Milrinone is a positive inotropic/vasodilator agent in both preclinical and clinical studies. Milrinone has been shown previously to inhibit specific type III PDE isolated from different sources. To investigate the effect and the mechanism of milrinone on the corpus cavernosum, we have studied on the human and rabbit corpus cavernosum using organ bath and measured the levels of cAMP and cGMP after treatment of milrinone and papaverine. Our results show that milrinone relaxes human and rabbit corpus cavernosal tissue in a dose- dependent manner. And significant increases in cAMP content were evident with milrinone. These indicate that the accumulation of cAMP resulting from the inhibition of type III PDE plays an important role in milrinone on rabbit corpus cavernosum. And these may reflect the impotence of cAMP dependent second messenger systems for the relaxation of penile smooth muscle. These results suggest a possible potential for milrinone in the treatment of impotence.
Baths ; Erectile Dysfunction ; Humans* ; Male ; Milrinone* ; Muscle, Smooth ; Papaverine ; Relaxation ; Second Messenger Systems

BACKGROUND: Hemodynamic derangement during off-pump coronary artery bypass surgery (OPCAB) is mainly attributed to impaired filling and diastolic dysfunction. An elevated ratio of the mitral velocity to the early-diastolic velocity of the mitral annulus (E/e' > 15) is a relatively new indicator of diastolic function, and this was reported to be associated with impaired hemodynamics during OPCAB. We investigated the efficacy of milrinone on the perioperative hemodynamics and short term outcomes of patients with an E/e' > 15 and who underwent OPCAB. METHODS: The patients were randomly allocated into either group C (control, n = 31) or group M (n = 31) and they were treated with the same amount of either normal saline or milrinone (0.5 microg/kg/min) without bolus loading after completion of internal mammary artery harvest until the end of operation. Hemodynamic measurements were recorded after the induction of anesthesia (T1), 5 min after starting each distal anastomosis of the left anterior descending artery (T2), left circumflex artery (T3) and right coronary artery (T4), and 5 min after sternum closure (T5). RESULTS: The mixed venous oxygen saturation (SvO2) was lower through T2-T4 compared to the baseline value in both groups, while the degree of the decrease was significantly less in group M than that in group C. The other hemodynamic variables, the operative data and the postoperative outcomes were similar between the two groups. CONCLUSIONS: Intraoperative infusion of milrinone did not significantly improve the perioperative hemodynamics and the subsequent short term outcomes for the patients with preexisting diastolic dysfunction as represented by an elevated E/e' value, although it reduced the degree of decrease of the SvO2 during OPCAB.
Anesthesia ; Arteries ; Coronary Artery Bypass, Off-Pump ; Coronary Vessels ; Hemodynamics ; Humans ; Mammary Arteries ; Milrinone ; Oxygen ; Sternum

BACKGROUND: AVP (arginine vasopressin) shows unique hemodynamic characteristics, as a vasopressor. AVP has been tried in many cathecholamine refractory vasodilatory situations, and sometimes resulted in effective hemodynamic improvement. In this study, we hypothesized that low dose AVP infusion could recover the decreased SVR (systemic vascular resistance) induced by milrinone infusion with minimal effect on PVR (pulmonary vascular resistance). METHODS: Sixteen patients undergoing OPCAB participated in this study. After a loading dose milrinone was infused, low dose vasopressin infusion was started and titrated until the systemic blood pressure increased by 20%. During the study, hemodynamic factors including pulmonary capillary wedge pressure and cardiac output were measured using a continuous thermodilution technique with a Swan-Ganz catheter. RESULTS: Milrinone infusion reduced both SVR and PVR. And vasopression infusion increased SVR, but show relatively less effect on PVR. CONCLUSIONS: Low-dose vasopressin infusion could be used to recover the SVR decrease caused by milirinone infusion with little effect on PVR.
Blood Pressure ; Cardiac Output ; Catheters ; Hemodynamics* ; Humans ; Milrinone* ; Pulmonary Wedge Pressure ; Thermodilution ; Vasopressins*

