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Gastric hemodynamics
l’olume
Number
65
Annotalions
6
stration of a lack of statistically significant separation between two groups with respect to a phenomenon may be attributable merely to inadequacy of methods rather than to the absence of such a relationship; and that positive observations should be accepted at face value unless failure to confirm rests on exact repetition of the experiments. This is a plea, therefore, to “accentuate the positive” but not to “eliminate the negative.” Multiple
Gastric
failure of confirmation techniques vary, but, tion even with varying weight.
843
is important, even if the generally, positive confirmamethods should carry more Milton MendEowitz, M.D. The Mount Sinai Hospital 100th St. and Fifth Aw. New York 29, N. Y.
hemodynamics
Within the past several years there has been a renewal of interest in the circulation of the stomach and the relationship of hemodynamics to gastric secretory function. Earlier studies suggested a possible dependancy of gastric secretion upon blood flow.‘-3 The relationship of pressure and flow in the gastric vascular bed has been investigated, and there does not appear to be any evidence of autoregulation.4 Increase in the rate of blood flow to the perfused canine stomach or increase in the pressure gradient across the circulation of the stomach was followed by a decline in gastric vascular resistance. The response of the gastric vascular bed to a series of pharmacologic agents or procedures which have an effect on the rate of glandular secretion in the stomach suggests that blood flow may be a determinant of gastric secretion within physiologic limits. Peters and Womack6 demonstrated that histamine increases the arteriovenous oxygen difference across the canine stomach. They also showed that the size of glass beads which could pass through the circulation of the stomach was decreased by histamine. From this information they inferred that histamine closed large-bore submucosal arteriovenous shunts and redistributed blood to the smaller vessels of the actively metabolizing mucosa. Menguy injected large amounts of histamine and induced systemic hypotension and a faIL in total blood flow to the stomach; blood flow through the actively secreting fundic area of the stomach increased, however, at the expense of nonsecreting regions of the stomach. Delanev. Weiner and Grim7 found that histamine increased the diameter of gastric mucosal arterioles, and also increased the amount of K42 or microspheres which could be sequestered in the gastric mucosal circulation, while reducing the amounts of these substances collected in the nonsecreting muscular layers of the stomach. Wangensteen and his associates**9 have found increments in total blood flow to the stomach in response to several gastric secretory stimulants, including histamine, serotonin, reserpine, and sympathectomy. Conversely, inhibitors of gastric blood flow, including epinephrine, levarterenol, vasopressin, and vagotomy, were associated with
diminished gastric secretion. Jacobsonr”~rr has demonstrated a decrease in gastric vascular resistance in the constant-flow perfused stomach in response to the gastric secretory stimulants histamine, bradykinin, gastrin and acetylcholine. These studies and others12.r3 imply a relation_between gastric blood flow and secretion. In addition, mechanical increase in blood flow to the stimulated or unstimulated stomach is associated with an increase in the volume of gastric secretion.14,*6 These studies have not been able to exclude the possibility that physiologic or pharmacologic stimuli to gastric secretion may act directly upon oxyntic cells, and that increased blood flow may be either a local supportive response to the enhanced metabolic activity of hypersecretion or, pari passu, another unrelated action of many gastric secretory stimulants.. Resolution of this dilemma has been hampered by the lack of adequate methods for a continuous measurement of gastric mucosal microcirculatory hemodynamics. Perhaps the recently described thermocouple technique of Demling and Wachsmann’6 may provide a better approach to this problem. The clinical implications of a relationship between blood flow and secretion in the stomach are intriguing. Womack and his associatesrr reported successful treatment of 2 patients with. massive hypersecretion by means of ligation of part of the arterial inflow to the stomach. Older experiments, however, failed to demonstrate any protective effect of surgical reduction in blood flow upon the production of experimental peptic ulcers.‘* Eugene D. Jacobson, M.D. Department of Applied Immunology Walter Reed Army Institute of Research Walter Reed Army Medical Center Washington 12, D.C. REFERENCES 1. Cutting, W. C., Dodds, E. C., Noble, R. L., and Williams, P. C.: The effect of alterations in blood flow on gastric secretion, Proc. Roy. Sot., B, 123:39, 1937.
844
2.
3.
4.
5.
6. 7.
8.
9.
10.
