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)

We experienced an extremely low birth weight (ELBW) infant complicated with pulmonary atresia and necrotizing enterocolitis. She was born at 25 weeks of gestation with a birth weight of 752 g. Five hours after birth, she manifested cyanosis and was diagnosed as having pulmonary atresia with intact ventricular septum (PAIVS). Infusion of lipo-prostaglandin E1 (PGE1) was started to keep the ductus open along with infusion of dopamine and dobutamine. At 8 days of life she developed hypotension and metabolic acidosis, and the diagnosis of intestinal perforation was made by free air in the abdomen. The excessive shunt flow to the pulmonary vasculature via the ductus was suspected to have caused an inadequate systemic flow leading to the intestinal ischemia and necrotizing enterocolitis. Lipo-PGE1 was discontinued to decrease the shunt flow through the ductus. Brock's operation (closed transventricular pulmonary valvotomy) was performed at the age of 8 and 11 days and the ligation of the ductus arteriosus was performed at the age of 13 days. Propranolol was administered to inhibit the pulmonary outflow tract constriction along with catecholamines to stabilize hemodynamics. She recovered slowly and her trachea was extubated at 58 days of life.
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PMID:[An extremely low birth weight infant with pulmonary atresia complicated with necrotizing enterocolitis]. 1171 52

The Cardiac Arrhythmia Suppression Trial has shown that treatment with flecainide is associated with an increased incidence of cardiac death in patients following myocardial infarction. It is believed that there is a complex mechanism involving an interaction between flecainide, sympathetic activation, and acute ischemia that is responsible for the increased risk of sudden death. The purpose of this study was to determine the effects of flecainide on muscle sympathetic nerve activity (MSNA) in humans. We measured MSNA using microneurography and cardiac output using the dye dilution method in 30 healthy individuals. Measurements were made at rest and after the oral administration of flecainide (200mg, n=12) or placebo (n=9), or intravenous administration of propranolol (0.2 mg/kg, n=9). Flecainide significantly increased heart rate and decreased the cardiac index (both p<0.01). Flecainide increased the burst rate from 16.7 +/- 3.5 to 23.3 +/- 4.1 bursts/min and the burst incidence from 26.6 +/- 5.1 to 34.7 +/ -5.6bursts/100 heartbeats (both p<0.01). For all of the hemodynamic parameters except heart rate, the effects of propranolol were similar to those of flecainide. Propranolol also increased the burst rate by 52 +/- 34% and the burst incidence by 106 +/- 39%. These results suggest that flecainide suppresses myocardial contractility and produces reflex-mediated increases in sympathetic nerve firing in humans.
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PMID:Flecainide augments muscle sympathetic nerve activity in humans. 1195 53

The role of adrenergic stimulation in Rb(+) uptake in normal and ischemic areas of pig hearts was investigated using an agonist (dobutamine) and an antagonist (S-propranolol). The left anterior descending artery (LAD) in isolated pig hearts was cannulated to maintain adequate perfusion of the LAD bed (2.2-2.8 ml/min/g). Rb(+) loading was initiated by switching perfusion to Rb(+)-containing Krebs-Henseleit (KH) buffer in the presence of 0.1 microM dobutamine, 0.5 microM propranolol, or no drug (control), and the LAD flow was reduced to 10% of the baseline for 120 min. The flow through the LAD was then restored to normal and the drugs were removed. In all groups the rate of Rb(+) uptake obtained from serial (87)Rb images was severely depressed in the ischemic anterior wall relative to that in the normal posterior wall. Dobutamine increased the rate of Rb(+) uptake in the posterior wall (6.3% +/- 1.4% vs. 2.5% +/- 0.25% per minute in control) and did not affect the rate in the anterior wall (0.86% +/- 0.40% vs. 1.14% +/- 0.19% per minute in control). Propranolol did not affect Rb(+) uptake in either of these areas. We conclude that the stimulation of Rb(+) uptake by dobutamine is related to activation of Na(+)/K(+) ATPase and passive Na(+) influx in normal tissue. The lack of any effect of propranolol implies a low level of endogenous norepinephrine during low-flow (LF) ischemia.
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PMID:Effect of adrenergic stimulation on Rb(+) uptake in normal and ischemic areas of isolated pig hearts: (87)Rb MRI study. 1211 27

