Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

OPC-18790, (+/-)-6-[3-(3,4-dimethoxybenzylamino)-2-hydroxypropoxy]-2(1H)-quin olinone, is a novel positive inotropic agent, and its mechanism of positive inotropic action involves not only phosphodiesterase inhibition, but also a prolongation of action potential duration in ventricular muscle. Prolongation of action potential duration is also a property of class III antiarrhythmic agents; therefore, we examined the cardiohemodynamic effects and arrhythmogenicity of a combination of OPC-18790 and dopamine in halothane-anesthetized dogs. Dopamine (5 micrograms/kg/min) alone increased the peak of the first derivative of left ventricular pressure (LVdP/dtmax) and cardiac output (CO) by 43-48% and 16-20%, respectively, while OPC-18790 (10 micrograms/kg/min) increased these parameters by 56% and 22%, respectively. The combination of OPC-18790 (10 micrograms/kg/min) and dopamine (5 micrograms/kg/min) and dopamine alone at an increased dose of 10 micrograms/kg/min further increased LVdP/dtmax and CO by 104-113% and 29-30%, respectively. Thus, positive inotropic effects were equally observed in both groups, and the effects of OPC-18790 and dopamine seemed to be additive. The other hemodynamic effects were similar among all groups. Arrhythmias such as premature ventricular contraction developed in 5 out of 7 dogs (71.4%) in the 10-micrograms/kg/min dopamine group, while only one premature ventricular contraction was observed in 1 of 7 dogs (14.3%) in the OPC-18790 (10 micrograms/kg/min) and dopamine (5 micrograms/kg/min) combination group. These results suggest that the combination of OPC-18790 and dopamine may provide new therapeutic options for the treatment of heart failure.
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PMID:Cardiovascular effects of the combination of OPC-18790 and dopamine in halothane-anesthetized dogs. 869 31

Dopamine is administered frequently in the operating theatre and intensive care unit patients undergoing mechanical ventilation with the aim of specifically enhancing renal blood flow. In an uncontrolled, open study, we administered sequentially different doses of dopamine (0, 2, 4, 8 and 0 microgram kg-1 min-1) during a 1-h period each. Systemic haemodynamic and renal haemodynamic variables were measured simultaneously using a pulmonary artery catheter and radiopharmaceuticals, respectively. We studied seven haemodynamically stable patients (mean age 66 yr), with a serum creatinine concentration < 160 mumol litre-1, after elective infrarenal abdominal aortic reconstruction. All patients received extradural analgesia with bupivacaine and sufentanil, and none had a previous history of heart failure. Dopamine induced a dose-dependent increase in cardiac index which returned to baseline after cessation of the dopamine infusion. Glomerular filtration rate (GFR) increased with all doses of dopamine, whereas renal blood flow (RBF) increased significantly only with the 2- and 4-microgram kg-1 min-1 doses. However, the ratio RBF/cardiac output remained unchanged with the 2- and 4-microgram kg-1 min-1 doses, but decreased with 8 micrograms kg-1 min-1 from 14 (1.5)% to 10 (1.3)%. We conclude that dopamine increased RBF and GFR as a result of an increase in cardiac output.
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PMID:Lack of specific renal haemodynamic effects of different doses of dopamine after infrarenal aortic surgery. 934 41

Dopamine (DA) is known to increase diuresis and natriuresis through its action on renal dopaminergic receptors. Augmentation of intra-renal DA concentration by enhancement of its in situ production is greatly dependent on the availability of its precursor L-DOPA to the sites of its renal decarboxylation. Vicia faba (Vf) is a ubiquitous plant rich in easily absorbable L-DOPA. Following ingestion of 40 g freshly chopped Vf containing 120-130 mg of L-DOPA, plasma L-DOPA and urinary sodium and DA excretion increased significantly. The DA/Cre ratio reached a maximum level (280 +/- 58 micrograms/g) 60 minutes after Vf ingestion. This was significantly higher than the DA/Cre ratio after a control meal (1.8 +/- 0.2 micrograms/g; P < 0.0005). The Na/Cre ratio reached the maximal level (2.85 +/- 0.42 mmol/g) 90 minutes after Vf ingestion. This was significantly higher than the Na/ Cre ratio after the control meal (1.4 +/- 0.24 mmol/g; P < 0.005). We suggest that Vf might be of value in treating conditions such as hypertension, heart failure, renal failure, and liver cirrhosis in which natriuresis and diuresis are medically beneficial.
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PMID:The influence of Vicia faba (broad bean) seedlings on urinary sodium excretion. 922 6

