Proximal Perfusion Research Articles

PREBOA vs ER-REBOA impact on blood utilization and resuscitation requirements: A pilot analysis.

Partial occlusion of the aorta is a resuscitation technique designed to maximize proximal perfusion while allowing a graduated amount of distal flow to reduce the ischemic sequelae associated with complete aortic occlusion. The pREBOA catheter affords the ability to titrate perfusion as hemodynamics allows, however, the impact of this new technology for REBOA on blood use and other resuscitative requirements is currently unknown. We hypothesize pREBOA's ability to provide partial occlusion, when appropriate, decreases overall resuscitative requirements when compared to ER-REBOA. The entire AAST AORTA Registry was used to compare resuscitation requirements between all ER-REBOA and pREBOA. Unpaired t-tests were used to compare resuscitation strategies including packed red blood cells (PRBCs), fresh frozen plasma (FFP), platelets, cryoprecipitate, crystalloids, and need for pressors. When comparing ER-REBOA (n=800) use to pREBOA (n=155), initial patient presentations were similar except for age (44 vs 40 p=0.026) and rates of blunt injury (78.4% vs 78.7% p<0.010). Zone-1 occlusion was used less often in ER-REBOA (65.8 vs 71.7 p=0.046). Partial occlusion was performed in 85% of pREBOA compared to 11% in ER-REBOA (p<0.050). Vitals at the time of REBOA were worse in ER-REBOA, and received significantly more units of PRBCs, FFP, platelets, and liters of crystalloids than pREBOA (p<0.05). Rates of ARDS and septic shock were lower in pREBOA (p<0.05). When comparing pREBOA to ER-REBOA, there has been a rise in Zone-1 and partial occlusion. In our pilot analysis of the AORTA Registry, there was a reduction in administration of pRBC, FFP, platelets, and crystalloids. Though further prospective studies are required, this is the first to demonstrate an association between pREBOA, partial occlusion, and reduced blood use and resuscitative requirements.

Organ blood flow assessment with the ModulHeart cardiorenal support device.

ModulHeart (Puzzle Medical Devices Inc) is a novel percutaneous flow entrainment pump anchored in the descending aorta. The current study evaluates the hemodynamic effect of ModulHeart support and its impact on cerebral, myocardial, and renal blood flow. ModulHeart was implanted in the descending aorta of four healthy calves. A ramp protocol (2000 RPM increments) was performed with the pump operating at five different speeds from 14 000 to 22 000 RPM. For each speed, pressures proximal and distal to the pump, and right heart catheterization measurements were recorded. Stable-isotope labeled microspheres were injected in the left ventricle to evaluate organ perfusion. Thermodilution cardiac output increased by 23% at 22 000 RPM. Greater pump speeds resulted in greater pump gradients, up to 10 mm Hg in mean arterial pressure at 22 000 RPM, without significant reduction of proximal perfusion pressures. Arterial pulse pressure remained stable at all speeds. ModulHeart was not associated with a reduction in cerebral or myocardial blood flow at any speed. Renal cortical and medullary blood flow increased by up to 50% and 40%, respectively. The ModulHeart device implanted in the descending aorta of healthy calves resulted in significant arterial pressure gradients and preserved pulse pressure. Greater pump speeds translated into greater increases in renal blood flow, with no decrease in cerebral or myocardial perfusion.

Resuscitative endovascular balloon occlusion of the aorta

Resuscitative endovascular balloon occlusion of the aorta (REBOA) reduces sub-diaphragmatic haemorrhage while increasing proximal perfusion in non-compressible truncal exsanguination.1 A catheter-borne balloon is inflated in the descending aorta, initially to complete occlusion then partially deflated, the aim being to optimise coronary and cerebral perfusion, while minimising distal haemorrhage and ischaemia. Resuscitative endovascular balloon occlusion of the aorta can be considered in blunt or penetrating sub-diaphragmatic injury with life-threatening bleeding or traumatic cardiac arrest in centres with an established, protocolised system for its deployment.

