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Electrophysiological basis for arrhythmias in left ventricular hypertrophy
No full textLeft ventricular hypertrophy has been associafed with an increased
incidence of cardiac arrhythmias. Spontaneous/y hypertensive rats ($HR) deve/op
cardiac hypertrophy during aging. Papillary muscles isolafed ttom 18-month old
SHR had an enhanced responsiveness to the arrhythmogenic action of 13-
adrenergic stimulapon compared to tbose ttom 2-month old SHR and agematched
normotensivé'Wrstar Kyoto rats (WKY). Myocytes isolated from the heart
of 18-month old WKY and SHR were sfudied with the pafch c1amp technique.
Action pofential duration was greatly prolonged in SHR compared to WKY. The
f basis for this pbenomenoti seems to be a selecfive reduction of tne; K+
repolarizing current lto The obse.rved elecfrophysiological alterafion may
contribufe to the increased arrhythmogenicify of fhe hypertrophied heart
Electrophysiologic study of lercanidipine and its enantiomers
No full textLercanidipine is a new dihydropyridine (DHP) derivative with calcium antagonistic properties. In vitro and in vivo experiments have shown that it relaxes vascular musculature without exerting negative inotropic effects. The two ester groups present in positions 3 and 5 of the DHP ring lead to the existence of two enantiomers. We studied the electrophysiologic properties of lercanidipine and its enantiomers in multicellular preparations (i.e., rabbit and guinea pig papillary muscles) and patch-clamped isolated guinea pig ventricular myocytes. Lercanidipine (1 μM) affected neither action potential characteristics nor contraction amplitude of papillary muscles. It did not reduce sodium current or L-type calcium current (ICa) recorded from cells kept at a normal polarized membrane potential (-80 mV), both at low (0.2 Hz) and high stimulation frequency (1 Hz). (R)-Lercanidipine decreased (10.6 ± 1.6 vs. 12.1 ± 1.2 pA/pF; p < 0.05) and (S)-lercanidipine increased ICa (17.1 ± 1.0 vs. 12 8 ± 0.9 pA/pF;p<0.05). However, blocking activity on the calcium current by lercanidipine or its enantiomers was apparent when the cells were kept at a depolarized holding potential (HP = -40 mV). With long conditioning pulses (5 s), a marked shift of the steady-state inactivation curve for ICa was observed. Voltage of halfmaximal activation was shifted from -34 mV (control) to -43.1 mV, -45.0, and -43.8 mV in the presence of lercanidipine, (S)-lercanidipine, and (R)-lercanidipine, respectively. ICa blockade and recovery from blockade developed slowly with both enantiomers and the racemate, being markedly slower than that observed with nimodipine under the same experimental conditions. At HP = -40 mV, block of ICa by either (S)- or (R)-lercanidipine was markedly usedependent. At the tenth pulse, current amplitude was reduced to 11.5 ± 3.2% (n = 4) and 20.5 ± 4.9% (n = 5) of the value recorded during the first pulse by (R)-lercanidipine and (S)-lercanidipine, respectively. In conclusion, lercanidipine and its enantiomers have selective calcium antagonistic properties, which develop only at low membrane potentials
Occurrence and properties of the hyperpolarization-activated current I(f) in ventricular myocytes from normotensive and hypertensive rats during aging
No full textCellular electrophysiological alterations may contribute to arrhythmogenesis in cardiac hypertrophy. An L-like current occurs in left ventricular myocytes (LVMs) isolated from the hypertrophied heart of old spontaneously hypertensive rats (SHR). Factors that influence L occurrence during development of cardiac hypertrophy were studied by determining its presence, amplitude, characteristics, and beta-adrenoceptor modulation.
