The effect of atrial dilatation on the genesis of atrial arrhythmias.

The effect of atrial stretching on the genesis of atrial arrhythmias was studied in 26 dogs. Left atrial dilatation was produced by inflation of a balloon catheter. Electrophysiological studies were performed by programmed electrical stimulation of the atrium and ventricle. The irritability of the atrium markedly increased when it was distended and atrial arrhythmias (sustained or non-sustained atrial tachyarrhythmias) could regularly be induced by administration of an early extrastimulus or--more rarely--by atrial burst pacing. In 10 cases spontaneous atrial tachycardia appeared during atrial balloon dilatation. The atrial effective refractory period shortened and the atrial conduction time lengthened on atrial stretching, while other electrical variables (cycle length, sinus node recovery time, atrioventricular conduction time, intraventricular conduction, ventricular refractory period, QT interval) remained unchanged. Atrial balloon dilatation was not accompanied by marked haemodynamic changes, and the left ventricular pressure curve, the contractility of the left ventricle and the central venous pressure did not change significantly on atrial stretching. The experimental data suggest that the atrial dilatation plays an important part in the pathogenesis of atrial arrhythmias.

Intrapericardial infusion of endothelin-1 induces ventricular arrhythmias in dogs.

OBJECTIVES: Recently, extremely high levels of endothelin-1 (ET-1) were detected in the pericardial fluid of patients with heart disease; however, the pathophysiological importance of this finding is not known. The present study was designed to characterize ET-1 levels in canine pericardial fluid and to investigate the effects of local high concentrations of exogenous ET-1 in vivo. METHODS: In anesthetized, open-chest dogs ET-1 (Groups 1 and 2: 11 and 33 pmol.kg-1.min-1; n = 6 and 6, respectively) or physiological saline (Group 3, n = 5) were infused into the closed pericardial sac for 40 min. In serial pericardial fluid and aortic blood plasma samples, ET-1 levels were measured by radioimmunoassay, and analysed by high-performance liquid chromatography (HPLC). Systemic arterial blood pressure, heart rate, cardiac output (CO), standard ECG and right ventricular endocardial monophasic action potentials (MAPs) were recorded. RESULTS: Basal pericardial fluid ET-1 levels were significantly higher than respective plasma levels (342 +/- 210 vs. 8.0 +/- 5.2 pmol.l-1, n = 14, P < 0.001. In HPLC analysis pericardial fluid ET-1 was indistinguishable from ET-1(1-21). Infusion of exogenous ET-1 into the pericardial space induced ventricular arrhythmias in all instances, which were associated with 9.7-fold increase in pericardial fluid ET-1 levels. Ventricular tachycardias developed in 9 of 12 animals. The arrhythmogenic effect of ET-1 was more apparent in dogs with the larger dose. Before the onset of arrhythmias, intrapericardial infusion of ET-1 increased QT time (Group 1: 207 +/- 18 to 230 +/- 23 ms, P < 0.01; Group 2: 220 +/- 12 to 277 +/- 17 ms, P < 0.01) and MAP duration at 90% repolarization (at 300 ms cycle length) (Group 1: 192 +/- 9 to 216 +/- 9 ms, P < 0.01; Group 2: 205 +/- 9 to 255 +/- 9 ms, P < 0.001). Hemodynamic variables did not change significantly prior to the onset of ventricular tachyarrhythmias. In Group 3, arrhythmias were not observed and all electrophysiological and hemodynamic parameters remained unchanged. CONCLUSIONS: Administration of exogenous ET-1 into the pericardial space induces ventricular arrhythmias associated with prolongation of QT time and MAP duration. Whether pericardial fluid ET-1 under pathophysiological conditions can ever reach sufficiently high levels to induce ventricular arrhythmias remains to be elucidated.

Effect of two week lymphatic occlusion on the mechanical properties of dog femoral arteries.

