Direct measurement of arteriovenous anastomotic blood flow in the septic canine hindlimb.

Absolute blood flow through hindlimb capillaries and arteriovenous anastomoses (AVA) was determined by the radioactive microsphere technique of relative shunt measurement combined with direct (electromagnetic) measurement of femoral artery blood flow. Studies were performed before and 72 hours after infection was created in six dogs by implanting fecal-contaminated wicks in one hindlimb. Three control dogs had sterile wicks implanted. Septic dogs demonstrated decreased arterial pressure and increased core temperature with no change in mean cardiac index. Infected legs had increased total femoral blood flow, decreased peripheral resistance, decreased arteriovenous (A-V) O2 difference, but unchanged oxygen consumption, Paw temperature increased in both infected and normal contralateral limbs. Muscle blood flow (MBF) (Xe133 clearance) increased only in infected legs. A-V shunting increased five-fold and AVA flow increased seven-fold in infected hindlimbs, significantly more than that in contralateral or control limbs. Increased A-V shunting correlated highly (r=0.95) with increased total femoral blood flow in infected legs, but increased MBF was not correlated (r=0.05). Despite increased MBF, increased AVA flow occurs in septic canine hindlimbs and contributes to the low-resistance, high-flow, but unchanged oxygen consumption described in this model.     

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 μg/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 ≥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.     

Revascularization of the ischemic canine hindlimb by arteriovenous reversal.

Arteriovenous reversal (AVR) for revascularization of ischemic tissues has previously failed to meet theoretical, experimental, and clinical expectations despite recurrent trials. The efficacy of a new staged approach to AVR was tested against a canine ischemic limb preparation in which global ligation of ipsilateral collaterals inevitably led to limb gangrene. In 12 animals the complications of direct, single-stage end-to-end femoral AVR, inevitably accompanied by the development of extreme edema, were demonstrated. However, when the ischemic preparation was accompanied by a staged AVR, in which an initial end-artery-to-side-vein arteriovenous fistula was converted 1 week later to AVR by ligation of the central venous limb, 20 of 20 animals survived, and 19 of 20 were ambulatory long-term survivors with only mild edema. Serial angiograms at 1 week, 1 month, and 4 months demonstrated patency rates of 100, 84, and 63%, respectively. Histologic examination of animals electively killed from 4 to 24 months showed normal skeletal muscle histology, venous intimal thickening, and mild edema. In the acutely ischemic canine hind limb, a staged AVR can provide both viability and function with only mild edema formation.     

Hemodynamic effects of multiple arteriovenous fistulae in the canine hindlimb.

The effects of multiple arteriovenous fistulae upon regional and central hemodynamic events were studied in anesthetized dogs. Fistulae between a femoral artery and vein were constructed from autogenous carotid artery in a manner which permitted placement of flowmeter transducers on the fistulae. A single fistula increased proximal femoral arterial flow from a mean control of 91 ± 16 (SE) to 357 ± 53 ml min^?1 (P < 0.01). Insertion of a second fistula distal to the first further increased this flow significantly (P < 0.01) to 492 ± 68 ml min^?1. Flow through the femoral artery distal to the fistulae was 65 ± 10 ml min^?1 with both fistulae closed. Opening one fistula reduced this value to 38 ± 7 ml min^?1; opening both fistulae further reduced flow to 21 ± 3 ml min^?1. Both these reductions, were significantly below control (P < 0.05, P < 0.01) and from each other (P < 0.05). Flows through either fistula alone approximated arterial and venous flows. An additional fistula increased arterial and venous flows, but reduced flow through the initial fistula. Either fistula increased arterial pulse above control and both fistulae together further increased pulse. Reciprocal effects on arterial pressure were recorded. These observations indicate that the addition of a second arteriovenous fistula in an extremity will not only (1) increase the chance of left ventricular strain and ultimate heart failure, but will also (2) decrease flow through the initial fistula and thus jeopardize its longevity, as well as (3) decrease perfusion of the extremity distal to the fistulae.     

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.     

