Effects of single administration of a phosphodiesterase III inhibitor during cardiopulmonary bypass: comparison of milrinone and amrinone. (1/66)

The effects of phosphodiesterase III (PDE III) inhibitors administered after aortic declamping during cardiopulmonary bypass (CPB) for open heart surgery were investigated. Ten patients (group M) were administered milrinone (50 microg/kg) after aortic declamping during CPB, 10 patients were administered amrinone (1 mg/kg) at the same time during their surgery (group A), and 10 patients served as controls with no drug administered (group C). Soon after bolus infusion of the PDE III inhibitor, perfusion pressure dropped significantly in groups M and A. However, after release of CPB and at the end of surgery, there was no difference in aortic pressure between the 3 groups. There were also no differences between the groups in heart rate, pulmonary artery pressure, and pulmonary capillary wedge pressure. After weaning from CPB, the cardiac index was high and systemic vascular resistance index was low in groups M and A. There were no significant differences in the need for additional catecholamines and time for rewarming between groups. No adverse reactions were observed. A single administration of a PDE III inhibitor during CPB was useful for post-CPB management of patients undergoing open heart surgery. Amrinone reduced perfusion pressures more than milrinone, but cardiac indices and aortic pressures after weaning from CPB showed no differences between group M and group A patients.  (+info)

Effects of amrinone on ischaemia-reperfusion injury in cirrhotic patients undergoing hepatectomy: a comparative study with prostaglandin E1. (2/66)

The effects of amrinone, a selective phosphodiesterase III inhibitor, on liver ischaemia reperfusion injury have not yet been clarified. Forty-five patients with hepatocellular carcinoma who underwent partial liver resection using Pringle's manoeuvre were studied. Patients were divided into three groups: those given amrinone, those given prostaglandin E1 (PGE1) and those not treated (controls). An indocyanine green (ICG) clearance test was performed before the operation and three times during surgery: just before induction of liver ischaemia, just after liver resection and 60 min after reperfusion. Blood lactate and base excess were measured at the same times. Systolic and diastolic arterial pressure, heart rate, cardiac index and oesophageal temperature were monitored. Aminotransferase levels were recorded the day before surgery, 1 h after operation and on the first and third postoperative days. These data were compared between groups. The ICG elimination rate, lactate and base excess in the amrinone group differed significantly from those in controls during the observation period (P = 0.03, P = 0.04 and P = 0.03, respectively). The differences between the PGE1 and control groups were not significant. There were no significant differences between the groups in perioperative vital signs, cardiac index or postoperative aminotransferase. Amrinone enhanced intraoperative ICG elimination in cirrhotic patients who underwent liver resection.  (+info)

Effects of the specific phosphodiesterase inhibitors on alloxan-induced diabetic rabbit cavernous tissue in vitro. (3/66)

An experimental study was done to examine a potential role of phosphodiesterase (PDE) inhibitors in the treatment of diabetic erectile dysfunction. Relaxant effect of specific PDE inhibitors were measured in strips of corpus cavernosum smooth muscle taken from control and diabetic groups. Diabetes mellitus was induced in New Zealand white rabbits using alloxan. Penises excised from diabetic rabbits 8 weeks after the induction of diabetes mellitus. In the organ bath strips from control and diabetic rabbit corpus cavernosum were precontracted and increasing doses of several PDE inhibitors were added. In the precontracted rabbit cavernous tissue, sulmazole and zaprinast specific PDE V inhibitors were equally potent and efficacious in vitro but amrinone, a specific PDE III inhibitor, exhibits low relaxant effects. All PDE inhibitors tested showed a similar relaxation effect on corpus cavernosum smooth muscle from control and 8-week diabetic rabbits. The present study provides the possibility of using selective PDE III and V inhibitors in the treatment of diabetic impotence.  (+info)

Lack of role for nitric oxide in cholinergic modulation of myocardial contractility in vivo. (4/66)

