PURPOSE: Evaluate efficacy and safety of short-term thrombolysis with recombinant human-tissue plasminogen activator (rtPA). METHODS: Thrombolysis with rtPA was performed in 29 patients with angiographically documented severe acute pulmonary embolism (Miller score of 20/34 or more). All patients received 100 mg rtPA through peripheral veins within the first 2 hr, followed by a continuous infusion of rtPA (0.05 mg/kg/hr) over a 4-hr period. Concomitant intravenous heparin 1000 U/hr infusion was applicated for the first 6 hr. RESULTS: Using this treatment, 83% of our patients showed clinical improvement objectified by the Miller score, by the clinical stage (Grosser), and by the pulmonary artery mean pressure (PAPm). The treatment regimen was unsuccessful if the clinical history lasted more than 3 days. Complications occurred in 10 patients (34%), and 3 patients (10%) died of acute right heart failure. CONCLUSION: The success of rtPA treatment appears to depend on the interval between onset of symptoms and start of thrombolytic therapy. Otherwise the technique leads to objectifiable improvement within 6 hr with an acceptable bleeding risk.

Adult↗

PubMedDate not supplied

Effects of adenosine on electrical activity of isolated guinea pig hearts.

Negative chronotropic and dromotropic effects of adenosine seem to be responsible for its antiarrhythmic action on supraventricular tachyarrhythmias. To further characterize the effects of adenosine on supraventricular arrhythmias heart rate, conduction, refractoriness, the time to steady-state of AV-nodal conduction slowing and of sinus rate reduction were evaluated. Changes of heart rate, conduction intervals and effective refractory periods were determined by the use of a high-resolution ECG recording technique in isolated guinea pig hearts perfused by the method of Langendorff. Adenosine in concentrations of 3 and 10 microM reduced sinus rate and prolonged AV-nodal conduction significantly, while intraventricular and His bundle conduction were not altered. The maximal effect of adenosine on the sinus node and AV nodal conduction occurred after 636 +/- 109 and 111 +/- 35 (mean +/- SE) beats, respectively. During programmed stimulation at a cycle length of 250 ms, adenosine reduced atrial ERP in a dose-dependent manner. At cycle lengths of 170 and 200 ms, adenosine increased the atrial ERP at 3 microM, and then progressively shortened the ERP at higher doses. At all adenosine concentrations used, the usual rate-dependent adaption in ERP was suppressed. These observations explain the efficacy of adenosine against supraventricular tachyarrhythmias where the AV-node forms a part of a reentrant circuit. Adenosine shortened the atrial ERP, but at high pacing rates also led to a relative prolongation of the atrial ERP as the rate-dependent adaption was suppressed. These opposite effects of adenosine may explain earlier contradictory findings of its action on atrial arrhythmias.

Adenosine↗

PubMedDate not supplied

Stereoselective electrophysiological effects of propafenone in Langendorff perfused guinea pig hearts.

The present study was focused on the stereoselective electrophysiological effects of (R)- and (S)-propafenone.HCl evaluated in isolated Langendorff perfused guinea pig hearts. Conduction intervals were measured using an ECG-recording method of high resolution. Refractory periods of the different parts of the myocardium were determined by stimulation with premature stimuli, as well as by stimulation with increasing pacing rate (rate-dependent/refractory periods). Drug concentrations of 0.1, 1 and 3 microM were tested. Both compounds induced a dose-dependent increase in AV-nodal, His-bundle, and intraventricular conduction time which reached significance (p less than 0.01) following 3 microM of either compound. Sinus rate was also dose-dependently and significantly reduced. (R)- and (S)-propafenone.HCl induced a marked prolongation of the rate-dependent refractory period of sino-atrial (by 140 +/- 22%, p less than 0.01 and by 141 +/- 14%, p less than 0.01, respectively) and AV-nodal (by 34 +/- 22%, p less than 0.01 and by 42 +/- 15%, p less than 0.01, respectively) conduction and of the atrial (by 182 +/- 21%, p less than 0.01 and by 195 +/- 15%, p less than 0.01, respectively) and ventricular (by 93 +/- 16%, p less than 0.01 and by 88 +/- 16%, p less than 0.01, respectively) myocardium. The effective refractory periods evaluated by stimulation with premature stimuli were also significantly prolonged under the influence of (R)- and (S)-propafenone.HCl, except the ventricular myocardial refractoriness by (R)-propafenone.HCl (increase to 114 +/- 23%, n.s.). Both compounds showed a strong rate-dependence of their effects and, thus, the refractory periods evaluated by stimulation with increasing pacing rate were significantly more prolonged than the refractory periods evaluated by stimulation with premature stimuli. The main difference between the effects of (R)- and (S)-propafenone.HCl on the cardiac electrical activity is the lack of effect of (R)-propafenone.HCl on the ventricular myocardial refractoriness evaluated by stimulation with premature stimuli.

