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Biomedical subjects

W Haverkamp

Publications and source records attributed to W Haverkamp.

140 records · Page 8Linked to original sources
PubMed1989

[Ion regulation disorders and cardiac arrhythmia. The relevance of sodium, potassium, calcium, and magnesium].

1. Among the dysionemias hyper- and hypokalemia are particularly important for clinical arrhythmogenesis. Disorders in sodium- and calcium concentrations, however, are relevant only in single cases. The impact of magnesium concentration disorders on cardiac rhythm is not yet totally elucidated. 2. In hypokalemia tachycardic arrhythmias are most important, while bradycardic and tachycardic arrhythmia can be caused by hyperkalemia. An important factor in arrhythmogenesis is the rate of development of hypo- or hyperkalemia. Hypokalemically-induced arrhythmia can be suppressed by potassium substitution. 3. Although the importance of a magnesium dysionemia for arrhythmogenesis has not been confirmed, magnesium can be used for the treatment of arrhythmias with good results. Besides an antiarrhythmic efficacy, an antifibrillatory activity is suggested in acute myocardial ischemia.

Animals↗
PubMed1989

Electrophysiologic, haemodynamic and antiarrhythmic effects of the new class Ic agent 1-(2'-biphenyloxy)-2-tert.-butylamino-propanol-2-hydrochloride.

The electrophysiological, antiarrhythmic and haemodynamic profile of the new compound GK 23-G (1-(2'-biphenyloxy)-2-tert.-butylamino-propanol-2-hydrochloride, proposed INN: bipranol) was examined using dogs models relevant to conditions in humans. In the first part of the study, dose-related effects of cumulatively increasing doses of GK 23-G (0.2-12.8 mg/kg) on intracardiac conduction, ventricular refractoriness and on haemodynamic parameters of the non-ischemic heart were determined in six anesthetized mongrel dogs. In the second part of the study, antiarrhythmic actions of bipranol on "delayed reperfusion ventricular arrhythmias" following release of coronary artery occlusion after 2 h of obstruction were investigated in another six dogs. The results show: GK 23-G causes a significant prolongation of HV-time, QRS-duration and ventricular refractory period at mid-range and high doses (greater than or equal to 3.2 mg/kg). QT-time does not change. Atrial refractory period is significantly lengthened at the maximum dose of 12.8 mg/kg. There are no significant changes in heart rate, systolic and diastolic aortic pressure and cardiac output. Up to 12.8 mg/kg, GK 23-G does not influence left ventricular contractility (dp/dtmax). In acute myocardial necrosis "delayed reperfusion arrhythmias" are almost completely abolished at a dose of 1.6 mg/kg + 50 micrograms/kg x min. Thus, because of its antiarrhythmic potency, further experimental and clinical testing of the new compound seems promising.

Animals↗
PubMed1988

[Experimental and initial clinical experiences with the new class Ib anti-arrhythmia agent barucainide].

Barucainide is a new class Ib-antiarrhythmic compound which causes a reduction of the upstroke velocity and shortens the duration of the action potential in a dose-dependent fashion. The electrophysiological, hemodynamic and antiarrhythmic effects of the new drug were analyzed in experimental and clinical investigations. The results show that barucainide, in a dose range varying between 0.125-4.0 mg/kg i.v. fails to exert any significant effect on cardiac conduction and refractory times, heart rate, arterial blood pressure, cardiac output and left ventricular contractility. In a standardized animal model of ventricular arrhythmia, barucainide proved to be superior to lidocaine with respect to its antiarrhythmic potency. In a group of patients displaying chronic, otherwise therapy-resistant ventricular arrhythmias, the drug was effective in the majority of cases. Tolerance was excellent over a maximum observation period of 18 months. According to our first experimental and clinical observations, further testing of barucainide appears promising. The drug may be of particular value for treatment of ventricular arrhythmias in cases with left ventricular dysfunction, heart failure and severe conduction disturbances.

