Abstract
Despite the proven clinical efficacy of phosphodiesterase inhibitors in the treatment of erectile dysfunction (ED), some patients do not respond to the medication. By means of nailfold capillary microscopy in patients with concomitant coronary artery disease (CAD) and ED, it was evaluated whether the extent of microvascular dysregulation predicts the responsiveness to tadalafil (TAD) in terms of erectile function. The ED of each patient was assessed by the International Index of Erectile Function (IIEF). Patients presenting both, documented CAD and ED, showed a significantly reduced capillary red blood cell velocity (vRBC) at rest and after 3 min of ischemia compared with age-matched controls. At 2 h after intake of 20 mg of TAD, a significant increase of vRBC at rest as well as during postischemic hyperemia was found. Patients who reported no improvement of their ED after the use of TAD demonstrated no changes in the duration of postischemic (DpH) hyperemia, or even a reduction of the DpH. The majority of the patients, who reported at least one successful sexual intercourse due to TAD, had a prolongation of DpH. We conclude that assessment of microvascular regulation by nailfold capillary microscopy can predict the probability of a treatment failure with phosphodiesterase inhibitors in patients with ED. Moreover, as endothelial dysfunction is the common underlying pathophysiological process of ED and cardiovascular diseases, the test may help to identify patients at risk for the development of atherosclerosis and following cardiovascular events.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 8 print issues and online access
$259.00 per year
only $32.38 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Billups KL . Erectile dysfunction as an early sign of cardiovascular disease. Int J Impot Res 2005; 17(Suppl 1): S19–S24.
Solomon H, Man JW, Jackson G . Erectile dysfunction and the cardiovascular patient: endothelial dysfunction is the common denominator. Heart 2003; 89: 251–253.
Yang Z, Ming XF . Recent advances in understanding endothelial dysfunction in atherosclerosis. Clin Med Res 2006; 4: 53–65.
Landmesser U, Hornig B, Drexler H . Endothelial function: a critical determinant in atherosclerosis? Circulation 2004; 109: II27–II33.
Li H, Forstermann U . Nitric oxide in the pathogenesis of vascular disease. J Pathol 2000; 190: 244–254.
Dean RC, Lue TF . Physiology of penile erection and pathophysiology of erectile dysfunction. Urol Clin North Am 2005; 32: 379–935.
Esposito K, Giugliano D . Obesity, the metabolic syndrome, and sexual dysfunction. Int J Impot Res 2005; 17: 391–398.
Kuthe A, Wiedenroth A, Magert HJ, Uckert S, Forssmann WG, Stief CG et al. Expression of different phosphodiesterase genes in human cavernous smooth muscle. J Urol 2001; 165: 280–283.
Bossaller C, Habib GB, Yamamoto H, Williams C, Wells S, Henry PD . Impaired muscarinic endothelium-dependent relaxation and cyclic guanosine 5′-monophosphate formation in atherosclerotic human coronary artery and rabbit aorta. J Clin Invest 1987; 79: 170–174.
Kaiser DR, Billups K, Mason C, Wetterling R, Lundberg JL, Bank AJ . Impaired brachial artery endothelium-dependent and -independent vasodilation in men with erectile dysfunction and no other clinical cardiovascular disease. J Am Coll Cardiol 2004; 43: 179–184.
Kaya C, Uslu Z, Karaman I . Is endothelial function impaired in erectile dysfunction patients? Int J Impot Res 2006; 18: 55–60.
Elesber AA, Solomon H, Lennon RJ, Mathew V, Prasad A, Pumper G et al. Coronary endothelial dysfunction is associated with erectile dysfunction and elevated asymmetric dimethylarginine in patients with early atherosclerosis. Eur Heart J 2006; 27: 824–831.
Jung F, Kolepke W, Spitzer S, Kiesewetter H, Ruprecht KW, Bach R et al. Primary and secondary microcirculatory disorders in essential hypertension. Clin Investig 1993; 71: 132–138.
Koscielny J, Latza R, Wolf S, Kiesewetter H, Jung F . Early rheological and microcirculatory changes in children with type I diabetes mellitus. Clin Hemorheol Microcirc 1998; 19: 139–150.