Dopamine receptor agonists can be useful in the treatment of hypertension or heart failure. Consequently, the present study investigated the hemodynamic profile of the novel dopamine D1/D2 receptor agonist Z1046 in open-chest, pentobarbital-anesthetized swine. Z1046 was administered in a dose of 10 micrograms/kg (n = 9) or 100 micrograms/kg (n = 8), which was injected over 1 minute; hemodynamic responses were studied for 90 minutes after administration. Both doses of Z1046 produced sustained decreases in mean aortic blood pressure (15-20%). The hypotension produced by the lower dose was principally due to a decrease in cardiac output, as the trend toward a lower systemic vascular resistance failed to reach levels of statistical significance. Conversely, the decrease in mean arterial blood pressure produced by the higher dose of Z1046 was mainly due to a decrease in systemic vascular resistance (up to 17%), as the trend toward a decrease in cardiac output at 60 and 90 minutes after administration was not different from the changes in the saline-treated group. Heart rate decreased slightly with both doses of Z1046. Z1046 decreased left ventricular myocardial blood flow (up to 28 +/- 9%, p < 0.05) in parallel with the decrease in myocardial oxygen consumption (up to 24 +/- 7%, p < 0.05), with no change in the transmural distribution of myocardial blood. Z1046 in a dose of 10 micrograms/kg did not produce significant vasodilation of regional vascular beds, but in a dose of 100 micrograms/kg produced vasodilator responses in the small intestine (34 +/- 2% decrease in vascular resistance), spleen (43 +/- 7%), and kidneys (22 +/- 3% all p < 0.05 vs. baseline). In conclusion, Z1046 produced systemic hypotension with negligible reflex activation of sympathetic tone.
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PMID:Cardiovascular actions of the dopamine receptor agonist Z1046 in swine. 935 58

The efficacy of dopamine infusions in doses of 2 to 10 micrograms/kg/min and combinations thereof with prolonged epidural lidocaine anesthesia (3.7 +/- 0.7 micrograms/kg/day) was assessed in 47 cardiosurgical patients with acute cardiac failure in the immediate postperfusion period. Dopamine increased cardiac output by boosting heart rate and directly increasing the pumping function of the myocardium. High epidural blocking (ThIV-ThV) decreased the chronotropic effect of dopamine, increased the cardiac output by 48.7%, the left ventricular pumping coefficient by 37.9% and the right ventricular by 38.1% and decreased the total peripheral vascular resistance by 36.4% and pulmonary vascular resistance by 52.1%. Epidural anesthesia used in intensive care of cardiac failure in cardiosurgical patients is believed to potentiate the inotropic effect of dopamine.
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PMID:[The intensive therapy of acute heart failure directly after heart operations performed under artificial circulation conditions]. 938 19