Adult↗
PubMed1988

[Results of thrombolytic therapy in acute myocardial infarct].

Acute thrombosis of highly stenosed coronary arteries often results in acute myocardial infarction. The rationale for thrombolytic therapy is to restore blood flow before irreversible myocardial cell damage develops. In this review the results of more than 60 interventional studies in which reperfusion or "patency" rates, left ventricular function, infarct size, as well as intrahospital and long-term mortality following thrombolytic therapy were assessed, are reported and analyzed with respect to the patterns of applying thrombolytic therapy (different thrombotic agents and percutaneous transluminal coronary angioplasty). The results show that a significant reduction in infarct size, improvement in left ventricular function, and decrease in early- as well as late-mortality can be achieved when successful recanalization is established within four hours after onset of symptoms. Thrombolytic efficacy with respect to patency rates is highest after intravenous application of so-called fibrin-selective thrombolytic agents (rt-PA) and APSAC (71% and 73%), intracoronary application of streptokinase (69%), and primary percutaneous transluminal coronary angioplasty (88%). By contrast, intravenous infusion of streptokinase results in recanalization of only 56% of occluded vessels. However, the improved reperfusion rates after treatment with rt-PA or intracoronary application of streptokinase are associated with a relatively high incidence of reocclusion (up to 20%). Patients' prognosis after successful initial thrombolysis is essentially influenced by additional interventions, e.g., percutaneous transluminal coronary angioplasty and surgical revascularisation. At present, several questions about the ideal thrombolytic agents or the optimal timing of additional interventions need to be clarified. Further studies are necessary to answer these questions.

Angioplasty, Balloon↗
PubMed1988

[Preventive antifibrillatory treatment of sudden cardiac death in acute myocardial infarct].

The pathophysiological basis of sudden cardiac death due to ventricular arrhythmias in acute myocardial infarction has been extensively investigated in experimental as well as in some clinical studies. Numerous clinical studies have been performed with the aim to establish the feasibility of antifibrillatory prophylaxis of sudden cardiac death by pretreatment with antiarrhythmic drugs. Using class I-antiarrhythmic drugs the reported findings were contradictory. While the antiarrhythmic efficacy of Lidocaine and other, newer class I-antiarrhythmic drugs is well established, the antifibrillatory effects of these drugs in the early phase of acute myocardial infarction remain uncertain. In clinical studies with the endpoint of mortality in patients at risk, longterm administration of orally effective class I-antiarrhythmic drugs did not prove to be superior to placebo. However, beta-sympatholytic agents have been shown to reduce mortality in patients at risk in several large clinical studies. The basic mechanism seems to be primarily a reduction in sudden cardiac death which is caused predominantly by ventricular fibrillation. The antifibrillatory properties of beta-blockers was demonstrated as well by a reduction in the number of episodes of ventricular fibrillation. The recognition of patients at risk who profit most from chronic beta-blocker therapy remains the main problem when treatment of numerous low-risk patients is avoided. In the ISIS I-study with Atenolol intravenous administration of a beta-blocker in the early phase of acute myocardial infarction has been shown to be beneficial if hemodynamic monitoring, for example using flow-directed heart catherization is performed. In general this does not apply to the treatment with calciumantagonists, especially with Verapamil and Nifedipine. These drugs do not improve prognosis of acute myocardial ischemia, obviously because of hemodynamic side effects. The antifibrillatory efficacy of Verapamil-type calciumantagonists, shown in the experimental model, could not be demonstrated in the clinical setting. Nevertheless, further clinical studies performing longterm prophylactic treatment of patients at risk before the onset of myocardial ischemia seem to be worthwhile. Concerning class III-antiarrhythmic agents, clinical experience in the setting of acute myocardial infarction is limited; hence a final conclusion about their antifibrillatory efficacy under clinical conditions at present is impossible.

