Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. We have already shown that the left ventricular (LV) end-systolic pressure-volume relationship (ESPVR) of rat hearts in situ is an upward convex curve and that LV end- systolic pressure (ESP(mLVV)) and the systolic pressure-volume area (PVA(mLVV)) at a mid-range LV volume (mLVV) sensitively reflect acute changes in LV contractility and work capability. Milrinone is a non-glycosidic, non-sympathomimetic drug that increases myocardial cAMP concentrations by selective inhibition of cardiac phosphodiesterase III. Therefore, milrinone could act on the entire cardiovascular system and cause an increase in inotropy, arterial vasodilatation and venodilatation. The aim of the present study was to investigate whether the approach we have recently instituted is able to detect the effects of milrinone on the entire cardiovascular system. 2. We measured simultaneously, in anaesthetized rats, continuous LV pressure using a catheter-tip micromanometer and LV volume by LV volumetry using a conductance catheter. We obtained steady state LV pressure-volume loops and intermittently obtained the LV ESPVR by gradual occlusion of the ascending aorta. We then evaluated LV function by assessing milrinone-induced changes in the ESPVR (i.e. ESP(mLVV) and PVA(mLVV)) and vasodilator actions by assessing milrinone-induced changes in ESP(ESV) and effective arterial elastance (Ea), defined as the ESP(ESV)/stroke volume ratio. 3. Milrinone (total dose 49.5 microg; infusion rate 3.3-6.7 microg/min, 7-10 microg/kg per min; blood concentration 53.9 ng/mL) largely shifted the ESPVR upwards and, thus, significantly increased end-systolic pressure (ESP(0.08)) and the systolic pressure-volume area (PVA(0.08)) at a mid-range LV volume (= 0.08 mL/g myocardium). Milrinone also significantly decreased LV ESP(ESV) and decreased Ea, although these decreases were not significant. 4. The results of the present study suggest that our own recently instituted approach to evaluate LV function by measuring LV pressure-volume loops and ESPVR succeeded in detecting a cardiotonic action of milrinone with arterial vasodilatation in normal rat hearts.
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PMID:Effects of milrinone on left ventricular end-systolic pressure-volume relationship of rat hearts in situ. 1155 33

Phosphodiesterase inhibitors including milrinone produce positive inotropic effects by slowing the hydrolysis of cyclic adenosine monophosphate in the myocardium. With a loading dose of 50 microg/kg followed by an infusion of 0.5 microg x kg(-1) x min(-1), milrinone increases stroke volume index and left ventricular velocity of circumferential fiber shortening after weaning from cardiopulmonary bypass. Milrinone has potential for the treatment and prevention of internal mammary artery spasm because of its vasodilative effect, which is similar to that of papaverine, and is a potent pulmonary vasodilator for patients with right ventricular dysfunction and pulmonary vasoconstriction. Low-dose milrinone may have antiinflammatory properties and potentially can improve splanchnic perfusion.
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PMID:Intravenous milrinone in cardiac surgery. 1183 47

The objective of this study was to examine the efficacy of milrinone in chronic congestive heart failure. In this randomized, double-blind, placebo-controlled trial, 30 patients with class III or IV chronic congestive heart failure were randomly assigned to receive milrinone (n = 15) or placebo (n = 15). The results showed that in the milrinone group, stroke volume increased from 38.50 +/- 5.34 to 64.93 +/- 6.46 ml (P < 0.001), cardiac output increased from 3.39 +/- 0.42 to 5.28 +/- 0.55 L/min (P < 0.001), cardiac index increased from 2.01 +/- 0.42 to 3.21 +/- 0.57/min/m2 (P < 0.001) and ejection fraction increased from 0.23 +/- 0.05 to 0.35 +/- 0.06(P < 0.001). In the placebo group, no hemodynamic effects were found. Milrinone favourably influenced the symptoms and heart function in 11/15(73.3%) patients. In the placebo group, only 4/15(26.7%) patients had such response (P < 0.05). These data indicate that milrinone is effective for improving the hemodynamics status and heart function in patients with chronic heart failure.
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PMID:[Response to milrinone treatment in patients with chronic congestive heart failure]. 1251 50