Differential regional perfusion of the human anterior cruciate ligament: quantitative magnetic resonance imaging assessment

PurposeSurgical reconstruction is the current standard for ACL rupture treatment in active individuals. Recently, there is renewed interest in primary repair of proximal ACL tears. Despite this, ACL biology and healing potential are currently not well understood. Vascularity is paramount in ACL healing; however, previous ACL vascularity studies have been limited to qualitative histological and dissection-based techniques. The study objective was to use contrast-enhanced quantitative-MRI to compare relative perfusion of proximal, middle, and distal thirds of the in situ ACL. We hypothesized perfusion would be greatest in the proximal third.MethodsFourteen cadaveric knees were studied (8 females, 6 males), age 25–61 years. Superficial femoral, anterior tibial, and posterior tibial arteries were cannulated; without intraarticular dissection. Contrast-enhanced quantitative-MRI was performed using a previously established protocol. ACL regions corresponding to proximal, middle, and distal thirds were identified on sagittal-oblique pre-contrast images. Signal enhancement (normalized to tibial plateau cartilage) was quantified to represent regional perfusion as a percentage of total ACL perfusion. Comparative statistics were computed using repeated measures ANOVA, and pairwise comparisons performed using the Bonferroni method.ResultsRelative perfusion to proximal, middle, and distal ACL zones were 56.0% ±17.4%, 28.2% ±14.6%, and 15.8% ±16.3%, respectively (p = 0.002). Relative perfusion to the proximal third was significantly greater than middle (p = 0.007) and distal (p = 0.001). No statistically relevant difference in relative perfusion was found to middle and distal thirds (p = 0.281). Post-hoc subgroup analysis demonstrated greater proximal perfusion in males (66.9% ± 17.3%) than females (47.8% ± 13.0%), p = 0.036.ConclusionUsing quantitative-MRI, in situ adult ACL demonstrated greatest relative perfusion to the proximal third, nearly 2 times greater than the middle third and 3 times greater than the distal third. Knowledge of differential ACL vascular supply is important for understanding pathogenesis of ACL injury and the process of biological healing following various forms of surgical treatment.

Arc of Riolan-Dominant Colonic Perfusion Identified by Indocyanine Green After High Ligation of Inferior Mesenteric Artery: Critical in Preventing Anastomotic Ischemia.

Arc of Riolan is a collateral mesenteric vessel observed in up to 17.8% of individuals1 bridging the superior mesenteric artery (SMA) and inferior mesenteric artery (IMA) systems perfusing the descending colon besides the marginal artery. Proximal perfusion of the anastomosis after the high division of the IMA during left-sided colorectal resections is maintained by the marginal artery, but in some, this may be absent or small-caliber at the Griffiths point.2 Identification and preservation of the arc of Riolan has been associated with a decrease in acute anastomotic ischemia events requiring resection and Hartmann's procedure, although not totally eradicated the number of anastomotic leaks requiring lesser interventions.1 This video shows the vascular supply of the left colon during a robotic ultra-low anterior resection for low rectal cancer. The arc of Riolan is identified and preserved at its usual anatomical position during the isolation and division of the inferior mesenteric vein inferior to the pancreas, lengthening the descending colon for a tension free anastomosis. The arc of Riolan is temporarily occluded with an endoscopic vascular clamp after the IMA's high division. 4mg of intravenous indocyanine green (ICG) is infused to visualize the perfusion of the descending colon for 3 minutes, which is ICG's half-life.3 The fluorescence image of the descending colon is noted to be less than expected and another 3mg of ICG is infused after unclamping the arc of Riolan, revealing a visibly higher fluorescent descending colon confirming the dominant perfusion from this vessel. ICG has clearly demonstrated the arc of Riolan's dominance in perfusing the left colon. Armed with prior knowledge, its preservation can be a critical step in preventing anastomotic ischemia after IMA's high ligation in patients with potentially weak marginal artery, whilst division of a non-dominant arc of Riolan makes splenic flexure mobilization technically less challenging. See Video Abstract at http://links.lww.com/DCR/B439.

