SELECTIVE DILATION OF THE CONSTRICTED SUPERIOR MESENTERIC ARTERY

Transcription

1 GASTROENTEROLOGY Copyright 1972 by The Williams & Wilkins Co. Vol. 62, No.1 Printed in U. S.A. SELECTIVE DILATION OF THE CONSTRICTED SUPERIOR MESENTERIC ARTERY HARVEY B. ULANO, PH.D., M.D., ELMER TREAT, M.D., LINDA L. SHANBOUR, PH.D., AND EUGENE D. JACOBSON, M.D. Departments of Physiology and Biophysics and Surgery, University of Oklahoma Medical Center, Oklahoma City, Oklahoma Intraarterial infusion of potent vasoactive dl1,.lgs was assessed in the constricted mesenteric circulation of dogs. Animals were anesthetized and superior mesenteric artery blood flow was measured with electromagnetic blood flow transducers. Systemic arterial and portal venous pressures were measured, and the resistance to blood flow across the gut was calculated. After control measurements, 30% of the blood volume was removed to produce persistent hypotension, mesenteric ischemia, and arteriolar constriction in the intestinal circulation. Direct infusion of prostaglandin EI (0.1 J,Lg per kg-min), glucagon (0.5 J,Lg per kg-min), and isoproterenol (0.5 J,Lg per kg-min) into the constricted mesenteric artery dilated the vessel and restored blood flow nearly to prehemorrhage values without altering systemic arterial pressure. Intraarterial dopamine (10 J,Lg per kg-min) failed to dilate the mesenteric artery or increase its blood flow. Effects of the vasodilator agents did not persist after cessation of drug infusion. These findings indicate that selective infusion of potent vasodilator drugs can reverse severe mesenteric constriction and ischemia in the experimental animal and suggests a new avenue for treatment of nonocclusive ischemic disease of the gut. Over the last 10 years, nonocclusive mesenteric ischemia has been recognized as a major clinical entity. It is often associated with congestive heart failure, use of digitalis, and profound states of shock. I, 2 The etiology of this intestinal vascular spasm is not well understood and treatment is most often unsuccessful. In a complete diagnostic study of the patient with mesenteric ischemic disease, the artery is catheterized for purposes of angiographic visualization. This procedure provides an opportunity for selective dila- Received July 1, Accepted August 9, Address requests for reprints to: Dr. Eugene D. Jacobson, Program in Physiology, University of Texas Medical School at Houston, Houston, Texas Dr. Ulano's present address is: Jackson Memorial Hospital, 1700 N.W. 10th Avenue, Miami, Florida tion of the intestinal circulation, if nonocclusive ischemia is present. While many agents could be used to augment intestinal blood flow, optimal characteristics of the arteriolar dilator would include: (1) high potency to allow intraarterial infusion of minute quantities; (2) rapid disappearance from the circulation to obviate distant effects on other blood vessels; and (3) antiplatelet aggregating properties to prevent formation of microthrombi in the mesenteric circulation. Prostaglandin E I, a derivative of prostanoic acid found in various tissues including the gut, possesses these properties This study describes hemodynamic responses of the constricted mesenteric circulation of dogs to intraarterial infusion of several potent vasoactive agents, including prostaglandin E I, isoproterenol, glucagon, and dopamine.

