Otto F. Muller

The hypotensive effect of imipramine hydrochloride in patients with cardiovascular disease

The untoward effects of imipramine hydrochloride were studied in a group of 41 patients under 60 years of age who were without demonstrable cardiovascular disease and compared with those in a group of 50 patients with various degrees of generalized or coronary atherosclerosis. Effects on the following were investigated: recumbent and standing blood pressures, pulse, electrocardiograms, blood coagulation (bleeding time, clotting time, prothrombin time), liver function (SGOT, alkaline phosphatase, cephalin flocculation, thymol turbidity), and formed elements in the blood (hemoglobin, white blood cells with differential count, platelets).

Adams-Stokes syndrome due to sinoatrial block

Abstract A case of a 29 year old female patient with sinoatrial block, first degree A-V heart block and Adams-Stokes seizures since the age of 11 is reported. The mechanism of the syncopal attacks was established by continuous radioelectrocardiographic monitoring as episodes of sinoatrial heart block or arrest, or both. There was no evidence of inflammatory, degenerative or congenital heart disease, and the patient had never received drugs assocated with the production of Adams-Stokes seizures. From the etiologic standpoint exaggerated vagal effects undoubtedly played a role; the existence of a congenital abnormality of the conduction system must, however, be taken into consideration. Treatment with artificial pacemaker stimulation proved effective and prevented further Adams-Stokes attacks.

Familial congenital A-V dissociation

Abstract Four cases of incomplete A-V dissociation with ventricular capture occurring in the same family have been presented. Two of them definitely had no other congenital cardiac abnormality as proved by cardiac catheterization; 1 was probably not associated with an additional congenital lesion, and in the fourth case transposition of the great vessels was diagnosed as an associated finding. Various aspects of congenital cardiac arrhythmias have been discussed.

Glycogen-storage disease. Report of a case with generalized glycogenosis and review of the literature.

A case of glycogen-storage disease (Coritype II), with accumulation of glycogen in the myocardium, skeletal muscle, smooth muscle, liver, kidney, central nervous system, and autonomic ganglia is presented. Glycogen storage in the autonomic ganglia of the intestinal tract (Plexus-myentericus-Auerbach), which gave rise clinically to Hirschsprungs disease, could explain the feeding problems and constipation often observed in these cases. The classification into four different types of Cori and Andersen appears to be the most satisfactory one at the present time. These types are different disease entities with the same expression of abnormality, the deposition of glycogen; but the pathogenesis and the clinical and pathologic findings are strikingly different. Glycogen storage of the heart is probably more common than the review of the literature indicates. Many of these cases are missed, mainly types III and IV, because the possibility is not considered and the patient is inadequately studied in life and during necropsy.

EFFECT OF NICOTINE ON THE CORONARY BLOOD FLOW IN THE PRESENCE OF CORONARY INSUFFICIENCY: AN EXPERIMENTAL STUDY IN DOGS*

I t has been shown that nicotine and tobacco smoke in the normal dog and in the human increase the coronary blood This is associated with an increase in oxygen consumption and an increase in cardiac work, which can be readily accomplished in the normal heart with normal coronary arteries. The problem that requires investigation is the determination of the effect of nicotine in the presence of various types and degrees of coronary insufficiency, for example, in narrowing of the lumen of the coronary arteries or in the presence of coronary artery disease. This point would appear to be of considerable theoretical and practical importance because many patients over the age of 45 or 50 years with varying degrees of coronary disease and/or coronary occlusion are subjected to the effects of nicotine in tobacco smoke. To meet the demand of increased cardiac work, the coronary blood flow must increase. However, there is little data available relative to the response of the coronary blood flow in the presence of coronary artery narrowing and/or myocardial impairment.

Cardiac toxicity of methylphenidate. Report of two cases.

METHYLPHENIDATE, a cerebrocortical stimulant, has been studied in a wide variety of clinical settings for its mood-elevating effects. Recently, it has been used in the treatment of drug-induced let...

QRS alterations produced by auricular and ventricular paroxysmal tachycardia in the presence of bundle branch block patterns. An experimental study in dogs.

