sildenafil-citrate and Myocardial-Ischemia

Topics: Contraindications; Erectile Dysfunction; Humans; Male; Myocardial Ischemia; Piperazines; Purines; Sildenafil Citrate; Sulfones

This article examines the relationships among depression, ischemic heart disease, and erectile dysfunction. Depression is an independent risk factor for the development of ischemic heart disease, and depression in the post-myocardial infarction patient is associated with increased morbidity and mortality. Ischemic heart disease and erectile dysfunction are also frequently comorbid and share many common risk factors including age, hypertension, diabetes, dyslipidemia, obesity, sedentary lifestyle, and smoking. Depression and erectile dysfunction often occur together; however, the causal relation may be difficult to determine because erectile dysfunction may be a symptom of depression, social distress accompanying erectile dysfunction may precipitate depressive symptoms, or both conditions may result from a common factor such as vascular disease.

Topics: Adult; Aged; Blood Circulation; Catecholamines; Comorbidity; Depressive Disorder; Erectile Dysfunction; Humans; Hydrocortisone; Male; Middle Aged; Models, Biological; Myocardial Ischemia; Piperazines; Purines; Risk Factors; Sildenafil Citrate; Sulfones; Treatment Outcome

Diabetes can induce sexual disorders by different mechanisms. These troubles are more frequent in diabetics subjects. Thus, management of sexual impotence is an important aspect of diabetes care. However, most diabetologists are not trained to treat sexual disorders. The recent availability of oral drugs, i. e. Sildenafil (Viagra), has partly simplified the treatment of sexual impotence, particularly in diabetic patients. However, Viagra is efficient in only 60% cases in diabetic subjects. In the remaining cases, intracavernosal injections or vacuum can be used. Since Viagra has been available, more diabetic patients complained with sexual disorders, and ask for treatment of impotence. Cardio-vascular diseases must retain more attention in diabetic patients who are exposed to silencious myocardial ischemia. In such subjects, Viagra is not contra-indicated, but must be used after myocardial explorations, especially if the patients have cardio-vascular risk factors. However, patients and their doctors have been threatened by death cases reported with Viagra in United States. The lack of detailed informations has restrained Viagra's prescription. The following explains how to manage sexual disorders as part of diabetes care, and suggests rules for Viagra's prescription in diabetic patients.

Topics: Cardiovascular Diseases; Contraindications; Diabetes Complications; Diabetes Mellitus; Diabetic Angiopathies; Erectile Dysfunction; Humans; Male; Myocardial Ischemia; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

Erectile dysfunction (ED) is common in men with cardiovascular disease. The introduction of sildenafil citrate, the first oral agent for the treatment of this disorder, has increased awareness about the risks of sexual activity in cardiac patients and raised concerns about the safety of sildenafil in patients being treated for coronary disease. Sildenafil is a potent and selective inhibitor of phosphodiesterase type 5 (PDE5), the enzyme responsible for the degradation of cyclic guanosine monophosphate (cGMP). Sildenafil acts along the same general pathway as nitric oxide donors to increase cGMP levels and enhance erections. Sildenafil is a modest vasodilator that causes small decreases in systemic arterial pressure and mild preload and afterload reductions. It does not cause major decreases in blood pressure when administered with one or more standard antihypertensive agents. Because PDE5 is also present in small amounts in the systemic vasculature, sildenafil can cause a synergistic and major decrease in pressure when combined with organic nitrates. Use of organic nitrates is the only contraindication to sildenafil use. Data on sildenafil in patients with recent (less than 6 months) myocardial infarction (MI), unstable angina, stroke, and recent life-threatening arrhythmias are not available, so the drug should be used with caution in patients with unstable cardiac conditions. Placebo-controlled and open-label phase 2/3 trials including men with ischemic heart disease did not show an increase in MI or serious cardiovascular events in patients treated with sildenafil versus placebo. None of the serious cardiovascular events reported in these trials were considered treatment related by the investigators. There is a small but finite increased risk of developing ischemia or infarction with sexual activity. Therefore, before prescribing sildenafil or any current or future treatment for ED to patients with known cardiac disease or multiple cardiovascular risk factors, physicians should discuss the potential cardiac risk of sexual activity and perform a complete medical assessment, including an exercise stress test if appropriate.

Topics: Antihypertensive Agents; Contraindications; Drug Synergism; Erectile Dysfunction; Humans; Male; Myocardial Ischemia; Nitrates; Phosphodiesterase Inhibitors; Piperazines; Purines; Risk Factors; Sex Factors; Sildenafil Citrate; Sulfones; Vasodilation; Vasodilator Agents

Erectile dysfunction is a common condition in middle-aged and older men and frequently occurs in association with various chronic illnesses, particularly cardiovascular diseases. As there is a degree of cardiac risk associated with sexual activity, clinicians should consider the patient's cardiovascular status before initiating any treatment for erectile dysfunction. This is particularly relevant for men with decreased exercise tolerance as a result of their ischemic heart disease. We examined 2 patients with no history of cardiovascular disease suffering from myocardial ischemia after sildenafil administration. The literature about a correlation between sildenafil and coronary artery disease is reviewed.

