Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151814 (coronary occlusion)
 3,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coronary occlusion in the dog results in irreversible myocardial cell injury which develops first in subendocardial areas of severe ischemica and subsequently spreads into mid and subepicardial areas of moderate ischemia. The effect of propranolol on this progression of ischemic injury was evaluated. Three groups of dogs were studied: 1) untreated, 2) treated with propranolol before and throughout coronary ligation, and 3) treated with propranolol beginning three hours after ligation. Dogs were sacrificed 24 hours after coronary ligation and necrosis was quantitated from histologic sections of transmural slices through the posterior papillary muscle. Propranolol reduced infarct size by preventing necrosis in peripheral (subepicardial) areas of moderately ischemic myocardium. Pretreatment with propranolol reduced necrosis from 85 +/- 3% (untreated) to 52 +/- 4% (P less than 0.05). Delayed propranolol therapy was about half as effective as pre-treatment and reduced necrosis to 71 +/- 3% (P less than 0.05). Propranolol also limited microvascular injury so that perfusion defects, detected with the dye thioflavin S, were smaller in treated dogs.
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PMID:Infarct size reduction by propranolol before and after coronary ligation in dogs. 91 40

To evaluate the concordance between elevated plasma MB CPK and irreversible myocardial ischemic injury, coronary occlusion was induced for 10 minutes to 48 hours in 21 open chest dogs and 13 conscious animals. Results of plasma CPK and MB CPK assayed in samples obtained serially ofr 24 hours were compared to microscopic changes in hearts from the same animals examined 48 hours after occlusion. Twelve of the 34 dogs died within two hours after coronary occlusion. Among the surviving 22 dogs, one failed to exhibit gross of electrocardiographic evidence of ischemia and was therefore excluded. Twelve had coronary occlusion maintained for 30 minutes or longer and in 11 of these peak plasma MB CPK activity exceeded thenormal range (mean +/- 2 SD) and baseline values by at least 100%. Necrosis was present in the hearts from each manifested by nuclear pyknosis, eosinophilia, shrinkage of cytoplasm, and leukocytic infiltration. In the remaining nine dogs with occlusion for less than 30 minutes, peak plasma MB CPK activity was not elevated and necrosis was not detected. The close concordance between plasma MB CPK elevations and myocardial necrosis was significant (chi2 = 14.5, P less than 0.001), and thus, increased plasma MB CPK activity reflected irreversible myocardial ischemic injury.
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PMID:The association of increased plasma MB CPK activity and irreversible ischemic myocardial injury in the dog. 93 19

Recent studies have suggested that propranolol decreases the extent of myocardial injury in acute ischemia. Although other studies have shown that global myocardial performance is depressed, zonal effects of propranolol in this setting are unknown. Therefore, the effect of propranolol (1.0 mg. per kilogram) was investigated in nine dogs with the use of Walton-Brodie strain gauge arches and local epicardial electrograms (10 to 12 sites). The heart rate effects of propranolol were controlled by atrial pacing. After coronary occlusion, heart rate increased slightly without a significant change in blood pressure. Following the infusion of propranolol, heart rate decreased significantly from 165.0 +/- 3.5 to 126.2 +/- 4.7 beats per minute (p less than 0.001) while both the systolic and diastolic blood pressures showed insignificant changes. After coronary occlusion, nonischemic zone tension showed no significant changes; however, propranolol decreased total tension from 105.2 +/- 2.5 per cent to 66.8 +/- 4.7 (p less than 0.001). Similarly, propranolol further decreased total tension in the border zone from 84.4 +/- 6.7 per cent (p less than .02) to 50.6 +/- 5.1 (p less than 0.01). Ischemic zone tension also fell further (p less than 0.025) after propranolol. Restoration of prepropranolol heart rate had no significant effect on tension development. Following coronary occlusion, sigmaST increased from 5.7 +/- 2.2 to 72.9 +/- 20.1 mv. (p less than 0.001). Coincident with the decrease in heart rate and tension development induced by propranolol, sigmaST decreased to 60.8 +/- 18.8 mv. (p less than 0.05). When the heart rate was restored to prepropranolol level, sigmaST again rose to 73.2 +/- 16.9 mv. (p less than .005). Thus, propranolol does effect an improvement in ischemic injury which is related, at least in part, to the induced decrease in heart rate. A concomitant substantial decrease in local tension development also occurs, however. The latter observations may limit the potential usefulness of propranolol in this setting.
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PMID:Propranolol in experimental myocardial ischemia: dissociation of effects on contraction and epicardial ST segments. 96 87

