Arteriovenous Shunt Flow Research Articles

Key Biophysical and Physiological Properties Impacting the Oxygenation Status of Breast Cancers During Thermo-radiotherapy.

Mild hyperthermia at 39-43°C for 30-60 min is applied locoregionally to improve the oxygenation status of recurrent breast cancers, thus enhancing the efficacy of radio-, chemo-, and immunotherapy. In this context, estimated (or even conflicting) data are often used in computational modelling of tumour oxygenation and simulation of O2 transport. In this chapter, we present information that may help to improve adjuvant thermotherapy delivered immediately prior to radiotherapy of recurrent breast cancers. Data are preferentially derived from clinical investigations; in some cases, measurements in experimental breast cancers are included.The biophysical properties presented for healthy, mostly postmenopausal, human breast (composite glandular-adipose-fibrous tissue) measured under normothermic (NT) conditions and in therapeutically heated breast cancers include tissue water content and tissue density. In general, averaged values of parameters reported for NT conditions are higher in breast cancers than in normal breast tissue, i.e., all ratios breast cancer/normal breast are >1. Mean values observed in breast cancers during mild hyperthermia (mHT) are consistently higher than those in NT tumours. Parameters determining convective transports in healthy breast tissue and breast cancer include blood flow rates, blood volume, exchanging water space, arterio-venous shunt flow, interstitial fluid flow rate, interstitial fluid pressure, microvascular permeability, interstitial hydraulic conductivity, and interstitial flow velocity. In general, averaged values of parameters measured under NT conditions are higher in breast cancers than in healthy breast. Except for interstitial fluid pressure, these values increase upon mHT treatment of cancers. Prime factors determining and describing the oxygenation status of the healthy breast, and in NT- versus mHT-treated breast cancers, include: oxygen (O2) delivery rates, O2- extractions, O2- consumption rates, subepidermal microvascular HbO2, tissue oxygen solubility, oxygen diffusion coefficients, mean O2 partial pressures pO2, hypoxic fractions HF<5mmHg, oxygen enhancement ratio, and mitochondrial ROS production. With the exception of the mean pO2, O2 extraction rate and tissue O2 saturation all parameters listed are distinctly higher in breast cancers under NT conditions compared to normal breast. Mild hyperthermia results in therapeutically relevant improvements of the oxygenation status of cancers and enhances mitochondrial ROS production, thus improving radiosensitivity. Note: The oxygenation status of the healthy (postmenopausal) breast is very similar to that of the normal human subcutis.

Endovascular repair for arterio-venous fistula treatment: a case report

BackgroundArterio-venous fistula is a rare clinical entity that occurs as a result of a ruptured abdominal aortic aneurysm into the inferior vena cava or iliac vein. Open surgery has been considered the treatment of choice for this condition; however, endovascular repair has become an evolving therapeutic option over the past 20 years. The endovascular treatment has contributed to a decrease in the perioperative mortality; nevertheless, some endovascular repair specific concern for residual fistula still remains.Case presentationA 70-year-old man was referred to our department for an enlarged inferior vena cava without any complaint. Contrast-enhanced computed tomography demonstrated a 40-mm AAA and a 42-mm right saccular CIAA, with a fistula between the CIAA and left CIV. Endovascular aneurysm repair which focused on the exclusion of the right CIAA and prevention of endoleak formation was performed. To prevent type 2 endoleaks, which cause residual arterio-venous shunt flow, right internal iliac artery was embolized with a vascular plug prior to stent graft procedure. Successful aneurysm exclusion without residual arterio-venous shunt flow was confirmed with a final angiographic examination. The patient had an uneventful recovery, and computed tomography 1 month later showed no sign of persistent fistula.ConclusionsAlthough endovascular treatment for AVF has a negative possibility of residual shunt, stent graft with a focus on type 2 endoleak prevention can be an attractive treatment option, reducing the incidence of residual AVF.