Despite intensive investigation, the role of nitric oxide (NO) in cholinergic modulation of myocardial contractility remains unresolved. The left anterior descending coronary artery of 34 anesthetized, open-chest dogs was perfused via an extracorporeal circuit. Segmental shortening (SS) was measured with ultrasonic crystals and coronary blood flow (CBF) was measured with an ultrasonic flow transducer. An intracoronary infusion of ACh (20 microg/min) was performed, with CBF held constant, under baseline and during dobutamine, CaCl(2), or amrinone at doses increasing SS by approximately 50% (10 microg/min, 15 mg/min, and 300 microg/min ic, respectively). ACh-induced responses during dobutamine were also assessed following treatment with the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME; 300 microg/min ic for 15 min). The effects of sodium nitroprusside (SNP; 80 microg/min ic), an exogenous NO donor, bradykinin (2.5 microg/min ic), a nonmuscarinic releaser of endothelial NO, and bilateral vagal stimulation (before and after L-NAME) were evaluated during dobutamine. ACh had no effect on SS under baseline or during CaCl(2), but it decreased SS during dobutamine or amrinone (-23 +/- 4% and -30 +/- 5%, respectively). Vagal stimulation also reduced SS during dobutamine. L-NAME did not alter the ACh- or vagal-induced decreases in SS during dobutamine. Neither SNP nor bradykinin affected SS during dobutamine. In conclusion, ACh and vagal stimulation have a negative inotropic effect during stimulation of the beta-adrenergic receptors that is independent of NO. The persistence of this effect during amrinone suggests that a mechanism downstream from adenylate cyclase is involved.  (+info)

In contrast to forskolin and 3-isobutyl-1-methylxanthine, amrinone stimulates the cardiac voltage-sensitive release mechanism without increasing calcium-induced calcium release. (5/66)

The objective of this study was to determine whether the voltage-sensitive release mechanism (VSRM) can be stimulated independently from Ca(2+)-induced Ca(2+) release (CICR) by drugs that elevate intracellular cAMP. Contractions were measured in voltage-clamped guinea pig ventricular myocytes at 37 degrees C. Na(+) current was blocked. We compared effects of agents that elevate cAMP through activation of adenylyl cyclase (1 microM forskolin), nonspecific inhibition of phosphodiesterases (PDEs) [100 microM 3-isobutyl-1-methylxanthine (IBMX)], and selective inhibition of PDE III (100-500 microM amrinone) on contractions initiated by the VSRM and CICR. Forskolin and IBMX significantly increased peak Ca(2+) current and CICR. In addition, these agents also markedly increased contractions elicited by test steps from -65 to -40 mV, which activate the VSRM. However, because these steps also induced inward current in the presence of forskolin or IBMX, CICR could not be excluded. In contrast, amrinone caused a large, concentration-dependent increase in VSRM contractions but had no effect on CICR contractions or Ca(2+) current. Sarcoplasmic reticulum Ca(2+), assessed by rapid application of caffeine (10 mM), was increased only modestly by all three drugs. Normalization of contractions to caffeine contractures indicated that amrinone increased fractional release by the VSRM, but not CICR. Forskolin and IBMX increased fractional release elicited by steps to -40 mV. Increases in CICR induced by forskolin and IBMX were proportional to caffeine contractures. Thus, positive inotropic effects of cAMP on VSRM contractions may be compartmentalized separately from effects on Ca(2+) current and CICR.  (+info)

Amrinone can accelerate the cooling rate of core temperature during deliberate mild hypothermia for neurosurgical procedures. (6/66)

We investigated the effects of i.v. amrinone on intraoperative changes of core temperature during deliberate mild hypothermia for neurosurgery. The patients in a control group (n=10) did not receive amrinone and patients in the amrinone group (n=10) received amrinone 5 microg kg(-1) min(-1) after a loading dose of 1.0 mg kg(-1). Anaesthesia was maintained with nitrous oxide in oxygen, propofol and fentanyl. After the induction of anaesthesia, patients were cooled and tympanic membrane temperature was maintained at 34.5 degrees C. After completion of the main surgical procedures, patients were rewarmed in the operating room. Tympanic membrane temperatures between 30 and 90 min after cooling were significantly lower in the amrinone group than in the control group. During cooling, the times taken to cool to 35 degrees C and to the lowest temperature were significantly shorter in the amrinone group than in the control group. These results suggest that i.v. amrinone can accelerate the cooling rate of core temperature during deliberate mild hypothermia for neurosurgical procedures.  (+info)

High-dose amrinone is required to accelerate rewarming from deliberate mild intraoperative hypothermia for neurosurgical procedures. (7/66)