Animals↗

PubMedDate not supplied

An extended kinetic analysis of valinomycin-induced Rb-transport through monoglyceride membranes.

The time course of the current following a voltage jump, which is applied to monoglyceride bilayers in the presence of valinomycin, shows two relaxation times. This is basically in agreement with a simple carrier model which has been described in full detail formerly. Relaxation times and amplitudes allow a calculation of the rate constants of the transport model. The presented data supplement an analysis which was hitherto based only on the slower relaxation process and on information derived from the nonlinearity of current-voltage characteristics. The additional resolution of the faster relaxation time allowed an approximate determination of the voltage dependence of the translocation rate constant for carrier-ion-complex and provided evidence for a small voltage dependence of the interfacial reaction. The dependence of the relaxation parameters on the ion concentration in the aqueous phase was interpreted assuming a saturation of the ion concentration at the reaction plane at high bulk concentrations.

Biological Transport↗

PubMedDate not supplied

Detection and continuous monitoring of intracardiac low-level potentials from the surface of the Langendorff-perfused heart.

By appropriate placement of two electrodes on the epicardiac surface of Langendorff-perfused hearts, His-bundle and preatrial signals can be recorded by the surface electrogram (S-ECG). These signals are difficult to detect because of their low amplitude of a few microvolts. To improve the monitoring of these low-level potentials we studied the His-bundle spike as detected by intracardiac electrodes and by epicardial records (S-ECG) and compared these signals in the time and frequency domain. The frequency spectra of these cardiograms were used to develop appropriate filters and high-gain amplifiers for a continuous monitoring of the His-bundle signal from the epicardiac surface. By means of such a monitoring system, high-frequency components of preatrial activities could be resolved also. The time coincidence of these spikes to the simultaneously recorded intraatrial electrogram from electrodes positioned near the sinus node and near the His-bundle is demonstrated. Hence, the early atrial signals likely yield information about sinoatrial conduction. Application examples of monitoring His-bundle signals and preatrial signals in a beat-to-beat manner are described also for various conduction blocks or arrhythmias. With this monitor the evaluation of characteristic parameters of the conduction system of the heart like HV-, AH- and A'H-time, and likely, SACT can easily be performed for every heartbeat on a digital oscilloscope with low resolution or a two-channel chart recorder. Small and intact hearts can be used with this system to detect intracardiac low-level potentials during the heart beat.

Animals↗

PubMedDate not supplied

Continuous ECG measurements of intracardiac activity from the surface of Langendorff-perfused guinea pig hearts.

The present paper describes a method by which it is possible to continuously detect early atrial and His-bundle activity from the surface of intact Langendorff-perfused guinea-pig hearts, by appropriate placement of two electrodes and the use of a custom designed instrumentation-amplifier. In some experiments the surface ECG recordings were compared with intracardiac ECG recordings. No difference in ECG durations could be observed between intracardiac and extracardiac measurements. In further experiments changes in ECG durations and heart rate were measured for 2 h. After 30 min equilibration time, no changes in heart rate and conduction time could be observed. In order to locate the best surface electrode positions to detect His-bundle activity, vector ECG recordings were taken at high gain. This vector ECG signal contained a His-loop which was split into a larger and a smaller part. The main and initial vector was directed to the left and the smaller to the right ventricle. The best recordings of the His-bundle activity could be observed when the electrodes were positioned as follows; one in a posterior position, near the valve plane and the other one in the opposite position near the initial part of the anterior interventricular artery and in the direction of the large His-loop. We conclude that the ECG surface recordings are a valuable tool for measuring impulse propagation through various segments of the cardiac conduction system in preparations of guinea-pig hearts, perfused by the Langendorff method.

