title: Early hemodynamic and biochemical changes in overloaded swine ventricle.
abstract: The present study was undertaken to investigate, in an animal model, the relationship between sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) activity, phospholamban phosphorylation, acylphosphatase activity, and hemodynamic changes that occur in the early phase of pressure overload. In 54 study-group pigs, weighing 40±5 kg each, an aortic stenosis was created with a band of umbilical tape tied around the aorta; 18 sham-operated pigs formed our control group. Eight animals (6 study and 2 control) were randomly assigned to each experimental time (0.5, 3, 6, 12, 24, 48, 72, 96, and 168 hr). All indices of left ventricular function declined significantly, with a peak at 6 hr and a return to baseline at 168 hr. At each observational time, SERCA2a activity, Ca2+ uptake, and acylphosphatase activity rose significantly, with a maximum increase at 6 hr. These changes indicated a higher expression of these proteins; conversely, phospholamban did not show significant changes in its concentration or in its phosphorylation status. Nuclear proto-oncogene c-fos expression rose at 6 hr. A strong inverse correlation was found when Ca2+-ATPase activity, Ca2+-ATPase expression, Ca2+ uptake, and acylphosphatase were compared with indices of systolic function. In our model of induced pressure overload, an initial phase of depressed myocardial contractility was accompanied by an increased sarcoplasmic reticulum function and by higher Ca2+-ATPase and Ca2+ uptake activities mediated by acylphosphatase. This new finding of Ca2+ homeostasis might indicate a compensatory mechanism for mechanical stress. Further studies are needed to confirm our findings.
authors.affiliation: Experimental Surgery Unit, Heart and Vessels Department, Careggi Hospital, 50134 Florence, Italy. sandro.gelsomino@libero.it
authors.forename: Sandro
authors.initials: S
authors.lastname: Gelsomino
authors.forename: Fabiana
authors.initials: F
authors.lastname: Lucà
authors.forename: Chiara
authors.initials: C
authors.lastname: Nediani
authors.forename: Sandra Zecchi
authors.initials: SZ
authors.lastname: Orlandini
authors.forename: Daniele
authors.initials: D
authors.lastname: Bani
authors.forename: Antonio S
authors.initials: AS
authors.lastname: Rubino
authors.forename: Attilio
authors.initials: A
authors.lastname: Renzulli
authors.forename: Roberto
authors.initials: R
authors.lastname: Lorusso
authors.forename: Andrea
authors.initials: A
authors.lastname: Consolo
authors.forename: Antonino
authors.initials: A
authors.lastname: Lo Cascio
authors.forename: Jos
authors.initials: J
authors.lastname: Maessen
authors.forename: Gian Franco
authors.initials: GF
authors.lastname: Gensini
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000503:physiopathology* / Q000601:surgery; D015415:Biomarkers / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D006439:Hemodynamics; D006706:Homeostasis; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D010766:Phosphorylation; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D034421:Sus scrofa; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D016277:Ventricular Function, Left; D000097024:Acylphosphatase; D000099211:Phospholamban
chemical_list: D017766:Acid Anhydride Hydrolases; D015415:Biomarkers; D002118:Calcium; D002135:Calcium-Binding Proteins; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000097024:Acylphosphatase; D000099211:Phospholamban
keywords: Aortic valve stenosis/pathology; calcium; calcium-transporting ATP-ases; disease models, animal; hemodynamics; myocardial contraction/physiology; sarcoplasmic reticulum calcium-transporting ATPases; sarcoplasmic reticulum/physiology; swine
references.citation: Pediatr Res. 2001 Aug;50(2):246-53
references.pmid: 11477211
references.citation: Nat Med. 2004 Mar;10(3):248-54
references.pmid: 14966518
references.citation: FEBS Lett. 1999 Jan 29;443(3):308-12
references.pmid: 10025953
references.citation: J Mol Cell Cardiol. 2000 Jan;32(1):131-42
references.pmid: 10652197
references.citation: Circulation. 1980 Jun;61(6):1119-25
references.pmid: 7371124
references.citation: Nat Rev Mol Cell Biol. 2003 Jul;4(7):566-77
references.pmid: 12838339
references.citation: Circulation. 1985 Feb;71(2):266-72
references.pmid: 3155498
references.citation: Circulation. 1977 Apr;55(4):613-8
references.pmid: 138494
references.citation: Am J Cardiol. 1994 Oct 15;74(8):794-8
references.pmid: 7942552
references.citation: N Engl J Med. 1992 Oct 1;327(14):998-1008
references.pmid: 1518549
references.citation: J Biol Chem. 1996 Aug 9;271(32):19066-73
references.pmid: 8702578
references.citation: Am J Physiol Heart Circ Physiol. 2004 Jun;286(6):H2314-21
references.pmid: 15148059
references.citation: Am J Physiol. 1995 Jan;268(1 Pt 1):C252-8
references.pmid: 7840154
references.citation: Exp Neurol. 1987 Nov;98(2):357-69
references.pmid: 2822459
references.citation: Am J Physiol. 1991 Oct;261(4 Suppl):23-6
references.pmid: 1833991
references.citation: Circ Res. 1995 Oct;77(4):759-64
references.pmid: 7554123
references.citation: Am J Physiol Heart Circ Physiol. 2000 Sep;279(3):H976-85
references.pmid: 10993758
references.citation: J Am Coll Cardiol. 1994 May;23(6):1444-51
references.pmid: 8176105
references.citation: Biochemistry. 1986 Nov 18;25(23):7615-23
references.pmid: 2948562
references.citation: J Clin Invest. 1975 Jul;56(1):56-64
references.pmid: 124746
references.citation: Biochim Biophys Acta. 2003 Jul 30;1638(3):217-26
references.pmid: 12878322
references.citation: Circulation. 1978 Dec;58(6):1072-83
references.pmid: 709763
references.citation: Nature. 2002 Jan 10;415(6868):198-205
references.pmid: 11805843
references.citation: Am J Physiol. 1997 May;272(5 Pt 2):H2416-24
references.pmid: 9176313