Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An abnormal resting ST segment renders the stress ECG impossible to interpret. Therefore, one must substitute a radionuclide stress evaluation in the presence of digitalis, left bundle-branch block, left ventricular hypertrophy, a paced rhythm, or any other condition that would cause abnormal baseline ST segments. All these are more common in the elderly. Beta-blocker therapy is useful in patients with demand-related ischemia because it decreases two of the major determinants of myocardial oxygen demand: heart rate and contractility. Propranolol, timolol, and metoprolol have been shown to decrease the reinfarction and mortality rates in patients who have had an infarction.
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PMID:Angina: current approaches to diagnosis, drug therapy, and surgical referral. 286 6

This paper describes a method by which antianginal drugs can be evaluated in the dog heart in situ. Myocardial pH was measured continuously by a micro glass pH electrode inserted in the left ventricular endocardial layers of the dog anesthetized with pentobarbital. Occlusion of the left anterior descending coronary artery (LAD) decreased myocardial pH, and release of the LAD restored the pH. The myocardial acidosis induced by ischemia was metabolic in nature and accompanied by a decrease in the levels of adenosine triphosphate and creatine phosphate and an increase in the levels of lactate in the myocardium. Drugs were injected intravenously 30 min after incomplete (partial) occlusion ot the LAD, lasting until 60 min after drug injection. Propranolol, atenolol, and sotalol markedly attenuated the myocardial pH that had been decreased by LAD occlusion. Nitroglycerin, diltiazem, and nicorandil also attenuated the pH, but these drugs were less active in attenuating myocardial acidosis. Dipyridamole, nifedipine, and beta-2 adrenoceptor antagonists were least active in this regard. It is concluded that myocardial pH can be used as an indicator of myocardial regional ischemia and utilized for evaluation of antianginal drugs.
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PMID:A method for evaluating antianginal drugs in experimental animals: assessment of myocardial ischemia by myocardial pH. 287 74

The effect of beta-adrenoceptor blockade and activation on ischemic regional and microregional myocardial O2 supply/consumption parameters was assessed in 28 open chest, anesthetized dogs. Ten minutes after LAD occlusion, dogs were given i.v. saline, 2 mg/kg propranolol, 0.2 mg/kg pindolol, or 1 microgram/kg per min isoproterenol. Coronary blood flow was determined using radioactive microspheres before and 2 h after LAD occlusion while O2 supply/consumption parameters were determined using microspectrophotometry. Ischemia resulted in a 66% reduction in subendocardial flow in controls in the ischemic zone and no experimental treatment significantly altered this flow. Pindolol resulted in a significant improvement in the ischemic regional subendocardial/subepicardial flow ratio (from 0.69 in the control ischemic region to 0.88 during pindolol treatment). O2 extractions were significantly increased and O2 consumptions were significantly depressed in the ischemic regions of all groups. O2 extractions were increased to a lesser degree in the ischemic region with the use of pindolol and propranolol. Propranolol and pindolol both significantly decreased the proportion of veins with low (0-20%) O2 saturations in the ischemic region indicating an improved microregional distribution of blood flow and/or O2 consumption within the ischemic region.
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PMID:Beta-adrenoceptor stimulation and blockade during myocardial ischemia in dogs: effect on cardiac O2 supply and consumption. 289 41

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

The effects of nifedipine (60 to 90 mg/day) and propranolol (240 mg/day) on symptoms, angina threshold and cardiac function were compared in a placebo-controlled, double-blind, crossover study. Five-week treatment periods with nifedipine and propranolol were compared with 2 weeks of placebo treatment in 21 men with chronic stable angina pectoris, 13 of whom had symptoms both at rest and on exertion. Compared with placebo, New York Heart Association functional class improved in patients equally with nifedipine (p = 0.001) and propranolol (p = 0.006). Frequency of chest pain decreased with nifedipine (p = 0.001) and propranolol (p = 0.01), and nitroglycerin consumption similarly decreased with both treatments. Nifedipine significantly delayed the onset of chest pain (p = 0.01) and 1 mm of ST-segment depression (p = 0.002) during bicycle exercise; smaller increases with propranolol were not statistically significant. A preferential clinical response to nifedipine (9 patients) or propranolol (6 patients) was unrelated to the presence or absence of pain at rest or to any baseline hemodynamic finding. Nifedipine and propranolol were equally effective in relieving exertional ischemia as shown by improvements in ejection fraction at identical workloads, from 0.48 +/- 0.11 to 0.58 +/- 0.12 (p less than 0.001) and 0.56 +/- 0.14 (p less than 0.001), respectively. Exercise wall motion, assessed by a semiquantitative wall motion score, also improved with both drugs. Propranolol treatment decreased exercise cardiac output by 14% (p = 0.01) through its effect on heart rate. In contrast, nifedipine treatment had no effect on cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of nifedipine alone with propranolol alone for stable angina pectoris including hemodynamics at rest and during exercise. 308 64

