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PubMed1988

Effect of amrinone on diaphragm blood flow.

The purpose of the present study was to examine the effect of amrinone, a drug known to augment cardiac output and dilate peripheral vascular beds, on diaphragm blood flow. Studies were performed on 12 anesthetized mechanically ventilated dogs in which strips of left costal diaphragm were developed in situ. Strip blood flow was assessed with a drop counter attached to a catheter tied into the phrenic veins' draining strips. Strip tension was measured with an isometric force transducer. Amrinone was administered as an intravenous bolus of 2 mg/kg followed by a continuous infusion of 25 micrograms.kg-1.min-1. Amrinone increased cardiac output and resting diaphragm blood flow [from 1.8 +/- 0.1 to 3.2 +/- 3 (SE) l/min and from 13 +/- 2 to 29 +/- 6 (SE) ml.100 g-1.min-1, respectively, P less than 0.001 for both comparisons]. Amrinone also increased blood flow during periods of rhythmic contraction (tension time indexes of 0.1-0.4, P less than 0.05 for comparisons of flow with and without amrinone at each tension time index) and increased the magnitude of the postcontraction hyperemia (P less than 0.02 for comparisons of hyperemic flow with and without amrinone at tension time indexes of 0.3 and 0.4). Graded occlusion of the inferior vena cava produced reductions in arterial pressure, cardiac output, and diaphragm blood flow both before and after amrinone. Both cardiac output and diaphragm blood flow were greater after amrinone, however, at all levels of blood pressure examined. These findings indicate that amrinone can override diaphragm vasoregulatory systems and augment diaphragm blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Amrinone↗
PubMed1983

Amrinone. A preliminary review of its pharmacological properties and therapeutic use.

Amrinone is a bipyridine derivative with positive inotropic effects and vasodilatory properties. However, in the clinical setting of congestive heart failure, the relative contribution of these factors remains a matter of conjecture. Its mode of action appears to be related to alterations in extracellular and intracellular calcium balance, probably mediated by increased levels of tissue cyclic adenosine monophosphate and possibly involving a sodium-dependent pathway. Clinical experience has mostly been short term and is limited to a relatively small number of patients with severe congestive heart failure, refractory to conventional treatment. Amrinone rapidly improves cardiac performance by decreasing systemic vascular resistance (afterload), decreasing the determinants of left ventricular filling pressure (preload) and improving the cardiac contractility. Improvements in exercise performance and clinical symptomatology occur without an increase in heart rate or decrease in mean arterial pressure. Amrinone has been compared with dopamine, dobutamine, pirbuterol and prazosin in preliminary short terms studies in patients with severe congestive heart failure, although more studies are needed before any relative clinical advantages or disadvantages can be ascribed to amrinone. Initial experience suggests that the addition of vasodilators such as hydralazine and isosorbide dinitrate to amrinone therapy may confer additional haemodynamic benefits. Preliminary medium term studies suggest that tolerance to the haemodynamic effects of amrinone does not usually occur, but long term studies are needed to determine whether amrinone alters the normal progression of the disease and whether overall mortality is affected. Amrinone has usually been administered as intravenous bolus doses (totalling 1.5 to 3.6 mg/kg/day) and/or continuous intravenous infusion, with varied results. Generally, an oral dose greater than the intravenous dose is required to achieve an equivalent level of response. Reversible, usually asymptomatic, thrombocytopenia occurs in about 20% of patients treated with amrinone. Arrhythmias and gastrointestinal disturbances have been reported, but wider clinical experience is required to determine the side effect profile of the drug.

Absorption↗
PubMed1992

A comparison of amrinone and glucagon therapy for cardiovascular depression associated with propranolol toxicity in a canine model.

