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

Three different syndromes produced by congeners of morphine have been identified in the nondependent chronic spinal dog. These syndromes have been attributed to interaction of agonists with three distinguishable receptors (mu, kappa and sigma). Morphine is the prototype agonist for the mu receptor, ketocyclazocine for the kappa receptor and SKF-10,047 for the sigma receptor. The morphine syndrome (mu) in the dog is characterized by miosis, bradycardia, hypothermia, a general depression of the nociceptive responses and indifference to environmental stimuli. Ketocyclazocine (kappa) constricts pupils, depresses the flexor reflex and produces sedation but does not markedly alter pulse rate or the skin twitch reflex. SKF-10,047 (sigma), in contrast to morphine and ketocyclazocine, causes mydriasis, tachypnea, tachycardia and mania. The effects of these three drugs can be antagonized by the pure antagonist naltrexone, indicating that they are agonists. Further, chronic administration of morphine, ketocyclazocine and SKF-10,047 induces tolerance to their agonistic effects. Morphine suppresses abstinence in morphine-dependent dogs while ketocyclazocine does not. Ketocyclazocine at best precipitated only a liminal abstinence syndrome in the morphine-dependent dog, indicating that it had little affinity for the morphine receptor. Ketocyclazocine thus appears to be a selective agonist at the kappa receptor. Further, it has been shown that buprenorphine is a partial agonist of the mu type which both suppressed and precipitated abstinence in the morphine-dependent dog while morphine and propoxyphene are stronger agonists. Apomorphine and SKF-10,047 produce similar pharmacologic effects suggesting that sigma activity may involve a dopaminergic mechanism.
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PMID:The effects of morphine- and nalorphine- like drugs in the nondependent and morphine-dependent chronic spinal dog. 94 47

In 22 dogs, we compared the protective effects of combining topical hypothermia and cardioplegia to those of either technique alone on myocardial flow, distribution, metabolism, compliance, and performance after 1 hour of aortic cross clamping. Topical hypothermia alone caused redistribution of coronary flow away from the subendocardium (endocardial/epicardial flow fell from 1.13 to 0.77) and reduced left ventricular compliance and performance severely (48% depression of ventricular function). Cardioplegia alone caused redistribution of flow toward the subendocardium (endocardial/epicardial flow increased to 1.4) and decreased compliance and function moderately (31% depression). In contrast, combined topical hypothermia and cardioplegia caused no significant change in left ventricular flow distribution, compliance, or performance. We concluded that the normal heart can be cross clamped safely for up to 60 minutes (no myocardial depression) only when cardioplegia and topical hypothermia are used in combination (P less than 0.01).
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PMID:Improved myocardial performance after aortic cross clamping by combining pharmacologic arrest with topical hypothermia. 99 19

Electrocardiogram changes and pharmacologic responses were studied in 28 cases of brain death. Cardiac activity in this condition is possibly determined by the dynamic balance between the depressant action of hypothermia and the stimulating action of the sympathetic nervous system (without any vagal or central influence). The electrocardiographic alterations are the results of this dual influence, and are probably characteristic of this condition. In the initial stage of brain death the ECG shows J waves in the terminal part of the QRS, prolongation of the QT interval and the ST-T changes; in the advanced stages, progressive showing of the heart rate and the depolarization and repolarization processes are observed (manifested by gradual accentuation of the findings mentioned above); in the terminal stage dynamic electrocardiographic changes (among them, progressive depression of sinus activity, atrial fibrillation, atrioventricular and intraventricular conduction disturbances and severe ST-T changes) appear. It is possible that additional factors, like metabolic changes and possible myocardial damage in some instances, may have some influence on the electrocardiographic pattern. Final conclusions cannot be drawn from these preliminary observations. The atropine test was found to be an efficient and simple diagnostic aid in cases of brain death.
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PMID:Electrocardiographic findings in brain death; description and presumed mechanism. 112 70

A total activity and isoenzyme spectrum of LDH from liver tissue were studied in rats, which were cooled down to the body temperature of 18-22 degrees and were kept in conditions of artificial hypobiosis for a long time (24 and 30 hrs). In cooled rats an increase in total LDH activity was observed. The increase might be a reflection of a stress-reaction to cooling since the method of developing of a hypobiosis involved an incomplete depression of thermoregulation. Subsequent extention of hypobiosis caused a gradual decrease in the total activity of LDH from liver tissue. The LDH activity reached values which were lower than the initial level. This phenomenon was probably due to attenuation of the stress-reaction and to a decrease in metabolic processes under effect of hypothermia. The alterations noted in the total LDH activity were determined by changes in the activity of a prevailing isoenzyme--LDH5. The increase in the LDH5 activity was assumed to be associated with activation of neoglucogenesis and determined by an orientation of the LDH-reaction in the direction of pyruvate.
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PMID:[Overall activity and isoenzymatic spectrum of liver lactate dehydrogenase in hypobiotic rats]. 113 98