2 40 ULAND ET AL. Vol. 62, No. 1 Methods Thirty-eight mongrel dogs of both sexes weighing 15 to 25 kg each were anesthetized with pentobarbital sodium (30 mg per kg) injected intravenously. The trachea was intubated by mouth and the animals breathed spontaneously. A femoral artery and vein were cannulated, and the arterial catheter was connected to a pressure transducer (Sanborn Co., Waltham, Mass.). The contralateral femoral artery was cannulated for subsequent use during hemorrhage. A midline laparotomy was performed in all dogs. Viscera were retracted to the left of the midline and the proximal superior mesenteric artery was exposed by longitudinal dissection. A small proximal branch of the mesenteric artery was cannuulated, and the tip of a polyethylene tube was positioned at the junction of the main artery and the cannulated branch, thereby assuring that infused solutions would be distributed to the remainder of the mesenteric arterial tree. An electromagnetic blood flow probe (Micron Instruments, Inc., Los Angeles, Calif.) of either 3.0 or 3.5 mm (internal diameter) was positioned around the superior mesenteric artery proximal to the first branch. The flow probe was connected to a blood flow amplifier (Micron Instruments, Inc.). The entire system had been calibrated previously with whole blood. Zero flow determinations were performed with a vascular clamp at regular intervals. A small splenic vein was isolated and a catheter was advanced to the junction of the splenic and the portal veins. The catheter was connected to a venous pressure transducer (Statham Instruments, Inc., Oxnard, Calif.) and utilized for monitoring portal venous pressure. Heart rates were monitored on all animals with lead II of the electrocardiogram. The laporatomy incision was covered with moist sponges and the animals were allowed to stabilize for 15 min. The following measurements were continuously recorded on a four-channel polygraph (Sanborn) : systemic arterial and portal pressures, superior mesenteric artery blood flow, and heart rate. Fifteen minutes after stabilization all animals in the study were subjected to hemorrhagic shock by bleeding 2.7% of body weight from the femoral artery (circa 30% of blood volume). The bleeding period was approximately 10 min. Measurements were taken at 15-min intervals over the next 2.5 hr. At 1 hr after hemorrhage the infusion catheter in the mesenteric arterial branch was connected to a constant infusion pump (Harvard Apparatus Co., Millis, Mass.). Six animals received normal saline 5 ml per min, four groups of 7 animals each received one of the following drugs (dose expressed as the base) : prostaglandin E l, kindly supplied by Dr. John Pike of the Upjohn Company, (0.1 ij.g per kg-min); glucagon, Eli Lilly and Co., (0.5 ij.g per kgmin); isoproterenol, Winthrop Laboratories, (0.5 ij.g per kg-min); and dopamine, Arner Stone Labs., Inc., (10 ij.g per kg-min). The volume rate of drug solution infused never exceeded 5 ml per min. Infusions were maintained for 1 hr and then discontinued. In pilot studies drug doses were determined on the basis of amounts producing maximal changes in mesenteric blood flow without altering arterial pressure. Mesenteric vascular resistance was calculated as (arterial-portal) pressure to blood flow and expressed as mm Hg per ml per min. Statistical evaluation of the pair-wise comparison of means within each group was carried out using Duncan's New Multiple Range test. 5 Values in results are expressed as mean ± standard error. All directional changes described in results were significant with a probability less than Results Saline series (fig. 1, tables 1 and 2). In the 6 animals receiving an intraarterial infusion of saline mean control values before hemorrhage were: systemic arterial pressure (SAP), 135 ± 8 mm Hg; portal venous pressure (PVP), 6.8 ± 0.7 mm Hg; superior mesenteric arterial blood flow (SMAQ), 390 ± 33 ml per min; superior mesenteric arterial resistance (SMAR), 0.35 ± 0.04 mm Hg per ml per min; and heart rate (HR), 154 ± 12 beats per min. 200 i (.) 100 ;;.. / r1 / / / /r-r-rt-t-t-r-rt-1 f 30 Hemorrhage! Saline infusion SMAR FIG. 1. Effects of isotonic saline infusion (control study) on systemic arterial blood pressure (SAP), superior mesenteric arterial blood flow (SMAQ), and resistance (SMAR) at 1 hr posthemorrhage in 6 animals.