This study's objective is to evaluate the ability of glucagon and amrinone to reverse propranolol induced cardiovascular depression in a canine model, compared to a control of normal saline. The study design included 18 animals which received intravenous propranolol (10 mg/kg) resulting in significant depression in heart rate, cardiac output, mean arterial pressure, maximal ventricular dP/dt and stroke volume. Each canine was randomly assigned to one of three treatment groups; controls (normal saline only), glucagon (20 micrograms/kg bolus) and amrinone (4 mg/kg bolus). Cardiovascular parameters were monitored at 1, 6, 11, 21 and 31 min after treatment was rendered. Multiple comparison procedures at each time period controlled the overall alpha-level at .05. Compared to control animals, both amrinone and glucagon were effective in reversing propranolol-induced depression of dP/dtmax at 6 and 11 min for glucagon and 11 min for amrinone and cardiac output at 1, 6 and 11 min for glucagon and 1 min for amrinone. Amrinone and glucagon significantly increased stroke volume over control values at 1 min and tended to do so at the remaining time periods. The two days caused a similar degree of arteriolar vasodilation which was significantly greater than that seen in control animals at 1 and 6 min. Beta blocker induced bradycardia did not respond significantly to amrinone while glucagon induced a tachycardia which is unique to canines. It is concluded that in this canine model, amrinone appears to be an effective therapeutic alternative to glucagon for reversing depressed dP/dtmax, cardiac output and stoke volume induced by propranolol toxicity. Unlike glucagon, amrinone appears to lack positive chronotropic activity which may limit its clinical utility in the treatment of beta blocker overdose.

Amrinone↗
PubMed1982

Positive inotropic effect of amrinone in relation to cyclic nucleotide metabolism in the canine ventricular muscle.

Experiments were carried out in the canine isolated right ventricular muscle in order to study the positive inotropic effect of amrinone in relation to the cyclic AMP and cyclic GMP metabolism. The positive inotropic effect of amrinone was accompanied by accumulation of cyclic AMP in the tissue: the cyclic AMP level was elevated in a similar time course to that of the increase in force of contraction and in a concentration-dependent manner in the presence of a beta adrenoceptor blocking agent, pindolol (3 X 10(-8) M). An excellent correlation was found between the force of contraction and cyclic AMP level in the presence of amrinone: the relationship was similar to that obtained previously with papaverine, a cyclic AMP phosphodiesterase inhibitor. The cyclic GMP level determined simultaneously was not changed by amrinone. The amrinone-induced increases in force of contraction and cyclic AMP level were markedly depressed by carbachol (3 X 10(-6) M); the relationship between the force of contraction and cyclic AMP level in the presence of amrinone was not changed by carbachol. Amrinone inhibited the cyclic AMP phosphodiesterase purified from the canine right ventricular muscle and enhanced the positive inotropic effect of isoproterenol. Amrinone shortened the time required for relaxation of a single contraction to the same extent as isoproterenol and cyclic AMP phosphodiesterase inhibitors such as 1-methyl-3-isobutylxanthine and papaverine. These results altogether strongly suggest that the change in cyclic AMP metabolism is involved in the positive inotropic effect of amrinone on the canine ventricular muscle.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1982

Inotropic and electrophysiologic effects of amrinone in untreated and digitalized ventricular tissues.

The purposes of this study were to determine whether amrinone induces oscillatory afterpotentials (OAP) or aftercontractions (AC) in Purkinje tissue or myocardium, to determine whether a relationship exists between the production of OAP or AC and the inotropic effects of amrinone and to determine possible effects of amrinone on the oscillations and the positive inotropic effect produced by digitalis. Isolated canine papillary and trabecullar muscles, as well as false tendons, were exposed to 5.3 X 10(-4) M amrinone. Some of the preparations had been pretreated with acetylstrophanthidin (AS) in a dose just sufficient to induce OAP or AC. Standard electrophysiologic techniques were used to record transmembrane action potentials. Developed tension also was recorded. Amrinone by itself did not induce OAP or AC in myocardium or false tendons. This was true even when the resting membrane potential of the false tendons was reduced by means of focal current application. Amrinone increased the amplitude of AS-induced oscillations in both myocardium and false tendons. Amrinone increased strength of contraction of untreated myocardium at all basic cycle lengths and of AS-treated myocardium, especially at shorter basic cycle lengths. Amrinone decreased strength of contraction both of untreated and AS-treated false tendons at all basic cycle lengths. The results suggest that there may be important differences in the mechanisms of action of amrinone and digitalis.

