Research in
ExperimentalMedicine
Res. Exp. Med. (Berl.) 175, 181--185 (1979)
@ Springer-Verlag 1979
Regional Gastric Mucosal Blood Flow in Hypovolemic Shock M. Starlinger l, R. Jakesz 1, P. Bratusch-Marrain 2, and R. Schiessel 1 1Abteilung fiir experimentelle Chirurgie (Prof. Dr. R. Gottlob) der I. Chirurg. Univ.-Klinik (Prof. Dr. A. Fritsch), Alserstrage 4, A-1097 Wien, Austria 2 I. Medizinische Univ.-Klinik (Prof. Dr. E. Deutsch), A-1097 Wien, Austria
Summary. The effect of hypovolemia on the mucosal blood flow of the gastric corpus and antrum were tested with the microsphere method 30 and 60 min after induction of hemorrhagic shock in the rat. The results demonstrate a marked reduction after 30 and 60 min without any significant differences between the corpus and the antrum. This reduction is largely dependent on cardiac and circulatory function. It is concluded that the differences in energy metabolism, which have been implicated as explanation for the different susceptibility to develop stress lesions by Menguy and Masters, cannot be attributed to different degrees of ischemia. Key words: Stress ulcer - Regional mucosal blood flow - Microspheres Hypovolemic shock
Zusammenfassung. Der Effekt von Hypovolfimie auf die Schleimhautdurchblutung von Corpus und Antrum des Rattenmagens wurde mittels der Mikrosphfirenmethode 30 und 60 rain nach Einleitung eines h~imorrhagischen Schocks untersucht. Die Ergebnisse demonstrieren eine deutliche Herabsetzung ohne regionale Unterschiede zwischen Antrum und Corpus. Diese Minderdurchblutung korreliert eng mit der Senkung yon Herzzeitvolumen und arteriellem Blutdruck. Regionale Unterschiede im Energiehaushalt der Schleimhaut, die als Erkl~irung ftir die im Corpus h6here Anfiilligkeit ftir Stressl/isionen herangezogen wurden, k6nnen nicht auf regional unterschiedliche Herabsetzung der Durchblutung zuriickgeftihrt werden. Sehliisselwiirter: Strel3ulcus - regionale Schleimhautdurchblutung - Mikrosphfiren - h~imorrhagischer Schock Offprint requests to: M. Starlinger, M. D. (address see above) Abbreviations: GMBF: gastric mucosal blood flow; AMBF: antral mucosal blood flow; CMBF: corpus mucosal blood flow; CO: cardiac output; AP: arterial pressure
0300-9130/79/0175/0181/$1.00
182
M. Starlinger et al.
H e m o r r h a g i c shock is a well established model for the p r o d u c t i o n of gastric stress ulcus in the rat [5]. Characteristically, this type of m u c o s a l i n j u r y tends to be located in the p r o x i m a l p o r t i o n of the stomach, n o t only in the rat, b u t also in other species like dogs [9], rabbits, pigs, as well as in h u m a n s [10]. A n e x p l a n a t i o n for this different susceptibility was first given b y M e n g u y a n d Masters [5], when they d e m o n s t r a t e d a more p r o f o u n d i m p a i r m e n t of cell m e t a b o l i s m in the corpus t h a n in the a n t r a l mucosa. Results a b o u t the role of the mucosal b l o o d flow are controversial [3, 5, 9]. This study was u n d e r t a k e n to clarify the q u e s t i o n whether regional differences of gastric m u c o s a l b l o o d flow ( G M B F ) , i.e., differences between corpus m u c o s a l flow ( C M B F ) a n d b l o o d flow to the a n t r u m m u c o s a ( A M B F ) , could be the reason for this interesting peculiarity.