Anti-Arrhythmia Agents↗
PubMed1988

[The incidence of ventricular arrhythmia following direct current ablation, high-frequency current ablation and laser photo-ablation].

Incidence and severity of ventricular arrhythmias (VA) following transvenous catheter ablation have so far not been fully elucidated. In the present study we evaluated the comparative incidence of postablation ventricular arrhythmias following high voltage-direct current electrical ablation (DCA), radiofrequency-ablation (RFA), and laser-photoablation (LPA). Experiments were performed on a total of 26 anesthetized mongrel dogs (BW: 20-30 kg). DCA (n = 14; 150-200 J) and RFA (n = 7; 38.5-72.5 J) were performed unipolarly via a 6F USCI catheter, LPA (n = 5; 40-80 J) was delivered through a quarz core fiber (diameter 0.4 mm) housed within a special designed catheter. Energies were delivered to various sites of free wall and apical endocardium of the left ventricle. Immediately after DCA fast runs of ventricular tachycardia (VT) developed in 13 out of 14 dogs degenerating into ventricular fibrillation in two animals. Mean cycle length of induced VT was 298 +/- 86 ms. Persistent VA, morphologically mainly characterized by an accelerated idioventricular rhythm interrupted by runs of ventricular salvoes, occurred in 12 animals (mean rate: 78 +/- 13 VPB/min 3 h after ablation). During VT early endocardial activations were recorded from the ablation site. No significant correlation between total applied energy (150-550 J) and incidence of arrhythmogenic effects was observed. RFA and LPA induced ventricular salvoes and runs of non-sustained ventricular tachycardia, in one animal ventricular fibrillation occurred during RFA; however, no persistent arrhythmic activity developed after RFA and LPA, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Calcium antagonists and acute myocardial ischemia: comparative effects of gallopamil and nifedipine on ischemia-induced and reperfusion-induced ventricular arrhythmias, epicardial conduction times, and ventricular fibrillation thresholds.

The comparative effects of the calcium-antagonists gallopamil and nifedipine on ischemia-induced and reperfusion-induced ventricular arrhythmias, particularly ventricular fibrillation (VF), were assessed in a total of 40 mongrel dogs in two experimental preparations. In part I of the study, changes in the time course of spontaneous ventricular arrhythmias and VF parallel to changes in epicardial conduction following acute coronary artery occlusion lasting 20 minutes and followed by subsequent reperfusion were determined. In part II, repeated coronary artery occlusions (20 min) followed by reperfusion (60 min) were performed, and changes in ventricular fibrillation threshold (VFT) were assessed. Gallopamil proved to be highly effective in preventing ventricular arrhythmias and VF following coronary delay was reduced. The ischemia-induced fall in conduction delay was reduced. The ischemia-induced fall in VFT occurring during the first few minutes after occlusion (phase Ia) was significantly reduced. In contrast, nifedipine failed to influence the incidence of ventricular arrhythmias and VF. Following reperfusion, neither drug reduced the incidence of VF nor the associated fall in VFT at the onset of reperfusion. The time course of recovery of epicardial conduction was not affected by either drug. However, the increase in the VFT during the early postreperfusion period was significantly enhanced by both agents. The effects of gallopamil were more pronounced than those of nifedipine. Delayed reperfusion ventricular arrhythmias arising 5 to 10 minutes after release of coronary artery obstruction were significantly reduced by gallopamil whereas nifedipine proved ineffective. The results show that calcium antagonists display direct antiarrhythmic and cardioprotective actions in acute transient myocardial ischemia. The different effectiveness of gallopamil compared to nifedipine can be explained by differences in electrophysiological properties of the drugs. Enhanced ventricular vulnerability following acute transient coronary artery occlusion and subsequent release of coronary artery obstruction, first described by Tennant and Wiggers, has been extensively investigated over the past decade in a variety of experimental and clinical settings. However, the basic mechanisms underlying ischemia- and reperfusion-induced ventricular arrhythmias and ventricular fibrillation (VF) have not yet been fully elucidated. Furthermore, the results of pharmacological approaches to prevent ventricular arrhythmic activity are conflicting. The present study aimed to evaluate the antiarrhythmic efficacy of calcium antagonists in acute myocardial ischemia and reperfusion. We have examined the effects of gallopamil and nifedipine on the time course of ventricular arrhythmias during the first 20 minutes after acute coronary artery occlusion and subsequent reperfusion. We have studied the underlying mechanisms by mapping epicardial conduction and by assessing the electrically induced ventricular fibrillation threshold (VFT) both within and outside ischemic areas.

