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ANTIDOTE TO SUXAMETHONIUM
819
depots in certain areas had noted the difficulty described by Dr. Cumming during routine servicing of the H.A.F.O.E. head tent, and minor modifications have already been introduced to enable the user to clean the Venturi tube as often as necessary. As manufacturers, our experience is that many authorities actively oppose the use of filters which, if neglected, may constitute a greater hazard than dust-borne infection. In very adverse circumstances we find an increasing tendency to use, for the nursing of high-risk postoperative cases, our standard oxygen tent, which can be very lightly pressurised to provide virtual isolation of the patient from airborne infection."
MYOCARDIAL VASCULAR REACTIVITY
SIR,-We read with interest Dr. Mendel’s letter (March 12)
propranolol in the treatment of angina of effort. We have shown (Feb. 12) that propranolol decreases myocardial bloodflow in dogs; Dr. Mendel does not dispute this fact, but raises a reasonable query as to our interpretation that this effect is primarily due to a reduction in sympathetic vasodilator tone. It is of course impossible to state categorically that propranolol decreases coronary blood-flow entirely through " vasoconstrictor " action on the vessels (by blockade of vascular p-receptors) rather than indirectly through a decrease in the oxidative requirements of the myocardium. It seems to us, however, that there is clear evidence, both for the existence of P-receptors in the myocardial vasculature and for an intrinsic adrenergic mechanism for vasodilatation,"--5 and we would expect that blockade of these vascular receptors would tend to reduce coronary blood-flow. This interpretation is also supported by the fact that coronary sinus oxygen-content decreases after propranolol administration, as described by Dr. Redding and Dr. Rees (March 5). If the reduction in blood-flow after -blockade resulted only from decreased myocardial oxygen requirements, one would expect coronary-sinus Po2 to remain relatively unchanged. An increase in myocardial oxygen requirements (such as occurs, for example, during sympathetic nerve stimulation 6) results in a corresponding increase in coronary blood-flow while a decrease in myocardial oxygen requirements (such as occurs during rest 7) results in a decrease in coronary flow, but under both conditions the oxygen tension of the coronary-sinus blood remains relatively constant. It is probably reasonable to conclude with Dr. Redding and Dr. Rees that if the coronary-sinus Po2 is decreased this reflects a primary effect of propranolol in decreasing coronary flow by an action on the vessels themselves. Dr. Mendel’s own experiments are very clear, and confirm that the main effect of propranolol on the heart is a reduction of contractile force. The supposition that after -blockade the heart may put out a larger stroke-volume for less expenditure of energy has already been demonstrated. Thus in the experiments of Kako et al. stroke-volume was reduced by 20 % and stroke-work was also reduced slightly (3%) after (3-blockade, and this effect is accompanied by a reduction on myocardial oxygen consumption, as described by Dr. Redding and Dr. Rees. The blood-flow requirements would indeed be less under these conditions, but we doubt whether, by themselves, they would account for a 34% decrease in myocardial blood-flow. The main point of our article was, however, not to demonstrate that -blockade reduces myocardial flow, but to show that after propranolol there is a striking alteration in myocardial vascular responses to adrenergic transmitters. After -blockade, adrenaline release leads to a pronounced increase in myocardial
on
1. 2. 3. 4. 5.
Doutheil, U., Ten Bruggencate, H. G., Kramer, J. Pflugers Arch. ges. Physiol. 1964, 281, 181. Parratt, J. R. Br. J. Pharmac. Chemother. 1965, 24, 601. Folle, L. E., Aviado, D. M. J. Pharmac. exp. Ther. 1965, 149, 79. Klocke, F. J., Kaiser, G. A., Ross, J., Braunwald, E. Circulation Res. 1965, 16, 376. Rayford, C. R., Khouri, E. M., Gregg, D. E. Am. J. Physiol. 1965, 209,
680. 6. Granata, 7. 8.
R.
