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EFFECT OF PROPRANOLOL
1026 result of either a low level of the factor itself or a diminished concentration of its evolver (activator). In other words, in certain cases the in-vitro level of a blood-clotting factor (as in von Willebrand’s syndrome) does not represent the in-vivo level. This, combined with the ability of ellagic acid2 to evolve factor xil and of certain chemicals3 evolve other clotting factors, suggests the possibility that thrombosis is essentially dependent (as far as the role of blood-clotting factors is concerned) on the abnormal in-vivo evolvement of certain blood-clotting factors. Such an explanation would support the doubt as to the efficacy of present anticoagulant therapy; ideally we require an anticoagulant acting not by lowering the levels of some bloodclotting factors but by inhibiting their evolvement in the circulation of patients, particularly those with advanced atherosclerotic disease. Department of Pathology,
as a
Shenley Hospital,
F. NOUR-ELDIN.
Hertfordshire.
EFFECT OF PROPRANOLOL SIR,-As a result of their research Parratt and Grayson4 gave it as their opinion that propranolol reduces the myocardial blood-supply more than it decreases the myocardial requirement for oxygen. In reply to a letter from one of us challenging this opinion they cited 6 Redding and Russell Rees7 who found decreased oxygen saturation of coronary-sinus blood after administering propranolol. This view was cited last week (p. 917) by Dr. Balcon and his colleagues, and if true would support the idea that the adequacy of myocardial blood-supply is decreased after propranolol. Redding and Russell Rees were kind enough to show us their results, which were obtained in dogs. The dogs were heavily drugged, which may in itself alter the effects of the drug being tested, and the data came from few experiments which, perhaps because of the anaesthesia, showed rather a large scatter. We therefore decided to obtain coronary-sinus blood, before and after administration of propranolol, from patients undergoing cardiac catheterisation for other reasons. As is customary in our laboratory, no drugs of any sort were given before catheterisation, except her usual dose of digitalis in one of our patients. 5 mg. of propranolol was administered intravenously ill/,-2 hours after the procedure had started; from the pulse-rates 30 minutes before, and immediately before, the propranolol was given, it can be seen (see accompanying table) that the patients were calm and in a steady state. We
hope
to publish more cases in full later, but they take to collect, and we therefore decided to report the
some time results of the first four cases, since
2. 3. 4. 5. 6. 7.
they
were
identical, and do
Botti, R. E., Ratnoff, O. D. J. Lab. clin. Med. 1964, 64, 385. Nour-Eldin, F. Ann. N.Y. Acad. Sci. (in the press). Parratt, J. R., Grayson, J. Lancet, 1966, i, 338. Mendel, D. ibid. p. 597. Parratt, J. R., Grayson, J. ibid. p. 819. Redding, V. J., Russell Rees. ibid. p. 548. EFFECT OF PROPRANOLOL
(5
mg.
support a concept which may impair the understanding of the mode of action of a drug which is widely used. The reduction of pulse-rate in each patient was greater than 10%, and this is evidence that an effective dose had been given. These first four cases show no change in the coronary-sinus oxygen saturation after the administration of propranolol, and this despite a fall in the oxygen saturation of mixed venous blood in the two patients in whom it was measured.
not
It is reasonable to conclude from these results that the decrease in coronary blood-flow caused by the administration of propranolol is in proportion to the decreased amount of work that the heart, beating more slowly with a lower blood-pressure and a slower rate of change of pressure,5 has to perform. Although for obvious reasons we did not give the drug to patients with failing hearts, we think that the cause of the deaths associated with the administration of propranolol to such patients is more likely to be due to a reduction of an already diminished cardiac output by bradycardia in a patient who is incapable of increasing his stroke volume, than to any disproportionate reduction of coronary flow. DAVID MENDEL St. Thomas’ Hospital, EDWARD BYRNE-QUINN. London S.E.1.
FALLACIES IN ELECTROCARDIOGRAPHY? SIR,-Recent articles on application of electrodes for electrocardiographic recording have used fallacious arguments to discredit the need for abrasive pastes,89 or indeed for any electrode jelly.10 The first fallacy is based upon a misconception or neglect of the effect of lead-selection circuitry on the potentials of the Wilson " neutral " and Goldberger " indifferent" electrodesa point discussed quite thoroughly some years agoY-13 Later references to the point 14 show an awakening awareness of this aspect, without any attempt to consider its implications. It is necessary to stress that Lewes’ incorrect reference to " electrocardiographs of input impedance of 2 megohms or " more 8 refers only to the amplifier section, since the input resistances presented by his various instruments across the limb leads are only about 200, 10, and 100 kohms respectively, when recording unipolar lead potentials, according to the manufacturer’s report. Moreover, any evidence of success using the low-impedance (10 kohms) connection of his instrument for such recording (the only really crucial test of his hypothesis) is omitted. The second and consequent fallacy results from generalising from a few particular cases, without considering the 8. 9. 10. 11.
Lewes, D. Br. Heart J. 1965, 27, 105. Lancet, 1965, i, 795. Lewes, D. ibid. 1965, ii, 17. Rappaport, M. B., Williams, C., White, P. D. Am. Heart J. 1949, 37, 892. 12. Rappaport, M. B. Sanborn Technical Bulletin, November, 1957. 13. Dower, G. E. Circulation, 1963, 28, 483. 14. Lewes, D. Wld med. Electron. 1966, 4, 240.
