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)

Subendocardial hemorrhagic necrosis in an important cause of death following cardiopulmonary bypass. The transmural distribution of flow across the left ventricle (LV), septum (SP), and right ventricle (RV) is a complex interaction of vascular resistance and myocardial compressive resistance. We studied the change in transmural blood flow in LV, SP, and RV, and left ventricular volume, following administration of cardiotonic and vasoactive drugs in the fibrillating heart. The drugs studied included calcium with and without ATP-induced vasodilation, isoproterenol, epinephrine, angiotensin, and ouabain. Calcium produced underperfusion of LV subendocardium with or without previous ATP vasodilation. Isoproterenol also caused underperfusion of LV subendocardium. Both calcium and isoproterenol decreased ventricular volume. Angiotensin increased resistance in the subepicardium and increased flow in the subendocardium, with no change in ventricular volume. Epinephrine and ouabain caused no consistent changes in transmural flow. The decreased ventricular volume produced by calcium and isoproterenol restricts flow in the subendocardium because of increased compressive resistance. Increased subendocardial flow with angiotensin indicates that subepicardial vasodilation in the fibrillating heart causes epicardial "steal," which contributes to subendocardial ischemia.
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PMID:Effect of cardiotonic and vasoactive drugs on transmural flow distribution and ventricular volume in the fibrillating heart on cardiopulmonary bypass. 4 21

The effects of isoproterenol and dopamine on regional myocardial blood flow were studied in 10 open-chest dogs after acute stenosis of the proximal circumflex coronary artery. Blood flow was determined by the radioactive microsphere technique. Isoproterenol led to a homogenous increase in blood flow in the normal myocardium. In the myocardium with compromised coronary blood flow, isoproterenol led to a relative subendocardial ischemia. This occurred despite increased aortic flow and peak left ventricular dp/dt. Dopamine also increased aortic flow and peak left ventricular dp/dt, but it did not cause regional myocardial ischemia. The findings suggest that dopamine is the preferable inotropic agent in managing low cardiac output in patients with significant coronary artery disease.
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PMID:The effects of isoproterenol and dopamine on regional myocardial blood flow after stenosis of circumflex coronary artery. 83 34

Effect of lignocaine and centbucridine against isoproterenol-induced biochemical changes was studied in the rat. Isoproterenol (40 mg/kg twice) increased the heart weight, level of manolaldehyde (MDA) and activity of acid phosphatase, but decreased the myocardial phospholipid content at 48 h. In addition, increase in plasma triglyceride, cholesterol, MDA and creatine phosphokinase activity was observed. Pretreatment of the animals with lignocaine (10 mg/kg) or centbucridine (1, 3 and 10 mg/kg) protected the animals against these biochemical changes. However, increase in heart weight consequent to isoproterenol treatment could not be prevented. Total protection against creatine phosphokinase release in the blood was also not observed. The results suggest that the two drugs inhibit lipolysis. They may also inhibit phospholipases leading to protection against ischemia-induced changes in the rat.
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PMID:Effect of centbucridine & lignocaine on biochemical changes in isoproterenol induced ischemia in rats. 195 64

To investigate the mechanisms of development in ischemic myocardial injury, intracellular pH and high energy phosphates in perfused guinea-pig hearts were measured using 31P-MRS method. During 60 minutes' global ischemia, intracellular ATP level decreased to 1.2% and 26.4% of control, respectively with and without preischemic administration of isoproterenol, while intracellular pH declined to 6.48 and 6.03. In hearts loaded with isoproterenol, approximately 50% of ATP was depleted with little pH decline. After 40 minutes' reperfusion with a standard perfusate, ATP levels were 23.3% and 46.1%. Cardiac contractility (LVdp/dt) were 16.3% and 45.0% of control value respectively. When hearts were reperfused with inosine, cardiac functions recovered to 52.3% and 81.6% respectively with and without preischemic administration of isoproterenol, while ATP increased to 59.4% and 78.1% after 6 hours' reperfusion. Recovery of ATP level correlated with recovery of contractility. Isoproterenol stole the ability of ATP synthesis from a plenty of ischemic myocytes and progressed irreversible myocardial ischemic injury. ATP depletion was a critical factor in the onset of irreversibility rather than accumulation of anerobic glycolytic products. Measurement of ability of ATP synthesis, with administration of inosine, was supposed to be an usable method to evaluate any organ's viability using 31P-MRS.
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PMID:Mechanisms of myocardial ischemic injury assessed by phosphorus-31 magnetic resonance spectroscopy (effects of catecholamine on ischemic hearts). 238 36