L., Olsson, A., Huvos, A., Gregg, 1965, 16, 114. Gregg. D. E., Khouri, E. M., Rayford, C. R. ibid. p. 102. Kako, K., Krayenbühl, H. P., Hegglin, R. Arch. exp. Path. Pharmak. 1964, 246, 297. D. E. Circulation Res.
vascular resistance. Furthermore, there is also some rather disturbing evidence that the vasodilator effects of myocardial hypoxia are reduced by -blockade.3 A patient with angina may indeed be quite happy with propranolol-but let his wife drop the soup tureen or let his favourite pipe be broken by his small child, and the result may well be serious. Department of Physiology, J. R. PARRATT University of Ibadan, J. GRAYSON. Ibadan, Nigeria.
ANTIDOTE TO SUXAMETHONIUM SIR,-Iwas interested by the letter by Dr. Levin (March 19) who mentioned that the level of serum-pseudocholinesterase (P.C.E.) remained constant in fresh-frozen serum stored at - 20°C during a shelf-life of about twenty-one days. Hutchinson et al.1 reported that P.C.E. retained its activity for at least a year if serum is kept at -4°C, and I was able to confirm this in samples of serum kept at -4°C for four months.2 Geriatric Unit, Stracathro Hospital,
Brechin, Angus.
C. COHEN.
ASSESSMENT OF GASTRIC ACID SECRETION SIR,-We read with interest the article by Mr. Burns and Dr. Laws (Jan. 8) reporting good correlation between acid output after maximal histamine stimulation and grade of gastroduodenal rugosity in patients without focal gastric lesions. Such a correlation, without taking into account factors known to influence gastric acid output like age and sex,3 presence of anaemia,4 and the region to which the subjects belong,5 is open to serious criticism. The spurious nature of this correlation is apparent from the observations of Mr. Burns and Dr. Laws. But for the inclusion of females, the mean acid output in grade-2 and grade-3 patients would not have been different. Almost all the females in grade 2 secreted less acid than the males in that grade, and thus brought down the mean acid value. Even in grade 1, with the exclusion of females the mean value would have been higher. Moreover, the maximal acid output represents maximal secretory capacity of the stomach rather than acid secretion under more physiological conditions, which is represented by the basal acid output. Zollinger-Ellison syndrome, and some other causes of prominent duodenal mucosal folds like Brunnergland hyperplasia, are particularly associated with basal hypersecretion, and involve a higher proportion of the secretory capacity of the stomach, put out under basal conditions.It would have been useful if Mr. Burns and Dr. Laws had mentioned the type of correlation between radiological appearances and basal acid secretion. We have also observed patients showing prominent mucosal folds in stomach, duodenum, and upper part of jejunum associated with gastric acid hypersecretion. One such patient secreted 18-1 and 30-6 mEq. hydrochloric acid per hour under basal conditions and after histamine stimulation, respectively; the ratio of basal to maximal acid output was 59-1:100.° But this feature was not seen in 29 North Indian male patients, of comparable socioeconomic status, with ansemia due to hookworm disease (mean haemoglobin 4-46 [S.E. 0-24] g. per 100 ml.), whom we investigated radiologically. Their gastric acid secretion was assessed by the augmented histamine test as modified by Marks -(titrating the gastric contents with 0-1 N sodium hydroxide, using phenolphthalein [pH 8-3-8-5] as indicator). Many of these patients had prominent gastroduodenal folds (grades 4 and 5, according to Mr. Burns and Dr. Laws), but thev showed reduced maximal acid output as 1.
2. 3. 4. 5. 6. 7.
Hutchinson, A. D., McCance, R. A., Widdowson, E. M. Spec. Rep. Ser. med. Res. Coun. 1951, no. 275, p. 216. Cohen, C. Geront. clin. 1964, 6, 324. Baron, J. H. Gut, 1963, 4, 136. Callender, S. T., Retief, F. P., Witts, L. J. ibid. 1960, 1, 326. Goyal, R. K., Gupta, P. S., Chuttani, H. K. ibid. (in the press). Marks, I. N., Selzer, G., Louw, J. H., Bank, S. Gastroenterology, 1961, 41, 77. Marks, I. N. See ibid. p. 599.
depots in certain areas had noted the difficulty described by Dr. Cumming during routine servicing of the H.A.F.O.E. head tent, and minor modifications have already been introduced to enable the user to clean the Venturi tube as often as necessary. As manufacturers, our experience is that many authorities actively oppose the use of filters which, if neglected, may constitute a greater hazard than dust-borne infection. In very adverse circumstances we find an increasing tendency to use, for the nursing of high-risk postoperative cases, our standard oxygen tent, which can be very lightly pressurised to provide virtual isolation of the patient from airborne infection."
