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)

We examined phosphatidylcholine (PC) effects on the isolated rat heart subjected to low- or zero-flow ischemia followed by reperfusion. Untreated hearts subjected to 30 min of low-flow ischemia recovered 15% contractility following reperfusion compared to time-control hearts. Phosphatidylcholine (0.005%) addition either 10 or 20 min before ischemia significantly enhanced recovery to approximately 61% and reduced the incidence of arrhythmias during ischemia and reperfusion. Contracture during ischemia and reperfusion was significantly reduced when PC was added 20 min before ischemia. Phosphatidylcholine was ineffective when administered at the time of reperfusion except for a moderate reduction in arrhythmia development. Phosphatidylcholine also produced a salutary effect when added 20 min prior to zero-flow ischemia. Subsarcolemmal mitochondria (SLM) and, to a much lesser degree, interfibrillar mitochondria (IFM) of untreated hearts subjected to low-flow ischemia and reperfusion exhibited depressed oxidative phosphorylation which was prevented by PC. Both mitochondrial populations exhibited a marked depression in ADP/ATP translocase activity; however, this was generally unaffected by PC. Subsarcolemmal mitochondria but not IFM of zero-flow ischemic reperfused hearts also exhibited significantly depressed oxidative phosphorylation, which was unaffected by PC. Zero-flow ischemia produced a rapid and total cessation of contractility. Both populations exhibited a substantial PC-insensitive reduction in translocase activity. Our results demonstrate, for the first time, a protection by PC on the reperfused ischemic heart. The PC-induced protection following low-flow but not zero-flow ischemia is associated with improved SLM oxidative phosphorylation suggesting dissimilar contribution of mitochondria to reperfusion-associated myocardial injury.
J Cardiovasc Pharmacol 1990 Jan
PMID:Protection of the reperfused ischemic isolated rat heart by phosphatidylcholine. 168 76

Positive inotropic and chronotropic responses to (-)-isoprenaline were recorded in guinea pig isolated paced left and spontaneously beating right atria. Concentration-response curves were determined before and after incubation with 10(-6) M (-)-isoprenaline for various times from 0.5 to 8 h. Before construction of the postincubation curve, isoprenaline was washed from the tissue for either 0.5 or 1 h. Preincubation curves were corrected from controls for time-dependent changes in sensitivity. After a 2-h incubation with 10(-6) M isoprenaline and a 0.5-h washout, there was a significant rightward shift of the right atrial rate curve [concentration ratio (CR) 10.6 +/- 2.1]. This was reversed by extending the washout to 1 h. After a 4-h incubation, however, a poorly reversible desensitization occurred, the curve still being significantly shifted after a 1-h washout (CR, 17.4 +/- 6.2). A higher incubation concentration, 10(-5) M, appeared to produce greater desensitization as a depression of the maximum response, however, this was an artifact caused by the failure to wash the isoprenaline from the tissue. When left atria were paced throughout the incubation period, a substantial nonspecific depression of the maximum response to 73.7 +/- 7.6% occurred. When pacing was stopped during incubation, only a rightward shift of the curve was produced by incubation with isoprenaline (10(-6) M), with no change of maximum (96.5 +/- 6.3%). There was no cross-desensitization of histamine in either the left (unpaced while incubating) or right atria after a 4-h incubation period with isoprenaline (10(-6) M). The desensitization was therefore beta-adrenoceptor specific and of the homologous type. After an 8-h incubation, there was an additional depression of the postincubation maximum which was greater in the left (68.9 +/- 2.3%) than right atria (85.2 +/- 5.4%). This true reduction of the maxima indicates that desensitization had effectively removed a proportion of the beta adrenoceptors.
J Cardiovasc Pharmacol 1990 Feb
PMID:Desensitization of beta-adrenoceptor-mediated functional responses of guinea pig atria by in vitro incubation with isoprenaline. 168 22