Annotations
Lim, R. K. S., Necheles, H., and Ni, T. G.: The vasomotor reactions of the vivi-perfused stomach, Clin. J. Physiol. 1:381, 1927. Burton-Opitz, R.: Uber die Stromung des Blutes in dem Gebiete der Pfortacher. Das Striimvolum der “Vena Gastrica”, Pfltiger’s Arch. ges. Physiol. 135:205, 1910. Jacobson, E. D., Scott, J. B., and Frohlich, E. D.: Hemodynamics of the stomach. I. Resistance-flow relationship in the gastric vascular bed. Am. 1. Digest. Dis. 7:779. 1962. Peters, R.” M.,“and Womack, N. A.: Hemodynamics of gastric secretion, Ann. Surg. 148:537, 19.58. Menguy, R.: Effects of histamine on gastric blood flow. Am. T. Digest. Dis. 7:383. 1962. Delaney, J. P., Weiner, D., and Grim, E.: Effects of epinephrine and norepinephrine on intramural distribution of gastric blood flow, Fed. Proc. 21:103, 1962. Peter, E. T., Nicoloff, D. M., Sosin, H., Walder, A. I., and Wangensteen, 0. H.: Relationship between gastric blood flow and secretion, Fed. Proc. 21:264, 1962. Sosin, H., Bernstein, E. F., Peter, E. T., and Wangensteen, 0. H. : The effect of serotonin and histamine on gastric blood flow, The Physiologist 5:214, 1962. Jacobson, E. D.: Effect of histamine, norepinephrine and acetylcholine on gastric vascular resistance, The Physiologist 5:160, 1962.
Physiologic low oxygen
11.
Jacobson, E. D.: Effects of gastrin and bradykinin on the stomach, Clin. Res. lO:291, 1962. 12. Dolcini, H. A., Zaidman, I., and Gray, S. J. : Hormonal and pharmacologic influences on microcirculation in the rat stomach, Am. J, Phvsiol. 199:1157. 1960. 13. Willox, G. L., Michalyshyn, B., and Kowalewski, K.: Gastric blood flow and temperature, Arch. int. Physiol. et Biochim. 69:668, 1961. 14. Thompson, J. E., and Vane, J. R.: Gastric secretion induced by histamine and its relationship to the rate of blood flow, J. Physiol. (London) 1X:433, 1953. 1.5. Jacobson, E. D., Scott, J. B., and Frohlich, E. D.: Hemodynamics of the stomach. II. Relation between gastric secretion and blood flow, Am. J. Digest. Dis. 7:786, 1962. 16. Demling, L., and Wachsmann, F.: A new method for measuring blood Row variations in the gastric mucosa, German Med. Monthly 6:189, 1961. 17. Hartrampf, C., Zeppa, R., and Womack, N. A.: Gastric hypersecretion and gastric blood supply. Presented at the 62nd Annual Meeting of The American Gastroenterological Association, May 26, 1961, Chicago, Ill. 18. Baronofsky, I. D.: An experimental evaluation of ligature of stomach vessels for peptic ulcer, Gastroenterology 10:301, 1948.
basis for the normally content
of coronary
Little attention by way of explanation has been given to the well-known fact that in man and in anesthetized or unanesthetized dogs the coronary venous blood has the lowest oxygen content (5 volumes per cent) or saturation (2.5 per cent) in comparison with the venous blood of other organs of the body. The only reference of which the author is aware is that of Gregg,’ who stated, “The very high oxygen extraction from the myocardial capillaries as compared with other vascular beds could result from a relatively low blood velocity, high metabolism, or high level of vascularity, the latter two of which are known to be high as compared with other tissues.” This explanation, although basic, appeared to be incomplete and required further elaboration. The observation that the myocardium is richly supplied with capillaries has been universally recognized.2 This by itself would tend to reduce the capillary blood velocity by increasing the total capillary cross-sectional area, provided that all other factors were to remain equal (coronary blood flow, perfusion pressure, extravascular compression, myocardial
venaus
blood
oxygen demand, etc.). However, when a tissue has more capillaries, it will have a greater Aow of blood because of a reduction in the total vascular resistance (other things being equal). Consequently, capillary blood velocity will depend on the quantitative relation between increase in flow and increase in total cross-sectional area of the capillaries. Unfortunately, there are no data on the mean velocity of blood in the coronary capillaries. The oxygen demand of the pumping myocardium in situ is one of the highest, approximately 10 to 1.5 ml. per minute per 100 grams of tissue.is3 This would undoubtedly contribute to the high extraction of oxygen, but it cannot entirely explain the low coronary venous saturation since other organs (e.g., thyroid, adrenal, brain) also have a high oxygen uptake,*-’ yet their venous oxygen content is much higher than that of heart muscle. An additional factor would be that the total flow through the myocardial capillaries per unit time is somewhat restricted in relation to the demand of the rhythmically contracting heart muscle cells. If this concept is accepted, one must seek an explanation for the
Number
65
Annotalions
6
stration of a lack of statistically significant separation between two groups with respect to a phenomenon may be attributable merely to inadequacy of methods rather than to the absence of such a relationship; and that positive observations should be accepted at face value unless failure to confirm rests on exact repetition of the experiments. This is a plea, therefore, to “accentuate the positive” but not to “eliminate the negative.” Multiple
Gastric
failure of confirmation techniques vary, but, tion even with varying weight.