Morphologic and hemodynamic changes that occur following coronary occlusion are examined. The effectiveness of hyperosmotic mannitol in lessening the extent of myocardial damage is assessed and mechanisms for its action discussed. Forty and 60 min of coronary vascular occlusion followed by 15 and 45 min of reflow were associated with a persistence of ischemia following reflow of blood, as established by infusions of silastic into the aortic root. Electron microscopic studies demonstrated myocardial and endothelial cell swelling at the end of the reflow period. The process of cell swelling appeared to be initiated during the period of arterial occlusion. This cell swelling was reduced by elevation of serum osmolality by 30-40 mOsm above control with the administration of mannitol during and following occlusion. There was an associated 40-50% reduction of vascular resistance following occlusion if mannitol was administered. In addition, the extent of necrosis, which was widespread in untreated hearts 12 hours after occlusion, was strikingly less in the hearts of dogs which received mannitol. Thus, in ischemic myocardium, elevation of osmolality by mannitol reduces myocardial necrosis, probably through its restoration of normal cell volume.
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PMID:The protective effect of hyperosmotic mannitol in myocardial ischemia and necrosis. 96 49

The effects of verapamil (0.02-0.2 mg/kg) on contractility in normal and partially ischemic myocardium were compared with the changes following propranolol (0.01-1.0 mg/kg). Regional contractile function was studied in open-chest dogs with ultrasonic crystals and ischemia was controlled by graded occlusion of a carotid-to-coronary artery shunt. Reduction in shunt perfusion pressure (40-55 mm Hg) resulted in hypokinesia. Verapamil depressed contractility in ischemic myocardium in 5/5 dogs, but did not alter the maximum velocity of shortening (max V) or end-diastolic segment length in normal myocardium. Propranolol in doses sufficient to depress ischemic myocardium also depressed contractile function in normal myocardium. In two dogs without coronary occlusion, verapamil (up to 1.0 mg/kg) increased end-diastolic segment length but did not reduce max V. We conclude that verapamil selectively depresses ischemic myocardium, a finding that may have clinical implication since ischemic injury can be decreased by reducing contractility (and thereby MVO2).
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PMID:Regional contractility. Selective depression of ischemic myocardium by verapamil. 96 50

Using epicardial electrograms others have established that infusion of isoproterenol increases myocardial injury after acute coronary occlusion. To define the contribution of alterations in collateral blood flow to this increased ischemia, isoproterenol was administered to 10 dogs. After pretreatment with practolol in doses that successfully block inotropic but not vascular effects of beta adrenergic stimulants, intracoronary isoproterenol continued to enhance the magnitude of S-T segment elevation in ischemic areas. Thus, vasodilation induced by isoproterenol appears to divert flow from the ischemic area. To test this hypothesis, intracoronary adenosine was given to cause coronary vasodilation without enhancing inotropy. S-T segment elevation at ischemic and adjacent sites was significantly increased. Neither agent had systemic effects, but each increased coronary blood flow while concomitantly decreasing collateral flow as evidenced by a reduction in retrograde coronary flow and peripheral coronary pressure. In addition, adenosine significantly diminished the rate of xenon-133 clearance from the ischemic myocardium. Thus, isoproterenol, in addition to its positive inotropic effect, increases myocardial injury by its vascular action. Collateral blood flow to acutely ischemic myocardium is diminished by the production of a coronary steal. Intravenously administered isoproterenol additionally diminishes collateral flow by decreasing coronary perfusion pressure. It is postulated that any agent that causes either a primary or secondary coronary vasodilation may cause a coronary steal and subsequently enhance myocardial injury.
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PMID:Coronary steal: its role in detrimental effect of isoproterenol after acute coronary occlusion in dogs. 99 23

Some of the laboratory difficulties in assessing infarction size produced by intermittent coronary artery occlusion were demonstrated by using an epicardial mapping technique in anesthetized open-chest dogs. Intermittent occlusion of a left anterior descending coronary artery branch resulted in a marked elevation of the ST segment above the baseline in the areas of the myocardium supplied by this vessel. Repeated occlusions after administration of normal saline as a control produced less ST-segment elevation thn that noted during control occlusions; however, repeated occlusions after infusion of quinidine produced a further lessening in ST-segment elevation. The problems encountered in interpreting these results are emphasized. Long-term coronary occlusion studies were performed in order to correlate epicardial electrograms with histological findings of ischemia or myocardial necrosis. Our investigations show that epicardial mapping tended to underestimate the area of injury, and this limits the interpretation of drug intervention studies such as those in which quinidine is administered. Therefore, caution should be exerted when using epicardial mapping techniques to assess the effect of various pharmacological interventions on infarction size in open-chest dogs.
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PMID:Problems in assessing infarction size by epicardial mapping: preliminary studies with quinidine. 100 38