Effects of three class I antiarrhythmic drugs (quinidine, lidocaine, and prajmaline) on transmembrane resting (RMP) and action potentials (AP) of isolated rabbit atrial and ventricular myocardium were studied at different stimulation rates. The frequency-dependent depression of the maximal upstroke velocity (Vmax) of the AP (sodium channel block) was analyzed according to the "guarded receptor" hypothesis. The resting block (Vmax depression after a resting period) induced by prajmaline (10(-6) M), quinidine (2.2 x 10(-5) M), and lidocaine (4.3 x 10(-5) M) was more expressed in the atrium (44, 28, and 19%, respectively) than in the ventricle (32, 9, and 0%, respectively). There were also significant (p less than 0.05) atrioventricular differences in the frequency-dependent extra block (Vmax reduction on stimulation at 3.3 Hz) for quinidine (39 vs. 26%) and lidocaine (4 vs. 25%). From the analysis, according to the guarded receptor hypothesis, it follows that the three compounds bind preferentially to inactivated sodium channels with about the same affinity to the atrium and ventricle, except for quinidine which shows a significantly smaller dissociation constant in the atrium (5 x 10(-6) M vs. 2.7 x 10(-5) M; p less than 0.001). We conclude that the atrioventricular differences in the resting block are mainly due to atrioventricular differences in the RMP, whereas the differences in the frequency-dependent extra block are based on the shorter atrial AP duration (lidocaine) or are due to higher affinity to atrial sodium channels (quinidine).
J Cardiovasc Pharmacol 1990 Feb
PMID:Comparative analysis of the action of class I antiarrhythmic drugs (lidocaine, quinidine, and prajmaline) in rabbit atrial and ventricular myocardium. 168 32

Amiodarone and its pharmacologically active metabolite desethylamiodarone have a sodium channel blocking action that explains some of their antiarrhythmic efficacy. However, the well-documented depression of the calcium channel-dependent sinus node and atrioventricular node function that occurs with amiodarone therapy suggests that amiodarone also blocks calcium influx through voltage-dependent calcium channels. Recent electrophysiologic data support the notion that amiodarone, but not desethylamiodarone, acts as a calcium channel antagonist. In this study, the effects of amiodarone and desethylamiodarone on calcium antagonist receptors associated with the voltage-dependent calcium channels were characterized. Amiodarone, but not its active metabolite desethylamiodarone, was a potent competitor at dihydropyridine and phenylalkylamine (verapamil-like) calcium antagonist binding sites in rat heart, brain, and skeletal and smooth muscles. Substantial inhibition of calcium antagonist binding was retained even after extensive washing of membranes and 2 days after in vivo treatment of rats with amiodarone. The pattern of inhibition of calcium antagonist binding suggests that amiodarone acts at phenylalkylamine binding sites. It is suggested that the acute effects of amiodarone--sinus and atrioventricular node inhibition, vasodilatation, and negative inotropic actions--may reflect calcium antagonist influences of amiodarone itself. Chronic effects of drug therapy, such as inhibition of ventricular conduction by sodium channel blockade, may selectively involve desethylamiodarone.
J Cardiovasc Pharmacol 1990 Mar
PMID:Differential effects of amiodarone and desethylamiodarone on calcium antagonist receptors. 169 76

Depression of rested state contractions (RSCs) and 0.1-0.25 Hz contractions by equianesthetic concentrations of isoflurane (2.5%), halothane (1.5%), and enflurane (3.5%) was studied in guinea pig papillary muscles in which tension development was enhanced by 0.1 microM isoproterenol. In a second series of experiments, an RSC was elicited, followed by a second contraction elicited with stimulus intervals of 300-600 ms. In both types of experiments, the results were similar. Halothane and enflurane depressed rapid initial tension development more than isoflurane. This initial tension development was also selectively depressed by 0.1 microM ryanodine, which specifically decreases Ca2+ release from the sarcoplasmic reticulum (SR). Isoflurane and also enflurane depressed a delayed and late peaking component of tension development, which was very prominent after rest and was depressed by 200 microM procaine or 500 microM benzocaine. Although isoflurane and enflurane were similar to the local anesthetics in depressing late tension, unlike the local anesthetics they prolonged the late phase of tension development as well. The late tension of the RSC is associated with Ca2+, which enters the rested myocyte on depolarization and may be transiently sequestered in the SR before release. Both early initial and late tension development are depressed to a similar degree by application of 10-20 nM nifedipine. These results emphasize the multiple differing actions of the volatile anesthetics on myocardial contractions, with halothane and isoflurane possessing distinct depressant characteristics.
J Cardiovasc Pharmacol 1990 Apr
PMID:Differential depression of myocardial contractility by volatile anesthetics in vitro: comparison with uncouplers of excitation-contraction coupling. 169 97

