The pancreas and oxygen consumption (Part 2). Steroids do not modify resting pancreatic oxygen consumption in dogs: a preliminary report.

In order to evaluate the effect of methylprednisolone sodium succinate (MPSS) on the alteration of pancreatic oxygen consumption (VO2) in hypovolemic shock, MPSS was administered to four normal canines and three hypovolemic animals. All were treated according to the protocol used in the initial report. (The Pancreas and Oxygen Consumption 1: Pancreatic Oxygen Consumption in Normo- and Hypovolemic Dogs.) All seven underwent a splenectomy at the beginning of the experiment. Pancreatic VO2, obtained by adding up VO2 for the head (minus the uncinate process) and tail of the pancreas, was equal to the product of regional blood flow, Q, determined electromagnetically on the gastroduodenal (GDA) and splenic (SA) arteries, times O2 extraction, (a-v)O2; O2 content (in mL%) was measured in the femoral artery (RFA), in the splenic (SV) and superior pancreaticoduodenal (SPDV) veins. Similar determinations were carried out on the right hind limb that served as a control. Recordings were made for 4 h in both groups, the first hour determinations (five in all) serving as reference values. Methylprednisolone did not appear to alter pancreatic VO2, which showed a significant increasing trend from + 77% 1 h after MPSS had been given, to + 98% 3 h later (vs + 56 and + 92%, respectively, in the control group). As in the control group, these increases were owing to augmented O2 extraction by the pancreas. No significant change was noted between the head and tail of the pancreas. In the hind limb, VO2 increased significantly the first 2 h and differed from control VO2 at the end of the first hour only.

The pancreas and oxygen consumption. 1. Pancreatic oxygen consumption in normo- and hypovolemic dogs.

Pancreatic oxygen consumption (VO2) was studied in hypovolemic shock: 4 dogs served as controls and 4 others were kept at 50 mm Hg of mean arterial blood pressure. All 8 were studied for a period of 3 h. Pancreatic VO2 was obtained by adding up VO2 for the head (minus the uncinate process) and tail of the pancreas both equal to the product of regional blood flow times O2 extraction. Regional blood flows were measured electromagnetically on the gastroduodenal (GDA) and the splenic (SA) arteries, whereas O2 extraction was derived from total hemoglobin (THb) and oxygen saturation of hemoglobin (%O2 Hb) determined on the right femoral artery (RFA), the superior pancreaticoduodenal (SPDV), and splenic (SV) veins. A splenectomy was performed in all 8 dogs. Controls showed a significantly elevated pancreatic VO2 from the first hour of observation on (+56% after 1 h, +92% after 3), whereas pancreatic VO2 remained strictly unchanged throughout shock (+2% and +6%, at one and 3 h, respectively), despite significant increases in O2 extraction. These findings give support to the deleterious effects of hypovolemia to the pancreas and that pancreatic O2 extraction indicates metabolic damage to be less severe than observed in experimental bile-trypsin-induced acute pancreatitis.

Steroids do not alter pancreatic blood supply in hypovolemic dogs: implications on steroid action in acute pancreatitis.

A recent report from our laboratory showed that pancreatic inflammation induced by hypovolemic shock can be explained to some extent by spoliation in pancreatic perfusion as revealed by electromagnetic flow determinations on the gastroduodenal artery (GDA). On the other hand, when given early in the course of hypovolemic shock, methylprednisolone sodium succinate (MPSS) alleviated pancreatic inflammation as evidenced by gross and histological findings. Five dogs (18-23 kg) were submitted to a 3-hour hypovolemic shock (mean arterial blood pressure, MABP = 50 mm Hg) and received during bleeding 35 mg/kg of MPSS over a 30 min period. Recordings of cardiac output (CO), MABP, regional blood flows in the GDA and superior mesenteric (SMA) arteries were taken every 15 min. The effect of MPSS was appreciated by comparing GDA flow variations in this group with those previously published of a control group comprised of 12 dogs submitted to 3 hours of hypovolemic shock without steroids; operative protocol was in all points similar in both groups. At no time were any significant changes noted when MPSS was added as far as CO and GDA flows were concerned. In other words, the beneficial action of steroids on hypovolemic pancreases cannot be explained by alteration in regional blood flow.

Effects of sodium bicarbonate in canine hemorrhagic shock.

We studied the use of sodium bicarbonate administration in a canine model of hemorrhagic shock to determine its effect on hemodynamics, arterial and venous blood gases, respiratory gases, and blood lactate levels. Thirteen dogs were anesthetized, paralyzed, mechanically ventilated, and hemodynamically monitored. Hypotension was induced and maintained at a mean arterial pressure of 40 to 45 mm Hg using controlled hemorrhage and reinfusion. After 2.5 h of shock, the dogs were randomized into two groups: one group (n = 6) received NaCl infusion; the other (n = 7) received sodium bicarbonate (1 mEq/kg followed by a continuous infusion of 2.5 mEq/kg.h for 2.5 h). CO2 production was increased in the alkali group, but there was no statistically significant difference between groups in any measured hemodynamic, blood gas, or respiratory gas variable. These included heart rate, BP, cardiac output, arterial and venous pH, CO2 production, and bicarbonate levels. Blood lactate levels, however, in the bicarbonate treated animals were significantly (p less than .01) higher than in the group treated with NaCl alone (10.1 +/- 3.2 vs. 5.1 +/- 1.2 mEq/L). These results are similar to the effects of bicarbonate found in other models of lactic acidosis, and suggest that bicarbonate therapy may have limited usefulness in the treatment of lactic acidosis.