Interaction of hindlimb blood flow,A-V shunting and A-V oxygen difference

The interactions of blood flow, A-V O₂ difference (AVDO₂), and A-V shunting were measured in normal hindlimbs of nine anesthetized dogs. An aorto-iliac nonpulsatile perfusion pump was used to change femoral artery blood flow from zero (collateral flow only) to twice its baseline level. Femoral AVDO₂ was measured by in-line spectrophotometric O₂ analysis. A-V shunting was measured with radio-labeled microspheres. Systemic hemodynamic parameters and temperature remained constant during the experiments. Despite changes in femoral mean arterial pressure (160 to 54 mm Hg) and AVDO₂ (1.8 to 8.2 ml O/₂/dl) that occurred with femoral blood flow reduction, peripheral A-V shunting remained constant at 4.1–5.5%. Alpha-adrenergic ablation (sympathectomy) was used to increase A-V shunting (up to 20%) during part of this experiment. When hindlimb blood flow was normal or increased, autoregulation of O₂ extraction maintained constant hindlimb O₂ consumption, despite sympathectomy-induced changes in A-V shunting. Subnormal femoral artery blood flow reduced hindlimb O₂ consumption, and in this setting the increased A-V shunting further decreased femoral AVDO₂ and O₂ consumption. Since AVDO₂ is dependent upon both blood flow and the variable efficiency of cellular O₂ extraction, it cannot be used as an accurate indicator of A-V shunting. Direct microsphere techniques should be applied to A-V shunt measurements in clinical settings where A-V shunting is suspected.     

Inferior canine hindlimb ischemia and reperfusion impairs femoral artery endothelium-dependent wall relaxation

This experimental investigation was carried out to study the endothelium-dependent ischemia-reperfusion injury upon the release of nitric oxide (NO) in the canine femoral artery. The tested experimental model was the inferior canine hindlimb ischemia induced by infrarenal abdominal aortic clamping followed by reperfusion. The research protocol was standardized in four experimental groups (n=6): (1) Control group; (2) Ischemia (120 minutes) group; (3) Ischemia (90 minutes) and reperfusion (60 minutes) group; and (4) Ischemia (120 minutes) and reperfusion (90 minutes) group. The femoral artery vascular reactivity was studied in vitro with the aid of an eight "organ chambers' setup, where segments from 4 to 5 mm, with and without endothelium, were suspended and connected to force transducers. The fundamental data of this study were as follows: (1) Ischemia caused by 120 minutes of infrarenal aortic clamping did not cause femoral artery endothelium dysfunction. (2) Ischemia caused by 90 minutes of clamping followed by 60 minutes of reperfusion also did not cause endothelium dysfunction, with an observed tendency to signal transduction impairment (studied by the sodium fluoride dose response curves). (3) Ischemia caused by 120 minutes of clamping followed by 90 minutes of reperfusion caused endothelium dysfunction, observed by the femoral artery impaired capacity of the endothelium-dependent NO release evoked by acetylcholine, adenosine diphosphate, and sodium fluoride. The present pharmacologic in vitro observations are concordant with the evidence that the NO-release impairment, caused by inferior canine hindlimb ischemia followed by reperfusion, is a consequence of endothelium cell membrane receptors, and G-proteins signal transduction dysfunction.     

Hemodynamic sequelae of combined arteriovenous injury in an experimental canine hindlimb model: Venous ligation vs. repair

The hemodynamic effects of combined venoarterial injury and stasis were studied in the hindlimbs of 10 dogs. Femoral arterial blood flow and pressure, peripheral venous pressure, and peripheral resistance were measured after the restoration of blood flow following venoarterial injury and a 4-hour period of occlusion for up to 72 hours. In one limb of each animal both the artery and vein were repaired, whereas only the artery was repaired in the other limb and the vein was ligated. Arterial blood flow was similar in both groups but was significantly diminished from baseline for the first 30 minutes after restoration of blood flow, but then it became significantly reduced in the limbs with venous ligation when compared with values in those with venous repair. By 72 hours the flow on both sides returned to control values. Peripheral venous hypertension and edema occurred in all 10 limbs with venous ligation and persisted for the 72-hour experimental period. In the 10 limbs with venous repair, edema occurred in four and venous hypertension in none. The peripheral resistance was elevated on both sides; this elevation persisted for 75 minutes and then dropped to control values. None of the repaired arteries and only one repaired vein thrombosed during the experiment. Combined venous and arterial occlusion for 4 hours reduced both the amount of arterial flow and its subsequent rate of increase compared with changes seen after release of an actue venous occlusion. The rate of increase was enhanced by repair of the affected venous segment compared with simple venous ligation.Supported by the William Beaumont Hospital Research Institute and Department of Surgery, RI-91-41RM.Presented at the Sixteenth Annual Meeting of the Midwestern Vascular Surgical Society, Cleveland, Ohio, September 11–12, 1992.     

