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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Beta antagonists competitively block beta 1-adrenoceptors that mediate both the rate and force of myocardial contraction. Their precise mechanism of anti-anginal action is uncertain. A reduction in oxygen demand may relative pain and improve effort tolerance. Alternatively inhibition of the adrenergic drive to contraction may offset the increased ventricular wall tension due to incomplete relaxation. Partial agonist activity in a beta-antagonist does not influence efficacy nor protect against airflow obstruction. Membrane stabilising activity is clinically trivial. Cardioselectivity makes airflow obstruction less likely at low but not at high blood concentrations of drug. Alpha-receptor antagonism may also prevent broncho-constriction; it has not been assessed in coronary vasospasm. The dosage and choice of drugs are based on pharmaco-kinetic and dynamic data in animals and man. The major side-effects of beta-blockade are heart failure and airflow obstruction. Cardiotoxicity from overdosage may be treated with isoprenaline, dopamine or glucagon while beta 2-agonists will reverse bronchoconstriction. Since beta-antagonists raise-peripheral vascular impedance, reduction of preload with nitrates enhances their antianginal efficacy. Combining a beta-antagonist with nifedipine seems especially useful. Beta-blockade is worth trying in angina with normal coronary arteries. In acute coronary insufficiency beta-blockade reduces both the work-load on the heart and the somatic features of anxiety, so preparing patients for investigations, like coronary arteriography, aimed at definitive treatment.
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PMID:Clinical pharmacology of beta-adrenoceptor antagonism in angina pectoris: an overview. 611 11

Two cases of severe beta-blocker overdose are presented that were treated successfully with glucagon therapy. The effects of glucagon in reversing the cardiovascular depression of profound beta-blockade, including its mechanism of action, onset and duration of action, dosage and administration, cost and availability, and side effects are reviewed. Medical complications of beta-blocker overdose include hypotension, bradycardia, heart failure, impaired atrioventricular conduction, bronchospasm and, occasionally, seizures. Atropine and isoproterenol have been inconsistent in reversing the bradycardia and hypotension of beta-blocker overdose. Glucagon increases heart rate and myocardial contractility, and improves atrioventricular conduction. These effects are unchanged by the presence of beta-receptor blocking drugs. This suggests that glucagon's mechanism of action may bypass the beta-adrenergic receptor site. Because it may bypass the beta-receptor site, glucagon can be considered as an alternative therapy for profound beta-blocker intoxications. The doses of glucagon required to reverse severe beta-blockade are 50 micrograms/kg iv loading dose, followed by a continuous infusion of 1-15 mg/h, titrated to patient response. Glucagon-treated patients should be monitored for side effects of nausea, vomiting, hypokalemia, and hyperglycemia. The high cost and limited availability of glucagon may be the only factors precluding its future clinical acceptance.
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PMID:Glucagon therapy for beta-blocker overdose. 614 98

Therapy for severe beta-blocker poisoning should be based upon careful supportive therapy. In most cases of poisoning, elimination techniques cannot be expected to remove significant amounts of the drug. Inotropic drugs such as isoproterenol, prenalterol and glucagon in adequate (i.e. large) doses may be necessary to counteract cardiac failure.
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PMID:Beta-adrenoceptor blocker toxicity: clinical features and therapy. 615 69

Glucagon is an important therapeutic agent in critical care medicine. Although its endogenous hormonal functions have been well described, its clinical uses are rarely discussed. Glucagon is effective in the treatment of hypoglycemia, cardiogenic shock and heart failure, propranolol overdose, esophageal meat impaction, ureteral colic due to calculi, and acute diverticulitis. It may prove useful in the treatment of endotoxin and hypovolemic shock as well as toxicity due to excesses of procainamide, quinidine, or ouabain.
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PMID:Glucagon: hormone or therapeutic agent? 637 66

