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)

During coronary artery bypass graft (CABG) surgery, patients pretreated with the combination of beta-blocking drugs and Ca2+ antagonists for control of myocardial ischemia often respond inadequately to adrenergic stimulants administered after cardioplegic arrest. In this study, the effects of the combination of a beta-blocker (propranolol) and a Ca2+ antagonist (nifedipine) on the spontaneous recovery, as well as the adrenergic response of the isolated, perfused, working rat heart after a period of cardioplegic arrest were evaluated. After pretreatment of the animals with propranolol and/or nifedipine, hearts were removed, perfused in the presence of pretreatment drugs, subjected to 45 minutes of normothermic cardioplegic arrest, reperfused, and finally stimulated with exponentially increasing concentrations of a sympathomimetic drug. Propranolol, and to a lesser extent nifedipine, protected the hearts during cardioplegic arrest, as indicated by the improved recovery and maximum response to adrenergic stimulation after cardioplegia. Isoprenaline, a beta-stimulant, (at a 100 x higher than conventional concentration), elicited an adequate inotropic and chronotropic response. Stimulation by the alpha, beta-stimulant adrenaline or dobutamine improved only the inotropic response of propranolol and combination treated hearts. Cautious extrapolation of the results to human may suggest continuation of drug therapy of patients before CABG surgery.
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PMID:Effects of beta-blockers and Ca(2+)-antagonists on the response of the isolated working rat heart to adrenergic stimulants after cardioplegic arrest. 801 59

Cardiovascular problems are among the most frequently seen medical complaints related to cocaine use, with chest pain as the most commonly encountered cardiac emergency. Multiple studies and case reports have documented myocardial infarction in young, otherwise low-risk cocaine users. Treatment should be consistent with that of any patient with myocardial ischemia, with particular attention devoted to decreasing the sympathomimetic effects of the cocaine. A 24-hour observation period identifies close to 100% of patients sustaining an acute myocardial infarction after cocaine use.
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PMID:Cocaine chest pain. 818 89

In acute myocardial ischemia, noradrenaline is released locally from sympathetic varicosities by a Ca(2+)-independent nonexocytotic release mechanism that is effectively suppressed by inhibitors of the neuronal noradrenaline carrier (uptake1). The purpose of the present study was to elucidate the significance of free axoplasmic amine concentration and disturbed neuronal sodium homeostasis for nonexocytotic noradrenaline release in the human heart by comparing the release induced by anoxia with that induced by reserpine, tyramine, or veratridine. The overflow of endogenous noradrenaline and dihydroxyphenylethyleneglycol was assessed in human atrial tissue incubated in calcium-free Krebs-Henseleit-solution to prevent interferences by exocytotic release. The overflow of dihydroxyphenylethyleneglycol served as indicator of the free axoplasmic noradrenaline concentration. When vesicular uptake was blocked by the reserpine-like agent Ro 4-1284, high dihydroxyphenylethyleneglycol overflow was observed without concomitant noradrenaline overflow. If, however, Ro 4-1284 was combined with sodium pump inhibition (by omission of extracellular potassium) or with alteration of the transmembrane sodium gradient (by lowering the extracellular sodium concentration), both dihydroxyphenylethyleneglycol and noradrenaline were released. The indirectly acting sympathomimetic tyramine induced a marked increase in noradrenaline overflow which was accompanied by overflow of high amounts of dihydroxyphenylethyleneglycol, indicating interference of the drug with both vesicular catecholamine transport and amine transport via uptake1. Likewise, veratridine induced an overflow of noradrenaline (which was prevented by blockade of uptake1) and dihydroxyphenylethyleneglycol indicating a reserpine-like action of the drug. A disturbed energy status of the sympathetic neuron induced by cyanide intoxication or anoxia caused noradrenaline overflow which was suppressed by uptake1 blockade. Blockade of sodium channels by tetrodotoxin effectively reduced noradrenaline overflow during cyanide intoxication but not during anoxia. Anoxia-induced noradrenaline release, however, was markedly suppressed by inhibition of Na+/H+ exchange with ethylisopropylamiloride, indicating the Na+/H+ exchange as the predominant pathway for sodium entry into the sympathetic neuron during anoxia. The results demonstrate that disturbed neuronal sodium homoeostasis and impaired vesicular storage function are critical conditions, causing nonexocytotic noradrenaline release in anoxic human cardiac tissue.
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PMID:Nonexocytotic noradrenaline release induced by pharmacological agents or anoxia in human cardiac tissue. 883 82

