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Inotropic Effects (inotropic + effects)

Distribution by Scientific Domains

Medical Sciences	85%

Selected Abstracts

Structure,activity relationships of isoeugenol-based chlorophenylpiperazine derivatives on serotonergic/adrenergic receptor, platelet aggregation, and lipid peroxidation

DRUG DEVELOPMENT RESEARCH, Issue 5 2010
Kuo-Ping Shen
Abstract Three isoeugenol-based eugenosedin chlorphenylpiperazine derivatives, Eu-A, Eu-B, and Eu-C, were synthesized and tested for their serotonergic, adrenergic antagonist, antioxidant, and anti-aggregation activities. In radioligand binding assays, all three agents displayed significant binding affinities on ,1, ,2, ,1, 5-HT1B, and 5-HT2A receptors. In human platelet, they inhibited epinephrine and 5-HT-induced aggregation, and in human platelet with ,2 and 5-HT2A receptors they had a competitive binding effect. Eu-B and Eu-C were more potent than Eu-A. All compounds had antioxidant effects derived from aryloxypropanolamine. Eu- A, Eu-B, or Eu-C (1, 3, 5,mg/kg iv) given to normotensive Wistar rats produced a dose-dependent decrease in mean arterial blood pressure and heart rate and when injected into the cisternum, Eu-A, Eu-B, or Eu-C (0.3, 0.03,µmol) increased blood pressure within 15,min. Pretreatment with any of the three agents inhibited clonidine (38,pmol)-induced hypotension. In vitro experiments, Eu-A, Eu-B, or Eu-C (1, 10, and 100,µM) competitively antagonized norepinephrine-, clonidine-, and 5-HT (10,8,10,4,M)-induced vasocontraction in isolated rat aorta, and competitively antagonized isoproterenol (10,8,10,4,M)-induced positive inotropic effects in a concentration-dependent manner in the isolated rat left atrium. In isolated rabbit ear arteries sensitized with 16,mM K+, all three agents antagonized 5-nonyloxytryptamine- and 5-HT-induced vasocontractions. These findings show that Eu-A, Eu-B, and Eu-C possess functional ,1, ,2, ,1, 5-HT1B, and 5-HT2A receptor blocking activities. In conclusion, the changes in the position of chloride at phenylpiperazine influenced the serotonergic receptor, adrenoceptor antagonistic activities, but not anti-aggregation and antioxidant activities. Drug Dev Res 71:1,9, 2010. © 2010 Wiley-Liss, Inc. [source]

Xenon and isoflurane improved biventricular function during right ventricular ischemia and reperfusion

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2010
M. HEIN
Background: Although anesthetics have some cardioprotective properties, these benefits are often counterbalanced by their negative inotropic effects. Xenon, on the other hand, does not influence myocardial contractility. Thus, xenon may be a superior treatment for the maintenance of global hemodynamics, especially during right ventricular ischemia, which is generally characterized by a high acute complication rate. Methods: The effects of 70 vol% xenon and 0.9 vol% isoflurane on biventricular function were assessed in a porcine model (n=36) using the conductance catheter technique, and the expression of the type B natriuretic peptide (BNP) gene was measured. The animals underwent 90 min of right ventricular ischemia followed by 120 min of reperfusion. A barbiturate-anesthetized group was included as a control. Results: Cardiac output was compromised in unprotected animals during ischemia by 33±18% and during reperfusion by 53±17%. This was mainly due to impaired contractility in the left ventricle (LV) and increased stiffness. Isoflurane attenuated the increase in stiffness and resulted in a higher preload. In contrast, xenon increased the right ventricular afterload, which was compensated by an increase in contractility. Its effects on diastolic function were less pronounced. Upregulation of BNP mRNA expression was impeded in the remote area of the LV by both isoflurane and xenon. Conclusions: Xenon and isoflurane demonstrated equipotent effects in preventing the hemodynamic compromise that is induced by right ventricular ischemia and reperfusion, although they acted through somewhat differential inotropic and vasodilatory effects. [source]

Anti-thrombotic effect of milrinone is caused by inhibition of calcium release from the dense tubular system in human platelets,

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2003
N. Hiramatsu
Aim: Milrinone, a phosphodiesterase III inhibitor, exerts positive inotropic effects which induce an increase in the intracellular calcium concentration by raising the cyclic adenosine monophosphate level in cardiac muscle. Milrinone was also reported to inhibit platelet aggregation, however, its mechanism remains unknown. Therefore, we investigated the effects of milrinone on intracellular calcium mobilization when platelets were activated. Methods: Washed platelets, obtained from six healthy volunteers, were preincubated with milrinone (0.9 µM) for 1 min and then exposed to 0.015 iµ ml,1 thrombin for 5 min. The effect of milrinone on changes in the intracellular calcium level using a fluorescent dye, fura-2, was also observed. Calcium mobilizations via plasma membrane calcium channels and the dense tubular system were assessed differentially. Results: Milrinone (0.9 µM) significantly suppressed the aggregation ratios at 5 min compared with those in controls (86±5%) to 75±8%. The increase in the intracellular calcium concentration was also significantly suppressed (controls, 915±293 nM vs. 405±240 nM) when stimulated by thrombin. Milrinone also significantly inhibited the release of calcium from the dense tubular system (controls, 284±111 nM vs. 158±51 nM). Calcium influx through the plasma membrane was suppressed by milrinone 2.4 µM. Conclusion: Milrinone (0.9 µM) inhibited thrombin-induced platelet aggregation. This inhibitory effect was mainly mediated by suppressing calcium release from the dense tubular system. [source]