This study tests the hypothesis that particulate (p) guanylyl cyclase (GC) and soluble (s) GC are involved in the distinct roles for the regulation of cGMP-PDE-cAMP signaling and of mechanical and secretory functions in the heart. Experiments were performed in perfused beating rabbit atria. C-type natriuretic peptide (CNP) and SIN-1, an NO donor, or BAY 41-2272 (BAY), a direct activator for sGC, were used to activate pGC and sGC, respectively. CNP and SIN-1 increased cGMP and cAMP efflux in a concentration-dependent manner. Increase in cAMP was a function of cGMP. The changes in cAMP efflux concentration in terms of cGMP were much more prominent in the atria treated with CNP than in the atria treated with SIN-1. Increase in cAMP efflux concentration was blocked by milrinone but not changed by EHNA. BAY increased cGMP but not cAMP in a concentration-dependent manner. CNP and SIN-1 decreased atrial stroke volume and myocytic ANP release. The decreases in terms of cGMP efflux concentration were much more prominent in the atria treated with CNP than in the atria treated with SIN-1 or BAY. Milrinone accentuated GC agonist-induced decreases in atrial stroke volume and ANP release. In the presence of ODQ, SIN-1 or BAY induced effects were not observed. These data suggest that pGC and sGC activations have distinct roles via cGMP-PDE3-cAMP signaling in the cardiac atrium: high and low gain switches, respectively, for the regulation of cAMP levels and contractile and secretory functions.
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PMID:High and low gain switches for regulation of cAMP efflux concentration: distinct roles for particulate GC- and soluble GC-cGMP-PDE3 signaling in rabbit atria. 1498 25

This study evaluated the effects of milrinone, adrenaline and dobutamine with pressure-volume loops and isolated atrial tissue. Agonist dose-response curves to incremental drug infusions were acquired in 11 anesthetised rabbits using pressure-volume loops and preload recruitable stroke work indicated contractility. Agonist concentration-response curves were completed in eight guinea pig isolated atria, for effects on atrial rate and force. Adrenaline and dobutamine increased contractility (P = 0.006 and 0.044), whereas milrinone did not (P = 0.895). Only adrenaline increased myocardial stiffness (P < 0.001). Milrinone decreased vascular resistance (P < 0.001) and elicited the greatest fall in mean arterial pressure (P < 0.001) and increased ejection fraction (P < 0.001). Adrenaline decreased heart rate (P < 0.001), whereas dobutamine and milrinone increased it (P = 0.006 and 0.011). Milrinone increased the force of left atrial contraction, but its inotropic effect was weak and significantly less than with dobutamine and adrenaline (P < 0.001). Adrenaline acted as an inoconstrictor, dobutamine an inodilator and milrinone predominantly a vasodilator
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PMID:The cardiovascular effects of adrenaline, dobutamine and milrinone in rabbits using pressure-volume loops and guinea pig isolated atrial tissue. 1744 5

In an attempt to search for more potent positive inotropic agents, a series of 2-(4-(4-substituted benzyloxy)-3-methoxybenzyl)-1,4-diazepan-1-yl)-N-(4,5-dihydro-1-methyl[1,2,4]triazolo[4,3-a]quinolin-7-yl)acetamides was synthesized and their positive inotropic activities were evaluated by measuring left atrium stroke volume on isolated rabbit-heart preparations. Several compounds showed favorable activity compared with the standard drug Milrinone among which 2-(4-(4-(2-chlorobenzyloxy)-3-methoxybenzyl)-1,4-diazepan-1-yl)-N-(4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-yl)acetamide 6e was found to have the most desirable potency with the 6.79 +/- 0.18% increased stroke volume (Milrinone: 1.67 +/- 0.64%) at a concentration of 1 x 10(-5) M in our in-vitro study. The chronotropic effects of those compounds having inotropic effects were also evaluated in this work.
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PMID:Synthesis and positive inotropic evaluation of 2-(4-(4-substituted benzyloxy)-3-methoxybenzyl)-1,4-diazepan-1-yl)-N-(4,5-dihydro-1-methyl[1,2,4]triazolo[4,3-a]quinolin-7-yl)-acetamides. 1900 92