Thromboresistance and endothelial healing in polymer-coated versus polymer-free drug-eluting stents: Implications for short-term dual anti-platelet therapy

BackgroundShort-term dual antiplatelet therapy (DAPT) is a suitable strategy after stent implantation especially in patients at high risk for bleeding. The thromboresistant characteristics and the healing profile permanent polymer stents such as the Resolute Onyx- drug-eluting stent (DES) has never been tested against the current approved stents for short-term DAPT, the polymer free (PF) biolimus-eluting stent (PF-BES) and bare metal stents (BMS) in dedicated preclinical models. MethodsAn ex-vivo porcine arteriovenous shunt and in-vivo flow loop model were used to evaluate thromboresistance. The healing profile was assessed in the rabbit model at 28 days by confocal microscopy (CM), scanning electron microscopy (SEM) and histology. Onyx-DES was separately compared with Onyx-BMS in first experiment and PF-BES in second experiment. ResultsIn an ex-vivo shunt model, CM and SEM showed significantly less platelet adhesion for Onyx-DES relative to Onyx-BMS and PF-BES. In a flow loop model using human blood, platelet adhesion was also significantly less in Onyx-DES as compared to PF-BES and Onyx-BMS. In the healing study, Onyx-BMS showed significantly greater healing profile relative to Onyx-DES as expected, whereas Onyx-DES showed equivalent endothelial coverage by SEM and significantly less Evan's blue uptake and comparable colocalization of p120 and vascular endothelial-cadherin when compared with PF-BES. ConclusionsOnyx-DES showed qualities of thomboresistance and healing which appear to be compatible with short-term DAPT. Thromboresistance was superior to PF-BES and healing was equivalent to PF-BES in this pre-clinical study. Onyx-DES might provide advantages when considering short-term DAPT especially in patients at high risk of bleeding.

Effects of pumpless extracorporeal lung assist on hemodynamics, gas exchange and inflammatory cascade response during experimental lung injury.

Pumpless extracorporeal lung assist (pECLA) has been reported to efficiently remove the systemic CO2 production and provide mild to moderate oxygenation, thereby allowing for ventilator settings and modes prioritizing oxygenation and lung protection. However, an adequate bypass flow, the capacity to provide respiratory support and the effect on the inflammatory cascade response and tissue perfusion require further study to be determined. After induction of acute lung injury (ALI) by oleic acid injection, pECLA was implemented in 12 anaesthetized and mechanically ventilated dogs for 48 h. Improved oxygenation [partial oxygen pressure (PaO2) and oxygen saturation (SaO2) was measured by arterial blood gas analysis, and increased by 29 and 18%, respectively] and CO2 elimination (partial CO2 pressure decreased by 43.35%) were obtained after pECLA implementation. A maximum arterio-venous shunt flow of up to 25% of the foundational CO resulted in stable hemodynamics. The pECLA procedure did not elicit any further increase in the concentration of tumor necrosis factor-α, interleukin (IL)-6, IL-8 and endothelin-1 compared with that in the group subjected to oleic acid injection only. In addition, the pECLA procedure had no effect on lactate levels and urine production. In conclusion, pECLA is an efficient and promising strategy for providing a mild to moderate oxygenation and adequate decarboxylation, while avoiding excessive inflammatory cascade response and tissue hypoperfusion in an experimental ALI model.

A Case of De Novo Anterior Condylar Dural Arteriovenous Fistula Long after Curative Transvenous Embolization of Contralateral Anterior Condylar Arteriovenous Fistula.

We report on a 55-year-old man who developed a de novo DAVF in left ACC 5 years after curative transvenous embolization for DAVF in right ACC. Angiography revealed that the de novo lesion demonstrated more aggressive arteriovenous shunt flow than the initial lesion. Successful transvenous embolization was performed for also the second lesion. The authors describe the possible pathophysiological mechanisms and management strategies for this rare occurrence.

Complex Alterations of Intracranial 4-Dimensional Hemodynamics in Vein of Galen Aneurysmal Malformations During Staged Endovascular Embolization.

Vein of Galen aneurysmal malformations (VGAMs) are rare congenital cerebral arteriovenous shunts often treated by staged endovascular embolization early in life. Treatment-induced changes in intracranial hemodynamics and their impact on the clinical management of VGAM patients remain unclear. To evaluate hemodynamic alterations in the cerebral arterial and venous network in pediatric patients with VGAMs during staged embolizations. Serial 4-dimensional flow magnetic resonance imaging (21 scans) was performed in 6 VGAM patients (3 female; mean age, 2.1 ± 4.0 years) undergoing staged embolization. Time-integrated pathlines were used to visualize 3-dimensional blood flow changes in intracranial arterial and venous systems. Total cerebral arterial inflow (flow in bilateral internal carotid arteries plus basilar artery), arteriovenous shunt flow, and blood flow in other major cerebral arteries (middle cerebral artery; posterior cerebral artery) were quantified for all patients. Intracranial 3-dimensional blood flow visualization demonstrated marked reduction of arteriovenous shunting and distinct hemodynamic alterations after embolization. From baseline to endpoint embolization, total cerebral arterial inflow dropped by 40.2% (from 22.70 ± 6.54 mL/s to 13.57 ± 4.87 mL/s), corresponding to arteriovenous shunt flow reduction of 73.5% (from 9.69 ± 6.16 mL/s to 2.57 ± 3.79 mL/s). In addition, the ipsilateral posterior cerebral artery/middle cerebral artery flow ratio decreased by 86.9% (from 4.20 ± 6.28 to 0.55 ± 0.23). Hemodynamic alterations in VGAMs after embolization can be visualized and quantified using 4-dimensional flow magnetic resonance imaging. Cerebral arterial inflow and arteriovenous shunt flow reduction and complex flow redistribution after embolization illustrate the potential of 4-dimensional flow magnetic resonance imaging to better evaluate the efficacy of interventions and monitor treatment effects.