Abstract P1115: Decreased Tubuloglomerular Feedback (TGF) Response in High-Fat Diet Induced Obesity

Obesity is associated with increased renal and glomerular damage and hypertension, but the mechanisms are not clear. Normally, kidneys autoregulate to keep the glomerular capillary pressure (P GC ), renal blood flow and glomerular filtration rate in a steady state. In obesity, the kidney loses its autoregulatory capacity, leading to higher P GC , renal blood flow and glomerular filtration rate. Together, these may lead to glomerular damage. P GC is controlled mainly by the afferent arteriole (Af-Art) resistance. Af-Art resistance in turn is regulated by an intrinsic renal feedback mechanism known as tubuloglomerular feedback (TGF). TGF causes Af-Art constriction in response to an increase in sodium chloride (NaCl) in the macula densa, via the Na-K-2Cl cotransporter NKCC2. We previously found that in the Zucker rat model of obesity, TGF was decreased and this was associated with higher blood pressure (BP) and proteinuria. However, it is not known whether obesity induced by a high fat diet in normal Sprague Dawley (SD) rats could also affect TGF. We hypothesized that TGF would be attenuated in obesity caused by 16 weeks of high fat fed (HFD) feeding (60% fat) in SD rats. SD rats fed normal-fat diet (12% fat, NFD) served as control. HFD fed rats exhibited higher body weight (HFD: 833.7±33.3 vs. NFD: 682.3±24.8 grams, p&lt;0.05) and were hypertensive under Inactin anesthesia (mean BP HFD: 131.4±3.6 vs.115.8±3.8 mmHg, p&lt;0.05). We performed in-vivo renal micropuncture of individual rat nephrons while measuring stop-flow pressure (P SF ), an index of P GC. P SF decreases with an increase in Af-Art resistance. TGF response was measured as a decrease in P SF induced by changing the rate of late proximal perfusion from 0 to 40nl/min. Maximal TGF response was significantly smaller in HFD fed rats compared to the NFD rats (HFD: 4.1±0.9 vs. NFD: 10.2±0.6 mmHg, p&lt;0.05) indicating attenuation of TGF by HFD. Baseline P GC was higher in HFD rats compared to NFD rats (HFD: 41.6±0.8 vs. NFD: 38.7.2±0.5 mmHg, p&lt;0.05). We conclude that TGF is attenuated in HFD fed obese SD rats and this may contribute to increased renal blood flow and GFR observed in obesity. Hypertension, combined with an attenuated TGF response and increased P GC may explain higher renal damage caused by obesity.

Abstract 358: Aortic Balloon Occlusion Augments the Efficacy of External Cardiopulmonary Resuscitation After Traumatic Cardiac Arrest in Swine

Introduction: Following hemorrhage-induced traumatic cardiac arrest (TCA), the effectiveness of standard cardiopulmonary resuscitation (CPR) would be weakened or lost due to an inadequate circulating volume. Previous investigations demonstrated that aortic balloon occlusion (ABO) could control the bleeding and increase proximal organ perfusion during severe traumatic hemorrhage. In this study, we investigated the effect of ABO on the efficacy of CPR in a swine model of TCA. Hypothesis: ABO initiated during CPR would increase cardiac and cerebral perfusion so as to improve the outcomes of resuscitation after TCA in swine. Methods: Twenty-seven male domestic swine weighing 33±4 kg were utilized. Forty percent of estimated blood volume was removed within 20 mins. The animals were then subjected to 5 mins of untreated ventricular fibrillation and 5 mins of CPR. Coincident with the start of CPR, the animals were randomized to receive ABO (n=15) or control (n=12). Meanwhile, normal saline was intravenously infused at a speed of 0.7 ml/kg/min in all animals. Results: During CPR, significantly greater coronary perfusion pressure, regional cerebral oxygen saturation and end-tidal CO 2 were observed in animals treated with ABO when compared with the control group (Table). Consequently, the rate of resuscitation success was significantly higher in the ABO group than in the control group (15/15 vs. 9/12, p = 0.040). Additionally, shorter duration of CPR (5.1±0.5 vs. 7.5±4.5 min, p = 0.054) and less number of shocks (1.1±0.3 vs. 2.0±1.8, p = 0.058) were required for establishing spontaneous circulation in the ABO group compared to the control group. Conclusion: The implementation of ABO during CPR significantly increased cardiac and cerebral perfusion and improved the outcomes of resuscitation in TCA following massive hemorrhage.