Despite its widespread clinical use, the precise mechanism of action of amiodarone (AMI) has not been completely defined. We examined the effects of AMI (20 micrograms/ml) on Vmax and on conduction velocity (theta) during longitudinal (LP) and transverse (TP) propagation with respect to fiber orientation, in 10 strips of uniform anisotropic epicardial muscle obtained from the left ventricle of adult canine hearts. Mean values +/- SEM (standard error of the mean) were calculated as normalized values (beat 50/beat 1) after 4 h of AMI superfusion at five different basic cycle lengths (BCL). Vmax decreased from 0.99 +/- 0.01 at a BCL of 5,000 ms to 0.43 +/- 0.03 at a BCL of 300 ms during LP. During TP, Vmax decreased from 0.99 +/- 0.01 at a BCL of 5,000 ms to 0.54 +/- 0.05 at a BCL of 300 ms. The differences in the relative changes between both directions at a BCL of 300 ms, as well as at intermediate values of 1,000, 500, and 400, were significant (p less than 0.01). theta during LP (theta L) was depressed from 0.99 +/- 0.01 at a BCL of 5,000 ms to 0.80 +/- 0.04 at a BCL of 300 ms. In contrast, theta during TP (theta T) did not change as the BCL was decreased. In consequence, theta L was significantly more depressed than theta T at BCLs shorter than 1,000 ms (p less than 0.05). Moreover, theta T after AMI was not statistically different from control at any BCL studied. The lack of depression of theta T associated with a marked depression of Vmax during either LP or TP suggests that in addition to its sodium channel blocking properties, AMI could produce a decrease in the effective axial resistivity.
J Cardiovasc Pharmacol 1990 Jun
PMID:Differential effects of amiodarone on Vmax and conduction velocity in anisotropic myocardium. 169 14

The hemodynamic effects of the calcium antagonist isradipine (code name PN 200-110) and the arteriolar vasodilator dihydralazine were compared in atherosclerotic (cholesterol-fed) and normal conscious rabbits with implanted catheters. Regional blood flows were measured using the microsphere technique. Cardiac output and blood flow to several organs, especially to the gastrointestinal system, but not to the heart and brain, were lower in atherosclerotic rabbits than in normal ones. Intravenous isradipine (10 and 30 micrograms/kg) increased heart rate less in atherosclerotic than in normal rabbits. Isradipine had no effect on the surface electrocardiogram (ECG). In contrast, 0.4 mg/kg dihydralazine caused depression of the ST segment while decreasing blood pressure similarly. This was explained partly by an intramyocardial maldistribution of coronary blood flow (using microspheres). Isradipine increased and dihydralazine decreased flow to the brain. Isradipine redistributed cardiac output in atherosclerotic and normal animals in favor of the heart, brain, and skeletal muscle. However, in atherosclerotic animals, the high dose was less effective than the low dose in some vascular beds. Thus, isradipine is not a general vasodilator in either atherosclerotic or in normal animals, but favors the vital organs. This redistribution of cardiac output contrasts favorably with that induced by dihydralazine.
J Cardiovasc Pharmacol 1990
PMID:Comparative hemodynamic studies of isradipine and dihydralazine in atherosclerotic and normal rabbits. 169 97

