Effect of intravenous glucagon on the survival of rats after acute occlusive mesenteric ischemia

The purpose of this study was to determine the optimal timing of intravenous glucagon infusion for the treatment of acute occlusive mesenteric ischemia. The superior mesenteric artery (SMA) was occluded for 85 min in 106 Sprague--Dawley anesthetized rats. The animals were divided into 12 treatment groups according to the timing of glucagon and saline administration, and survival was measured to 48 hr. Without treatment, all rats died within 24 hr. Intravenous saline (10 ml/kg/hr) for 2 hr did not significantly improve 48-hr survival (17-33%). Glucagon (1.6 [mu]g/kg/min iv) plus saline (10 ml/kg/hr iv) for 2 hr after SMA occlusion significantly improved survival from 33% (saline control) to 83% (P P < 0.02). Adequate saline infusion was required for glucagon efficacy after ischemia, as shown by an intermediate 48-hr survival of 50% when only maintenance saline (1.5 ml/kg/hr) was given. These data suggest that glucagon therapy should be delayed until after operative release of an acute SMA occlusion and should be accompanied by vigorous volume expansion.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25685/1/0000239.pd

Major Lower Extremity Amputation in Veterans Affairs Medical Centers

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42433/1/10016-14-3-216_00140216.pd

Outcomes after Abdominal Aortic Aneurysm Repair in Those ≥80 Years of Age: Recent Veterans Affairs Experience

= 231) of the patients. A total of 5833 patients underwent repair of nonruptured AAA: mortality was 4.1% (228/5627) in those <80 and 8.25% (17/206) in those ≥80 years old ( p < 0.009). Logistic regression analysis indicated age ≥80 was independently associated with higher mortality (odds ratio 1.834:1, 95% bounds 1.117-3.012). Octogenarian status (defined as ≥80 years of age), however, had a less important association with in-hospital death than did surgical complications of the heart or genitourinary tract, postoperative hemorrhage, septicemia, respiratory insufficiency, myocardial infarction (MI), acute renal failure, surgical complications of the central nervous system (CNS), aneurysm rupture, postoperative shock, or disseminated intravascular coagulation (DIC), in ascending order of importance. Only 5.9% ( n = 25) of the 427 patients undergoing repair of ruptured AAA were ≥80 years old. In those ≥80 undergoing repair of ruptured aneurysms, mortality was 48% which did not differ from the 45% mortality in those <80 (NS). The likelihood that one would be operated for rupture was statistically greater (1.66:1) for those ≥80 years ( p < 0.025). Length of stay (LOS) for those ≥80 undergoing AAA repair was longer being 22.3 ± 14.8 days versus 18.3 ± 13.2 days for younger patients ( p < 0.001). Mortality and LOS after AAA repair were statistically greater for those ≥80 years of age. Severity of illness, however, was also greater for octogenarians. Patient Management Category (PMC) software defined illness severity was 4.06 ± 1.22 in octogenarians versus 3.84 ± 1.13 for those younger ( p < 0.005). Though age ≥80 was independently associated with increased mortality, selected elderly patients could benefit from AAA repair.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42431/1/10016-12-2-106_12n2p106.pd

Comparative hemodynamic effects of selective superior mesenteric arterial and peripheral intravenous glucagon infusions

This experiment was designed to determine whether any hemodynamic benefits attend administration of equal pharmacologic doses of glucagon (1 [mu]g/kg/m) by continuous intravenous infusion (Group I, n = 6) versus selective intraarterial infusion (Group II, n = 6) via the superior mesenteric artery (SMA) in dogs. Cardiac output, heart rate, mean arterial pressure, total peripheral resistance, pulmonary vascular resistance, superior mesenteric artery flow (SMAQ), SMA vascular resistance, and portal venous pressure were measured at baseline (BL) and at 5, 15, 30, and 45 min during glucagon infusion. SMAQ virtually doubled at 5 min from a baseline of 570 +/- 60 ml/min to 1158 +/- 146 ml/min in Group I (P P P P &lt; 0.05). Changes in systemic hemodynamic parameters, as well as glucagon and glucose levels were not statistically different between Groups I and II at any time period. Glucagon is a potent mesenteric vasodilator and the resultant profound splanchnic hemodynamic effects are as marked during intravenous administration as during selective SMA infusion.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25582/1/0000126.pd

Dissociation of glucagon's central and peripheral hemodynamic effects: Mechanisms of reduction and redistribution of canine hindlimb blood flow

