Vai ai contenuti. | Spostati sulla navigazione | Spostati sulla ricerca | Vai al menu | Contatti | Accessibilità

| Crea un account

Cesari, Maurizio (2008) Long-term modifications in left ventricular structure and function after adrenalectomy or medical treatment in patients with primary aldosteronism. [Tesi di dottorato]

Full text disponibile come:

[img]
Anteprima
Documento PDF
380Kb

Abstract (inglese)

Background and aim: hyperaldosteronism has been related to collagen deposition, myocardial fibrosis, and ventricular remodeling in experimental studies. More recent evidence suggest that these detrimental effects can develop independently of blood pressure and a significant decrease in the mortality rate of patients with heart failure who were treated with aldosterone antagonists has been reported. Primary aldosteronism (PA) is a form of secondary arterial hypertension that offers an important clinical opportunity for assessing the effects of hyperaldosteronism on the left ventricular (LV) anatomy and function because, in this condition, its effects are isolated from those of the renin-angiotensin axis.
In the literature, only few longitudinal studies have evaluated cardiac changes after treatment of hyperaldosteronism with either surgical or medical treatment. Hence, in the present study we have explored the relationship between aldosterone and the heart by assessing cardiac anatomic and functional evolution of a large number of patients with PA surgically or medically-treated.
Methods and Results: fifty-five patients with PA were enrolled in a prospective study and were followed for a mean of 6.4 years (range: 4.5 to 8 years) after adrenalectomy (n=41) or medical treatment (n=14). The diagnosis of APA (aldosterone producing adenoma) was based on adrenal vein sampling and pathology results and on follow-up data. At baseline and at follow-up we performed Doppler echocardiography for estimation of LV wall thickness and dimensions and transmitral LV filling flow velocity indexes.
At baseline, PA patients who subsequently underwent adrenalectomy were younger and had lower body mass index and lower diastolic blood pressure than PA patients medically-treated. The former showed an excess LV hypertrophy and concentric remodeling, but with a less degree of diastolic dysfunction compared with the latter.
At follow-up, despite a greater reduction of antihypertensive drugs in surgically treated patients (number of drugs: 1.7±1.4 vs 2.6±0.8 in surgically and medically-treated, respectively, p= 0.024) in both groups there was a significant reduction of blood pressure levels. A significant (p< 0.001) reduction in LV end-diastolic diameter, a reduction in LV mass index but with an increase in the relative wall thickness was observed in both groups. However, the last two parameters were significant only in the surgically treated PA. As regards the diastolic function, no significant modification was observed in the surgically treated PA. At variance, a significant (p= 0.002) reduction in the atrial contribution to LV filling was observed in medically-treated PA, possibly because they showed a higher degree of diastolic dysfunction at baseline.
In both groups LV mass decrease was independent from pre-treatment blood pressure, body mass index, age, known duration of hypertension, follow-up interval and medical treatment.
Conclusions: in PA patients, the excess aldosterone is associated with both increased LV wall thickness and mass. Treatment of hyperaldosteronism with either surgical or medical treatment induce a reduction in blood pressure levels, LV end-diastolic diameter, a reduction in LV mass index and an increase in the relative wall thickness, particularly in the surgically treated PA. With a similar fall of blood pressure and despite a greater reduction of antihypertensive drugs, these changes were more prominent in the adrenalectomized patients. Treatment can improve the diastolic function, but this was observed only in the medically-treated PA patients, likely because they had a higher degree of diastolic dysfunction at baseline.


Statistiche Download - Aggiungi a RefWorks
Tipo di EPrint:Tesi di dottorato
Relatore:Rossi, Gianpaolo
Dottorato (corsi e scuole):Ciclo 19 > Corsi per il 19simo ciclo > IPERTENSIONE ARTERIOSA E BIOLOGIA VASCOLARE
Data di deposito della tesi:2008
Anno di Pubblicazione:2008
Parole chiave (italiano / inglese):left ventricular hypertrophy, primary aldosteronism, Conn's adenoma, echocardiography, diastolic dysfunction
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/11 Malattie dell'apparato cardiovascolare
Struttura di riferimento:Dipartimenti > Dipartimento di Medicina Clinica e Sperimentale
Codice ID:302
Depositato il:27 Ott 2008
Simple Metadata
Full Metadata
EndNote Format

