T. R. Harrison

The relation of age to the duration of contraction, ejection, and relaxation of the normal human heart

Abstract The chief findings in healthy persons with advancing age were as follows: (1) Progressive prolongation of the period of dicates that the pulse transmission time is the same at the end as at the beginning of ejection. Thus, the carotid upstroke-carotid incisura interval appears to be a reliable guide to the duration of ejection. (3) No significant change in the duration of ejection when corrected for heart rate. (4) Slight reduction in the excitation-carotid upstroke interval. However, the excitation-ejection time (i.e., the excitation-carotid upstroke interval corrected for pulse transmission time) tended to lengthen slightly with advancing age. The findings have led to the following tentative conclusions: (a) The prolongation of relaxation may be a factor of some importance in regard to the relative inability of old normal hearts to tolerate tachycardia. Rough calculations suggest that, as an average, a sustained rate of 120, or more, cannot be tolerated beyond the age of 70. (b) The basic mechanisms responsible for initiating pressure, for sustaining pressure, and for relaxation appear to vary independently. These findings and conclusions are based on data secured by indirect methods. Pending confirmation (or refutation) by more precise techniques, they should be considered as points of departure for further studies rather than as established concepts.

Effect of Rigid Sodium Restriction on Blood Pressure and Survival of Hypertensive Rats

Summary Drastic sodium restriction was shown to result in a marked drop in the blood pressure of rats with experimental hypertension. This drop in blood pressure was demonstrated to be accompanied by a prolongation of the survival of the animals. The drop was inhibited by the administration of large doses of choline.

Some unanswered questions concerning enlargement and failure of the heart

Abstract Certain observations and certain related but as yet incompletely answered questions may now be listed. 1. 1. Hypertrophy may exist in the absence of clear evidence of coexisting or pre-existing dilatation. Does this mean: (a) that undetected dilatation has necessarily been previously present, or (b) that dilatation is not an invariable antecedent to hypertrophy, which is caused rather by an increase in the mean systolic tension? 2. 2. Dilatation may be either beneficial or harmful. Is it possible that the net effect depends on the change in shape, i.e., on the relative predominance of increased stretch (beneficial) versus increased radius (harmful)? 3. 3. Atrioventricular asynergy. Distortion of the normal temporal relationship between atrial and ventricular contraction reduces the effectiveness of the latter. Is this due to an abnormal type of valve closure, i.e., by ascent with displacement of blood into the atrium as compared to normal closure by descent? 4. 4. A decline in the ratio of essential work to wasted work necessarily implies a decrease in ventricular effectiveness. To what extent is this quotient comparable to the ratio of ejection work to shape work during systole? 5. 5. Intraventricular asynergy. There is ample evidence that a variety of conditions, including, among others, hypertrophy, ischemia, extreme tachycardia, prolongation of ventricular excitation, and abnormal pathways of excitation, may lead to a marked increase in shape (and/or positional) work, as shown by exaggerated outward systolic motion. This signifies disturbed teamwork (asynergy) between the different parts of a single ventricle. Is the quantitative significance of this sufficient to be a highly important factor in the production of heart failure? 6. 6. The extreme phase of cardiac asynergy is ventricular fibrillation, in which the chamber has a flat Starling curve. Is it permissible to look on lesser degrees of ventricular asynergy as conditions in which the different portions of the same chamber have different Starling curves? In closing this discussion, two points should be emphasized. First, the concepts herein mentioned have stemmed from the work of a group of investigators and not solely from that of myself. Second, these ideas, although derived from past research, have little merit except as avenues of approach to future studies. Although they appear to be compatible with presently known facts, their validity can only be established by the accumulation of many new facts. The efforts of our own group in these directions will be more fruitful if modified and augmented by those of others. It is my hope that Grady Reddick, had he been with us, would have enjoyed this presentation. If so, we know that he would have had something pertinent and original to say about it. He was your colleague and mine. He was my friend and yours. He was a wise physician and a brilliant teacher, a kindly gentleman, and a strong man. I shall be permanently grateful to you for this occasion and for this opportunity to join with you in perpetuating his name and in paying tribute to his memory.

A study of the renal arteries in relation to age and to hypertension

Abstract A quantitative study has been made of the arteries, arterioles and glomeruli, in sections from the kidneys of elderly subjects with benign hypertension, of middle-aged individuals with malignant hypertension and of young persons with hypertension associated with glomerulonephritis. For purposes of comparison sections from the kidneys of nonhypertensive subjects in the same age groups have also been studied. The chief findings and conclusions are as follows: 1. 1. Narrowing of the large renal arteries is predominantly related to advancing age, the degree of change varying markedly in different subjects. Individuals with hypertension exhibit on the average more change in these vessels than do subjects of the same age dying of other diseases. 2. 2. Narrowing of the afferent glomerular arterioles appears to be mainly the result of hypertension, increasing age being a less important factor than in the case of the larger renal arteries. 3. 3. Narrowing of the small renal arteries is related both to hypertension and to increasing age, neither factor being particularly predominant. 4. 4. The small arteries in the pancreas exhibit less marked narrowing than do those of the kidney. 5. 5. The arterioles in the pancreas and those in the adrenals show approximately the same degree of change as do those in the kidneys. 6. 6. With increasing age there is a progressive decrease in the number of glomeruli per microscopic field, the change being more marked in hypertensive than in nonhypertensive subjects. Narrowing of the arterioles and arteries is one factor, but additional factors also seem to play roles in the diminution in the number of glomeruli. The possibility that involutionary changes, similar to those occurring in certain lower animals, are also concerned is discussed.

