The effect of tetrodotoxin (TTX), lidocaine, and quinidine on the transient inward current (TI) was studied in voltage-clamped sheep cardiac Purkinje fibres. The TI was induced by elevation of extracellular Ca or addition of strophanthidin. Reduction of external Na had a biphasic effect on the steady state TI magnitude; a moderate (less than 50%) reduction of external Na had an enhancing effect on the TI; a further decrease of extracellular Na was accompanied by a decline of TI amplitude. The TI could not be induced in Na-free medium (external Ca less than or equal to 9.0 mM). TTX, lidocaine, and quinidine reduced the magnitude of the TI in a dose-dependent way. The blocking effect of these agents could be compensated for by a moderate (less than 50%) reduction of external Na or an elevation of extracellular Ca. It is suggested that the blocking effect of TTX, lidocaine, and quinidine on the TI is due to a reduction of intracellular Na, which causes a decay of intracellular Ca via the Na-Ca exchange mechanism.

Animals↗

PubMedDate not supplied

Vulnerability of the right ventricle to cathodal, anodal, and bipolar stimulation at double diastolic threshold strength.

UNLABELLED: The repetitive ventricular response (RVR) to three stimulation techniques (bipolar, cathodal and anodal) was investigated in 35 patients. 26 patients suffered from coronary heart disease and 9 patients from dilative cardiomyopathy. The stimulation study was performed at a ventricular driving rate of 120/min with one and two premature ventricular extrastimuli. We used rectangular impulses of 1.8 ms duration at double diastolic threshold strength. RVR was scored as follows: 0: no RVR, 1: one nonstimulated RVR, 2: two nonstimulated RVR, 3: three nonstimulated RVR, 4: four to ten nonstimulated RVR, 5: more than ten nonstimulated RVR lasting less than 2 minutes, 6: sustained ventricular tachycardia or ventricular fibrillation. We found that with unipolar anodal stimulation the diastolic threshold was significantly greater and the effective refractory period of the right ventricle was significantly shorter as compared to the other stimulation techniques. Between the three different electrode configurations there were no significant differences concerning the number of consecutive ventricular depolarizations following premature stimulation. CONCLUSION: the phenomenon of RVR is not influenced by the stimulation technique (bipolar, cathodal and anodal) at double diastolic threshold.

Adult↗

PubMedDate not supplied

Biplane transesophageal color Doppler echocardiography for assessment of mitral valve area with mitral inflow jet widths.

Biplane transesophageal color Doppler echocardiography can image the mitral valve orifice in two orthogonal views. If the maximal stenotic jet width through the mitral valve obtained with the vertical transducer represents the major axis, the stenotic jet width dissected by the horizontal transducer should be the minor axis of the mitral orifice. Thus the mitral valve area can be calculated assuming an oval shape of mitral orifice. Nineteen patients with mitral stenosis were investigated. Maximal mitral stenotic jet width (JW1) was searched on a vertical plane and the jet width from the orthogonal view (JW2) was obtained on a horizontal plane. Mitral valve areas from the color Doppler jet widths were calculated by pi.JW1/2.JW2/2 and compared with those derived from Gorlin's formula. Adequate quality of echocardiographic images could be obtained in all patients for transesophageal color Doppler jet width measurements or Doppler pressure half-time determinations and in 16 of 19 patients for transthoracic planimetery of the mitral orifice at the parasternal short axis. Mitral valve areas derived from biplane transesophageal color Doppler imaging (1.31 +/- 0.53 cm2) were not different from those calculated according to Gorlin's formula from the catheterization data (1.25 +/- 0.50 cm2), those determined by transthoracic echocardiographic planimetery (1.38 +/- 0.5 cm2), or those calculated from the Doppler pressure half-time method (1.32 +/- 0.41 cm2) (difference not significant by analysis of variance). There was a very strong correlation between transesophageal echocardiographic mitral valve areas and those derived from catheterization data (r = 0.94; standard error of the estimate = 0.13 cm2). A similar correlation was obtained for the planimetric echocardiographic method (r = 0.94; standard error of the estimate = 0.14 cm2). A slightly less strong correlation was found between mitral valve areas derived from the Doppler pressure half-time method and those derived from Gorlin's formula (r = 0.83; standard error of the estimate = 0.24 cm2). The pressure half-time method accurately predicted the mitral valve area in most (15/19) patients, but it significantly (> 0.4 cm2) overestimated mitral valve area in two patients with aortic regurgitation and underestimated (< 0.4 cm2) mitral valve area in two patients with left ventricular hypertrophy. Determination of mitral valve area by color Doppler biplane transesophageal echocardiography is an alternative for accurate estimation of mitral valve area and may be most useful in intraoperative monitoring during surgical or balloon mitral commissurotomy or in the case of inadequate imaging quality of transthoracic echocardiography.