Topics: Electrocardiography; Humans; Male; Middle Aged; Myocardial Ischemia; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

Sexual intercourse involves mild to medium severe physical exertion of the cardiovascular system. The risk of sudden death associated with sexual activity is very low, and so is the risk of developing infarction. In patients with pre-existing ischaemic heart disease sexual activity is safe in case of controlled angina with tolerance of a medium-grade load on examination on a treadmill. After acute myocardial infarction with a non-complicated course sexual activity can be resumed in a familiar environment with a familiar partner after about 10 days. In stabilized anginous patients sildenafil administration is safe assuming that the patient does not take long-acting nitrates and does not need frequent administration of short-term acting nitrates. It is important to avoid nitrates also in the treatment of acute ischaemic conditions in these patients. At present we do not possess adequate information on the clinical importance of influencing sildenafil elimination by competition with other substances excreted by the same route.

Topics: Erectile Dysfunction; Humans; Male; Myocardial Ischemia; Phosphodiesterase Inhibitors; Piperazines; Purines; Risk Factors; Sildenafil Citrate; Sulfones

A large proportion of patients who have erectile dysfunction also have coronary artery disease (CAD). In these patients, nitrate therapy is a contraindication to the use of sildenafil. To assess whether the metabolic anti-ischemic agent, trimetazidine, is effective in controlling episodes of myocardial ischemia during sexual activity in patients who have CAD and use long-term nitrate therapy, we studied 38 men (57 +/- 6 years of age) who had proved CAD. Patients underwent 24-hour ambulatory electrocardiographic monitoring at baseline, after 1 week of oral nitrate therapy (20 mg 3 times a day), and after 1 week of trimetazidine (20 mg 3 times a day). Patients were asked to engage in >/=1 session of sexual intercourse during each session of ambulatory electrocardiographic monitoring. They were instructed to take sildenafil (100 mg) 1 hour before sexual intercourse performed at baseline and during therapy with trimetazidine and sildenafil or placebo (blinded) during therapy with nitrates. A decrease in total ischemic burden was observed with nitrates and trimetazidine compared with baseline (-3 +/- 1.2 episodes/patient/24 hours vs -5 +/- 1.3 episodes/patient/24 hours and -6 +/- 5 min/patient/24 hours vs -8 +/- 3 min/patient/24 hours, p <0.01 for nitrates and trimetazidine vs baseline). Trimetazidine plus sildenafil was more effective in controlling episodes of myocardial ischemia during sexual activity than nitrates alone (-45 +/- 11% vs -18 +/- 7%, p <0.04). In conclusion, in patients who have CAD, combination therapy with sildenafil and trimetazidine is more effective than nitrate therapy in the control of ischemic episodes during sexual activity, suggesting that long-term nitrate therapy may be safely switched to trimetazidine therapy when therapy for erectile dysfunction is required.

Topics: Adult; Aged; Analysis of Variance; Coitus; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Electrocardiography, Ambulatory; Erectile Dysfunction; Humans; Male; Middle Aged; Myocardial Ischemia; Nitrates; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Treatment Outcome; Trimetazidine; Vasodilator Agents

Animal studies have demonstrated that administration of sildenafil can limit myocardial damage induced by prolonged ischemia, an effect that appears to be mediated by opening of adenosine triphosphate-sensitive potassium (K(ATP)) channels. No study has investigated whether sildenafil can also prevent the impairment in endothelium-dependent vasodilatation induced by ischemia-reperfusion (IR) in humans.. In a double-blind, placebo-controlled, crossover design, 10 healthy male volunteers (25 to 45 years old) were randomized to oral sildenafil (50 mg) or placebo. Two hours later, endothelium-dependent, flow-mediated dilatation (FMD) of the radial artery was measured before and after IR (15 minutes of ischemia at the level of the brachial artery followed by 15 minutes of reperfusion). Seven days later, subjects received the other treatment (ie, placebo or sildenafil) and underwent the same protocol. Pre-IR radial artery diameter and FMD, as well as baseline radial artery diameter after IR, were similar between visits (P=NS). After placebo administration, IR significantly blunted FMD (before IR: 7.9+/-1.1%; after IR: 1.2+/-0.7%, P<0.01). Importantly, sildenafil limited this impairment in endothelium-dependent vasodilatation (before IR: 7.0+/-0.9%; after IR: 6.2+/-1.1%, P=NS; P<0.01 compared with placebo). In a separate protocol, this protective effect was completely prevented by previous administration of the sulfonylurea glibenclamide (glyburide, 5 mg), a blocker of K(ATP) channels (n=7; FMD before IR: 10.3+/-1.5%; after IR: 1.3+/-1.4%, P<0.05).. In humans, oral sildenafil induces potent protection against IR-induced endothelial dysfunction through opening of K(ATP) channels. Further studies are needed to test the potential clinical implications of this finding.

