1,720,972 research outputs found
Levosimendan induces NO production through p38 MAPK, ERK and Akt in porcine coronary endothelial cells: role for mitochondrial K(ATP) channel
No full textBackground and purpose: Levosimendan acts as a vasodilator through the opening of ATP-sensitive K + channels (K ATP) channels. Moreover, the coronary vasodilatation caused by levosimendan in anaesthetized pigs has recently been found to be abolished by the nitric oxide synthase (NOS) inhibitor N ω-nitro-L-arginine methyl ester, indicating that nitric oxide (NO) has a role in the vascular effects of levosimendan. However, the intracellular pathway leading to NO production caused by levosimendan has not yet been investigated. Thus, the purpose of the present study was to examine the effects of levosimendan on NO production and to evaluate the intracellular signalling pathway involved. Experimental approach: In porcine coronary endothelial cells (CEC), the release of NO in response to levosimendan was examined in the presence and absence of N ω-nitro-L-arginine methyl ester, an adenylyl cyclase inhibitor, K ATP channel agonists and antagonists, and inhibitors of intracellular protein kinases. In addition, the role of Akt, ERK, p38 and eNOS was investigated through Western blot analysis. Key results: Levosimendan caused a concentration-dependent and K +-related increase of NO production. This effect was amplified by the mitochondrial K ATP channel agonist, but not by the selective plasma membrane K ATP channel agonist. The response of CEC to levosimendan was prevented by the K ATP channel blockers, the adenylyl cyclase inhibitor and the Akt, ERK, p38 inhibitors. Western blot analysis showed that phosphorylation of the above kinases lead to eNOS activation. Conclusions and implications: In CEC levosimendan induced eNOS-dependent NO production through Akt, ERK and p38. This intracellular pathway is associated with the opening of mitochondrial K ATP channels and involves cAMP. Mandarin translation of abstrac
Intracoronary intermedin 1-47 augments cardiac perfusion and function in anesthetized pigs: role of calcitonin receptors and beta-adrenoreceptor-mediated nitric oxide release
No full textSystemic intermedin (IMD)1-47 administration has been reported to result in vasodilation and marked hypotension through calcitonin-related receptor complexes. However, its effects on the coronary circulation and the heart have not been examined in vivo. The present study was therefore planned to determine the primary in vivo effect of IMD1-47 on coronary blood flow and cardiac function and the involvement of the autonomic nervous system and nitric oxide (NO). In 35 anesthetized pigs, IMD1-47, infused into the left anterior descending coronary artery at doses of 87.2 pmol/min, at constant heart rate and arterial blood pressure, augmented coronary blood flow and cardiac function. These responses were graded in a further five pigs by increasing the infused dose of IMD1-47 between 0.81 and 204.1 pmol/min. In the 35 pigs, the blockade of cholinergic receptors (intravenous atropine, 5 pigs), alpha-adrenoceptors (intravenous phentolamine, 5 pigs), and beta1-adrenoceptors (intravenous atenolol, 5 pigs) did not abolish the cardiac response to IMD1-47, the effects of which were prevented by blockade of beta2-adrenoceptors (intravenous butoxamine, 5 pigs), NO synthase (intracoronary N(omega)-nitro-l-arginine methyl ester, 5 pigs), and calcitonin-related receptors (intracoronary CGRP8-37/AM22-52, 10 pigs). In porcine coronary endothelial cells, IMD1-47 induced the phosphorylation of endothelial NO synthase and NO production through cAMP signaling leading to ERK, Akt, and p38 activation, which was prevented by the inhibition of beta2-adrenoceptors, calcitonin-related receptor complexes, and K+ channels. In conclusion, IMD1-47 primarily augmented coronary blood flow and cardiac function through the involvement of calcitonin-related receptor complexes and beta2-adrenoreceptor-mediated NO release. The intracellular signaling involved cAMP-dependent activation of kinases and the opening of K+ channels
Intracoronary infusion of levosimendan to treat postpericardiotomy heart failure
No full textSystemic hypotension limits the intravenous use of levosimendan, particularly in coronary disease. Published reports show that the intracoronary administration of levosimendan in animal models causes an increase of coronary blood flow without systemic hypotension. In this case report, the intracoronary administration of levosimendan bolus in a 74-year-old man with postpericardiotomy heart failure elicited beneficial cardiac effects, increasing both systolic and diastolic functions and blood flow in all of the grafts. No changes of heart rate and systemic arterial blood pressure were observe
Impact of prosthetic mitral rings on aortomitral apparatus function: a cardiac magnetic resonance imaging study
No full textBACKGROUND:
The circumference of the aortic annulus adjusts proportionally with changes in left ventricular volume. These dimensional changes in the aortic annulus improve the left ventricular outflow tract (LVOT) hemodynamics and enhance the anterior mitral valve leaflet (AML) movement. In this study, we investigated the impact of circumferential and partial circumference prosthetic mitral rings on aortomitral apparatus function.
METHODS:
Forty patients who underwent coronary artery bypass graft surgery and restrictive annuloplasty of the mitral valve annulus through either a partial circumference flexible ring (group A = 20 patients) or a circumferential rigid ring (group B = 20 patients) were evaluated using cardiac magnetic resonance imaging. Imaging was performed at the end of a 2-year follow-up period. Variations in LVOT diameter, transmitral valve gradient, and effective mitral valve area were measured and compared.