Bibliografia

I riferimenti della bibliografia possono essere cercati con Cerca la citazione di AIRE, copiando il titolo dell'articolo (o del libro) e la rivista (se presente) nei campi appositi di "Cerca la Citazione di AIRE".
Le url contenute in alcuni riferimenti sono raggiungibili cliccando sul link alla fine della citazione (Vai!) e tramite Google (Ricerca con Google). Il risultato dipende dalla formattazione della citazione.

1. Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP: Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N.Engl.J.Med. 322:1561-1566, 1990 Cerca con Google

2. Koren MJ, Devereux RB, Casale PN, Savage DD, Laragh JH: Relation of left ventricular mass and geometry to morbidity and mortality in uncomplicated essential hypertension. Ann.Intern.Med. 114:345-352, 1991 Cerca con Google

3. Tarazi RC, Sen S, Saragoca M, Khairallah P: The multifactorial role of catecholamines in hypertensive cardiac hypertrophy. Eur.Heart J. 3 Suppl A:103-110, 1982 Cerca con Google

4. Muscholl MW, Schunkert H, Muders F, Elsner D, Kuch B, Hense HW, Riegger GA: Neurohormonal activity and left ventricular geometry in patients with essential arterial hypertension. Am.Heart J. 135:58-66, 1998 Cerca con Google

5. Schunkert H, Hense HW, Muscholl M, Luchner A, Kurzinger S, Danser AH, Riegger GA: Associations between circulating components of the renin-angiotensin-aldosterone system and left ventricular mass. Heart 77:24-31, 1997 Cerca con Google

6. Schunkert H, Hense HW, Holmer SR, Stender M, Perz S, Keil U, Lorell BH, Riegger GA: Association between a deletion polymorphism of the angiotensin-converting-enzyme gene and left ventricular hypertrophy. N.Engl.J.Med. 330:1634-1638, 1994 Cerca con Google

7. Morgan HE, Baker KM: Cardiac hypertrophy. Mechanical, neural, and endocrine dependence. Circulation 83:13-25, 1991 Cerca con Google

8. Izumo S, Nadal-Ginard B, Mahdavi V: Protooncogene induction and reprogramming of cardiac gene expression produced by pressure overload. Proc.Natl.Acad.Sci.U.S.A 85:339-343, 1988 Cerca con Google

9. Weber KT: Extracellular matrix remodeling in heart failure: a role for de novo angiotensin II generation. Circulation 96:4065-4082, 1997 Cerca con Google

10. Rossi MA: Pathologic fibrosis and connective tissue matrix in left ventricular hypertrophy due to chronic arterial hypertension in humans. J.Hypertens. 16:1031-1041, 1998 Cerca con Google

11. Weber KT, Brilla CG: Pathological hypertrophy and cardiac interstitium. Fibrosis and renin-angiotensin-aldosterone system. Circulation 83:1849-1865, 1991 Cerca con Google

12. Weber KT, Brilla CG: Myocardial fibrosis and the renin-angiotensin-aldosterone system. J.Cardiovasc.Pharmacol. 20 Suppl 1:S48-S54, 1992 Cerca con Google

13. Eghbali M, Tomek R, Woods C, Bhambi B: Cardiac fibroblasts are predisposed to convert into myocyte phenotype: specific effect of transforming growth factor beta. Proc.Natl.Acad.Sci.U.S.A 88:795-799, 1991 Cerca con Google

14. Agabiti-Rosei E, Muiesan ML: Left ventricular diastolic function in essential hypertension. Contrib.Nephrol. 106:174-178, 1994 Cerca con Google

15. Brilla CG, Maisch B, Weber KT: Myocardial collagen matrix remodelling in arterial hypertension. Eur.Heart J. 13 Suppl D:24-32, 1992 Cerca con Google

16. Brilla CG, Maisch B, Weber KT: Renin-angiotensin system and myocardial collagen matrix remodeling in hypertensive heart disease: in vivo and in vitro studies on collagen matrix regulation. Clin.Investig. 71:S35-S41, 1993 Cerca con Google

