Sudden cardiac death (SCD) continues unabated. Coronary care units, while effective in lowering hospital mortality, cannot significantly reduce SCD which occurs primarily outside the hospital and accounts for the majority of deaths from coronary heart disease (CHD). In view of the frequent precipitous nature of SCD, only a program which identifies and protects the victim prior to the event can hope to be successful in preventing the majority of SCD. Since it is likely that SCD is due to an arrhythmia, drug prophylaxis might prove effective. In view of the toxicity of currently available agents, it is mandatory to preselect a population at highest risk before embarking on a drug trial. Ventricular premature beats (VPB) may identify subjects susceptible to SCD. Epidemiologic and physiologic information on VPB is reviewed, and proposals are made for studies designed to establish the usefulness of VPB as a risk factor for SCD.

Approaches to Sudden Death from Coronary Heart Disease

Recovery of excitability of ventricular muscle was measured at numerous points in exposed dog ventricles at varying distances along six radial axes from a primary point of stimulation. Temporal dispersion of recovery of excitability at various points equidistant from the point of stimulation was minimal after a basic beat but was increased after an early premature beat. The degree of dispersion following a basic beat was increased by stimulation of the cardiac sympathetic nerves, administration of chloroform, ouabain intoxication, administration of higher doses of quinidine, myocardial ischemia, and hypothermia, but it was decreased by administration of sympathomimetic amines.

Nonuniform Recovery of Excitability in Ventricular Muscle

The long Q-T syndrome.

https://vincentbourquin.files.wordpress.com/2009/11/broad-spectrum.pdf

Increased Central Venous Pressure Is Associated With Impaired Renal Function and Mortality in a Broad Spectrum of Patients With Cardiovascular Disease

The arrhythmogenic role of increased dispersion of repolarization (dispersion) was studied in 23 open-chest dogs using six simultaneously recorded monophasic action potentials (MAPs) from the ventricular surface and programmed ventricular premature stimulation (VPS). Increased dispersion was induced by generalized hypothermia (29 degrees C) and regional warm blood (38-43 degrees C) perfusion through a coronary artery branch. Hypothermia and regional warm blood perfusion increased maximum dispersion from 13 +/- 10 to 111 +/- 16 msec (p less than 0.001), predominantly because of the increased MAP duration difference (10 +/- 15 vs 97 +/- 16 msec, p less than 0.001). The maximal difference between activation times was not significantly changed, but the QRS duration increased from 47 +/- 6 to 52 +/- 7 msec (p less than 0.01). Ventricular arrhythmia did not occur spontaneously but was induced by a single VPS in all 23 dogs during hypothermia and regional warm blood perfusion when dispersion reached a critical magnitude. The critical magnitude of dispersion required to induce ventricular arrhythmia was documented in 16 dogs by stepwise increments or decrements of dispersion. In four dogs, an increase in atrial pacing rate of 24 beats/min prevented induction of ventricular arrhythmia by decreasing dispersion from a critical magnitude of 103 +/- 5 msec to a nonarrhythmogenic value of 86 +/- 9 msec (p less than 0.05). In six dogs, we compared the stimulation site-dependent effects of VPS applied in the region with short and long MAPs. In all dogs, ventricular arrhythmia was inducible only by VPS from the region with a short MAP. Premature impulses from this region propagated more slowly than those from the region with a long MAP. Our results show that the large dispersion of repolarization facilitates the development of a conduction delay necessary to induce sustained arrhythmia by an early premature stimulus applied at the site with a short MAP.

Characteristics and possible mechanism of ventricular arrhythmia dependent on the dispersion of action potential durations.

It is generally believed that in order to induce ventricular fibrillation by electric currents they must not only have a minimal intensity but must act for a fair interval of time (ca, several seconds). Indeed, the variation in duration of a current has been used as a criterion of the sensitivity of the heart (1). In 1934 King (2) and in 1936, Ferris, King, Spence and Williams (3) reported that shocks as short as 0.03 second are effective in fibrillating the ventricles provided they are applied during the occurrence of the T wave, which they interpreted as the partial refractory phase. Previous to this, de Boer (4) had shown that a process similar to fibrillation in mammalian hearts can be induced in the frog’s ventricle by induction shocks applied near the end of the systole, but he believed only during a hypodynamic state. Andrus, Carter and Wheeler (5) found that an induction shock similarly introduced into normal auricles of dogs caused auricular fibrillation. During 1923-24 the senior author (6) in studying the response of the dog’s ventricles to strong induction shocks demonstrated that the mammalian ventricle is not refractory to stimuli for a considerable, though apparently variable, interval of systole (last 0.03-0.09 sec. of systole). In order to produce premature contractions by shocks applied during systole it was necessary to utilize very strong break shocks, and in the zeal to elicit such contractions ventricular fibrillation all too often terminated the experiment. A survey of many records has shown that this was due to single shocks and that all were delivered somewhere during the non-refractory phase of ventricular systole. In view of the importance of observations that a very brief shock is capable of inducing fibrillation even when the exciting current traverses only a small area of the ventricle, it seemed important

Ventricular fibrillation due to single, localized induction and condenser shocks applied during the vulnerable phase of ventricular systole

Effect of increased renal venous pressure on renal function.

The effects of myocardial ischemia on the fibrillation threshold—the mechanism of spontaneous ventricular fibrillation following coronary occlusion

In the past thirty years, numerous observations have been made on the hemodynamic effects of arteriovenous fistulae. Arteriovenous fistulae of variable size and location have been studied in patients as well as in animals. Such studies have consisted a) in observing the effect of suddenly opening and closing a fistula in acute experiments, b) in studying the effects of suddenly closing and opening a fistula in an animal or a patient who had had such a fistula for a relatively long time, and c) in recording the effect of complete surgical eradication of a long-standing fistula. While some agreement has been reached on many points, there persists some controversy about most of them (1). It is now generally agreed that an

/pdf/an-experimental-study-of-the-immediate-hemodynamic-wid1nt0vgp.pdf

An experimental study of the immediate hemodynamic adjustments to acute arteriovenous fistulae of various sizes

In acute experiments on the anesthetized dog, partial or complete occlusion of the left innominate vein resulting in a rise of pressure in the venous territory into which the thoracic duct drains, commensurate with the venous pressure rise seen in congestive heart failure, reduces the flow of lymph in the thoracic duct. This decrease in thoracic duct lymph flow is due, at least partially, to the accumulation of lymph in the lymphatic system and possibly the intercellular spaces. The present acute experiments suggest the possibility that this factor may play a role in the genesis of the systemic edema of chronic congestive heart failure, although only chronic experiments now under way will permit definitive conclusions.

René Wégria

Papers

Ventricular fibrillation due to single, localized induction and condenser shocks applied during the vulnerable phase of ventricular systole

Effect of increased renal venous pressure on renal function.

The effects of myocardial ischemia on the fibrillation threshold—the mechanism of spontaneous ventricular fibrillation following coronary occlusion

An experimental study of the immediate hemodynamic adjustments to acute arteriovenous fistulae of various sizes

Effect of systemic venous pressure on drainage of lymph from thoracic duct.