METHODS AND RESULTS:
Patch-clamped LVMs from young (2 to 3 months old) or old (18 to 24 months old) normotensive Wistar-Kyoto rats (WKY) and SHR were used. A diastolic depolarization phase was present in old SHR. An If-like current occurred in > 90% of LVMs from old SHR and WKY and in approximately = 15% of LVMs from young rats (P < .05). Activation curves of If were similar in old rats, with the midpoint at -92.9 +/- 2.9 mV in WKY (n = 42) and -88.1 +/- 1.5 mV in SHR (n = 25); maximal specific conductance was 54.4 +/- 1.7 in SHR and 20.1 +/- 0.5 picosiemens/picofarad in WKY (P < .05). In WKY, If amplitude was linearly related to membrane capacitance, an index of cell size (r = .53, P < .001). This relation was absent in SHR, in which a significant positive correlation was found between the heart weight to body weight ratio and I(f) density. In both old WKY and old SHR, 0.1 mumol/L (-)-isoproterenol increased I(f) amplitude by shifting its activation curve toward more positive potentials.
CONCLUSIONS:
In LVMs from both WKY and SHR, the occurrence of I(f) increases with aging. Density appears linearly related to the severity of cardiac hypertrophy and increases with beta-adrenoceptor stimulation, which suggests that I(f) may contribute to an increased propensity of the hypertrophied heart for arrhythmias
Characterization of the hyperpolarization-activated current, I(f), in ventricular myocytes isolated from hypertensive rats.
No full textLeft ventricular myocytes isolated from the heart of young (2-month-old) and old (18- to 20-month-old) spontaneously hypertensive rats (SHRs) were studied in the whole-cell configuration. Since multicellular preparations from old SHRs show a diastolic depolarization phase, we performed experiments to test whether it was associated with the presence of a hyperpolarization-activated If-like current. 2. In control Tyrode solution, a time-dependent increasing inward current activated by hyperpolarization was recorded in myocytes from old SHRs showing a diastolic depolarization phase. A barium-insensitive, caesium-sensitive, time-dependent inward current was recorded in a minority (4 of 33) of cells from young SHRs (membrane capacitance, 160 +/- 7 pF) but in 93% (25 of 27, P < 0.01) of myocytes from old SHRs (membrane capacitance, 355 +/- 19 pF, P < 0.01). 3. The current was fully activated at -120 mV and voltage of half-maximal activation was -88.1 +/- 1.5 mV; it was blocked by extracellular CsCl (4 mM) in a voltage-dependent manner. Reducing [K+]o from 25 to 5.4 mM caused a shift of the reversal potential from -17.3 +/- 3.8 to -25.7 +/- 2.7 mV and a 60% decrease of current conductance. 4. These findings suggest that an If-like current is present in rat ventricular myocytes from old SHRs, where it might favour the occurrence of spontaneous action potentials
From in vivo plasma composition to in vitro cardiac electrophysiology and in silico virtual heart: the extracellular calcium enigma
No full textCardiac electrophysiological effects of a new dihydrophyridine calcium antagonist (BBR 2160)
No full textBBR 2160 is a new dihydropyridine derivative belonging to the group of the so-called tiampidines. We used intracellular microelectrodes to characterize the electrophysiological properties of BBR 2160 on sheep Purkinje fibres and guinea-pig papillary muscle. BBR 2160 (10(-7) and 10(-6) M) dose dependently decreased the contractility of driven Purkinje fibre and papillary muscle. This effect was associated with a lowering of the plateau phase and a shortening of action potential duration in papillary muscle. The effect of the drug developed quite slowly over time. The amplitude and Vmax of normal action potential were not affected by BBR 2160. Instead BBR 2160 reduced the amplitude and Vmax of the slow action potentials (which are a relatively good index of the slow inward current) induced by histamine (10(-5) M) in K(+)-depolarized (22 mM) papillary muscle. The results suggest that BBR 2160 has calcium-antagonistic properties in cardiac tissue
NADPH oxidase is related with lipid peroxidation and redox-sensitive kinase activation in human failing hearts
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