17. Brilla CG, Reams GP, Maisch B, Weber KT: Renin-angiotensin system and myocardial fibrosis in hypertension: regulation of the myocardial collagen matrix. Eur.Heart J. 14 Suppl J:57-61, 1993 Cerca con Google

18. Klug D, Robert V, Swynghedauw B: Role of mechanical and hormonal factors in cardiac remodeling and the biologic limits of myocardial adaptation. Am.J.Cardiol. 71:46A-54A, 1993 Cerca con Google

19. Swynghedauw B: Molecular mechanisms of myocardial remodeling. Physiol Rev. 79:215-262, 1999 Cerca con Google

20. Brilla CG, Rupp H, Funck R, Maisch B: The renin-angiotensin-aldosterone system and myocardial collagen matrix remodelling in congestive heart failure. Eur.Heart J. 16 Suppl O:107-109, 1995 Cerca con Google

21. Mazzolai L, Pedrazzini T, Nicoud F, Gabbiani G, Brunner HR, Nussberger J: Increased cardiac angiotensin II levels induce right and left ventricular hypertrophy in normotensive mice. Hypertension 35:985-991, 2000 Cerca con Google

22. Zannad F, Dousset B, Alla F: Treatment of congestive heart failure: interfering the aldosterone-cardiac extracellular matrix relationship. Hypertension 38:1227-1232, 2001 Cerca con Google

23. Brown NJ: Aldosterone and end-organ damage. Curr.Opin.Nephrol.Hypertens. 14:235-241, 2005 Cerca con Google

24. Robert V, Van Thiem N, Cheav SL, Mouas C, Swynghedauw B, Delcayre C: Increased cardiac types I and III collagen mRNAs in aldosterone-salt hypertension. Hypertension 24:30-36, 1994 Cerca con Google

25. Young M, Head G, Funder J: Determinants of cardiac fibrosis in experimental hypermineralocorticoid states. Am.J.Physiol 269:E657-E662, 1995 Cerca con Google

26. Rossi G, Boscaro M, Ronconi V, Funder JW: Aldosterone as a cardiovascular risk factor. Trends Endocrinol.Metab 16:104-107, 2005 Cerca con Google

27. Brilla CG, Janicki JS, Weber KT: Impaired diastolic function and coronary reserve in genetic hypertension. Role of interstitial fibrosis and medial thickening of intramyocardial coronary arteries. Circ.Res. 69:107-115, 1991 Cerca con Google

28. Funder JW: Minireview: aldosterone and the cardiovascular system: genomic and nongenomic effects. Endocrinology 147:5564-5567, 2006 Cerca con Google

29. Funder JW, Duval D, Meyer P: Cardiac glucocorticoid receptors: the binding of tritiated dexamethasone in rat and dog heart. Endocrinology 93:1300-1308, 1973 Cerca con Google

30. Funder JW, Pearce PT, Smith R, Campbell J: Vascular type I aldosterone binding sites are physiological mineralocorticoid receptors. Endocrinology 125:2224-2226, 1989 Cerca con Google

31. Funder JW, Feldman D, Edelman IS: The roles of plasma binding and receptor specificity in the mineralocorticoid action of aldosterone. Endocrinology 92:994-1004, 1973 Cerca con Google

32. Ward MR, Kanellakis P, Ramsey D, Funder J, Bobik A: Eplerenone suppresses constrictive remodeling and collagen accumulation after angioplasty in porcine coronary arteries. Circulation 104:467-472, 2001 Cerca con Google

33. Young MJ, Moussa L, Dilley R, Funder JW: Early inflammatory responses in experimental cardiac hypertrophy and fibrosis: effects of 11 beta-hydroxysteroid dehydrogenase inactivation. Endocrinology 144:1121-1125, 2003 Cerca con Google

34. Young M, Fullerton M, Dilley R, Funder J: Mineralocorticoids, hypertension, and cardiac fibrosis. J.Clin.Invest 93:2578-2583, 1994 Cerca con Google