The onset and duration of tolerance to three effects of delta9-tetrahydrocannabinol (delta9-THC) given orally to mice were compared. The effects of delta9-THC studied were: hypothermia, the depression of intestinal motility and the effect on spontaneous locomotor activity. When mice were dosed and tested at 24 hrs intervals it was apparent that tolerance was complete to its hypothermic and locomotor depressant effects after the first doses and to depression of intestinal motility after the fourth dose. Duration of tolerance also differed so that the normal hypothermic response had returned after 12 dose-free days, but not after 5 drug-free days; the effect on locomotor activity had returned within 4 days; and apparent partial tolerance to the depressant effect of an acute challenging dose of delta9-THC on intestinal motility still existed after 19 dose-free days. It is apparent that the time of onset and the duration of tolerance to delta9-THC in mice showed a different pattern in the three parameters studied. It seems unlikely therefore that any one mechanism, such as metabolic tolerance, explains all the results observed and that several mechanisms should be explored to explain the phenomenon of tolerance to delta9-THC.
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PMID:Tolerance to the effect of delta9-tetrahydrocannabinol in mice on intestinal motility, temperature and locomotor activity. 116 92

In 19 cats anesthetized with chloralose and urethrane, d-tubocurarine (d-TC) was continuously infused to produce constant 90% depression of twitch tension prior to injection of 5, 10 or 20 mug/kg of neostigmine. The required mean infusion rates of d-TC were 3.6 +/- 0.6, 5.1 +/- 0.3, 8.5 +/- 0.3 and 8.9 +/- 0.5 mug/kg/min at body and muscle temperatures of 28, 31, 37 and 41 degrees C, respectively. The doses of neostigmine needed for 50% antagonism of the d-TC-induced depression of twitch height were 8.7, 9.2, 10.5 and 12.0 mug/kg at 28, 31, 37 and 41 degrees, respectively. The time to peak effect and duration of action of 5 and 10 mug/kg of neostigmine were longer at 28 and 31 degrees C than at 37 and 41 degrees C. Although these times also were longer at 27 and 31 degrees C with the 20 mug/kg dose of neostigmine, they were not statistically different. We conclude that hypothermia augments a d-TC neuromuscular blockade. Hypothermia prolongs time-to-peak effect and duration of neostigmine but does not affect peak magnitude of antagonism of d-TC by neostigmine.
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PMID:The effect of temperature on a d-tubocurarine neuromuscular blockade and its antagonism by neostigmine. 118 93

In order to assess the long-term effects of cardiopulmonary bypass (CPB) in combination with pupular methods of myocardial protection, 37 dogs were placed on CPB for 100 minutes with the use of a bubble oxygenator without hemodilution. A separate group (I) of eight normal dogs served as a control for assessment of hemodynamic changes. The operative groups were as follows: II, continuous coronary perfusion with an empty, beating heart for 60 minutes at 35 degrees C.; III, hypothermic anoxic arrest (aortic occlusion) for 60 minutes with topical cold saline lavage (4 degrees C.); IV, anoxic arrest for 60 minutes at 35 degrees C. Subgroups of Groups III and IV received intracoronary perfusion with Ringer's lactate or Sacks' solution during aortic occlusion and were compared with those animals receiving no perfusion. Survival in Groups II and III was significantly better than in Group IV (82 and 92 per cent vs. 45 per cent). Coronary perfusion with Ringer's lactate or Sack's solution did not influence survival. The 23 survivors from all groups underwent left heart catheterization and LV cineangiography 5 months after operation. All three operative groups had significant elevation of LVEDP and depression of maximum developed dp/dt when compared with normal dogs. Ejection fraction was significantly depressed in Groups III and IV, and there was evidence of left ventricular hypokinesia and/or akinesia in all three operative groups. Differences in function between Groups II, III, and IV were not significant. The use of intracoronary solutions during anoxic arrest did not significantly influence these functional alterations. Evidence of subendocardial fibrosis was found in each of the operative groups, with the most marked changes found in the normothermic arrest group. Moderate fibrosis was present, however, in some survivors in both the continuous coronary perfusion and topical hypothermic arrest groups. These data indicate that although survival is greatly enhanced when coronary artery perfusion or topical hypothermia is used, neither method prevents chronic deterioration in ventricular function nor the development of subendocardial fibrosis.
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PMID:Long-term morphologic and hemodynamic evaluation of the left ventricle after cardiopulmonary bypass. A comparison of normothermic anoxic arrest, coronary artery perfusion, and profound topical cardiac hypothermia. 118 84