To elucidate the role played by catecholamines in the early phase of ischemic derangement of the myocardial energy metabolism, effects of beta-blockers (propranolol, pindolol, and celiprolol) and isoproterenol, and of pretreatment with reserpine and 6-hydroxydopamine (6-OHDA), were studied using the isolated perfused rat heart. beta-Blockers and isoproterenol were infused for 12 min prior to induction of global ischemia. The myocardial energy consumption rate was assessed by calculating the product of left ventricular pressure and heart rate (LVP x HR). The myocardial cell creatine phosphate (CP), ATP and pH were determined with 31P nuclear magnetic resonance (31P-NMR). Global ischemia induced by cross-clamping of the aortic inflow line for 15 min resulted in falls in CP, ATP, and pH. Propranolol (6 x 10(-8) and 1.8 x 10(-7) mol/min) and pindolol (6 x 10(-7) mol/min) produced a decrease in LVP x HR and suppressed the pH fall during ischemia. Celiprolol was without significant effects on these two parameters. Isoproterenol (6 x 10(-12) mol/min) produced an increase in LVP x HR and tended to accelerate the pH fall. Catecholamine depletion with reserpine or 6-OHDA produced no beneficial effects on the pH fall. It was concluded that the beneficial effects of beta-blockers on the pH fall during early ischemia were not due to the specific beta-blocking action but to the nonspecific cardiodepressant effects of these compounds.
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PMID:Effects of beta-blockers on the fall of pH in the early phase of ischemia in the isolated perfused rat heart: a nuclear magnetic resonance study. 245 26

The changes in myocardial K+ balance during alpha- and beta-adrenoceptor stimulation were compared in 10 anesthetized open-chest pigs by intracoronary isoproterenol and phenylephrine infusions. K+ concentration was continuously recorded by polyvinyl chloride catheter-valinomycin minielectrodes in arterial and coronary sinus blood. The arterial-coronary sinus difference and accumulated myocardial K+ uptake were calculated after computerized data sampling. Isoproterenol (2.5 nmol/min ic) reduced coronary sinus K+ transiently to a nadir of 0.37 (0.23-0.53) mM (median and 95% confidence interval) below control. The accumulated K+ uptake amounted to 139 (63-215) mumol/100 g. After beta-blockade by propranolol, phenylephrine (100 nmol/min ic) induced a transient coronary sinus K+ lowering of 0.16 (0.13-0.21) mM and an accumulated K+ uptake of 30 (20-41) mumol/100 g, both values less than those of isoproterenol (P less than 0.001). Myocardial contractility increased only during isoproterenol infusion, arterial blood pressure rose slightly by phenylephrine, but changes in myocardial O2 extraction and lactate uptake did not indicate cardiac ischemia. We conclude that both alpha- and beta-adrenoceptor stimulation induce a myocardial K+ uptake presumably due to increased Na-K pump activity, the latter more efficiently.
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PMID:Myocardial potassium uptake during alpha- and beta-adrenoceptor stimulation. 288 72

Impaired energy production has been proposed as one mechanism to explain the contractile abnormality in post-ischemic "stunned" myocardium. If energy production were impaired, administration of inotropic agents should result in a deterioration of cellular energy stores because of an inability of ATP synthesis to match the rate of increased utilization. In this study we correlated changes in myocardial high energy phosphates, measured by 31P-NMR spectroscopy, with changes in left ventricular function and energy requirement in buffer perfused rabbit hearts following ischemia and reperfusion, and during stimulation with isoproterenol. Hearts were stunned by 20 min of zero flow global ischemia at room temperature. After reperfusion, isovolumic developed pressure returned to 77.8 +/- 2.2% of baseline and ATP content was reduced to 80.9 +/- 4.1% of baseline. Isoproterenol (5 x 10(-8) M for 10 min) caused increases in developed pressure and rate-pressure product (to 134.1 +/- 12.6% and 195.0 +/- 21.4% of baseline, respectively) without a decrease in ATP or phosphocreatine (PCr) content (80.0 +/- 7.1% and 103.0 +/- 3.8% of preischemia, respectively), and without functional or metabolic deterioration of the hearts after discontinuation of the drug. Control hearts not subjected to ischemia showed similar functional and metabolic responses to isoproterenol. The phosphocreatine/inorganic phosphate (PCr/Pi) ratio, an index of the balance between energy production and utilization, was higher (not lower) than baseline in stunned hearts, thus confirming that energy production was not intrinsically impaired. Together these data indicate that despite reduced myocardial ATP content, mitochondrial function in stunned hearts is capable of sustaining a large increase in function and energetic requirements.
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PMID:Preserved high energy phosphate metabolic reserve in globally "stunned" hearts despite reduction of basal ATP content and contractility. 343 54