35. Funder JW: Is aldosterone bad for the heart? Trends Endocrinol.Metab 15:139-142, 2004 Cerca con Google

36. Qin W, Rudolph AE, Bond BR, Rocha R, Blomme EA, Goellner JJ, Funder JW, McMahon EG: Transgenic model of aldosterone-driven cardiac hypertrophy and heart failure. Circ.Res. 93:69-76, 2003 Cerca con Google

37. Swedberg K, Eneroth P, Kjekshus J, Wilhelmsen L: Hormones regulating cardiovascular function in patients with severe congestive heart failure and their relation to mortality. CONSENSUS Trial Study Group. Circulation 82:1730-1736, 1990 Cerca con Google

38. Milliez P, Girerd X, Plouin PF, Blacher J, Safar ME, Mourad JJ: Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J.Am.Coll.Cardiol. 45:1243-1248, 2005 Cerca con Google

39. Catena C, Colussi G, Nadalini E, Chiuch A, Baroselli S, Lapenna R, Sechi LA: Cardiovascular outcomes in patients with primary aldosteronism after treatment. Arch.Intern.Med. 168:80-85, 2008 Cerca con Google

40. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J: The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N.Engl.J.Med. 341:709-717, 1999 Cerca con Google

41. Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M: Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N.Engl.J.Med. 348:1309-1321, 2003 Cerca con Google

42. Pitt B, Reichek N, Willenbrock R, Zannad F, Phillips RA, Roniker B, Kleiman J, Krause S, Burns D, Williams GH: Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: the 4E-left ventricular hypertrophy study. Circulation 108:1831-1838, 2003 Cerca con Google

43. Rossi GP, Sacchetto A, Visentin P, Canali C, Graniero GR, Palatini P, Pessina AC: Changes in left ventricular anatomy and function in hypertension and primary aldosteronism. Hypertension 27:1039-1045, 1996 Cerca con Google

44. Rossi GP, Sacchetto A, Pavan E, Palatini P, Graniero GR, Canali C, Pessina AC: Remodeling of the left ventricle in primary aldosteronism due to Conn's adenoma. Circulation 95:1471-1478, 1997 Cerca con Google

45. Rossi GP, Di B, V, Ganzaroli C, Sacchetto A, Cesari M, Bertini A, Giorgi D, Scognamiglio R, Mariani M, Pessina AC: Excess aldosterone is associated with alterations of myocardial texture in primary aldosteronism. Hypertension 40:23-27, 2002 Cerca con Google

46. Salvetti M, Muiesan ML, Paini A, Monteduro C, Bonzi B, Galbassini G, Belotti E, Movilli E, Cancarini G, Agabiti-Rosei E: Myocardial ultrasound tissue characterization in patients with chronic renal failure. J.Am.Soc.Nephrol. 18:1953-1958, 2007 Cerca con Google

47. Kozakova M, Buralli S, Palombo C, Bernini G, Moretti A, Favilla S, Taddei S, Salvetti A: Myocardial ultrasonic backscatter in hypertension: relation to aldosterone and endothelin. Hypertension 41:230-236, 2003 Cerca con Google

48. Rossi GP, Bernini G, Caliumi C, Desideri G, Fabris B, Ferri C, Ganzaroli C, Giacchetti G, Letizia C, Maccario M, Mallamaci F, Mannelli M, Mattarello MJ, Moretti A, Palumbo G, Parenti G, Porteri E, Semplicini A, Rizzoni D, Rossi E, Boscaro M, Pessina AC, Mantero F: A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients. J.Am.Coll.Cardiol. 48:2293-2300, 2006 Cerca con Google

49. Rossi GP: Cardiac consequences of aldosterone excess in human hypertension. Am.J.Hypertens. 19:10-12, 2006 Cerca con Google

50. Matsumura K, Fujii K, Oniki H, Oka M, Iida M: Role of aldosterone in left ventricular hypertrophy in hypertension. Am.J.Hypertens. 19:13-18, 2006 Cerca con Google