Aminopyridines↗
PubMed1996

Relaxation of human isolated pulmonary arteries by amrinone.

Amrinone, a selective phosphodiesterase III inhibitor, has been developed as a nonglycoside, noncatecholamine agent with positive inotropic effect. In this study, we examined the effect of amrinone on human pulmonary arterial strips in vitro to understand its action on human pulmonary circulation. Amrinone (10(-5)-10(-3) g/ml) caused dose-dependent relaxation of human pulmonary arterial strips precontracted with 60 mM KCl. Preincubation with either meclofenamate (3.1 microM), a cyclooxygenase inhibitor, or L-N(G)-nitroarginine (100 microM), a competitive inhibitor of EDRF/NO, failed to inhibit amrinone-induced pulmonary vasodilation. The cyclic AMP (cAMP) levels in the supernatant of the lung vessel homogenates increased after incubation with amrinone (10(-3) g/ml). These findings indicate that amrinone causes vasodilation of human pulmonary artery in vitro, and suggest a possible role for cAMP in the mechanisms of amrinone-induced pulmonary vasodilation. Because it is suggested that amrinone has not only positive inotropic effect but also pulmonary vasodilative effect in human in this study, we speculate that amrinone could be an useful agent for the treatment of an increase in right heart afterload and consequent pulmonary hypertension and right heart failure after lung resection in human.

Adult↗
PubMed1986

Inhibition of cyclic AMP-dependent protein kinase activity by the cardiotonic drugs amrinone and milrinone.

Amrinone and milrinone are new cardiotonic drugs that have potent inotropic and vasodilatory properties. The mechanism of action of these agents is controversial, but the positive inotropic component is thought to be due to the inhibition of phosphodiesterase. Because amrinone and milrinone have been shown to be involved primarily in cyclic AMP-mediated processes, we examined the effect of these agents on cyclic AMP-dependent protein kinase. The results indicate that amrinone and milrinone inhibit cyclic AMP-dependent protein kinase activity by competing with ATP but not cyclic AMP binding sites. Dissociation constants (Ki) of amrinone and milrinone for ATP binding sites on protein kinase were calculated to be 100-300 microM and 842 microM, respectively. The phosphodiesterase inhibitor isobutylmethylxanthine (1 mM) had no effect on protein kinase activity. Amrinone and milrinone inhibited the catalytic subunit of protein kinase to the same degree as the holo-enzyme by competitively inhibiting the binding of ATP. Amrinone and milrinone had no effect on phospholipid-sensitive, calcium-dependent protein kinase indicating that there may be differences in the ATP binding sites on these two protein kinases. Inhibition of cyclic AMP-dependent protein kinase by amrinone and milrinone occurs at concentrations higher than those used clinically. However, because amrinone and milrinone are lipophilic drugs, they may be useful tools for the investigation of protein kinase mediated reactions.

1-Methyl-3-isobutylxanthine↗
PubMed1984

Amrinone in the treatment of chronic cardiac failure.

The efficacy and safety of oral amrinone were examined in 17 patients with moderately severe to severe heart failure that was refractory to standard medical therapy and vasodilators. The short-term and 28 week response to open amrinone therapy was assessed first, followed by a placebo-controlled, double-blind withdrawal study of two 13 week stages in nine patients. Rest and exercise ventricular function were determined before and after 32 hours of amrinone; aerobic capacity was serially assessed. After 2 hours, 1.64 mg/kg amrinone produced a 40% (p less than 0.001) increase in cardiac output and a 32% (p less than 0.02) decrease in pulmonary wedge pressure without altering heart rate or blood pressure. The exercise cardiac index-wedge pressure curve obtained 32 hours after the first oral dose was significantly shifted (p less than 0.05) above control values. A sustained improvement in maximal oxygen uptake was noted during long-term open amrinone therapy. Subsequently, seven of the patients randomized to placebo therapy had a significant deterioration of symptoms or exercise tolerance, or both. After 4 weeks of readministration of amrinone, clinical stability was once again established and exercise tolerance was improved by Weeks 8 to 16. Adverse effects of thrombocytopenia (one patient) and hepatic dysfunction (one patient) attributable to amrinone were observed. It is concluded that amrinone is effective in the long-term treatment of chronic cardiac failure.