Animals↗
PubMed1987

Use of diprafenone, a new potent propafenone-analogue, in acute experimental myocardial ischaemia and infarction.

Diprafenone (D) is a new class I c antiarrhythmic agent, structurally similar to propafenone. We assessed its antiarrhythmic and anti-fibrillatory effects during acute coronary occlusion and reperfusion and the underlying mechanisms of action by epicardial mapping of the conduction delay; also the effects of D on stimulus-induced ventricular tachycardia 18-24 h after permanent coronary occlusion were assessed. Experiments were performed on 32 mongrel dogs with temporary coronary occlusion lasting 20 min and subsequent reperfusion. Control ligations in 16 animals were compared to ligations after pretreatment with D (2 mg kg-1) in 6 dogs. In another 10 dogs a permanent coronary occlusion was performed and the inducibility of ventricular tachycardia was assessed by programmed stimulation before and after D (2.4 mg kg-1). Following D the incidence of ventricular arrhythmias including rapid ventricular tachycardias was not reduced during acute coronary occlusion, but even enhanced in some animals, whereas the frequency of ventricular fibrillation was diminished. No significant difference was observed following reperfusion. Conduction delay in the ischaemic area increased significantly during both phase Ia and Ib following pretreatment with D. During reperfusion conduction delay was significantly prolonged in the D group. At 18-24 h after permanent coronary occlusion the new compound proved to be highly effective in suppressing stimulus-induced ventricular tachycardia. During acute coronary occlusion D diminished the incidence of ventricular fibrillation. D is similar to other class Ic compounds; however, there are some important differences with respect to its additional beta-sympatholytic activity.

Acute Disease↗
PubMed1987

Comparative investigations on the antiarrhythmic and electrophysiological effects of various calcium antagonists (diltiazem, verapamil, gallopamil, nifedipine) following acute transient coronary artery occlusion and reperfusion.

The effects of various calcium antagonists on ventricular arrhythmias, particularly fibrillation (VF), in relation to epicardial conduction delay during acute myocardial ischaemia and reperfusion were investigated in 40 open-chest anaesthetized dogs. Acute transient coronary artery occlusion lasting 20 min was performed in all animals. Sixteen dogs served as controls; diltiazem (D) (0.5 mg kg-1 iv), verapamil (V) (0.25 mg kg-1 iv), gallopamil (G) (0.13 mg kg-1 iv) and nifedipine (N) (0.04 mg kg-1 iv) were given in six animals each 5 min prior to coronary occlusion. Epicardial conduction delay was assessed by means of an epicardial mapping electrode array consisting of 42 bipolar electrodes. In the control group, conduction delay showed a bimodal time course in the ischaemic area with a maximum of 38 +/- 10 ms 6 min after coronary occlusion followed by partial improvement. After pretreatment with D, V or G the peak in conduction delay as well as the maximum dispersion of conduction times in the ischaemic area were significantly diminished, whereas N failed to improve conduction in the ischaemic area. Correspondingly, ventricular arrhythmias and VF were almost completely suppressed by D, V or G, but not affected by N. Following release of coronary artery occlusion none of the compounds proved to influence the rapid and heterogeneous improvement of conduction immediately after the onset of reperfusion. Correspondingly, none of the drugs diminished the incidence of VF immediately after release. Delayed ventricular reperfusion arrhythmias, arising parallel to complete restoration of conduction, were significantly reduced by D, V and G but not affected by N. Delayed and inhomogeneous activation of the ischaemic myocardium plays an important role in the genesis of ventricular arrhythmias in the early stage of acute myocardial ischaemia; thus a reduction in conduction delay and dispersion of conduction times seems to be a precondition for antiarrhythmic action. The different effects of calcium antagonists type V and type N on ischaemia-induced conduction delay and ventricular arrhythmias can be assumed to result from differences in the electropharmacological properties of the compounds.

