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Byline: Guo-Wei He, Cheng-Qin Yang Abstract: Objective: The radial artery is a spastic coronary bypass graft. We investigated the effect of the phosphodiesterase III inhibitor milrinone on the human radial artery. Methods: Radial artery segments (n = 76) taken from 15 patients were studied in an organ chamber. Concentration-relaxation curves for milrinone were established in the radial artery precontracted with 3 vasoconstrictors (phenylephrine, K.sup.+, and U46619). In radial artery rings incubated with therapeutic plasma concentrations of milrinone (7 and 70 [mu]mol/L) for 10 minutes, concentration-contraction curves for the 3 vasoconstrictors were constructed. Results: Milrinone caused a submaximal relaxation in phenylephrine- (98.6% [+ or -] 1.4%), K.sup.+- (89.1 [+ or -] 4.5%), or U46619- (74.2 [+ or -] 8.0%) precontracted radial arteries at -4.5 log.sub.10 M. The EC.sub.50 was higher against K.sup.+ (-5.85 [+ or -] 0.24 log.sub.10 M, P = .02) or U46619 (-5.21 [+ or -] 0.61 log.sub.10 M, P = .03) than phenylephrine (-6.68 [+ or -] 0.11 log.sub.10 M). Pretreatment with milrinone depressed the contraction by phenylephrine from 70.0% [+ or -] 7.9% to 23.5% [+ or -] 9.3% (P = .003) and by K.sup.+ from 138.6% [+ or -] 5.8% to 73.0% [+ or -] 13.9% (P = .006) and shifted the EC.sub.50 3.8-fold higher (P = .03) for phenylephrine and 2.2-fold higher for K.sup.+ (P = .01). Milrinone reduced the U46619 contraction at low concentration (-8.5 log.sub.10 M) but had little effect on the maximal contraction. Conclusion: Milrinone is a potent vasodilator for the radial artery, with possibly higher potency in [alpha]-adrenoceptor- and depolarizing agent K.sup.+-mediated, but less potency in thromboxane A.sub.2-mediated, contraction. Because it also has a positive inotropic effect, this vasodilator may be particularly indicated for use in patients receiving radial artery grafts in coronary artery bypass grafting. (J Thorac Cardiovasc Surg 2000;119:1039-45) Author Affiliation: Starr Academic Center for Cardiac Surgery, St Vincent Hospital, Portland, Ore, and the Division of Cardiothoracic Surgery and Cardiovascular Research Laboratory, Grantham Hospital, Department of Surgery, University of Hong Kong, Hong Kong Article History: Received 16 April 1999; Revised 3 June 1999; Revised 15 December 1999; Accepted 10 January 2000 Article Note: (footnote) [star] Supported by Hong Kong Research Grants Council (Grant HKU7280/97M & HKU7246/99M) and St Vincent Medical Foundation, Providence Health System, Portland, Ore., [star][star] Address for reprints: Professor Guo-Wei He, MD, PhD, Chair of Cardiothoracic Surgery, The University of Hong Kong, Grantham Hospital, 125 Wong Chuk Hang Road, Aberdeen, Hong Kong (E-mail: gwhe@hkucc.hku.hk ).

In a previous study of propranolol poisoning, glucagon and milrinone significantly increased cardiac output, but the improvement caused by glucagon was almost entirely due to the chronotropic effect. This study investigates the combined effect of glucagon, in a dose not inducing tachycardia, and milrinone on beta-blocker poisoning. Following the administration of 10 mg/kg propranolol IV over ten minutes, dogs (N = 20) were divided into four treatment groups, group S (saline), group G (glucagon 2.5 [micro]g/kg), group M (milrinone 100 [micro]g/kg), and group G + M (glucagon 2.5 [micro]g/kg plus milrinone 100 [micro]g/kg). Hemodynamic parameters were observed over the next thirty minutes. Heart rate, cardiac output, and mean arterial pressure were decreased in all groups after the administration of propranolol. Heart rate, mean arterial pressure, cardiac output, and stroke volume recovered to the baseline values in group G + M. However, heart rate in group G + M showed a significant increase versus the other three groups. In a canine model of severe propranolol poisoning, the combined effect of glucagon 2.5 [micro]g/kg and milrinone 100 [micro]g/kg brought about a significant hemodynamic improvement, but it was accompanied by an excessive increase of heart rate. Combined therapy of milrinone and glucagon may not be preferable therapy in beta-blocker poisoning in the canine model., (Key Words: glucagon; milrinone; propranolol poisoning, animal; adrenergic beta-antagonists.) INTRODUCTION As glucagon can increase cyclic adenosine monophosphate (cAMP) without involvement of the beta-adrenoceptor (1), it has been the most consistently [...]

