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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pharmacologic support of the failing neonatal heart to maintain cardiac output, which is vital for sufficient end organ perfusion, is a challenging task for the pediatric intensivist, especially since strategies which have been proven to be effective in adults cannot necessarily be extrapolated to neonates. The unique biochemical properties and structure of the neonatal heart, including the increased non-contractile tissue mass, a lower responsiveness to beta adrenergic agents and the heart rate dependent cardiac output with a limited ability to increase stroke volume, favor some of the new inotropes of the Ca+ sensitizer family. Focusing on the after load reduction, inodilators as phosphodiesterase inhibitors and human brain natriuretic peptide offer treatment options for the neonatal myocardium. Additionally, thyroxine and steroids have been investigated in neonates with low cardiac output after surgery for congenital heart disease. Gene therapy, in particular cardiac-selective gene transfer, might offer perspectives for future support for the neonatal heart. This text reviews some of the most recent pharmacologic strategies targeting the failing myocardium in the critically ill newborn and infant.
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PMID:New inotropic pharmacologic strategies targeting the failing myocardium in the newborn and infant. 1684 28

Compartmentation and dynamics of cAMP and PKA signaling are important determinants of specificity among cAMP's myriad cellular roles. Both cardiac inotropy and the progression of heart disease are affected by spatiotemporal variations in cAMP/PKA signaling, yet the dynamic patterns of PKA-mediated phosphorylation that influence differential responses to agonists have not been characterized. We performed live-cell imaging and systems modeling of PKA-mediated phosphorylation in neonatal cardiac myocytes in response to G-protein coupled receptor stimuli and UV photolysis of "caged" cAMP. cAMP accumulation was rate-limiting in PKA-mediated phosphorylation downstream of the beta-adrenergic receptor. Prostaglandin E1 stimulated higher PKA activity in the cytosol than at the sarcolemma, whereas isoproterenol triggered faster sarcolemmal responses than cytosolic, likely due to restricted cAMP diffusion from submembrane compartments. Localized UV photolysis of caged cAMP triggered gradients of PKA-mediated phosphorylation, enhanced by phosphodiesterase activity and PKA-mediated buffering of cAMP. These findings indicate that combining live-cell FRET imaging and mechanistic computational models can provide quantitative understanding of spatiotemporal signaling.
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PMID:Systems analysis of PKA-mediated phosphorylation gradients in live cardiac myocytes. 1690 51

Stimulation of several G-protein-coupled receptors (GPCRs) promotes intracellular production of cyclic adenosine 3',5'-monophosphate (cAMP) and subsequently activates protein kinase A (PKA). In the heart, beta-adrenergic receptor (beta-AR) stimulation increases contractile performance and heart rate as part of the 'fight-or-flight' stress response. Molecular organisation of PKA-effector association occurs by A kinase anchoring proteins (AKAPs), which target kinase action to specific intracellular sites. Some AKAPs interact directly with specific cAMP-hydrolysing phosphodiesterase (PDE) isoforms allowing for the assembly of multi-protein complexes that create focal points of intracellular cAMP signalling. Certain PDE isoforms co-localise with PKA as part of negative feedback mechanisms which may protect from excess beta-AR stimulation of Ca2+ transporters during cardiac excitation-contraction coupling. Pharmacological PDE inhibition increases intracellular cAMP concentrations and augments excitation-contraction coupling in heart failure. However, chronic PDE inhibitor treatment causes severe cardiac side effects and increases mortality. Moreover, cAMP hydrolysing PDE activity was found decreased in heart failure which may contribute to disease progression via chronic PKA-dependent dysregulation of Ca2+ transport proteins. The authors review the contribution of PDE activity in the heart to contractile stress adaptation, the significance of altered cAMP signalling in heart failure, and the effects of PDE inhibition in heart disease.
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PMID:Phosphodiesterase 4D and heart failure: a cautionary tale. 1698 25