Using an isolated nonworking rat heart model, this study investigated the role of beta-adrenergic preconditioning (beta-PC) to attenuate myocardial dysfunction after an ischemia/reperfusion injury. After a 20-min stabilization period, the noradrenaline depleted hearts were perfused for 5 min with isoproterenol (ISO) before 40-min global ischemia (I) followed by 30-min reperfusion (R). ISO 0.02 microM provided significant protection versus unconditioned in vivo reserpinized IR control, causing a decrease of creatine kinase (CK) release (mIU/min/g wet weight) on reperfusion in coronary effluent, a preservation of the mean coronary flow (MCF) and preservation of left ventricular function assessed by the rate-pressure product (RPP). These beneficial effects were similar to those of ischemic preconditioning (I-PC) in both nonreserpinized and reserpinized rats. Propranolol (1 microM) and atenolol (10 microM) completely suppressed the ISO preconditioning. In contrast, ICI 118551 (2 microM) a highly selective beta -blocker, did not blunt the salutary effects of ISO on CK release and MCF preservation. These results indicate that ISO pretreatment provides a significant cardioprotection against prolonged ischemic myocardial injury. Although endogenous catecholamines are not necessary for I-PC in isolated rat hearts, cardioprotection provided by beta-adrenergic stimulation is quite similar to I-PC. This significant cardioprotection is mediated less by beta -adrenoceptor than by beta -adrenoceptor activation, which seems to play a crucial role in the beta-PC mechanism.
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PMID:Role of beta 1- and beta 2-adrenoceptor subtypes in preconditioning against myocardial dysfunction after ischemia and reperfusion. 1260 18

Anti-arrhythmic compounds with multiple actions reduce arrhythmic death risk in post-myocardial infarction (MI) patients. Sudden death prevention, however, may rely more on implantable defibrillators than anti-arrhythmic drugs due to ineffective pharmacologic intervention. Widespread use of implantable defibrillators should not obscure the need for development of new anti-arrhythmic drugs. This study tested the hypothesis that combined blockade of I(Na) and I(Ca(L)) prevents ischemia-dependent ventricular fibrillation (VF) in conscious dogs after MI. I(Na) and I(Ca(L)) blockade was accomplished with levosemotiadil in 11 dogs known to be at high risk for VF during 2 min of coronary occlusion during submaximal treadmill exercise 30 days after MI. Negative chronotropic effect of levosemotiadil was examined using the heart rate response to isoproterenol and comparing it with response to propranolol. Levosemotiadil prevented VF in 64% (7 of 11) of the high-risk animals. Heart rate responses to myocardial ischemia and to graded doses of isoproterenol were blunted by the high dose of levosemotiadil. Propranolol prevented VF in 73% (8 of 11) of the dogs. Levosemotiadil had approximately one half the beta-blocking activity of propranolol. The combination of I(Na) and I(Ca(L)) channel blockade coupled with partial beta-adrenergic blockade was equally effective in preventing VF as propranolol.
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PMID:Combined sodium and calcium channel blockade in prevention of lethal arrhythmias. 1271 95