Adult↗

PubMedDate not supplied

Electrophysiological actions of lorcainide in patients with cardiac disease.

Lorcainide is a new antiarrhythmic agent which effectively suppresses ventricular premature contractions. Its electrophysiological actions were studied in 15 cardiac patients with and without cardiac conduction abnormalities. In a dose of 2 mg/kg body weight, lorcainide decreased the sinus cycle length (SCL) and increased the corrected sinus node recovery time. The intra-atrial, atrioventricular (AV), and intraventricular conduction times were prolonged. A third-degree AV block developed in 2 patients with pre-existing conduction abnormalities. QRS widening showed that intramyocardial conduction was also affected. The effective refractory period of the atrioventricular node (ERP-AVN) was shortened, whereas the effect on the functional refractory period of the AVN was variable. The decrease in SCL and ERP-AVN may be due to a possible anticholinergic effect of the drug. The accessory pathway was blocked in 3 patients with a Wolff-Parkinson-White syndrome. The ERP of the ventricle was slightly prolonged. The electrophysiological profile of the drug, i.e., slowing of conduction velocity throughout the heart combined with shortening of SCL and ERP-AVN, differs from other antiarrhythmic agents.

Acetanilides↗

PubMedDate not supplied

Clinical electrophysiological properties of N-allyl-clonidine (ST 567) in man.

The electrophysiological properties of N-allyl-clonidine (ST 567) were studied in 18 patients. Four of these patients were pretreated with intravenous propranolol, 0.2 mg/kg, and atropine, 0.04 mg/kg, to induce autonomic blockade. ST 567 produces a sustained bradycardiac effect at a dose of 40 mg, i.v., in patients without (group I) and with (group II) autonomic blockade. The mean increase in Group I was 23% and in group II, 42%. The sinus node recovery time increased in both groups, from 1,151 +/- 73 to 1,310 +/- 81 msec in group I, and from 995 +/- 145 to 1,599 +/- 248 msec (means +/- SEM) in group II. The corrected sinus node recovery time was unaffected by ST 567 in Group I and increased from 165 +/- 50 to 427 +/- 117 msec in group II. The sinoatrial conduction time was unaffected by ST 567 in group I. The effective refractory period of the right atrium, the atrioventricular node and the right ventricle, as well as the functional refractory period of the atrioventricular node, were unaffected by ST 567 in patients without autonomic blockade. Intra-atrial, atrioventricular, and intraventricular conduction were also not altered by this drug. Thus, the electrophysiological profile of ST 567 differs from other bradycardia-inducing agents such as beta-blockers or calcium antagonists.

Adult↗

PubMedDate not supplied

Pharmacokinetic and pharmacodynamic properties of alinidine in man.

The elimination kinetics of alinidine and the changes in heart rate and blood pressure were determined in five health subjects following intravenous and oral administration of single doses of 40 mg alinidine. The plasma concentration after the intravenous injection declined at least biexponentially with time, with mean half-lives of 0.6 +/- 0.15 h and 3.9 +/- 0.28 h for the distribution and the elimination phase, respectively. The mean total clearance amounted to 40.3 +/- 8.9 L/h and the renal clearance to 33.6 +/- 12.3 L/h. The bioavailability following oral administration was nearly complete (0.92 +/- 0.06). Alinidine produced a modest bradycardia effect in healthy subjects. The maximal decrease in the heart rate was 19.2 +/- 7.7% (p less than 0.05) and 14.2 +/- 8.1% (p less than 0.05) following intravenous and oral administration, respectively. Time intervals in surface electrocardiogram (duration of the P- wave, PG time, QRS duration, and QTc) were not significantly altered by alinidine after both routes of administration. There was also a slight but consistent decrease in the systolic blood pressure (3-8%) after both routes of administration, whereas the diastolic blood pressure remained unchanged.