Dopamine plays an important role in the regulation of renal sodium excretion. The synthesis of dopamine and the presence of dopamine receptor subtypes (D1A, D1B, as D1-like and D2, and D3 as D2-like) have been shown within the kidney. The activation of D1-like receptors located on the proximal tubules causes inhibition of tubular sodium reabsorption by inhibiting Na,H-exchanger and Na,K-ATPase activity. The D1-like receptors are linked to the multiple cellular signaling systems (namely, adenylyl cyclase, phospholipase C, and phospholipase A2) in the different regions of the nephron. Defective renal dopamine production and/or dopamine receptor function have been reported in human primary hypertension as well as in genetic models of animal hypertension. There may be a primary defect in D1-like receptors and an altered signaling system in the proximal tubules that lead to reduced dopamine-mediated effects on renal sodium excretion in hypertension. Recently, it has been shown in animal models that the disruption of either D1A or D3 receptors at the gene level causes hypertension in mice. Dopamine and dopamine receptor agonists also provide therapeutic potential in treatment of various cardiovascular pathological conditions, including hypertension. However, because of the poor bioavailability of the currently available compounds, the use of D1-like agonists is limited to the management of patients with severe hypertension when a rapid reduction of blood pressure is clinically indicated and in acute management of patients with heart failure. In conclusion, there is convincing evidence that dopamine and dopamine receptors play an important role in regulation of renal function, suggesting that a defective dopamine receptor/signaling system may contribute to the development and maintenance of hypertension. Further studies need to be directed toward establishing a direct correlation between defective dopamine receptor gene in the kidney and development of hypertension. Subsequently, it may be possible to use a therapeutic approach to correct the defect in dopamine receptor gene causing the hypertension.
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PMID:Renal dopamine receptor function in hypertension. 971 42

Dopamine is widely used in critical care to prevent renal function loss. Nevertheless sufficient evidence is still lacking of reduction in end points like mortality or renal replacement therapy. Dopaminergic treatment in chronic heart failure (CHF) has provided an example of unexpected adverse outcome. Pharmacoepidemiological data. Provide additional evidence, finding excess mortality in current ibopamine users (relative risk 2.03 in NYHA I-II CHF, 1.37 in NYHA III-IV), while no relation was found with antiarrhythmic use. In critical care, studies after infrarenal aortic surgery or during septic shock, respectively, failed to find, expected specific renal effects of dopamine. Effects on splanchnic flow mainly depend on baseline flow levels. The implications of recently documented unwanted effects of dopamine, like reduced ventilation and oxygenation during hypoxia, are discussed. In conclusion, controlled clinical trials remain mandatory to assess the overall clinical effects of dopamine in critical care.
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PMID:Dopamine in heart failure and critical care. 1080 32

The purpose of our study is to compare haemodynamic responses and the ischaemic potential of commonly used inotropes (dopamine, dobutamine and milrinone) using a computer model of the cardiovascular system. Cardiotropic drugs interact with the model by changing ventricular elastance and resistance of the individual circulation. All three drugs increase cardiac index in a dose-dependent manner. Dopamine at medium and high infusion rates increases heart rate, systemic vascular resistance and arterial blood pressure. The associated increase in coronary blood flow, however, is not sufficient to account for increased oxygen demand. Both dobutamine and milrinone decrease vascular resistance and increase coronary blood flow. The more pronounced increase in heart rate associated with dobutamine, however, results in a higher ischaemic potential for this drug. Our simulation demonstrates that although all the drugs studied improve cardiac function in simulated patients with heart failure, milrinone accomplishes this at a lower energy cost. The computer simulation developed can be used to assess the complex effect of cardiotropic drugs and possibly suggest optimal drug therapy in specific clinical situations.
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PMID:Comparison of cardiotropic drug effects on haemodynamic and myocardial energetics in patients with heart failure: a computer simulation. 1103 74