Topics: Adult; Cross-Over Studies; Double-Blind Method; Endothelium, Vascular; Glyburide; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardial Reperfusion Injury; Piperazines; Placebo Effect; Potassium Channels; Purines; Sildenafil Citrate; Sulfones

We tested the hypothesis that sildenafil increases myocardial dilator reserve in humans with ischemic heart disease.. Positron emission tomography measured myocardial blood flow in 14 patients with ischemic heart disease. Patients were studied twice, in double-blind, placebo-control, cross-over design with sildenafil (or placebo) given approximately 2-3 h before measurements of hemodynamics and myocardial blood flow: at rest, with cold pressor stress and with adenosine. All myocardial segments of each patient with myocardial blood flow <1.65 ml/min per g with adenosine under placebo conditions were combined into one abnormal zone for that patient. Segments with myocardial blood flow >1.65 ml/min per g were averaged and combined into a normal zone for that patient.. At rest, rate pressure product (heart rate x systolic arterial pressure, mmHg/min) was comparable, as was abnormal zone myocardial blood flow (ml/min per g; 0.76+/-0.48 placebo versus 0.64+/-0.20 sildenafil, both P=NS; mean+/-SD). Both rate pressure product and myocardial blood flow increased (P<0.01) with cold pressor stress (11+/-3 K and 1.14+/-0.59 placebo versus 10+/-3 K and 1.21+/-0.62 sildenafil). However, sildenafil failed to improve the myocardial blood flow response to cold pressor stress in abnormal or normal zones. In contrast, abnormal zone myocardial blood flow reserve with adenosine and sildenafil (2.6+/-0.7) exceeded that with adenosine and placebo (2.0+/-1.3, P<0.04, paired sign test).. Sildenafil improves myocardial blood flow dilator response to adenosine in abnormal zones, possibly by augmenting nitric oxide-mediated increases in cGMP because adenosine response in part is nitric oxide dependent. Failure to improve myocardial blood flow response to cold pressor stress suggests that alpha-adrenergic constriction may offset enhanced nitric oxide effects. Clinically, the data suggest sildenafil may exert an anti-ischemic effect in patients with coronary artery disease.

Topics: Adult; Aged; Analysis of Variance; Blood Pressure; Coronary Circulation; Coronary Vessels; Double-Blind Method; Heart; Humans; Male; Middle Aged; Myocardial Ischemia; Piperazines; Positron-Emission Tomography; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents

We studied the effects of sildenafil, a phosphodiesterase 5 inhibitor, on coronary and peripheral vascular function, platelet activation, and myocardial ischemia.. Nitric oxide vasodilates and inhibits platelet activation by generating cyclic guanosine 5'-monophosphate, which is metabolized by phosphodiesterase type 5.. The effect of oral sildenafil on resting coronary vascular tone, endothelium-dependent and -independent function and platelet activation was measured in 24 patients. An additional 24 patients with coronary artery disease (CAD) and ischemia during exercise, and 12 control subjects received either 100 mg of sildenafil, 10 mg of isosorbide dinitrate (ISDN) or placebo during exercise on three separate days in a randomized, double-blind manner. Flow-mediated dilation of the brachial artery was measured, and CAD patients underwent treadmill exercise testing.. Sildenafil (100 mg) vasodilated epicardial coronary arteries (+6.9 +/- 1.3%, p < 0.0001). Coronary epicardial and microvascular responses with acetylcholine and cold-pressor testing improved, with a greater enhancement in patients with CAD and endothelial dysfunction. Verapamil responses were unchanged. Both resting and adenosine diphosphate-stimulated platelet IIb/IIIa receptor activation was inhibited by sildenafil (p < 0.05). Brachial arteries dilated in response to sildenafil in controls. Peak flow-mediated dilation was similar, but the duration of hyperemia was prolonged after sildenafil administration (p < 0.001). Compared with placebo, ISDN improved myocardial ischemia during exercise (p < 0.05), whereas the effect of sildenafil was intermediate between the two.. Sildenafil dilates epicardial coronary arteries, improves endothelial dysfunction and inhibits platelet activation in patients with CAD. It has an intermediate effect on myocardial ischemia compared with ISDN and placebo.