Pulmonary hypertension is characterised by a progressive increase in pulmonary vascular resistance and a poor prognosis. The exact underlying mechanisms are still poorly understood; however, it is hypothesised that pulmonary medial hypertrophy and endothelial dysfunction lead to impaired production of vasodilators such as nitric oxide (NO) and prostacyclin, and increased expression of vasoconstrictors such as endothelin-1. The current treatment modalities for pulmonary hypertension include conventional supportive therapies and more specific pharmacological therapies that are targeted at abnormalities of endothelial function. NO and phosphodiesterase type 5 (PDE5) inhibitors induce pulmonary vasodilation by increasing intracellular cyclic guanosine monophosphate (cGMP) concentrations. Sildenafil citrate is a highly selective inhibitor of PDE5. Investigations in animal models and recent clinical case reports with some studies in the paediatric population suggest that sildenafil may be a promising agent in treating pulmonary hypertension. The effect of sildenafil on pulmonary vasculature appears to be independent of the underlying cause, thereby providing a role in idiopathic pulmonary arterial hypertension (PAH), PAH associated with congenital heart disease, pulmonary hypertension secondary to lung disease or persistent pulmonary hypertension of the newborn. It may also be beneficial in postoperative pulmonary hypertension and in neonates who are difficult to wean from inhaled NO. It is easily administered and effective, and has minimal systemic adverse effects. Although the reported results in children with pulmonary hypertension are promising, it is an experimental drug and large-scale randomised controlled studies are required to validate the safety, efficacy and dosage in the paediatric population.
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PMID:Therapeutic applications of sildenafil citrate in the management of paediatric pulmonary hypertension. 1720 64

Pulmonary hypertension (PH) denotes a poor prognosis in patients with left-sided heart disease. No study has demonstrated long-term benefit from PH drugs such as prostanoids, endothelin antagonists, and phosphodiesterase-5 inhibitors. In some cases, cautious use of PH drugs may be indicated. However, theoretic and practical concerns limit any formal recommendations.
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PMID:Pulmonary hypertension associated with left-sided heart disease. 1733 38

Some of the active phytochemicals in herbal medicine are finding therapeutic use. For example, patients with heart disease are reported to benefit from treatment with herbal medicine with fewer side effects. Previous studies showed the inhibitory effects of tetramethylpyrazine, an active component of medicinal herb, on phosphodiesterase that is associated with heart disease and the cardio-protective effects of other herbal medicine that was used to protect ischemia-reperfusion injury of rat hearts. Individual herbal medicines show antipyretic, analgesic and anti-inflammatory and anti-cancer effects. In addition to sharing many therapeutic activities, the active components of herbal medicine are also used in nutrient supplement for cardiovascular disease. Numerous in vitro studies of herbal medicine on different cell lines and in vivo study of herbal medicine have been reported. However, the mechanism of actions remains unclear. The present review aims to give an overview of the recent development of herbal medicine in treatment of cardiovascular disease, and covers the possible mechanism of action of some of active principles. The study will provide insights into drug action and demonstrate the therapeutic benefits of herbal medicine for the treatment of cardiovascular disease.
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PMID:Pharmacological activity of cardiovascular agents from herbal medicine. 1797 89