Acute Disease↗
PubMed1987

Comparative investigations on the antiarrhythmic and electrophysiologic effects of class I-IV antiarrhythmic agents following acute coronary artery occlusion.

The effects of class I to IV antiarrhythmic drugs on ventricular arrhythmias, particularly ventricular fibrillation, in relation to epicardial conduction delay during acute myocardial ischaemia were investigated in 40 open-chest anaesthetized dogs. In these animals transient coronary artery occlusion lasting 20 minutes was performed. Sixteen dogs served as controls; four groups of 6 dogs each received lidocaine (2 mg kg-1 + 50 micrograms kg-1 over 20 minutes), metoprolol (2 mg kg-1 i.v.), d-sotalol (5 mg kg-1 i.v.) and verapamil (0.25 mg kg-1 i.v.), respectively 5 minutes prior to coronary occlusion. Epicardial conduction delay was assessed by means of an epicardial mapping electrode array consisting of 42 bipolar electrodes. In the control group conduction delay displayed a bimodal time course in the ischaemic area with a maximum of 38 +/- 10 ms 6 minutes after coronary occlusion followed by a partial improvement after 12 to 15 minutes. After pretreatment with lidocaine the peak conduction delay in the ischaemic area was significantly increased (43.2 +/- 12), whereas metropolol (21.5 +/- 1.9), d-sotalol (16.6 +/- 3.7) and verapamil (16.3 +/- 3.1) significantly reduced conduction delay. Correspondingly, ventricular arrhythmias and fibrillation were almost completely prevented by metoprolol, d-sotalol or verapamil, but increased by lidocaine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Electrophysiologic effects of asocainol, a new antiarrhythmic agent with predominant class I action.

In experiments on 6 mongrel dogs the electrophysiologic effects of the new antiarrhythmic compound (+/-)-6,7,8,9-tetrahydro-2,12-dimethoxy-7-methyl-6-phenethyl-5H- dibenz[d,f]azonin-1-ol (asocainol) were examined in the non-ischemic heart. The PR interval increased significantly following doses of 5 mg/kg caused by a conduction delay in the His-Purkinje system. At high doses (10 mg/kg) the QRS duration was also prolonged. Atrial and ventricular effective refractory periods were only slightly increased. Asocainol significantly increased the atrial fibrillation threshold, whereas the ventricular fibrillation threshold was not altered. Hemodynamics were not changed except for a slight increase in heart rate after 10 mg/kg asocainol. Thus asocainol predominantly exhibited class Ia antiarrhythmic properties, whereas calcium antagonistic actions could not be established in this intact dog heart model.

Animals↗
PubMedDate not supplied

Anisotropic conduction characteristics in ischemia-reperfusion induced chronic myocardial infarction.