51. Janota T, Hradec J, Kral J: Heart in adrenal diseases. Cor Vasa 34:115-122, 1992 Cerca con Google

52. Denolle T, Chatellier G, Julien J, Battaglia C, Luo P, Plouin PF: Left ventricular mass and geometry before and after etiologic treatment in renovascular hypertension, aldosterone-producing adenoma, and pheochromocytoma. Am.J.Hypertens. 6:907-913, 1993 Cerca con Google

53. Shigematsu Y, Hamada M, Okayama H, Hara Y, Hayashi Y, Kodama K, Kohara K, Hiwada K: Left ventricular hypertrophy precedes other target-organ damage in primary aldosteronism. Hypertension 29:723-727, 1997 Cerca con Google

54. Tanabe A, Naruse M, Naruse K, Hase M, Yoshimoto T, Tanaka M, Seki T, Demura R, Demura H: Left ventricular hypertrophy is more prominent in patients with primary aldosteronism than in patients with other types of secondary hypertension. Hypertens.Res. 20:85-90, 1997 Cerca con Google

55. Fallo F, Veglio F, Bertello C, Sonino N, Della MP, Ermani M, Rabbia F, Federspil G, Mulatero P: Prevalence and characteristics of the metabolic syndrome in primary aldosteronism. J.Clin.Endocrinol.Metab 91:454-459, 2006 Cerca con Google

56. Catena C, Colussi G, Lapenna R, Nadalini E, Chiuch A, Gianfagna P, Sechi LA: Long-term cardiac effects of adrenalectomy or mineralocorticoid antagonists in patients with primary aldosteronism. Hypertension 50:911-918, 2007 Cerca con Google

57. Suzuki T, Abe H, Nagata S, Saitoh F, Iwata S, Ashizawa A, Kuramochi M, Omae T: Left ventricular structural characteristics in unilateral renovascular hypertension and primary aldosteronism. Am.J.Cardiol. 62:1224-1227, 1988 Cerca con Google

58. Yoshihara F, Nishikimi T, Yoshitomi Y, Nakasone I, Abe H, Matsuoka H, Omae T: Left ventricular structural and functional characteristics in patients with renovascular hypertension, primary aldosteronism and essential hypertension. Am.J.Hypertens. 9:523-528, 1996 Cerca con Google

59. Yoshitomi Y, Nishikimi T, Abe H, Yoshiwara F, Suzuki T, Ashizawa A, Nagata S, Kuramochi M, Matsuoka H, Omae T: Comparison of changes in cardiac structure after treatment in secondary hypertension. Hypertension 27:319-323, 1996 Cerca con Google

60. Rizzoni D, Muiesan ML, Porteri E, Salvetti M, Castellano M, Bettoni G, Tiberio G, Giulini SM, Monteduro C, Garavelli G, Agabiti-Rosei E: Relations between cardiac and vascular structure in patients with primary and secondary hypertension. J.Am.Coll.Cardiol. 32:985-992, 1998 Cerca con Google

61. Goldkorn R, Yurenev A, Blumenfeld J, Fishman D, Devereux RB: Echocardiographic comparison of left ventricular structure and function in hypertensive patients with primary aldosteronism and essential hypertension. Am.J.Hypertens. 15:340-345, 2002 Cerca con Google

62. Weinberger MH, Fineberg NS: The diagnosis of primary aldosteronism and separation of two major subtypes. Arch.Intern.Med. 153:2125-2129, 1993 Cerca con Google

63. Iwaoka T, Umeda T, Naomi S, Inoue J, Sasaki M, Yamauchi J, Sato T: The usefulness of the captopril test as a simultaneous screening for primary aldosteronism and renovascular hypertension. Am.J.Hypertens. 6:899-906, 1993 Cerca con Google

64. Rossi GP, Belfiore A, Bernini G, Desideri G, Fabris B, Ferri C, Giacchetti G, Letizia C, Maccario M, Mallamaci F, Mannelli M, Palumbo G, Rizzoni D, Rossi E, Agabiti-Rosei E, Pessina AC, Mantero F: Comparison of the captopril and the saline infusion test for excluding aldosterone-producing adenoma. Hypertension 50:424-431, 2007 Cerca con Google