The hemodynamic, hormonal and electrolyte effects of prenalterol, a synthetic selective beta 1 agonist, were studied in six patients with New York Heart Association functional class II and III heart failure. Prenalterol was infused incrementally at 60, 120 and 240 nmol/min, each rate for 24 hours, producing steady-state plasma prenalterol levels of 52 +/- 3, 121 +/- 6 and 194 +/- 9 nmol/1, respectively (mean +/- SEM). Hemodynamic and hormonal measurements were performed before, during and after prenalterol administration under conditions of constant body posture and a regulated intake of dietary sodium and potassium. Prenalterol induced a statistically significant increase in cardiac index (from 2.6 +/- 0.2 to 3.1 +/- 0.3 1/min/m2), with parallel increases in stroke index (from 28 +/- 2 to 34 +/- 2 ml/beat/m2). Forearm blood flow measurements increased (from 2.9 +/- 0.5 to 4.1 +/- 0.6 ml/min/100 g), while calculated systemic vascular resistance fell, as did pulmonary capillary wedge pressure (from 13.7 +/- 1.6 to 10.5 +/- 1.7 mm Hg). The drug did not alter heart rate, arterial pressure, right heart pressures or the frequency of ventricular premature beats. Prenalterol increased plasma renin activity (from 2.9 +/- 0.8 to 6.6 +/- 1.8 nmol/1/hour), angiotensin II (from 59 +/- 12 to 89 +/- 22 pmol/1), urinary aldosterone excretion (from 41 +/- 10 to 78 +/- 34 nmol/day) and plasma insulin (from 10.6 +/- 2.2 to 19.8 +/- 3.9 mU/1). Circulating catecholamines, cortisol, glucose, glucagon or pancreatic polypeptide did not change. Dose-response studies in five patients showed dose-dependent increments in hemodynamic variables, while hormonal changes plateaued at the second dose level. We conclude that prenalterol infusion augments myocardial contractility, reduces systemic vascular resistance, and stimulates insulin release and the renin-angiotensin-aldosterone system.
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PMID:Hemodynamic, hormonal and electrolyte responses to prenalterol infusion in heart failure. 682 3

Digitalis causes vasoconstriction of peripheral vasculature and has been shown to markedly decrease splanchnic blood flow in experimental animals in doses that are comparable to therapeutic doses in man. The effect of digitalis on splanchnic blood flow in heart failure in experimental animals and in man has been controversial. We found that i.v. ouabin reduced ESBF by 30% to 40% (p less than 0.001) in normal volunteer human subjects, that i.v. digoxin reduced ESBF by 15% to 25% (p less than 0.01) in normal subjects, and that oral digoxin had no discernible effect on ESBF in normal subjects. The difference between the effects of i.v. and oral administration appeared to be due to differences in peak blood levels, which were almost 10 times higher after i.v. administration. Glucagon prevented the effect of i.v. digoxin on ESBF in normal subjects. For patients in heart failure, the effect of i.v. digoxin on ESBF was variable: some patients had decreased ESBF but two had increased ESBF that seemed to be associated with a greater increase in cardiac output.
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PMID:Effect of digitalis on estimated splanchnic blood flow. 705 51

We have previously shown that volume overload heart failure is associated with a depressed inotropic response to isoprenaline, noradrenaline, glucagon, and calcium. In these present experiments, the inotropic response of the failing heart to ouabain was examined because ouabain has a mechanism of action that is different from these other agents. The studies were conducted in dogs with heart failure resulting from an aortocaval fistula. The principal finding was that during heart failure the inotropic response to isoprenaline was markedly depressed while the inotropic response to ouabain was unaltered. These findings, coupled with our previous observations, suggest that heart failure is not associated with some common defect in the excitation-contraction coupling mechanism that reduces the response to inotropic agents. Additionally, we made the first measurements of plasma noradrenaline levels in this model of heart failure and found them to be elevated four-fold.
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PMID:A differential inotropic responsiveness to isoprenaline and ouabain in dogs with heart failure. 721 96

