A time-dependent, cesium-sensitive increasing inward current, that we had previously described having the electrophysiological properties of the pacemaker current I(f), was elicited by negative steps (-60 to -130 mV) from a holding potential of -40 mV. Boltzmann fit of control activation curves gave a midpoint (V1/2) of -88.9 +/- 2.6 mV (n = 14). 5-HT (1 microM) consistently caused a positive shift of V1/2 of 11.0 +/- 2.0 mV (n = 8, p < 0.001) of the activation curve toward less negative potentials, thus increasing the amount of current activated by clamp steps near the physiological maximum diastolic potential of these cells. The effect was dose-dependent, the EC50 being 0.14 microM. Maximum current amplitude was not changed by 5-HT. 5-HT did not increase I(f) amplitude when the current was maximally activated by cAMP perfused into the cell. The selective 5-HT4 antagonists, DAU 6285 (10 microM) and GR 125487 (1 microM), completely prevented the effect of 5-HT on I(f). The shift of V1/2 caused by 1 microM 5-HT in the presence of DAU 6285 or GR 125487 was 0.3 +/- 1 mV (n = 6) and 1.0 +/- 0.6 mV (n = 5), respectively (p < 0.01 versus 5-HT alone). The effect of 5-HT4 receptor blockade was specific, since neither DAU 6285 nor GR 125487 prevented the effect of 1 microM isoprenaline on I(f). Thus, 5-HT4 stimulation increases I(f) in human atrial myocytes; this effect may contribute to the arrhythmogenic action of 5-HT in human atrium.
Cerebral damage remains one of the hazards related to cardiac surgery with cardiopulmonary bypass. The use of biochemical markers of cerebral injury may be of practical value. We investigated the plasma release patterns of S-100 protein and neuron-specific enolase (NSE) during the intervention and their relationship with the development of neuropsychological deficits assessed 6 months after the intervention in 16 patients undergoing elective cardiac surgery with cardiopulmonary bypass. Both S-100 and NSE significantly increased peri- and postoperatively. Significant correlations were found between values measured at several time points and impaired performance in a few tests at the 6-month follow-up. A stratification into two age subgroups led to the hypothesis that age might have a confounding or a modifying effect on the association between S-100 and NSE levels, and cognitive impairment.
Because of its high specificity and sensitivity, serial measurements of cTnI provide a rapid and accurate method for confirming or excluding the diagnosis of perioperative myocardial injury. cTnI evaluation can therefore be used both as an independent prognostic marker for patients undergoing cardiac surgery and as a powerful tool for detecting smaller PMIs often missed with standard PMI diagnostic criteria.
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