Carvedilol competitively blocks beta 1, beta 2 and alpha 1 receptors. The drug lacks sympathomimetic activity and has vasodilating properties that are exerted primarily through alpha 1-blockade. Animal models indicate that carvedilol confers protection against myocardial necrosis, arrhythmia and cell damage caused by oxidising free radicals, and the drug has no adverse effects on plasma lipid profiles. Recent data have confirmed the antihypertensive efficacy of carvedilol in patients with mild to moderate essential hypertension. Carvedilol has similar efficacy to other beta-blocking agents, calcium antagonists, ACE inhibitors and hydrochlorothiazide. Carvedilol also improves exercise tolerance and ischaemic symptoms in patients with stable angina pectoris. Significant reductions in serious cardiac events after acute myocardial infarction and in frequency and severity of ischaemic events in patients with unstable angina have also been demonstrated. Interest in the use of carvedilol in patients with congestive heart failure (CHF) has culminated in the publication of a cumulative analysis of data from 1094 patients with mild to severe CHF who participated in the US Carvedilol Heart Failure Study Program (4 trials). After a median follow-up of 6.5 months, a significant overall reduction in mortality relative to placebo (3.2 vs 7.8%) was revealed in patients who had received carvedilol 6.25 to 50 mg twice daily (plus diuretics and ACE inhibitors). All-cause mortality, risk of hospitalisation for cardiovascular reasons and hospitalisation costs were also reduced significantly (by 65, 28% and 62%, respectively) in these trials. In addition, the Australia and New Zealand Heart Failure Research Collaborative Group showed a 26% reduction in the combined risk of death or hospitalisation with carvedilol 12.5 to 50 mg/day relative to placebo after a mean 19-month follow-up period in 415 patients with CHF (relative risk 0.74). Adverse events with carvedilol appear to be less frequent than with other beta-blocking agents, are dosage-related and are usually seen early in therapy. Events most commonly reported are related to the vasodilating (postural hypotension, dizziness and headaches) and the beta-blocking (dyspnoea, bronchospasm, bradycardia, malaise and asthenia) properties of the drug. Carvedilol appears to date to have little effect on the incidence of worsening heart failure. Concomitant administration of carvedilol with some medications requires monitoring. Carvedilol is therefore likely to have a beneficial role in the management of controlled CHF, but further clinical studies are required to show the place of beta-adrenoceptor blocking therapy in general in this indication, and the position of carvedilol relative to other similar agents. Carvedilol is also confirmed as effective in the management of mild to moderate hypertension and ischaemic heart disease.
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PMID:Carvedilol. A reappraisal of its pharmacological properties and therapeutic use in cardiovascular disorders. 921 Oct 87

Arbutamine, a new sympathomimetic compound, appears to elicit a more balanced inotropic and chronotropic response than dobutamine, currently used as a pharmacologic stress agent. The present study was performed to compare standard dobutamine stress testing with arbutamine for the detection of myocardial ischemia with technetium (Tc)-99m sestamibi tomographic imaging and 2-dimensional echocardiography in patients with coronary artery disease. Twenty-six patients with evidence of coronary artery disease underwent dobutamine infusion of 5 to 40 microg/kg/min in 3-minute stages. On a separate day, arbutamine was administered by an automated, computerized, closed-loop device monitoring both heart rate and blood pressure. Both infusions were terminated upon achievement of target heart rate, completion of maximal infusion dose (dobutamine), heart rate saturation (arbutamine), or standard clinical end points. Tc-99m sestamibi was injected before termination of both infusions followed by tomographic myocardial perfusion imaging, whereas echocardiography was performed at baseline and throughout the infusions. There were no significant differences in maximal heart rate, blood pressure, and rate-pressure product as well as in the development of anginal symptoms or electrocardiographic changes during both infusions. The location and severity of myocardial perfusion defects and echocardiographic wall motion abnormalities were similar between both agents. It is concluded that arbutamine produces similar imaging results compared with standard dobutamine stress with both Tc-99m sestamibi single-photon emission computed tomographic myocardial perfusion imaging and 2-dimensional echocardiography.
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PMID:Direct comparison of arbutamine and dobutamine stress testing with myocardial perfusion imaging and echocardiography in patients with coronary artery disease. 931 75