Right ventricular (RV) failure due to chronic pressure overload is a main determinant of outcome in congenital heart disease. Medical management is challenging because not only contractility but also the interventricular relationship is important for increasing cardiac output. This study evaluated the effect of milrinone alone and in combination with epinephrine or dopamine on hemodynamics, ventricular performance, and the interventricular relationship. RV failure was induced in 21 Danish landrace pigs by pulmonary artery banding. After 10 wk, animals were reexamined using biventricular pressure-volume conductance catheters. The maximum pressure in the RV increased by 113% (P < 0.0001) and end-diastolic volume by 43% (P < 0.002), while left ventricular (LV) pressure simultaneously decreased (P = 0.006). Concomitantly, mean arterial pressure (MAP; -16%, P = 0.01), cardiac index (CI; -23%, P < 0.0001), and mixed venous oxygen saturation (SvO2 ; -40%, P < 0.0001) decreased. Milrinone increased CI (11%, P = 0.008) and heart rate (HR; 21%, P < 0.0001). Stroke volume index (SVI) decreased (7%, P = 0.03), although RV contractility was improved. The addition of either epinephrine or dopamine further increased CI and HR in a dose-dependent manner but without any significant differences between the two interventions. A more pronounced increase in biventricular contractility was observed in the dopamine-treated animals. LV volume was reduced in both the dopamine and epinephrine groups with increasing doses In the failing pressure overloaded RV, milrinone improved CI and increased contractility. Albeit additional dose-dependent effects of both epinephrine and dopamine on CI and contractility, neither of the interventions improved SVI due to reduced filling of the LV.
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PMID:Effects of milrinone and epinephrine or dopamine on biventricular function and hemodynamics in an animal model with right ventricular failure after pulmonary artery banding. 2595 22

Right ventricular failure (RVF) secondary to pulmonary regurgitation (PR) impairs right ventricular (RV) function and interrupts the interventricular relationship. There are few recommendations for the medical management of severe RVF after prolonged PR. PR was induced in 16 Danish landrace pigs by plication of the pulmonary valve leaflets. Twenty-three pigs served as controls. At reexamination the effect of milrinone, epinephrine, and dopamine was evaluated using biventricular conductance and pulmonary catheters. Seventy-nine days after PR was induced, RV end-diastolic volume index (EDVI) had increased by 33% (P = 0.006) and there was a severe decrease in the load-independent measurement of contractility (PRSW) (-58%; P = 0.003). Lower cardiac index (CI) (-28%; P < 0.0001), mean arterial pressure (-15%; P = 0.01) and mixed venous oxygen saturation (SvO2) (36%; P < 0.0001) were observed compared with the control group. The interventricular septum deviated toward the left ventricle (LV). Milrinone improved RV-PRSW and CI and maintained systemic pressure while reducing central venous pressure (CVP). Epinephrine and dopamine further improved biventricular PRSW and CI equally in a dose-dependent manner. Systemic and pulmonary pressures were higher in the dopamine-treated animals compared with epinephrine-treated animals. None of the treatments improved stroke volume index (SVI) despite increases in contractility. Strong correlation was detected between SVI and LV-EDVI, but not SVI and biventricular contractility. In RVF due to PR, milrinone significantly improved CI, SvO2, and CVP and increased contractility in the RV. Epinephrine and dopamine had equal inotropic effect, but a greater vasopressor effect was observed for dopamine. SV was unchanged due to inability of both treatments to increase LV-EDVI.
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PMID:Effects of milrinone and epinephrine or dopamine on biventricular function and hemodynamics in right heart failure after pulmonary regurgitation. 2609 88

It is not known whether there are positive or negative interactions on ventricular function when a calcium-sensitizing inotrope is added to a phosphodiesterase inhibitor in the clinical setting of acute left ventricular (LV) dysfunction. We hypothesized that when levosimendan is added to milrinone treatment, there will be synergetic inotropic and lusitropic effects. This was tested in an anesthetized porcine postischemic global LV injury model, where ventricular pressures and volumes (conductance volumetry) were measured. A global ischemic injury was induced by repetitive left main stem coronary artery occlusions. Load-independent indices of LV function were assessed before and after ventricular injury, after milrinone treatment, and finally after addition of levosimendan to the milrinone treatment. Nonparametric, within-group comparisons were made. The protocol was completed in 12 pigs, 7 of which received the inotrope treatment and 5 of which served as controls. Milrinone led to positive lusitropic effects seen by improvement in tau after myocardial stunning. The addition of levosimendan to milrinone further increased lusitropic state. The latter effect could however not be attributed solely to levosimendan, since lusitropic state also improved spontaneously in time-matched controls at the same rate during the corresponding period. When levosimendan was added to milrinone infusion, there was no increase in systolic function (preload recruitable stroke work) compared to milrinone treatment alone. We conclude that in this model of postischemic LV dysfunction, there appears to be no clear improvement in systolic or diastolic function after addition of levosimendan to established milrinone treatment but also no negative effects of levosimendan in this context.
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PMID:Effects of Combined Milrinone and Levosimendan Treatment on Systolic and Diastolic Function During Postischemic Myocardial Dysfunction in a Porcine Model. 2683 38


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