Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.4.1 (phosphodiesterase)
18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amrinone is more coronary vasodilatory than positive inotropic compared with other newer phosphodiesterase inhibitors. In order to explore possible involvements of ATP-sensitive K+ (KATP) and large-conductance Ca(2+)-activated K+ (KCa) channels in the vasodilator effect of amrinone, we investigated whether amrinone-induced vasodilation would be antagonized by glibenclamide, a blocker of KATP channels, or by charybdotoxin or tetraethylammonium, blockers of KCa channels. In isolated, blood-perfused canine papillary muscle preparations, the amrinone-induced increase in blood flow was not affected by glibenclamide given to support dogs. In canine large coronary arteries contracted with high (25 mM) KCl, amrinone-induced relaxation was not affected by glibenclamide, charybdotoxin and tetraethylammonium. These results suggest that the vasodilator mechanisms of amrinone do not involve the opening of either KATP or KCa channels.
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PMID:Vasodilator mechanisms of action of amrinone do not involve the opening of either ATP-sensitive or Ca(2+)-activated K+ channels. 752 Oct 74

Amrinone is a non-glycoside positive inotropic agent with an inhibitory effect on a cyclic adenosine monophosphate (AMP) phosphodiesterase isoenzyme. In the present study, we examined the immunosuppressive action of amrinone, since several other cyclic AMP-elevating agents have been shown to suppress T lymphocyte activation. First, the in vivo effects of amrinone were investigated. Oral amrinone treatment, at 40 mg/kg per day, significantly prolonged median cardiac allograft survival compared with non-treated controls (22.0 days versus 10.5 days, P < 0.01) when DBA/2 mouse hearts (H-2d) were heterotopically transplanted into C57B1/6 mice (H-2b). Histopathological examination showed that there was less prominent cellular infiltration in the amrinone-treated than in the non-treated allografts. Plasma amrinone concentrations of mice after a single oral dose of 40 mg/kg were within the range of clinical relevance. To clarify the mechanism of action, in vitro studies were done. The generation of specific cytotoxic T lymphocytes after mixed lymphocyte culture was significantly suppressed by addition of amrinone to the culture medium at 5 micrograms/ml. The production of IL-2 and the interferon-gamma during mixed lymphocyte culture was also suppressed by amrinone at 5 micrograms/ml. However, the level of intracellular cyclic AMP in mouse splenic lymphocytes was not affected significantly by the same dose of amrinone. In conclusion, amrinone has immunosuppressive actions at the therapeutic doses, and it may be a beneficial agent for therapy against acute cardiac allograft rejection.
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PMID:Beneficial effect of amrinone on murine cardiac allograft survival. 755 88

Amrinone, a new cardiotonic drug, has received attention as a better therapeutic agent than the cardiac glycosides in the treatment of congestive heart failure. In this study, the effects of amrinone on isolated rat uterus and its probable mechanism of action were investigated. At two different concentrations (0.1 and 0.5 mM), the inhibitory effects of amrinone on the spontaneous contractions of rat uterus were noted. In addition, amrinone (0.5 mM) was found to inhibit the tonic contractions induced by potassium sulphate (K2SO4)-Ringer solution (91.74%) and calcium chloride (CaCl2) (93.04%). These inhibitory effects were compared with regulators of the phosphodiesterase enzyme (PDE). It was concluded that amrinone could behave as a calcium antagonist and PDE inhibitor.
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PMID:The inhibitory effects of amrinone on isolated rat uterus. 785 49

Vesnarinone is a new, non vasodilating cardiotonic agent. This study compared the effects of vesnarinone and amrinone, a phosphodiesterase (PDE) inhibitors with vasodilating actions, on cultured smooth muscle cells from the porcine coronary artery. Application of vesnarinone (10(-4) M) or amrinone (10(-4) M) to the bath solution in cell-attached patches activated the KCa channel having a conductance of 133 pS (bath 2.7 mM K, pipette 140 mM K). Application of vesnarinone to the cytosolic side had no direct effect on KCa channel activities in inside-out patches. Activation of the KCa channel was suppressed when the intracellular production of cAMP was suppressed by preincubation with carbachol (10(-6) M). Amrinone, but not vesnarinone, lowered [Ca2+]i in the K(+)-depolarized smooth muscle cells (K+ = 70 mM). These results suggest that vesnarinone exerts an additional effect on [Ca2+]i that is independent of PDE inhibition. The difference in the effects on [Ca2+]i in vascular smooth muscle cells may explain in part the differing actions of these agents on vascular relaxation.
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PMID:Effects of vesnarinone (OPC-8212) on Ca(2+)-activated K channels and cytosolic Ca2+ in cultured smooth muscle cells from porcine coronary artery. 820 82