65. Rossi GP, Chiesura-Corona M, Tregnaghi A, Zanin L, Perale R, Soattin S, Pelizzo MR, Feltrin GP, Pessina AC: Imaging of aldosterone-secreting adenomas: a prospective comparison of computed tomography and magnetic resonance imaging in 27 patients with suspected primary aldosteronism. J.Hum.Hypertens. 7:357-363, 1993 Cerca con Google

66. Sahn DJ, DeMaria A, Kisslo J, Weyman A: Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation 58:1072-1083, 1978 Cerca con Google

67. Devereux RB: Detection of left ventricular hypertrophy by M-mode echocardiography. Anatomic validation, standardization, and comparison to other methods. Hypertension 9:II19-II26, 1987 Cerca con Google

68. Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, Grassi G, Heagerty AM, Kjeldsen SE, Laurent S, Narkiewicz K, Ruilope L, Rynkiewicz A, Schmieder RE, Boudier HA, Zanchetti A: 2007 ESH-ESC Practice Guidelines for the Management of Arterial Hypertension: ESH-ESC Task Force on the Management of Arterial Hypertension. J.Hypertens. 25:1751-1762, 2007 Cerca con Google

69. Verdecchia P, Schillaci G, Borgioni C, Ciucci A, Battistelli M, Bartoccini C, Santucci A, Santucci C, Reboldi G, Porcellati C: Adverse prognostic significance of concentric remodeling of the left ventricle in hypertensive patients with normal left ventricular mass. J.Am.Coll.Cardiol. 25:871-878, 1995 Cerca con Google

70. Verdecchia P, Schillaci G, Borgioni C, Ciucci A, Gattobigio R, Zampi I, Santucci A, Santucci C, Reboldi G, Porcellati C: Prognostic value of left ventricular mass and geometry in systemic hypertension with left ventricular hypertrophy. Am.J.Cardiol. 78:197-202, 1996 Cerca con Google

71. Nishimura RA, Abel MD, Hatle LK, Tajik AJ: Assessment of diastolic function of the heart: background and current applications of Doppler echocardiography. Part II. Clinical studies. Mayo Clin.Proc. 64:181-204, 1989 Cerca con Google

72. Rokey R, Kuo LC, Zoghbi WA, Limacher MC, Quinones MA: Determination of parameters of left ventricular diastolic filling with pulsed Doppler echocardiography: comparison with cineangiography. Circulation 71:543-550, 1985 Cerca con Google

73. Pearson AC, Labovitz AJ, Mrosek D, Williams GA, Kennedy HL: Assessment of diastolic function in normal and hypertrophied hearts: comparison of Doppler echocardiography and M-mode echocardiography. Am.Heart J. 113:1417-1425, 1987 Cerca con Google

74. Kuo LC, Quinones MA, Rokey R, Sartori M, Abinader EG, Zoghbi WA: Quantification of atrial contribution to left ventricular filling by pulsed Doppler echocardiography and the effect of age in normal and diseased hearts. Am.J.Cardiol. 59:1174-1178, 1987 Cerca con Google

75. Rosner B: Fundamentals of Biostatistics. Boston, Mass., PWS Publisher, 1996 Cerca con Google

76. Rocha R, Stier CT, Jr.: Pathophysiological effects of aldosterone in cardiovascular tissues. Trends Endocrinol.Metab 12:308-314, 2001 Cerca con Google

77. Rossi GP, Cesari M, Pessina AC: Left ventricular changes in primary aldosteronism. Am.J.Hypertens. 16:96-98, 2003 Cerca con Google

78. Rossi GP, Bernini G, Desideri G, Fabris B, Ferri C, Giacchetti G, Letizia C, Maccario M, Mannelli M, Matterello MJ, Montemurro D, Palumbo G, Rizzoni D, Rossi E, Pessina AC, Mantero F: Renal damage in primary aldosteronism: results of the PAPY Study. Hypertension 48:232-238, 2006 Cerca con Google

79. Rossi GP: Surgically correctable hypertension caused by primary aldosteronism. Best.Pract.Res.Clin.Endocrinol.Metab 20:385-400, 2006 Cerca con Google

Download statistics

Solo per lo Staff dell Archivio: Modifica questo record