3 January 1972 MESENTERIC VASODILA TION 41 Series TABLE 1. Portal venous pressure (PVP), mm Hg Time o min 15 min 30 min 45 min 60 min 75 min 90 min loi, min 120 min 135 min min Infusion period Saline series PVP , ±SE Prostaglandin series PVP ±SE Glucagon series PVP ± SE Isoproterenol series PVP ± SE.. " Dopamine series PVP ±SE TABLE 2. Heart rate (HR), beats per minute Series o min 15 min 30 min 45 min Time 60 min 75 min 90 min 105 min 120 min 135 min min Saline series HR ±SE Prostaglandin series HR ±SE Glucagon series HR ± SE Isoproterenol series HR ± SE Dopamine series HR ±SE Infusion period Within 15 min after hemorrhage SAP fell significantly (P < 0.05) from 135 to 68 mm Hg and then began to recover partially. At 30 min SAP was 84 mm Hg. SAP increased gradually over the next 2 hr and reached 105 mm Hg at min. All values posthemorrhage were lower than control; however, values from 60 to min were significantly higher than preceding values. PVP fell 41% from 6.8 to 4.0 mm Hg at 15 min after hemorrhage (table 1), and then began to recover gradually. All posthemor- rhage values were significantly lower than control. During the 60 min of saline infusion PVP did not change appreciably. SMAQ fell after hemorrhage from 390 to 137 ml per min at 15 min, and thereafter gradually increased (fig. 1). All posthemorrhage SMAQ values were significantly lower than control. The saline infusion did not influence the gradual increase of SMAQ which reached 188 ml per min at min. This latter value was 52% less than prehemorrhage control.

4 42 ULAND ET AL. Vol. 62, No.1 SMAR was increased 78% from 0.35 to 0.62 mm Hg per ml per min at 15 min posthemorrhage, and fluctuated around the latter value during the -min observation period. All values posthemorrhage were significantly higher than control. The saline infusion did not appreciably change SMAR. HR was increased at all times posthemorrhage and rose from 154 to 169 beats per min at 30 min and to 175 beats per min at min (table 2). The saline infusion had no effect on Hr. Prostaglandin (PGE I) series (fig. 2, tables 1 and 2). Mean control values before hemorrhage were as follows: SAP, 120 ± 8 mm Hg; PVP, 6.0 ± 0.4 mm Hg; SMAQ, 385 ± 31 ml per min; SMAR, 0.29 ± 0.02 mm Hg per ml per min; and HR, 148 ± 7 beats per min. SAP was decreased at all times after hemorrhage, and fell from 120 to 72 mm Hg at 15 min (P < 0.05). Thereafter SAP began to increase slowly until at 60 min it was 90 mm Hg. During the PGE 1 infusion SAP decreased to 81 mm Hg at 105 min. When the infusion was stopped SAP rose to 90 mm Hg at 135 min. PVP fell from 6.0 to 3.3 mm Hg at 15 min posthemorrhage, and increased at the start of PGE 1 infusion from 4.1 mm Hg at 60 min to 5.3 mm Hg at 75 min (P < 0.05) (table 1). When the infusion was discontinued at 120 min PVP fell again from 6.1 to 5.0 mm Hg at 135 min (P < 0.05). SMAQ fell 65% from 385 to 134 ml per min at 15 min posthemorrhage, and recovered to ml per min at 60 min. With PGE 1 infusion SMAQ increased from 200 SMAR SMAO t Prosfagiandin infusion! r Hemorrhage FIG. 2. Effects of prostaglandin E 1 infusion on SAP, SMAQ, and SMAR at 1 hr posthemorrhage in 7 dogs. to 329 ml per min at 75 min (P < 0.05). The latter value was within 14% of prehemorrhage control flow. SMAQ remained elevated during PGE 1 infusion and fell significantly from 325 at 120 min to 170 ml per min at 135 min with cessation ofpge I infusion. SMAR increased 109% at 15 min posthemorrhage (0.29 to 0.61 mm Hg per ml per min) and fluctuated about this value until the start of PGE 1 PGE 1 lowered resistance from 0.60 at 60 min to 0.23 mm Hg per ml per min at 75 to 120 min (P < 0.05). The latter value was approximately 20% lower than prehemorrhage resistance. With cessation of PGE h SMAR rose from 0.23 to 0.58 mm Hg per ml per min at min (P < 0.05). HR was increased significantly at all times posthemorrhage (table 2), and rose from 148 to 169 beats per min at 60 min. PGE 1 had no significant effect on HR. A recording