In order to study the long-term effect of impaired lymphatic drainage on the mechanical properties of the arterial wall, cylindrical femoral artery segments from 10 mongrel dogs after 2 weeks of hindlimb lymphatic occlusion were subjected to in vitro mechanical test and compared with the contralateral, sham-operated segments. Smooth muscle contraction was induced by norepinephrine (7.4 X 10(-6) M) and smooth muscle relaxation by papaverine (1.6 X 10(-4) M). As a result of 2 weeks of lymphatic occlusion, wall thickness increased from 243 +/- 18 to 343 +/- 35 microns (P less than 0.02), inner radius decreased from 1.69 +/- 0.11 to 1.42 +/- 0.12 mm (P less than 0.01) and elastic modulus decreased from 1.23 X 10(6) to 0.55 X 10(6) N/m2 (P less than 0.01), when determined at 100 mm Hg (13.3 kPa) intraluminal pressure and with relaxed smooth muscle. The contractile apparatus was able to produce active strain in the vessels with lymphostasis and at physiological pressures not significantly different from the controls (0.89 +/- 0.02 vs. 0.91 +/- 0.02), but at significantly lower levels of tangential stress. Active stress decreased significantly. This study shows that a reorganization of the vessel wall mechanical force-bearing elements occurs in lymphostasis, which, in some respects, resembles the mechanical alterations found in different forms of atherosclerosis.

Investigating the dual nature of endothelin-1: ischemia or direct arrhythmogenic effect?

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide, which may also elicit severe ventricular arrhythmias. The aims of our study were to compare the effects of total left anterior descending coronary artery (LAD) occlusion to intracoronary (ic.) ET-1 administration and to investigate the pathomechanism of ET-1 induced arrhythmias in 3 groups of anesthetized, open-chest mongrel dogs. In group A (n=10) a total LAD occlusion was carried out for 30 min, followed by a 60 min reperfusion period. In groups B and C ET-1 was administered into LAD for 30 min at a rate of 30 pmol/min (n=6) and 60 pmol/min (n=8). Epi- and endocardial monophasic action potential (MAP) recordings were performed to detect electrophysiologic changes and ischemia Blood samples for lactate measurements were collected from the coronary sinus (CS) and from the femoral artery. Infrared imaging was applied to follow epimyocardial heat emission changes. At the end of the ET-1 infusion period coronary blood flow (CBF) was reduced significantly in groups B and C (deltaCBF30MIN B: 21+/-2%, p<0.05; C: 35+/-2%, p<0.05), paralleled by a significant epimyocardial temperature decrease in group C (deltaT30MIN: -0.65+/-0.29 degrees C, p<0.05). Two dogs died of ventricular fibrillation (VF) in the reperfusion period in group A. Ventricular premature contractions and non-sustained ventricular tachycardic episodes appeared in group B, whereas six dogs died of VF in group C. Significant CS lactate level elevation indicating ischemia was observed only in group A from the 30th min occlusion throughout the reperfusion period (control vs. 30 min: 1.3+/-0.29 vs. 2.2+/-0.37 mmol/l, p<0.05). Epi- and endocardial MAP durations (MAPD90) and left ventricular epicardial (LV(EPI)) upstroke velocity decreased significantly in group A in the occlusion period. ET-1 infusion significantly increased LV(EPI) MAPD90 in group B and both MAPD90-s in group C. In conclusion, ischemic MAP and CS lactate changes were observed only in group A. Although ET-1 reduced CBF significantly in groups B and C, neither MAP nor lactate indicated ischemic alterations. ET-1 induced major ventricular arrhythmias appeared before signs of myocardial ischemia developed, though reduced CBF presumably contributed to sustaining the arrhythmias.

Arteriovenous shunts associated with peripheral obliterative arterial disease. Haemodynamic, arteriographic and isotope studies.

