Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0151744 (myocardial ischemia)
31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Results are reported of a study of the lipid peroxidation (LP) in 33 patients with ischemic heart disease (IHD), hypertensive disease (HD) and their associations during anaprilin treatment. During deterioration of the course of HD and IHD there occurs initiation of LP of membranes most pronounced in association of these diseases. Anaprilin reduces the activity of LP products.
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PMID:[The dynamics of lipid peroxidation in patients with ischemic heart disease and hypertension during anaprilin treatment]. 227 64

We hypothesized that the antiarrhythmic efficacy of propranolol during acute myocardial ischemia could be dose related. Propranolol was administered in two equally divided doses 30 min before and 10 min after ligation of the anterior descending coronary artery (CAL) in anesthetized open-chest pigs. Only the lowest dose of propranolol, i.e., 0.1 mg/kg intravenously (i.v.) (plasma level 22 +/- 2 ng/ml) decreased the incidence of ventricular fibrillation (VF), i.e. 3 of 12 versus 16 of 20 in control group (p less than 0.01). VF incidence with propranolol 0.5 or 3 mg/kg was 4 of 6 and 8 of 9, respectively (both NS vs. control group). Propranolol 0.1 mg/kg did not change left ventricular (LV) blood flow. Propranolol 3 mg/kg reduced blood flow in the peripheral ischemic myocardium to 13.2 +/- 1.2 versus 19.2 +/- 1.4 ml/100 g/min in control group (p less than 0.01), and in the midischemic zone to 4.4 +/- 0.5 versus 7.0 +/- 0.9 ml/100 g/min in control group (p less than 0.001). Propranolol 0.1 mg/kg prevented a disparity of levels of cyclic AMP from arising between ischemic and non-ischemic myocardium, whereas propranolol 3.0 mg/kg did not. Furthermore, LV mechanical function was suppressed by propranolol 3 mg/kg. Only the lowest dose of propranolol (i.e., 0.1 mg/kg) decreased the incidence of VF in this model.
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PMID:Critical role of dose in protection by propranolol against ventricular fibrillation in a pig model of acute myocardial ischemia. 246 45

We have previously reported that alpha 2-adrenoceptor stimulation enhances adenosine-induced coronary vasodilation. In the present study, we tested the hypothesis that alpha 2-adrenoceptor activity exerts beneficial effects on myocardial ischemia through augmentation of vasodilatory effects of released adenosine. In open-chest dogs, the left anterior descending coronary artery was perfused through an extracorporeal bypass tube from the carotid artery. Propranolol was infused into the bypass tube to exclude the metabolic effects of norepinephrine. When clonidine (0.24 micrograms/kg/min i.c.) was infused for 10 minutes after reduction of coronary blood flow by partial occlusion of the bypass tube, coronary blood flow was increased by 43% from 27 +/- 1 ml/100 g/min despite no changes in coronary perfusion pressure (38 +/- 5 mm Hg) and a slight decrease in adenosine release. Both fractional shortening and lactate extraction ratio of the perfused area were significantly improved (fractional shortening, 1.8 +/- 1.0 to 10.9 +/- 1.5%, p less than 0.001; lactate extraction ratio, -57.8 +/- 6.5 to -31.9 +/- 2.4%, p less than 0.005). Identical results were observed in the denervated hearts, indicating that the beneficial effect of clonidine is not attributed to the prevention of norepinephrine release from the sympathetic nerve terminals. The beneficial effects of clonidine were prevented by yohimbine, an alpha 2-adrenoceptor blocking agent. An adenosine receptor antagonist, 8-phenyltheophylline, also prevented the beneficial effects of clonidine, indicating that these beneficial effects are mediated by effects of adenosine. Furthermore, the extent of augmentation of coronary flow in the ischemic heart was coincided with that of augmentation of exogenous adenosine-induced hyperemic flow (40%) by clonidine. Production of cyclic AMP in the coronary artery during myocardial ischemia was augmented by clonidine. In 12 other dogs, myocardial ischemia was produced by intracoronary embolization of microspheres (15 microns in diameter). Clonidine enhanced (39%) the hyperemic coronary flow and improved both fractional shortening and lactate extraction ratio. Thus, we conclude that alpha 2-adrenoceptor stimulation can ameliorate myocardial ischemia mainly due to enhancement of vasodilatory effects of adenosine released from the ischemic myocardium.
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PMID:Beneficial effects of alpha 2-adrenoceptor activity on ischemic myocardium during coronary hypoperfusion in dogs. 255 78