843
is important, even if the generally, positive confirmamethods should carry more Milton MendEowitz, M.D. The Mount Sinai Hospital 100th St. and Fifth Aw. New York 29, N. Y.
hemodynamics
Within the past several years there has been a renewal of interest in the circulation of the stomach and the relationship of hemodynamics to gastric secretory function. Earlier studies suggested a possible dependancy of gastric secretion upon blood flow.‘-3 The relationship of pressure and flow in the gastric vascular bed has been investigated, and there does not appear to be any evidence of autoregulation.4 Increase in the rate of blood flow to the perfused canine stomach or increase in the pressure gradient across the circulation of the stomach was followed by a decline in gastric vascular resistance. The response of the gastric vascular bed to a series of pharmacologic agents or procedures which have an effect on the rate of glandular secretion in the stomach suggests that blood flow may be a determinant of gastric secretion within physiologic limits. Peters and Womack6 demonstrated that histamine increases the arteriovenous oxygen difference across the canine stomach. They also showed that the size of glass beads which could pass through the circulation of the stomach was decreased by histamine. From this information they inferred that histamine closed large-bore submucosal arteriovenous shunts and redistributed blood to the smaller vessels of the actively metabolizing mucosa. Menguy injected large amounts of histamine and induced systemic hypotension and a faIL in total blood flow to the stomach; blood flow through the actively secreting fundic area of the stomach increased, however, at the expense of nonsecreting regions of the stomach. Delanev. Weiner and Grim7 found that histamine increased the diameter of gastric mucosal arterioles, and also increased the amount of K42 or microspheres which could be sequestered in the gastric mucosal circulation, while reducing the amounts of these substances collected in the nonsecreting muscular layers of the stomach. Wangensteen and his associates**9 have found increments in total blood flow to the stomach in response to several gastric secretory stimulants, including histamine, serotonin, reserpine, and sympathectomy. Conversely, inhibitors of gastric blood flow, including epinephrine, levarterenol, vasopressin, and vagotomy, were associated with
diminished gastric secretion. Jacobsonr”~rr has demonstrated a decrease in gastric vascular resistance in the constant-flow perfused stomach in response to the gastric secretory stimulants histamine, bradykinin, gastrin and acetylcholine. These studies and others12.r3 imply a relation_between gastric blood flow and secretion. In addition, mechanical increase in blood flow to the stimulated or unstimulated stomach is associated with an increase in the volume of gastric secretion.14,*6 These studies have not been able to exclude the possibility that physiologic or pharmacologic stimuli to gastric secretion may act directly upon oxyntic cells, and that increased blood flow may be either a local supportive response to the enhanced metabolic activity of hypersecretion or, pari passu, another unrelated action of many gastric secretory stimulants.. Resolution of this dilemma has been hampered by the lack of adequate methods for a continuous measurement of gastric mucosal microcirculatory hemodynamics. Perhaps the recently described thermocouple technique of Demling and Wachsmann’6 may provide a better approach to this problem. The clinical implications of a relationship between blood flow and secretion in the stomach are intriguing. Womack and his associatesrr reported successful treatment of 2 patients with. massive hypersecretion by means of ligation of part of the arterial inflow to the stomach. Older experiments, however, failed to demonstrate any protective effect of surgical reduction in blood flow upon the production of experimental peptic ulcers.‘* Eugene D. Jacobson, M.D. Department of Applied Immunology Walter Reed Army Institute of Research Walter Reed Army Medical Center Washington 12, D.C. REFERENCES 1. Cutting, W. C., Dodds, E. C., Noble, R. L., and Williams, P. C.: The effect of alterations in blood flow on gastric secretion, Proc. Roy. Sot., B, 123:39, 1937.
844
2.
3.
4.
5.
6. 7.
8.
9.
10.