Aged↗
PubMed2005

Phosphodiesterase-III-inhibition with amrinone leads to contracture development in skeletal muscle preparations of malignant hyperthermia susceptible swine.

BACKGROUND AND OBJECTIVE: The phosphodiesterase-III (PDE-III) inhibitor enoximone-induced marked contractures in skeletal muscle specimens of malignant hyperthermia (MH) susceptible (MHS) human beings and swine. Whether this is a substance specific effect of enoximone or caused by inhibition of PDE-III remained unclear. Therefore, the effects of the PDE-III inhibitor amrinone in porcine MH normal (MHN) and MHS skeletal muscles were investigated. METHODS: MH-trigger-free general anaesthesia was performed in eight MHS and eight MHN swine. The MH status of the swine was determined by detection of the Arg615-Cys point mutation on chromosome 6 indicating MH susceptibility. Skeletal muscle specimens were excised for the in vitro contracture tests with amrinone. Amrinone was added cumulatively every 5 min to muscle specimens in order to obtain organ bath concentrations between 20 and 400 micromol L(-1). The in vitro effects of amrinone on muscle contractures and twitches were measured. RESULTS: Amrinone-induced contractures in all skeletal muscle preparations. MHS muscles developed contractures at significantly lower bath concentrations of amrinone than MHN muscles. Contractures of MHS compared to MHN muscles were significantly larger at bath concentrations of 80, 100, 150, 200 and 400 micromol L(-1) amrinone. Muscle twitches remained unchanged up to and including 200 micromol L(-1) amrinone. CONCLUSIONS: Inhibition of PDE-III in general elicited higher contractures in MHS than in MHN muscles. Therefore, a contribution of PDE-III and the cyclic adenosine monophosphate (cAMP) system in the pathophysiology of MH must be suspected.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1984

Responses of isolated dog arteries to amrinone.

Helically-cut strips of dog cerebral, coronary, mesenteric, renal and femoral arteries contracted with prostaglandin (PG) F2 alpha or K+ responded to amrinone (10(-5) to 10(-4) mol X litre-1) with relaxation, which was not influenced by treatment with propranolol, atropine, cimetidine, aminophylline or aspirin. The contractile response of mesenteric arteries to transmural electrical stimulation (2, 5 and 20 Hz) and noradrenaline was attenuated by amrinone (3 X 10(-5) and 10(-4) mol X litre-1); the attenuation of the response to nerve stimulation and noradrenaline did not significantly differ. Ca2+-induced contractions in mesenteric arteries exposed to Ca2+-free media and depolarised by excess K+ were inhibited by amrinone, and the inhibition could not be reversed by the addition of excess Ca2+. Treatment with amrinone potentiated the relaxant responses of mesenteric arteries to adenosine but did not alter the response to isoprenaline. Amrinone in concentrations sufficient to produce moderate and marked relaxation did not significantly alter the content of cyclic AMP in mesenteric arteries. Attenuation by amrinone of the contractile response to transmural stimulation, noradrenaline and Ca2+ and the relaxation of a variety of arteries induced by amrinone may not be due to interference with the transmembrane influx of Ca2+ and intracellular accumulation of cyclic AMP but to a nonspecific action on arterial smooth muscle. Amrinone appears to increase the metabolic vasodilatation by potentiating the vasodilator action of adenosine.

Adenosine↗
PubMed1988

Haemodynamic effects of amrinone in the anaesthetized pig.