Animals↗

PubMedDate not supplied

Modulation of cardiac impulse generation and conduction by nifedipine and verapamil analyzed by a refined surface ECG technique in Langendorff perfused guinea pig hearts.

Using a modified Langendorff system, a special ECG recording technique and appropriate placement of two silver wire electrodes, early atrial and His bundle activity can be detected continuously from the surface of intact and spontaneously beating guinea pig hearts. This new method was applied to measure the direct and inhibitory effects of nifedipine and verapamil on impulse generation and conduction in isolated and perfused guinea pig hearts. Depression of sinoatrial conduction was the most prominent effect of nifedipine. In all concentrations applied (10(-7) M, 10(-6) M, 10(-5) M) nifedipine predominantly led to sinoatrial blocks of different degrees. Heart rate decreased slightly in a dose-dependent manner. PQ and HV duration remained essentially constant. In the highest concentration of nifedipine (10-5) M), sinus node activity was so depressed that AV dissociation or ventricular rhythm developed. Only in one out of eight experiments with cumulative increase of nifedipine concentrations to 10(-5) M was the AV node affected by nifedipine and a second-degree AV block developed (10(-6) M). Verapamil's inhibitory effects on the rate of impulse initiation in the sinus node were more pronounced than those of nifedipine, but the inhibition of sinoatrial conduction by verapamil was less marked. At 10(-6) M verapamil, the incidence of sinoatrial blocks and of ventricular rhythm was similar to the incidence of first degree AV blocks. PQ time (+14%) but also HV time (+12%) were prolonged under the influence of this concentration of verapamil. At the highest concentration of verapamil (10(-5) M) applied for 10 min, ventricular rhythm developed in five out of eight experiments, as well as one second and two third-degree AV blocks. The results confirm that the simultaneous measurements of sinus node activity of sinoatrial and atrioventricular conduction and of HV duration is feasible with this ECG technique, to evaluate the inhibitory effects of Ca-antagonists on sinus and AV node activity in the intact heart.

Animals↗

PubMedDate not supplied

The effects of the propranolol enantiomers on the intracardiac electrophysiological activities of Langendorff perfused hearts.

The optical isomers of the beta blocking agent propranolol exert beta receptor blocking as well as membrane stabilizing effects. The latter is thought to be responsible for the antiarrhythmic effect of the drug. In this study we quantified the electrophysiological effects of both isomers of propranolol on the conduction and pacemaker system of the heart. The experiments were performed on isolated hearts using a special ECG recording and stimulation technique. To abolish isoproterenol's beta adrenergic stimulatory effect on heart rate, 30-times higher concentrations of (+)propranolol were necessary than of (-)propranolol in order to be consistent. Both isomers caused a similar and marked slowing of conduction velocity through the bundle of His and ventricular myocardium. Also, heart rate, as well as atrio-ventricular conduction velocity were significantly slowed by a concentration of 10 microM of either drug, (-)propranolol being slightly more effective. Only in the presence of (-)propranolol did significant changes of atrio-ventricular and His-bundle conduction occur at a concentration of 1 microM. During programmed stimulation sinus node recovery time was more prolonged by (-)propranolol than during perfusion with (+)propranolol. The highest rate of pacing with 1:1 conduction of the sino-atrial conduction, the atrial and ventricular myocardium was significantly depressed to a comparable degree by either isomers of propranolol. These effects appear to be primarily responsible for the antiarrhythmic effects of both isomers. Because of the minor effects of (+)propranolol on sinus- and AV-node activity, as well as on beta adrenergic receptors, this isomer may have potential clinical importance in the treatment of arrhythmias.

Animals↗