The use of phosphodiesterase-III-inhibitors (PDI) as inotropic substances in the treatment of cardiac failure can be associated with hyperglycaemia. This phenomenon could be caused by hepatic events induced by PDI. The purpose of our study was to investigate the effects of the PDI enoximone on hepatic carbohydrate metabolism and bile flow. In the rat liver perfusion model, hepatic glucose and lactate production, portal flow and bile flow were determined. Administration of enoximone (1, 10, 100 microM) increased hepatic glucose output and bile acid-independent bile flow in a dose-dependent manner. The PDI enhanced the glycogenolytic effects of glucagon (from 15.7 to 38.6 mumol glucose/g/20 min), of epinephrine (from 7.1 to 38.7 mumol glucose/g/20 min), of norepinephrine (from 9.8 to 32 mumol/g/20 min) and of phenylephrine (from 25.5 to 40.8 mumol glucose/g/20 min). Furthermore, lactate production was significantly reduced by enoximone. The effect of epinephrine and phenylephrine on portal flow was blocked or diminished by enoximone administration. In summary, it was shown that the PDI enoximone is able to enhance hepatic glucose production. Bile acid-independent bile flow was increased by the inhibition of phosphodiesterase-III. The effects of enoximone and glycogenolytic hormones on glucose release were synergistic. The vasoconstrictive action of catecholamines was reduced or completely prevented by enoximone. In conclusion, enoximone has glycogenolytic, vasodilatory and choleretic properties in the liver.
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PMID:Enhancement of hepatic glucose release and bile flow by the phosphodiesterase-III-inhibitor enoximone in the perfused rat liver. 772 1

Glucagon has been reported to be one of the most effective treatments for severe beta-blocker poisoning. Recently, amrinone was suggested as an alternative therapeutic choice for beta-blocker poisoning. Milrinone, a derivative of amrinone, acts independently of beta-adrenoceptors and increases cyclic AMP. Therefore milrinone may also be effective in the treatment of beta-blocker poisoning. In the present study, we compared the effect of glucagon and milrinone in treating severe beta-blocker poisoning. Following the administration of 10 mg/kg propranolol i.v. over 10 min, heart rate, cardiac output, mean arterial pressure, stroke volume, and end tidal CO2 were depressed, while central venous pressure, and pulmonary capillary wedge pressure increased significantly (p < 0.05). Following the administration of saline (Group S, N = 3), glucagon 20 micrograms/kg (Group G, N = 5), and milrinone 300 micrograms/kg (Group M, N = 5), hemodynamic parameters were observed for 30 min. In group M, mean arterial pressure, cardiac output and stroke volume recovered to their baseline values, while central venous pressure and pulmonary capillary wedge pressure decreased. Although there were no significant differences between groups G and M, the heart rate, central venous pressure and pulmonary capillary wedge pressure, mean arterial pressure and stroke volume did not return to baseline values in group G. Milrinone administration produced a significant hemodynamic improvement without increasing the heart rate in the canine model of severe heart failure caused by propranolol. In the glucagon treatment group, central venous pressure and pulmonary capillary wedge pressure improved less than the milrinone group. Although more data are needed before a clinical recommendation, milrinone might be an effective drug to treat beta-blocker poisoning.
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PMID:Milrinone versus glucagon: comparative hemodynamic effects in canine propranolol poisoning. 800 35

To determine if exercise intolerance and fatigue in chronic heart failure could be exacerbated by an abnormal metabolic response to exercise, we studied 12 patients with stable chronic heart failure and 12 normal volunteers during symptom-limited maximal treadmill exercise. Peak VO2 was 17.2 (15.1-19.2) ml.kg-1 x min-1 in patients and 29.9 (26.3-33.5) in controls (mean and 95% confidence intervals; P < 0.0001, t-test). Overall, levels in peripheral venous blood of glucose, glycerol and free fatty acids were greater in patients, although the differences became less marked with increasing exercise intensity. Noradrenaline was elevated in patients at rest, but the peak exercise response was similar to controls. Responses of adrenaline, insulin and glucagon were similar in both groups. We conclude that depletion of the levels of circulating substrates is not contributory to exercise intolerance and fatigue in chronic heart failure. Greater levels of glycerol and free fatty acids may be mediated by excess sympathetic nervous system activity, reflected in elevated noradrenaline levels.
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PMID:Metabolic responses to graded exercise in chronic heart failure. 829 29


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