from 1 animal hemorrhaged and subsequently infused with PGE 1 is shown in figures 3A and 3B. Hemorrhage caused a proportionally greater fall in SMAQ than in SAP indicating a marked increase in SMAR (fig. 3A). With infusion of PGE 1 intraarterially (fig. 3B) SMAQ and PVP returned approximately to prehemorrhage levels, while SAP decreased only slightly. This sequence of changes is due to a pronounced decrease in SMAR at the time of PGE 1 infusion. Glucagon (GLU) series (fig. 4, tables 1 and 2). Mean control values before hemorrhage were: SAP, 117 ± 3 mm Hg; PVP, 6.1 ± 0.4 mm Hg; SMAQ, 388 ± 33 ml per min; SMAR, 0.28 ± 0.03 mm Hg per ml per min; and HR, 133 ± 8 beats per min. Mean SAP fell from 117 to 55 mm Hg at 15 min and increased to 85 mm Hg at 60 min. SAP was approximately 85 mm Hg during intraarterial infusion of GLU. After GLU was discontinued SAP rose slowly to 94 mm Hg at min. All posthemorrhage values were significantly lower than control. PVP fell from 6.1 to 3.3 mm Hg at 15 min, and increased to 4.7 mm Hg at 60 min (table 1). GLU infusion increased PVP significantly at all time periods when compared to any of the posthemorrhage values before infusion of GLU. When the drug infusion was discontinued PVP fell from

5 A - 0 _ SMAQ ml/min ECG - 10 ~ -5-0 PVP mm Hg SAP mmhg T START OF HEMORRHAGE 1~lmin""l B r-----~-~ 'I 2 o SMAQ ml/min ECG '-. \ PVP mmhg ~ SAP - 0 mmhg i PGE, INFUSION (O.lpg/kg-min) FIG. 3. A, actual recording of changes in systemic arterial pressure (SAP)' portal venous pressure (PVP), electrocardiogram (ECG), and superior mesenteric arterial blood flow (SMAQ) after rapid arterial hemorrhage of 30% of blood volume in 1 animal. B, recording from the same animal as in figure 3A 1 hr later. Effect of PGE 1 infusion on SAP, PVP, ECG, and SMAQ. 43

6 44 ULANO ET AL. Vol. 62, No ~ "0.. HemOfrhogt FIG. 4. Effects of glucagon infusion on SAP, SMAQ, and SMAR 1 hr posthemorrhage in 7 animals. 6.6 at 120 min to 5.3 mm Hg at min (P < 0.05). SMAQ was 388 ml per min and decreased to 125 ml per min at 15 min. SMAQ was still only 153 ml per min before GLU, but rose to 331 ml per min after 15 min of GLU infusion (P < 0.05). SMAQ was within 15% of prehemorrhage values during the GLU infusion. When GLU was discontinued SMAQ fell from 343 at 120 min to 199 ml per min at min (P < 0.05). SMAR increased from 0.28 to 0.43 mm Hg per ml per min at 15 min posthemorrhage and continued to increase until at 60 min it was 0.55 mm Hg per ml per min. GLU decreased SMAR significantly from 0.55 to 0.25 mm Hg per ml per min. GLU decreased SMAR significantly from 0.55 to 0.25 mm Hg per ml per min after 15 min of infusion. SMAR fluctuated about this latter value during the 60 min of infusion, and these values corresponded to a 12 to 19% decrease in resistance when com pared to the prehemorrhage control. SMAR increased again when GLU was stopped and rose from 0.24 at 120 min to 0.47 mm Hg per ml per min at min (P < 0.05). HR increased from 133 to 147 beats per min at 15 min posthemorrhage (table 2). At 60 min HR was 164 and increased significantly to 200 beats per min after 15 min of GLU infusion. HR remained significantly elevated from the preglucagon values to min at which time it was 191 beats per min. Isoproterenol (ISOP) series (fig. 5, tables 1 and 2). Mean control prehemorrhage values in this group were: SAP, 125 ± 6 mm Hg; PVP, 7.0 ± 0.2 mm Hg; SMAQ, 358 ± 17 ml per min; SMAR, 0.33 ± 0.03 mm Hg per ml per min; and HR, 162 ± 11 beats per min. SAP decreased from 125 to 72 mm Hg at 15 min posthemorrhage, and increased to 81 mm Hg at 60 min. ISOP infusion lowered SAP to 76 mm Hg within 15 min, but pressure gradually recovered to 83 mm Hg after 60 min of infusion (120 min posthemorrhage). SAP was 84 mm Hg at min. All posthemorrhage values were significantly lower than control SAP. PVP was 7.0 mm Hg before hemorrhage and fell to 5.1 mm Hg at 15 min and gradually rose to 5.4 at 60 min (table 1). After 15 min of ISOP infusion PVP rose to 6.7 mm Hg and