Separation of the direct myocardial and vasodilator actions of milrinone administered by an intracoronary infusion technique.

Ludmer, Paul L.; Wright, Richard F.; Arnold, J. Malcolm O.; Ganz, Patricia A.; Braunwald, Eugene; Colucci, Wilson S.

doi:10.1161/01.cir.73.1.130

Cited by 123 publications

(42 citation statements)

References 25 publications

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“…Moreover, we emphasize that our studies examined only the direct positive inotropic actions of these agents in vitro. In vivo, drugs like amrinone and milrinone possess peripheral vascular actions that lead to vasodilation and significant afterload reduction, which may contribute to a favorable therapeutic response.26 40,41 The preservation of a positive inotropic response to acetylstrophanthidin in myocardium from patients with heart failure was striking in contrast to the relative diminution of the effects of the other standard agents; similar results have been reported by Wilmshurst et …”

Section: Methodsmentioning

confidence: 52%

Deficient production of cyclic AMP: pharmacologic evidence of an important cause of contractile dysfunction in patients with end-stage heart failure.

Feldman¹,

Copelas²,

Gwathmey³

et al. 1987

Circulation

466

122

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We studied the effects of different classes of inotropic drugs on human working myocardium in vitro that was isolated from the hearts of patients with end-stage heart failure, and compared the responses to these drugs with those noted in muscles from nonfailing control hearts. Although peak isometric force generated in response to increased extracellular calcium reached control levels in the muscles from patients with heart failure, the time course of contraction and rate of relaxation were greatly prolonged. The inotropic effectiveness of the ,B-adrenergic agonist isoproterenol and the phosphodiesterase inhibitors milrinone, caffeine, and isobutylmethylxanthine was markedly reduced in muscles from the patients with heart failure. In contrast, the effectiveness of inotropic stimulation with acetylstrophanthidin and the adenylate cyclase activator forskolin was preserved. After a minimally effective dose of forskolin was given to elevate intracellular cyclic AMP levels, the inotropic responses of muscles from the failing hearts to phosphodiesterase inhibitors were markedly potentiated. These data indicate that an abnormality in cyclic AMP production may be a fundamental defect present in patients with end-stage heart failure that can markedly diminish the effectiveness of agents that depend on generation of this nucleotide for production of a positive inotropic effect.

show abstract

Section: Methodsmentioning

confidence: 52%

Deficient production of cyclic AMP: pharmacologic evidence of an important cause of contractile dysfunction in patients with end-stage heart failure.

Feldman¹,

Copelas²,

Gwathmey³

et al. 1987

Circulation

466

122

View full text Add to dashboard Cite

show abstract

“…1) Milrinone has positive inotropic and vasodilator effects in patients suffering from congestive heart failure. 3,4,17) Intravenous infusion of milrinone and delivery by a slow-releasing pellet are equally and satisfactorily effective against cerebral vasospasm after SAH in a canine model. 13) Intraarterial and intravenous Patients and Methods…”

Section: Introductionmentioning

confidence: 99%

Milrinone Reduces Cerebral Vasospasm After Subarachnoid Hemorrhage of WFNS Grade IV or V

Arakawa

Kikuta

Hojo

et al. 2004

Neurol. Med. Chir.(Tokyo)

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The preventative effect of cisternal irrigation with milrinone against vasospasm was evaluated in 12 patients with subarachnoid hemorrhage (SAH) of World Federation of Neurosurgical Societies grade IV or V treated between September 1999 and September 2000. All aneurysms were clipped or embolized within 72 hours of the onset of SAH. Inlet and outlet tubes were placed in either the supratentorial cisternal space, lateral ventricle, or spinal subarachnoid space. Lactated Ringer solution containing urokinase (120 IU/ml), ascorbic acid (3.5 mg/ml), and milrinone (3.6 mg/ml) was continuously infused at 30 ml/hr for as long as 2 weeks. Angiographical vasospasm was detected in only two of the 11 patients who received milrinone irrigation and underwent postoperative angiography. Vasospasm may have resulted from irrigation obstruction associated with pneumocephalus in one patient and clot in the sylvian fissure in the other patient. The outcome of the milrinone irrigation therapy was significantly better than that of the conventional therapy. This study suggests that cisternal irrigation with milrinone is safe and effective, and reduces the occurrence of vasospasm in patients with poor grade aneurysmal SAH.

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“…Hydrolysis of cAMP by PDE3s is potently inhibited by cGMP, cilostamide, and a number of compounds, such as milrinone and enoximone, with inotropic/vasodilatory/ antiplatelet aggregatory properties ( 11,(23)(24)(25)(26)(27). The subcellular distribution of PDE3s varies, with the enzyme predominantly microsomal in adipocytes (11,12,28,29) and liver (19,20), cytosolic in platelets (13,30), and both cytosolic and membrane-associated in myocardium (31)(32)(33).…”

Section: Introductionmentioning

confidence: 99%

Distinctive anatomical patterns of gene expression for cGMP-inhibited cyclic nucleotide phosphodiesterases.

et al. 1995

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Type III cGMP-inhibited phosphodiesterases (PDE3s) play important roles in hormonal regulation of lipolysis, platelet aggregation, myocardial contractility, and smooth muscle relaxation. We have recently characterized two PDE3 subtypes (PDE3A and PDE3B) as products of distinct but related genes. To elucidate their biological roles, in this study we compare cellular patterns of gene expression for these two enzymes during rat embryonic and postnatal development using in situ hybridization. PDE3A mRNA is abundant in adipose tissue and is also expressed in hepatocytes throughout development. This mRNA is also highly abundant in embryonic neuroepithelium including the neural retina, but expression is greatly reduced in the mature nervous system. Finally, PDE3A mRNA is localized in spermatocytes and renal collecting duct epithelium in adult rats.PDE3B mRNA is highly expressed in the cardiovascular system, including myocardium and arterial and venous smooth muscle, throughout development. It is also abundant in bronchial, genitourinary and gastrointestinal smooth muscle and epithelium, megakaryocytes, and oocytes. PDE3B mRNA demonstrates a complex, developmentally regulated pattern of gene expression in the central nervous system. In summary, the two different PDE3s show distinctive tissue-specific patterns of gene expression suggesting that PDE3A is involved in hormonal regulation of lipolysis and glycogenolysis, while regulation of myocardial and smooth muscle contractility appears to be a function of PDE3B. In addition, the present findings suggest previously unsuspected roles for these enzymes in gametogenesis and neural development. (J. Clin. Invest. 1995Invest. . 95:1528Invest. -1538

show abstract

Separation of the direct myocardial and vasodilator actions of milrinone administered by an intracoronary infusion technique.

Cited by 123 publications

References 25 publications

Deficient production of cyclic AMP: pharmacologic evidence of an important cause of contractile dysfunction in patients with end-stage heart failure.

Deficient production of cyclic AMP: pharmacologic evidence of an important cause of contractile dysfunction in patients with end-stage heart failure.

Milrinone Reduces Cerebral Vasospasm After Subarachnoid Hemorrhage of WFNS Grade IV or V

Distinctive anatomical patterns of gene expression for cGMP-inhibited cyclic nucleotide phosphodiesterases.

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