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

In heart failure, an increase in the activity of the sympathetic nervous system takes place to maintain perfusion pressure to vital organs, resulting in increased levels of noradrenaline in the blood of these patients. This permanent stimulation produces a down-regulation of cardiac beta-adrenoceptors. Since noradrenaline acts primarily on the cardiac beta 1-adrenoceptor subtype, beta 1-adrenoceptors decrease in number, whereas the beta 2-adrenoceptor subpopulation remains unchanged in most instances. Consequently, the positive inotropic response to beta-adrenoceptor agonists is diminished. However, there is also a decrease in the positive inotropic effect of beta 2-adrenoceptor agonists, histamine and cAMP-phosphodiesterase inhibitors such as milrinone, whereas the positive inotropic effect of cAMP-independent Na(+)-channel activators such as DPI 206-106 and the effects of cardiac glycosides are not diminished. These observations suggest a more generalised alteration of the cAMP-adenylate cyclase system in the failing heart. Stimulatory guanine nucleotide-binding protein (Gs) couples receptors to adenylate cyclase that stimulate cAMP formation, such as beta-adrenoceptors, histamine receptors and glucagon receptors. In the failing human heart, Gs content has been reported to remain unchanged as compared with that in non-failing myocardium. However, there is a 35%-40% increase in inhibitory guanine nucleotide-binding proteins (Gi), which are involved in the receptor-mediated inhibition of adenylate cyclase. Taken together, two defects of the cAMP-adenylate cyclase system have been identified: an increase in Gi content and a decrease in the number of beta-adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Alterations of the cAMP-adenylate cyclase system in the failing human heart. Consequences for the therapy with inotropic drugs]. 197 43

A 24-year-old woman was admitted to our hospital with acute paracetamol poisoning, and severe hepatic injury. The peak blood level of GOT, GPT and LDH were 32,600 U, 119,200 U and 36,500 U respectively. Glucagon-insulin and glutathione were administered to save the liver function. On the third hospital day, hemodialysis was administered to treat acute renal failure. On the 16th hospital day, when the liver and renal functions recovered, severe pulmonary congestion occurred and right heart catheterization revealed high pulmonary pressure. Echocardiography showed left ventricular enlargement accompanied by a severe diffuse impairment of left ventricular wall motion. Multi-focal ventricular arrhythmia was frequent during this period. Hemodialysis and artificial respiration were carried out for the treatment of heart failure. Three months after admission, myocardial perfusion scintigram showed patchy reduction in the uptake of Tl-201 throughout the myocardium, and left ventriculography showed mild diffuse impairment of the LV wall motion (ejection fraction: 49%). In this case, acute heart failure appeared approximately 2 weeks after the severe hepatic injury. Apparently myocardial damage following paracetamol overdosage is caused not only by direct toxicity but by severe metabolic derangement.
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PMID:A case of myocardial damage following acute paracetamol poisoning. 252 40

Five infants with persistent hypoglycaemia due to hyperinsulinism were reported. Provocative tests for insulin release were unhelpful. Diazoxide was useful in the treatment of three patients but many side-effects were observed. These included petechial rash, hypertrichosis, acute renal failure, fluid retention and cardiac failure. Two patients underwent spontaneous remission. Three patients had nesidioblastosis, two of whom were subjected to 95% pancreatectomy. Postoperatively, recurrence of hypoglycaemia was due to hyperinsulinism in one patient and to presumed glucagon deficiency in the other. Phenytoin effectively corrected the hypoglycaemia in the patient who had postoperative hyperinsulinism. It is recommended that medical therapy with diazoxide (10-15 mg/kg per day) together with a diuretic be commenced once hyperinsulinism is diagnosed. Subtotal pancreatectomy should be performed early in these patients if hypoglycaemia cannot be controlled with medical therapy or if side-effects of treatment are documented.
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PMID:Hyperinsulinism in infancy. 276 41