The vasodilator and inotropic actions of amrinone were investigated in mini-pigs under pentobarbitone anaesthesia. Left ventricular volume was determined angiocardiographically under afterload and isovolumetric conditions. Furthermore, aortic flow, left ventricular pressure and aortic pressure were measured. In some of the animals, the beta-adrenergic receptors were blocked with propranolol prior to the administration of amrinone. Without blockade of the beta-receptors, amrinone (2 mg kg-1) caused a significant reduction in mean aortic pressure. Due to less end-diastolic ventricular filling, stroke volume decreased, and thus ejection fraction remained constant. Since heart rate increased under amrinone, cardiac output remained constant. At the same time, the maximum rate of pressure rise increased, despite less end-diastolic ventricular filling. After blockade of the beta-adrenergic receptors, aortic pressure, end-diastolic ventricular filling, and stroke volume also decreased with amrinone. In contrast, heart rate remained practically constant, so that cardiac output declined. The maximum rate of pressure rise also declined due to less end-diastolic ventricular filling. It can be concluded from these results that, in situ, the primary action of amrinone occurs on vascular smooth muscle and that a positive inotropic activity with a normal dosage of amrinone is only an indirect outcome of reflex activation of the sympathetic system. Analysis of isovolumetric mechanograms and the ejection phase does not indicate a direct positive inotropic effect of amrinone. In the failing heart, however, beneficial effects can be expected, since the maxima curves follow a flatter course. Thus a reduction in afterload can lead to a significant increase in stroke volume, provided that aortic pressure does not fall below the critical coronary perfusion pressure.

Amrinone↗
PubMed1986

Comparative immediate hemodynamic and hormonal effects of amrinone and captopril in patients with severe chronic heart failure.

To compare the responses to oral inotropic and vasodilator drugs, maximally effective doses of amrinone (300 mg over 3 hours) and captopril (25 mg orally) were administered to 21 patients with severe chronic heart failure, who had not received either agent previously. Despite similar decreases in systemic vascular resistance with both drugs, amrinone produced greater increases in cardiac index (+ 0.56 vs. + 0.41/min/m2, p less than 0.05) and smaller decreases in mean arterial pressure (-11.1 vs. -15.2 mm Hg, p less than 0.05) than did captopril; three patients became symptomatically hypotensive with captopril, but none did so after amrinone. These differences were due to a significant decrease in heart rate with captopril (-6.3 beats/min, p less than 0.01), whereas heart rate increased with amrinone (+ 4.3 beats/min, p less than 0.01); the increases in stroke volume index with both drugs were similar. Despite similar decreases in left ventricular filling pressures, the decrease in mean right atrial pressure with amrinone was greater than with captopril (-5.6 vs. -3.2 mm Hg, p less than 0.01). This difference was the result of the greater decrease in pulmonary arteriolar resistance, and hence in right ventricular afterload, with amrinone than with captopril, (-33% vs. -16%, respectively), p less than 0.01. Despite these superior hemodynamic responses to amrinone, when patients received sequential long-term treatment with both drugs during the follow-up period, only 12% of patients benefitted during therapy with amrinone, whereas 64% improved clinically with captopril.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Amrinone and verapamil-propranolol induced cardiac depression during isoflurane anesthesia in dogs.

