The Potential Use of Type-5 Phosphodiesterase Inhibitors Viagra, Cialis, Levitra in Coronary Artery Bypass Graft Surgery: Pulmonary Hypertension and Cardiopulmonary Bypass

viagraIn addition to its responsiveness in the corpus cavernosum and coronary artery, PDE5 inhibitors also act selectively in the pulmonary vasculature, and patients with elevated pulmonary pressures appear to benefit significantly from its action even when administered orally. Published data have come primarily from the study of viagra.

A randomized double-blind trial found that viagra was protective against acute hypoxia (11% inspired oxygen) in healthy human volunteers, almost completely reversing the raised pulmonary artery pressure. In a study of five consecutive patients with pulmonary hypertension, oral viagra (50 mg q8h) decreased pulmonary capillary wedge pressures, increased cardiac index, improved functional capacity, and led to a reduction of right ventricular mass measured by MRI. Systolic and diastolic pressures were found to be unchanged in these patients. In another similar study, oral viagra, 50 mg tid, for 3 months significantly reduced pulmonary artery pressure and pulmonary vascular resistance, increased cardiac output and exercise tolerance (measured by using the 6-min walk test), and improved quality of life. A larger, double-blind, placebo-controlled crossover trial of 22 patients confirmed similar benefits: significant improvement in exercise tolerance (+ 44% measured by treadmill exercise time), improved cardiac index, and reduced pulmonary artery systolic pressure. Patient symptoms were reported to be improved in the above studies.

When comparing levitra, viagra and cialis on my canadian pharmacy, differential pulmonary vasorelaxant effects and arterial oxygenation were observed in a randomized prospective study of 60 consecutive patients with New York Heart Association class II-IV pulmonary arterial hypertension. The authors noted that significant improvement in arterial oxygenation equivalent to that produced by NO inhalation was only noted with viagra, and that the pulmonary to systemic vascular resistance ratio was different among the three.

PDE5 inhibitorsAlthough clinical data on the effects of PDE5 inhibitors in the cardiac surgical setting are still lacking, much valuable insight has been gained from studies of inhaled nitric oxide and its cardiopulmonary effects in cardiac surgical patients. Evidence suggests that pulmonary vascular relaxation in response to inhaled NO may be indicative of reversible pulmonary hypertension, a response that is not usually seen in individuals with relatively normal pulmonary vascular resistance at baseline. This reversibility or capacity to be dilated to inhaled NO is seen following on-pump CABG even in patients without significant preexisting pulmonary hypertension, suggesting the presence of postoperative pulmonary endothelial dysfunction. Activation of cytokines and the inflammatory responses as a result of cardiopulmonary bypass is thought to be responsible, > and off-pump CABG was found to produce less pulmonary endothelial dysfunction compared with on-pump CABG. It would be important to study PDE5 inhibitors in the context of cardiopulmonary bypass, whether such iatrogenic inflammatory state and pulmonary endothelial dysfunction can be reduced pharmacologically. Also, because of the differing metabolic demands of the heart during on-pump and off-pump CABG, the different cardioplegia solutions being used, and other physicochemical parameters that are being manipulated, thorough investigations into the use of PDE5 inhibitors may yield a useful addition to our armamentarium for the management of patients undergoing CABG.

In adult cardiac patients with postoperative pulmonary hypertension secondary to right ventricular infarction/dysfunction or following mitral valve surgery with the use of cardiopulmonary bypass, viagra alone or in combination with inhaled NO effectively lowered pulmonary artery pressure. Sildenafil has also been demonstrated to facilitate weaning of inhaled NO. In a study comparing the efficacy of inhaled NO and/or viagra in 13 consecutive patients with pulmonary hypertension waitlisted for heart-lung transplantation, a single oral dose of viagra was found to be as effective and selective as inhaled NO in producing pulmonary vasodilation. The authors concluded that viagra was superior to inhaled NO because it did not increase pulmonary capillary wedge pressure and decrease cardiac output as did NO, while exerting effective pulmonary vasodilating effects. Sildenafil also appears to confer benefits in hypertensive cardiac transplant recipients. As an adjunct to regular antihypertensive medications, endothelial function, brachial artery reactivity, and central and peripheral arterial BP were reportedly improved, in addition to a reduction in left ventricular afterload and systolic stress.

Conclusion

Sildenafil is a well-characterized PDE5 inhibitor that appears to be a favorable agent in patients undergoing CABG by virtue of its coronary vasodilating, endothelium-enhancing/preconditioning and platelet inhibitory effects, and its beneficial effects in the myocardium (Fig 1) and pulmonary vasculature have been demonstrated amply at the molecular and physiologic levels in animal and human studies. Although its potency is modest compared to other single agents that specifically target platelet adhesion/aggregation or constricted coronary arteries, its modulating antiplatelet effects, NO/cGMP-potenti-ating, and preconditioning effects on the endothelium may be what are desirable for its adjunctive use in CABG (Fig 2). Furthermore, patients administered a powerful antiplatelet agent such as GP IIb-IIIa inhibitor prior to coronary surgery are at high risk of bleeding complications and requirement for transfusion.

In addition to its being targeted in the treatment of patients with erectile dysfunction (my canadian pharmacy – help in the treatment of erectile dysfunction) and pulmonary hypertension, the preponderant localization of PDE5 in the coronary circulation allows it to be an attractive target for manipulation at the time of CABG. A large body of evidence has shown that viagra is safe and may confer substantial benefits to patients with various cardiovascular diseases. When these data are extrapolated to and interpreted in the context of CABG, it seems likely that the use of PDE5 inhibitors may enhance pulmonary hemodynamics, coronary flow, and myocardial perfusion, and may dampen the detrimental effects of platelet activation associated with CABG.

PDE5 inhibitors have substantial differences in their pharmacologic profiles and actions in the cardiopulmonary circuit that warrant further investigation. The beneficial effects of viagra on the cardiopulmonary circuit are promising, and its use at the time of CABG should be investigated thoroughly.

Fig1

Figure 1. Molecular mechanisms underpinning the cardioprotective and antihypertrophic/antiremodeling effects of viagra in cardiac myocyte. Physiologic responses or outcomes include early preconditioning (1), delayed preconditioning (2), decreased intracellular calcium and possibly reduced myocardial stunning or contracture (3), and antihypertrophic response to pressure overload (4). mito = mitochondrion; ch = channel; NPs = natriuretic peptides; SR = sarcoplasmic reticulum; PKC = protein kinase C.