Adult↗

PubMedDate not supplied

Pharmacokinetics and pharmacodynamics of the 5-HT2 receptor antagonist ketanserin in man.

We determined the pharmacokinetics of ketanserin and its effects on blood pressure and heart rate in eight healthy volunteers following single-dose intravenous (10 mg) and oral (20 mg) administration of ketanserin. Following intravenous injection, plasma concentration-time data could most adequately be described by an open, three-compartment model. Plasma concentration declined with a mean terminal half-life of 15.6 +/- 6.2 h (mean +/- SD). Total clearance and volume of distribution at steady state were 0.39 +/- 0.07 L/kg/h and 3.3 +/- 1.1L/kg, respectively. The free fraction in plasma determined by equilibrium dialysis was 9.36 +/- 0.56%. Following single oral doses, a bioavailability of 0.51 +/- 0.06 was estimated. The half-life of the elimination phase tended to be somewhat longer (18.5 +/- 5.1 h, p greater than 0.05) than after intravenous administration. In addition, pharmacokinetics and effects of ketanserin on blood pressure and heart rate were investigated in two healthy volunteers after continuous treatment with ketanserin (20 mg three times a day) over a period of 5 days. No evidence of time-dependent nonlinear changes in pharmacokinetics was observed. Following single-dose as well as continuous treatment with ketanserin, no significant changes either in systolic and diastolic blood pressure or in pulse rate could be detected.

Adult↗

PubMedDate not supplied

DDD(R) pacing with automatic mode switch in patients with paroxysmal atrial fibrillation following AV nodal ablation.

Optimal pacing in patients with paroxysmal atrial fibrillation/flutter following AV node ablation remains to be determined because VVIR pacing cannot restore AV synchronization and conventional DDD(R) pacing cannot properly cope with atrial tachyarrhythmias. The objective of the present investigation was to study the clinical outcome of 16 of these patients who received a new DDDR pacemaker with an automatic mode switch (Thera DR; Medtronic) immediately after AV node ablation. Arrhythmia-related symptoms before ablation were palpitations in 12, dizziness in 10, exercise intolerance in 8, and syncope in 6 patients. Pacing modes at hospital discharge were DDDR (n = 14) and DDD (n = 2) with an activated mode switch in all patients. After 1 month 12 patients were symptom free. Clinical events occurred in 4 patients (palpitations in 2, dizziness in 1, chest pain in 1, and fatigue in 1), which could be relieved in 3 patients. At discharge as well as at the 1-month follow-up, Holter ECG recorded a total of 12 episodes of atrial fibrillation in 5 patients, which were correctly detected by the pacemaker and followed by mode switching. At the 3-month follow-up (n = 14), 12 patients were symptom free and 2 continued to report symptoms which could not be resolved. All patients remained on an automatic mode switch in either the DDDR (n = 12) or DDD (n = 2) mode. There were no hints of inappropriate mode switching or reports of pacemaker syndrome, and there were no new symptoms related to automatic mode switching. The patients studied were highly symptomatic before implantation due to paroxysmal atrial fibrillation/flutter. After the first follow-up, 81% of the patients reported no symptoms. Paroxysmal atrial fibrillation/flutter combined with a high-degree AV-block seems no longer to be a contraindication for AV-synchronous pacing.

Atrial Fibrillation↗

PubMedDate not supplied

[Cholestyramine interrupts the enterohepatic circulation of phenprocoumon: a new therapeutic possibility in the treatment of phenprocoumon overdose].

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4-Hydroxycoumarins↗