Assessment of cerebral autoregulation from ectopic heartbeats.
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Transfer function analysis of spontaneous fluctuations in BP (blood pressure) and CBFV (cerebral blood flow velocity) has been widely used to study dynamic CA (cerebral autoregulation). The inverse Fourier transform and its integral, giving the impulse and step responses, have been used to gain perspective of the state of dynamic CA from the frequency and time domains respectively. The occurrence of ectopic heartbeats in the data has usually been treated as an artefact. Data containing multiple ectopic heartbeats were selected from a data set compiled for an acute stroke study which also included bilateral middle CBFV, concurrent surface ECG and non-invasive beat-to-beat BP recordings. Transfer function analysis and impulse and step responses were calculated from these data by (i) retaining ectopic heartbeats, (ii) after removal of ectopic heartbeats and replacement by linear interpolation, and (iii) using a narrow window of data surrounding selected ectopic heartbeats. Coherent averaging of the raw data of the selected ectopic heartbeats also allowed direct visualization of the relationship between BP changes and CBFV. The impulse and step responses were similar in shape whether or not ectopic heartbeats had been removed and showed characteristics of active dynamic CA. Removal of ectopic heartbeats from the CBFV and BP tracings, by linear interpolation or other methods, is not necessary to provide reliable estimates of dynamic autoregulation in subjects with ectopic heartbeat rates of up to eight per min. Additionally, impulse-like disturbances of BP induced by single-beat ectopic heartbeats provide enough information to characterize the autoregulatory response of the subject in agreement with more traditional methods of dynamic autoregulation assessment. (+info)
RSD1235 blocks late INa and suppresses early afterdepolarizations and torsades de pointes induced by class III agents.
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OBJECTIVE: RSD1235 is a novel antiarrhythmic drug with atria-selective electrophysiological actions on Na(+) and K(+) currents. The mechanism for its protection of ventricular repolarization was assessed by its action on Purkinje fibers, and by block of late sodium current active during repolarization. Further, RSD1235's ability to reverse the pro-arrhythmic actions of the class III agents dofetilide and clofilium was assessed in isolated Purkinje fibers and an in vivo model of torsades de pointes (TdP). METHODS: Action potential and early after-depolarization (EAD) recordings were made from in situ and isolated rabbit Purkinje fibers at 37 degrees C using floating sharp microelectrodes; late I(Na) was recorded using a whole-cell patch clamp technique of Nav1.5 expressed in HEK cells at 22 degrees C; In vivo, anesthetized methoxamine-sensitized rabbits were used to test the ability of RSD1235 to suppress clofilium-induced TdP. RESULTS: RSD1235 (0.5-30 microM) had minor dose-dependent effects on action potential duration (APD) at 50% and 90% repolarization in Purkinje fibers, but pre-treatment significantly attenuated the APD-prolonging effects of dofetilide (300 nM). EADs induced by 300 nM dofetilide were terminated by 30 microM RSD1235 in all experiments (n=7). RSD1235 blocked a late component of Na current (I(Na)), which can produce inward currents contributing to EAD formation. RSD1235 pre-treatment (1 micromol/kg/min) or acute infusions prevented/terminated TdP induced by clofilium in 8 of 9 rabbits, and reduced the duration of TdP episodes from 71 +/- 23 s in control to 17 +/- 7 and 14 +/- 14 s at infusion rates of 0.3 and 1.0 micromol/kg/min, respectively (n = 9, p < 0.001). CONCLUSION: RSD1235 itself has minor actions on repolarization in Purkinje fibers, but can reverse the AP-prolonging actions of class III agents and terminate arrhythmias in a model of TdP. We suggest that these protective actions of RSD1235 may result, at least in part, from its ability to inhibit late I(Na) during action potential repolarization. (+info)
Effects of bigeminies and paired-pulse stimulation on oxygen consumption in dog left ventricle.