Doppler sonographic evaluation of arteriovenous shunt flow in a fetus with dural sinus malformation

Dural sinus malformation (DSM) is a rare congenital malformation characterized by a dilated dural sinus pouch. We present a case of prenatally diagnosed DSM and propose a parameter to predict poor fetal outcome. Detailed ultrasonography at 26 weeks of our patient showed an intracranial cyst in the left posterior fossa. Color Doppler study indicated an arteriovenous shunt within the cyst with increased blood flow velocity. Based on these findings, fetal DSM with arteriovenous shunt was diagnosed. Because of fetal hydrops with high-output cardiac failure and maternal pregnancy-induced hypertension, labor was induced at 32 weeks and resulted in stillbirth. In conclusion, based on the present case, we can deduce that color Doppler study is useful for prenatal diagnosis of DSM with arteriovenous shunt and that a high-flow velocity to the cystic lesion is a possible predictor of hydropic change in such fetuses.

Pumpless arterio-venous extracorporeal lung assist compared with veno-venous extracorporeal membrane oxygenation during experimental lung injury

Extracorporeal lung support is effective to prevent hypoxaemia and excessive hypercapnia with respiratory acidosis in acute respiratory distress syndrome. Miniaturized veno-venous extracorporeal membrane oxygenation (mECMO) and arterio-venous pumpless extracorporeal lung assist (pECLA) were compared for respiratory and haemodynamic response and extracorporeal gas exchange and device characteristics. After induction of acute lung injury by repeated lung lavage, 16 anaesthetized and mechanically ventilated pigs were randomized to mECMO (Medos Hilite/Deltastream) or pECLA (iLA Novalung) for 24 h. Improved gas exchange allowed reduced ventilation and plateau pressure in both groups. An arterio-venous shunt flow of up to 30% of cardiac output resulted in a left cardiac work of 6.8 (2.0) kg m for pECLA compared with 5.0 (1.4) kg m for mECMO after 24 h (P<0.05). Both devices provided adequate oxygen delivery to organs. The oxygen transfer of pECLA was lower than mECMO due to inflow of arterial oxygenated blood [16 (5) compared with 64 (28) ml min(-1) after 24 h, P<0.05]. Unexpectedly, the carbon dioxide transfer rate was also lower [58 (28) compared with 111 (42) ml min(-1) after 24 h, P<0.05], probably caused by a Haldane effect preventing higher transfer rates in combination with lower extracorporeal blood flow. Both devices have the potential to unload the lungs from gas transfer sufficiently to facilitate lung-protective ventilation. Although technically less complex, oxygen uptake and carbon dioxide removal are limited in pECLA, and cardiac work was increased. mECMO overcomes these limitations and might provide better cardiopulmonary protection.

Microvascular dysfunction in diabetic foot disease and ulceration

Diabetic foot disease and ulceration is a major complication that may lead to the amputation of the lower limbs. Microangiopathy may play a significant role in the pathogenesis of tissue breakdown in the diabetic foot. However, the precise mechanisms of this process remain unclear and poorly understood. Microvasculature in the skin is comprised of nutritive capillaries and thermoregulatory arteriovenous shunt flow. It is regulated through the complex interaction of neurogenic and neurovascular control. The interplay among endothelial dysfunction, impaired nerve axon reflex activities, and microvascular regulation in the diabetic patient results in the poor healing of wounds. Skin microvasculature undergoes both morphologic changes as well as functional deficits when parts of the body come under stress or injury. Two important theories that have been put forward to explain the abnormalities that have been observed are the haemodynamic hypothesis and capillary steal syndrome. With advances in medical technology, microvasculature can now be measured quantitatively. This article reviews the development of microvascular dysfunction in the diabetic foot and discusses how it may relate to the pathogenesis of diabetic foot problems and ulceration. Common methods for measuring skin microcirculation are also discussed.

