We investigated the hypothesis that increased intracellular [Na + ] i in heart failure contributes to preservation of SR Ca 2+ load which may become particularly evident at slow heart rates.[Na + ] i in SBFI-loaded myocytes from rabbits with pacing-induced heart failure (PHF) was significantly higher at each frequency as compared to Sham-operated animals. Furthermore, PHF rabbits demonstrated reduced SR Ca 2+ -ATPase protein levels (À 37%, p < 0.04) but unchanged Na + /Ca 2+ exchanger protein levels. At 0.25 Hz, isometric force was similar in cardiac trabeculae from PHF rabbits as compared to control (PHF, 3.6 T 1.3; Sham, 4.4 T 0.6 mN/mm 2 ). Rapid cooling contractures (RCCs) were unchanged indicating preserved SR Ca 2+ load at this frequency. In Sham, isometric twitch force increased with rising frequencies to 29.0 T 2.8 mN/mm 2 at 3.0Hz ( p < 0.05) as compared to 0.25 Hz. RCCs showed a parallel increase by 186 T 47% ( p < 0.01). In PHF, frequency-dependent increase in force (15.8 T 4.7 mN/mm 2 at 3.0 Hz) and RCCs (increase by 70 T 40%) were significantly blunted.Thus, in PHF in rabbits SR Ca 2+ load is preserved at low frequencies despite decreased SR Ca 2+ -ATPase expression. This may result from [Na + ] i -dependent changes in Na + /Ca 2+ exchanger activity.

Interventional closure of muscular VSD is possible in newborns and infants and presents an eligible treatment option. New occlusion systems with miniaturized introducer sheaths of 4-6 French have extended the spectrum of treatable lesions. An individual and interdisciplinary risk-benefit stratification is required to choose from surgical, interventional, or combined strategies.

α 1 -adrenergic stimulation and mechanical load are considered crucial for the expression of sarcolemmal Na + /Ca 2+ exchanger (NCX1). However, the interaction between these processes is unknown.We investigated electrically stimulated (1 Hz, 1.75 mmol/L Ca 2+ ) rabbit ventricular trabeculae at physiological preload under stimulation by the selective α 1 -agonist phenylephrine (PE, 10 μmol/L). Using quantitative real-time PCR, downregulation of mRNA to 76.5% ( p b 0.05) was found, while B-type natriuretic peptide (BNP) was increased to 569.5% ( p b 0.05) compared to control. These changes were abolished in the presence of both the α 1 -blocker prazosin (13 μmol/L) and the PKC inhibitor GF109203X (1 μmol/L). Furthermore, no changes in NCX mRNA levels under the influence of PE were found in unstretched trabeculae or in unstretched isolated rabbit myocytes (24 h), while BNP was increased in both preparations. In addition, since the α 1 -adrenergic effect could be Ca 2+ -dependent we tested increased extracellular Ca 2+ (3.0 mmol/L) in stretched trabeculae and found downregulation of NCX1 to 75.2% ( p b 0.05).α 1 -stimulation decreases NCX1 mRNA in rabbit myocardium via PKC. This is critically load-dependent and may be mediated by changes in [Ca 2+ ]. In hypertrophy and heart failure, distinct phenotypes with respect to NCX1 expression may result from the interaction between mechanical load and α 1 -adrenergic stimulation.

No abstract