hypoxia in isolated rat heart. 916 Aug 71

With the use of a crossover study design, we investigated the respiratory and cardiovascular effects of naloxone administration in eight healthy Rocky Mountain wapiti (Cervus elaphus nelsoni) anesthetized with carfentanil (10 microg/kg i.m.) and xylazine (0.1 mg/kg). Anesthetized animals showed profound hypoxemia with mild hypercapnia, tachycardia, hypertension, and acidosis prior to naloxone administration. After monitoring equipment was placed, animals were administered either naloxone (2 microg/microg carfentanil i.v.) or an equivalent volume of normal saline. Mean values for PaO2, PaCO2, heart rate, and respiratory rate were significantly different between naloxone- and saline-treated groups, but mean blood pressure, hematocrit, and serum electrolyte concentrations were not. Mean PaO2 was 23.0 +/- 4.1 mm Hg prior to administration of naloxone or saline and increased to 50.2 +/- 7.3 mm Hg after naloxone administration. Mean PaO2 of saline-treated animals did not change significantly. Electrocardiograms of three saline-treated animals suggested myocardial hypoxia. Hypoxemia appeared to be caused by respiratory depression, hemodynamic alterations, and lateral recumbency. All but one animal remained anesthetized after naloxone administration. Anesthesia in all animals was reversed in < or = 4 min with naltrexone (100 mg/mg carfentanil i.v. s.c.) and yohimbine (0.1 mg/kg i.v.). One bolus of naloxone improved oxygenation in carfentanil-xylazine-anesthetized wapiti.
 ...
PMID:Use of naloxone to reverse carfentanil citrate-induced hypoxemia and cardiopulmonary depression in Rocky Mountain wapiti (Cervus elaphus nelsoni). 1279 Apr

Sepsis-associated myocardial depression is associated with calcium desensitization and adrenergic uncoupling. We conducted a prospective randomized investigation on the effects of the calcium sensitizer, levosimendan, on hemodynamics, myocardial blood flow, and myocardial lactate metabolism during porcine endotoxemia. Twelve pigs were studied. Oxygen consumption was measured by indirect calorimetry, and myocardial blood flow was measured by retrograde thermodilution. Pulmonary, arterial, and venous indwelling catheters allowed measurements of cardiac output, vascular pressures, and blood sampling. Fluids were given at an average of 15 mL . kg . h. After baseline measurements (0 min), an infusion of Escherichia coli LPS (2 microg . kg . min) was started in all animals. Beginning at 100 min, six animals received levosimendan (50 microg . kg . h), whereas six control animals received placebo. The study lasted for 300 min. All animals responded to endotoxin with pulmonary hypertension, a transient decrease in cardiac output, tachycardia, and systemic hypotension. Levosimendan infusion decreased systemic vascular resistance (P = 0.001), coronary vascular resistance (P = 0.004), and mean arterial (P < 0.001) and coronary perfusion pressures (P < 0.001), whereas pulmonary hypertension was unaffected. Heart rate progressively increased in both groups and was significantly higher in the levosimendan group (P = 0.048). Myocardial blood flow remained unchanged in both groups; however, 80 min after the start of levosimendan infusion, left ventricular myocardial hypoxia ensued, as evidenced by a negative myocardial lactate gradient (P = 0.01). Two control and five levosimendan animals died before the end of the study. Early administration of levosimendan during porcine endotoxemia increased heart rate, caused arterial vasodilation, and decreased coronary perfusion pressure, resulting in myocardial hypoxia.
 ...
PMID:Cardiovascular effects of levosimendan in the early stages of endotoxemia. 1751 May 99


1