Effects of Isoflurane and Sevoflurane Anesthesia on Arteriovenous Shunt Flow in the Lower Limb of Diabetic Patients without Autonomic Neuropathy

Failure of sympathetic nerve control caused by diabetic neuropathy results in vasodilation of arteriovenous shunts. The aim of this study was to test the hypothesis that the function of arteriovenous anastomoses was disordered in mild diabetic patients without apparent neuropathy, and that volatile anesthetics opened arteriovenous shunts more greatly in nondiabetic patients than diabetic patients. Autonomic system function was assessed by cardiovascular reflex tests. Arterial-venous oxygen content difference (A-VDeltaO2) and partial oxygen pressure index (Pvo2/Pao2, the ratio of oxygen tension in femoral vein blood to that in femoral artery blood) were measured before and during isoflurane or sevoflurane anesthesia in 16 diabetic and 22 nondiabetic patients. Skin temperatures of the foot and leg were measured in 14 diabetic and 15 nondiabetic patients using thermography before and during anesthesia. Pvo2/Pao2 before anesthesia was significantly higher in diabetic patients. In nondiabetics, venous oxygen content significantly increased and A-VDeltaO2 markedly decreased during anesthesia, but these parameters were unchanged in diabetics. Foot temperatures were higher in diabetics before anesthesia, and increased gradually and significantly in both groups during anesthesia, but with a greater increase in nondiabetic patients. Induction of anesthesia caused a larger decrease in leg temperature in diabetics than in nondiabetics. Diabetic patients have a higher Pvo2/Pao2 and a small core-to-peripheral temperature gradient before anesthesia, suggesting latent dysfunction of the autonomic nerve system, even in the absence of autonomic neuropathy. Volatile anesthesia opens the arteriovenous shunt in nondiabetics to a greater extent than in diabetic patients.

Intracranial Pial Arteriovenous Fistula -Case Report-

A 33-year-old woman presented with a rare intracranial pial arteriovenous fistula manifesting as monoparesis and hypesthesia of the right lower extremity. Computed tomography demonstrated an approximately 10-mm diameter subcortical hematoma in the left postcentral gyrus. Two months after suffering the ictus, angiography demonstrated a pial arteriovenous fistula in the late arterial phase fed by the left paracentral artery and drained into the left precentral vein. No nidus or dural arteriovenous fistula was detected. Left parietal craniotomy was performed and the pial arteriovenous fistula was extirpated by electrocoagulation. Intraoperative angiography demonstrated disappearance of the fistula. She experienced no postoperative neurological deterioration, but hypesthesia of the right leg persisted. Obliteration of the pial arteriovenous fistula was reconfirmed by postoperative angiography. She suffered no rebleeding episodes during the 36-month follow-up period. Pial arteriovenous fistula causing mild symptoms should be treated by flow disconnection because the direct arteriovenous shunt and attendant high blood flow usually results in huge venous varices. To determine whether direct surgery or endovascular treatment is appropriate, the position and shape of the lesion must be known.

Investigation of the fluid dynamical properties of helical pipes from a mixing perspective

Ischemic heart disease is more apparent in the subendocardial than in subepicardial layers. We investigated coronary pressure–flow relations in layers of the isolated rat left ventricle, using 15 μm microspheres during diastolic and systolic arrest in the vasodilated coronary circulation. A special cannula allowed for selective determination of left main stem pressure–flow relations. Arterio-venous shunt flow was derived from microspheres in the venous effluent. We quantitatively investigated the pressure–flow relations in diastolic arrest (n=8), systolic arrest at normal contractility (n=8) and low contractility (n=6). In all three groups normal and large ventricular volume was studied. In diastolic arrest, at a perfusion pressure of 90 mmHg, subendocardial flow is larger than subepicardial flow, i.e., the endo/epi ratio is ∼1.2. In systolic arrest the endo/epi ratio is ∼0.3, and subendocardial flow and subepicardial flow are ∼12% and ∼55% of their values during diastolic arrest. The endo/epi ratio in diastolic arrest decreases with increasing perfusion pressure, while in systole the ratio increases. The slope of the pressure–flow relations, i.e., inverse of resistance, changes by a factor of ∼5.3 in the subendocardium and by a factor ∼2.2 in the subepicardium from diastole to systole. Lowering contractility affects subendocardial flow more than subepicardial flow, but both contractility and ventricular volume changes have only a limited effect on both subendocardial and subepicardial flow. The resistance (inverse of slope) of the total left main stem pressure–flow relation changes by a factor of ∼3.4 from diastolic to systolic arrest. The zero-flow pressure increases from diastole to systole. Thus, coronary perfusion flow in diastolic arrest is larger than systolic arrest, with the largest difference in the subendocardium, as a result of layer dependent increases in vascular resistance and intercept pressure. Shunt flow is larger in diastolic than in systolic arrest, and increases with perfusion pressure. We conclude that changes in contractility and ventricular volume have a smaller effect on pressure–flow relations than diastolic–systolic differences. A synthesis of models accounting for the effect of cardiac contraction on perfusion is suggested.