remained elevated until the infusion was stopped. PVP fell from 6.7 at 120 min to 5.9 mm Hg at 135 min (P < 0.05) with cessation of ISOP. After hemorrhage, SMAQ declined from 358 to 108 ml per min at 15 min and was 129 ml per min at 60 min. ISOP increased SMAQ from 129 to 272 ml per min after 15 min of infusion. During the infusion SMAQ was significantly increased from all posthemorrhage values and was within 25% of the prehemorrhage control. When ISOP was discontinued SMAQ fell from 289 at 120 min to 143 ml per min at min (P < 0.05). SMAR increased after hemorrhage from 0.33 to 0.67 mm Hg per ml per min and was 0.62 at 60 min. ISOP infusion evoked a significant decrease in resistance to 0.26 mm Hg per ml per min at 75 min. During the infusion SMAR was 21 % below the prehemorrhage control and significantly lower than all posthemorrhage values before drug infusion. With cessation of infusion SMAR rose from 0.27 at 120 min to 0.57 e g o 100 "0 /1f'r-r-1\ I \ I \ I \ / \ \ LL_ Hemorrhage SMAR SMAO FIG. 5. Effects of isoproterenol infusion on SAP, SMAQ, and SMAR 1 hr posthemorrhage in 7 dogs.

7 January 1972 MESENTERIC VASODILATION 45 mm Hg per ml per min at min (P < 0.05). HR was increased significantly at all points posthemorrhage (table 2), and at 60 min had increased by 20 beats to 182 beats per min. ISOP infusion evoked an additional increase to 193 beats per min at 75 min. HR was significantly elevated above all preceding values during drug infusion. With cessation of ISOP, HR decreased from 195 beats per min at 120 min to 189 beats per min at min. Dopamine series (fig. 6, tables 1 and 2). Mean control values before hemorrhage were: SAP, 115 ± 6 mm Hg; PVP, 6.0 ± 0.9 mm Hg; SMAQ, 254 ± 33 ml per min; SMAR, 0.46 ± 0.06 mm Hg per ml per min; and HR, 164 ± 11 beats per min. SAP fell from 115 to 61 mm Hg at 15 min and thereafter increased to 78 mm Hg at 30 min. SAP was 86 mm Hg at 60 min and increased to 90 mm Hg during the dopamine infusion. SAP was 84 mm Hg at min. PVP decreased after hemorrhage from 6.0 to 3.5 mm Hg at 15 min (table 1). Thereafter, PVP gradually increased to 4.3 mm Hg at 60 min. Dopamine infusion did not significantly alter mean PVP. SMAQ was significantly lower than the prehemorrhage control at all times and fell from 254 to 107 ml per min at 15 min. Flow gradually rose to 139 ml per min at 60 min and was transiently elevated to 159 ml per min after 15 min of dopamine infusion (75 min posthemorrhage). From 75 to 120 min flow fell significantly and was 111 ml per min at 120 min. With cessation of dopamine flow increased from 111 at 120 min to 155 ml per min at min (P < 0.05). SMAR was increased by hemorrhage from 0.46 to 0.59 mm Hg per ml per min at 15 min and was 0.63 at 60 min. Dopamine infusion transiently lowered SMAR to 0.59, but resistance quickly rose to 0.79 and was 0.82 mm Hg per ml per min at 120 min. The latter value was significantly above the predopamine infusion value of 0.63 at 60 min. With cessation of dopamine, SMAR fell from 0.82 at 120 min to 0.53 mm Hg per ml per min (P < 0.05). HR increased significantly after hemorrhage by 20 beats per min at 60 min (table 2). Dopamine infusion transiently lowered HR to 170 beats per min after 15 min of drug, ".. o 1 Hemorrhage SMAR SAP SMAO FIG. 6. Effects of dopamine infusion on SAP, SMAQ, and SMAR at 1 hr posthemorrhage in 7 dogs. but the rate was 178 and 180 beats per min at 120 and min posthemorrhage, respectively. Discussion The mesenteric vascular bed autoregulates its blood supply,6 but is also influenced by the sympathetics, circulating catecholamines, and the renin-angiotensin system. Sympathetic stimulation to the gut as well as circulating catecholamines cause initial transient decreases in intestinal blood flow which soon escapes to prestimulation levels despite continued nerve stimulation or catecholamine infusion. 