BACKGROUND: Dobutamine, isoproterenol, and milrinone are inotropic agents with vasodilatory properties, and are frequently used perioperatively. We undertook to examine the effects of these three drugs on the pulmonary vasculature, excluding cardiovascular effects, by determining their effects on pulmonary artery pressure and hypoxic pulmonary vasoconstriction in an isolated rat lung model. METHODS: Thirty Sprague-Dawley rats were divided into a dobutamine group (n = 10), an isoproterenol group (n = 10) and a milrinone group (n = 10). Dobutamine 50microgram, 500microgram, and 5,000microgram, isoproterenol 0.4microgram, 4microgram, and 40microgram, and milrinone 2.5microgram, 25microgram, and 250microgram were added to perfusate sequentially during normoxic ventilation (21% O2-5% CO2-balanced N2). Baseline pulmonary artery pressure changes and subsequent hypoxic pressor responses during hypoxic ventilation (5% O2-5% CO2-balanced N2) were observed. RESULTS: Dobutamine, isoproterenol, and milrinone all decreased baseline pulmonary artery pressures and hypoxic pressor responses in a dose-dependent manner (P < 0.05). The last dose listed for each of the three drugs reversed hypoxic pulmonary vasoconstriction nearly completely. The calculated dose required to reduce the hypoxic pressor response to 50% of the initial response before drug administration (ED50) was 155microgram (95% CI: 80-263microgram) for dobutamine, 0.23microgram (95% CI: 0.011-0.75 microgram) for isoproterenol and 6.31microgram (95% CI: 3.1-10.8microgram) for milrinone. The relative potency of the drugs on HPV, based on ED50 was dobutamine 10: isoproterenol 0.015: and milrinone 0.41. CONCLUSIONS: Dobutamine, isoproterenol, and milrinone all reduced pulmonary vascular resistance and hypoxic pulmonary vasoconstriction in a dose dependent manner. (Korean J Anesthesiol 2004; 46: 454~461)
Animals ; Dobutamine* ; Isoproterenol* ; Lung* ; Milrinone* ; Pulmonary Artery ; Rats* ; Rats, Sprague-Dawley ; Vascular Resistance ; Vasoconstriction* ; Ventilation

BACKGROUND: The aims of this study were to test if amrinone or milrinone reverses cardiac depression induced by the exposure to isoflurane in the isolated heart and to determine whether amrinone or milrinone dilates the coronary artery directly. METHODS: Using the isolated Sprague-Dawley rat hearts, heart rate, left ventricular pressure, dp/dt (differentiated rate of pressure development), O2 delivery(DO2), myocardial oxygen consumption(MVO2), and percent O2 extraction were measured. After the isolated hearts were exposed to isoflurane at 1.2 vol% during 10 min, amrinone(10, 50, 100 M) or milrinone(1, 5, 10 M) was separately given to six groups. RESULTS: Amrinone and milrinone reversed, not statistically significant, the depression of cardiac contractility induced by isoflurane, while the isoflurane-induced bradycardia substantially returned to normal by amrinone 100 M. And amrinone and milrinone elevated coronary flow, DO2, MVO2, while isoflurane increased in coronary flow and DO2, except MVO2. CONCLUSIONS: These results suggest that amrinone and milrinone did not counteract the isoflurane-induced cardiac depression and indirectly increased in coronary blood flow through the elevation of cardiac work.
Amrinone* ; Animals ; Bradycardia ; Coronary Vessels ; Depression ; Heart Rate ; Heart* ; Isoflurane ; Milrinone* ; Myocardium* ; Oxygen ; Rats* ; Rats, Sprague-Dawley ; Ventricular Pressure

Severe portopulmonary hypertension (PPHT) is considered a contraindication for liver transplantation (LT) because of the associated high mortality and poor prognosis. We report the case of a 57-year-old cirrhotic woman with severe PPHT (mean pulmonary artery pressure [mPAP] > 65 mmHg), who underwent a successful living donor LT. Intra-operative use of inhaled iloprost, milrinone, dobutamine, and postoperative use of inhaled nitric oxide and oral sildenafil failed to lower the pulmonary artery pressure (PAP). The patient responded only to nitroglycerin and drainage of massive ascites. Meticulous intra-operative volume control, which included minimizing blood loss and subsequent transfusion, was carried out. The use of vasopressors, which may have elevated the PAP, was strictly restricted. Intra-operative PAP did not show an increase, and the hemodynamics was maintained within relatively normal range, compared to the preoperative state. The patient was discharged without any complications or related symptoms.
Ascites ; Dobutamine ; Drainage ; Female ; Hemodynamics ; Humans ; Hypertension* ; Iloprost ; Liver Transplantation* ; Living Donors ; Middle Aged ; Milrinone ; Mortality ; Nitric Oxide ; Nitroglycerin ; Prognosis ; Pulmonary Artery ; Reference Values ; Sildenafil Citrate

Pulmonary aspiration of gastric contents is one of the most frightening complications during anesthesia. Although pulmonary aspiration of gastric contents in general surgical patients is not common and resulting long-term morbidity and mortality are rare, severe hypoxemia and other sequelae of pulmonary aspiration continue to be reported. We report a case of massive aspiration of gastric contents during induction of general anesthesia, resulting in cardiac arrest due to severe pulmonary hypertension and myocardial infarction. Sustained cardiac arrest and shock that did not respond the conventional resuscitation was successfully treated using milrinone. The patient was discharged without complications in 20 days.
Anesthesia ; Anesthesia, General ; Anoxia ; Heart Arrest ; Humans ; Hypertension, Pulmonary ; Milrinone* ; Mortality ; Myocardial Infarction ; Respiratory Aspiration of Gastric Contents ; Resuscitation ; Shock ; Shock, Cardiogenic*