Depressed postoperative myocardial performance (low output syndrome) requiring inotropic drugs or balloon counterpulsation is due to subendocardial ischemic damage. Before July, 1972, we needed inotropic drugs in 30 to 52 per cent of 189 patients undergoing coronary revascularization or aortic or mitral valve replacement in whom we used ischemic arrest, profound topical hypothermia, and ventricular fibrillation. The mortality rate ranged from 10 to 17 per cent. Our experimental studies show that morbidity and death in such cases are caused by ischemic injury to the heart resulting from inadequate myocardial protection during bypass. Based on these experimental studies, we have, since July, 1972, employed the following principles clinically: (1) Maintain beating empty heart whenever possible; (2) maintain adequate coronary perfusion pressure (less than 80 mm. Hg); (3) avoid extreme hemodilution; (4) avoid ventricular fibrillation; (5) avoid prolonged hypothermic arrest, limiting ischemic periods to less than 15 minutes; (6) repay myocardial ischemic oxygen debt with total (vented) bypass; and (7) optimize DPTI/TTI (supply/demand ratio) pre- and postoperatively. These principles were followed in 189 consecutive operations, and postoperative inotropic drugs were needed in only 12. The principles were violated in 4 of the 12 patients (6 per cent), and 5 others had identifiable causes of myocardial depression; low output syndrome was unexplained in only 3 patients (1.7 per cent).
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PMID:Depressed postoperative cardiac performance. Prevention by adequate myocardial protection during cardiopulmonary bypass. 118 89

Experiment 1. The acute effects of delta9-THC (1.25, 2.50, 5.00, and 10.00 mg/kg) and delta8-THC (1.25, 2.50, 5.00, and 10.00 mg/kg) was an approximately equipotent, dose related depression of water intake in water-deprived rats. Animals given hashish, inhaled as smoke, showed a depression of water consumption comparable to rats given the highest dose of either of the synthetic THCs. Water intake after chevril smoke was similar to that seen after vehicle injections. Experiment 2. A dose related depression of water-and-food intake, and reduction of body weight with a gradual recovery was found in rats, maintained on a Limited Time of drinking schedule (LT, 2 hr) and subchronically (21 days) treated with delta9-THC (1.25, 2.50, or 5.00 mg/kg). From the 22nd day all animals were given the vehicle only for 10 days. There were no indications of withdrawal effects due to the drug termination. Reinstating the drug after the 10 day drug free period suggested an increased sensitivity to THC as compared to the 21st injection. Experiment 3. In non-deprived rats delta9-THC caused similar effect as in Exp. 2, although to less extent. From both experiments it is concluded that there is an inhibition or even loss of body weight and that food intake seems more severely depressed than water intake. The temperature recordings suggest that the predominant consequence of lower, behaviorally, effective doses of THC on rectal temperature of rats is hyperthermia rather than hypothermia. Initially this effect was most pronounced for the lowest dose (1.25 mg/kg) but with repeated injections the two higher doses (2.50 and 5.00 mg/kg) showed hyperthermia to the same extent as the lowest dose. Hypothermia was seen after a high dose of delta8-THC (20.00 mg/kg) but after 3 daily injections this effect was gone.
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PMID:Acute and subchronic influences of tetrahydrocannabinols on water and food intake, body weight, and temperature in rats. 118 35

The mechanism of the hypothermia produced in mice by the naturally occurring cannabinoids, delta9-tetrahydrocannabinol, cannabinol, and cannabidiol, was investigated by evaluating the direct effect of these drugs on the oxygen consumption of tissue homogenates and isolated mitochondria. The tissues studied were brain, liver, skeletal muscle, and heart; the mitochondrial preparations were limited to brain and skeletal muscle. The in-vitro studies included a description of the influence of various cannabinoid vehicles containing Tween 80, ethanol, Pluronic F68, and albumin on the oxygen consumption of tissue preparations. Of these vehicles, only albumin was without effect on all tissues. The other vehicles produced diverse responses, including some that were qualitatively different; the data illustrate that the influence of each vehicle on oxygen consumption must be defined for each tissue employed. In spite of the different vehicle effects, delta9-tetrahydrocannabinol generally reduced oxygen consumption of all tissue preparations; however, the vehicles were capable of modifying the dose-effect relationship. The results of all three drugs prepared in Pluronic F68 on brain and skeletal muscle indicated that the cannabinoids generally cause a dose-related depression of oxygen consumption. The findings demonstrate that the cannabinoids can directly decrease oxidative metabolism of tissue and isolated mitochondria and that a marked response occurs in the concentration range of 1 X 10(-5) to 1 X 10(-4) M. Because these concentrations can exist in tissues following the in-vivo administration of delta9-tetrahydrocannabinol, the results suggest that the depressant effect of the cannabinoids on metabolic rate may contribute to the mechanism of the hypothermia produced by the drugs.
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PMID:The influence of delta9-tetrahydrocannabinol, cannabinol and cannabidiol on tissue oxygen consumption. 119 14


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