The drugs, new and old, useful in the treatment of acute cardiac failure, are reviewed in the light of its pathophysiological mechanisms and of the biochemical aspects of myocardial contraction. Two major classes of drugs are considered, those that stimulate cell membrane adenylcyclase, i.e. beta-agonists (dopamine, dobutamine and dopexamine) and alpha-agonists (glucagon, forskolin, calcium agonists) and those that inhibit the cellular phosphodiesterases, i.e. bipyridine derivatives (amrinone and milrinone) and imidazolone derivatives (fenoximone and piroximone). Virtually, all the inotropic agents act by increasing the entry of calcium into the cell by increasing the intracellular AMPc concentration. Dopamine has a dose-related triphasic activity. At low doses, stimulation of renal dopaminergic receptors increases renal blood flow, glomerular filtration rate and sodium clearance. At moderate doses, dopamine stimulates, for the most part, cardiac beta-adrenergic receptors. Higher doses stimulate alpha-1-adrenergic receptors, with an increase in systemic arterial and venous pressures. Dobutamine exerts a potent positive inotropic action, with little effect on vascular tone and less tachycardia than with other catecholamines, resulting in only a slight increase in myocardial oxygen consumption. The dopamine analogue, dopexamine, increases renal blood flow, myocardial contractility and produces peripheral vasodilation. The haemodynamic effects of phosphodiesterase inhibitors are similar to those of dobutamine, except that these drugs are vasodilators, their positive inotropic properties are weak and their haemodynamic effects persist for at least 8 h after a single dose in heart failure patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Use of new inotropic agents in the treatment of acute cardiac failure]. 289 79

Alpha cell tumours of the pancreatic islets of Langerhans are rare. The glucagonoma syndrome is caused by excess glucagon secretion from such a tumour. Physiologically, glucagon is important in the control of the homeostatis of glucose and certain amino acids. Pharmacologically, it has been used to treat heart failure. Problems with both glucose homeostasis and myocardial function could, therefore, theoretically be anticipated following resection of a glucagonoma. This paper describes the peri-operative management of such a case, where, despite measured changes in glucagon, no problems of this nature were encountered.
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PMID:Anaesthetic management of glucagonoma. 298 82

Although early experiments in animals and humans suggested that digitalis glycosides increased cardiac output only in the failing heart, later studies showed that these cardiotonic agents increase intraventricular systolic pressure and decrease relaxation time in the normal animal. The controversy concerning the peripheral vascular or direct cardiac effects of digitalis was finally resolved when new methods were applied to the study of the effects of this drug on intraventricular pressures and cardiac contractile force. Other positive inotropic agents, such as the adrenergic agonists, have also been tested for the treatment of heart failure. However, during long-term oral or intravenous therapy, the effectiveness of these drugs appears to diminish. Clinical studies of glucagon, a polypeptide with positive inotropic and chronotropic effects, have revealed its potential for causing side effects and its reduced activity in patients with chronic heart failure. With the discovery of several new types of inotropic agents, i.e., the bipyridines and the imidazole and benzimidazole derivatives, interest in revising our therapeutic approach to congestive heart failure has increased. This review discusses recent developments in this area.
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PMID:Historical perspectives on inotropic agents. 351 Jul 79

Haemodynamic effects of pharmacological doses of insulin during acute ischaemic heart failure were studied in 8 dogs. Severe depression of left ventricular function was induced by the injection of 50 micron plastic microspheres into the left main coronary artery. This was demonstrated by a significant increase in left ventricular end-diastolic pressure and a significant decrease in the maximum rate of left ventricular pressure rise (LVdP/dtmax), stroke volume and cardiac output. Eighty-five minutes after the embolization procedure, 300 IU of insulin free of glucagon and calcium was injected as a bolus. This was followed by infusion of glucose and potassium to maintain physiological levels of these factors. Five minutes after insulin administration, there was a significant improvement in left ventricular performance as shown by decreased left ventricular end-diastolic pressure (P less than 0.01) and increased LVdP/dtmax (P less than 0.01), stroke volume (P less than 0.05) and cardiac output (P less than 0.05). A significant reduction in heart rate occurred. A non-significant increase in mean aortic blood pressure and reduction in total peripheral resistance were seen. In conclusion, pharmacological doses of insulin significantly improve cardiac pump function during acute ischaemic left ventricular failure in dogs.
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PMID:Haemodynamic effects of high doses of insulin during acute left ventricular failure in dogs. 389 50