Topics: Adult; Aged; Brachial Artery; Case-Control Studies; Coronary Circulation; Double-Blind Method; Endothelium, Vascular; Exercise Test; Female; Flow Cytometry; Hemodynamics; Humans; Male; Middle Aged; Myocardial Ischemia; Phosphodiesterase Inhibitors; Piperazines; Platelet Activation; Purines; Sildenafil Citrate; Sulfones; Vasodilation; Vasodilator Agents

It has been suggested that phosphodiesterase 5 (PDE5) inhibition is potentially hazardous and that it increases the risk of cardiac events in patients with coronary artery disease. This study sought to evaluate whether PDE5 inhibition with sildenafil exerts any effect on exercise-induced myocardial ischemia in patients on beta-blockers.. Fourteen patients underwent a baseline exercise test off-therapy and were then started on atenolol (100 mg once daily). After a run-in phase of 1 week, patients underwent a second exercise test and were randomized to receive either sildenafil (50 mg) or placebo given in a random order on two different occasions, 2 days apart. Exercise test was repeated 2 hours after the administration of sildenafil or placebo.. All patients had a > 1 mm ST-segment depression while off-therapy. Eight patients had a negative exercise test response after atenolol, which was unaltered by the adjunct of either sildenafil or placebo. In the remaining subjects, atenolol significantly prolonged the time to 1 mm ST-segment depression and the exercise time. Sildenafil and placebo did not reverse the beneficial effect of atenolol upon exercise-induced myocardial ischemia.. PDE5 inhibition does not worsen exercise capacity and exercise-induced myocardial ischemia in patients with chronic stable angina whose symptoms and exercise test response are well controlled by beta-blocker therapy.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Angina Pectoris; Atenolol; Blood Pressure; Chronic Disease; Contraindications; Drug Interactions; Exercise Test; Heart Rate; Humans; Male; Middle Aged; Myocardial Ischemia; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

Nitric oxide (NO) induces the formation of intracellular cyclic guanosine monophosphate (cGMP) by guanylate cyclase. Sildenafil, which selectively inhibits phosphodiesterase type 5 (PDE5) found predominantly in the corpora cavernosa of the penis, effectively blocks the degradation of cGMP and enhances erectile function in men with erectile dysfunction. The NO-cGMP pathway also plays an important role in mediating blood pressure. It is, therefore, possible that the therapeutic doses of sildenafil used to treat erectile dysfunction may have clinically significant effects on human hemodynamics. Three studies were undertaken to assess the effects of intravenously, intra-arterially, and orally administered doses of sildenafil on blood pressure, heart rate, cardiac output, and forearm blood flow and venous compliance in healthy men. A fourth study evaluated the hemodynamic effects of intravenous sildenafil in men with stable ischemic heart disease. In healthy men, significant (p <0.01) decreases in supine systolic and diastolic blood pressures were observed with intravenous sildenafil (20, 40, and 80 mg) at the end of the infusion period when plasma levels of sildenafil were highest (mean decreases from baseline of 7.0/6.9 and 9.2/6.7 mm Hg, for the 40- and 80-mg doses, respectively). These changes were transient and not dose related. Modest reductions in systemic vascular resistance also were observed (maximum decrease 16%), although heart rate was not affected by sildenafil administration when compared with placebo. Single oral doses of sildenafil (100, 150, and 200 mg) produced no significant changes in cardiac index from 1-12 hours postdose between placebo- and sildenafil-treated subjects. The approved dosage strengths of sildenafil citrate are 25 mg, 50 mg, and 100 mg. The 80-mg intravenous dose and the 200-mg oral dose of sildenafil produced comparable plasma levels at twice the maximum therapeutic dose (recommended range, 25-100 mg). After brachial artery infusion of sildenafil (up to 300 microg/min), there was a modest vasodilation of resistance arteries and a reversal of norepinephrine-induced preconstriction of forearm veins. These hemodynamic effects were similar to but smaller in magnitude than those of nitrates. In a small pilot study of men with ischemic heart disease, decreases from baseline in pulmonary arterial pressure (-27% at rest and -19% during exercise) and cardiac output (-7% at rest and -11% during exercise) were observed after 40-mg in

Topics: Administration, Oral; Aged; Arm; Blood Flow Velocity; Blood Pressure; Exercise Test; Heart Rate; Hemodynamics; Humans; Injections, Intra-Arterial; Injections, Intravenous; Male; Middle Aged; Myocardial Ischemia; Phosphodiesterase Inhibitors; Pilot Projects; Piperazines; Purines; Reference Values; Sildenafil Citrate; Single-Blind Method; Stroke Volume; Sulfones; Time Factors; Vascular Resistance

