Cardiac Ca2+ current (I") was shown to be regulated by cGMP in a number of different species. Recently, we found that the NO-donor SIN-1 (3-morpholino-sydnonimine) exerts a dual regulation of Ic. in frog ventricular myocytes via an accumulation of cGMP. To examine whether NO also regulates Ca2" channels in human heart, we investigated the effects of SIN-1 on Ic. in isolated human atrial myocytes.An extracellular application of SIN-1 produced a profound stimulatory effect on basal IC. at concentrations > 1 pM.Indeed, 10 pM SIN-1 induced a s 35% increase in Ic.. The stimulatory effect of SIN-1 was maximal at 1 nM ( z 2-fold increase in ICa) and was comparable with the effect of a saturating concentration (1 ,uM) of isoprenaline, a 13-adrenergic agonist. Increasing the concentration of SIN-1 to 1-100 ,uM reduced the stimulatory effect in two thirds of the cells. The stimulatory effect of SIN-1 was not mimicked by SIN-1C, the cleavage product of SIN-1 produced after liberation of NO. This suggests that NO mediates the effects of SIN-1 on ICa. Because, in frog heart, the stimulatory effect of SIN-1 on Ic. was found to be due to cGMP-induced inhibition of cGMP-inhibited phosphodiesterase (cGI-PDE), we compared the effects of SIN-1 and milrinone, a cGI-PDE selective inhibitor, on Ic. in human. Milrinone (10 ,uM) induced a strong stimulation of 'Ca (-150%), demonstrating that cGI-PDE controls the amplitude of basal Ic. in this tissue. In the presence of milrinone, SIN-1 (0.1-1 nM) had no stimulatory effect on ICa, suggesting that the effects of SIN-1 and MIL were not additive. We conclude that NO may stimulate ICa in human atrial myocytes via inhibition

Our data show that insulin stimulates the L-type calcium current in isolated human atrial myocytes in a dose-dependent and reversible manner which appears to involve the insulin receptor tyrosine kinase. Insulin regulation of ICa,L in human atrial myocytes may be an interesting system for the analysis of the metabolic syndrome in man.

The peak endocardial acceleration (PEA, unit g) shows a near correlation with myocardial contractility during the isometric systolic contraction of the heart (dP/dtmax), with sympathetic activity and, thus, with physiological heart rate modulation. The (Biomechanical Endocardial Sorin Transducer (BEST) sensor is incorporated in the tip of a pacing lead and measures PEA directly near the myocardium. In an international study, the lead was implanted with the dual chamber pacemaker Living-1 (Sorin) in 105 patients. The behavior of the PEA signal was tested under conditions of physical and mental stress and during daily life activities by 24-hour recordings of PEA (PEA Holter) at 1 to 2 months and approximately 1 year after implantation. Implantation of the BEST lead was performed without complications in all patients. The sensor functioned properly in the short- and long-term in 98% of patients. Although PEA values differed from patient to patient, the values closely reflected the variations in sympathetic activity due to physical and mental stress in each patient. During exercise and during daily life activities a close correlation between PEA and heart rate was observed among patients with normal sinus rhythm. Peak endocardial acceleration allows a nearly physiological control of the pacing rate.

In patients with FA taking aspirin and clopidogrel, selective thrombin injection is more effective than manual compression.