Cardiovascular stability during arteriovenous extracorporeal therapy: a randomized controlled study in lambs with acute lung injury

IntroductionClinical application of arteriovenous (AV) extracorporeal membrane oxygenation (ECMO) requires assessment of cardiovascular ability to respond adequately to the presence of an AV shunt in the face of acute lung injury (ALI). This ability may be age dependent and vary with the experimental model. We studied cardiovascular stability in a lamb model of severe ALI, comparing conventional mechanical ventilation (CMV) with AV-ECMO therapy.MethodsSeventeen lambs were anesthetized, tracheotomized, paralyzed, and ventilated to maintain normocapnia. Femoral and jugular veins, and femoral and carotid arteries were instrumented for the AV-ECMO circuit, systemic and pulmonary artery blood pressure monitoring, gas exchange, and cardiac output determination (thermodilution technique). A severe ALI (arterial oxygen tension/inspired fractional oxygen <200) was induced by lung lavage (repeated three times, each with 5 ml/kg saline) followed by tracheal instillation of 2.5 ml/kg of 0.1 N HCl. Lambs were consecutively assigned to CMV treatment (n = 8) or CMV plus AV-ECMO therapy using up to 15% of the cardiac output for the AV shunt flow during a 6-hour study period (n = 9). The outcome measures were the degree of inotropic and ventilator support needed to maintain hemodynamic stability and normocapnia, respectively.ResultsFive of the nine lambs subjected to AV-ECMO therapy (56%) died before completion of the 6-hour study period, as compared with two out of eight lambs (25%) in the CMV group (P > 0.05; Fisher's exact test). Surviving and nonsurviving lambs in the AV-ECMO group, unlike the CMV group, required continuous volume expansion and inotropic support (P < 0.001; Fisher's exact test). Lambs in the AV-ECMO group were able to maintain normocapnia with a maximum of 30% reduction in the minute ventilation, as compared with the CMV group (P < 0.05).ConclusionAV-ECMO therapy in lambs subjected to severe ALI requires continuous hemodynamic support to maintain cardiovascular stability and normocapnia, as compared with lambs receiving CMV support.

Subendocardial and subepicardial pressure–flow relations in the rat heart in diastolic and systolic arrest

Ischemic heart disease is more apparent in the subendocardial than in subepicardial layers. We investigated coronary pressure–flow relations in layers of the isolated rat left ventricle, using 15 μm microspheres during diastolic and systolic arrest in the vasodilated coronary circulation. A special cannula allowed for selective determination of left main stem pressure–flow relations. Arterio-venous shunt flow was derived from microspheres in the venous effluent. We quantitatively investigated the pressure–flow relations in diastolic arrest ( n=8), systolic arrest at normal contractility ( n=8) and low contractility ( n=6). In all three groups normal and large ventricular volume was studied. In diastolic arrest, at a perfusion pressure of 90 mmHg, subendocardial flow is larger than subepicardial flow, i.e., the endo/epi ratio is ∼1.2. In systolic arrest the endo/epi ratio is ∼0.3, and subendocardial flow and subepicardial flow are ∼12% and ∼55% of their values during diastolic arrest. The endo/epi ratio in diastolic arrest decreases with increasing perfusion pressure, while in systole the ratio increases. The slope of the pressure–flow relations, i.e., inverse of resistance, changes by a factor of ∼5.3 in the subendocardium and by a factor ∼2.2 in the subepicardium from diastole to systole. Lowering contractility affects subendocardial flow more than subepicardial flow, but both contractility and ventricular volume changes have only a limited effect on both subendocardial and subepicardial flow. The resistance (inverse of slope) of the total left main stem pressure–flow relation changes by a factor of ∼3.4 from diastolic to systolic arrest. The zero-flow pressure increases from diastole to systole. Thus, coronary perfusion flow in diastolic arrest is larger than systolic arrest, with the largest difference in the subendocardium, as a result of layer dependent increases in vascular resistance and intercept pressure. Shunt flow is larger in diastolic than in systolic arrest, and increases with perfusion pressure. We conclude that changes in contractility and ventricular volume have a smaller effect on pressure–flow relations than diastolic–systolic differences. A synthesis of models accounting for the effect of cardiac contraction on perfusion is suggested.

