Dieter Pelzer

Altered cardiac automaticity and conduction in experimental diabetes mellitus

Abstract The electrophysiological and ultrastructural alterations that occur in chronic diabetes mellitus were studied in isolated, superfused atria including sinoatrial (SA) and atrioventricular (AV) nodes that were obtained from rabbits subjected to alloxan-diabetes for 100 days. Transmembrane action potentials were recorded simultaneously with the His bundle electrogram. The results were compared with corresponding values observed in atria from normal, non-diabetic rabbits. The abnormalities of automaticity and conduction found in atria of alloxan-diabetic rabbits included lower sinus rate, longer poststimulatory sinus-node recovery time, inhomogeneity of atrial conduction and the occurrence of AV nodal block. Ultrastructural analysis of the diabetic preparations revealed intracellular accumulation of abundant glycogen and various mitochondrial abnormalities but a normal appearance of the small coronary vessels. It was concluded that chronic alloxandiabetes mellitus may directly alter the electrophysiological and ultrastructural properties of nodal and atrial fibers in the absence of vascular damage.

Combined effects of glucose and hypoxia on cardiac automaticity and conduction

Abstract The combined effects of glucose and graded hypoxia on automaticity and conduction were studied in the isolated sinoatrial (SA) node, right atrium and atrioventricular (AV) node of the rabbit heart, and in the conducting system of isolated right canine ventricles. Transmembrane action potentials were recorded simultaneously with the extracellular His bundle electrogram. At normoxia (PO 2 460 mmHg), variations in the extracellular glucose concentration between 0 and 50 m m had no significant effect on automaticity and conduction within the different cardiac regions. At moderate hypoxia (PO 2 130 mmHg), absence of glucose significantly prolonged the post-stimulatory sinus-node recovery time but the sinus rate and the conduction parameters were not significantly related to the extracellular glucose concentration. At severe hypoxia (PO 2 40 mmHg), the nodal electrical activity including sinus rate, SA and AV nodal potential amplitude and conduction were markedly dependent on the extracellular glucose concentration; 50 m m glucose considerably improved the depressed nodal function. In contrast, the atrial and particularly the ventricular conduction parameters were much less sensitive to substrate-free media even at severe hypoxia. The results indicate that glucose combined with hypoxia predominantly affects the slow response activity but has only little action on the fast Na inward current.

Effects of hypercholesterolaemia without ischemia on some electrophysiological and ultrastructural properties of the rabbit heart

Abstract The electrophysiological and ultrastructural alterations that occur in chronic hypercholesterolaemia were studied in isolated atria including sinoatrial (SA) and atrioventricular (AV) nodes that were obtained from rabbits subjected in 1% cholesterol diet for 18 weeks. Transmembrane action potentials were recorded simultaneously with the His bundle electrogram. The results were compared with corresponding values obtained in normal control atria. During sinus rhythm or constant atrial stimulation, the electrophysiological studies demonstrated no significant alterations of the electrical activity of the SA node, crista terminalis and AV node in preparations obtained from cholesterol-fed rabbits. Premature atrial stimulation at a critical range of coupling intervals initiated supraventricular tachycardias in 7 12 of the high cholesterol preparations but in none of the controls. Premature atrial impulses within this critical range were characterized by slow conduction through the AV node. Ultrastructural analysis of hearts obtained from cholesterol-fed rabbits revealed highly selective degenerative changes of the AV nodal cells and diffuse degeneration processes of the cardiac nerves but no obstructive coronary lesions. It was concluded that hypercholesterolaemia per se without myocardial ischemia may result in electrophysiological and ultrastructural abnormalities of the AV node and the cardiac neural tissue.