This study was designed to investigate the possibility of whether verapamil diminishes the effects of amrinone, whether amrinone can reverse verapamil-propranolol depression, and also to evaluate whether the order of administering the drugs would have any effect during 1.7-1.8% end-tidal isoflurane anesthesia in dogs. At 3-4-week intervals, each of six conditioned mongrel dogs (23 +/- 1 kg) received amrinone (A) (4 mg/kg plus 100 micrograms X kg-1 X min-1), verapamil (V) (200 micrograms/kg plus 7.5 micrograms X kg-1 X min-1) and propranolol (P) (150 micrograms/kg plus 0.8 microgram X kg-1 X min-1) in four different orders of administration: VAP, AVP, VPA, and PVA. Plasma levels achieved were 15 +/- 1 to 24 +/- 2 micrograms/ml for amrinone, 24 +/- 2 to 59 +/- 10 ng/ml for propranolol, and 81 +/- 10 to 163 +/- 17 ng/ml for verapamil, equivalent to high therapeutic (amrinone) and therapeutic (propranolol, verapamil) levels in humans. The results of this study show that amrinone is able to reverse many of the effects of verapamil (group VAP) and also many of the effects of verapamil-propranolol or propranolol-verapamil (groups VPA, PVA) combinations. Amrinone improved cardiac index, left ventricular dP/dtmax, pulmonary capillary wedge pressure, and central venous pressure without increasing catecholamines. However, mean arterial pressure remained decreased with decreased systemic vascular resistance, which necessitates careful consideration depending upon patient circumstances. The results also show that verapamil-propranolol can reverse the positive inotropic effects of amrinone (group AVP).(ABSTRACT TRUNCATED AT 250 WORDS)

Amrinone↗
PubMedDate not supplied

Cardiac effects of amrinone on rabbit papillary muscle and guinea pig Langendorff heart preparations.

Amrinone (50-1,000 microgram/ml) produces a dose-dependent inotropic action on rabbit papillary muscle. The hypodynamic state following prolonged stimulation is prevented or abolished by amrinone, and contractile force remains significantly elevated over drug-free controls throughout the ensuing 3-h duration of exposure. In a concentration of 1 mg/ml, dysrhythmic phenomena occasionally appeared, e.g., bigeminy, automaticity, and elevated threshold to electrical stimulation. Bigeminy could be abolished either by increasing the external K+ concentration in the bathing media, or by raising the stimulating voltage. However, amrinone failed to alter the refractory period following 60 min of exposure. In isolated perfused guinea pig Langendorff heart preparations, amrinone (50 microgram/ml) significantly increased coronary flow, myocardial oxygen consumption (MVO2), cardiac work, and, during the period of peak activity, dP/dt. However, it had no significant effect on cardiac efficiency. And, as in the papillary muscle preparation, the effect of amrinone was easily reversed by perfusing the preparation with fresh (no-drug) media. Preliminary evidence shows that amrinone fails to reverse the negative inotropic action of verapamil as well as calcium-free media, although the effects on heart rate, coronary flow, and MVO2 were reversed. However, the higher the external calcium concentration, the greater was the level of contractile response achieved by amrinone. Thus, the mechanism of amrinone-induced augmentation appears to be dependent upon the availability of calcium.

Aminopyridines↗
PubMedDate not supplied

Electrophysiological actions of amrinone in dogs with cardiac lesions.

We examined the actions of amrinone in five models using dogs to determine under what circumstances intravenous amrinone might exert arrhythmogenic or antiarrhythmic properties. In dogs with 24-h post-coronary artery ligation arrhythmias, amrinone, given at incrementally increasing doses of 1.5, 3.0, and 6.0 mg/kg at 30-min intervals, produced significant increases of cardiac contractility without altering the severity of the arrhythmia. In dogs with 2- to 6-day-old ischemic lesions and 90-100% sinus beats, a bolus dose of 3.0 mg/kg amrinone was followed by an increased incidence of abnormal beats (p = 0.013); neither 1.5 nor 6.0 mg/kg caused a significant incidence of arrhythmias. Acute occlusion of the left anterior descending coronary artery followed by reperfusion caused fibrillation in nine of 15 control dogs and two of 14 dogs treated with 2.3 mg/kg amrinone. This difference was significant at the level p less than 0.05. In ouabain-intoxicated dogs, amrinone at 1.0 and 3.0 mg/kg neither worsened nor improved the arrhythmias. In the atrial circus flutter arrhythmia, amrinone increased ventricular heart rate by a significantly greater amount than it increased atrial rate, suggesting that amrinone facilitates atrioventricular conduction.

Aminopyridines↗
PubMedDate not supplied

Amrinone and energy output of rabbit papillary muscles.