Microvascular Arteriovenous Shunting is a Probable Pathogenetic Mechanism in Erythromelalgia

Erythromelalgia is a condition consisting of red, warm, and burning painful extremities. Symptoms are relieved by cold and aggravated by heat. A wide variety of etiologic conditions can cause erythromelalgia, but one common pathogenetic mechanism, microvascular arteriovenous shunting, has been hypothesized. The aim of this study was to test this hypothesis. Quantification of skin microvascular perfusion using laser Doppler perfusion imaging and skin temperature at rest and after central body heating was performed in 14 patients with erythromelalgia and 11 controls. Attacks of erythromelalgia were induced in eight patients after heat provocation. In the plantar region of the foot, the location of numerous anatomical arteriovenous shunts, these patients significantly increased the skin perfusion as compared with asymptomatic patients with erythromelalgia and controls. In the dorsal region with few arteriovenous shunts no significant differences between the groups were demonstrated. The results show a relation between clinical symptoms and increased perfusion in the region of numerous anatomical arteriovenous shunts, and support the hypothesis of increased thermoregulatory arteriovenous shunt flow during attacks in primary erythromelalgia.

Comparison of two types of arterialized venous forearm flaps for oral reconstruction and proposal of a reliable procedure

The mechanism of survival of venous flaps is not yet completely understood. To determine the conditions for reliable success, in 1996 and 1997 we used arterialized venous forearm flaps for oral reconstruction in patients with neoplastic disease. Building on earlier experience with flow-through flaps, we compared two different designs obeying the following specifications: five so-called arterialized flow-through flaps, elevated from the ulnar flexor side of the forearm, with a single vein for orthograde inflow and outflow, diameter not larger than 2 mm (type 1); and five arterialized flaps with two parallel veins on the proximal side of the flap, also with a diameter of 1-2 mm, to avoid by-passing of flap tissue by 'catching' the blood in the venous/capillary system (type 2). There were nine male and one female patients with a mean age of 55.7 years. We covered defects of the anterior or anterolateral floor of the mouth to avoid folding of the flaps. Microsurgical anastomosis was done to the facial artery, the cranial thyroid artery and the external jugular vein or the facial vein. Average size of the flaps was 23 +/- 7.28 cm2 (type 1) and 25 +/- 5 cm2 (type 2). Four flaps of type 1 showed total or subtotal success and only one was lost because of a haematoma. In comparison with this we saw three losses in type 2 and only one partial and one total success, respectively. Analysis showed regularly occurring problems: there was failure of venous drainage in the lost type 2 flaps one day after microsurgery. In the flow-through flaps and the surviving type 2 flaps which had visible communicating branches between the two veins, the partial by-passing of the arterial input avoided this problem. There was no donor site morbidity after covering with a split-thickness skin graft. It could be shown that survival of arterialized venous forearm flaps is based on a combination of an arteriovenous shunt and capillary blood flow. In conclusion, we define six rules for a reliable venous forearm flap.

Thermoregulatory vasodilation increases the venous partial pressure of oxygen.