Exercise-induced hyperemia unmasks regional blood flow deficit in experimental hindlimb ischemia

Many experimental models of hindlimb ischemia are characterized by spontaneous and rapid normalization of resting muscle blood flow (BF) rates which complicates the long-term evaluation of angiogenic therapies to reverse limb ischemia. We tested the hypothesis that peroneal nerve stimulation in an ischemic hindlimb would increase the oxygen (O(2)) demand and BF rate, thereby unmasking a severe blood flow deficit that is not apparent at rest. METHODS: Ischemia was induced in adult rats by ligation of the left common iliac, femoral arteries, and their branches. Peroneal nerves were stimulated to allow measurement of exercise-induced regional BF rates with fluorescent microspheres. Hemodynamics were monitored. Fluorescent microspheres were injected before and after 5 min of nerve stimulation 3, 10, and 24 days postischemia. The tibialis anterior (TA) and gastrocnemius (GC) muscles and skin were harvested and weighed, and fluorescence was measured. BF rate was calculated as milliters per minute per gram of tissue and compared to normal muscle and skin of unoperated control rats. In order to determine the accuracy of BF rate measurements in ischemic muscle when <400 microspheres was delivered per specimen, 3 rats were studied by simultaneous injection of 4 x 10(5) blue and 1 x 10(5) yellow-green fluorescent microspheres. The correlation coefficient between the number of different colored microspheres delivered was measured. RESULTS: The ischemia caused atrophy of the TA and GC muscles. The mean muscle mass of the ischemic TA and GC as a percentage of total body weight decreased over time vs control [TA 0.13 +/- 0.05% vs 0.25 +/- 0.03%, P < 0.05; GC 0.51 +/- 0.27% vs 0.70 +/- 0.07%, P = 0.07 at 24 days (24D)]. Despite clinical evidence of severe hindlimb ischemia in experimental groups, i.e., pressure sores, muscle atrophy, and weakness, resting BF rates were not significantly different from those of control. The BF rate of the TA was of 0.11 ml/min/g after 3D of ischemia, 0.14 ml/min/g after 10D, and 0.13 ml/min/g after 24D. The mean BF rate in normal muscle of unoperated controls was 0.16 ml/min/g (P > 0.05). However, the exercise-induced hyperemia in the skeletal muscle was significantly blunted in all of the ischemic groups. The unoperated control TA had a greater than 10-fold increase in BF to 1.95 ml/min/g in response to exercise while the ischemic TA had no increase in BF at 3D, 2-fold increase at 10D, and a 5-fold increase at 24D. Parallel findings were noted in the GC muscles. There was no significant difference in the BF rate in the skin. The accuracy of this microsphere technique in measuring very low BF rates found in ischemic muscle was supported by the significant correlation coefficient (r = 0.99) comparing two quantities of microspheres injected simultaneously. CONCLUSION: Despite clinical signs of severe hindlimb ischemia, resting BF rates in the ischemic groups were not significantly decreased. Peroneal nerve stimulation resulted in up to 10-fold increase in BF rate and unmasked a severe deficit in vascular reserve in the ischemic groups. Resting BF rate is not always an accurate reflection of the flow deficit in models of critical limb ischemia, and this model of exercise-induced hindlimb hyperemia may allow better long-term evaluation of angiogenic therapies designed to reverse critical limb ischemia.     

A canine model of multiple portosystemic shunting.

The objective of this study was to develop and describe an experimental canine model of multiple acquired portosystemic shunts (PSS) similar in nature to spontaneously occurring PSS. Sixteen dogs were used and were divided into a control (n = 6) and a diseased group (n = 10). Dogs of the diseased group were administered dimethylnitrosamine (2 mg/kg of body weight, po) twice weekly, and clinicopathologic, ultrasonographic, and hepatic scintigraphic findings were recorded during the development of hepatic disease and PSS. Surgery was then performed to permit visual verification of multiple shunts, catheter placement for portography examination, and biopsy of the liver. All diseased dogs developed severe hepatic disease and multiple PSS as documented visually at surgery and on portography. Based on this study, dimethylnitrosamine-induced portosystemic shunting appears to be an appropriate model for spontaneously occurring multiple PSS secondary to portal hypertension.     