Pulmonary hypertension (PH) is a hemodynamic state characterized by elevation in the mean pulmonary arterial pressure and pulmonary vascular resistance leading to right ventricular failure and premature death. PH can be the result of a variety of diseases of different etiologies. Pulmonary arterial hypertension (PAH) should be distinctly differentiated from pulmonary venous hypertension (PVH) as a result of left heart disease. PAH is commonly caused by or associated with an underlying pulmonary, cardiac, or systemic disease (APAH). In the absence of an identifiable etiology or associated underlying disease, PAH is referred to as idiopathic (IPAH). IPAH, formerly known as primary pulmonary hypertension (PPH), is a rare disease most commonly seen in women of childbearing age. Presenting symptoms and signs are nonspecific and include dyspnea on exertion, fatigue, and a loud pulmonary component of the second heart sound. Transthoracic Doppler echocardiography is an excellent noninvasive test to detect the presence of pulmonary hypertension, although every patient should receive a right heart catheterization to confirm the diagnosis. A detailed work up, including laboratory tests and imaging studies, is also indicated to rule out known causes of pulmonary hypertension. Several targeted treatment options have become available in recent years and include parenteral and inhaled prostanoids, oral endothelin receptor antagonists, and oral phosphodiesterase type-5 inhibitors. As a result of their complex care, patients should be referred to centers with expertise in pulmonary hypertension.
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PMID:Pulmonary hypertension: evaluation and management. 1800 30

Prevalence and severity of erectile dysfunction (ED) increase with aging and are often associated with illnesses, like diabetes mellitus, heart disease, and hypertension, pathologically characterized by endothelial dysfunction and whose prevalence increases with age. The assumption that ED is mainly a neurovascular disease is supported by the evidence that specific phosphodiesterase type 5 (PDE5) inhibition produces an efficient erection in a wide range of ages and conditions. The availability of specific PDE5 inhibitors has enabled the development of effective treatment strategies, in this contest, tadalafil may be considered as the least "typical" PDE5 inhibitor. In clinical trials, tadalafil significantly enhanced, in patients of different ages, all efficacy outcomes across disease etiologies and severities. With an effectiveness lasting up to 36h, tadalafil allows patients to choose when to have sexual activities without the need to time it, showing positive feedback in terms of quality of life related to the treatment. Headache and dyspepsia were the most frequent side-effects of tadalafil, followed by back pain, nasal congestion, myalgia, and flushing, but the impact that long time action could have on effectiveness and safety is not yet entirely defined. The aim of this article is to critically review the available evidence from the tadalafil clinical research program and give the physician a rational approach for intervention in the treatment of ED and related diseases.
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PMID:Tadalafil in the treatment of erectile dysfunction; an overview of the clinical evidence. 1804 21

There is increased awareness regarding the close association between cardiovascular disease and erectile dysfunction, especially because both conditions share common risk factors such as diabetes mellitus, hypertension, smoking, hyperlipidemia, and a sedentary lifestyle. Recent studies suggest that erectile dysfunction could be considered a potential marker for underlying silent cardiac or vascular disease processes. Endothelial dysfunction seems to play a major role in both sexual dysfunction and heart disease. With the initiation in 1998 of vasoactive drugs such as the phosphodiesterase-5 inhibitors for the treatment of erectile dysfunction, the underlying vascular components of erectile dysfunction have become a more prominent focus of attention in the clinical and research setting. This review critically examines the background, pathophysiology, and mechanisms behind erectile dysfunction and its close correlation to cardiovascular disease.
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PMID:The relationship between erectile dysfunction and cardiovascular disease. Part I: pathophysiology and mechanisms. 1819 44

Pulmonary arterial hypertension is an idiopathic process or can be associated with another circumstances (connective tissue diseases, congenital heart disease, portal hypertension, exposure to appetite suppressants or another drugs or infectious agents such as HIV). Most patients are diagnosed as the result of an evaluation of symptoms, whereas others are diagnosed incidentally or during screening of asymptomatic populations at risk. We reviews systematic screening for the approach to diagnosing pulmonary arterial hypertension. A diagnostic algorithm can guide the evaluation but it can be modified according to specific clinical circumstances. The number of therapeutic options has increased.in the last years. We reviews the use of calcium-channel blockers, prostacyclin (and analogues), endothelin-receptor antagonists, and phosphodiesterase-5 inhibitors, and the use of combination therapy, and provides specific recommendations about the actual treatment.
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PMID:[Diagnosis and treatment of pulmonary hypertension]. 1827 69


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