Thermoregulatory arteriovenous shunt vasoconstriction may facilitate deep-vein thrombosis by producing relative venous stasis and hypoxia. Accordingly, we evaluated the effect of vasomotion on leg blood flow and venous oxygen tension. We studied five male volunteers, each of whom was warmed enough to trigger vasodilation and then cooled sufficiently to provoke thermoregulatory vasoconstriction. The process was then repeated during N2O/desflurane anesthesia. Venous oxygen tension and saturation (with a fraction of inspired oxygen of 1.0) were evaluated in blood samples taken from a catheter that was inserted into a saphenous vein at the ankle and advanced until the tip was proximal to the knee. Thermoregulatory vasodilation with or without general anesthesia significantly increased arteriovenous shunt flow by approximately 10-fold, and increased total leg flow approximately sixfold. However, vasodilated flows were similar with and without general anesthesia, as were vasoconstricted flows. Before induction of anesthesia, thermoregulatory vasodilation increased venous oxygen tension from 46 +/- 6 to 187 +/- 99 mm Hg and venous saturation from 79% +/- 6% to 99% +/- 2%. After induction of anesthesia, thermoregulatory vasodilation increased venous oxygen tension from 55 +/- 11 to 356 +/- 103 mm Hg and venous saturation from 84% +/- 8% to 100% +/- 0%. Our data thus indicate that thermoregulatory vasodilation markedly increases both leg flow and venous oxygenation; and that both factors may help prevent perioperative venous thrombosis. Thermoregulatory arteriovenous shunt vasoconstriction may facilitate deep-vein thrombosis by producing related venous stasis and hypoxia. In male volunteers, the authors found that when vasodilation induced by warming was produced, both blood flow and venous oxygenation increased, both of which may help prevent perioperative venous thrombosis.

Organ Blood Flow During Arteriovenous Carbon Dioxide Removal

Animal models of arteriovenous carbon dioxide removal (AVCO2R) have achieved lung rest during treatment of severe respiratory failure, with total CO2 removal at arteriovenous shunt flow rates of 10% to 25% of cardiac output (CO). Previously, no statistically significant changes were reported in heart rate, cardiac output, mean arterial pressure, or pulmonary arterial pressure during prolonged (7 days) AVCO2R with shunt flows to 25% of CO. In this study, to determine the effect of various shunt levels on organ blood flow, colored microspheres were used in a conscious ovine model of AVCO2R. A low resistance 2.5 m2 oxygenator was placed in a simple carotid-to-jugular arteriovenous circuit. The AVCO2R flow (Qb) was incrementally increased to 5%, 10%, 15%, 20%, and 25% of baseline CO. After equilibration, colored microspheres were injected into a left atrial catheter while reference blood was withdrawn from an arterial line at a constant rate. Organ blood flow obtained by measuring microspheres in the tissues, showed approximately a 10-20% decrease at a 5% shunt, but remained relatively unchanged thereafter at up to a 25% shunt, and was well tolerated without hemodynamic sequelae or evidence of end organ ischemia. It was concluded that AVCO2R can achieve lung rest during respiratory failure at flow rates of 10-25% CO, with a resultant mild decrease in critical organ blood flow that appears well tolerated.

Reversal of defective peripheral nerve conduction velocity, nutritive endoneurial blood flow, and oxygenation by a novel aldose reductase inhibitor, WAY-121,509, in streptozotocin-induced diabetic rats

The main aim was to investigate whether 1 month of aldose reductase inhibitor treatment could correct a deficit in sciatic nerve nutritive blood flow following 1 month of untreated streptozotocin-induced diabetes in rats. Treatment was with two doses of WAY-121,509, both of which completely blocked neuronal sorbitol accumulation. The high dose fully corrected a motor conduction velocity deficit, whereas the low dose caused 51.3% amelioration. Nutritive endoneurial blood flow, monitored by hydrogen clearance, was 43.4% reduced after 1 month of diabetes. This was completely corrected by the high dose of WAY-121,509. In addition, vascular conductance was supranormal and there was a decrease in arteriovenous shunt flow. Low dose treatment caused a 55.6% improvement of the nutritive endoneurial blood flow deficit, paralleling the conduction velocity effect. WAY-121,509 did not alter nerve perfusion in nondiabetic rats. Data from multiple sciatic nerve penetrations by oxygen sensitive microelectrodes revealed a 42.0% deficit in mean endoneurial oxygen tension with diabetes, whereas tensions were in the nondiabetic range for high dose WAY-121,509 treatment. Thus, the data highlight neurovascular actions of aldose reductase inhibition, and suggest that neuronal polyol pathway metabolite levels are a poor predictor of functional efficacy.