7 In nonocclusive mesenteric vascular disease autoregulation and the escape mechanism fail to maintain normal blood flow to the gut. McNeill et al. 8 showed that angiotensin and/or vasopressin cause constriction of the intestinal resistance vessels after hemorrhage in cats, and this response was not altered by an a adrenergic blocking agent. The sympathetic nervous system and circulating catecholamines did not significantly contribute to this response. In nonocclusive mesenteric vascular disease angiotensin and/or vasopressin may elicit intestinal vasoconstriction that cannot be overcome by autoregulatory escape mechanisms. In this disease state current therapy has had disappointing results. I We used the constricted mesenteric vascular bed of oligemic dogs to mimic the constricted but not occluded mesenteric circulation in the human disorder. In all dogs in our study, rapid arterial

8 46 ULANO ET AL. Vol. 62, No.1 hemorrhage produced a significant and sustained fall in arterial and portal pressures and mesenteric blood flow with a significant and sustained rise in mesenteric resistance and heart rate. Shehadeh et al. 9 have shown that intraarterial infusion of PGE 1 increased superior mesenteric arterial flow approximately 100% under normovolemic nonshocked conditions, and evoked significant vasodilation. Nakano and Cole 10 reported that PGE 1 increased heart rate, cardiac output, and myocardial contractility, and decreased blood pressure and total and peripheral resistances in dogs when injected intravenously. They also noted that PGE 1 was substantially metabolized in the liver and probably in the lungs. For this reason mesenteric infusions of PGE 1 had no significant peripheral systemic activity at the dose we utilized. The potent dilating action of PGE 1 is most likely due to its direct action on vascular smooth muscle." 12 Intraarterial infusion of PGE 1 has also been shown to increase blood flow and decrease resistance in the coronary, brachial, femoral, carotid, and renal arteries. 13 In our study PGE 1 infused into the constricted mesenteric bed of the bled dog restored mesenteric blood flow to 86% of prehemorrhage values. Furthermore, PGE 1 lowered the resistance to blood flow through the gut to values of 79% of the prehemorrhage level. Heart rate was not altered by PGE 1 infusion and arterial pressure was lowered somewhat. The response to PGE 1 in the mesenteric bed was maintained only during its administration, and all parameters returned rapidly toward pre infusion levels with cessation of the drug. Thus, intraarterial PGE 1 can overcome potent mesenteric constrictor activity and maintain adequate gut perfusion in the hypovolemic state without any marked effect on either the heart or the rest of the circulation. Glucagon has been shown to increase ascending aortic, coronary, and renal artery blood f10w following intravenous administration. 14 In the splanchnic bed Tibblin et al. 15 have shown that intravenous glucagon increased blood f10w by 180% and there was no significant difference in responses between conscious and anesthetized dogs. Since blood pressure was slightly decreased, the increase in f10w was ascribed to a decrease in mesenteric resistance. In experiments where the liver was temporarily excluded from the circulation and blood glucose concentration decreased, glucagon was shown to produce essentially the same f10w response in the mesenteric circulation as with an intact liver blood flow. 16, 17 In hemorrhagic shock glucagon has been shown to increase cardiac output, stroke volume, heart rate, and central venous pressure and decrease blood pressure and peripheral resistance. 