From among 210 patients with severe peripheral obliterative arterial disease, the presence of an arteriovenous shunt was demonstrated in 17 cases. Arteriovenous communications were visualized by serial angiographic records and 99mTc macroaggregate isotope testing. The regulation of the limb circulation was investigated using the venous isotope dilution method. Characteristic haemodynamic changes were revealed in arteriovenous shunts associated with peripheral arterial obliterative disease: total limb blood was comparatively high, arteriovenous difference was low and limb O2 consumption was decreased. The clinical significance of the haemodynamic changes in arteriovenous shunting associated with obliterative arterial disease is discussed.

The association of carotid artery stenosis with carotid sinus hypersensitivity. Transitory cerebral ischaemic attack provoked by carotid sinus reflex.

The association of internal carotid stenosis with the carotid sinus syndrome represents a special clinical entity. Transitory cerebral ischaemic attack (TIA) will usually be manifested by activation of carotid sinus reflex. Eighteen patients were observed suffering from both carotid sinus hypersensitivity and TIA. The patients had had TIA's for many years. Unilateral internal carotid stenosis was detected in 15 cases, while 3 patients had bilateral carotid stenosis. On carotid sinus stimulation, syncope appeared and a TIA could be provoked. The mean duration of the syncopic attack was 5500 ms and was based on sinus arrest in 14 cases and on third degree AV block in 4 cases. In all patients carotid artery disobliteration was performed; in 14 patients pacemaker implantation was necessary, while 4 patients could be treated by atropine medication. The development of a TIA could be abolished in every patient and 14 patients remained totally symptom free.

The effect of isolated perfusion on limb circulation in peripheral arterial occlusion.

The effects of isolated limb perfusion were studied in 12 patients suffering from peripheral arterial occlusion. The hemodynamic investigations show that the vascular resistance decreases considerably during isolated limb perfusion. After administration of a vasodilator cocktail, added to the perfusion, the vascular resistance continues to decrease. Angiographic records, made before, during and after the perfusion, suggest that the calibre of the collateral vessels increases significantly and besides new collaterals can also be observed. The mechanism of the effects of isolated hyperbaric limb perfusion and its clinical value are discussed.

Characteristics of the limb circulation in hypertension.

The aim of this study was to investigate the effect of hypertension on the regulation of limb circulation. The study group consisted of 50 patients suffering from hypertension; in 21 cases the peripheral circulation was intact, while 29 patients had peripheral obliterative arterial disease (POAD) (clinical symptoms: intermittent claudication or rest pain). The control group consisted of 67 normotensive patients. In 33 subjects of the control group the peripheral circulation was intact, while 34 patients suffered from POAD (clinical symptoms: intermittent claudication or rest pain). The total limb blood flow (LBF) was measured by using venous isotope dilution technique. In hypertensive patients the limb vascular resistance (LVR) was markedly elevated, but the LBF remained in the normal range. In patients suffering from both hypertension and POAD the LVR was pathologically elevated and the LBF markedly diminished. After acute vasodilator therapy the LBF significantly increased, despite the drop in blood pressure owing to the extensive decrease of the LVR. It appears that in hypertension the elevation of the LVR is the most characteristic change of the limb circulation. The elevation of the arterial blood pressure has no favorable effect on the limb circulation, and the LBF compared with the blood pressure is relatively low.

CLS 2210, hyaluronidase and the cardiac lymphatic system.

Earlier studies have shown that hyaluronidase exerts a potent influence upon the lymphatic system of the myocardium and that it reduces the size of myocardial infarcts after coronary occlusion. In this study we compared, in mongrel dogs, the effect of intravenous hyaluronidase or CLS 2210 upon the cardiac lymphatic vessels. We observed that in CLS 2210-treated animals the number of visualized cardiac lymphatic vessels was significantly higher than in the hyaluronidase-treated control group. We have previously demonstrated a cardioprotective effect of hyaluronidase in the treatment of acute myocardial infarction. The present experimental data indicate that intravenous CLS 2210 may have a definite role in the management of acute coronary occlusion. Further studies are needed to confirm these preliminary findings.

Effect of acute cardiac lymph stasis on metabolic coronary adaptation in the dog.

Surgical blockade of cardiac lymph drainage was performed in dogs to examine the effect of acute cardiac lymph stasis on coronary adaptive mechanisms. Coronary blood flow (CBF) was measured using an electromagnetic flow probe on the left anterior descending (LAD) artery. Metabolic autoregulatory capacity was assessed by eliciting reactive hyperemic responses after flow interruptions of 10-60 second duration and by administering submaximal doses (250-500 micrograms) of adenosine, the putative transmitter of reactive hyperemia, into the left heart. The effect of lymph stasis was tested in two experimental groups, one hour and 48 hours after lymph obstruction and the data compared to control dogs. Although cardiac lymph stasis did not notably affect baseline arterial pressure and CBF, both reactive hyperemic response and adenosine-induced coronary vasodilation were reduced significantly (equal to or less than 50% control). On occasion, a complete absence of autoregulation was observed. These findings suggest that cardiac lymph stasis decreases vascular responsiveness to physiologic vasodilator stimuli and/or retards diffusion of biologically unstable substance(s) presumably involved in autoregulation. Persistently impaired coronary autoregulation in the lymphedematous heart may contribute to progressive ischemic damage as for example after myocardial infarction.

Arteriovenous shunts in peripheral lymphedema: hemodynamic features and isotopic visualization.

The hemodynamic characteristics of peripheral lymphedema were studied in 28 patients with uni- or bilateral leg swelling. Leg blood flow was measured by venous isotope dilution (a technique for nutritive--capillary blood flow) and arteriovenous shunts were visualized by perfusion scintigraphy using radiolabelled macroaggregated albumin. Arteriovenous communications were uniformly detected in lymphedema, with a calculated "shunt flow" of 200 to 600 ml/min. Other features in the lymphedematous leg included an elevated limb blood flow rate and narrowed arteriovenous oxygen difference.

Ultrastructural and electrophysiologic changes of experimental acute cardiac lymphostasis.

Experimental impairment of cardia lymph flow in dogs produced histologic and electrophysiologic changes in the heart. Interstitial edema, lipid swelling of myofibrils, dilatation of lymph vessels, and fibrinoid degeneration of small coronary arteries occurred in and near the sinus node and the atrioventricular conduction system. On electrical stimulation of the heart, significant shortening of the atrial and ventricular effective refractory periods, increases in the sinus node recovery time and in the atrioventricular conduction time, and ventricular extrasystoles and ventricular fibrillation were observed. Many of these EKG changes are similar to those observed in sick sinus syndrome in man. An attempt was made to create dynamic lymphatic insufficiency by rapid electrical stimulation of the heart. EKG abnormalities observed in these cases could be prevented by intravenous injection of calcium dobesilate.

Coronary arteriopathy after lymphatic blockade: an experimental study in dogs.

The effects of lymph stasis on the histological and biochemical properties of the coronary arterial wall and on the coronary circulation were studied in 72 dogs. Cardiac lymph stasis was produced in 52 dogs by cardiac lymphatic blockade whereas in 20 dogs only a sham operation was performed. Blockade of cardiac lymph drainage promoted characteristic injury to the coronary arteries including subendothelial edema with plasma inbibition, interstitial and intracellular edema in the tunica media with degeneration in the smooth muscle layer, swelling of the adventitial space with dilated lymph vessels and, later, fibrosis. The biochemical properties of the coronary arterial wall also were adversely affected by cardiac lymph stasis. Thus, the collagen and hexosamine content of the coronary arteries increased and the metabolism of the coronary wall shifted in an anaerobic direction. Whereas coronary blood flow was slightly decreased with lymph blockade, the coronary circulatory reserve capacity and the adaptability of the coronary vascular system was markedly reduced. The histological changes were most apparent in the smaller coronary arteries. The coronary microvasculature was also pathologically altered with the development of numerous coronary arteriovenous microshunts. These findings in conjunction with other experimental and clinical information suggest that impaired cardiac lymph drainage contributes to the pathogenesis and progression of coronary artery disease.

Lymphatic arteriopathy: damage to the wall of the canine femoral artery after lymphatic blockade.

The effect of lymph stasis on the histological, biochemical, and elastic properties of the femoral artery were studied after regional lymphatic blockade in 36 dogs. Dogs were sacrificed 4-21 days after operation. Histologic changes of the femoral arterial wall (interstitial edema, degeneration in the muscle layer or media, thickened adventitia with dilated lymph vessels, and fibrosis) developed after regional lymphatic blockade. Characteristic metabolic alterations of the arterial wall (anaerobic catabolism of carbohydrate, increased lactate and glycosamine content) accompanied the morphological changes. Distensibility of the femoral artery decreased and greater elastic stiffness developed after regional lymphatic blockade. These results in conjunction with other experimental and clinical data support the concept that insufficient lymphatic transport within the blood vessel wall may contribute to the genesis and progression of arteriopathies.

The effect of cardiac lymphostasis on the microcirculation of the heart: effect of cardiac lymphoedema on the development of an arteriovenous shunt circulation.

The effect of cardiac lymphostasis on the microcirculation of the heart was studied in 18 dogs. By ligation of the main lymph trunks and regional lymph nodes of the heart, cardiac lymphoedema--lymphogenic cardiomyopathy--was induced in 9 dogs, while 9 served as control animals. For microcirculatory investigations: 1) gelatin Indian ink injection, 2 benzidine reaction, 3) PVC injection corrosion preparation was applied. Characteristic changes were demonstrated in the microcirculation and capillary circulation of the heart in cardiac lymphostasis. In some capillaries-mainly where the interstitial oedema exists--the capillary circulation decreased: inhomogeneously vessel-free spots were formed in the heart. Around the vessel-free capillaries, elongated capillaries were found including very dilated pre- and post-capillary vessel sections. Arteriovenous shunts can be revealed in the heart in consequence of lymphoedema. The pathogenesis of the microcirculatory circulation changes caused by cardiac lymphostasis was discussed.

Autonomic sinus node dysfunction and its treatment.

The clinical, electrocardiographic, pharmacologic, electrophysiologic and Holter monitoring findings are described in four patients with autonomic sinus node dysfunction and one patient with autonomic binodal disease. All showed cerebral symptoms, and had attacks of dizziness, weakness, near-syncope or syncope. After a pharmacologic autonomic blockade with propranolol and atropine, all patients had normal intrinsic heart rates. Electrophysiological studies revealed normal corrected intrinsic node recovery time (less than or equal to 240 msec) a gradual return to the basic cycle length in the secondary postpacing cycles after autonomic blockade, and no intrinsic paroxysmal atrioventricular block. Continuous ECG monitoring (1-3 X 24 hours) revealed severe sinus bradycardia, SA-block, severe sinus arrest, cardiac standstill, atrial fibrillation and in two patients associated AV-block. Autonomic blockade with electrophysiological studies exclude the intrinsic involvement of the sinoatrial and atrioventricular node. Holter monitoring is the best method for assessing the autonomic neurovegetative component of dysrhythmias. Therapy regarding isolated autonomic sinus node dysfunction depended on the pathomechanisms of rhythm disorders: two patients received permanent pacemakers, antiarrhythmic drugs were applied in the case of two patients, and etiological treatment in the case of one. During the follow-up, all patients became symptom-free.

[Malignant arrhythmia]. / Malignus aritmiák.

About 5 percent of the arrhythmias are serious, life threatening, malignant arrhythmias (MA). The MA is regularly associated with organic heart diseases (coronary heart disease, cardiomyopathy, valvular heart diseases), but a MA can develop without cardiac disorders e.g. in long QT syndrome or WPW syndrome. The most frequent type of the MA is the ventricular tachycardia (VT), mostly the sustained VT, not rarely degenerating to ventricular fibrillation (VF). The primary VF represents a rarer form of MA. The usual type of MA is the tachycardiac form, but there exists a MA with dominating bradycardia (bradycardia syncope, tachycardia associated with long lasting bradycardia). In the diagnosis of MA new investigatory methods (signal averaged electrography with high amplification, Holter monitoring, programmed electrical stimulation) play an important role. In the therapy of the MA the first step is the treatment of the cardiac disease involved in the pathogenesis of the MA. At present only about the 40% of the MA can be effectively treated with antiarrhythmic drugs. The pacemaker therapy is very efficacious in the bradycardiac type of MA. Cardiodefibrillator pacemaker can be used for the treatment of grave VT or VF. Electrical transvenous catheter ablation, heart surgical intervention can also be applied in the treatment of special MA. The prognosis of VA was very serious a decade ago, now with application of newer therapeutical procedure the prognosis of MA is permanently improving.

[Regulation of blood circulation in the extremities in intermittent claudication]. / A végtagi keringés regulációja claudicatio intermittensben.

UNLABELLED: The study was aimed to investigate the characteristics of the limb circulation in patients suffering from intermittent claudication. The study group consisted of 71 patients with intermittent claudication. As control served the data of 60 patients with intact peripheral circulation and 24 patients suffering from rest pain, too. The limb blood flow was measured by the venous isotope dye-dilution method. RESULTS: 1. The limb blood flow will be diminished in intermittent claudication already in resting state. The decrease of the limb blood flow is more expressed in severe claudication (with short claudication distance). 2. The pathological condition of the limb circulation in intermittent claudication can be characterized by the elevation of the limb vascular resistance. 3. The O2 consumption of the limb tissues will decrease in intermittent claudication. The data of the study are indicating that the regulation of the limb circulation will pathologically be changed in claudication. The reserves of the peripheral circulation are diminished and the insufficiency of the limb circulation will be manifested on walking.

[Intermittent Romano-Ward syndrome]. / Intermittáló Romano-Ward-syndroma.

Two cases are described to have intermittent long QT syndrome. This type of long QT syndrome is not easy to recognize and the result could be fatal in case taking I/A type antiarrhythmic drugs. The first patient who was investigated had got "chinidin syncope" two years earlier, the second one had symptoms of syncope and dizziness for 3 months. The long QT syndrome was diagnosed in both cases by Holter monitoring. For these reason this paper underline the value of Holter monitoring as a diagnostic tool to establish the diagnosis of long QT syndrome. The monophasic action potential showed early after depolarisations in both cases.

[Iatrogenic sinus node disease and iatrogenic AV block]. / Az iatrogén színuszcsomó betegség és az iatrogén AV block.

The appearance of long lasting bradycardia due to damage of the sinus node (iatrogen sick sinus syndrome; or the atrioventricular conduction system, iatrogen AV block) is not a rare event after open heart surgery. In the course of 5093 heart operations the development of iatrogen sick sinus syndrome was observed in 234 patients (4.6%) and iatrogen AV block in 91 cases (1.8%). The incidence rate of iatrogen sick sinus syndrome or iatrogen AV block was quite divergent depending mostly on the type of operation. Comparing the data of our earlier (1977-1982) and later (1983-1991) cardiac surgical interventions, the prevalence of iatrogen sinus node disease and iatrogen AV block seems to decrease, mainly due to the progress in techniques of cardiac surgery. With the appearance of iatrogen sick sinus syndrome or AV block, urgent temporary pacing is indicated to prevent the deleterious hemodynamic effect of bradycardia. In the cases of persistent iatrogen sick sinus syndrome and iatrogen AV block, permanent pacemaker implantation is needed. It is remarkable that although the incidence rate of iatrogen sick sinus syndrome is greater than that of iatrogen AV block, in iatrogen sick sinus syndrome the regression is quite frequent, while in iatrogen AV block the 2nd or 3rd degree AV block is usually permanent. We performed pacemaker implantation in 56 cases of iatrogen sick sinus syndrome (24%) and in 57 patients of iatrogen AV block (63%). With pacemaker therapy the outcome of iatrogen sick sinus syndrome and iatrogen AV block is very favourable.