Femororadial Pressure-delta and Thermoregulation

James M. Hynson, M.D., Assistant Professor.Daniel I. Sessler, M.D., Associate Professor.Jeffrey A. Katz, M.D., Professor of Clinical Anesthesia, Department of Anesthesia, University of California, San Francisco, UCSF/Mount Zion Medical Center, 1600 Divisadero Street, San Francisco, California 94115.In Reply:--Pauca incorrectly claims we "concluded that thermoregulation and anesthesia produced the post-CPB [aortofemoral blood pressure gradient]." Our study was an investigation of factors that could contribute to this phenomenon. Rewarming during cardiopulmonary bypass often causes sweating. [1]Because forearm blood flow increases during sweating [2,3]and increased upper extremity flow will produce greater resistive losses along the brachial and radial arteries, we tested the hypothesis that thermoregulatory sweating is associated with a femoral-to-radial artery blood pressure difference (gradient). Our hypothesis was confirmed by the presence of increased upper extremity blood flow and a consistent 5-mmHg difference between radial and femoral artery mean pressures in volunteers during thermoregulatory sweating. [4]We therefore postulated that thermoregulatory factors contribute to observed aortoradial artery blood pressure differences in the postcardiopulmonary (CPB) bypass period. A conclusion about the role of thermoregulation in the production of the post-CPB aortoradial artery blood pressure difference can be made only after completion of a carefully planned and controlled study that adequately examines thermoregulatory responses in patients undergoing cardiopulmonary bypass.Pauca argues that data obtained in young, healthy volunteers are not helpful in understanding physiologic responses in middle-aged and elderly patients undergoing cardiopulmonary bypass. We disagree. We studied young healthy volunteers to minimize complexity and to isolate the effects of thermoregulatory factors and anesthesia on blood pressure differences. Older surgical patients will have varying degrees of vascular disease and will have less compliant arteries. However, these conditions would likely increase the central-to-radial artery blood pressure differences during sweating because increased flow (due to distal vasodilation) through a fixed proximal resistance will augment the pressure gradient. The reported forearm blood flow measurements were performed exactly as described. [4]The hand was deliberately not excluded by a wrist tourniquet because we were interested in total forearm blood flow--including that traversing hand arteriovenous shunts. Nonetheless, we also measured forearm flow during hand compression, which comparably excludes distal flow (Table 1). Hand compression during vasoconstriction (with minimal arteriovenous shunt flow) had no effect on forearm blood flow. As expected, hand compression decreased forearm blood flow when shunt flow was large. These interesting but irrelevant data do not, of course, alter the conclusions of our study.Pauca incompletely describes the effect of heating on forearm blood flow. Cutaneous blood flow in the forearm will increase greatly if sweating is present. [2,3]The increase in flow during sweating results from active vasodilation in nonacral skin. [2,3]Pauca is thus incorrect when stating that the large increase in forearm blood flow during sweating was due to "failure to exclude the hand circulation." Induction of anesthesia increased forearm blood flow because propofol [5]and nitrous oxide [6]reduce the vasoconstriction threshold, thus increasing arteriovenous shunt flow. [7]It is therefore not surprising that hand compression during propofol/nitrous oxide decreased forearm blood flow.Finally, Pauca concludes on theoretical grounds that our fingertip flow measurements were performed incorrectly and inaccurate. His first concern is that we positioned the venous occlusion cuff over the proximal rather than middle phalanx. However, the review that Pauca cites to support his position specifies that many investigators position the cuff proximally because there is less inflation artifact (an increase in fingertip volume resulting from blood pushed distally during cuff inflation). [8]Pauca's other concern about our plethysmographic measurements is that we based flow on the linear phase of the volume versus time curves rather than uniformly using the first few seconds after venous cuff inflation. Proper interpretation of the volume versus time curves requires identification of the linear region and use of this portion to determine the slope. Always using the slope of the first few heart beats is obviously incorrect; the finger will not have begun to fill at low flows, whereas the finger volume will be saturated at high flows. Pauca illustrates this error in his Figure 1: The slope indicated by his dashed line obviously reflects a period during which finger volume is saturated and no longer increasing linearly. A slope calculated from this dashed line would grossly underestimate flow, whereas the solid line (as in our original publication) provides the correct value.In summary, our strain-gauge measurements of forearm blood flow were appropriate for our study questions, and our fingertip flow measurements were performed correctly. Our methods and results thus support our conclusions that thermoregulatory and anesthetic-induced alterations in upper extremity vascular tone and blood flow influence the difference between femoral and radial artery blood pressures.James M. Hynson, M.D., Assistant Professor.Daniel I. Sessler, M.D., Associate Professor.Jeffrey A. Katz, M.D., Professor of Clinical Anesthesia, Department of Anesthesia, University of California, San Francisco, UCSF/Mount Zion Medical Center, 1600 Divisadero Street, San Francisco, California 94115.(Accepted for publication July 3, 1995.)