Traumatic cardiac arrest and resuscitative endovascular balloon occlusion of the aorta (REBOA): a preliminary analysis utilizing high fidelity invasive blood pressure recording and videography.

Aortic occlusion (AO) increases proximal perfusion and may improve rates of return of spontaneous circulation (ROSC). The objective of this study was to investigate the hemodynamic effects of cardiopulmonary resuscitation (CPR) and AO by REBOA on patients in traumatic cardiac arrest. Patients admitted between February 2013 and May 2017at a tertiary center who suffered traumatic arrest, had an arterial line placed during resuscitation, and received CPR and REBOA which were included. In-hospital CPR data were obtained from videography. Arterial waveforms were recorded at 240Hz. 11 consecutive patients were included, 82% male; mean (± SD) age 37 ± 19years. 55% suffered blunt trauma and the remaining penetrating injuries. 64% arrested out of hospital. During compressions with AO, the mean systolic blood pressure (SBP) was 70 ± 22mmHg, mean arterial pressure (MAP) 43 ± 19mmHg, and diastolic blood pressure (DBP) 26 ± 17mmHg. Nine (82%) had ROSC, with eight having multiple periods of ROSC and arrest in the initial period. In-hospital mortality was 82%. Cardiac ultrasonography was used during arrest in 73%. In two patients with arterial line data before and after AO, SBP (mmHg) improved from 51 to 73 and 55 to 96 during arrest after AO. High-quality chest compressions coupled with aortic occlusion may generate adequate perfusion pressures to increase the rate of ROSC. New technology capable of transducing central arterial pressure may help us to understand the effectiveness of CPR with and without aortic occlusion. REBOA may be a useful adjunct to high-quality chest compressions during arrest.

Abstract WMP15: A Simple Tool to Predict Target Mismatch in Ischemic Stroke Patients with Anterior Circulation Occlusion

Introduction: The efficacy of endovascular thrombectomy in an extended time window for acute ischemic stroke patients with Target Mismatch (TM) on perfusion imaging was shown in a recent study and the ongoing DEFUSE-3 trial is studying thrombectomy in a 6-16 hour window for TM patients. A limitation of TM is that perfusion imaging is not widely available. We sought to identify a tool to predict TM based on clinical factors and CT angiogram (CTA) imaging, which is available at most hospitals. Methods: We reviewed acute ischemic stroke patients from 2010-2014 with proximal middle cerebral artery occlusion, CTA and CT perfusion (CTP) at hospital admission. TM was identified on CTP using the Olea Sphere volumetric analysis software with Bayesian deconvolution. TM was defined by the DEFUSE-3 criteria. ASPECTS was derived from the non-contrast CT head and the CTA source images (CTA-ASPECTS). Two collateral scores were derived from CTA source images. Results: 61 patients met inclusion criteria. The mean±SD age was 61±18 years and 61% were male. Mean NIH Stroke Scale (NIHSS) was 14.1±8.0 and median (IQR) follow-up modified Rankin Scale was 3 (1,6). TM was present in 35/61 (57%), who had lower mRS at follow-up (z=3.5, p&lt;0.001). The predictor variables are shown in Table 1. The best combination of predictors was CTA-ASPECTS &gt;4 and NIHSS &lt;16, which had a sensitivity of 80% and specificity of 85% for TM (Figure 1). Discussion: We report a reliable, accessible, and clinically useful tool for predicting TM. This score warrants further study as a tool to guide transfer decisions from primary or secondary stroke centers to tertiary centers where endovascular intervention would be possible for selected patients.