To investigate the effects of carteolol, which is a nonselective beta-adrenergic agent with intrinsic sympathomimetic activity, on silent myocardial ischemia, exercise-induced myocardial ischemia, indexes of heart rate variability, and pain-modulating system, 20 patients (mean 60 +/- 9 years) with chronic stable angina underwent exercise treadmill testing and 24-hour ambulatory electrocardiographic monitoring during 2 weeks of carteolol administration (15 mg/day) in a double-blind, placebo-controlled design. Plasma levels of beta-endorphin and bradykinin and electrical pain stimulation to the skin were measured at rest and peak exercise. Indexes of heart rate variability of both time-domain and frequency-domain analysis were derived from 24-hour ambulatory electrocardiographic monitoring. Carteolol decreased maximal heart rate responses to daily activities during ambulatory monitoring and significantly reduced the median frequency and duration of silent myocardial ischemic episodes (from 1.0 to 0.0 events/24 hr and from 16 to 0 min/24 hr, respectively). Carteolol significantly decreased the rate-pressure product at rest and during exercise with improving maximal ST segment depression, suggesting amelioration of exercise-induced myocardial ischemia. Carteolol did not significantly affect plasma levels of beta-endorphin and bradykinin or pain threshold. It significantly decreased some indexes (standard deviation of all normal sinus R-R intervals in the entire 24-hour recording and standard deviation of the mean of all 5-minute segments of normal R-R intervals of a 24-hour recording) of heart rate variability. These results suggest that carteolol may reduce total myocardial ischemic burden by the reduction of cardiac oxygen demand during daily activities and exercise stress, while not affecting plasma levels of beta-endorphin, bradykinin, and pain threshold. Because carteolol tended to decrease indexes of heart rate variability, significant caution might be necessary in prescribing the beta-blocking agents with intrinsic sympathomimetic activity like carteolol to patients with potential serious arrhythmia.
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PMID:Effect of carteolol on silent myocardial ischemia, variability in heart rate, and the pain-modulating system. 939 8

Recently, different beta-blockers have been shown to be effective in the treatment of chronic heart failure (CHF), but the importance of their ancillary properties is not clear. Epanolol is a selective beta1-blocker with intrinsic sympathomimetic activity, which has been shown useful in angina pectoris, but its value in patients with left ventricular (LV) dysfunction and CHF is unknown. We examined the effects of epanolol in patients with LV dysfunction (n = 8; mean LV ejection fraction, 0.33 +/- 0.08) and compared them with patients with normal LV function (n = 8; mean LV ejection fraction, 0.52 +/- 0.04). Measurement of invasive hemodynamics and neurohormones was performed at rest and during myocardial ischemia, which was induced by atrial pacing. All measurements were performed before and after epanolol. Before epanolol, pacing-induced ischemia led to a similar increase in norepinephrine and coronary sinus blood flow in both groups. After epanolol, the increase in neurohormones was more pronounced in the group with LV dysfunction (norepinephrine, 1,130 +/- 164 pg/ml for patients with LV dysfunction vs. 637 +/- 41 pg/ml for normal subjects; p < 0.05). A similar effect was observed for angiotensin II. Further, in the LV-dysfunction group, coronary sinus blood flow increased less, and coronary vascular resistance decreased less (both values, p < 0.05). Despite the fact that the increase in double product was decreased to a similar extent in both groups, ischemia was reduced only in normal LV function (p < 0.05). In ischemic LV dysfunction, neurohumoral activation after epanolol may impair adequate coronary flow response, and this may limit its antiischemic properties. Because of the small size of the study, no definitive inference on the clinical benefit of epanolol in patients with ischemic LV function can be made from this study.
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PMID:Effects of epanolol, a selective beta1-blocker with intrinsic sympathomimetic activity, in patients with ischemic left ventricular dysfunction. 955 97