OBJECTIVES: Anisotropic properties of cardiac tissue play an important role in initiation and perpetuation of ventricular tachycardia. However, anisotropic conduction properties in different morphologic types of chronic myocardial infarctions as well as frequency dependency still need to be elucidated. In the present study, the characteristics of anisotropic conduction were investigated in situ in the setting of ischemia-reperfusion induced chronic myocardial infarction. METHODS: Myocardial infarction was induced in 12 dogs by a percutaneous transcatheter left anterior descending coronary artery occlusion-reperfusion technique. Four additional dogs served as normal controls. After 14 to 20 days, epicardial mapping was performed using simultaneous unipolar recordings from 240 electrodes of a plaque electrode array placed on the epicardial border zone overlying the infarctions. Constant rate pacing with five cycle lengths (CL) ranging from 500 to 200 ms as well as programmed electrical stimulation (PES) with four basic cycle lengths (BCL) ranging from 430 to 300 ms and single extrastimuli (S2) were performed. RESULTS: Two anatomically different patterns of epicardial surface morphology were analyzed, designated as type I and type II. In seven animals, there was a continuous thin layer of surviving epicardial muscle fibers overlying the infarction (type I). During pacing with CL of 500 vs 200 ms, conduction velocity longitudinal to fiber orientation (theta L) decreased significantly in the infarcted animals compared to control group (10.9% vs 5.2%, p < 0.05) whereas conduction velocity transverse to fiber axis (theta T) decreased to a similar degree in control and infarcted animals (6.9 vs 7.4%, n.s.). After premature stimulation, there was considerably greater reduction in theta L in infarcted animals than in controls (39.8% vs 31.5%, p < 0.05) whereas theta T decreased to a similar extend in infarcted and control animals (22.2% vs 21.4%, n.s.). During constant rate pacing and premature stimulation, no functional conduction block was induced in type I infarctions. In five animals, the transmural infarctions clearly extended to the epicardial surface, but continuous strands of surviving epicardial muscle fibers traversed the area of necrosis (type II). During PES with S2, functional conduction block and areas of very slow conduction were observed in each case. CONCLUSIONS: In ischemia-reperfusion induced chronic myocardial infarctions, different epicardial patterns of morphology were observed. Anisotropic conduction was frequency dependent in the longitudinal but not in the transverse direction. In type I infarctions, functional conduction block was not inducible during PES whereas in type II infarctions, prerequisites for reentrant arrhythmias like functional conduction block and very slow conduction were induced in each case by single extrastimuli.

Animals↗
PubMedDate not supplied

Simultaneous in utero assessment of AV nodal and ventricular electrophysiologic parameters in the fetal sheep heart.

BACKGROUND: Fetal tachyarrhythmias are usually of supraventricular origin. To investigate whether specific electrophysiologic properties of the fetal heart contribute to this preponderance by either favoring supraventricular tachycardias or by rendering ventricular tachycardias unlikely, we measured fetal electrophysiologic parameters in utero using transuterine fetal transesophageal electrocardiograms in fetal sheep. Since overdrive pacing may help to establish the mechanism of an arrhythmia and may be used to treat fetal tachycardias, different modes of transesophageal pacing in utero were also assessed. METHODS AND RESULTS: Decapolar electrophysiology catheters were fetoscopically inserted into the esophagus of 9 fetal sheep (pregnancy duration 94- 105 days, term = 145 days). Electrocardiograms were recorded simultaneously from all adjacent bipoles and from two pacing wires sutured onto the fetal shoulders. Pacing was attempted either via two adjacent electrodes of the intraesophageal catheter or via the most distal and most proximal electrode. Fetal cycle length, PQ, and QT intervals were close to (approx. 75 %), but fetal QRS duration was < 20 % of maternal values, thus shifting the relation between activation and repolarization towards longer excitation wave lengths. Fetal QT dispersion was small (< or = 10 ms). Atrial pacing was achieved in all fetuses using distant electrodes, and with lower thresholds when compared to closely spaced bipolar electrodes (p < 0.05). CONCLUSIONS: (I) An altered relation between ventricular activation and repolarization and a low dispersion of ventricular repolarization may protect the fetal heart against ventricular reentrant tachycardias. (II) Relatively normal fetal AV nodal conduction delay already provides one of the prerequisites for supraventricular reentrant tachycardias involving the AV node at this stage of fetal development. (III) High-rate esophageal pacing of the fetal atria is best achieved using widely spaced bipolar pacing electrodes.

Animals↗