18 In our studies glucagon evoked an almost identical response in mesenteric hemodynamics as that described for PGE l' Blood pressure remained essentially unchanged while portal pressure and mesenteric blood f10w increased significantly. Resistance decreased during glucagon infusion. Glucagon also increased heart rate significantly. These changes in mesenteric perfusion were quickly dissipated when glucagon was discontinued. The well known vasodilatory and chronotropic effects of isoproterenol were reaffirmed in these studies. In comparison to PGE 1 and glucagon, isoproterenol at the dose utilized restored mesenteric blood flow to almost comparable values. Effects of isoproterenol on other measured parameters were similar to those of glucagon. Dopamine has been shown to produce vasodilation and increased blood flow in the mesenteric arterial distribution of the anesthetized cat after comparable intraarterial doses to those used in our studies. 19 However, dopamine infusion in the constricted mesenteric bed of dogs in this study exerted no beneficial effect on blood flow or resistance. These studies indicate that direct intraarterial infusion of PGE 1, glucagon, and isoproterenol into the constricted superior mesenteric artery of dogs in hemorrhagic shock is of value in improving gut perfusion, at least during the infusion period. Blood f10w can be restored to levels only 15 to 20% below normal at significantly reduced perfusion pressures. What-

9 January 1972 MESENTERIC VASODILATION 47 ever factor or factors evoke constriction and decreased blood flow are easily overcome by these three agents. All these agents have other actions on the cardiovascular system, but their effects were minimal, and certainly not detrimental at the doses utilized. An implication of this work is that it is possible to increase intestinal perfusion with catheterization of the major inflow vessel and proper selection of drug and drug dose. Nonocelusive mesenteric vascular disease usually terminates fatally. Intraarterial infusion of a potent vasodilator, such as PGE h with its anti platelet aggregating properties and rapid disappearance from the circulation merits consideration in a disease for which there is no effective current therapy. REFERENCES 1. Price WE, Rohrer GV, Jacobson ED: Mesenteric vascular diseases. Gastroenterology 57: , Pierce GE, Brochenbrough EC: The spectrum of mesenteric infarction. Am J Surg 119: , Lee JB: Prostaglandins. Physiologist 13: , Sekhar NC: Effect of eight prostaglandins on platelet aggregation. J Med Chern 1:39-44, Steel RGD, Torrie JH: Principles and Procedures of Statistics. New York, McGraw-Hill Book Co, Johnson PC: Origin, localization, and homeostatic significance of auto-regulation in the intestine. Circ Res 15: , Shanbour LL, Jacobson ED: Autoregulatory escape in the gut. Gastroenterology 60: , McNeill JR, Stark RD, Greenway CV: Intestinal vasoconstriction after hemorrhage: roles of vasopress in and angiotensin. Am J Physiol 5: , Shehadeh Z, Price WE, Jacobson ED: Effects of vasoactive agents on intestinal blood flow and motility in the dog. Am J Physiol 216: , Nakano J, Cole B: Effects of prostaglandins E, and F 2 on systemic, pulmonary and splanchnic circulations in dogs. Am J Physiol 217 : , Nakano J: Effect of prostaglandins E" A, and F 2 on cardiovascular dynamics in dogs, Prostaglandin Symposium of the Worcester Foundation for Experimental Biology. Edited by PW Ramwell, JE Shaw. New York, Wiley and Sons, Inc, 1968, p Nakano J, McCurqy JR: Cardiovascular effects of prostaglandin E,. J Pharmacol Exp Ther 156: , Nakano J : Effects of prostaglandin E" A, and F 2 on the coronary and peripheral circulations. Proc Soc Exp Bioi Med 127: , Kock NG, Tibblin S, Schenk WG: Hemodynamic responses to glucagon. An experimental study of central, visceral and peripheral effects. Ann Surg 171 : , Tibblin S, Kock NG, Schenk WG: Splanchnic hemodynamic responses to glucagon. Arch Surg 100:84-89, Kock NG, Tibblin S, Schenk WG: Mesenteric blood flow response to glucagon administration during temporary exclusion of the liver. Arch Surg 100: , Tibblin S, Kock NG, Schenk WG: Dissociation of the hyperglycemic and vascular effects of glucagon. Surgery 67: , Bower MG, Okude S, Jolley WB, et al: Hemodynamic effects of glucagon following hemorrhagic and endotoxic shock in the dog. Arch Surg 101 : , Ross G, Brown HW: Cardiovascular effects of dopamine in the anesthetized cat. Am J Physiol 212: , 1967