by 1967, every State will not only have finished its iniut will have established the processes of continuous planelopment that are necessary to assure that communities ze can be reached. With the enactment of Public Law = assistance toward the personnel costs of centers, fewer to delay construction projects for lack of funds to operitial year. With support from the $50 million requested persons to whom a community based continuum of mental available, when and as needed, will be increased by apn citizens. FRIDAY, MARCH 4, 1966. NATIONAL HEART INSTITUTE WITNESSES DR. WILLIAM J. ZUKEL, ACTING DIRECTOR, NATIONAL HEART INSTITUTE DR. JAMES A. SHANNON, DIRECTOR, NATIONAL INSTITUTES OF HEALTH R. H. HENSCHEL, EXECUTIVE OFFICER, NATIONAL HEART INSTITUTE JOHN H. REEDER, BUDGET OFFICER CHARLES MILLER, FINANCIAL MANAGEMENT OFFICER, NATIONAL INSTITUTES OF HEALTH DR. WILLIAM H. STEWART, SURGEON GENERAL HARRY L. DORAN, CHIEF FINANCE OFFICER JAMES B. CARDWELL, DEPARTMENT DEPUTY COMPTROLLER 1 Includes capital outlay as follows: 1965, $477,000; 1966, $461,000; 1967, $515,000. 2 Selected resources as of June 30 are as follows: Unpaid, undelivered orders, 1964, $2,238,000 (1965 adjustments $41,000); 1965, $1,299,000; 1966, $1,299,000; 1967, $1,299,000. Mr. FOGARTY. The committee will come to order. We will now take up the appropriation request for the Heart Institute. Dr. Zukel, will you present that justification? BIOGRAPHY OF PRINCIPAL WITNESS Dr. ZUKEL. Mr. Chairman and members of the committee, I shall try to justify the appropriation request which is before you. First, Mr. Chairman, I would like to indicate that my position at the National Heart Institute is that of the Associate Director for Collaborative Studies. I have had this position for the past 5 years. In October I was designated as Acting Director of the Heart Institute for the interval period until the new director would be selected. My back ground, however, has been in cardiovascular disease since the time I entered the Service in 1949 and although I have not had a chance to become thoroughly familiar with all the details of the total Institute's program, I believe that I have participated in enough Heart Council meetings and in its general planning meetings that I have the feel of our Heart Institute staff and of our advisors for the program which we are presenting. Do you wish me to read the statement? Mr. FOGARTY. I think that would be best. GENERAL STATEMENT Dr. ZUKEL. Mr. Chairman and members of the committee: During 1965, the programs of research conducted and supported by the National Heart Institute resulted in major contributions to our steadily accumulating fund of scientific knowledge of the cardiovascular system and its diseases and a number of noteworthy advances in the prevention. diagnosis, and clinical management of cardiovascular disorders. Attesting to the scope and productivity of these programs are the more than 3,000 scientific papers and abstracts on every conceivable phase of cardiovascular research that were published during the year by NHI scientists and grantees. The summaries presented here represent only a very small sampling of their results. HEART INSTITUTE RESEARCH ATHEROSCLEROSIS Recent NHI studies have shed new light on the mechanisms by which certain hormones control the release of fatty acids from adipose tissue to supply metabolic fuels during fasting, exercise, or stress. The scientists have isolated from adipose tissue two systems that appear to mediate the effects of these fat-mobilizing hormones. Under the influence of these hormones, one system converts enzymes called lipases from an inactive to an active form. The activated lipases break down stored depot fat to fatty acids, which are released into the blood to meet current energy needs. When the hormonal influence is withdrawn, the second system rapidly inactivates the lipase enzymes thereby curbing or halting further outpouring of fatty acids from adipose tissue. The NHI has also introduced a new method of recognizing and classifying excesses in blood cholesterol and other fats on the basis of plasma lipoprotein patterns, obtained by a simple, low-cost technique. The NHI scientists are particularly interested in using it to find out how many different inheritable diseases among Americans are expressed in high blood-fat concentrations and, sometimes, in accelerated blood-vessel disease. Already they have demonstrated several syndromes not previously recognized as separate diseases and have pointed out the strong association of some of these with diabetes. This "NIH classification" is now being set up in laboratories in other countries and promises a basis for establishing the prevalence of these diseases in other populations of the world. HYPERTENSION In the sympathetic nervous system, norepinephrine is the chemical transmitter that acts between the nerve endings and the receptors of target organs. A large number of drugs that affect blood pressure appear to do so by influencing various aspects of norepinephrine metabolism. With the recent development of compounds that effectively block the production of norepinephrine in the various tissues of the body, hopes have been high that these agents might provide a promising new approach to the treatment of hypertension and possibly other disorders. Recently, alpha-methyl-p-tyrosine, the most potent of these agents, has been cautiously tested in a small number of patients with essential hypertension. The drug produced significant inhibition of norepinephrine synthesis, sedation, and tranquilization, but had little effect on blood pressure. Since submaximal doses of the drug were used in these preliminary trials, two questions remain to be answered: (1) will larger doses of the drug be more effective in reducing blood pressure? and (2) If so, will the sedative side effects also be intensified? Clinical studies currently in progress should provide answers to both questions. More promising clinical results have been achieved with this drug in patients with pheochromocytoma, a tumor that produces and secretes large quantities of norepinephrine, causing hypertension, elevated metabolic rate, headaches, and other distressing symptoms. Alpha-methyl-p-tyrosine sharply curbed norepinephrine synthesis by the tumor and also reduced blood pressure in these patients. These preliminary results suggest that this or similar drugs may prove useful in the clinical management of inoperable pheochromocytoma. They may also reduce the hazard of surgery for this condition by rendering the tumor nonfunctional prior to operation. Both possibilities are currently being explored. CONGESTIVE HEART FAILURE Earlier NHI studies had indicated that persistent hyperactivity of the sympathetic nervous system in patients with congestive heart failure could eventually lead to significant depletion of their cardiac stores of norepinephrine, a powerful cardiac stimulant that increases the vigor and efficiency of heart-muscle contraction. It was suggested that this norpinephrine depletion might be an important factor in the deterioration of heart performance observed in the later stages of congestive heart failure. Subsequent studies have confirmed that the reduced norepinephrine content of the failing heart does greatly reduce its responsiveness to sympathetic stimulation and to those cardiac stimulants that act through the release of norepinephrine. However, basal heart-muscle contractility is not depressed by norepinephrine depletion, and there is no impairment of its responsiveness to digitalis and other therapy for improving heart performance. Aldosterone, an adrenal cortical hormone that promotes salt and water retention by the kidney, is often secreted in excessive quantities in patients with congestive heart failure. But hyperaldosteronism alone cannot account for the chronic salt retention and edema that so often accompany this disorder. In normal subjects, large daily doses |