Phosphorylation of phospholamban (PLB) at Ser16 (protein kinase A site) and at Thr17 [Ca2+/calmodulin kinase II (CaMKII) site] increases sarcoplasmic reticulum Ca2+ uptake and myocardial contractility and relaxation. In perfused rat hearts submitted to ischemia-reperfusion, we previously showed an ischemia-induced Ser16 phosphorylation that was dependent on beta-adrenergic stimulation and an ischemia and reperfusion-induced Thr17 phosphorylation that was dependent on Ca2+ influx. To elucidate the relationship between these two PLB phosphorylation sites and postischemic mechanical recovery, rat hearts were submitted to ischemia-reperfusion in the absence and presence of the CaMKII inhibitor KN-93 (1 microM) or the beta-adrenergic blocker dl-propranolol (1 microM). KN-93 diminished the reperfusion-induced Thr17 phosphorylation and depressed the recovery of contraction and relaxation after ischemia. dl-Propranolol decreased the ischemia-induced Ser16 phosphorylation but failed to modify the contractile recovery. To obtain further insights into the functional role of the two PLB phosphorylation sites in postischemic mechanical recovery, transgenic mice expressing wild-type PLB (PLB-WT) or PLB mutants in which either Thr17 or Ser16 were replaced by Ala (PLB-T17A and PLB-S16A, respectively) into the PLB-null background were used. Both PLB mutants showed a lower contractile recovery than PLB-WT. However, this recovery was significantly impaired all along reperfusion in PLB-T17A, whereas it was depressed only at the beginning of reperfusion in PLB-S16A. Moreover, the recovery of relaxation was delayed in PLB-T17A, whereas it did not change in PLB-S16A, compared with PLB-WT. These findings indicate that, although both PLB phosphorylation sites are involved in the mechanical recovery after ischemia, Thr17 appears to play a major role.
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PMID:Role of dual-site phospholamban phosphorylation in the stunned heart: insights from phospholamban site-specific mutants. 1276 47

The effects of pretreatment with cariporide on myocardial infarction and ventricular arrhythmias in a rat model of ischemia/reperfusion were compared with those of nicorandil, propranolol, and nifedipine. Each drug was administered intravenously before coronary occlusion. Cariporide at 0.1, 0.3, and 1 mg/kg significantly reduced the infarct size (infarct mass/risk mass) from 28 +/- 4% (vehicle control value) to 9 +/- 3, 9 +/- 3, and 5 +/- 2%, respectively. Propranolol at 2.5 mg/kg also significantly reduced the infarct size to 11 +/- 1%. Neither nicorandil nor nifedipine was effective when given at 0.1 mg/kg. Cariporide dose dependently decreased the number of ischemia-induced ventricular premature beats (VPB), incidence and duration of ventricular tachycardia, and the number of reperfusion-induced VPB. Nicorandil was effective against only VPB after reperfusion, and propranolol reduced only postischemic arrhythmias, but nifedipine had no effect on either type of arrhythmia. In summary, cariporide reduced the infarct size and dose dependently suppressed arrhythmias induced by ischemia/reperfusion in rats. In contrast, in the present rat model, the doses of the other three drugs used in this study did not show comparable effects.
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PMID:Effects of cariporide (HOE642) on myocardial infarct size and ventricular arrhythmias in a rat ischemia/reperfusion model: comparison with other drugs. 1468 9

Apomorphine (Apo), a dopaminergic agonist used for treatment of Parkinson disease, is a potent antioxidant. In addition to its antioxidative effects, the dopaminergic and adrenergic effects of Apo were studied. Isolated perfused rat hearts were exposed to 25 min of no-flow global ischemia (37 degrees C) and 60 min of reperfusion (I/R, control). Drugs were introduced for the first 20 min of reperfusion. The LVDP of the control group recovered to 54.6 +/- 3.3%. Apo-treated hearts had significantly improved recovery (61.6 +/- 5%, p < 0.05). The recovery of the work index LVDP x HR was even bigger: 67.8 +/- 3.7% (Apo treatment) vs 41.7 +/- 4.6% (control, p < 0.001). Haloperidol, a dopaminergic antagonist, did not affect the recovery with Apo. Propranolol, a beta-adrenergic blocker, initially inhibited the effect of Apo. However, the recovery of the combined group (Apo + propranolol) increased and reached significance (LVDP, p < 0.05 vs control group) after cessation of propranolol perfusion. At 60 min of reperfusion this group was superior to Apo-treated hearts (LVDP, p < 0.05). Propranolol (without Apo) did not improve the hemodynamic recovery. The same pattern of recovery applies also to the recovery of the +dP/dt during the reperfusion. L-DOPA was less effective than Apo. I/R caused significant increase in carbonylation of proteins. Apomorphine inhibited the increase in carbonylation. Haloperidol did not affect this beneficial effect of Apo. L-DOPA significantly decreased the carbonylation of proteins. We conclude that the antioxidative effect of Apo is its main mechanism of cardioprotection.
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PMID:Apomorphine-induced myocardial protection is due to antioxidant and not adrenergic/dopaminergic effects. 1667 10

