**11. References**


AF progression is reported to be associated with greater PV diameter (Knackstedt et al., 2003; Tsao et al., 2001) as a consequence of PV remodeling (Scharf et al., 2003). Although the relation of AF and PV contraction remains to be fully investigated, augmentation of **Ar** wave (e.g., PVBV) may cause cyclic stretching of highly compliant myocardial sleeves in PV, repetitive ectopic beats and loss of 'sphincter' function, which underlie further PV regurgitation. Therefore, **D** and **Ar** waves augmentation, PV myocardial sleeve stretching and ectopic beats form a vicious cycle leading to PV remodeling. A possible mechanism by

AF is the most common clinical arrhythmia showing progressive features. There has been evidence to suggest PV as a source of abnormal electrical activities initiating and sustaining AF. Currently, PVF recording is feasible in routine Doppler echocardiography, and is essential for evaluation of LA functioning three roles during an entire cardiac cycle such as 'booster pump', 'reservoir' and 'conduit'. This flow pattern recognition is of clinical importance not only in assessing global cardiac performance but also for obtaining considerable information with respect to the pathophysiology and management of AF. There has been a consensus with respect to the PVF pattern during ongoing AF or in patients with permanent AF. However, there has been a controversy concerning PVF profile during sinus rhythm in patients with paroxysmal AF. This indicates the anatomical and pathophysiological complexities of PV-LA junction and AF itself. Time-dependent recovery of LA contractile function (LA stunning) and neuroanatomical modification of PV-LA junction by radiofrequency catheter ablation make this controversy further complicated. In spite of such controversy and complexity, PVF recording has potential benefits to assess

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**7** 

*USA* 

**Phosphodiesterase-5 Inhibitors Improve Left** 

Impaired systolic performance and/or diastolic function have long been detrimental consequences of acute myocardial infarction (AMI), which remains a major cause of morbidity and mortality worldwide. Despite considerable therapeutic improvements, left ventricular dysfunction secondary to infarction continues to pose serious health complications, including heart failure (HF), wherein the heart is unable to maintain a cardiac output appropriate for the requirements of the body. Several factors contribute to HF, including adverse ventricular remodeling, progressive hypertrophy and sustained cell death by apoptosis. Therefore, the search for a therapeutic strategy to overcome or mitigate the

Sildenafil citrate (ViagraTM) is the first PDE-5 inhibitor approved for treatment of erectile dysfunction. The discovery of this drug in 1989 was the result of extensive research on chemical agents that hold potential promise in the treatment of coronary heart disease. Initial clinical studies on sildenafil in the early 1990s were not promising with respect to its anti-anginal potential. However, a remarkable side effect was reported by a number of volunteers participating in these investigations; sildenafil seemed to enhance penile erections, which soon thereafter became the main focus of further studies. More than 10 million men worldwide have been treated with sildenafil since its market debut in 1998. Sildenafil is highly specific for PDE-5 inhibition with relatively minor cross-reactivity with PDE-6 (Laties & Fraunfelder, 1999). It has a chemical structure similar to cGMP and inhibits PDE-5 by binding to the cGMP-catalytic sites (Corbin & Francis, 2002) thereby allowing the accumulation of cGMP in the erectile tissue. Two additional agents in this class (vardenafil [LevitraTM] (Porst et al., 2001) and tadalafil [CialisTM]) have also been developed and approved by the FDA for treatment of erectile dysfunction and recently sildenafil and tadalafil were approved for treatment of pulmonary arterial hypertension (PAH) (Corbin & Francis, 2002). PDE-5 inhibitors are structurally similar to cGMP and therefore compete with cGMP for binding to PDE-5 at the catalytic site (reviewed in Kukreja et al., 2005). Interestingly, PDE expression has been reported to change in pathologic conditions. For instance, in patients with cardiovascular disease or diabetes, nitric oxide (NO) levels are

**1. Introduction** 

**1.1 PDE-5 Inhibitors** 

progression of HF is of paramount importance.

**Ventricular Function in Failing Hearts** 

Fadi N. Salloum and Rakesh C. Kukreja

*Virginia Commonwealth University Medical Center Richmond, Virginia* 