STUDIES IN CONGESTIVE HEART FAILURE: V. The Potassium Content of Skeletal Muscle Obtained by Biopsy

As a result of their studies of the respiratory exchange of decom-pensated cardiac patients during and after exercise, Eppinger, Kisch and Schwarz (1927) concluded that the buffering power of the tissues was diminished. Laszlo (1928) found diminished phosphate content of the cardiac and skeletal muscle of such individuals. Harrison and Pilcher determined oxygen utilization during various degrees of edema (1930a) and oxygen debt in patients with congestive heart failure (1930b). In both studies the findings were believed to be indicative of diminished alkaline reserve in the muscles. Observations by Pil-cher, Clarke and Harrison (1930) of the hydrogen ion concentration of the blood of patients with congestive heart failure after exercise lead to the same conclusion. In order to obtain more direct data on this point it was thought advisable to investigate the chemical changes in the tissues themselves. As potassium is the most abundant basic element in muscle tissue it seemed wise to study it first. Harrison, Pilcher and Ewing (1930) analyzed samples of cardiac and skeletal muscle obtained from patients who had died of congestive heart failure and found them to be abnormally poor in potassium. It seemed conceivable that such a phenomenon might be related to changes after death and consequently, before proceeding further with our studies on postmortem tissues, it was deemed wise to analyze tissues obtained during life. Such a procedure had the additional advantage of allowing us to make more than one observation on the same patient and hence to follow changes in potassium content under various conditions.

PRECORDIAL MOVEMENTS IN RELATION TO AGE.

Abstract The precordial motions have been compared in various age groups. All subjects were free of clinical or electrocardiographic evidence of cardiac disease. Despite variations within a given age group, certain general trends were noted. Increasing age was accompanied by evidence of: (1) a progressive decline in those motions ascribed to right ventricular activity, and a relative increase in those attributed to contraction of the left ventricle and/or interventricular septum; (2) certain changes which resemble in type, but not in extent, those seen in patients with congestive heart failure—(a) diminution of the outward movement due to passive filling, (b) a trend, despite wide variations within a given age group, toward increase in those right parasternal motions which are related to atrial contraction, and (c) a reduction in the ratio of filling motions to atrial motions. This indirect evidence of decline in output in relation to stretch points toward diminished efficiency in older hearts.

Studies in congestive heart failure

The cardinal symptoms of heart disease are dyspnea, edema, and pain. The recent important publication of Keefer and Resnik (1928) has done much to remove the subject of cardiac pain from the realm of controversy, and to lead to a better understanding of the mechanism by which it is produced, and hence, to a clearer clinical concept of its significance. Unlike cardiac pain, edema and dyspnea are ordinarily indications of congestive heart failure and although these two symptoms have been the subject of many valuable studies there is not yet entire agreement as to the exact physiological disturbances which lead to their production.

The action of drugs on cardiac output

Abstract 1. 1. The output per minute of the intact hearts of normal, unnarcotized, and of morphinized dogs, as determined according to the Fick principle, has been studied before and after the intravenous and subcutaneous administration of caffeine sodiobenzoate in doses of 7.5, 15 and 30 mg. per kilogram. 2. 2. After doses comparable to therapeutic doses for humans (7.5 and 15 mg. per kilogram), the average change in the minute cardiac output was a decrease in both instances of less than 10 per cent. This change was independent of changes in oxygen consumption. 3. 3. Larger doses produced a proportionately greater decrease in the cardiac output per minute. 4. 4. These experiments suggest that caffeine sodiobenzoate in therapeutic doses has no direct beneficial action on the circulation. 5. 5. No significant change was observed in the respiratory rate or depth. It is believed that this phase of the drugs action demands further investigation.

The psychologic management of patients with cardiac disease

Abstract Dangerous disorders which threaten life, and serious disorders which threaten happiness are not the same. Death is inevitable; its occurrence before ones expected time is, at worst, only a quantitative tragedy. But misery of spirit lasting for decades is not inevitable; its occurrence at all is a qualitative tragedy. Sedatives and tranquilizers have their proper place as weapons against fear but are far inferior to the wise physician. He, by his words, actions, and feelings, can do much to banish this most common and most distressing of the symptoms related to disease of the heart. He must avoid the mistake of binding a vigorous Prometheus to the rock of Misery with chains of Fear forged either by a false diagnosis of structural heart disease or by an erroneous evaluation of its functional significance. Neither the electrocardiogram, the fluoroscope, nor the cardiac catheter can tell the physician what to say or how to say it. Science is no bubstitute for wisdom.

STUDIES IN CONGESTIVE HEART FAILURE: VIII. The Effect of the Administration of Dibasic Potassium Phosphate on the Potassium Content of Certain Tissues

Previous investigations have shown that the potassium contents of both the skeletal and the cardiac musde of patients dying of congestive heart failure were diminished (Harrison, Pilcher and Ewing, 1930). Analyses of tissue obtained by biopsy indicated that edema was probably the cause of the loss of potassium from the skeletal muscle (Pilcher, Calhoun, Cullen and Harrison, 1930). Studies on hearts of subjects dying under various conditions led to the belief that overwork was probably responsible for the loss of potassium from the cardiac muscle (Calhoun, Cullen, Clarke and Harrison, 1930). In order to determine whether or not this chemical change is irreversible the observations described in this paper were carried out.