Ishibashi Y, Takahashi N, Shimada T, Sugamori T, Sakane T, Umeno T et al. Short duration of reactive hyperemia in the forearm of subjects with multiple cardiovascular risk factors. Circ J 2006; 70: 115–123.
Shamim-Uzzaman QA, Pfenninger D, Kehrer C, Chakrabarti A, Kacirotti N, Rubenfire M et al. Altered cutaneous microvascular responses to reactive hyperaemia in coronary artery disease: a comparative study with conduit vessel responses. Clin Sci (Lond) 2002; 103: 267–273.
Bonetti PO, Pumper GM, Higano ST, Holmes Jr DR, Kuvin JT, Lerman A . Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia. J Am Coll Cardiol 2004; 44: 2137–2141.
Simonsen U, Garcia-Sacristan A, Prieto D . Penile arteries and erection. J Vasc Res 2002; 39: 283–303.
Park JW, Mrowietz C, Chung N, Jung F . Sildenafil improves cutaneous microcirculation in patients with coronary artery disease: a monocentric, prospective, double-blind, placebo-controlled, randomized cross-over study. Clin Hemorheol Microcirc 2004; 31: 173–183.
Sommer F, Schulze W . Treating erectile dysfunction by endothelial rehabilitation with phosphodiesterase 5 inhibitors. World J Urol 2005; 23: 385–392.
Montorsi F, Briganti A, Salonia A, Rigatti P, Burnett AL . Can phosphodiesterase type 5 inhibitors cure erectile dysfunction? Eur Urol 2006; 49: 979–986.
de Tejada IS . Therapeutic strategies for optimizing PDE-5 inhibitor therapy in patients with erectile dysfunction considered difficult or challenging to treat. Int J Impot Res 2004; 16(Suppl 1): S40–S42.
Gruenwald I, Shenfeld O, Chen J, Raviv G, Richter S, Cohen A et al. Positive effect of counseling and dose adjustment in patients with erectile dysfunction who failed treatment with sildenafil. Eur Urol 2006; 50: 134–140.
Hatzimouratidis K, Moysidis K, Bekos A, Tsimtsiou Z, Ioannidis E, Hatzichristou D . Treatment strategy ‘non-responders’ to tadalafil and vardenafil: a real-life study. Eur Urol 2006; 50: 126–132.
Scanlon PJ, Faxon DP, Audet AM, Carabello B, Dehmer GJ, Eagle KA et al. ACC/AHA guidelines for coronary angiography. A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines (Committee on Coronary Angiography). Developed in collaboration with the Society for Cardiac Angiography and Interventions. J Am Coll Cardiol 1999; 33: 1756–1824.
Rosen RC, Riley A, Wagner G, Osterloh IH, Kirkpatrick J, Mishra A . The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology 1997; 49: 822–830.
Klyscz T, Jünger M, Jung F, Zeintl H . Cap image—a new kind of computer-assisted video image analysis system for dynamic capillary microscopy. Biomed Technik 1997; 42: 168–175.
Salerud EG, Tenland T, Nilsson GE, Oberg PA . Rhythmical variations in human skin blood flow. Int J Microcirc Clin Exp 1983; 2: 91–102.
Ostergren J, Fagrell B . Skin capillary blood cell velocity in patients with arterial obliterative disease and polycythaemia: a disturbed reactive hyperaemia response. Clin Physiol 1985; 5: 35–43.
Jung F, Toonen H, Mrowietz C, Wolf S, Kiesewetter H, Wenzel E et al. Error analysis, biological modification factors and variance of peri-ungual video-capillary microscopy]. Biomed Tech (Berl) 1990; 35: 195–204.
Berg B, Solberg HE, Nilsson JE, Tryding N . Practical experience in the selection and preparation of reference individuals: empirical testing of the provisional Scandinavian recommendations. In: Gräsbeck R, Alström T (eds). Reference Values in Laboratory Medicine. John Wiley & Sons: New York, 1981.
Lue TF . Erectile dysfunction. N Engl J Med 2000; 342: 1802–1813.
Liao JK, Bettmann MA, Sandor T, Tucker JI, Coleman SM, Creager MA . Differential impairment of vasodilator responsiveness of peripheral resistance and conduit vessels in humans with atherosclerosis. Circ Res 1991; 68: 1027–1034.