Pycnogenol increases the probability of the contraction state in chick embryonic cardiomyocytes, indicating inotropic effects

PHYTOTHERAPY RESEARCH, Issue 2 2007
Noboru Hasegawa
Abstract The influence of pycnogenol on the probability of contraction was studied in chick cardiomyocytes. Ventricles from 9,11 day chicken embryos were cultured. After 10,11 days in culture, stable spontaneous contractions were recorded and the contraction kinetics analysed. Isoproterenol and pycnogenol increased the probability of the contraction state. After pretreatment with the , -receptor antagonist, propranolol reduced the isoproterenol- and pycnogenol-increased probability of contraction state. These data suggested that pycnogenol has inotropic effects via stimulation of , -receptor mediated activity. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Changes in extracellular K+ concentration modulate contractility of rat and rabbit cardiac myocytes via the inward rectifier K+ current IK1

THE JOURNAL OF PHYSIOLOGY, Issue 3 2004
Ron Bouchard
The mechanisms underlying the inotropic effect of reductions in [K+]o were studied using recordings of membrane potential, membrane current, cell shortening and [Ca2+]i in single, isolated cardiac myocytes. Three types of mammalian myocytes were chosen, based on differences in the current density and intrinsic voltage dependence of the inwardly rectifying background K+ current IK1 in each cell type. Rabbit ventricular myocytes had a relatively large IK1 with a prominent negative slope conductance whereas rabbit atrial cells expressed much smaller IK1, with little or no negative slope conductance. IK1 in rat ventricle was intermediate in both current density and slope conductance. Action potential duration is relatively short in both rabbit atrial and rat ventricular myocytes, and consequently both cell types spend much of the duty cycle at or near the resting membrane potential. Rapid increases or decreases of [K+]o elicited significantly different inotropic effects in rat and rabbit atrial and ventricular myocytes. Voltage-clamp and current-clamp experiments showed that the effects on cell shortening and [Ca2+]i following changes in [K+]o were primarily the result of the effects of alterations in IK1, which changed resting membrane potential and action potential waveform. This in turn differentially altered the balance of Ca2+ efflux via the sarcolemmal Na+,Ca2+ exchanger, Ca2+ influx via voltage-dependant Ca2+ channels and sarcoplasmic reticulum (SR) Ca2+ release in each cell type. These results support the hypothesis that the inotropic effect of alterations of [K+]o in the heart is due to significant non-linear changes in the current,voltage relation for IK1 and the resulting modulation of the resting membrane potential and action potential waveform. [source]

Rapid clinical assessment of hemodynamic profiles and targeted treatment of patient with acutely decompensated heart failure

CLINICAL CARDIOLOGY, Issue S5 2004
Greegg C. Fonarow M.D.
Abstract Acutely decompensated heart failure (ADHF) is characterized by hemodynamic abnormalities and neurohormonal activation that contribute to heart failure (HF) symptoms, end-organ dysfunction, arrhythmias, and progressive cardiac failure. The management of ADHF in the emergency department (ED) can be simplified and improved by a 2-min bedside assessment that identifies any of four possible hemodynamic profiles on the basis of clinical signs and symptoms. The profiles are based on whether congestion is present or absent (wet or dry) and perfusion is adequate or limited (warm or cold). A wet-warm profile is seen more frequently in the ED than any of the other three profiles (wet-cold, dry-warm, and dry-cold). The four clinically determined profiles have been shown to predict clinical outcomes and may be used to guide initial HF therapy. The goals of treating ADHF are to stabilize the patient, reverse acute hemodynamic abnormalities, rapidly reverse dyspnea and/or hypoxemia caused by pulmonary congestion, and initiate treatments that will decrease disease progression and improve survival. An ideal agent for the wet-warm profile would rapidly reduce pulmonary congestion, produce balanced arterial and venous dilation, promote natriuresis, lack direct positive inotropic effects, and not cause reflex neuroendocrine activation. Intravenous nesiritide in conjunction with loop diuretics has been found safe and effective as initial treatment for patients with the wet-warm profile. For the wet-cold profile, more intensive therapy and invasive hemodynamic monitoring may prove useful. This review will discuss the rapid clinical determination of hemodynamic profiles in patients presenting to the ED with ADHF and the options for their initial medical management. Case studies representing the wet-warm, wet-cold, dry-warm, and dry-cold profiles will be presented and discussed. [source]