September 22, 1915 - February 23, 2016
I was born in the German speaking region of Czechoslovakia near Karlovy Vary, in the year 1915. I studied medicine at the Charles University in Prague. I had a leading position in the student movement against fascism and war. I edited a student journal for this movement. I was a member of Czechoslovak delegation to the World Congress of Students against War and Fascism in Paris in the summer of 1937. After the border regions where I was born, were given to Hitler by the agreements of Munich and Godesberg I was excluded from the University, and I left the country illegally. I lived in France, but I got an official permission to stay in France only after Hitler made Czechoslovakia a “protectorate” of Germany. I started to work as a volunteer in the University clinic in Paris, in the morning, in the afternoon and evening I tried to make a living by all sorts of activities.
When WWII started, I volunteered for the Czechoslovak Army in Exile, formed in the South of France in October 1939. In the summer1940 we defended France against Hitler's invasion from the North. Without proper weapons and equipment, the front retreated. The Czechoslovak Army units were shipped to England. Reorganized as Armed Brigade of the British Army, we took part in the English costal defense. Subsequently, we participated in the liberation of France. In December 1944 on a voluntary mission, I was gravely wounded. I was evacuated by air to a special military hospital in Basingstoke England. Several operations and, mainly, just introduced penicillin saved my life.
After the war I decided to return to my country which, we were told, had been liberated by the Russian army. I finished my medical degree, worked in a hospital and later I became a cofounder of the Cardiovascular Research Institute in Prague. I started to work on the pathogenesis and therapy of hypertensive disease. The official concept propagated by the Russians was that the disease is generated by the cortex of the brain and that it is treated successfully with sleep therapy. Many papers appeared in the countries behind the Iron Curtain were describing this success. We could not find any difference in nervous activity of hypertensive people and of controls. We tried several methods of sleep therapy, and found that the longer the therapy is applied, the more difficult it becomes, to prolong the sleep we could not confirm the therapeutic effect of sleep. We reported the results to the health ministry and on conferences. The use of the therapy was discontinued in hospitals. Our paper, however, was never published.
We tested several therapies which were praised in the medical literature as being successful, for instance, an extract from the Indian plant Rauwolfia, produced by CIBA as Reserpine.
All papers reported that after medication with Reserpine for a week or two, all patients could be released home with lowered blood pressure. That happened also to our patients. As we continued treating these patients and followed them weekly, we observed that the pressure returned to the original high values. We gave Reserpine to our experimental dogs in a dosage by kg weight comparable to the dosage used in humans. Their normal pressure fell also in the first weeks and later returned to their original value. However the dogs were trained to recognize a tone preceding feeding from a different tone not combined with feeding. The condition tone was accompanied by salivation, heart rate and respiratory rate increase. The tone not connected with feeding elicited a far smaller response [discriminatory inhibition]. Under the influence of Reserpine, the reaction to the conditioned signal and the signal for no food disappeared. The reactions became similar. This made us pay special attention to the spirits and mental activity of our patients taking Reserpine, and we found that the patients were tired and depressed. We wrote a paper about these results, each journal, we offered our paper, sent it to Dry Bein, who headed the Reserpine section of Ciba. He always rejected the paper.t was never published. Finally the famous writer Hemingway committed suicide. Journalists found out he had been depressed in the last months, and that he was on reserpine. After this, many papers reported that reserpine caused depression. Reserpine was an inefficient and dangerous drug.
We helped our own patients out of the depression by giving them small doses of methylphenidate called Ritalin. We tested Ritalin on our dogs. We expected this psychotropic drug to strengthen the conditioned reflex to food signals [more salivation, more heart rate increase]. This did not happen. The psychotropic drug weakened the reaction to the signal which did not mean food. It improved the discrimination between the signals. We learned this way that the more sensitive function of the mental activity is the discrimination. We tested still several other substances suggested at this time for the treatment of hypertension. We combined the results of our experimental studies in a monograph: “Pharmacodynamische Analyze…” edited by Gustav Fischer Verlag, Jena. We discussed our results at a symposium held by the WHO. I was visiting professor in Poland, Hungary and Russia.
After working ten years in the Institute, a committee of the communist party was created to investigate me, as happened at this time also to other people, who were during the war in the West or taking part in the Czech army or fought in the Spanish Brigade. I was charged to be an enemy, to disregard Soviet science, to attract too many Jews to work in the Institute etc. These investigations were terrible and usually led to criminal court, prison and worse. Then in the newspaper appeared a notice that some processes against Jewish physicians in Leningrad were revised. Then Stalin died. My investigation ended without prosecution. The decision was made that I made mistakes and I should leave the Institute. I was transferred to the Institute of Hygiene. This had different aims of research, had no patients, no animal research
I was invited by the University of Michigan. The authorities did not permit me to accept. The Michigan University did not accept no for an answer and complained at the government level. Finally I could go. I arrived in November 63, stayed for a month in Michigan, and then travelled for five months to many other universities. I was impressed by the free life and discussion at the universities, and by the instrumentation. Especially important was the development of flow meters. It made it possible to measure not only flow, but also changes in flow in intact vessels.
After I returned to my family at home, I decided to get to the USA mainly because I wanted my children to study and live in freedom. It took three years to organize our difficult and dangerous escape. I accepted the invitation to work from a group of highly qualified and supportive scientists at Hopkins University. Most of our research was done with awake, intact and behaving dogs. We measured flow in the ascending aorta and in the circumflex coronary artery, pressure in the right atrium, the aorta and the pleural space. On the first graph we show the flow in the ascending aorta and the flow in the coronary artery: in the aorta the flow is continuous and the pulse wave starts with the contraction of the heart. In the coronary artery the flow decreases during the contraction of the heart. The coronaries are filled quickly during diastole.
In the second graph, the changes of cardiac output, heart rate, stroke volume, coronary flow, blood pressure, heart rate and right atrial pressure from rest values are shown. These mean values were obtained from 20 experiments in one dog. Even though the cardiac output increases immediately from the onset of exercise, the aortic blood pressure does not change. This shows that at the beginning of exercise, the flow through muscles increases substantially, the blood pressure falls, and the lowering of the afterload increases cardiac output. The aortic valve opens earlier and closes later. The pressure in the atria falls. This shows that the circulatory reaction to exercise is initiated by the metabolic needs of the muscles and the increase of flow is regulated by the arterial beds.
In narcotized dogs we compressed the femoral artery quickly to zero flow, we got a straight line with a pressure intersect of 40 mmHg. We compressed the descending aorta quickly to zero, and got a straight line with a similar intercept.
These and other results taught us that the upstream pressure for flow in the arterial bed is in the ascending aorta. The downstream pressure is the pressure at the opening of the capillary vessels. The opening of the capillaries is determined by the metabolic needs of the organs. The capillaries direct the flow. In exercise the muscles need much blood. I he blood pressure falls. The aortic valves open early close later, more blood is pumped out. The pressure rises again to the pre-exercise level.
This schema helps to explain also the pathogenesis of hypertension.