INTRAVENOUSLY) ON PULSE-RATE, AND CORONARY-SINUS AND PULMONARY-ARTERY % IN 4 PATIENTS UNDERGOING CARDIAC CATHETERISATION
OXYGEN-SATURATION
as a
Shenley Hospital,
F. NOUR-ELDIN.
Hertfordshire.
EFFECT OF PROPRANOLOL SIR,-As a result of their research Parratt and Grayson4 gave it as their opinion that propranolol reduces the myocardial blood-supply more than it decreases the myocardial requirement for oxygen. In reply to a letter from one of us challenging this opinion they cited 6 Redding and Russell Rees7 who found decreased oxygen saturation of coronary-sinus blood after administering propranolol. This view was cited last week (p. 917) by Dr. Balcon and his colleagues, and if true would support the idea that the adequacy of myocardial blood-supply is decreased after propranolol. Redding and Russell Rees were kind enough to show us their results, which were obtained in dogs. The dogs were heavily drugged, which may in itself alter the effects of the drug being tested, and the data came from few experiments which, perhaps because of the anaesthesia, showed rather a large scatter. We therefore decided to obtain coronary-sinus blood, before and after administration of propranolol, from patients undergoing cardiac catheterisation for other reasons. As is customary in our laboratory, no drugs of any sort were given before catheterisation, except her usual dose of digitalis in one of our patients. 5 mg. of propranolol was administered intravenously ill/,-2 hours after the procedure had started; from the pulse-rates 30 minutes before, and immediately before, the propranolol was given, it can be seen (see accompanying table) that the patients were calm and in a steady state. We
hope
to publish more cases in full later, but they take to collect, and we therefore decided to report the
some time results of the first four cases, since
2. 3. 4. 5. 6. 7.
they
were
identical, and do
Botti, R. E., Ratnoff, O. D. J. Lab. clin. Med. 1964, 64, 385. Nour-Eldin, F. Ann. N.Y. Acad. Sci. (in the press). Parratt, J. R., Grayson, J. Lancet, 1966, i, 338. Mendel, D. ibid. p. 597. Parratt, J. R., Grayson, J. ibid. p. 819. Redding, V. J., Russell Rees. ibid. p. 548. EFFECT OF PROPRANOLOL
(5
mg.
support a concept which may impair the understanding of the mode of action of a drug which is widely used. The reduction of pulse-rate in each patient was greater than 10%, and this is evidence that an effective dose had been given. These first four cases show no change in the coronary-sinus oxygen saturation after the administration of propranolol, and this despite a fall in the oxygen saturation of mixed venous blood in the two patients in whom it was measured.
not
It is reasonable to conclude from these results that the decrease in coronary blood-flow caused by the administration of propranolol is in proportion to the decreased amount of work that the heart, beating more slowly with a lower blood-pressure and a slower rate of change of pressure,5 has to perform. Although for obvious reasons we did not give the drug to patients with failing hearts, we think that the cause of the deaths associated with the administration of propranolol to such patients is more likely to be due to a reduction of an already diminished cardiac output by bradycardia in a patient who is incapable of increasing his stroke volume, than to any disproportionate reduction of coronary flow. DAVID MENDEL St. Thomas’ Hospital, EDWARD BYRNE-QUINN. London S.E.1.
FALLACIES IN ELECTROCARDIOGRAPHY? SIR,-Recent articles on application of electrodes for electrocardiographic recording have used fallacious arguments to discredit the need for abrasive pastes,89 or indeed for any electrode jelly.10 The first fallacy is based upon a misconception or neglect of the effect of lead-selection circuitry on the potentials of the Wilson " neutral " and Goldberger " indifferent" electrodesa point discussed quite thoroughly some years agoY-13 Later references to the point 14 show an awakening awareness of this aspect, without any attempt to consider its implications. It is necessary to stress that Lewes’ incorrect reference to " electrocardiographs of input impedance of 2 megohms or " more 8 refers only to the amplifier section, since the input resistances presented by his various instruments across the limb leads are only about 200, 10, and 100 kohms respectively, when recording unipolar lead potentials, according to the manufacturer’s report. Moreover, any evidence of success using the low-impedance (10 kohms) connection of his instrument for such recording (the only really crucial test of his hypothesis) is omitted. The second and consequent fallacy results from generalising from a few particular cases, without considering the 8. 9. 10. 11.
Lewes, D. Br. Heart J. 1965, 27, 105. Lancet, 1965, i, 795. Lewes, D. ibid. 1965, ii, 17. Rappaport, M. B., Williams, C., White, P. D. Am. Heart J. 1949, 37, 892. 12. Rappaport, M. B. Sanborn Technical Bulletin, November, 1957. 13. Dower, G. E. Circulation, 1963, 28, 483. 14. Lewes, D. Wld med. Electron. 1966, 4, 240.
INTRAVENOUSLY) ON PULSE-RATE, AND CORONARY-SINUS AND PULMONARY-ARTERY % IN 4 PATIENTS UNDERGOING CARDIAC CATHETERISATION
OXYGEN-SATURATION