Amrinone, a phosphodiesterase inhibitor, and epinephrine, an alpha- and beta-adrenergic receptor agonist, are inotropic drugs used during cardiac surgery to reverse myocardial depression after cardiopulmonary bypass. However, these drugs have not been compared separately, or in combination, in this patient population. We hypothesized that the combination might have complementary actions in improving myocardial function. We, therefore, compared amrinone, epinephrine, and the combination of amrinone and epinephrine in a randomized, blinded, placebo-controlled study in patients undergoing coronary artery bypass grafting. Forty patients with ejection fractions > 0.45 were studied. Right ventricular ejection fraction pulmonary artery catheters and radial arterial catheters were inserted before fentanyl-midazolam anesthesia. After separation from bypass, patients received either a placebo (n = 20) or amrinone bolus (1.5 mg/kg, n = 20) at time 0 and a placebo (n = 20) or epinephrine (30 ng.kg-1.min-1, n = 20) infusion at time 5 min. This resulted in four study groups, n = 10 in each group. Data were collected every 2.5 min for 10 min. Epinephrine, amrinone, and the combination of both drugs significantly increased cardiac output, stroke volume, O2 delivery, and left ventricular stroke work. The increase in stroke volume (P < 0.05) was 12 +/- 6, 16 +/- 4, and 30 +/- 4 mL/beat with epinephrine, amrinone, and the combination of amrinone and epinephrine, respectively. The amrinone-epinephrine combination increased stroke volume as much as the sum of amrinone and epinephrine given separately. Systemic vascular resistance and pulmonary vascular resistance decreased with amrinone and amrinone-epinephrine, but not with epinephrine. Epinephrine increased mean arterial and mean pulmonary arterial pressures. Right ventricular ejection fraction did not significantly increase (P = 0.09) with epinephrine, but increased significantly with amrinone (0.45 to 0.53, P = 0.01), and with the combination (0.43 to 0.55, P = 0.006). These data indicate that amrinone and epinephrine effectively increase myocardial performance during cardiac surgery. Right ventricular function especially was improved with amrinone and the combination of amrinone and epinephrine. The combined effects of amrinone and epinephrine may be useful in patients recovering from the ischemia and reperfusion injury resulting from coronary artery bypass grafting.
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PMID:Combined inotropic effects of amrinone and epinephrine after cardiopulmonary bypass in humans. 821 47

A crucial element for weaning patients from cardiopulmonary bypass (CPB) rests on the selection of an appropriate therapeutic regimen. Amrinone, a phosphodiesterase III inhibitor, combines inotropic support with pulmonary and systemic vasodilatation, without increasing heart rate (HR) or myocardial oxygen consumption. These characteristics should be useful in the failing heart during weaning from CPB. Nineteen patients were included in this prospective, open-labelled, phase IV study when systolic blood pressure (DPAP) > 15 mmHg or central venous pressure (CVP) > 15 mmHg, during progressive separation from CPB. At that moment, CPB flow was increased to alleviate heart failure and amrinone administered as a bolus (0.75 mg.kg-1) followed by an infusion (10 micrograms.kg-1.min-1). Weaning from CPB was then resumed and haemodynamic variables (SBP, DPAP, CVP and HR) were compared with those measured at CPB flow when failure had first occurred. Failure to wean from CPB occurred at 57 +/- 28% of full pump flow. After the amrinone bolus, DPAP and CVP decreased by 20% and 21% respectively. Subsequently, 16 patients required the infusion of norepinephrine (4-8 micrograms.min-1) to maintain a SBP > 80 mmHg. Heart rate remained unchanged after the bolus of amrinone, after separation from CPB, and no arrhythmias were noted. Successful weaning from CPB was possible 12 +/- 8 min after the amrinone bolus. Weaning resulted in a cardiac index similar to that measured pre-bypass. Amrinone is rapidly effective during weaning from CPB and, in combination with norepinephrine, provides the necessary inotropic support during this unstable period.
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PMID:Amrinone, in combination with norepinephrine, is an effective first-line drug for difficult separation from cardiopulmonary bypass. 840 12