The appropriate choice of anesthesia for patients (pts) undergoing renal transplantation (Ktx) requires minimal toxicity and accurate monitoring for pts at high risk for metabolic, cardiovascular, and respiratory perioperative complications. We evaluated the anesthetic management and postoperative follow-up in pediatric Ktx performed in the last 12 years in our institution. From 1988 to 1999, 75 ASA class II-III pts (45 males, 22 females) younger than 18 years scheduled for Ktx were studied: 49 received a graft from a cadaveric donor (CD) and 26 from a living donor (LD). All pts were treated with dialysis within 24 h before the procedure. Standard monitoring consisted of an electrocardiogram, central venous pressure, non-invasive arterial pressure, pulse oximetry, and inspiratory and expiratory gas analysis. If necessary, an arterial cannula and pediatric pulmonary catheter were introduced. Anesthesia was induced with sodium thiopental, propofol, halothane, or sevoflurane and maintained with isoflurane and/or fentanyl and droperidol in O2:N2O (FiO2 0.4%). As muscle relaxants atracurium or cisatracurium besilate were used, except in allergic pts, in whom vecuronium or rocuronium bromide was administered. Dopamine, 20% mannitol, and furosemide were used to increase diuresis. Continuous morphine and ketoralac infusions were used for postoperative pain relief. The surgical technique was the same in all cases. Complications and renal-function (RF) recovery were evaluated relating to CD and LD using the chi-square test; differences in mean anesthesia and surgical time were evaluated by Student's t-test; survival curves were calculated from the day of Ktx to death or last follow-up and estimated by the Kaplan-Meier method. Values of P below 0.05 were considered significant. Postoperative immunosuppressive therapy was based on cyclosporine together with other conventional drugs. Mean anesthesia time was 228 +/- 65 min. Mean kidney ischemia time for CD was 16.5 +/- 4 h. Four pts (3 CD, 1 LD) died within 72 h postoperatively: 3 due to cardiac failure and 1 to metabolic coma. Six pts showed cardiovascular and 3 had infective complications, all successfully treated. Three pts (2 CD, 1 LD) died within 2 to 12 months after, surgery; 10 (6 CD, 4 LD) had graft failure and are still alive on dialysis; 58 (38 CD, 20 LD) are alive in good health after a mean follow-up of 57.6 +/- 36.6 months (range 12-120 months). Fifteen of 26 pts younger than 12 years (21 CD and 5 LD) recovered RF intraoperatively (10 CD, 5 LD); 1 with CD and 1 with LD showed postoperative graft failure and 2 with CD died within 72 h postoperatively, 22 (18 CD and 4 LD) are alive in good health. This group showed no statistical difference compared to pts older than 12 years. Of 16 pts (15 CD and 1 LD) with body weight (BW) less than 25 kg, 6 showed intraoperative (5 CD, 1 LD) recovery of RF. The 3 deaths were all in CD pts, 2 within 72 h and one 2 months after surgery; only 1 LD had postoperative graft failure. Twelve pts (75%) (12 CD, 80%) are alive in good health. Compared to pts with BW of 25 kg or more, this group showed lower intraoperative recovery of RF (P < or = 0.05). No peri- and postoperative complications occurred in all 26 LD pts (100%). Recent advances in surgery, anesthesia, immunosuppression, and antimicrobial prophylaxis have made Ktx a more predictable procedure even in pediatric pts. For high-risk pts, mortality and morbidity can be controlled by accurate surgical, anesthetic, and postoperative management. Pts younger than 12 years and with BW less than 25 kg are more likely to develop peri- and postoperative complications.
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PMID:Pediatric renal transplantation: anesthesia and perioperative complications. 1131 82

Dopamine agonists have been studied in chronic heart failure, but earlier reports with non-selective compounds demonstrated unfavourable long-term effects. CHF 1035 is an orally active, new selective dopamine agonist, primarily activating DA2- and alpha2 receptors, thereby inhibiting norepinephrine release, which may be beneficial in heart failure. We conducted a double-blind, placebo-controlled comparison of CHF 1035 (10 mg/day, n = 20) and placebo (n = 9) in patients with mild to moderate chronic heart failure (left ventricular ejection fraction <0.45). Patients were clinically stable on diuretics and angiotensin converting enzyme inhibitors. Both acute and chronic assessments were made, including plasma neurohormones and 24-hr Holter monitoring for heart rate variability analysis. CHF1035 was generally well tolerated during the study. After 10 days, there were no significant changes between the groups regarding heart rate and blood pressure. Compared to placebo, plasma norepinephrine levels decreased on CHF1035, both in the first 4 hours and after 10 days (p<0.05 between groups). Other neurohormones (natriuretic peptides, renin, aldosteron and endothelin) were not significantly affected. Heart rate variability parameters generally increased on CHF1035, but were unaffected by placebo (p < 0.05 between groups). Short-term treatment with the selective dopaminergic agonist CHF1035 is well tolerated, reduces plasma norepinephrine concentrations and increases heart rate variability in mild chronic heart failure.
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PMID:Autonomic and hemodynamic effects of a new selective dopamine agonist, CHF1035, in patients with chronic heart failure. 1166 7


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