RESULTS:
Mean variation in LVOT diameter was significantly higher in group A compared with group B (12.7% +/- 4% versus 3.6% +/- 5%, p = 0.0005). Transmitral valve gradient was higher in group B than in group A (6.2 +/- 3 mm Hg versus 4.6 +/- 2 mm Hg, p = 0.007), whereas effective mitral valve area was larger in group A than group B (3.9 +/- 4 cm(2) versus 3.1 +/- 6 cm(2), p = 0.009). The long-axis cardiac magnetic resonance imaging of patients in group B demonstrated that movement at the base of the AML was hindered with the AML pivotal point appearing to shift posteriorly.
CONCLUSIONS:
This study demonstrated that the use of circumferential annular rings significantly impairs overall aortomitral apparatus function by reducing outflow diameter and AML movement
Intracoronary melatonin increases coronary blood flow and cardiac function through β-adrenoreceptors, MT1/MT2 receptors, and nitric oxide in anesthetized pigs
No full textMelatonin is involved in the regulation of the cardiovascular system through the modulation of sympathetic function and the nitric oxide (NO)-related pathway and interaction with MT1/MT2 receptors. However, information regarding its direct actions on coronary blood flow and cardiac function is scarce. This study therefore determined the primary in vivo effect of melatonin on cardiac function and perfusion and the involvement of the autonomic nervous system, MT1/MT2 receptors, and NO. In 35 pigs, melatonin infused into the coronary artery at 70 pg for each mL/min of coronary blood flow while preventing changes in heart rate and arterial pressure increased coronary blood flow, dP/dt(max), segmental shortening, and cardiac output by about 12%, 14%, 8%, and 23% of control values (P < 0.05), respectively. These effects were accompanied by an increase in coronary NO release of about 46% (P < 0.05) of control values. The aforementioned responses were graded in a further five pigs. Moreover, the blockade of muscarinic cholinoreceptors (n = 5) and α-adrenoreceptors (n = 5) did not abolish the observed responses to melatonin. After β(1)-adrenoreceptors blocking (n = 5), melatonin failed to affect cardiac function, whereas β(2)-adrenoreceptors (n = 5) and NO synthase inhibition (n = 5) prevented the coronary response and the effect of melatonin on NO release. Finally, all effects were prevented by MT1/MT2 receptor inhibitors (n = 10). In conclusion, melatonin primarily increased coronary blood flow and cardiac function through the involvement of MT1/MT2 receptors, β-adrenoreceptors, and NO release. These findings add new information about the mechanisms through which melatonin physiologically modulates cardiovascular function and exerts cardioprotective effect
Hemodynamic effect of intracoronary administration of levosimendan in the anesthetized pig
No full textIn this study the hemodynamic effects of intracoronary injection of levosimendan in anesthetized pigs and the mechanisms involved were examined. In 12 anesthetized pigs instrumented for measurement of heart rate (HR), aortic blood pressure (ABP), central venous pressure (CVP), left ventricular end-diastolic blood pressure, left ventricular contractility and relaxation, and mean coronary blood flow (CBF), levosimendan has been injected into the left anterior descending coronary artery at doses corresponding to the ones commonly used in clinics as bolus administration but adapted to the measured CBF. In a further 9 pigs levosimendan has been administered after the blockade of alpha and beta adrenoceptors, muscarinic receptors, and coronary nitric oxide synthase (NOS) to investigate the action mechanism of the drug. The intracoronary bolus administration of doses of levosimendan corresponding to 12 and 24 microg/kg in 10 minutes exerted, respectively, CBF increases of 26.3% and 41.3% of the control values in the absence of changes in the other hemodynamic variables. The blockade of the autonomic nervous system did not prevent the coronary vasodilation, which was, however, abolished by the NOS inhibition. The intracoronary administration of levosimendan exerts positive effects on myocardial blood supply without changes in ABP, HR, CVP, or in myocardial kinetics. The coronary effects of levosimendan are related to NO productio
EVALUATION OF ATRIAL FUNCTION AFTER SURGICAL ABLATION OF ATRIAL FIBRILLATION: A SPECKLE TRACKING STUDY
No full textModulation of calcium movements by urocortin II in endothelial cells
No full textBackground: In endothelial cells urocortin II has recently been found to activate nitric oxide synthase through cAMP-dependent and Ca2+- related pathway. Aim: The present study was therefore planned to determine the mechanisms of urocortin II effect on Ca2+ movements. Methods. In Fura-2 loaded porcine aortic endothelial cells (PAE), the effects of urocortin II on [Ca2+]c were analyzed and compared with those of various K + channels agonists/antagonists. Results: In Fura-2 loaded PAE, urocortin II promoted a transient increase of [Ca2+]c mainly originating from an intracellular pool sensitive to thapsigargin and slightly from the extracellular space. In addition, urocortin II caused the hyperpolarization of plasma membrane through the opening of K+ channels, which contributed to the increased [Ca2+]c. These effects were abolished by the corticotropin releasing factor receptors (CRFR2) blocker, the adenylyl cyclase and Ca2+-calmodulin-kinase (CaMKII) inhibitors and by blockers of K+ channels. In addition, in PAE cultured in Na+-free medium or loaded with the plasma-membrane Ca2+ pump inhibitor the urocortin II-evoked Ca2+ transient was slower. Conclusion: The results obtained show that urocortin II affects intracellular Ca2+ homeostasis in PAE by both promoting a discharge of intracellular pool and by interfering with the operation of store-dependent channels through CRFR2-cAMP-CaMKII related signalling and K+ channels opening
Double patch repair through a single ventriculotomy for ischemic ventricular septal defects
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