Induction of ventricular fibrillation (VF) is an important part of the process of inserting implantable cardioverter defibrillators (ICDs), allowing the measurement of defibrillation thresholds. However, animal studies have revealed that repeated cycles of VF and defibrillation result in depressed left ventricular (LV) function and reduced cardiac output. Short intervals of VF do not affect myocardial contractility but longer periods produce heart failure. Induced VF was used in a canine model to study profound myocardial stunning leading to heart failure, as well as the therapeutic potential of the phosphodiesterase inhibitor, amrinone (combined with epinephrine and norepinephrine). Amrinone was found to significantly (p < 0.05) increase contractility when added to a stable preparation supported by epinephrine and norepinephrine infusion; amrinone or catecholamines alone had no effect. In the clinical setting, the following factors may affect LV contractility during ICD surgery: catecholamines released as a result of hypotension; negative VF; ischemia; antiarrhythmic drugs; anesthetics; and bradycardia after device testing. Patients (n = 125) have tolerated ICD insertion well. Early data reveals no significant changes in ejection fraction. Though rare, death due to myocardial stunning and LV power failure can occur during ICD insertion. It may be possible to use arterial pressure monitoring to predict this event in vulnerable patients.
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PMID:Does ventricular fibrillation cause myocardial stunning during defibrillator implantation? 846 13

Cardiotonic effect of 4-(4'-n-butylaniline)-7,8-dimethoxy- 5H-pyrimido[5,4-b]indole (B11) was investigated in isolated cardiac tissue preparations. The action of this agent on force of contraction, beating frequency and cyclic nucleotide phosphodiesterase (PDE) activity was studied. Amrinone was used for comparison. B11 produced concentration-dependent (5 x 10(6)-1 x 10(-4)M) positive inotropic and positive chronotropic responses in guinea-pig atrial tissues. The potency of B11 was greater than that of amrinone. The cardiotonic effects of B11 were not modified by beta-adrenoceptor blockade. Carbachol inhibited the positive inotropic effect of B11. The activity of B11 was increased in desensitized left atrial tissues. B11 inhibited the activities of PDE isoenzymes (type I, II, IV and V) from dog heart ventricle and PDE type IV from guinea-pig heart ventricle nonselectively. It is concluded that B11 possesses potent positive inotropic activity in guinea-pig atria, and the effect is probably mediated by a non-selective inhibition of PDE activity.
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PMID:Inotropic and chronotropic effects of 4-(4'-n-butylaniline)-7,8- dimethoxy-5H-pyrimido[5,4-b]indole in guinea-pig atria. 856 29

Amrinone, a phosphodiesterase III inhibitor, is known to exert inotropic and vasodilating effects. This study was undertaken to investigate the hemodynamic effects and optimal dose of amrinone in patients undergoing coronary artery bypass surgery. Seventeen patients with ejection fraction > 0.45 were included. In both group B and C, amrinone 0.5 mg.kg-1 was administered in the venous reservoir near the end of cardiopulmonary bypass (CPB), and doses of 1 and 5 micrograms.kg-1.min-1 by an intravenous infusion. Additional group of A did not receive amrinone. In group B, amrinone increased cardiac index by 79% and stroke index by 81% while decreased mean arterial pressure by 19% and systemic vascular resistance by 59% in comparison with group A. Heart rate did not increase. In group C, changes of hemodynamic variables were almost the same compared with group B. These data suggests that amrinone improves left ventricular performance without increasing myocardial oxygen demand while recovering from CPB. However, a high dose of amrinone should be used in combination with catecholamines because its vasodilating action is potentiated by hyperdynamic state after CPB.
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PMID:[Hemodynamic effects of amrinone during emergence from cardiopulmonary bypass]. 858 58

Amrinone, a positive inotropic agent, is a selective phosphodiesterase III inhibitor and exerts vasodilatory effect on venous vessels. The present study was undertaken to compare the venodilatory effect of amrinone and theophylline, a nonselective phosphodiesterase inhibitor, in eight healthy male subjects. In a randomized crossover design, one of these drugs was infused into the dorsal hand vein preconstricted by phenylephrine and its diameter was measured using a linear variable differential transformer. The value of maximum vasodilation for amrinone (mean +/- standard deviation, 106% +/- 17%) was similar to that for theophylline (mean +/- standard deviation, 108% +/- 14%). However, the infusion rate of amrinone needed to induce 50% of maximum vasodilation was significantly less than that of theophylline (25 +/- 15 micrograms/minute vs. 192 +/- 87 micrograms/minute, respectively; P < 0.01). These findings suggest that the venodilatory activity of amrinone is more potent than that of theophylline in human subjects.
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PMID:Comparison of venodilatory effect of amrinone and theophylline in human subjects. 862 79


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