The behaviour of some enzymatic activities, such as monoamino oxidase (MAO), diamino oxidase (DAO), catalase, peroxidase and creatin chinase (CPK) have been studied both in blood serum and myocardial tissue of acute infarcted dogs (obtained by coronary occlusion). The most significant results are the changes of the DAO activity (--50% from the control) and peroxidase activity (+60%), 6 hours after acute ischemia. The effect of reperfusion was studied 2 hours later. A recovery of DAO activities was shown, while the peroxidase activities stayed elevated. All the enzymatic activities studied were evaluated in the serum, under the same experimental conditions. An increase of all these activities was observed until 6th hour of coronary occlusion. The reperfusion of acute ischemia, after six hours, causes a further increase of CPK and MAO activities and a decrease of catalase peroxidase and particulary evident DAO activities. The results of this experiment show that reoxygenation, under our experimental conditions, increases a further enzymatic release and in part causes a metabolic recovery of heart muscle.
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PMID:[Experimental revascularization of acute myocardial infarction. II: Activity of various oxidoreductive tissutal and serum enzymes (author's transl)]. 101 Jan 98

The effects on myocardial function, metabolism and ultrastructure of 60 minutes of reperfusion, instituted after 30, 60 and 90 minutes of occlusion of the left anterior descending coronary artery, were studied in 48 dogs. Twelve sham-operated dogs served as controls. Coronary occlusion for 60 or 90 minutes caused significant depression in the first derivative of left ventricular pressure (dP/dt) (P less than 0.05) that could not be reversed by reperfusion. Upon reperfusion, creatine phosphate stores in myocardium made ischemic for 30 and 60 minutes, but not for 90 minutes, returned toward control levels, but stores of adenosine triphosphate (ATP) and total nucleotides and the ATP/adenosine diphosphate ratio of myocardium subjected to 60 and 90 minutes of ischemia were further decreased. After 60 and 90 minutes of ischemia, swelling of the sarcoplasmic reticulum and mitochondrial damage (swelling, decreased matrix density and partial loss of cristae) were seen. Myofibrils were relaxed in all these groups. Reperfusion produced gross contraction of myofibrils and aggravated these changes in mitochondria and sarcoplasmic reticulum. In the hearts subjected to 90 minutes of ischemia these changes were gross. The levels of creatine phosphokinase, glutamic oxaloacetic transaminase and lactic dehydrogenase in the coronary sinus blood increased dramatically (P less than 0.05) upon reperfusion after 60 or 90 minutes of occlusion, indicating severe impairment of cell membranes. This secondary rise in serum enzyme activity during reperfusion should be taken into consideration when estimating the size of a myocardial infarct from enzyme changes alone. It appears that 60 and 90 minutes of ischemia cause severe myocardial damage that is not reversed by reperfusion maintained for 1 hour although longer periods of reperfusion may be beneficial.
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PMID:Alterations in energy metabolism and ultrastructure upon reperfusion of the ischemic myocardium after coronary occlusion. 108 Mar 52

Nineteen mongrel dogs survived chronic occlusion of the left circumflex and of the right coronary artery without infarction due to the timely development of a collateral circulation. Only 38 per cent of the conductance of the arteries before occlusion was restored by collateral vessels. In these animals and in 15 control dogs with normal coronary arteries myocardial contractility, contractility reserve, and myocardial blood flow were studied. The same was done in dogs with chronic coronary artery occlusion after aortocoronary bypass. Myocardial blood flow was determined woth the tracer microsphere technique. Contractility reserve was tested and defined as isovolumetric left ventricular pressure and dp/dt max with norepinephrine infusion and cross-clamping of the aorta. Contractile reserve was not significantly different between normal dogs and dogs with chronic coronary artery occlusion before and after aortocoronary bypass. Myocardial blood flow during control conditions was homogenously distributed in all three groups studied. The ratio of blood flow to the endocardium and the epicardium was not significantly different from inity. Coronary reserve was determined at peak reactive hyperemia following a 20 second period of coronary artery occlusion, with ongoing norepinephrine infusion. Under these conditions subendocardial fow in normal dogs rose by a factor of 7.9 while subepicardial flow increased 7.4 times. In dogs with chronic occlusion of two coronary arteries the increase of myocardial flow was nonnomogenous; subendocardial flow to areas supplied by a normal coronary artery rose by a factor of 7.0 while subepicardial flow increased 5.7 times control. Subendocardial collateral flow rose by a factor of 2.4 and subepicardial collateral flow increased 3.5 times control. In normal dogs norepinephrine alone did not result in maximal coronary flow but only 57 per cent thereof. Dogs with chronic coronary occlusion, however, required the entire coronary reserve in areas that were supplied by a normal coronary artery, whereas areas supplied by collaterals became ischemic. Opening of an aortocoronary bypass restored normal flow to previously ischemic areas, and reduced the flow to areas supplied by a normal artery. With the bypass open no differences existed between normal dogs and those with two occluded coronary arteries. We conclude that the norepinephrine-stimulated contractile reserve of hearts with chronic coronary occlusion was comparable to that of normal hearts; however, norepinephrine forced these hearts to spend the entire flow reserve of the remaining normal artery while producing ischemia in collateral-dependent areas. The same dose of norepinephrine did not require the entire flow reserve of normal dogs.
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PMID:Vascular and cardiac contractile reserve in the dog heart with chronic multiple coronary occlusions. 108 88


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