1. Ischaemia-reperfusion injury is known to be associated with a range of functional and structural alterations in the liver. However, the effect of this injury on drug disposition is not well understood. The present study was designed to examine the effects of hypoxia/reperfusion on the disposition of glutamate and propranolol in the rat isolated perfused liver. Both glutamate and propranolol are mainly metabolised in the pericentral region of the liver. 2. Hypoxia/reperfusion was established using the slow flow-reflow method of perfusion in both anterograde and retrograde perfusion. Glutamate metabolism was measured by the recovery of [(14)C]-glutamic acid and [(14)C]-labelled metabolites in a single pass in both anterograde and retrograde perfusion in the presence of a steady state concentration of unlabelled glutamic acid. Propranolol disposition, mean transit time and normalized variance were assessed from the outflow concentration-time profile of unchanged [(3)H]-propranolol determined after a bolus injection of [(3)H]-propranolol using HPLC and liquid scintillation counting. 3. Hypoxia/reperfusion of livers did not affect oxygen consumption, but caused significant changes in enzyme release, lignocaine hepatic availability and bile flow. 4. Hypoxia/reperfusion did not affect the hepatic metabolism of glutamate to carbon dioxide or the hepatic extraction of propranolol. Small but significant changes were evident in the distribution parameters of mean transit time and vascular disposition for the hypoxic-ischaemic liver. 5. It is concluded that reperfusion injury induced by slow flow-reflow perfusion did not influence the extraction of glutamate or propranolol, but may have affected pericentral morphology and solute distribution.
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PMID:Effects of hypoxia/reperfusion injury on drug disposition in the rat isolated perfused liver. 1732 46

Arrhythmias correlate with disorders of either K(2+) channels in sarcolemma or calcium modulating system in sarcoplasmic reticulum which handles Ca(2+) intracellularly. We hypothesized that an activated endothelin (ET) signaling pathway, which may be associated with an alteration of K(+) channels and Ca(2+) uptake activity in the myocardium, participated in the exaggerated ventricular fibrillation (VF) incidence in cardiomyopathy (CM) induced by L-thyroxin. We intended to test if a dual endothelin receptor antagonist CPU0213 is effective to suppress VF correlating with a reversal of abnormalities in expression of the ion channels in sarcolemma and sarcoplasmic reticulum. The CM was induced by L-thyroxin administration for 10 days, and the altered expression of ion channels and the ET system was examined and the susceptibility to VF was evaluated by 10-min ischemia followed by reperfusion (I/R). Rats were treated with either propranolol or CPU0213 from day 6-10 of L-thyroxin medication. An increased VF incidence on I/R episode in the CMwas found relative to control. An elevated myocardial ET-1 and preproET-1 expression were associated with abnormal mRNAlevel of sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase 2a (SERCA2a), phospholamban (PLB), and ERG, MinK, and Kv4.2 in sarcolemma. Propranolol and CPU0213 were equally effective in reversing the alterations of gene phenotype and exaggerated VF in CM hearts. In conclusion, an activated ET receptor signaling plays a role in the progression of augmented VF in association with abnormal expression of ion channels in both sarcolemma and sarcoplasmic reticulum in the CM.
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PMID:Endothelin receptor antagonist CPU0213 suppresses ventricular fibrillation in L-thyroxin induced cardiomyopathy. 1765 31


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