Hypovolemic shock, pancreatic blood flow, and pancreatitis.

Electromagnetic blood flow determinations were carried out on the superior pancreatic duodena (SPDA), the splenic (SA) and the superior mesenteric (SMA) arteries and compared to cardiac output (CO, thermodilution technique) in 12 anesthetized dogs submitted to hypovolemic shock of various duration: 5 dogs underwent a one-hour and 7 a three-hour period of shock. A 50 mm Hg level of mean arterial blood pressure (MABP) was maintained throughout hypovolemia. Dogs were then reinfused. Control preshock values were 4.12 l/min for CO, 38.0 ml/min for SPDA, 405.9 ml/min for SA, and 963.6 ml/min for SMA. SPDA, SA and SMA flows expressed as % of CO amounted to 0.9, 9.8 and 23.4% respectively. No significant changes in SPDA and SMA flows were noted within the first hour of shock. However, from the end of the second hour on, both flows differed significantly (P less than 0.01), SMA increasing from -75.6% of its control value at the end of bleeding to -61.0%, and SPDA decreasing from -75.6 to -86.9%. Similar observations were made when respective flows were considered as % of CO. The SA behaved somewhat in an intermediate fashion. This relative spoliation in pancreatic blood supply as hypovolemia proceeds supports an ischemic etiology of acute pancreatitis (AP), which could account for some of the so-called idiopathic cases of AP.

Venous hypercarbia in canine hemorrhagic shock.

The venous-arterial PCO2 gradient may increase in certain low-flow states, such as CPR and canine endotoxemia. To determine whether venous hypercarbia also occurs in hemorrhagic shock, we studied 12 anesthetized, mechanically ventilated dogs. We performed laparotomies on the animals, inserting catheters into their renal, superior mesenteric, and external iliac veins. Flow in the corresponding arteries were determined using electromagnetic flow probes. The dogs were randomized into a control group (n = 6), and a hemorrhagic shock group (n = 6) which was bled to a mean arterial pressure of 45 to 50 mm Hg and maintained at this pressure for the 6-h study. The results demonstrated a significant (p less than .05) increase in lactate and venous-arterial PCO2 gradient systemically and in all three regional beds. A significant decrease of venous blood pH accompanied these changes which are consistent with our previous findings in low-flow, canine endotoxemia. We conclude that venous hypercarbia is a nonspecific phenomenon, common to low-flow states. The increased CO2 represents both an increased CO2 production and a decreased removal, secondary to low-flow.

Foot blood flow measurements improve venous plethysmographic studies.

The time for foot volume restoration after exercise is widely used as a measure of venous regurgitation. Since this is also a function of arterial inflow rate, we have tested the hypothesis that uncorrected for arterial inflow, these tests may be misleading. Change in venous foot volume after elevation and on exercise was measured in 44 subjects. Arterial inflow was also determined. In a few patients arterial flow was varied by cooling or by exercise. The times of half-volume restoration were measured. Calculated were: the rate of total blood flow into the foot; the rate of venous regurgitation; and "venous sufficiency indices" for elevation and for exercise with and without correction for arterial inflow rate. These indices combine volume and time data in a single numeric value. Volume change on elevation was uninfluenced by the rate of arterial inflow. Volume change on exercise and the halftime of volume restoration varied significantly with the rate of arterial inflow as did the "venous sufficiency indices." These variances were significantly reduced by correcting for arterial inflow rate. We conclude that for foot volume studies to measure regurgitation and for data obtained at different times to be comparable, corrections must be made for the rate of arterial inflow to the foot.

Hemodynamic effects of verapamil in the beta-blocked dog.

The use of the calcium channel-blocking agent, verapamil, in beta-blocked patients has been the subject of intense investigation, particularly because both verapamil and the beta-blockers can produce negative inotropic effects. We studied the hemodynamic effects of verapamil in beta-blocked dogs to establish specific measurements that could be used clinically for early identification of combined negative inotropism. Seven anesthetized, mongrel dogs were beta-blocked with propranolol, and then given 2.5-, 5.0-, and 10.0-mg iv boluses of verapamil. The 2.5- and 5.0-mg boluses represent clinical doses, whereas the 10.0-mg bolus is a large pharmacologic dose. Hemodynamic measurements showed that verapamil was well tolerated at clinical doses; increases in stroke volume compensated for decreases in mean arterial pressure. At high doses of verapamil this response was not observed and left ventricular stroke work decreased. Cardiac and stroke indices were not useful indicators of combined drug toxicity in this dog model.

Noninvasive evaluation of chronic venous insufficiency. Use of foot mercury strain-gauge plethysmography.

Twenty-seven patients (40 extremities) with chronic venous insufficiency and 30 controls (60 extremities) were studied using noninvasive measurements of foot volume (foot mercury strain-gauge plethysmography [FMSGP]). Tests were performed with exercise (sitting) and with elevation (Trendelenburg), with and without tourniquets, to evaluate muscle pump efficiency and valvular competence. Empiric venous sufficiency indexes were calculated for exercise and for Trendelenburg's test. Test results were compared with invasive ambulatory venous pressure (AVP) data (13) and with ascending and retrograde venography (25). Distinctive plethysmographic patterns revealed the insufficiency was saphenous (four), calf perforators (14), saphenous plus perforators (seven), and deep venous (15), including occlusion (four). Correlation with AVP and venography was good but FMSGP was more discriminating, providing precise anatomical information, better reproducibility, and distinguishing poor muscle pump function from regurgitation. Patients accept FMSGP well. Repeated postoperative data are readily obtained for evaluation of surgical procedures.