Glucagon has been reported to be one of the most effective treatments for severe beta-blocker poisoning. Recently, amrinone was suggested as an alternative therapeutic choice for beta-blocker poisoning. Milrinone, a derivative of amrinone, acts independently of beta-adrenoceptors and increases cyclic AMP. Therefore milrinone may also be effective in the treatment of beta-blocker poisoning. In the present study, we compared the effect of glucagon and milrinone in treating severe beta-blocker poisoning. Following the administration of 10 mg/kg propranolol IV over 10 min, heart rate, cardiac output, mean arterial pressure, stroke volume, and end tidal [CO.sub.2] were depressed, while central venous pressure, and pulmonary capillary wedge pressure increased significantly (p < 0.05). Following the administration of saline (Group S, N = 3), glucagon 20 [mu]g/kg (Group G, N = 5), and milrinone 300 [mu]g/kg (Group M, N = 5), hemodynamic parameters were observed for 30 min. In group M, mean arterial pressure, cardiac output and stroke volume recovered to their baseline values, while central venous pressure and pulmonary capillary wedge pressure decreased. Although there were no significant differences between groups G and M, the heart rate, central venous pressure and pulmonary capillary wedge pressure, mean arterial pressure and stroke volume did not return to baseline values in group G. Milrinone administration produced a significant hemodynamic improvement without increasing the heart rate in the canine model of severe heart failure caused by propranolol. In the glucagon treatment group, central venous pressure and pulmonary capillary wedge pressure improved less than the milrinone group. Although more data are needed before a clinical recommendation, milrinone might be an effective drug to treat beta-blocker poisoning., INTRODUCTION As a treatment for severe beta-blocker ([beta]-blocker) poisoning, glucagon is the most consistently effective treatment reported in the literature[1-4]. Glucagon can increase cAMP without involvement of the [beta]-adrenoceptor[5]. Amrinone [...]

Congestive heart failure is the inability of the heart to pump effectively, and leads to fluid congestion or accumulation in the lungs. In patients with congestive heart failure, the cardiovascular drug milrinone increases heart muscle contraction and dilates blood vessels. Milrinone may increase the entry of calcium into cells, and calcium is essential for heart muscle contraction. Milrinone was shown to improve heart failure resulting from treatment with verapamil and propranolol, but may worsen ventricular arrhythmias or abnormal heart rhythms, which are common in patients with congestive heart failure. The effect of milrinone on ventricular arrhythmias was assessed in 24 patients with congestive heart failure. The results reveal that milrinone increased the frequency of ventricular arrhythmias; these findings are consistent with previous reports. A proarrhythmic effect of milrinone (ability of this drug to increase the frequency of arrhythmias) was observed in eight patients. Patients with proarrhythmia died 41 to 750 days after entry into the study, and sudden death occurred in four of these patients. Among 16 patients without proarrhythmia, 13 died within 166 days after entry into the study, including 6 cases of sudden death. The high death rate among these patients may be related to the severity of congestive heart failure and to impaired function of the left ventricle. (Consumer Summary produced by Reliance Medical Information, Inc.)

Background: The management of congestive heart failure has undergone a number of modifications over the past 5 to 10 years. Methods: These include assaying the role of inotropic drugs, evaluating the role of phosphodiesterase inhibitors, considering the role of intermittent inotropic infusion in ambulatory patients, and recognizing the importance of angiotensin-converting enzyme inhibitors. Very recently, the important role of angiotensin II receptor blocking agents and the use of beta blockade have provided additional modalities for the control of congestive heart failure. The relative usefulness of such therapy has been reviewed in this article. Conclusion: The management of congestive heart failure has undergone considerable change with the use of newer and more effective drugs. Arch Intern Med. 1999;159:1177-1183