Effect of 5-HT4 receptor stimulation on the pacemaker current I(f) in human isolated atrial myocytes.

OBJECTIVE: 5-HT4 receptors are present in human atrial cells and their stimulation has been implicated in the genesis of atrial arrhythmias including atrial fibrillation. An I(f)-like current has been recorded in human atrial myocytes, where it is modulated by beta-adrenergic stimulation. In the present study, we investigated the effect of serotonin (5-hydroxytryptamine, 5-HT) on I(f) electrophysiological properties, in order to get an insight into the possible contribution of I(f) to the arrhythmogenic action of 5-HT in human atria. METHODS: Human atrial myocytes were isolated by enzymatic digestion from samples of atrial appendage of patients undergoing coeffective cardiac surgery. Patch-clamped cells were superfused with a modified Tyrode's solution in order to amplify I(f) and reduce overlapping currents. RESULTS AND CONCLUSIONS: 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.

Cardiac tamponade secondary to intrapericardial rupture of a hepatic amoebic abscess.

We report the case of a patient who underwent an emergency subxiphoid pericardiectomy with evacuation of 1700 cc of anchovy sauce-like fluid. On pericardial inspection a fistulous communication was seen with a cavity in the left hepatic lobe. No loculi or adhesions were found in the pericardial sac and no further surgical procedure was advised. The hepatic cavity and pericardium were drained: bacteriological investigation of the fluid yielded entamoeba histolytica and chloroquine was administered. Apart from the rarity of the observation in western countries, we discuss surgical approaches in cases of unknown purulent pericardial effusions, stressing the possibility of achieving a good surgical result even with a minor surgical procedure such as subxiphoid pericardiectomy and drainage.

A major involvement of the cardiovascular system in patients affected by Marfan syndrome: novel mutations in fibrillin 1 gene.

The aim of our study was to characterize the molecular defect in Italian Marfan patients, thus contributing to the effort of correlating the genotype with the phenotype. In particular, our ultimate goal was to identify the region(s) of the fibrillin 1 (FBN1) gene mainly involved in the health of the heart and of the aorta in terms of the cardiovascular system. We searched for a molecular defect in three patients with classic Marfan syndrome (MFS). The mutations were detected applying heteroduplex analysis to each of the 65 exons of the FBN1 gene amplified by polymerase chain reaction (PCR). Exons containing heteroduplex bands were sequenced directly from PCR products. This study reports the detection of three unique missense mutations in the FBN1 gene in three Italian patients: a 44-year-old adult male and 36-year-old female affected by classic MFS (with all the cardinal manifestations in the cardiovascular, ocular and skeletal systems), and an 11-year-old male affected by infantile (earlier onset) classic MFS. The first two are sporadic cases and present a Cys-->Arg amino acid substitution (T-->C substitution at nucleotide 7729) in exon 62 and a Cys-->Tyr amino acid substitution (G-->A substitution at nucleotide 6695) in exon 54. The third is a familial case which presents a Cys-->Trp aminoacidic substitution (C-->G substitution at nucleotide 3546) in exon 28. Our data confirm that cysteine substitutions in calcium binding epidermal growth factor (cbEGF)-like domains cause severe Marfan phenotype. Exon 24-32 cluster seems to produce an even more severe phenotype. The early characterization may be of clinical relevance for prevention and early surgical treatment of aortic aneurysm or dissection.

Cardiac troponin I and Q-wave perioperative myocardial infarction after coronary artery bypass surgery.

OBJECTIVE: To monitor cardiac troponin I (cTnI), a newly developed biochemical index for cardiac damage, in patients during and after coronary artery bypass surgery (CABS) to determine whether the measurement of the serum levels of this marker could be of value in formulating an early diagnosis of Q-wave perioperative myocardial infarction (PMI). DESIGN: Prospective study with sequential measurements of biological markers in a selected surgical patient group. SETTING: University research laboratory and general university hospital (Cardiac Surgery Unit and Anesthesiology and Reanimation Unit). PATIENTS: Forty-two patients undergoing elective CABS without concomitant valvular replacement. INTERVENTIONS: There were no interventions required for this study. However, patients entered into the study had CABS, sequential arterial blood samples, ECG recordings, and echocardiograms performed. MEASUREMENTS AND MAIN RESULTS: Pre-, intra-, and postoperative (up to 48 hrs) measurements of cardiac troponin I, MB-CK, and total creatine kinase, as well as serial electrocardiograms and echocardiograms. Perioperative infarction was assessed as the development of new persistent regional wall motion abnormalities in echocardiography together with electrocardiographic alterations and MB-CK increases. Eight patients had Q-wave PMI. All PMI patients had elevated peak cTnI values (all >9.2 ng/mL), whereas the 34 nonPMI patients had peak values <9.0 ng/mL; therefore, sensitivity and specificity (with a 9.0 ng/mL cut-off value) are 100%. MB-CK measurement peak values did not demonstrate such a high specificity and sensitivity. CONCLUSIONS: 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.