Adolescent ; Child ; Child, Preschool ; Female ; Heart Failure ; drug therapy ; Humans ; Infant ; Male ; Milrinone ; adverse effects ; pharmacology ; therapeutic use ; Phosphodiesterase Inhibitors ; therapeutic use

BACKGROUND: Valvular heart surgery (VHS) utilizing cardiopulmonary bypass (CPB) is inevitably associated with ischemic-reperfusion injury, which is known to depend on oxygen tension during reperfusion. The aim of this study was to evaluate the effect of arterial oxygen tension during reperfusion on myocardial recovery in patients undergoing VHS. METHODS: Fifty-six patients undergoing isolated VHS were randomly exposed to an oxygen fraction of 0.7 (hyperoxic group, n = 28) or 0.5 (normoxic group, n = 28) during reperfusion. All patients received an oxygen fraction of 0.7 during CPB. In the normoxic group, the oxygen fraction was lowered to 0.5 from the last warm cardioplegia administration to 1 minute after aortic unclamping, and was then raised back to 0.7. Hemodynamic data were measured after induction of anesthesia, weaning from CPB, and sternum closure. The frequency of cardiotonic medications used during and after weaning from CPB, and the short-term outcomes during the hospital stay were also assessed. RESULTS: The frequency of vasopressin and milrinone use during weaning from CPB, but not norepinephrine, was significantly less in the normoxic group. The post-operative cardiac enzyme levels and short-term outcomes were not different between the groups. CONCLUSIONS: Normoxic reperfusion from the last cardioplegia administration to 1 minute after aortic unclamping in patients undergoing VHS resulted in significantly less frequent use of vasopressin and inotropics during weaning from CPB than hyperoxic reperfusion, although it did not affect the post-operative myocardial enzyme release or short-term prognosis.
Anesthesia ; Cardiopulmonary Bypass ; Heart ; Heart Arrest, Induced ; Hemodynamics ; Humans ; Length of Stay ; Milrinone ; Norepinephrine ; Oxygen ; Prognosis ; Reperfusion ; Reperfusion Injury ; Sternum ; Thoracic Surgery ; Vasopressins ; Weaning

PURPOSE:Persistent pulmonary hypertension of the newborn (PPHN) is life threatening neonatal disease. Nitric oxide (NO) has been proven to improve oxygenation, however its usage is limited and 30% of patients with PPHN are NO nonresponders. Milrinone decreases right ventricular afterload and has selective pulmonary vasodilator effect. We studied the effects of milrinone on neonates with respiratory failure originated in PPHN. METHODS:Six neonates, who had oxygen index above 20 and responded poorly to other management, were treated with intravenous milrinone after confirming pulmonary hypertension with echocardiography. We reviewed their medical records retrospectively. Intravenous milrinone was started at a dose of 0.375 microgram/kg/min. Respiratory indices (Oxygenation index [OI], ventilation settings, and arterial blood gas) and cardiovascular stability (mean arterial pressure and heart rate) were documented just before; and at 6, 12, 24, 36, 48, and 72 hours after commencement of milrinone therapy. The primary outcome was the effect of milrinone on oxygenation, which was 40% reduction in OI. RESULTS:Primary cause of PPHN was meconium aspiration syndrome in three infants, respiratory distress syndrome (RDS) in the other three. Milrinone was commenced at a median age of 22.3+/-6.1 hours with a dose of 0.375 microgram/kg/min except one infant (0.5 microgram/kg/min) and infants were treated for median 58.3+/-16.7 hours. OI of all infants showed 40% reduction within 24 hours. There were no mortality, and no infants with hypotension, and intraventricular hemorrhage. CONCLUSION:Milrinone proved to be effective for PPHN by improving oxygenation. It did not cause any complications in clinical trials for newborns. It is suggested that Milrinone can replace NO or can be used as adjunct to NO in the treatment of PPHN.
Arterial Pressure ; Echocardiography ; Heart ; Hemorrhage ; Humans ; Hypertension, Pulmonary* ; Hypotension ; Infant ; Infant, Newborn* ; Meconium Aspiration Syndrome ; Medical Records ; Milrinone* ; Mortality ; Nitric Oxide ; Oxygen ; Respiratory Insufficiency ; Retrospective Studies ; Ventilation