Cardiac sympathetic innervation and control of potassium channel function.
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Animals↗
Biomedical subjects
Dobromir Dobrev
Publications and source records attributed to Dobromir Dobrev.
Decreased ATP-sensitive K(+) current density during chronic human atrial fibrillation.
Chronic atrial fibrillation (AF) is associated with shortening of action potential duration (APD), which involves modified activity of atrial ion currents. However, little is known about the activity of ATP-sensitive K(+) channels (I(K,ATP)) during chronic AF. An AF-related increase in the activity of I(K,ATP) would reduce APD and could contribute to initiation and/or perpetuation of AF. Here, we studied the activity of I(K,ATP) in atrial myocytes from patients with sinus rhythm (SR) and chronic AF. Human atrial myocytes were isolated from atrial tissue obtained from patients undergoing open-heart surgery. Inward rectifier currents were measured with the whole-cell patch-clamp technique by applying a depolarizing ramp pulse (1245 ms) from -100 to +40 mV (0.5 Hz). I(K,ATP) was activated with the I(K,ATP) channel opener rilmakalim. The inward rectifier I(K1) and I(K,ATP) were identified by their sensitivity to 1 mM Ba(2+). Density of I(K1) did not differ between cells from patients with AF (at -100 mV: -14.8 +/- 1.3 pA/pF, n = 38/10 (cells/patients)) and SR (-13.8 +/- 1.5 pA/pF, n = 33/16). In both types of cells, rilmakalim stimulated I(K,ATP) (defined as rilmakalim-inducible current) in a concentration-dependent manner (0.3-10 microM). However, maximum activation of I(K,ATP) with 10 microM rilmakalim was smaller in AF than in SR cells (at -100 mV: -5.3 +/- 0.8 pA/pF, n = 22/7 vs. -11.2 +/- 2.9 pA/pF, n = 19/9; at +40 mV: +9.6 +/- 2.1 pA/pF, n = 22/7 vs. +23.7 +/- 3.4 pA/pF, n = 19/9 for AF and SR, respectively; P < 0.05). Only aortic valve disease and pulmonary hypertension were found to be independent contributors to I(K,ATP) current density. We provide evidence that chronic AF is associated with a downregulation of ATP-sensitive K(+) currents. These changes may provide an additional molecular mechanism for electrical remodeling in chronic AF.
Action Potentials↗
What is a good tutorial from the student's point of view? Evaluation of tutorials in a newly established PBL block course "Basics of Drug Therapy".
Problem-based learning (PBL) within a tutorial is the core element in a 6-week block course "Basics in Drug Therapy" recently introduced into the medical curriculum of an eastern German university. Under the supervision of one tutor a group of 6-9 students solved a total of six clinical cases related to drugs used in general anaesthetics; to analgetic/antiphlogistic, antihypertensive, cardiovascular and lipid-lowering drugs; to drugs acting on the central nervous system; and to intoxicating agents. By answering questionnaires students and tutors extensively evaluated each individual case as well as the whole block course. Factors evaluated also included students' and tutors' behaviour during sessions. The purpose of the analysis was to identify factors associated with the students' perception of tutorials with the aim of improving future courses. The ratings which tutorials, cases and tutor performance received by the students differed significantly between 14 groups that could be analysed. A ranking order of groups was established according to the scores they gave for the cases and the three groups with top ratings were further compared with the three groups with lowest ratings. We found significant differences between the two groups in their assessment of tutor performance and perception of team-work during tutorials. The tutors of the groups giving top ratings were considered to have more effectively supported the students' work during tutorials. Furthermore, self-assessment of the tutors judging their own ability to facilitate PBL correlated with their familiarity with case content. The marks achieved in the first national exam (i.e. "Physikum", equivalent to medical school entrance exams), performance in triple jump examination and multiple choice test at the end of the course, or marks obtained in the first state board exam after the course, did not differ between the two groups. From students' point of view, the main characteristics for a good tutorial as far as tutors are concerned consist of allowing enough time for discussion, accepting students as partners, refraining from interference and having expertise. As a consequence we will increase our efforts to optimise case quality as well as support and training of tutors in order to improve our new PBL course.
Education, Medical, Undergraduate↗
Human inward rectifier potassium channels in chronic and postoperative atrial fibrillation.
OBJECTIVE: We showed recently that the 825T allele of the G-protein beta 3-subunit C825T polymorphism is associated with large inward rectifier K(+) currents I(K1) but low acetylcholine-activated K(+) current I(K,ACh) amplitudes. During chronic atrial fibrillation (AF), I(K1) and I(K,ACh) current densities were increased when compared to sinus rhythm (SR). It is unknown whether chronic AF and G beta 3 gene status are independent contributors to atrial K(+) current activity. We measured I(K1) and I(K,ACh) in tissue from AF patients with different G beta 3 genotypes and assessed the relation between the I(K1) and I(K,ACh) amplitudes and the incidence of postoperative AF. METHODS: We measured the amplitudes of I(K1) and I(K,ACh) in atrial myocytes from 26 patients with sinus rhythm (SR) and from 16 patients with chronic AF (>6 months). The K(+) currents were measured with standard patch-clamp techniques. The G beta 3 gene status of the patients was determined by PCR and restriction analysis. RESULTS: At -100 mV, the amplitude of I(K1) was larger in AF (10.9+/-1.0 pA/pF, n=49/16, cells/patients) than in SR (6.3+/-0.6 pA/pF, n=68/26, P<0.05), whereas the amplitude of I(K,ACh) was smaller in chronic AF (2.9+/-0.7 pA/pF, n=49/16) than in SR (6.3+/-0.7 pA/pF, n=68/26, P<0.05). These changes were independent of the patient G beta 3 gene status. Eight patients out of 26 in the SR group (31%) developed postoperative AF. When analysed based on incidence of postoperative AF, current amplitudes did not differ significantly. CONCLUSION: We provide evidence for up-regulation of I(K1) but down-regulation of I(K,ACh) in chronic AF which are independent of G beta 3 gene status. Atrial myocytes from patients who are in SR but later develop postoperative AF have no manifestation of altered I(K1) and I(K,ACh) at the time of cardiac surgery. Our results suggest that the AF-related changes of I(K1) and I(K,ACh) may be a consequence of or a contributory factor to chronic AF.
Acetylcholine↗
Problem-based learning: a new pathway to competence?
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Clinical Competence↗
Rate-adaptive pacing using intracardiac impedance shows no evidence for positive feedback during dobutamine stress test.
BACKGROUND: The Inos2 DDDR pacemaker senses unipolar intracardiac impedance signals for adapting heart rate to meet the haemodynamic needs of physical activity. Theoretically, such pacing devices could be limited by positive feedback since increase in beating frequency per se enhances contractility. We have addressed this problem in patients with chronotropic incompetence who were subjected to a pharmacological stress test. METHODS AND RESULTS: Twelve patients with chronically implanted Inos2 DDDR pacemakers were studied using the standard protocol of stress echocardiography. Most of the patients reached the programmable maximum closed-loop rate during the incremental dobutamine challenge. The time courses for increase in as well as for recovery of heart rate were not different from control patients receiving routine diagnostic stress echocardiography. CONCLUSIONS: In patients implanted with the Inos2 DDDR pacemaker acute stimulation with intravenous dobutamine leads to a robust increase in paced heart rate without any evidence of positive feedback.
Cardiac Pacing, Artificial↗