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Acta Physiologica 2009; Volume 195, Supplement 669
The 88th Annual Meeting of The German Physiological Society
3/22/2009-3/25/2009
Giessen, Germany
STIMULATION OF THE CALCIUM RECEPTOR: A NEW POSITIVE INOTROPIC INTERVENTION OF THE POST-ISCHEMIC HEART
Abstract number: KN88
Schreckenberg1 R., Abdallah1 Y., Schluter1 K.-D.
1Institute of Physiology, Giessen
Background:
Acute heart failure as a result of a myocardial infarction is characterized by a critical drop in blood pressure and cardiac output. At present, pharmacologic therapies for acutely decompensated heart failure include Dobutamine, Adrenaline or calcium sensitizer. The major potential disadvantages of these drugs are the induction of arrhythmias and the acceleration of the heart rate. An imbalance of the polyamine metabolism in post-ischemic myocytes leads to an accumulation of putrescine, a physiological agonist of the Calcium Receptor (CR). The aim of this study was to investigate the potential of CR stimulation as a positive inotropic principle using isolated cardiomyocytes and isolated perfused hearts.
Methods:
CR was stimulated by putrescine (Put, 1mM) or gadolinium (Gd, 200nM), NPS (10 mM) was used for blocking the receptor. Ventricular cardiomyocytes were isolated from adult rats, paced at different frequencies and cell shortening was monitored. The alteration of cytosolic calcium was measured using fura-2AM as fluorophore. Results of these experiments were transferred to the Langendorff heart. Isolated perfused hearts were subjected to 45 min no-flow ischemia and 120 min reperfusion. Myocardial function was evaluated by continuous assessment of left ventricular developed pressure and heart rate.
Results:
After incubation with Put cell shortening and shortening dynamics of isolated myocytes increased frequency-dependent by 7.5% (1.0Hz) and 12.0% (2.0Hz), (n=62, p<0,05), Gd improved cell shortening by 13.0% (1,0 Hz) and 22.5% (2Hz), (n=62, p<0,05). Simultaneous, both agonists induced a rise in systolic calcium up to 23% whereas the diastolic calcium remains unchanged. The improved calcium transient could be suppressed by the receptor blocker NPS and the IP3 inhibitor Xestospongin D. An improvement of the relaxation velocity was accompanied by an acceleration of the calcium sequestration. Treatment with Put also improved functional performance in normoxic hearts by 32% (Gd: 31%) and in post-ischemic hearts by 23% (Gd: 26%). Both agonists did not affect the enddiastolic pressure. Early perfusion with NPS blocks cardioprotective effects of Put/Gd in normoxic and post-ischemic hearts.
Conclusion:
Stimulation of the myocardial CR induces an IP3-dependent release of calcium from the sarcoplasmatic reticulum. This mechanism improves contractile activity without any effects on the diastolic relaxation.
To cite this abstract, please use the following information:
Acta Physiologica 2009; Volume 195, Supplement 669 :KN88