Microvascular coronary dysfunction (MCD) is associated with symptoms and signs of ischemia, and also adverse outcomes in women without macrovascular obstructive coronary artery disease (M-CAD). Although MCD can be quantified using coronary flow reserve (CFR), treatment is poorly defined.. Phosphodiesterase type 5 (PDE-5) inhibition acutely improves MCD in these women.. The subjects were 23 symptomatic women (age 54 ± 11 y) participating in an ancillary study of the Women's Ischemia Syndrome Evaluation with baseline CFR ≤3.0 (Doppler flow wire and intracoronary adenosine) and without M-CAD. Coronary flow reserve was remeasured 45 minutes after PDE-5 inhibition (100 mg oral sildenafil). The primary measure of interest was change in CFR adjusted for baseline variables.. The relationship between log(2)-transformed CFR post-PDE-5 inhibition (adjusted) and baseline was different from the line of identity (slope: 0.55 vs 1.0, P = 0.008; intercept: 0.73 vs 0.0, P = 0.01), indicating that PDE-5 inhibition improves CFR and the lower the baseline CFR, the greater the response. Among women with baseline CFR ≤2.5 (n = 11), CFR increased from 2.1 ± 0.2 to 2.7 ± 0.6 (P = 0.006). For women with baseline CFR >2.5 (n = 12), CFR did not change (3.1 ± 0.3 to 3.0 ± 0.6; P = 0.70).. For women with symptoms and signs of ischemia and no M-CAD, PDE-5 inhibition is associated with acute improvement in CFR, and the effect concentrates among those with CFR ≤2.5. If these acute effects are sustained, then PDE-5 inhibition would provide a rational strategy for management of MCD in symptomatic women without M-CAD. The longer-term effects warrant study in a randomized trial using a sustained-acting PDE-5 inhibitor.

Topics: Adenosine; Adult; Aged; Coronary Artery Disease; Coronary Circulation; Coronary Vessels; Echocardiography, Doppler; Female; Humans; Linear Models; Microcirculation; Microvessels; Middle Aged; Myocardial Ischemia; Phosphodiesterase 5 Inhibitors; Piperazines; Predictive Value of Tests; Prospective Studies; Purines; Sildenafil Citrate; Sulfones; Treatment Outcome; United States; Vasodilator Agents; Women's Health

Sildenafil may be beneficial during myocardial ischaemia/reperfusion, but this effect may be dose-dependent, accounting for previous conflicting results. We have explored the effects of two acute and one chronic administration regimen on left ventricular function.. The study was conducted on 36 Wistar rats (290 +/- 7 g). Sildenafil was administered 30 min before ischaemia at a low (0.7 mg/kg, n= 8) or high (1.4 mg/kg, n= 8)dosage. The chronic treatment arm (n= 8) consisted of two daily injections of sildenafil (0.7 mg/kg) for three weeks. The control group was formed by 12 rats. Ischaemic contracture, post-ischaemic recovery and hypercontracture were measured in isolated, Langendorff-perfused preparations.. Ischaemic contracture tended to be lower after high-dose sildenafil, while remaining unchanged after low-dose or chronic sildenafil administration. Compared with controls (62.9 +/- 2.0% of baseline developed pressure), post-ischaemic recovery was higher (P= 0.0069) after low dose (75.1 +/- 2.4%), unchanged (P= 0.13) after high dose (69.1 +/- 2.1%), but lower (P < 0.001) after chronic (42.9 +/- 4.5%) sildenafil administration. Compared with controls (71.8 +/- 3.9 mmHg), hypercontracture was higher (P= 0.0052) after chronic sildenafil administration (89.5 +/- 4.1 mmHg), but similar after acute low dose (65.7 +/- 3.3 mmHg, P= 0.33) or high dose (67.1 +/- 4.7 mmHg, P= 0.43).. The effects of sildenafil after ischaemia/reperfusion were strongly dose-dependent. Beneficial actions on left ventricular function were evident after acute pretreatment with a low dosage, but were lost after doubling the dose. Chronic sildenafil administration deteriorated left ventricular function during ischaemia and reperfusion.

Topics: Animals; Cardiotonic Agents; Dose-Response Relationship, Drug; Heart; In Vitro Techniques; Ischemic Contracture; Male; Myocardial Ischemia; Myocardial Reperfusion Injury; Phosphodiesterase Inhibitors; Piperazines; Purines; Random Allocation; Rats; Rats, Wistar; Sildenafil Citrate; Sulfones; Vasodilator Agents; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Pressure