BACKGROUND: Since the time available to provide the cooling and rewarming is limited during deliberate mild hypothermia, the technique to accelerate the cooling and rewarming rate of core temperature has been studied. Amrinone has been reported to accelerate the cooling rate but not the rewarming rate of core temperature during deliberate mild hypothermia. The failure of amrinone effect on the rewarming rate might be due to an insufficient dose of amrinone during hypothermic conditions. The authors therefore tested whether higher doses of amrinone can accelerate the rewarming rate of core temperature during deliberate mild hypothermia for neurosurgery. METHODS: After institutional approval and informed consent, 30 patients were randomly assigned to one of three groups. Patients in the control group (n = 10) did not receive amrinone; patients in the AMR 15 group (n = 10) received 15 microg x kg(-1) x min(-1) amrinone with a 1.0-mg/kg loading dose of amrinone at the beginning of cooling; and patients in the ReAMR group (n = 10) received 5 microg x kg(-1) x min(-1) amrinone with 1.0-mg/kg loading and reloading doses of amrinone at the beginning of cooling and rewarming, respectively. Administration of amrinone was started just after the induction of cooling and continued until the end of anesthesia. Anesthesia was maintained with nitrous oxide in oxygen, propofol, and fentanyl. After induction of anesthesia, patients were cooled, and tympanic membrane temperature was maintained at 34.5 degrees C. After completion of the main surgical procedures, patients were actively rewarmed and extubated in the operating room. RESULTS: The cooling and rewarming rates of core temperature were both significantly faster in both amrinone groups than in the control group. During the cooling and rewarming periods, forearm minus fingertip temperature gradient was significantly smaller in both amrinone groups than in the control group. During the rewarming period, heart rate and mean arterial pressure in the AMR 15 group were significantly faster and lower, respectively, than in the control group. Systemic vascular resistance in the AMR 15 group was smaller than in the control group throughout the study; on the other hand, only the value after the start of rewarming in the ReAMR group was smaller than in the control group. CONCLUSIONS: Amrinone at an infusion rate of 15 or 5 microg x kg(-1) x min(-1) with a reloading at the beginning of rewarming accelerated the rewarming rate of core temperature during deliberate mild hypothermia. This suggests that high-dose amrinone is required to accelerate rewarming from deliberate mild intraoperative hypothermia for neurosurgical procedures.  (+info)

Differential effects of amrinone and milrinone upon myocardial inflammatory signaling. (8/66)

BACKGROUND: Mounting evidence links systemic and local inflammatory cytokine production to myocardial dysfunction and injury occurring during ischemia-reperfusion, cardiopulmonary bypass, and heart failure. Phosphodiesterase inhibitors (PDEIs), used frequently in these states, can modulate inflammatory signaling. The mechanisms for these effects are unclear. We therefore examined the effects of 2 commonly used PDEIs, amrinone and milrinone, on cardiac cell inflammatory responses. METHODS AND RESULTS: Primary rat cardiomyocyte cultures were treated with endotoxin (LPS) or tumor necrosis factor-alpha (TNF-alpha), alone or in the presence of clinically relevant concentrations of amrinone or milrinone. Regulation of nuclear factor-kappa B (NFkappaB), nitric oxide synthase and cyclooxygenase isoforms, and cytokine production were assessed by electrophoretic mobility shift assays, Western immunoblotting, and enzyme-linked immunoassays, respectively. Both LPS and TNF-alpha induced significant NFkappaB activation, cyclooxygenase-2 (COX-2) expression, and inducible NO synthase (iNOS) and cytokine production; with the exception of COX-2 expression, all were significantly reduced by amrinone, beginning at concentrations of 10 to 50 micro mol/L. In contrast, milrinone increased nuclear NFkappaB translocation, iNOS and COX-2 expression, and cardiomyocyte production of interleukin-1beta. Cell-permeable cAMP increased inflammatory gene expression, whereas cell-permeable cGMP had no effect, indicating that the effects of amrinone were not due to phosphodiesterase inhibition. Similar results were seen in macrophages and coronary vascular endothelial cells. CONCLUSIONS: Both amrinone and milrinone have significant effects on cardiac inflammatory signaling. Overall, amrinone reduces activation of the key transcription factor NFkappaB and limits the production of pro-inflammatory cytokines, whereas milrinone does not.  (+info)

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