MYOCARDIAL VASCULAR REACTIVITY
SIR,-We read with interest Dr. Mendel’s letter (March 12)
propranolol in the treatment of angina of effort. We have shown (Feb. 12) that propranolol decreases myocardial bloodflow in dogs; Dr. Mendel does not dispute this fact, but raises a reasonable query as to our interpretation that this effect is primarily due to a reduction in sympathetic vasodilator tone. It is of course impossible to state categorically that propranolol decreases coronary blood-flow entirely through " vasoconstrictor " action on the vessels (by blockade of vascular p-receptors) rather than indirectly through a decrease in the oxidative requirements of the myocardium. It seems to us, however, that there is clear evidence, both for the existence of P-receptors in the myocardial vasculature and for an intrinsic adrenergic mechanism for vasodilatation,"--5 and we would expect that blockade of these vascular receptors would tend to reduce coronary blood-flow. This interpretation is also supported by the fact that coronary sinus oxygen-content decreases after propranolol administration, as described by Dr. Redding and Dr. Rees (March 5). If the reduction in blood-flow after -blockade resulted only from decreased myocardial oxygen requirements, one would expect coronary-sinus Po2 to remain relatively unchanged. An increase in myocardial oxygen requirements (such as occurs, for example, during sympathetic nerve stimulation 6) results in a corresponding increase in coronary blood-flow while a decrease in myocardial oxygen requirements (such as occurs during rest 7) results in a decrease in coronary flow, but under both conditions the oxygen tension of the coronary-sinus blood remains relatively constant. It is probably reasonable to conclude with Dr. Redding and Dr. Rees that if the coronary-sinus Po2 is decreased this reflects a primary effect of propranolol in decreasing coronary flow by an action on the vessels themselves. Dr. Mendel’s own experiments are very clear, and confirm that the main effect of propranolol on the heart is a reduction of contractile force. The supposition that after -blockade the heart may put out a larger stroke-volume for less expenditure of energy has already been demonstrated. Thus in the experiments of Kako et al. stroke-volume was reduced by 20 % and stroke-work was also reduced slightly (3%) after (3-blockade, and this effect is accompanied by a reduction on myocardial oxygen consumption, as described by Dr. Redding and Dr. Rees. The blood-flow requirements would indeed be less under these conditions, but we doubt whether, by themselves, they would account for a 34% decrease in myocardial blood-flow. The main point of our article was, however, not to demonstrate that -blockade reduces myocardial flow, but to show that after propranolol there is a striking alteration in myocardial vascular responses to adrenergic transmitters. After -blockade, adrenaline release leads to a pronounced increase in myocardial
on
1. 2. 3. 4. 5.
Doutheil, U., Ten Bruggencate, H. G., Kramer, J. Pflugers Arch. ges. Physiol. 1964, 281, 181. Parratt, J. R. Br. J. Pharmac. Chemother. 1965, 24, 601. Folle, L. E., Aviado, D. M. J. Pharmac. exp. Ther. 1965, 149, 79. Klocke, F. J., Kaiser, G. A., Ross, J., Braunwald, E. Circulation Res. 1965, 16, 376. Rayford, C. R., Khouri, E. M., Gregg, D. E. Am. J. Physiol. 1965, 209,
680. 6. Granata, 7. 8.
R.