Recently, targeting cyclic-GMP specific phosphodiesterase-5 (PDE5) has attracted much interest in several cardiopulmonary diseases, in particular myocardial ischemia (MI). Although multiple mechanisms were postulated for these beneficial effects at cellular level, early transcriptional changes were unknown. The aim of present study was to examine gene expression profiles in response to MI after 24 h of ischemia in murine model and compare transcriptional modulation by sildenafil, a popular phosphodiesterase 5 (PDE5) inhibitor. Mice were divided into four groups: Control sham (C), Sildenafil sham (S), Control MI (CMI) and Sildenafil MI (SMI). Sildenafil was given at a dose of 0.7 mg/kg intraperitoneally 30 min before LAD occlusion. cDNA microarray analysis of peri-infarct tissue was done using a custom cloneset and employing a looped dye swap design. Replicate signals were median averaged and normalized using LOWESS algorithm. R/MAANOVA analysis was used and false discovery rate corrected permutation p-values <0.005 were employed as significance thresholds. 156 genes were identified as significantly regulated demonstrating fold difference >1.5 in at least one of the four groups. 52 genes were significantly upregulated in SMI compared to CMI. For a randomly chosen subset of genes (9), microarray data were confirmed through real time RT-PCR. The differentially expressed genes could be classified into following groups based on their function: phosphorylation/dephosphorylation, apoptosis, differentiation, ATP binding. Our results suggest that sildenafil treatment might regulate early genetic reprogramming strategy for preservation of the ischemic myocardium.

Topics: Animals; Gene Expression Profiling; Gene Expression Regulation; Male; Mice; Mice, Inbred C57BL; Myocardial Ischemia; Myocardium; Oligonucleotide Array Sequence Analysis; Piperazines; Purines; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; Sildenafil Citrate; Sulfones; Transcription, Genetic

Chest pain is a common complaint in patients with pulmonary arterial hypertension (PAH). Left main coronary artery (LMCA) compression by an enlarged pulmonary artery trunk (PAT) has been associated with angina, but appropriate diagnostic and treatment approaches remain poorly defined. We present two cases of angina caused by LMCA compression from an enlarged pulmonary artery, one of which also presented with new, severe left ventricular systolic dysfunction attributed to myocardial ischemia. Diagnosis of LMCA stenosis was made via coronary angiography followed by computed tomography-gated coronary angiography (CT-CA), which confirmed pulmonary artery enlargement as the source of extrinsic compression. Restoring LMCA patency with percutaneous intervention and/or aggressive treatment of pulmonary hypertension led to significant improvement in angina, cardiac function and quality of life. Given the negative impact on cardiac function, prompt diagnosis and treatment of extrinsic LMCA compression should be considered a priority.

Topics: Adult; Angina Pectoris; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Stenosis; Echocardiography; Epoprostenol; Humans; Hypertension, Pulmonary; Male; Middle Aged; Myocardial Ischemia; Piperazines; Pulmonary Artery; Purines; Sildenafil Citrate; Stents; Sulfones; Tomography, X-Ray Computed; Ultrasonography, Interventional; Vasodilator Agents

In this column, the authors highlight a medication incident that occurred with Revatio (sildenafil), along with the learnings and recommendations from a previously published ISMP Canada Safety Bulletin. It is well-known to health care practitioners that use of nitroglycerin therapy is contraindicated in patients taking sildenafil (commonly known as Viagra). Many health care practitioners may be unaware that sildenafil is also marketed under the brand name Revatio for treatment of primary pulmonary hypertension or pulmonary hypertension secondary to connective tissue disease. The following incident signals the need to heighten the awareness that Revatio is a brand name for sildenafil.

Topics: Canada; Contraindications; Drug Interactions; Female; Humans; Hypertension, Pulmonary; Medication Errors; Medication Systems; Middle Aged; Myocardial Ischemia; Nitroglycerin; Piperazines; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents

Infants undergoing surgery for congenital heart disease are at risk for myocardial ischemia during cardiopulmonary bypass, circulatory arrest, or low-flow states. The purpose of this study was to demonstrate the effects of sildenafil, a selective phosphodiesterase-5 (PDE-5) inhibitor on myocardial functional improvement and infarct size reduction during ischemia/reperfusion injury in infant rabbits. Infant rabbits (aged 8 wk) were treated with sildenafil citrate (0.7 mg/kg i.v.) or normal saline 30 min before sustained ischemia for 30 min and reperfusion for 3 h. Transesophageal echocardiography (TEE) was used to assess left ventricular cardiac output (LVCO) and aortic velocity time integral (VTI). After ischemia/reperfusion, risk area was demarcated by Evan's blue dye and infarct size determined by computer morphometry of triphenyltetrazolium chloride-stained sections. The sildenafil-treated group had preservation and elevation in LVCO (143% of baseline, p < 0.05) and an elevated aortic VTI (145% of baseline, p < 0.05) after 30 min of ischemia compared with the control group LVCO (72% of baseline, p < 0.05) and aortic VTI (73% of baseline, p < 0.05). This is a statistically significant increase in LVCO and aortic VTI in the sildenafil group compared with controls (n = 6/group, p < 0.05). The sildenafil-treated group had significant reduction in infarct size (15.5 +/- 1.2 versus 33 +/- 2.3 in the saline group, % risk area, mean +/- SEM, n = 10-15/group, p < 0.05). For the first time, we have shown that sildenafil citrate promotes myocardial protection in infant rabbits as evidenced by postischemic preservation and elevation in LVCO and aortic VTI and reduction in infarct size.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Animals; Aorta; Cardiac Output; Cyclic Nucleotide Phosphodiesterases, Type 5; Echocardiography; Evans Blue; Heart; Hemodynamics; Male; Myocardial Infarction; Myocardial Ischemia; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Purines; Rabbits; Reperfusion Injury; Sildenafil Citrate; Sulfones; Time Factors; Vasodilator Agents; Ventricular Function, Left