The influence of cold on the threshold for myocardial ischemia and the efficacy of antianginal drugs in a cold environment were assessed in 24 patients with stable angina and exercise-induced ST depression. Treadmill exercise tests were done according to a randomized double-blind protocol 90 minutes after administration of placebo, 80 mg propranolol, or 120 mg diltiazem, each at both -8 degrees and 20 degrees C. Eight of the patients were classified by history as cold-sensitive before the study. For the entire group, none of the exercise end points differed significantly between cold and normal temperatures with placebo. However, cold-sensitive patients developed 1 mm ST depression 30% sooner (169 +/- 41 versus 244 +/- 38 seconds, p less than 0.01) at -8 degrees C compared with 20 degrees C. At the onset of ischemia, rate-pressure product was lower in the cold (19.8 +/- 1.0 versus 22.0 +/- 1.6 x 10(-3), p less than 0.05). Both propranolol and diltiazem prolonged time to onset of 1 mm ST depression at both temperatures. The magnitude of improvement at -8 degrees C was equal to that at 20 degrees C, and differences between the two drugs were not statistically significant. Only diltiazem prolonged total exercise duration. Thus, as assessed by exercise testing, cold does not worsen ischemic threshold in most stable angina patients. However, in a subgroup identifiable by history, ischemic threshold is lower in the cold. Propranolol and diltiazem are as effective for exercise-induced ischemia in a cold environment as at normal temperatures.
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PMID:Exercise-induced myocardial ischemia in a cold environment. Effect of antianginal medications. 271 70

The effects of beta-blocking and class I antiarrhythmic agents on free radical-mediated sarcolemmal lipid peroxidation were examined. Highly purified canine myocytic sarcolemmal membranes were pretreated with 10-800 microM of selected beta-blocking (propranolol, pindolol, metoprolol, atenolol, or sotalol) and class I (quinidine, lidocaine, procainamide, or diphenylhydantoin) antiarrhythmic agents at 37 degrees C for 10 minutes. Subsequently, a superoxide radical (derived from dihydroxyfumarate) driven, Fe3+-ADP catalyzed free radical generating system was added and incubated for up to 45 minutes. Lipid peroxidation of sarcolemma was determined by malondialdehyde formation. Pretreatment of the membranes with the five beta-blockers resulted in various degrees (20-95%) of inhibition of sarcolemmal peroxidation in a concentration- and time-dependent manner. All the class I agents were less effective (less than 20% inhibition). The order of potency of the beta-blockers was propranolol greater than pindolol greater than metoprolol greater than atenolol greater than sotalol and appeared to relate to their degree of lipophilicity. Propranolol, the most potent agent, achieved half-maximal inhibition of peroxidation at about 100 microM and achieved significance (p less than 0.01) at 20 microM. At pH 6.0, the efficacy of pindolol, metoprolol, atenolol, and sotalol diminished by 30-50% compared to pH 7.2, but the potency of propranolol remained unchanged. Since increased free radical production may occur during myocardial ischemia/reperfusion injury, the above findings suggest that the lipophilic beta-blockers may provide additional antiperoxidative protection of ischemic tissue.
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PMID:Protection by beta-blocking agents against free radical-mediated sarcolemmal lipid peroxidation. 289 7

