Isoproterenol (Iso) was a clinical therapeutic that is now used as a research means for the induction of cardiac hypertrophy. Currently, dobutamine (Dob) has replaced Iso as the preferred inotropic β-adrenergic agent to wean patients from cardiopulmonary bypass and to sustain adequate cardiac function during the postoperative period. We sought to compare the cardiac structural and functional effects of long-term administration (7days) of Iso with Dob at a dose of 40μg/mouse/day in 12-week-old C57BL/6 female mice. Cardiac function was determined with transthoracic echo cardiography (ECHO) 24 hours after the last dose. Cardiac wet weights increased 33% and 24% in the Iso and Dob groups compared with controls (p < 0.05). Dob and Iso significantly increased cardiac fibrosis and decreased cardiac function with chronic administration. Administration also resulted in increased left atrial size, suggesting that both Dob and Iso decreased LV compliance, but did not induce heart failure. In conclusion, chronic administration of Dob may have a detrimental effect on cardiac structure and function.
1 Chappel CI Rona G Balazs T . Severe myocardial necrosis produced by isoproterenol in the rat. Arch Int Pharmacodyn1951; 72: 123–128.
2.
2 Rona G Chappel CI Balazs T . The effect of breed, age, and sex on myocardial necrosis produced by isoproterenol in the rat. J Gerontol1959; 14: 169–173.
3.
3 Rona G Chappel CI Balazs T . An infarct-like myocardial lesion and other toxic manifestations produced by isoproterenol in the rat. Arch Pathol1959; 67: 443–455.
4.
4 Rona G Chappel C Kahn DS . The significance of factors modifying the development of isoproterenol-induced myocardial necrosis. Am Heart J1963; 66: 389–395.
6 Hohimer AR Davis LE Hatton DC . Repeated daily injections and osmotic pump infusion of isoproterenol cause similar increases in cardiac mass but have different effects on blood pressure. Can J Physiol Pharmacol2005; 83: 191–197.
7.
7 Capomolla S Febo O Opasich C . Chronic infusion of dobutamine and nitroprusside in patients with end-stage heart failure transplantation: safety and clinical outcome. European Society of Cardiol2000; 3: 601–610.
8.
8 Dudnakova TV Lakomkin VL Tsyplenkova VG Shekhonin BV Shirinsky VP Kapelko VI . Alterations in myocardial ultrastructure and protein expression after a single injection of isoproterenol. Molecular and Cellular Biochemistry2002; 252: 173–181.
9.
9 Liggett SB . Pharmacogenetics of beta-1 and beta-2-adrenergic receptors. Pharmacology2000; 61(3): 167–173.
10.
10 Morisco C Zebrowski DC Vatner DE Vatner SF Sadoshima J . β-adrenergic cardiac hypertrophy is mediated primarily by the β1-subtype in the rat heart. J Mol Cell Cardiol2000; 33: 561–573.
11.
11 Turner NA Porter KE Smith WHT White HL Ball SG Balmfort AJ . Chronic β2-adrenergic receptor stimulation increases proliferation of human cardiac fibroblasts via an autocrine mechanism. Cardiovascular Research2002; 57: 784–792.
12.
12 Chandrasekar B Marelli-Berg FM Tone M Bysani S Prabhu SD Murray DR . β-adrenergic stimulation induces interleukin-18 expression via β2-AR, PI3K, Akt, IKK, and NF-κB. Biochem Biophy Res Commun2004; 319: 304–311.
13.
13 Leenen FHH White R Yuan B . Isoproterenol-induced cardiac hypertrophy: role of circulatory versus cardiac renin-angiotensin system. Am J Physiol Heart Circ Physiol2001; 281: 2410–2416.
14.
14 Buttrick A Malhotra A Factor S Geenen D Scheuer J . Effects of chronic dobutamine administration on hearts of normal and hypertensive rats. Circ Res1988; 63: 173–181.
15.
15 Benjamin IJ Jalil JE Tan LB Cho K Weber KT Clark WA . Isoproterenol-induced myocardial fibrosis in relation to myocyte necrosis. Circ Res1989; 65(3): 657–670.
16.
16 Nakatsuji S Yamate J Kuwamura M Kotani T Sakuma S . In vivo responses of macrophages and myofibroblasts in the healing following isoproterenol-induced myocardial injury in rats. Virchows Arch1997; 430: 63–69.
17.
17 Pick R Jalil JE Janicki JS Weber KT . The fibrillar nature and structure of isoproterenol-induced myocardial fibrosis in the rat. Am J Pathol1989; 134: 365–371.
18.
18 Galderisi M . Diastolic dysfunction and diastolic heart failure: diagnostic, prognostic and therapeutic aspects. Cardiovasc Ultrasound2005; 3: 9 Review.
19.
19 Martini G Rabbia F Gastaldi L . Heart rate variability and left ventricular diastolic function in patients with borderline hypertension with and without left ventricular hypertrophy. Clin Exp Hypertens2001; 23(1-2): 77–87.
20.
20 Jalil JE Janicki JS Pick R Abrahams C Weber KT . Fibrosis-induced reduction of endomyocardium in the rat after isoproterenol administration. Circ Res1989; 65(2): 258–264.
21.
21 Stacy LB Yu Q Horak K Larson DF . Effect of angiotensin II on primary cardiac fibroblast matrix metalloproteinase activities. Perfusion2007; 22(1): 51–55.
22.
22 Kudej RK Iwase M Uechi M . Effects of chronic β-adrenergic receptor stimulation in mice. J Mol Cell Cardiol1997; 29: 2735–2746.
23.
23 Masson S Arosio B Luvara G . Remodeling of cardiac extracellular matrix during beta-adrenergic stimulation: upregulation of SPARC in the myocardium of adult rats. J Mol Cell Cardiol1998; 30(8): 1505–1514.
24.
24 Ocaranza MP Diaz-Araya G Chiong M . Isoproterenol and angiotensin I-converting enzyme in lung, left ventricle, and plasma during myocardial hypertrophy and fibrosis. J Cardiovasc Pharmacol2002; 40(2): 246–254.
26 Spinale FG . Bioactive peptide signaling within the myocardial interstitium and the matrix metalloproteinases. Circ Res2002; 91: 1082–1084.
27.
27 Pritchett AM Mahoney DW Jacobsen SJ Rodeheffer RJ Karon BL Redfield MM . Diastolic dysfunction and left atrial volume. J Am Coll Cardio2005; 48: 87–92.
28.
28 Vasan RS Benjamin MJ Levy D . Prevalence, clinical features and prognosis of diastolic heart failure: an epidemiologic perspective. J Am Coll Cardiol1995; 26(7): 1565–1574.
29.
29 Phibin E Rocco TA Lindenmuth NW , Ulrich, K, Jenkins PL. Systolic versus diastolic heart failure in community practice: clinical features, outcomes, and the use of angiotensin-converting enzyme inhibitors. Am J Med2000; 109(8): 605–613.