Isoproterenol has been used experimentally and clinically to elicit ischemia. The usefulness of this approach, however, in eliciting regional dysfunction in the presence of mild to moderate single-vessel coronary disease quantitated on the basis of coronary flow reserve measurements has not been previously defined. Open-chest, anesthetized dogs were instrumented with an electromagnetic flow probe, high-fidelity micromanometers, and subendocardial ultrasonic crystals. A rigid, screw occluder was used to produce five subcritical coronary stenoses in each dog associated with varying impairment of postocclusion reactive hyperemia at rest but no impairment of resting coronary blood flow. Regional function at rest and in response to the isoproterenol challenge (0.25 micrograms/kg/min) in nonstenotic and stenotic conditions was assessed. Relative regional function was maintained during the infusion until nearly total loss of coronary flow reserve. With this near-critical stenosis, function was lower than in the nonstenotic state but remained greater than resting control values. Moderate impairments of coronary flow reserve were not associated with isoproterenol-induced deterioration of regional function. In conclusion, detection of impaired coronary flow reserve at rest is a more sensitive index of the severity of a coronary stenosis than is detection of regional dysfunction during isoproterenol challenge. Failure to maintain the expected isoproterenol-induced increase in regional function is manifested only when stenoses are associated with nearly total loss of resting coronary flow reserve. This suggests that the clinical use of isoproterenol challenge is not effective in eliciting regional dysfunction when mild coronary disease is present.
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PMID:Relation between graded, subcritical impairments of coronary flow reserve and regional myocardial dysfunction induced by isoproterenol infusion in dogs. 356 41

Breast muscle of young chicks fed chow diets containing the creatine analog 1-carboxymethyl-2-iminoimidazolidine (cyclocreatine) accumulated up to 40 mumol/g wet weight of the synthetic phosphagen 1-carboxymethyl-2-imino-3-phosphonoimidazolidine (cyclocreatine-P2-). ATP levels were sustained at high values substantially longer in breast muscle of cyclocreatine-fed chicks, compared to control-fed chicks, during total ischemia initiated 2 h after injection of both groups with the beta-adrenergic agonist isoproterenol (5 mg/kg subcutaneous). For example, in chicks fed 0.5% cyclocreatine for 10-19 days ATP levels in isoproterenol-stimulated breast muscles after 1 h of ischemia at 37 degrees C were 6.1 mumol/g, compared to 1.9 mumol/g for the control-fed group, and after 2 h of ischemia were 3.5 mumol/g compared to 0.6 mumol/g for controls. Creatine-P reserves in isoproterenol-stimulated breast muscles of all dietary groups were essentially exhausted within the first hour of ischemia. In contrast, breast muscle of chicks fed either 1 or 0.5% cyclocreatine still contained 28 and 19 mumol/g of cyclocreatine-P, respectively, after 1 h of ischemia; after 2 h of ischemia, the respective cyclocreatine-P values were 20 and 13 mumol/g. Isoproterenol-stimulated chick breast muscle provides the first skeletal muscle model system for studying the molecular mechanisms by which dietary cyclocreatine helps sustain ATP levels during ischemia. Although adaptive factors are also involved, it is suggested that a significant portion of the ATP-sustaining activity of dietary cyclocreatine in ischemic breast muscle can be attributed to the unique thermodynamic properties of the accumulated cyclocreatine-P. These properties enable cyclocreatine-P to continue to thermodynamically buffer the adenylate system and transport high energy phosphate throughout the long muscle fibers at cytosolic pH values and phosphorylation potentials well below the range where the creatine-P system can function effectively. Synergism between glycolysis and this long-acting synthetic phosphagen might well help delay depletion of ATP levels in skeletal muscles during ischemia. Cyclocreatine feeding provides a unique experimental tool for quantitative evaluation of the proposed protective role of ATP against irreversible cellular damage in skeletal and cardiac muscles during ischemic episodes.
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PMID:Enhanced ability of skeletal muscle containing cyclocreatine phosphate to sustain ATP levels during ischemia following beta-adrenergic stimulation. 357 Dec 72

Effects of ischemia on the extraneuronal O-methylating system were investigated in the perfused rat heart. Ischemia was produced by stopping of the perfusion for 30 min. Isoproterenol (ISO) was used as a model substrate for the extraneuronal uptake of catecholamines. The accumulation of ISO when catechol-O-methyltransferase (COMT) (EC 2.1.1.6) was inhibited by 3',4'-dihydroxy-2-methylpropiophenone (U-0521) was decreased by ischemia to about 50% of the control value. Ischemia decreased the formation of 3-O-methyl-ISO, a major metabolite of ISO formed by COMT, to about 30% of that in the control hearts. The efflux of extraneuronally accumulated ISO in the heart with and without ischemia was measured. The diffusion constant calculated by the slope of the efflux rate of ISO or by the efflux rate divided by the amount of ISO remaining in the heart after ischemia was about 50% of the control. The experiments showed that ischemia suppressed the extraneuronal O-methylating system (extraneuronal uptake, COMT and diffusional flux) in the rat heart. Such suppression may lead to higher concentrations of local catecholamines in myocardial infarction.
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PMID:Impairment of the extraneuronal O-methylating system of isoproterenol by stop-flow ischemia in the perfused rat heart. 365 8


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