Methods Twenty Spraque-Dawley rats, weighing 310--390 g, were fasted 24 h prior to the experiment but were given tap water ad libitum. All animals were anesthetized with urethan and canulated through the femoral artery for blood collection and through the carotid artery into the left ventricle for injection of microspheres. Radioactive microspheres were utilized (diameter 9 ~tm, 3M Comp., St. Paul, Minn.) to measure gastric mucosal blood flow according to Archibald et al. [1]. Three different isotopes were used, 141 Ce, 51 Cr, and 85 Sr for three separate measurements taken 30 min apart. For each measurement, 0.2 ml of saline containing approximately 400,000 microspheres of either isotope were injected after vigorous manual agitation for about 3 min through the carotid artery catheter. Ten seconds prior to injection, the femoral artery catheter was opened and blood was withdrawn by means of a Havard withdrawal pump at a rate of 0.62 ml/min for exactly 1 min. In a separate previous experiment on 5 rats, complete removal of all microspheres by trapping in the capillary bed 10 s after injection without any evidence for recirculation could be demonstrated by sequential blood sampling every 10 s. Immediately after the first measurement, hypovolemia was established by withdrawal of 1.5 ml blood/100g body weight from the femoral artery within 5 min. Throughout the experiment, arterial pressure (AP) was continously recorded by means of a Statham transducer. Blood flow measurements were repeated 30 and 60 min after induction of shock. After the third injection of spheres the animals were killed, the stomach removed, the mucosa of the corpus as well as the antrum weighed and counted separately in a Packard gamma counter. The blood samples were also counted and all 141 Ce counts corrected for 51 Cr and 85 Sr spillage (12% and 22%, resp.). CMBF and AMBF were calculated as ml/min per g tissue wet weight: cpm/g tissue × fem. blood flow (ml/min) cpm femoral blood the cardiac output (CO) as ml/min per 100g body weight: cpm inject. × feml blood flow (ml/min) cpm femoral blood Statistical evaluation of these data was done with the U-test (Wilcoxon, Mann, Withney). In order to demonstrate the relationship of gastric mucosal blood flow regulation to the general circulation during shock, correlation and linear regression methods were applied. The variables were the relative differences between values at 60 and 30 min in dependence of the "60--n30 initial values (n= - )ofeachparameter tested. The probabilitiesofsignificantpositive(prono
duct moment) correlations were calculated.
Gastric Blood Flow in Shock
183
Table 1. Regional changes of gastric mucosal blood flow in hypovolemic shock (means and S.D. n = 20) 0
30'
AP (mm Hg)
97
+ 13
CO (ml/min/100g)
23.6 + 4.6
60'
* 42.5 +7
(44%)
n.s.
50
+ 15.6 (51.5%)
*
7.3 +1.9
(31%)
n.s.
9.0 + 5.6 (39%)
AMBF (ml/min/g)
0.68 + 0.20
*
0.21 +0.12 (35%)
n.s.
0.35+ 0.22 (51%)
CMBF (ml/min/g)
0.21 + 0.03
*
0.07+0.03 (33%)
n.s.
0.11+ 0.08 (52%)
* P
ExperimentalMedicine
Res. Exp. Med. (Berl.) 175, 181--185 (1979)
@ Springer-Verlag 1979
Regional Gastric Mucosal Blood Flow in Hypovolemic Shock M. Starlinger l, R. Jakesz 1, P. Bratusch-Marrain 2, and R. Schiessel 1 1Abteilung fiir experimentelle Chirurgie (Prof. Dr. R. Gottlob) der I. Chirurg. Univ.-Klinik (Prof. Dr. A. Fritsch), Alserstrage 4, A-1097 Wien, Austria 2 I. Medizinische Univ.-Klinik (Prof. Dr. E. Deutsch), A-1097 Wien, Austria
Summary. The effect of hypovolemia on the mucosal blood flow of the gastric corpus and antrum were tested with the microsphere method 30 and 60 min after induction of hemorrhagic shock in the rat. The results demonstrate a marked reduction after 30 and 60 min without any significant differences between the corpus and the antrum. This reduction is largely dependent on cardiac and circulatory function. It is concluded that the differences in energy metabolism, which have been implicated as explanation for the different susceptibility to develop stress lesions by Menguy and Masters, cannot be attributed to different degrees of ischemia. Key words: Stress ulcer - Regional mucosal blood flow - Microspheres Hypovolemic shock
Zusammenfassung. Der Effekt von Hypovolfimie auf die Schleimhautdurchblutung von Corpus und Antrum des Rattenmagens wurde mittels der Mikrosphfirenmethode 30 und 60 rain nach Einleitung eines h~imorrhagischen Schocks untersucht. Die Ergebnisse demonstrieren eine deutliche Herabsetzung ohne regionale Unterschiede zwischen Antrum und Corpus. Diese Minderdurchblutung korreliert eng mit der Senkung yon Herzzeitvolumen und arteriellem Blutdruck. Regionale Unterschiede im Energiehaushalt der Schleimhaut, die als Erkl~irung ftir die im Corpus h6here Anfiilligkeit ftir Stressl/isionen herangezogen wurden, k6nnen nicht auf regional unterschiedliche Herabsetzung der Durchblutung zuriickgeftihrt werden. Sehliisselwiirter: Strel3ulcus - regionale Schleimhautdurchblutung - Mikrosphfiren - h~imorrhagischer Schock Offprint requests to: M. Starlinger, M. D. (address see above) Abbreviations: GMBF: gastric mucosal blood flow; AMBF: antral mucosal blood flow; CMBF: corpus mucosal blood flow; CO: cardiac output; AP: arterial pressure