The effect of epinephrine in dogs with hypokalemia was investigated. Injection of epinephrine, 10 micrograms/kg, induced an elevation of serum creatine kinase (CK) activity and histological changes in myocardium of dogs with hypokalemia. The effect of epinephrine was little in dogs with normokalemia. Heart mitochondrial calcium content was elevated in parallel with the decrease in serum K+ in dogs with hypokalemia. Propranolol, a beta-blocker, did not prevent these changes. Since epinephrine increases coronary blood flow, these alterations cannot be ascribed to a reduction in coronary blood flow. It is likely that calcium overload alone, without ischemia, could develop myocardial injury in dogs with hypokalemia, and that beta-adrenergic action is not involved in this pathogenesis.
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PMID:Failure of beta-blocking agent to prevent epinephrine-induced myocardial injury in dogs with hypokalemia. 322 23

The effect of MCl-176 [2-(2,5-dimethoxyphenylmethyl)-3-(2-dimethylaminoethyl)-6- isopropoxy-4(3H)-quinazolinone hydrochloride], a novel calcium channel blocker, on ischemic myocardial acidosis was studied in the dog heart, in which the left anterior descending coronary artery was partially occluded for 90 min (partial occlusion). Myocardial pH (measured by a micro glass pH electrode) was about 7.60 in the nonischemic normal heart. The myocardial pH decreased rapidly in response to partial occlusion, and reached the steady state of about 6.85 within 30 min (i.e., the myocardial [H+] increased after partial occlusion). Saline or drug was injected i.v. 30 min after partial occlusion, and the drug effect was observed till the end of partial occlusion. Myocardial [H+], that had been increased by partial occlusion, restored slightly after the saline injection, and the restoration was about 30% 60 min after the injection. MCl-176 increased this spontaneous restoration of myocardial [H+] with a decrease in blood pressure and heart rate; the restoration induced by 0.1 mg/kg of MCl-176 was 74% 60 min after the injection. Even in the paced heart, MCl-176 (0.1 mg/kg) attenuated the ischemia-induced myocardial acidosis. Propranolol (1 mg/kg) also attenuated the myocardial acidosis, the restoration being 82%. These results indicate that MCl-176 attenuates the myocardial acidosis during ischemia as does propranolol, and that the mechanism of action of MCl-176 is not due primarily to a decrease in heart rate.
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PMID:MCl-176, a novel calcium channel blocker, attenuates the ischemic myocardial acidosis induced by coronary artery occlusion in dogs. 336 49

Propranolol has been shown to exert a protective effect in experimental myocardial, renal, and early acute focal cerebral ischemia. However, propranolol was not found to reduce infarct size in nitrous oxide-anesthetized, paralyzed, mechanically ventilated cats subjected to 6 hours of acute focal ischemia. The objective of the current investigation was to study further the effects of racemic (d,l)-propranolol on the evolution of acute focal cerebral ischemia in awake, conscious cats. Adult cats were anesthetized with halothane and underwent the implantation of an occluding device around the right middle cerebral artery. After a 48-hour recovery period, the right middle cerebral artery was occluded for 6 hours and then reopened, allowing reperfusion for an additional 6 hours. Neurological examinations were conducted every 2 hours throughout each experiment. Ten cats received d,l-propranolol (2 mg/kg) 1 hour before occlusion, immediately before occlusion, and every 2 hours throughout each experiment. Eleven cats serving as controls were not treated. The neurological examination significantly improved over time in the treated group when compared to the untreated group (P = 0.01). Carbon filling defects, gross brain swelling, and infarct size were reduced in treated cats. The results of this study suggest that propranolol does have beneficial effects in acute focal cerebral ischemia.
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PMID:Improved neurological outcome in experimental focal cerebral ischemia treated with propranolol. 396 Feb 88