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In 10 excised, cross-circulated, isovolumically beating dog left ventricles, we examined the effects of bigeminy, including paired-pulse stimulation, on cardiac oxygen consumption (VO2) and evaluated whether the VO2 versus pressure-volume area (PVA) relation obtained from regularly beating hearts in our previous studies could account for the changes in VO2 during bigeminies with various coupling intervals. The extrasystolic interval (ESI) was decreased in four steps from 300 msec (regular rhythm) to paired-pulse stimulation (less than or equal to 210 msec). The sum of ESI and the postextrasystolic interval was always held constant (600 msec); therefore, the number of excitations was 200/min at any ESI. Both VO2 and PVA were measured in four runs: a small volume run at a ventricular volume of 13 ml, a large volume of 12 ml, a calcium run in which contractility was enhanced by CaCl2 at a small volume of 12 ml, and a verapamil run in which contractility was depressed by verapamil at a large volume of 20 ml. In any run, both VO2 and PVA were unchanged at long ESIs (greater than or equal to 250 msec) from each control value at regular rhythm, but VO2 markedly increased at short ESIs (less than or equal to 230 msec). VO2s during bigeminies with various ESIs were comparable with the theoretical VO2 values that were calculated by the VO2-PVA relation at regular rhythm. However, the theoretical VO2 values underestimated the measured VO2 values at the shortest ESIs under a high volume loading and in a high contractile state. This indicates that the PVA concept can be expanded to various arrhythmias unless ESI becomes very short. (+info)
Treatment of catecholamine-sensitive right ventricular tachycardia by endocardial catheter ablation.
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Endocardial catheter ablation with direct current high voltage shocks was performed in a patient with recurrent syncope due to a catecholamine-sensitive ventricular tachycardia that was drug refractory and occurred in the absence of identifiable heart disease. Pace mapping and catheter activation mapping of the spontaneous and isoproterenol-induced ventricular tachycardia located the tachycardia origin in the right ventricular outflow tract. Ablation dramatically reduced spontaneous ventricular tachycardia and ectopic activity (from 50,000 to less than 100 ectopic beats/24 h). The patient has remained symptom free and without ventricular tachycardia recurrence for 3 years. These observations and review of previous studies suggest that catheter mapping can easily locate the arrhythmia focus in the right ventricular outflow tract and that catheter ablation can be performed at low risk. Catheter ablation is a viable option for the treatment of right ventricular catecholamine-sensitive tachycardias that are unresponsive to antiarrhythmic drugs. (+info)
Magnitude and time course of beta-adrenergic antagonism during oral amiodarone therapy.
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To examine the presence and time course of beta-adrenergic antagonism produced by amiodarone, the heart rate, QT interval and arrhythmia frequency in response to graded doses of isoproterenol were evaluated in eight patients treated with oral amiodarone for sustained ventricular tachycardia. Measurements were made before and every 2 days after beginning oral amiodarone therapy (600 mg twice daily). Isoproterenol was given in doses of 12.5, 25 and 50 ng/kg body weight per min. The mean heart rate at rest decreased from 73.1 +/- 17.8 beats/min on day 0 to 57.8 +/- 15.0 beats/min after 12 days of amiodarone therapy. A significant linear decline in heart rate at rest was observed until day 6 (p less than 0.05 for all comparisons). On all days isoproterenol produced a progressive increase in heart rate that reached 115.5 +/- 20.2 beats/min on day 0 and 94.2 +/- 18.5 beats/min on day 12. Amiodarone blunted the heart rate increase produced by isoproterenol on days 2 to 12 (p less than 0.05 versus day 0). This effect was present by day 2 and did not change significantly thereafter. The mean corrected QT (QTc) interval increased from 430 +/- 30 ms on day 0 to 449 +/- 63 ms on day 12. A significant linear increase in QTc interval was observed until day 6 (p less than 0.05 for all comparisons). There was no systematic effect of isoproterenol on the QTc interval. Five of eight patients had a significant number of isoproterenol-induced premature ventricular complexes. Ventricular ectopic activity in response to isoproterenol was abolished after 4 days of amiodarone therapy.(ABSTRACT TRUNCATED AT 250 WORDS) (+info)