Effects of orciprenaline on the sinoatrial and atrioventricular nodes in presence of hypoxia

Abstract The effects of orciprenaline on the isolated, superfused sinoatrial (SA) and atrioventricular (AV) nodes of the rabbit heart were studied under normoxic and hypoxic conditions. Transmembrane action potentials were recorded simultaneously with the extracellular His bundle electrogram. At PO 2 460 nmHg, orciprenaline 10 −8 to 4 × 10 −6 m increased SA nodal automaticity and shortened conduction time in the AV node. At moderate hypoxia (PO 2 130 mmHg), the positive chronotropic response to orciprenaline resembled that obtained under normoxic conditions. At severe hypoxia (PO 2 40 mmHg), orciprenaline 4 × 10 −6 m increased sinus rate and shortened AV conduction only during a short initial period after drug administration. Thereafter, marked sinus bradycardia and complete sinoatrial and atrioventricular block occurred associated with a pronounced decrease in action potential to amplitude of SA and AV nodal fibers. Following reoxygenation, normal AV conduction could be restored by administration of 4 × 10 −6 m orciprenaline. Intra-atrial conduction time and atrial action potential amplitude were not significantly affected by orciprenaline either under normoxic or under hypoxic conditions, and no rapid ectopic activity was observed. The results indicate that 4 × 10 −6 m orciprenaline restore the reduced nodal function at moderate hypoxia but markedly potentiate the depression of automaticity and conduction in SA and AV nodes at severe hypoxia.

Effect of glycolytic inhibitors on the sinoatrial node, atrium and atrioventricular node in the rabbit heart

Abstract The effect of unspecific noncompetitive (iodoacetic acid; IAA) and of specific competitive (deoxyglucose) glycolytic inhibitors were studied under aerobic and anaerobic conditions in the isolated sinoatrial (SA) node, right atrium and atrioventricular (AV) node of the rabbit heart. Transmembrane action potentials were recorded simultaneously with the His bundle electrogram. Under aerobic conditions ( P o 2 460 mmHg), 7.5 × 10 −5 m IAA caused no significant alterations of sinus rate, intraatrial and AV nodal conduction. Under hypoxic conditions ( P o 2 40 mmHg), 7.5 × 10 −5 m IAA resulted in rapid and complete abolition of the SA and AV nodal electrical activity and in a more delayed atrial inexcitability. Similar changes were never observed in the presence of hypoxia alone. Higher concentrations of IAA (5 × 10 −4 m ) severely depressed the sinus rate and the AV nodal conduction already under aerobic conditions. The action potential amplitude and the rate of diastolic depolarization of the SA nodal fibers was significantly reduced, the maximum diastolic potential remained unchanged. In atrial fibers, 5 × 10 −4 m IAA caused predominantly shortening of the action potential duration but had less marked and delayed depressant effects on the action potential amplitude. Electrophysiologic abnormalities included Mobitz type II sinoatrial block. The electrophysiological effects of deoxyglucose (50 m m ) under aerobic and hypoxic conditions resembled those obtained with 7.5 × 10 −5 m IAA. The results suggest that the “normal” nodal function is predominantly related to aerobic metabolism but that under hypoxic conditions glycolytic energy production can effectively contribute to the maintenance of nodal electrical activity. Also that the specific relation between cardiac metabolism and electrical activity of nodal and atrial cells may at least partly be explained by the particular electrical membrane properties of the various fiber types.

Inotropic and electrophysiological action of humoral factors released in cardiogenic shock after acute myocardial infarction

SummaryThe inotropic and electrophysiological effects of plasma obtained from patients and experimental dogs during cardiogenic shock following acute myocardial infarction were studied. Changes in the isometric contraction and the intracellular action potential were determined in isolated papillary muscles of rabbits. Control plasma collected from normal subjects produced no significant changes in the contraction or the electrical parameters. Plasma from shock patients decreased peak force by 42% and the maximum rate of force development by 38% in comparison to control values; the time to peak of contraction, the relaxation time and the action potential parameters were not significantly altered. Corresponding results were obtained with plasma from dogs before and during experimental cardiogenic shock. Biochemical determinations failed to identify a single specific “myocardial depressant factor” in the plasma of patients and dogs with cardiogenic shock. The results suggest that (1) various humoral factors released during cardiogenic shock may depress the contractile function of cardiac muscle and (2) that the observed negative inotropic effect is not due to electrical changes in the cell membrane.ZusammenfassungDie Irreversibilität eines kardiogenen Schocks nach Myokardinfarkt soll angeblich wesentlich durch die Freisetzung eines humoralen, negativ inotropen Peptids, des “myocardial depressant factor” (MDF), mibestimmt werden. Bei Patienten und Hunden wurde Plasma während eines kardiogenen Schocks nach akutem Myokardinfarkt gewonnen. Gemessen wurde die Wirkung von Plasmadialysaten auf die isometrische Kontraktion und auf intrazelluläre Aktionspotentiale an isolierten Papillarmuskeln von Kaninchen in vitro. Kontrollplasma von herzgesunden Normalpersonen hatte keinen signifikanten Einfluß auf die Kontraktion und die elektrischen Parameter. Wechsel der Superfusions-flüssigkeit von Kontrollplasma auf Schockplasma verursachte eine signifikante Abnahme von Kontraktionsamplitude und maximaler Kontraktionsgeschwindigkeit um 30–40%; Kontraktionszeit, Relaxationszeit und die elektrophysiologischen Parameter des Aktionspotentials blieben unverändert. Ähnliche Ergebnisse wurden mit Plasmaproben von Hunden beobachtet, die während eines experimentellen kardiogenen Schocks entnommen wurden. Biochemische Untersuchungen mit der Polyacrylamid-Gel-Elektrophorese und der High-Voltage-Elektrophorese ergaben keinen Unterschied zwischen den Peptidfraktionen in Kontrollplasma und Schockplasma. Die Ergebnisse deuten auf eine Beteiligung von unspezifisch negativ inotropen Plasmafaktoren bei der Entstehung eines kardiogenen Schocks hin; dagegen konnte das von mehreren Autoren postulierte spezifische MDF-Peptid mit den angewendeten empfindlichen analytischen Verfahren nicht nachgewiesen werden.