In 16 patients undergoing angioplasty of the left anterior descending coronary artery, the clinical, electrocardiographic, and hemodynamic effects of short-term intravenous nonselective beta-adrenergic blockade with propranolol (0.1 mg/kg) were assessed during temporary occlusion of the artery. Myocardial ischemia during coronary occlusion was prevented, delayed in onset, or diminished in magnitude by propranolol in 10 of the 16 patients. Propranolol decreased values for indexes of myocardial oxygen demand, such as heart rate and blood pressure and their product, in all patients. Surprisingly, in patients who derived clinical benefit, propranolol did not change indexes of myocardial oxygen supply to the left ventricular region perfused by the occluded artery. For example, great cardiac vein flow (40 +/- 15 to 41 +/- 17 ml/min, p = NS) and coronary collateral resistance (2.1 +/- 1.0 to 2.1 +/- 1.1 mm Hg/ml/min, p = NS) were unchanged. In contrast, a worsening of supply occurred in patients who were not benefited: great cardiac vein flow (50 +/- 10 to 39 +/- 6 ml/min, p less than .05) decreased and coronary collateral resistance (1.6 +/- 0.5 to 2.0 +/- 0.6 mm Hg/ml/min, p less than .05) increased. Information obtained from this study demonstrates the value of this new experimental preparation in helping assess potential clinical effectiveness of drug interventions during the initial phase of acute coronary occlusion and providing insight into the mechanisms of drug effect.
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PMID:Effect of propranolol on myocardial ischemia occurring during acute coronary occlusion. 293 33

Purified sarcolemmal and light vesicle (intracellular) fractions of beta-adrenergic receptors were used to examine the effects of propranolol on receptor translocation in guinea pig heart. Guinea pigs were given propranolol (0.15 mg/kg/hr) via minipumps for 7 days and either killed or made ischemic for 1 hour via a coronary ligature. Propranolol treatment led to an externalization of beta-receptors from light vesicle to sarcolemmal fractions. This externalization increased the number of surface beta-adrenergic receptors that were functional, as assessed by isoproterenol-stimulated adenylate cyclase activity. After chronic propranolol treatment, ischemia did not further alter receptor distribution. These results suggest that externalization of beta-adrenergic receptors from a light vesicle fraction to the sarcolemma contributes to up-regulation of beta-receptors that occur in response to both propranolol treatment and ischemia. Because propranolol-treated animals show blunting in externalization after myocardial ischemia, propranolol treatment and myocardial ischemia appear to access the same pool of intracellular beta-adrenergic receptors. Depletion of this pool of receptors along with receptor blockade may thus contribute to the mechanism by which the drug is efficacious in preventing some adverse effects of ischemia.
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PMID:Propranolol treatment externalizes beta-adrenergic receptors in guinea pig myocardium and prevents further externalization by ischemia. 303 72

Propranolol is a commonly used drug; of new and refilled prescriptions, it ranked no. 1 in 1984 and no. 2 in 1985. Medical conditions for its use include angina pectoris, myocardial infarction, hypertension, cardiac dysrhythmias, hypertrophic subaortic stenosis, migraine headache, hyperthyroidism, and pheochromocytoma. Almost all dental practitioners will treat a patient receiving propranolol for one of these conditions. The following recommendations seem appropriate at this time: The patient should continue to receive propranolol during dental treatment. Sudden withdrawal of the beta-blocker will cost the patient the benefit of propranolol therapy and may lead to acute myocardial ischemia. Acute stress should be minimized, as hypertensive responses may also be caused by endogenously released epinephrine. Short appointments scheduled in the morning, possibly with conscious sedation, should be considered. The dosage of adrenergic vasoconstrictors should be limited and gingival retraction cord containing epinephrine avoided entirely. The blood pressure should be taken approximately 5 minutes after local anesthesia is administered to determine if a systemic response has occurred. In the unlikely event of a hypertensive emergency, a rapidly acting, short-duration antihypertensive drug, such as the alpha-blocker phentolamine (Regitine, 5 mg intravenously) should be administered. Sublingual nitroglycerin (Nitrostat, 0.4 mg) may be useful as a nonparenteral alternative. These recommendations apply to other nonselective beta-blockers, including nadolol (Corgard) and timolol (Blocadren). They may also apply to labetalol (Normodyne, Trandate), a nonselective beta-antagonist with some alpha-blocking activity and to pindolol (Visken), a beta-blocker with some intrinsic beta 2-agonistic activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hypertensive response to levonordefrin in a patient receiving propranolol: report of case. 327 28