The aim of the present study was to describe the clinical and echocardiographic findings of ventricular noncompaction in adult patients. Fifty-three patients underwent complete clinical history, electrocardiogram, Holter and transthoracic echocardiogram. Forty patients (75%) were in class I/II of the New York Heart Association, and 13 (25%) in class III/IV. Ventricular and supraventricular escape beats were found in 40% and 26.4%, respectively. Holter showed premature ventricular contractions in 32% and sustained ventricular tachycardia in 7.5%. Ventricular noncompaction was an isolated finding in 74% of cases and was associated with other congenital heart disease in 26%. Noncompacted ventricular myocardium involved only left ventricle in 62% of the patients and both ventricles in 38%. The mean ratio of noncompacted to compacted myocardial layers at the site of maximal wall thickness was 3.4 +/- 0.87 mm (range 2.2-7.5). The presence of ventricular noncompaction in more than three segments was associated with a functional class greater than II and ventricular arrhythmia with demonstrable statistical significance by chi2(p < 0.003). CONCLUSION: a) Noncompacted cardiomyopathy is a congenital pathological entity that can occur in isolated form or associated with other heart disease and often involves both ventricles. b) A ratio of noncompacted to compacted myocardium greater than 3 and involvement of three or more segments are indicators of poor prognosis. c) Since the clinical manifestations are not sufficient to establish diagnosis, echocardiography is the diagnostic tool that makes it possible to document ventricular noncompaction and establish prognostic factors. (+info)
Evaluation of left ventricular mechanical restitution in closed-chest dogs based on single-beat elastance.
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The mechanical restitution of the left ventricle of closed-chest dogs was modeled as a monoexponential relation, using peak single-beat elastance as a measure of contractile strength. Data were obtained from nine dogs chronically instrumented with three sets of piezoelectric diameter gauges to assess ventricular volume and high-fidelity manometers to measure pressure. Mechanical restitution curves were obtained during both atrial and ventricular pacing in six dogs. The time constant of mechanical restitution was 64.3 +/- 11.4 msec for atrial and 122.2 +/- 26.3 msec for ventricular paced runs (p less than 0.01). These values are smaller than those previously reported from isolated hearts or isolated muscle segments. Although the time of onset of mechanical restitution was longer for atrial than for ventricular runs (255.1 +/- 14.3 versus 225.1 +/- 9.6 msec, p less than 0.05), the plateau to which mechanical function rose was not different. During ventricular pacing, fusion beats were noted in four dogs. The magnitude of the mechanical contribution of these fusion beats fell to a nadir at approximately 250 msec, suggesting that intracellular calcium available for crossbridge interaction is dropping during this time. In three additional dogs, the time constant of postextrasystolic restitution was found to vary depending on the preceding extrasystolic interval. Thus, mechanical restitution of the ventricle is a dynamic process that can be assessed using an elastance-based approach in the in situ heart. (+info)
[Ca2+]i transients in the cardiomyopathic hamster heart.
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Intracellular [Ca2+] transients were studied in isolated hearts of healthy and cardiomyopathic hamsters in late failure perfused with glucose or pyruvate. Hearts of healthy hamsters developed similar pressures when perfused with either glucose or pyruvate, and [Ca2+]i transients were comparable in amplitude when perfused with either substrate. On the other hand, hearts of cardiomyopathic hamsters in late failure developed normal pressure when perfused with pyruvate but developed depressed pressure (50%) when perfused with glucose. The amplitude of [Ca2+]i transients fell severely and was associated with a high diastolic [Ca2+]i in cardiomyopathic hamster hearts when the perfusate was switched from pyruvate to glucose. The high phosphomonoester sugars as evidenced by 31P nuclear magnetic resonance studies and the depressed oxygen consumption in the cardiomyopathic hamster hearts perfused with glucose reflect an inhibition in glycolysis and a subsequent decrease in mitochondrial activity. Without an adequate delivery of substrate to the mitochondria in the cardiomyopathic hamster, the myocardium is no longer capable of maintaining its [Ca2+]i homeostasis. (+info)