Cerebral venous and tissue gases and arteriovenous shunting in the dog.

Cerebral venous blood gas values have been used to indicate brain tissue oxygenation. However, it is not clear how cerebral tissue and venous measures may vary under physiologic conditions caused by arteriovenous shunt. The purpose of this study was to measure brain tissue and local cerebral venous oxygen (PO2) and carbon dioxide (P(CO2)) partial pressure during changes in ventilation and to calculate shunt fraction. Eight dogs were anesthetized with isoflurane. After a craniotomy, a Neurotrend probe (Diametrics Inc., St. Paul, MN) that measures P(O2), P(CO2), pH, and temperature was inserted into brain tissue, and a small vein that drained the same tissue was catheterized. Arterial, cerebral venous, and brain tissue P(O2) and Pco2 were measured during random changes in ventilation to produce five different levels of inspired oxygen (room air, 40%, 60%, 80%, 95%) at each of three different end-tidal Pco2 (20 mm Hg, 40 mm Hg, 60 mm Hg). Arteriovenous shunt was calculated from oxygen and C(O2) content in artery, vein, and tissue, representing capillary. Tissue P(CO2) was 8 mm Hg greater than vein Pco2 during hypocapnia and this difference increased to 20 mm Hg during hypercapnia. Vein P(O2) was 8 mm Hg higher than tissue P(O2) during hypocapnia, and this difference increased to 40 mm Hg during hypercapnia. Shunt fraction increased from 10%-20% during hypocapnia to 50%-60% during hypercapnia. These results show that brain vein and tissue P(O2) and P(CO2) differ because of arteriovenous shunting and this difference is increased as end-tidal P(CO2) increases. IMPLICATIONS: We found, in dogs, that the gradient between brain venous and tissue P(O2) and PCO2 is increased with increased arterial P(CO2). The divergence between tissue and venous gases can be described by arterial to venous shunting.     

Rapid arteriovenous shunting in a spinal cord ependymoma. Case report.

A case of ependymoma of the conus medullaris and cauda equina is described in which spinal angiography demonstrated rapid arteriovenous shunting, an angiographic sign which is typical of arteriovenous malformations and which has not been previously reported to occur with ependymomas.     

Visualization of angiographical arteriovenous shunting in perisylvian glioblastomas

Background

Arteriovenous shunting visualized by angiography is one of the major features of glioblastomas, and the visualization is dependent on the presence of extensive shunting. Extensive arteriovenous shunting is associated with the risk of poorly controlled intraoperative bleeding. When a tumor with extensive arteriovenous shunting is located in close proximity to the eloquent regions of the brain, a meticulous surgical procedure is necessary. In the present study, the site-oriented visualization of angiographical arteriovenous shunting was evaluated from the perspective of surgical treatment, with a particular focus on the perisylvian region that is in close proximity to motor and language regions (dominant hemisphere), as well as large arteries and veins.

Methods

Twenty-six consecutive patients underwent a resection of glioblastoma between February 2007 and September 2012. All patients were presurgically examined using digital subtraction angiography. The patients were subdivided into the following two groups based on the location of the tumor: 1) perisylvian glioblastoma (18 patients) and 2) non-perisylvian glioblastoma (eight patients). Angiography to detect the arteriovenous shunting was performed. In addition, the number of intratumoral vessels, tumor proliferative activity (MIB-1 labeling index), and volume of intraoperative bleeding were evaluated and compared between the two groups.

Results

Angiographical arteriovenous shunting was definitively visualized in 13 of 18 (72 %) perisylvian glioblastomas, in contrast to only one of eight (13 %) non-perisylvian glioblastomas (p?=?0.007). There were no significant differences between the two groups with respect to the number of intratumoral vessels, MIB-1 labeling index, and volume of intraoperative bleeding. However, massive intraoperative bleeding of > 2,000 mL occurred in one perisylvian glioblastoma patient.

Conclusions

Glioblastomas in the perisylvian region tend to be associated with extensive arteriovenous shunting that can be definitively visualized by performing an angiography. Because arteriovenous shunting carries the risk of intraoperative bleeding, perisylvian glioblastomas—particularly in the dominant hemisphere—should be resected with a meticulous surgical procedure and strategy.