0300-9130/79/0175/0181/$1.00
182
M. Starlinger et al.
H e m o r r h a g i c shock is a well established model for the p r o d u c t i o n of gastric stress ulcus in the rat [5]. Characteristically, this type of m u c o s a l i n j u r y tends to be located in the p r o x i m a l p o r t i o n of the stomach, n o t only in the rat, b u t also in other species like dogs [9], rabbits, pigs, as well as in h u m a n s [10]. A n e x p l a n a t i o n for this different susceptibility was first given b y M e n g u y a n d Masters [5], when they d e m o n s t r a t e d a more p r o f o u n d i m p a i r m e n t of cell m e t a b o l i s m in the corpus t h a n in the a n t r a l mucosa. Results a b o u t the role of the mucosal b l o o d flow are controversial [3, 5, 9]. This study was u n d e r t a k e n to clarify the q u e s t i o n whether regional differences of gastric m u c o s a l b l o o d flow ( G M B F ) , i.e., differences between corpus m u c o s a l flow ( C M B F ) a n d b l o o d flow to the a n t r u m m u c o s a ( A M B F ) , could be the reason for this interesting peculiarity.
Methods Twenty Spraque-Dawley rats, weighing 310--390 g, were fasted 24 h prior to the experiment but were given tap water ad libitum. All animals were anesthetized with urethan and canulated through the femoral artery for blood collection and through the carotid artery into the left ventricle for injection of microspheres. Radioactive microspheres were utilized (diameter 9 ~tm, 3M Comp., St. Paul, Minn.) to measure gastric mucosal blood flow according to Archibald et al. [1]. Three different isotopes were used, 141 Ce, 51 Cr, and 85 Sr for three separate measurements taken 30 min apart. For each measurement, 0.2 ml of saline containing approximately 400,000 microspheres of either isotope were injected after vigorous manual agitation for about 3 min through the carotid artery catheter. Ten seconds prior to injection, the femoral artery catheter was opened and blood was withdrawn by means of a Havard withdrawal pump at a rate of 0.62 ml/min for exactly 1 min. In a separate previous experiment on 5 rats, complete removal of all microspheres by trapping in the capillary bed 10 s after injection without any evidence for recirculation could be demonstrated by sequential blood sampling every 10 s. Immediately after the first measurement, hypovolemia was established by withdrawal of 1.5 ml blood/100g body weight from the femoral artery within 5 min. Throughout the experiment, arterial pressure (AP) was continously recorded by means of a Statham transducer. Blood flow measurements were repeated 30 and 60 min after induction of shock. After the third injection of spheres the animals were killed, the stomach removed, the mucosa of the corpus as well as the antrum weighed and counted separately in a Packard gamma counter. The blood samples were also counted and all 141 Ce counts corrected for 51 Cr and 85 Sr spillage (12% and 22%, resp.). CMBF and AMBF were calculated as ml/min per g tissue wet weight: cpm/g tissue × fem. blood flow (ml/min) cpm femoral blood the cardiac output (CO) as ml/min per 100g body weight: cpm inject. × feml blood flow (ml/min) cpm femoral blood Statistical evaluation of these data was done with the U-test (Wilcoxon, Mann, Withney). In order to demonstrate the relationship of gastric mucosal blood flow regulation to the general circulation during shock, correlation and linear regression methods were applied. The variables were the relative differences between values at 60 and 30 min in dependence of the "60--n30 initial values (n= - )ofeachparameter tested. The probabilitiesofsignificantpositive(prono
duct moment) correlations were calculated.
Gastric Blood Flow in Shock
183
Table 1. Regional changes of gastric mucosal blood flow in hypovolemic shock (means and S.D. n = 20) 0
30'
AP (mm Hg)
97
+ 13
CO (ml/min/100g)
23.6 + 4.6
60'
* 42.5 +7
(44%)
n.s.
50
+ 15.6 (51.5%)
*
7.3 +1.9
(31%)
n.s.
9.0 + 5.6 (39%)
AMBF (ml/min/g)
0.68 + 0.20
*
0.21 +0.12 (35%)
n.s.
0.35+ 0.22 (51%)
CMBF (ml/min/g)
0.21 + 0.03
*
0.07+0.03 (33%)
n.s.
0.11+ 0.08 (52%)
* P