Supraventricular arrhythmias in experimental myocardial infarction

SummaryThe electrophysiological mechanisms underlying supraventricular dysrhythmias that accompany acute myocardial infarction were studied in rabbits subjected to ligation of right coronary artery. In vivo, sinus bradycardia, atrioventricular block and rapid atrial arrhythmias were observed 2 to 5 hours after coronary occlusion; evidence of ventricular arrhythmias was absent. The bradyarrhythmias were markedly improved after iv administration of atropine. The infarcted hearts were then removed and the isolated sinoatrial (SA) node, right atrium and atrioventricular (AV) node were studied with intracellular microelectrodes in vitro. Rapid, repetitive atrial depolarizations occurring spontaneously or initiated by premature atrial stimulation were observed only in preparations obtained from infarcted hearts. In disseminated areas localized within the SA node and the atrium, the subendocardial fibers had a reduced action potential amplitude but showed also normal potentials in other regions as compared with noninfarcted preparations. Sinus rate, poststimulatory sinus-node recovery time, intraatrial conduction and the parameters of AV nodal function including action potential amplitude and conduction were not significantly different in preparations isolated from infarcted and noninfarcted hearts. The results suggest that the observed bradyarrhythmias accompanying acute myocardial infarction may be partly due to a vagomimetic reflex whereas the supraventricular tachycardias seem to result from direct cellular damage.ZusammenfassungDie elektrophysiologischen Mechanismen von supraventrikulären Arrhythmien bei akutem Myokardinfarkt wurden an Kaninchen untersucht, bei denen die rechte Koronararterie unterbunden wurde. In vivo wurden 2 bis 3 Stunden nach Koronarverschluß eine Sinusbradykardie, atrioventrikuläre Blockierungen und atriale Tachykardien beobachtet. Atropin (i.v.) führte zu einer signifikanten Rückbildung der Bradykardien. Anschließend wurden die infarzierten Herzen freipräpariert und der rechte Vorhof einschließlich sinuatrialem (SA) und atrioventrikulärem (AV) Knoten mit intrazellulären Mikroelektroden in vitro untersucht. Im Vergleich zu Kontrollpräparaten von nichtinfarzierten Herzen wurden bei Vorhöfen von infarzierten Herzen folgende Befunde beobachtet:1. Spontane atriale Tachykardien. 2. Abnahme der Amplitude des Aktionspotentials in disseminierten subendokardialen atrialen und SA nodalen Fasern, aber normale Aktionspotentiale bei der Mehrzahl der untersuchten Fasern. 3. Normale Sinusfrequenz, poststimulatorische Sinusknotenerholungszeit, intraatriale und AV nodale Leitungszeiten. Die Befunde deuten auf einen vagomimetischen Reflex als überwiegende Ursache der in vivo beobachteten Bradykardien hin, während die supraventrikulären Tachykardien möglicherweise durch eine direkte Schädigung der Zellmembran bedingt sind.