Since Sildenafil (Viagra) has become available, there have been reports of death and cardiac risks associated with its use. As large doses of Sildenafil medication is often prescribed particularly in diabetic patients with erectile dysfunction (ED), our study was designed to evaluate the coronary flow reserve (CFR) and possible resulting cardiac risk specifically in diabetic men.. Because these men often suffer from clinically significant ischaemic heart problems without their knowledge and without symptoms, all of our patients were examined by treadmill ECG and CFR.. In 44 men (35 - 74 years) with type I and II diabetes also suffering from ED objectified by FCDS measurement of the penile vessels, a surprisingly high rate of objective cardiac problems were found, which were then verified by coronary angiography. These patients are at risk for ischaemic problems during Sildenafil-assisted intercourse and were excluded from further study. Interestingly, only 3 of theses 11 men would have been detected by conventional examinations. Patients free of coronary stenosis who received 50 mg Sildenafil (20 patients) showed no cardiac problems during treadmill exercise and CFR measurement.. Coronary flow reserve in diabetic men lies at the lower end of the normal range, but is not further decreased by Sildenafil. However, diabetics with ED frequently showed coronary artery stenosis that was not clinically symptomatic. Furthermore, conventional cardiological examinations often fail to detect these patients, although they are at ischaemic risk during medically assisted intercourse. Furthermore, although 5 of 20 men who received Sildenafil had an increase in penile blood flow without sexual stimulation, only 7 of 20 were responders to Sildenafil after take home medication. Thus, Sildenafil medication is not a suitable test medication for organic erectile dysfunction.

Topics: Adult; Aged; Blood Flow Velocity; Contraindications; Coronary Circulation; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Echocardiography, Doppler, Color; Exercise Test; Humans; Impotence, Vasculogenic; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Penis; Piperazines; Purines; Regional Blood Flow; Risk Assessment; Sildenafil Citrate; Sulfones; Vasodilator Agents

Topics: Adult; Age Distribution; Aged; Cross-Sectional Studies; Erectile Dysfunction; Humans; Incidence; Male; Middle Aged; Myocardial Ischemia; Phosphodiesterase Inhibitors; Piperazines; Prevalence; Purines; Sildenafil Citrate; Sulfones; United Kingdom; Vasodilator Agents

Topics: Adult; Aged; Antidepressive Agents; Comorbidity; Depressive Disorder; Erectile Dysfunction; Hormone Replacement Therapy; Humans; Male; Middle Aged; Myocardial Ischemia; Piperazines; Prevalence; Purines; Sildenafil Citrate; Sulfones; Testosterone

Topics: Diabetes Complications; Erectile Dysfunction; Humans; Male; Myocardial Ischemia; Piperazines; Purines; Quality of Life; Sildenafil Citrate; Sulfones; Vasodilator Agents

The effects of sildenafil (Viagra), a specific inhibitor of phosphodiesterase 5, on ischemic myocardium was examined using an isolated rat heart model. Rats were pretreated with sildenafil at doses ranging from 0.001 mg to 0.5 mg/kg body weight. After 60 min, isolated hearts were subjected to ischemia for 30 min followed by 2 h of reperfusion. The results demonstrated that at 0.05 mg/kg (and to some extent at 0.01 mg/kg), sildenafil provided significant cardioprotection as evidenced by improved ventricular recovery, a reduced incidence of ventricular fibrillation and decreased myocardial infarction. At higher doses, it caused a significant increase in the incidence of ventricular fibrillation while at very low doses it had no effect on cardiac function. As expected, sildenafil increased cyclic 3',5'-monophosphate (cGMP) content in the heart. The results demonstrate for the first time that within a narrow dose range, sildenafil can protect the heart from ischemia/reperfusion injury, probably through a cGMP-signaling pathway.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Animals; Cardiotonic Agents; Cyclic GMP; Disease Models, Animal; Dose-Response Relationship, Drug; Electrocardiography; In Vitro Techniques; Male; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Piperazines; Purines; Rats; Rats, Sprague-Dawley; Sildenafil Citrate; Sulfones; Ventricular Fibrillation; Ventricular Function