Effects of parenterally administered pharmacologic doses of glucagon on canine hindlimb blood flow were studied. Cardiac output (CO), mean arterial pressure (MAP), total peripheral resistance (TPR), common femoral artery flow (CFAQ), common femoral artery resistance (CFAR), percentage shunt in the hindlimb (AVA%) determined by 99mTc microsphere technique, the volume of hindlimb shunt flow (AVAQ), and the volume of hindlimb nutrient capillary flow (NCQ) were determined at baseline and at 10, 20, and 30 min during continuous intravenous infusion of 1 [mu]g/kg/min glucagon (n = 8). Blood glucagon and glucose levels were measured at all time periods. Glucagon infusion significantly increased CO throughout the infusion, while reducing MAP and TPR. Unexpectedly, CFAQ decreased significantly despite the increase in CO. CFAR increased despite the reduction of TPR during glucagon infusion. The reduction of CFAQ was associated with diminished nonshunt hindlimb NCQ and increased AVA%. Changes in CFAQ, AVA%, AVAQ, and NCQ did not correlate in a linear fashion with the changes in either blood glucose or glucagon levels by linear regression analysis. Glucagon appeared to cause a major redistribution of peripheral blood flow. Hindlimb arteriolar dilatation was not an effect of this hormone in this experimental model. Glucagon appeared to have a salutary central hemodynamic effect, but was detrimental to canine extremity perfusion.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24416/1/0000686.pd

Early derangements of arteriovenous anastomotic and capillary blood flow in the canine hindlimb induced by supplemental pentobarbital anesthesia

Vasoactive effects of supplemental pentobarbital anesthesia in the canine hindlimb microcirculation were documented in two groups of animals previously anesthetized with 30 mg/kg pentobarbital: Group I with a 5 mg/kg intravenous (iv) bolus of pentobarbital (n = 8) and Group II with a 5 mg/kg 2-min iv infusion of pentobarbital (n = 7). In Group I, measurements at baseline (BL) and 5, 15, 20, and 30 min (min) following pentobarbital administration included cardiac output, mean arterial pressure, total peripheral vascular resistance, common femoral artery flow (CFAQ) and resistance (CFAR), percentage hindlimb arteriovenous anastomotic shunt (AVA%), absolute shunt flow (AVAQ), and hindlimb nutrient capillary flow (NCQ). In Group II these same measurements were made, but the study was continued until all hindlimb hemodynamic parameters returned to control values. CFAQ, AVA%, AVAQ, and NCQ were significantly increased, and CFAR was decreased in both groups. CFAQ and NCQ remained significantly elevated at 30 min in Group I. In Group II CFAR, AVA%, and AVAQ remained elevated at 30 min, but did return to BL by 40 min, as did all other hindlimb hemodynamic parameters measured. Pentobarbital resulted in both AVA and arteriolar dilation, with an increase in the percentage total flow distributed to AVAs. These alterations of microcirculatory flow should be considered during investigations of the distribution of peripheral blood flow, as well as during metabolic studies assessing arteriovenous substrate differences, if interpretative errors are to be avoided.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24920/1/0000347.pd

Glucagon and canine mesenteric hemodynamics: Effects on superior mesenteric arteriovenous and nutrient capillary blood flow

The objective of this investigation was to define the splanchnic hemodynamic effects of parenterally administered glucagon in a canine model. Measurements in six dogs at baseline and at 10, 20, and 30 min during constant intravenous infusion of glucagon at 1 [mu]g/kg/min included: Cardiac output (CO), mean arterial pressure, total peripheral vascular resistance (TPR), superior mesenteric artery flow (SMAQ), portal venous pressure (PVP), superior mesenteric artery vascular resistance (SMAR), percentage SMA flow through arteriovenous anastomoses (AVA%) determined by 99mTc microsphere technique, as well as volume flow through AVA (AVAQ), and volume flow through the SMA nutrient capillary circulation (NCQ). SMAQ rose significantly and disproportionately compared to the rise in CO. SMAQ more than doubled from a mean of 448 +/- 124 cc at baseline to a mean of 921 +/- 321 cc at 10 min, and remained elevated throughout drug infusion. SMAR and TPR both decreased significantly. Although percentage shunt was low at baseline, 1.79 +/- 0.94%, and did not change, both AVAQ and NCQ increased significantly during drug infusion. The increase in AVAQ was transient, but NCQ remained elevated throughout infusion. PVP increased significantly, and the change in PVP correlated significantly with the change in AVAQ at 30 min, a time when AVAQ was not elevated significantly above baseline levels. Nutrient capillary flow comprised &gt;=98% of total SMAQ during the experiment and, along with total SMAQ, doubled and remained elevated throughout drug infusion. Although glucagon may increase PVP by slightly increasing the absolute volume of mesenteric shunt flow, its primary action is that of a potent mesenteric arterial dilator, increasing NCQ strikingly more than AVAQ.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24413/1/0000683.pd