Abstract Experimental auricular and ventricular tachycardias have been produced at various sites of the heart in the presence of bundle branch block. The following conclusions can be made: 1. 1. Supraventricular tachycardias do not alter complete bundle branch block patterns significantly. They may, however, increase incomplete types of bundle branch block. 2. 2. Ventricular tachycardias from the ventricle below the intact branch produce bundle branch block patterns from the opposite side. 3. 3. The QRS morphology of ventricular tachycardias from the ventricle below the affected bundle branch depends upon the time of the cardiac cycle in which the stimuli occur. Between the T wave and the beginning of P, complete bundle branch block patterns are produced. Stimuli which fall into the P-R interval fuse with the activation wave coming from the auricle through the unaffected branch and result in narrowed or relatively normal QRS complexes. Fusion beats can be seen which exhibit the typical morphology of the WPW syndrome if the ventricular stimulus is discharged immediately after the P wave.

SYNTHESES AND BIOLOGICAL BEHAVIOR OF ADDITIONAL CORRINOID COENZYMES

The biological behavior of synthetic corrinoid coenzyme analogues gives an insight into the mode of action and the biochemical significance of certain structural elements of the coenzyme forms. While cobalamin coenzyme and cobinamide coenzyme were shown to be active in the methylmalonate isomerase system, Co-5’-deoxyinosylcobalamin was inactive.14 This points to a special function of the nucleoside ligand. The nucleotide portion on the other hand is not necessary. In order to examine the structural specificity, the synthesis of further cobalamin coenzyme analogues was undertaken. Co-5’-dexoyguanosylcobalamin already could be prepared. Following the principle of coenzyme ~ y n t h e s i s ~ J ~ ~ * ~ ~ ~ ~ we tried to isolate 5’-tosyl-2’,3’-isopropylidene-guanosine in the pure form. But this was not possible probably because of intramolecular reaction of the C ( 5 ’ ) and N( 3) position of the guanine, forming the cyclic nucleoside. As is known, the cyclic nucleoside is formed, as a by-product, by the synthesis of 2’,3‘isopropylideneS’-to~yladenosine.~ The greater tendency of the guanosine derivative to form the cyclic nucleoside appears to be clear, for its N(3) is more nucleophilic than the N(3) of the corresponding adenosine derivative on account of the neighboring amino-group on C(2) . But the synthesis of Co-5’-deoxyguanosyl-cobalamin is possible when the cobalamin-hydride is allowed to react with the crude mixture of the tosylation of 2’,3’-isopropylidene-guanosine in pyridine/dimethylformamide and subsequent removal of the isopropylidene-group by dilute sulphuric acid. On treatment with cyanide ions in the dark the splitting takes place in the same way as in the case of cobalamin coenzymei and Cod’-deoxyinosylcobalamin. The cyano-cobalamin and guanine obtained, were identified by means of chromatography, electrophoresis, and spectrophotometry. The discovery of the method for synthesizing corrinoid coenzymes and analogues opens another possibility for the study of the biochemical functions of corrinoids. The enzymatic transfer of a methyl-group from Comethylcobalamin to homocysteine8 demonstrates that not only the coenzyme forms of the corrinoids have a biochemical function. It is possible that the corrinoids also participate in other transfer-reactions, the intermediates of which can not be isolated because of their rapid transformation in biological systems. Nowadays it is possible to synthesize and to test supposed intermediates of biochemical transfer-reactions. Coenzyme analogues of cobalamin, for example, Co-5‘-deoxyinosylcobalamin, are transformed relatively rapidly, coenzyme analogues of cobinamide relatively slowly into the coenzyme forms by P. shermanii (FIGURE 1 ) . We presume the transformation to take place by an exchange

Effect of Hypothermia on Experimentally Produced Arrhythmias

The effect of hypothermia on experimentally produced rapid arrhythmias in the dog was studied. Rapid ectopic rhythms were produced in open-chest and “intact” animals by application of aconitine solution to the right atrial wall. In all experiments, a beneficial cardiac effect was obtained: marked slowing of the ventricular rate occurred in all cases, and in approximately half of the cases sinus rhythm was restored. On rewarming, although the heart rate increased, the sinus rhythm acquired during hypothermia persisted in most instances. The blood pressure fell when a rapid arrhythmia was produced. A further drop was observed in approximately half the cases during hypothermia. In the remaining cases no change, or a slight rise in blood pressure, occurred during cooling. The results obtained in the experimental animal would appear to have a bearing on the therapy of certain refractory arrhythmias in the human subject.