We studied the effects of amrinone (300 micrograms X ml-1) on the mechanical and energetic outputs of nonfailing rabbit papillary muscles at 27 degrees C using a myothermic technique. Amrinone was found to markedly stimulate the basal (i.e., nonbeating) metabolism. In mechanical experiments, at a 0.5-Hz stimulus rate, amrinone increased the rate of stress development and peak active stress but shortened the time to peak stress and the contractile duration. The linear relationship between total (active + passive) stress and heat production was altered by amrinone such that there was a 68% increase in the activation heat component (intercept) and an 11% increase in the energy cost per unit stress development (slope). In afterloaded isotonic experiments amrinone increased the capacity of papillary muscles to accomplish external work (W) by approximately 50% on average; however, this effect was associated with an increased total energy usage per beat (ET) such that the overall mechanical efficiency (W/ET X 100%) was not significantly altered at any load level. We conclude that amrinone greatly increases calcium delivery to the myofilaments and slightly increases the cost of stress development. These effects are examined in the light of amrinone's postulated mode of action, and possible reasons for the clinical observation of a decrease in myocardial oxygen consumption after amrinone administration are considered.

Aminopyridines↗
PubMed1999

Amrinone, a phosphodiesterase III inhibitor, and arachidonic acid metabolism in humans.

Amrinone-a phosphodiesterase III inhibitor-is used in the treatment of acute heart failure. In addition to its hemodynamic effects, amrinone has been shown to inhibit thromboxane synthesis in vitro. We investigated the effects of amrinone on thromboxane, prostaglandin, and leukotriene synthesis in humans. Eight healthy male volunteers took part in this single-blind study in which either amrinone (a 1.5-mg/kg bolus in 30 min and after that 10 microg/kg/min for 1 h 30 min) or placebo (0.9% NaCl) were infused. Amrinone infusion increased systolic blood pressure but had no significant effect on diastolic blood pressure or heart rate. Amrinone did not modulate thromboxane B2 synthesis stimulated by either spontaneous clotting or calcium-ionophore A23187 in whole blood. Amrinone had no effects on prostaglandin E2 or leukotriene E4 production in A23187-stimulated whole blood, nor did it affect urinary excretion of 11-dehydrothromboxane B2 or 2,3-dinor-6-keto-prostaglandin F1alpha, the index metabolites of thromboxane A2 and prostacyclin productions, respectively. We conclude that amrinone has no effects on eicosanoid production in humans at the dose level used in this study, and that the hemodynamic effects noticed are not mediated via cyclooxygenase or lipoxygenase products of arachidonic acid metabolism.

Adult↗
PubMed1991

Interactive effects of isoflurane and amrinone in the feline intestinal and renal circulation.

Interactive effects of the phosphodiesterase-III inhibitor amrinone and isoflurane were investigated in cats. Cardiac output (thermodilution method), and intestinal (IBF) and renal (RBF) blood flows (optical flowmetry) were measured. Intestinal (IVR) and renal (RVR) vascular resistances were derived. To discriminate between pressure-related local myogenic vascular responses and primary vascular drug effects, intestinal and renal perfusion pressures (50 mmHg; 6.7 kPa) were controlled. The protocol included steady-state recordings with and without isoflurane in a randomized order, both before and after the administration of amrinone (2 mg.kg-1 i.v. + 2 mg.kg-1.h-1 i.v.. Amrinone induced no significant changes in IVR or RVR during basal chloralose anesthesia. During administration of 0.8% isoflurane, amrinone produced decreases in IVR and RVR, which were more pronounced than the vasodilator responses induced by this dose of isoflurane alone. On the other hand, with 1.6% isoflurane, amrinone did not add to the vasodilation. The cardiac effects of isoflurane and amrinone were small. Our data indicate that the vascular tone before administration of amrinone could be crucial for the vascular response of the drug and that isoflurane can significantly influence the regional circulatory effects of amrinone.

Amrinone↗