Agewall S, Henareh L, Kublickiene K . Endothelial function in conduit and resistance arteries in men with coronary disease. Atherosclerosis 2006; 184: 130–136.
Montorsi F, Briganti A, Salonia A, Rigatti P, Margonato A, Macchi A et al. Erectile dysfunction prevalence, time of onset and association with risk factors in 300 consecutive patients with acute chest pain and angiographically documented coronary artery disease. Eur Urol 2003; 44: 360–364.
Vlachopoulos C, Rokkas K, Ioakeimidis N, Aggeli C, Michaelides A, Roussakis G et al. Prevalence of asymptomatic coronary artery disease in men with vasculogenic erectile dysfunction: a prospective angiographic study. Eur Urol 2005; 48: 996–1002.
Gazzaruso C, Pujia A, Solerte SB, Amici ED, Emanuele E, Falcone C et al. Erectile dysfunction and angiographic extent of coronary artery disease in type II diabetic patients. Int J Impot Res 2006; 18: 311–315.
Montorsi P, Ravagnani PM, Galli S, Rotatori F, Veglia F, Briganti A et al. Association between erectile dysfunction and coronary artery disease. Role of coronary clinical presentation and extent of coronary vessels involvement: the COBRA trial. Eur Heart J 2006; 27: 2632–2639.
Halcox JP, Nour KR, Zalos G, Mincemoyer RA, Waclawiw M, Rivera CE et al. The effect of sildenafil on human vascular function, platelet activation, and myocardial ischemia. J Am Coll Cardiol 2002; 40: 1232–1240.
Katz SD, Balidemaj K, Homma S, Wu H, Wang J, Maybaum S . Acute type 5 phosphodiesterase inhibition with sildenafil enhances flow-mediated vasodilation in patients with chronic heart failure. J Am Coll Cardiol 2000; 36: 845–851.
Robinson SD, Ludlam CA, Boon NA, Newby DE . Phosphodiesterase type 5 inhibition does not reverse endothelial dysfunction in patients with coronary heart disease. Heart 2006; 92: 170–176.
Rosano GM, Aversa A, Vitale C, Fabbri A, Fini M, Spera G . Chronic treatment with tadalafil improves endothelial function in men with increased cardiovascular risk. Eur Urol 2005; 47: 214–220.
Young JM, Feldman RA, Auerbach SM, Kaufman JM, Garcia CS, Shen W et al. Tadalafil improved erectile function at twenty-four and thirty-six hours after dosing in men with erectile dysfunction: US trial. J Androl 2005; 26: 310–318.
McMahon CG, Stuckey BG, Lording DW, Wittert GA, Murphy A, Shin J et al. A 6-month study of the efficacy and safety of tadalafil in the treatment of erectile dysfunction: a randomised, double-blind, parallel-group, placebo-controlled study in Australian men. Int J Clin Pract 2005; 59: 143–149.
De Rose AF, Gallo F, Carmignani G . Evaluation of sexual activity in patients treated with tadalafil: a randomized prospective placebo-controlled trial. Int J Impot Res 2005; 17: 76–79.
Garlanda C, Dejana E . Heterogeneity of endothelial cells. Arterioscler Thromb Vasc Biol 1997; 17: 1193–1202.
Gerritsen ME . Functional heterogeneity of vascular endothelial cells. Biochem Pharmacol 1987; 36: 2701–2711.
Anderson TJ, Uehata A, Gerhard MD, Meredith IT, Knab S, Delagrange D et al. Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol 1995; 26: 1235–1241.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Park, JW., Leithäuser, B., Mrowietz, C. et al. Cutaneous microcirculatory function predicts the responsiveness to tadalafil in patients with erectile dysfunction and coronary artery disease. Int J Impot Res 20, 150–156 (2008). https://doi.org/10.1038/sj.ijir.3901538
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.ijir.3901538
Keywords
This article is cited by
-
Effect of tadalafil on blood flow, pain, and function in chronic cold Complex Regional Pain Syndrome: a randomized controlled trial
BMC Musculoskeletal Disorders (2008)