Annotations
Lim, R. K. S., Necheles, H., and Ni, T. G.: The vasomotor reactions of the vivi-perfused stomach, Clin. J. Physiol. 1:381, 1927. Burton-Opitz, R.: Uber die Stromung des Blutes in dem Gebiete der Pfortacher. Das Striimvolum der “Vena Gastrica”, Pfltiger’s Arch. ges. Physiol. 135:205, 1910. Jacobson, E. D., Scott, J. B., and Frohlich, E. D.: Hemodynamics of the stomach. I. Resistance-flow relationship in the gastric vascular bed. Am. 1. Digest. Dis. 7:779. 1962. Peters, R.” M.,“and Womack, N. A.: Hemodynamics of gastric secretion, Ann. Surg. 148:537, 19.58. Menguy, R.: Effects of histamine on gastric blood flow. Am. T. Digest. Dis. 7:383. 1962. Delaney, J. P., Weiner, D., and Grim, E.: Effects of epinephrine and norepinephrine on intramural distribution of gastric blood flow, Fed. Proc. 21:103, 1962. Peter, E. T., Nicoloff, D. M., Sosin, H., Walder, A. I., and Wangensteen, 0. H.: Relationship between gastric blood flow and secretion, Fed. Proc. 21:264, 1962. Sosin, H., Bernstein, E. F., Peter, E. T., and Wangensteen, 0. H. : The effect of serotonin and histamine on gastric blood flow, The Physiologist 5:214, 1962. Jacobson, E. D.: Effect of histamine, norepinephrine and acetylcholine on gastric vascular resistance, The Physiologist 5:160, 1962.
Physiologic low oxygen
11.
Jacobson, E. D.: Effects of gastrin and bradykinin on the stomach, Clin. Res. lO:291, 1962. 12. Dolcini, H. A., Zaidman, I., and Gray, S. J. : Hormonal and pharmacologic influences on microcirculation in the rat stomach, Am. J, Phvsiol. 199:1157. 1960. 13. Willox, G. L., Michalyshyn, B., and Kowalewski, K.: Gastric blood flow and temperature, Arch. int. Physiol. et Biochim. 69:668, 1961. 14. Thompson, J. E., and Vane, J. R.: Gastric secretion induced by histamine and its relationship to the rate of blood flow, J. Physiol. (London) 1X:433, 1953. 1.5. Jacobson, E. D., Scott, J. B., and Frohlich, E. D.: Hemodynamics of the stomach. II. Relation between gastric secretion and blood flow, Am. J. Digest. Dis. 7:786, 1962. 16. Demling, L., and Wachsmann, F.: A new method for measuring blood Row variations in the gastric mucosa, German Med. Monthly 6:189, 1961. 17. Hartrampf, C., Zeppa, R., and Womack, N. A.: Gastric hypersecretion and gastric blood supply. Presented at the 62nd Annual Meeting of The American Gastroenterological Association, May 26, 1961, Chicago, Ill. 18. Baronofsky, I. D.: An experimental evaluation of ligature of stomach vessels for peptic ulcer, Gastroenterology 10:301, 1948.
basis for the normally content
of coronary
Little attention by way of explanation has been given to the well-known fact that in man and in anesthetized or unanesthetized dogs the coronary venous blood has the lowest oxygen content (5 volumes per cent) or saturation (2.5 per cent) in comparison with the venous blood of other organs of the body. The only reference of which the author is aware is that of Gregg,’ who stated, “The very high oxygen extraction from the myocardial capillaries as compared with other vascular beds could result from a relatively low blood velocity, high metabolism, or high level of vascularity, the latter two of which are known to be high as compared with other tissues.” This explanation, although basic, appeared to be incomplete and required further elaboration. The observation that the myocardium is richly supplied with capillaries has been universally recognized.2 This by itself would tend to reduce the capillary blood velocity by increasing the total capillary cross-sectional area, provided that all other factors were to remain equal (coronary blood flow, perfusion pressure, extravascular compression, myocardial
venaus
blood
oxygen demand, etc.). However, when a tissue has more capillaries, it will have a greater Aow of blood because of a reduction in the total vascular resistance (other things being equal). Consequently, capillary blood velocity will depend on the quantitative relation between increase in flow and increase in total cross-sectional area of the capillaries. Unfortunately, there are no data on the mean velocity of blood in the coronary capillaries. The oxygen demand of the pumping myocardium in situ is one of the highest, approximately 10 to 1.5 ml. per minute per 100 grams of tissue.is3 This would undoubtedly contribute to the high extraction of oxygen, but it cannot entirely explain the low coronary venous saturation since other organs (e.g., thyroid, adrenal, brain) also have a high oxygen uptake,*-’ yet their venous oxygen content is much higher than that of heart muscle. An additional factor would be that the total flow through the myocardial capillaries per unit time is somewhat restricted in relation to the demand of the rhythmically contracting heart muscle cells. If this concept is accepted, one must seek an explanation for the