To study the regional function of nonischemic myocardium after the onset of regional ischemia, graded circumflex coronary arterial stenosis was induced in 18 open-chest anesthetized dogs. Two-dimensional echocardiographic views were obtained at each degree of occlusion in a cross-sectional plane marked by two to three metal beads sewn to the left ventricular epicardium. Percent systolic thickening was measured at 16 equally spaced points around the left ventricle and correlated with microsphere-determined regional myocardial blood flow. Baseline thickening averaged 44.9 +/- 6.4%. During transmural ischemia percent systolic thickening decreased to -16.1 +/- 4.0% in the ischemic region and also decreased in adjacent nonischemic regions (to 2.4 +/- 2.4% in segments closest to the ischemic region [adjacent 1] and to 15.5 +/- 3.9 in segments further away [adjacent 2]), but was unchanged in segments directly opposite the ischemic region (remote region). During subendocardial ischemia, percent systolic thickening fell only in the ischemic and adjacent 1 regions (1.4 +/- 5.2% and 24.9 +/- 5.0%, respectively). Dipyridamole, 0.21 to 0.42 mg/min iv, given to seven dogs during transmural ischemia, caused a three- to fivefold increase in flow to the nonischemic and no change in flow to the ischemic region; function was not altered in any region. Propranolol, 0.1 mg/kg iv, was given to five dogs during transmural ischemia to depress contractility in the remote region. Percent systolic thickening fell in the remote (from 50.0 +/- 7.7% to 34.6 +/- 5.6%), but increased in adjacent 1 (from -0.25 +/- 3.7% to 15.2 +/- 3.9%) and in adjacent 2 (from 17.4 +/- 2.8% to 33.4 +/- 3.9%) regions, and remained unchanged in the ischemic region. We conclude the following: During transmural ischemia percent systolic thickening is markedly impaired in nonischemic myocardium immediately adjacent to the ischemic region, and is impaired to a lesser degree in regions located relatively far from the ischemic border. Dysfunction therefore overestimates the extent of regional ischemia after total coronary occlusion. During subendocardial ischemia function ceases in the ischemic region and functional impairment of nonischemic myocardium is restricted to immediately adjacent regions. Dysfunction of adjacent regions is not caused by "relative ischemia" related to increased local oxygen demands or to a steal phenomenon. Mechanical tethering of nonischemic myocardium adjacent to ischemic regions, secondary to changes in left ventricular shape during contraction, may contribute to the impairment of systolic thickening in adjacent regions during transmural ischemia.
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PMID:Impaired thickening of nonischemic myocardium during acute regional ischemia in the dog. 398 75

The relative extent of myocardial infarction produced by occlusion of the left anterior descendens coronary artery in anesthetized dogs was determined under control conditions or following treatment (4 h after ligation) with propranolol (1 mg/kg), bevantolol (3 mg/kg) or N-dimethyl propranolol (10 mg/kg). Doses of drugs were selected to provide similar reductions in heart rate, aortic blood pressure and contractility. Infarct size was estimated indirectly from levels of plasma creatine phosphokinase and measured histochemically by nitroblue tetrazolium stain. A significant ( p < 0.001) correlation between methods was found. Propranolol and bevantolol (beta adrenergic antagonists) produced a significant (p < 0.05) reduction (approximately 50% decrease) in infarct size, measured at 8 h following induction of ischemia, while N-dimemthyl propranolol (no beta antagonist activity) produced no effect. While all three agents produced similar hemodynamic actions and thereby reduced primary determinants of myocardial oxygen demand, only the beta blockers were able to afford protection of ischemic myocardium.
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PMID:Protection of ischemic myocardium: comparison of effects of propranolol, bevantolol and N-dimethyl propranolol on infarct size following coronary artery occlusion in anesthetized dogs. 610 14


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