Calcium antagonists retard the development of atherosclerosis in cholesterol-fed rabbits and modestly enhance regression after their return to a normal diet. Proliferative lesions following endothelial damage (from, for example, balloon catheter, electrical stimulation) are also diminished. Many mechanisms for these effects have been proposed and their relative importance is not yet clear. However, changes in blood lipid levels do not play an important role. Only a few investigations into how atherosclerosis affects the hemodynamic actions of calcium antagonists have been carried out. Thus, the effects of isradipine were compared in atherosclerotic and normal rabbits. Isradipine increased heart rate and cardiac output less in atherosclerotic rabbits than in normal ones while having no effect on the surface electrocardiogram (ECG). In contrast, the arteriolar vasodilator, dihydralazine, induced ST-segment depression with similar falls in blood pressure, partly explainable by reflex tachycardia and intramyocardial maldistribution of coronary blood flow. Flow to the brain increased with isradipine and decreased with dihydralazine. In atherosclerotic animals, the pressor effects of norepinephrine, phenylephrine, and angiotensin II (Ang II) were amplified. Isradipine partly corrected this enhanced responsiveness. Calcium antagonists thus elicit beneficial hemodynamic and antivasoconstrictor effects in atherosclerotic experimental animals, in addition to having a long-term prophylactic antiatherosclerotic action.
J Cardiovasc Pharmacol 1990
PMID:Hemodynamic, antivasoconstrictor, and antiatherosclerotic effects of calcium antagonists in animal models of atherosclerosis. 169 7

We studied the short-term effects of oral administration of nisoldipine (10 mg) and propranolol (80 mg) alone and in combination in 14 patients with chronic exertional angina pectoris in a double-blind, randomized, cross-over study. The 14 patients (13 men and 1 woman, mean age 56 +/- 7 years) performed symptoms-limited bicycle exercise stress test 3 h after placebo or active substance administration. Maximal work load, exercise duration, and time to 1-mm ST segment depression were significantly increased and ST depression at peak exercise was significantly decreased by drugs alone and in combination. Propranolol and nisoldipine alone improved exercise duration similarly and as well as the combination; however, a different response to the three pharmacologic interventions was found in patients treated with single drugs. The improvement in exercise tolerance was associated with rate-pressure product values at peak exercise, unchanged after nisoldipine and significantly reduced after both propranolol alone and in combination. After placebo, all patients had exercise-induced angina, in 9, 8, and 4 patients after nisoldipine, propranolol, and the combination of the two drugs, respectively. Nisoldipine is effective in the treatment of effort angina and its combination with propranolol may be useful and superior in patients who show poor response to monotherapy.
J Cardiovasc Pharmacol 1990 Aug
PMID:Acute effects of nisoldipine, propranolol, and their combination in patients with chronic stable angina: a double-blind, randomized, cross-over, placebo-controlled study. 169 90

In a double-blind cross-over study, 10 patients with stable angina pectoris owing to coronary heart disease were investigated in supine position during rest and bicycle exercise for the effect of 0.4 mg of intravenous (i.v.) isradipine in comparison to 2 mg i.v. nifedipine on cardiac hemodynamics and myocardial ischemia. At rest, both drugs significantly decreased total peripheral resistance (TPR) and mean arterial blood pressure (MAP), whereas heart rate (HR) increased. The pressures and resistance of the pulmonary circulation remained uninfluenced at rest. During symptom limited-exercise, both medications reduced TPR despite an unchanged MAP. Mean pulmonary artery pressure decreased significantly after both medications, whereas right atrial pressure (RAP), pulmonary capillary wedge pressure (PCWP), and pulmonary vascular resistance (PVR) decreased significantly only after nifedipine. The improvement of mean ischemic ST-segment depression averaged 44 +/- 6% (mean +/- SEM, p less than or equal to 0.01) after nifedipine and 45 +/- 7% (p less than or equal to 0.01) after isradipine. The time until angina appeared increased after isradipine by 89 +/- 28% (p less than or equal to 0.05) and after nifedipine by 105 +/- 42% (p less than or equal to 0.01). Significant differences between the two medications appeared only for cardiac output (CO) at rest (p less than or equal to 0.05), during which state the increase after isradipine was higher than after nifedipine, and for exercise HR (p less than or equal to 0.01), during which state only nifedipine induced a significant increase in frequency. We conclude that at the chosen dosages the hemodynamic and antiischemic effects of isradipine are similar to the effects that occur after nifedipine.
J Cardiovasc Pharmacol 1990 Nov
PMID:Antiischemic and hemodynamic effects of intravenous isradipine, a new calcium antagonist, in coronary heart disease: a comparative double-blind cross-over study with nifedipine. 170 98


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