Early hemodynamic and biochemical changes in overloaded swine ventricle

Sandro Gelsomino, Fabiana Lucà, Chiara Nediani, Sandra Zecchi Orlandini, Daniele Bani, Antonio S. Rubino, Attilio Renzulli, Roberto Lorusso, Andrea Consolo, Antonino Lo Cascio, Jos Maessen, Gian Franco Gensini

Research output: Contribution to journalArticlepeer-review

Abstract

The present study was undertaken to investigate, in an animal model, the relationship between sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) activity, phospholamban phos-phorylation, 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.

Original languageEnglish
Pages (from-to)235-245
Number of pages11
JournalTexas Heart Institute Journal
Volume40
Issue number3
Publication statusPublished - 2013

Keywords

  • Animal
  • Aortic valve stenosis/pathology
  • Calcium
  • Calcium-transporting atpases
  • Disease models
  • Hemodynamics
  • Myocardial contraction/ physiology
  • Sarcoplasmic reticulum calciumtransporting atpases
  • Sarcoplasmic reticulum/physiology
  • Swine

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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