Nebivolol is a new selective beta 1-adrenergic blocking agent, that possesses a peculiar pharmacodynamic profile and an original chemical structure, by which it differs from traditional beta 1-blockers. Nebivolol is a racemic mixture of two enantiomers in equal ratios. It is endowed with a highly selective beta 1-blocking activity, and does not show an intrinsic sympathomimetic activity. Nebivolol is endowed with peripheral vasodilating properties mediated by the modulation of the endogenous production of nitric oxide. It does not significantly decrease airway conductance compared with atenolol and propranolol. Nebivolol does not compromise the left ventricular function, but it may increase stroke volume, and does not reduce heart inotropism during exertion. Nebivolol is quite safe and is well tolerated, also when compared to traditional beta-blockers. The most common adverse effects are dizziness, headache and fatigue. Owing to its combined dual mechanism of action, nebivolol leads to a unique haemodynamic and therapeutic profile by which it may be advantageous in essential hypertension, ischaemic heart disease and congestive heart failure.
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PMID:Pharmacology of nebivolol. 999 Jun 50

Cocaine, a naturally occurring alkaloid, has increasingly been implicated in a myriad of medical complications. The majority of these relate to cardiovascular effects of the drug, a potent sympathomimetic. In addition, cocaine has effects on endothelin-1, the sodium channel, and nitric oxide which further enhance its untoward cardiovascular effects. The cardiovascular effects of cocaine include myocardial ischemia or infarction, ventricular arrhythmias and sudden death, cardiomyopathy, cerebral infarction or hemorrhage, and acute hypertension. Although hypertension has been described in the offspring of cocaine using mothers, two recent studies have not found an increased prevalence of chronic hypertension in adults. Nonetheless, long term abuse of cocaine can lead to the various forms of target organ damage usually associated with untreated essential hypertension, presumably due to frequent intermittent and severe elevations in blood pressure. (c)1999 by Le Jacq Communications, Inc.
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PMID:Cardiovascular Effects of Cocaine: Focus on Hypertension. 1141 15

Recently, much attention has been paid to small sized low density lipoprotein (LDL) as a risk factor for ischemic heart disease. We investigated the effect of celiprolol hydrochloride (CH), which is a beta 1 selective beta-blocker with high intrinsic sympathomimetic activity (ISA), on the LDL particle size. We treated 41 hypertensive patients with CH and studied the change in LDL particle size according to the score of fast beta lipoprotein and LDL relative mobility value (LDL-Rm) measured by lipoprotein polyacrylamide gel disc electrophoresis (PAGE). We also studied changes in blood pressure, total cholesterol (TC), trygiyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and midband on PAGE. Systolic and dyastolic blood pressure and pulse significantly decreased during treatment. TC levels were significantly decreased at 8 weeks in all subjects and at 4, 8 and 12 weeks in patients with a TC value of over 220 mg/dl. TG levels were significantly decreased at 4 and 8 weeks in patients with initial levels of over 150 mg/dl, and significantly increased at 4 and 8 weeks in those with initial levels of under 150 mg/dl of TG. HDL-C levels did not significantly change during treatment. LDL-C levels were significantly decreased at 4, 8 and 12 weeks in patients with initial levels of over 150 mg/dl. Apo AI, AII, B, CII, CIII and E levels did not significantly change during treatment. Fast beta lipoprotein scores did not significantly change overall during treatment, but were significantly decreased at 4 and 8 weeks in patients initial TG levels of over 150 mg/dl and at 4 and 12 weeks in those with initial levels of over 220 mg/dl of TC. LDL-Rm scores did not significantly change during treatment. Midband scores were significantly reduced overall at 8 weeks, and after 4 and 8 weeks in patients with initial TG levels of over 150 mg/dl and at 4, 8 and 12 weeks in those with initial TC levels of over 220 mg/dl. These results indicated that CH did not change LDL particle size. It was suggested that CH might be a beneficial beta-blocker from the standpoint of prevention for atherosclerosis.
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PMID:[The effect of celiprolol hydrochloride for lipid metabolism--especially for the low density lipoprotein particle size]. 1143 90


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