Intravenous picrotoxin injection has been established as a model of producing arrhythmias, mainly through enhanced central sympathetic outflow. The effects of calcium-channel blockers, and a beta-blocker on these arrhythmias were tested in chloralose-anesthetized cats. Picrotoxin (10 mg/kg, i.v.) produced mostly ventricular, sometimes supraventricular tachycardias and ectopic beats, as well as a marked elevation of arterial blood pressure. Nifedipine at the doses of 2 micrograms/kg (i.v. or i.c.) and 5 micrograms/kg (i.v.) transiently suppressed the arrhythmias in some of the cats tested. With the dose of 10 micrograms/kg (i.v.), it promptly and consistently abolished the arrhythmias without recurrence and significantly reduced the blood pressure (-62 +/- 8/-59 +/- 8 mmHg, delta systolic pressure/delta diastolic pressure, p less than 0.001, n = 9). A similar degree of blood pressure reduction (-69 +/- 8/-67 +/- 7 mmHg, n = 6) after sodium nitroprusside (4-5 mg/kg, i.v.) injection abolished the arrhythmias in 4 of 6 cats; however, there was marked ECG evidence of myocardial ischemia in 3 cats. Verapamil (50 micrograms/kg, i.v.) transiently abolished the arrhythmias and significantly decreased the blood pressure (7/7 cats), whereas a larger dose (150 micrograms/kg) had a persistent effect (2/4 cats). Propranolol at a dose of 240 micrograms/kg also consistently abolished the arrhythmias without recurrence in all 4 cats. We conclude that nifedipine, verapamil and propranolol are effective in the treatment of picrotoxin-induced arrhythmias. This result indicates that calcium-channel blockers or beta-blockers may be clinically effective in the treatment or prevention of arrhythmias caused by intracranial lesions with enhanced sympathetic outflow.
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PMID:Effects of calcium-channel blockers on picrotoxin-induced centrogenic arrhythmias in cats. 339 56

Membrane damage caused by phospholipase A action is thought to be an important factor in ischemic myocardial injury. Propranolol has been shown previously to have beneficial effects in both animal experiments and clinical trials, and it has membrane-stabilizing properties in vitro. To investigate the possibility that these effects might be due, in part, to effects on phospholipases, we determined the effects of propranolol on rat heart phospholipases A at physiological pH using small unilamellar liposomes of di[1-14C]oleoylphosphatidylcholine as substrate. Propranolol inhibited heart phospholipases A in vitro. The concentration required to give 50% inhibition was 0.2 mM for the mitochondrial and cytosolic phospholipases A and 2.9 mM for sarcoplasmic reticulum phospholipase A. The binding of [4-3H]propranolol to fresh membrane preparations was studied using an ultracentrifugation method. Propranolol bound readily to both membrane fractions in vitro with no significant difference in the saturation number (0.20 to 0.28 mol drug per mol phospholipid) but the association constant, KA, was higher for mitochondrial membranes (3760 +/- 350) than for the sarcoplasmic reticulum (2190 +/- 390). Our results show that propranolol inhibited heart phospholipases A in vitro at physiological pH. The mitochondrial and cytosolic phospholipases A were more susceptible to inhibition than the phospholipase A of sarcoplasmic reticulum. Propranolol bound to mitochondria and sarcoplasmic reticulum in vitro, suggesting the possibility that propranolol binding to heart membranes in vivo could result in drug concentrations in these membranes high enough to inhibit phospholipase A. This could represent an additional mechanism by which propranolol exerts beneficial effects in myocardial ischemia.
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PMID:Propranolol inhibition of the neutral phospholipases A of rat heart mitochondria, sarcoplasmic reticulum and cytosol. 368 50


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