L., Olsson, A., Huvos, A., Gregg, 1965, 16, 114. Gregg. D. E., Khouri, E. M., Rayford, C. R. ibid. p. 102. Kako, K., Krayenbühl, H. P., Hegglin, R. Arch. exp. Path. Pharmak. 1964, 246, 297. D. E. Circulation Res.
vascular resistance. Furthermore, there is also some rather disturbing evidence that the vasodilator effects of myocardial hypoxia are reduced by -blockade.3 A patient with angina may indeed be quite happy with propranolol-but let his wife drop the soup tureen or let his favourite pipe be broken by his small child, and the result may well be serious. Department of Physiology, J. R. PARRATT University of Ibadan, J. GRAYSON. Ibadan, Nigeria.
ANTIDOTE TO SUXAMETHONIUM SIR,-Iwas interested by the letter by Dr. Levin (March 19) who mentioned that the level of serum-pseudocholinesterase (P.C.E.) remained constant in fresh-frozen serum stored at - 20°C during a shelf-life of about twenty-one days. Hutchinson et al.1 reported that P.C.E. retained its activity for at least a year if serum is kept at -4°C, and I was able to confirm this in samples of serum kept at -4°C for four months.2 Geriatric Unit, Stracathro Hospital,
Brechin, Angus.
C. COHEN.
ASSESSMENT OF GASTRIC ACID SECRETION SIR,-We read with interest the article by Mr. Burns and Dr. Laws (Jan. 8) reporting good correlation between acid output after maximal histamine stimulation and grade of gastroduodenal rugosity in patients without focal gastric lesions. Such a correlation, without taking into account factors known to influence gastric acid output like age and sex,3 presence of anaemia,4 and the region to which the subjects belong,5 is open to serious criticism. The spurious nature of this correlation is apparent from the observations of Mr. Burns and Dr. Laws. But for the inclusion of females, the mean acid output in grade-2 and grade-3 patients would not have been different. Almost all the females in grade 2 secreted less acid than the males in that grade, and thus brought down the mean acid value. Even in grade 1, with the exclusion of females the mean value would have been higher. Moreover, the maximal acid output represents maximal secretory capacity of the stomach rather than acid secretion under more physiological conditions, which is represented by the basal acid output. Zollinger-Ellison syndrome, and some other causes of prominent duodenal mucosal folds like Brunnergland hyperplasia, are particularly associated with basal hypersecretion, and involve a higher proportion of the secretory capacity of the stomach, put out under basal conditions.It would have been useful if Mr. Burns and Dr. Laws had mentioned the type of correlation between radiological appearances and basal acid secretion. We have also observed patients showing prominent mucosal folds in stomach, duodenum, and upper part of jejunum associated with gastric acid hypersecretion. One such patient secreted 18-1 and 30-6 mEq. hydrochloric acid per hour under basal conditions and after histamine stimulation, respectively; the ratio of basal to maximal acid output was 59-1:100.° But this feature was not seen in 29 North Indian male patients, of comparable socioeconomic status, with ansemia due to hookworm disease (mean haemoglobin 4-46 [S.E. 0-24] g. per 100 ml.), whom we investigated radiologically. Their gastric acid secretion was assessed by the augmented histamine test as modified by Marks -(titrating the gastric contents with 0-1 N sodium hydroxide, using phenolphthalein [pH 8-3-8-5] as indicator). Many of these patients had prominent gastroduodenal folds (grades 4 and 5, according to Mr. Burns and Dr. Laws), but thev showed reduced maximal acid output as 1.
2. 3. 4. 5. 6. 7.
Hutchinson, A. D., McCance, R. A., Widdowson, E. M. Spec. Rep. Ser. med. Res. Coun. 1951, no. 275, p. 216. Cohen, C. Geront. clin. 1964, 6, 324. Baron, J. H. Gut, 1963, 4, 136. Callender, S. T., Retief, F. P., Witts, L. J. ibid. 1960, 1, 326. Goyal, R. K., Gupta, P. S., Chuttani, H. K. ibid. (in the press). Marks, I. N., Selzer, G., Louw, J. H., Bank, S. Gastroenterology, 1961, 41, 77. Marks, I. N. See ibid. p. 599.