To prospectively define the potential predictors of asymptomatic ischemic heart disease in patients with vasculogenic erectile dysfunction using a simple and practical method. Most patients with vasculogenic erectile dysfunction are known to have at least one significant cardiovascular risk factor.. After baseline evaluations, patients with erectile dysfunction of presumed vascular origin, who were older than 45 years and with no history of ischemic heart disease, were enrolled in the study. According to the results of repeated pharmacologic erection tests, we divided patients into responders and nonresponders. The cardiologic evaluations consisted of a comprehensive history taking, the assessment of cardiovascular risk factors, a physical examination, and an exercise treadmill test.. A total of 97 patients completed the study. Fifteen (32.6%) of 46 responders and 25 (49.0%) of 51 nonresponders, respectively, had two or more cardiovascular risk factors (P = 0.101). Ischemic ST-segment changes on the exercise treadmill test were only observed in 8 nonresponders (15.7%) (P = 0.006). All these patients were older than 55 years, and seven had two or more cardiovascular risk factors, including hypertension.. On the basis of these preliminary data, we suggest that cardiovascular evaluations may prove beneficial before prescribing sildenafil to patients with vasculogenic erectile dysfunction who are nonresponders to the pharmacologic erection test, are older than 55 years, and have two or more risk factors, including hypertension.

Topics: Age Factors; Comorbidity; Contraindications; Electrocardiography; Exercise Test; Humans; Hypertension; Impotence, Vasculogenic; Male; Middle Aged; Myocardial Ischemia; Physical Examination; Piperazines; Probability; Purines; Risk Factors; Sexual Behavior; Sildenafil Citrate; Sulfones

Erectile dysfunction is a common condition in men with cardiovascular disease, probably as a result of shared factors that impair hemodynamic mechanisms in the penile and ischemic vasculature. Sildenafil citrate, an orally active, selective inhibitor of phosphodiesterase type 5 (PDE5), has demonstrated excellent efficacy and safety profiles in men with erectile dysfunction of various etiologies. Sildenafil administration is contraindicated in patients who are taking nitrates or nitric oxide donors. This retrospective subanalysis of data from double-blind, placebo-controlled studies assessed the efficacy (9 studies) and safety (11 studies) of sildenafil in patients with erectile dysfunction and ischemic heart disease who were not taking nitrates. Of 3,672 patients randomized to receive sildenafil (5-200 mg) or placebo for 4-24 weeks in 11 double-blind, placebo-controlled studies, 357 (10%) reported a history (past or present) of ischemic heart disease and were not taking nitrates. Efficacy was assessed using end-of-treatment responses to Question 3 (ability to achieve an erection) and Question 4 (ability to maintain an erection) of the International Index of Erectile Function (IIEF), scores for the 5 domains of male sexual function assessed by the IIEF (erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction), and responses to a global efficacy question ("Did the treatment improve your erections?"). The responses to the 2 IIEF questions were graded on a scale of 1 (almost never or never) to 5 (almost always or always), with a score of 0 indicating no attempt at sexual intercourse. At the end of treatment, the mean scores for Question 3 and Question 4 of the IIEF for patients with erectile dysfunction and ischemic heart disease were significantly higher for the sildenafil group than for the placebo group (p <0.0001). Mean end-of-treatment scores for the IIEF domains also demonstrated significant increases for sildenafil-treated patients compared with those receiving placebo (p <0.05). At the end of treatment, improved erections were reported by 70% of patients who received sildenafil and by 20% of those in the placebo group p <0.0001). For the sildenafil group, the incidences of the most common adverse events (headache 25%, flushing 14%, and dyspepsia 12%) for patients with ischemic heart disease were similar to those in patients without this concomitant illness (21%, 15%, and 10%, respectively). Moreover, the

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adult; Aged; Aged, 80 and over; Double-Blind Method; Erectile Dysfunction; Humans; Male; Middle Aged; Myocardial Ischemia; Phosphodiesterase Inhibitors; Piperazines; Purines; Randomized Controlled Trials as Topic; Retrospective Studies; Sildenafil Citrate; Sulfones

There has been considerable media attention surrounding the commercialisation of Sildenafil. The advice of cardiologists is often solicited before its prescription because of its potential side effects; the cardiovascular stress due to sexual activity is generally modest, both in normal subjects and coronary patients with, however, important individual variations, the "legitimate" nature of the intercourse seeming to be one of the principal factors. Recent coronary events, poorly controlled hypertension and uncompensated cardiac failure are the main contra-indications; the prescription should be based on the results of maximal exercise stress testing in patients at risk.

Topics: Adolescent; Adult; Arrhythmias, Cardiac; Coronary Disease; Erectile Dysfunction; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Phosphodiesterase Inhibitors; Piperazines; Purines; Risk Factors; Sexuality; Sildenafil Citrate; Stress, Physiological; Sulfones

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Aged; Coitus; Contraindications; Drug Interactions; Erectile Dysfunction; Humans; Male; Myocardial Ischemia; Nitroglycerin; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones