[Two cases of Marfan syndrome complicated with aortic dissection during pregnancy].

Two women with Marfan syndrome who developed aortic dissection during pregnancy are reported. Case 1: A 38-year-old woman had experienced severe back pain five years before (at the age of 33) when she was in the 38th week of gestation, followed by labour with no problem. Three years ago, she was examined in our hospital for enlarged thoracic aorta pointed out in a somatoscopy and was diagnosed as having Marfan syndrome and aortic dissection of DeBakey type IIIb. Because her aortic dissection has been growing larger recently, surgical repair is scheduled electively. Case 2: A 32-year-old woman, who had been diagnosed as having Marfan syndrome because of ectopia lentis at 10 years old, was referred to our department for a painful tumor with pulsation which had emerged at the right-hand side of her neck in the 32nd week of gestation. Acute aortic dissection of DeBakey type I complicated with acute aortic regurgitation was diagnosed, and emergency operation (Cesarean section, reconstruction of ascending aorta and aortic arch, replacement of aortic valve and aorto-coronary bypass to right coronary artery) was performed. Post-operative course was uneventful and the patient and her baby were discharged safely. In general, aortic dissection during pregnancy of patients with Marfan syndrome is of poor prognosis. Full consent by the patient and her family is necessary to decide whether the pregnancy should go on, and close cooperation among participating departments is indispensable for the treatment for this condition.

[Objective assessment of senile changes in visual function by visually evoked cortical potentials].

The P100 peak latency of pattern visually evoked cortical potentials (P-VECP) was found to increase and amplitude decrease in the elderly depending on stimulus conditions. Using either of these as a criterion, changes of visual function with aging were quantitatively assessed both in humans and animals. Contrast threshold was found to increase at higher spatial frequency ranges and the luminance threshold increased more than 0.8 log unit. Also, the contrast threshold increased due to a smaller pupillary area and there was progressive decrease of the temporal frequency curves with age for lower frequency ranges of less than 10 rev/sec. In addition, a sensitivity decrease for the upper visual field was detected plus blue-yellow defects and a decrease in the amplitude of accommodation. In order to exclude the effect of senile changes of the crystalline lens, the luminance threshold, the accommodation power and color sense were investigated in pseudo-phakic eyes with a posterior chamber lens. No significant differences were found between phakic and pseudo-phakic eyes. Accordingly, it was suggested that reduced transparency and yellowish changes of the crystalline lens do not essentially contribute to the loss of function in the elderly found in the present study, but the neuronal pathway was responsible. As a clinical model of senescence, cases of juvenile parkinsonism were investigated, during L-dopa treatment and after ceasing it. The deficiency of the neural-transmitter of the higher visual pathway was indicated in the elderly, also. Animal experiments on neuronal dysfunction in rats and mice suggested no aging effects in ERGs, whereas VECP peak latency for higher temporal frequencies increased with age. The assumption that the elderly changes occur at the neuronal level was supported by a loss of optic nerve fibers in mice with age. The numbers of optic nerve fibers measured were 48,115, 50,875 in the 3-month-old and 6-month-old groups, respectively, and decreased to 43,175 in the 30-month-old group. Though our results indicated the senescence of visual function at the neuronal level, it was not as much as shown by other sensory organs. It was therefore presumed that there might be a certain feed-back system from the brain to the retina.

Long-term follow-up of patients with sick sinus syndrome: a comparison of clinical aspects among unpaced, ventricular inhibited paced, and physiologically paced groups.

To analyze the prognosis of the sick sinus syndrome (SSS), we compared the clinical aspects among unpaced, ventricular paced, and physiologically paced patients who were followed over a long period. Unpaced intrinsic SSS was not always progressive and patients did not necessarily require permanent pacing. The incidence of concomitant AV conduction disturbance was 65.6% before pharmacologic autonomic block, (PAB), but this was significantly reduced to 31.7% after PAB. Follow-up study of the physiologically paced groups revealed no development of either new or more than second degree AVB. The VVI group had significantly more complications (68%) than the physiologically paced groups, mainly chronic atrial fibrillation (36%) and thromboembolism (20%). In addition, cardiothoracic ratio (CTR) in the VVI group was significantly greater compared with that in the physiologic groups. Nine deaths occurred during the follow-up period in the pacing groups, including six with VVI and three with physiologic pacing. In the VVI pacing group, heart failure and thromboembolism were most commonly the causes of death, while in the physiologic pacing groups, the causes of death were noncardiac. Although the survival rate in the ventricular paced group was not significantly different from that in the physiologic pacing groups, cardiac deaths were fewer in the latter group. Considering our clinical data, the decision to use ventricular pacing needs to be carefully weighed in patients with sick sinus syndrome, and physiologic pacing is more highly recommended.

Effects of calcium channel blockers on sinoatrial conduction in the isolated and blood-perfused dog atrium.

Our previous study demonstrated that class I antiarrhythmics (fast sodium channel blockers) increased sinoatrial conduction time (SACT) in a dose-related fashion, indicating that a fast sodium current might play an important role in sinoatrial conduction. To assess a role of a slow calcium current in sinoatrial conduction, we examined effects of calcium channel blockers (diltiazem, verapamil, AQ-A 39, dilazep and bepridil) on SACT estimated by the constant atrial pacing in addition to on sinus cycle length (SCL) and on atrial developed tension (DT), using the isolated and blood-perfused dog right atrium. These calcium entry blockers except for bepridil were administered into the cannulated sinus node artery at an infusion rate of 0.2, 0.4 and 1.0 micrograms/min and bepridil at a rate of 0.6, 1.2 and 3.0 micrograms/min. The calcium antagonistic agents produced a dose-dependent decrease in DT and increase in SCL. The observed order of depression of inotropism was verapamil greater than diltiazem greater than bepridil = dilazep greater than AQ-A 39, while the order of negative chronotropism was diltiazem greater than verapamil greater than AQ-A 39 greater than dilazep greater than bepridil. However, as to dromotropism none of the five drugs exerted significant influences on SACT. From the previous and present results it is concluded that the fast sodium current may be predominantly important in sinoatrial conduction.

Differences between negative chrono-, dromo- and inotropic actions of cholinomimetics in the dog isolated atrium.

Both bethanechol and physostigmine produced dose-dependent negative chrono-, dromo- and inotropic effects in the dog isolated atrial preparation. Within a relatively small dose of bethanechol and physostigmine, negative inotropic effect was clearly induced but no significant chrono- and dromotropic changes were observed. With a relatively large dose, the two cholinomimetics caused negative chrono-, dromo- and inotropic effects. The order of the negative actions of the drugs in % changes was inotropism greater than dromotropism greater than or equal to chronotropism. These results indicate that pacemaker activity, sinoatrial conductivity and atrial contractility may be differentially sensitive to actions of cholinomimetics.

Comparative study of five beta-adrenoceptor blocking agents on sinoatrial conduction time in isolated blood-perfused canine atria.

We studied the effects of five beta-adrenoceptor blocking agents (propranolol, atenolol, sotalol, oxprenolol and carteolol) on sinus cycle length (SCL), sinoatrial conduction time (SACT) measured with a constant atrial pacing technique, and atrial developed tension (DT), using isolated blood-perfused canine atria. Except for carteolol, all tested beta-blockers were infused into the sinus node artery at a rate of 1-4 micrograms/min, and carteolol was given continuously at a rate of 0.1-0.4 micrograms/min. Atenolol and sotalol as well as propranolol prolonged SCL and SACT and reduced DT dose-dependently, although propranolol had more potent negative chrono-, dromo- and inotropisms than atenolol and sotalol. Oxprenolol did not change SCL significantly, but lengthened SACT at higher doses and decreased DT in a dose-related manner. Carteolol did not cause any significant changes in the three parameters. The relative potencies on deceleration of SA conduction on the basis of administration of doses which seems to be equipotent as to beta-blocking effect are as follows: propranolol greater than atenolol = sotalol greater than oxprenolol = carteolol. These results suggest that the membrane stabilizing action of beta-blockers may lengthen SACT but that the intrinsic sympathomimetic action of beta-blockers may resist such a prolongation of SACT.

A comparative study of sinoatrial conduction time with therapeutic doses of antiarrhythmic agents in isolated cross-perfused canine atria.

The effects of therapeutic doses of antiarrhythmic drugs (12 mg/Kg of procainamide, 2 mg/Kg of disopyramide and 0.2 mg/Kg of propranolol) on sinus cycle length (SCL), sinoatrial conduction time (SACT) estimated by a constant atrial pacing technique, and atrial developed tension (DT) were measured in isolated canine atria cross-perfused with heparinized arterial blood from donor dogs as well as on mean systemic blood pressure (SBP) and on heart rate (HR) in those dogs. Procainamide, which produced hypotension and bradycardia in the donor dog, did not change SACT significantly, although it increased SCL and decreased DT in the isolated atrium. However, disopyramide raising SBP slightly (but not significantly) and decreasing HR in the donor dog produced a significant prolongation of SACT and SCL and reduction of DT in the isolated atrium. Propranolol caused slight but insignificant hypotension and long-lasting bradycardia in the donor dog, accompanied by a significant increase in SCL and SACT, and decrease in DT in the isolated canine atrium. We concluded that SACT was significantly increased by a therapeutic dose of propranolol and disopyramide but was not altered by that of procainamide.

Chronotropic, dromotropic and inotropic effects of dilazep in the intact dog heart and isolated atrial preparation.

When dilazep was administered intravenously to the anesthetized donor dog, mean systemic blood pressure was dose dependently decreased. At a dose of 0.1 mg/Kg i.v., the mean blood pressure was not changed but a slight decrease in heart rate was usually observed in the donor dog. At the same time, a slight but significant decrease in atrial rate and developed tension of the isolated atrium was induced. Within a dose range of 0.3 to 1 mg/Kg i.v., dilazep caused a dose related decrease in mean blood pressure, bradycardia in the donor dog, and negative chronotropic, dromotropic and inotropic effects in the isolated atrium. At larger doses of 3 and 10 mg/Kg i.v., dilazep caused marked hypotension, frequently with severe sinus bradycardia or sinus arrest, especially in isolated atria. When dilazep was infused intraarterially at a rate of 0.2-1 micrograms/min into the cannulated sinus node artery of the isolated atrium, negative chrono- and inotropic effects were dose dependently induced. With respect to dromotropism, SA conduction time (SACT) was prolonged at infusion rates of 0.2 and 0.4 micrograms/min. But at 1 microgram, dilazep caused an increase or decrease of SACT, indicating a shift of the SA nodal pacemaker. It is concluded that dilazep has direct negative chrono-, dromo- and inotropic properties on the heart at doses which produced no significant hypotension.

Direct effects of catecholamines and tyramine on sinoatrial conduction in isolated and blood-perfused dog atria.

We have investigated the effects of catecholamines (dopamine, norepinephrine, epinephrine and isoproterenol) and tyramine on sinoatrial conduction time (SACT), sinus cycle length (SCL) and developed tension (DT) in isolated atrial muscle, using an isolated and blood-perfused dog atrial preparation, perfused with heparinized blood from the carotid artery of the anesthetized donor dog. Each substance was continuously administered intraarterially into the cannulated sinus node artery. They had dose-dependent positive chronotropic and inotropic effects. Each produced not only a shortening but a prolongation of SACT. In experiments in which only a shortening occurred, the order of the potency for inducing the shortening of the SACT was isoproterenol greater than norepinephrine = epinephrine greater than dopamine greater than tyramine. The ratio of doses required to produce roughly a 15-25% shortening of the SACT was 1: 10: 10: 100: 300, respectively. The isoproterenol-induced shortening of the SACT was inhibited by treatment with propranolol. Tyramine-induced shortening was inhibited by imipramine. From these results, it is suggested that sympathomimetic amines induce a shortening of SACT through adrenergic beta-receptors and also readily induce a pacemaker shift in the SA nodal area.

Effects of 4 antiarrhythmic drugs on sinoatrial conduction time in isolated and blood-perfused dog atria.

We examined the effects of four antiarrhythmic drugs (quinidine, disopyramide, procainamide and propranolol) on sinus cycle length (SCL), sinoatrial conduction time (SACT) measured by a constant atrial pacing technique, and atrial developed tension (DT), using isolated blood-perfused dog atrial preparations. When an infusion rate of 10-40 micrograms/min of quinidine, disopyramide or procainamide was continuously given into the sinus node artery and propranolol at a rate of 1-4 micrograms/min, all the agents prolonged SCL and SACT, and reduced DT dose-dependently, but not in the same fashion. Propranolol caused almost a parallel action in prolongation of SCL and SACT, and reduction of DT in increasing doses. Quinidine, disopyramide and procainamide caused negative inotropic and chronotropic effects with only a small prolongation of SACT in a relatively small dose. At larger doses, quinidine and disopyramide produced a relatively more marked prolongation of SACT than procainamide. In the doses used, quinidine, disopyramide and procainamide caused relatively small depression of DT in contrast to propranolol. The order of potencies for inducing a prolongation of SACT was propranolol greater than quinidine = disopyramide greater than procainamide.

Double-peaked positive chronotropic responses of isolated and cross-perfused dog atria to ATP.

The effects of a large amount of adenosine and ATP (100 to 3000 micrograms) were investigated on sinus rate and developed tension, using the isolated dog atrium which was perfused with arterial blood from a heparinized donor dog. Each of the substances used for study was administered into the cannulated sinus node artery of the isolated atrium. Adenosine caused monophasic negative chronotropic and inotropic effects in a dose-related manner. However, ATP induced two-peaked positive chronotropic phases during a long-lasting negative chronotropic phase, i.e., initially, brief positive (t-1) effects and secondarily, relatively longer positive chronotropic (t-2) effects. These responses were repetitively induced during the experiment. The t-1 and t-2 were not influenced by treatment with propranolol which significantly blocked the positive chronotropic effect of norepinephrine. Aminophylline treatment significantly suppressed t-2 but not t-1. Quinidine (100-1000 micrograms) did not affect either the t-1 or t-2. It is suggested that ATP-induced tachycardia in the dog is partially due to activation of the P1-purinoceptors named by Burnstock.

Cardiovascular effects of digitalis on intact dogs and isolated cross-perfused atria.

The chronotropic effects of digoxin and deslanoside were studied in canine atria cross-perfused with heparinized arterial blood from donor dogs. Intravenous injections of either drug (100 micrograms/Kg) into the donor dog produced bradycardia followed by ventricular tachyarrhythmia, with or without hypertension, in the donor dog. A significant increase in the developed tension was observed in the isolated atria, with or without slight sinus acceleration. These effects continued over 150 min after the injection. Digoxin (200 micrograms/Kg, i.v.) caused an immediate bradycardia followed by ventricular tachycardia. In addition, ventricular fibrillation occurred in 3 out of 5 donor dogs within 20 min of the drug administration. In isolated atria, there was a marked increase in the developed tension, usually with a little sinus tachycardia. Deslanoside (200 micrograms/Kg, i.v.) caused almost the same response patterns as digoxin. However, this dose of deslanoside caused ventricular fibrillation in all 6 experiments. Drug concentrations in the donor's arterial blood decreased rapidly for 15-20 min and then decreased slowly in all experiments. It is concluded that digoxin and deslanoside have no significant direct accelerating action on the SA node in doses which produced marked increases in the developed tension; only extremely high doses cause a direct, slight sinus acceleration.

The effects of aminophylline on adenosine and ATP actions on sinoatrial conduction in the isolated, blood-perfused dog atrium.

The effects of adenosine and adenosine triphosphate (ATP) on sinus cycle length (SCL) and sinoatrial conduction time (SACT) estimated by constant atrial pacing were studied in isolated, blood-perfused canine right atria. Adenosine and ATP were infused into the sinus node artery at a rate of 1, 2 and 4 micrograms/min. Both adenosine and ATP caused an increase in SCL and SACT in a dose-dependent manner and decreased atrial developed tension. There was no significant difference between the effect of adenosine and that of ATP on SCL and SACT. The prolongation of SACT induced by 4 micrograms/min of adenosine and ATP was significantly inhibited by a single injection of 1 to 3 mg of aminophylline, although this dose level of aminophylline did not significantly suppress the prolongation of SCL produced by adenosine and ATP. From these results it is concluded that both adenosine and ATP lengthen SCL and SACT in a dose-related manner, and that aminophylline blocks the increase in SACT much more easily than that in SCL.

Direct effects of digoxin and deslanoside on sinoatrial conduction in isolated, blood-perfused dog atria.

We studied the direct effects of digitalis on sinoatrial conduction time (SACT), atrial rate (AR) and developed tension (DT) in isolated atrial muscle, using an isolated dog atrial preparation perfused with heparinized blood from the carotid artery of an anesthetized donor dog. After digoxin or deslanoside (100 micrograms or 200 micrograms/Kg) was given intravenously to the donor dog, SACT, AR and DT of the isolated atrium were continuously measured. Following administration of 100 micrograms/Kg of digoxin, an immediate sinus bradycardia followed by various kinds of ventricular arrhythmias was observed in the donor dog, and the DT of the isolated atrium was augmented without any effects on the SACT and AR in all 3 experiments. With 200 micrograms/Kg of digoxin or deslanoside, ventricular fibrillation was induced in all 5 donor dogs within 75 min after digitalis administration. In these cases, the DT of the isolated atrium was immediately increased to over 200% of control DT, but SACT and AR were not affected until 20 min later, at which time increases in SACT and AR were finally induced. From these results, it is concluded that a large amount of digitalis has no distinct direct effect on SA nodal pacemaker activity and SA conductivity. Moreover, extremely large doses of digitalis which cause ventricular fibrillation might also induce a prolongation of SACT in addition to sinus tachycardia.