Metabolic effects of pharmacological doses of insulin were studied during acute ischaemic heart failure in 7 dogs. Severe depression of left ventricular performance was induced by embolization of the left main coronary artery with 50 micron plastic microspheres. This was followed by a significant reduction in myocardial blood flow and oxygen consumption. After a period of stabilization of the haemodynamic and metabolic variables, 300 IU of insulin free of glucagon and calcium was injected as a bolus dose. Glucose and potassium were given to maintain their plasma concentrations. Insulin significantly improved performance of the failing left ventricle. Myocardial blood flow was significantly increased, whereas myocardial oxygen consumption was unchanged. Insulin significantly reduced arterial concentrations and myocardial uptake of free fatty acids, while myocardial uptake of glucose and lactate showed a non-significant increase. In conclusion, pharmacological doses of insulin significantly improve cardiac pump function without increasing myocardial oxygen consumption during acute ischaemic left ventricular failure in dogs. This may be partly related to reduced myocardial uptake of free fatty acids relative to that of glucose.
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PMID:Metabolic effects of high doses of insulin during acute left ventricular failure in dogs. 389 51

The central and peripheral vascular haemodynamic effects of glucagon were studied in 29 patients. With a single dose method of 2 or 5 mg. glucagon intravenously the inotropic action of the drug produced immediate increased myocardial contractility with significant increase in cardiac output and enhanced cardiac performance, and lowering of pulmonary arterial pressure and pulmonary vascular resistance. No primary peripheral vascular effect was evident, and the increased systemic pressure and lowered systemic resistance appear to be secondary to the central action of the drug. With the dosage used there were no undesirable side-effects apart from a feeling of slight nausea. Though the haemodynamic effects are abrupt, reaching their maximum values in the first 10 minutes after injection, they tend to be dissipated within half an hour, presumably due to the very rapid destruction of the drug. Repeated booster doses rather than continuous infusion may be the method of choice to maintain an increased cardiac output. The positive chronotropic action of the drug may cause transient palpitations. Glucagon increased the cardiac output in the acute phase of myocardial infarction by 42 per cent. The haemodynamic effects in chronic rheumatic heart disease are more varied, and it may increase left atrial pressure in mitral stenosis, which is undesirable. Hyperglycaemia results from liver glycogenolysis but blood sugar levels rarely exceeded 200 mg./100 ml. These results warrant further study of the value of glucagon as a positive inotropic agent in low output heart failure, especially in acute myocardial infarction with cardiogenic shock, or after cardiac surgery, or in unrelieved chronic congestive heart failure.
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PMID:Haemodynamic effects of glucagon. 542 74

Although glucagon exerts positive inotropic effects in patients with no or mild impairment of cardiac function, similar effects are not consistently observed in patients with chronic heart failure. Accordingly, the inotropic effects of glucagon on papillary muscles from normal cats and cats in which right ventricular failure had been produced for 4-145 days by pulmonary artery banding were compared. At the peak of the concentration-response curve, glucagon increased peak isometric tension (T) in normal muscles from 4.4+/-0.4 to 6.6+/-0.5 g/mm(2) (P <0.001), and maximum rate of tension development (dT/dt) from 16.9+/-0.9 to 25.1+/-1.6 g/sec per mm(2) (P < 0.001). In contrast, glucagon produced no significant increases in T or dT/dt in failure muscles. The percentage increases in T and dT/dt caused by norepinephrine were the same in muscles from normal and failing hearts. Since the cardiac effects of glucagon and norepinephrine may be mediated by adenyl cyclase, responsiveness of adenyl cyclase was determined in particulate fractions of the right ventricle. Glucagon activated adenyl cyclase in normal, but had no effect in failure preparations. Norepinephrine-induced activation of adenyl cyclase, however, was unaltered by failure. Thus, in contrast to norepinephrine, glucagon loses the capacity to augment myocardial contractility and activate adenyl cyclase in hearts derived from cats in chronic failure.
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PMID:Effects of experimental heart failure on the capacity of glucagon to augment myocardial contractility and activate adenyl cyclase. 544 51


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