Abstract 062: Regulation of Nephron Afferent Arteriole Resistance in Obesity: Role of Connecting Tubule Glomerular Feedback

In obesity, renal damage is caused by increase in renal blood flow (RBF), glomerular capillary pressure (P GC ), and single nephron glomerular filtration rate but the mechanism behind this alteration in renal hemodynamics is unclear. P GC is controlled mainly by the afferent arteriole (Af-Art) resistance. Af-Art resistance is regulated by mechanism similar to that in other arterioles and in addition, it is regulated by two intrinsic feedback mechanisms: 1) tubuloglomerular feedback (TGF) that causes Af-Art constriction in response to an increase in sodium chloride (NaCl) in the macula densa, via sodium–potassium-2-chloride cotransporter-2 (NKCC2) and 2) connecting tubule glomerular feedback (CTGF) that causes Af-Art dilatation and is mediated by connecting tubule via epithelial sodium channel (ENaC). CTGF is blocked by the ENaC inhibitor benzamil. Attenuation of TGF reduces Af-Art resistance and allows systemic pressure to get transmitted to the glomerulus that causes glomerular barotrauma/damage. In the current study, we tested the hypothesis that TGF is attenuated in obesity and that CTGF contributes to this effect. We used Zucker obese rats (ZOR) while Zucker lean rats (ZLR) served as controls. We performed in-vivo renal micropuncture of individual rat nephrons while measuring stop-flow pressure (P SF ), an index of P GC. TGF response was measured as a decrease in P SF induced by changing the rate of late proximal perfusion from 0 to 40nl/min in stepwise manner.CTGF was calculated as the difference of P SF value between vehicle and benzamil treatment, at each perfusion rate. Maximal TGF response was significantly less in ZOR (6.16 ± 0.52 mmHg) when compared to the ZLR (8.35 ± 1.00mmHg), p&lt;0.05 , indicating TGF resetting in the ZOR. CTGF was significantly higher in ZOR (6.33±1.95 mmHg) when compared to ZLR (1.38±0.89 mmHg), p&lt;0.05 . When CTGF was inhibited with the ENaC blocker Benzamil (1μM), maximum P SF decrease was 12.30±1.72 mmHg in ZOR and 10.60 ± 1.73 mmHg in ZLR, indicating that blockade of CTGF restored TGF response in ZOR. These observations led us to conclude that TGF is reset in ZOR and that enhanced CTGF contributes to this effect. Increase in CTGF may explain higher renal blood flow, increased P GC and higher glomerular damage in obesity.

Abstract 118: Role of Connecting Tubule Glomerular Feedback in Tubuloglomerular Feedback Resetting After Unilateral Nephrectomy

Tubuloglomerular feedback (TGF) and connecting tubule glomerular feedback (CTGF) autoregulate nephronal afferent arteriolar resistance. In TGF, the macula densa signals the afferent arteriole to constrict when NaCl transport is enhanced by increased luminal NaCl, via sodium[[Unable to Display Character: &amp;#8211;]]potassium-2-chloride cotransporter-2 (NKCC2). CTGF is mediated by connecting tubule sodium transport via epithelial sodium channel (ENaC) and dilates the afferent arteriole. Attenuation or resetting of TGF occurs after unilateral nephrectomy (UNX), but the mechanism behind this resetting remains unclear. This TGF resetting after UNX has been implicated in progressive glomerular damage due to sustained increase in glomerular capillary pressure. Since TGF is attenuated after UNX, we sought to test the hypothesis that CTGF is enhanced and that it contributes to TGF resetting after UNX. To test this hypothesis, we performed right side UNX in Sprague Dawley (SD) rats. 24 hours after surgery, we performed micropuncture of individual rat nephrons while measuring stop-flow pressure (PSF), which is an index of glomerular capillary pressure and afferent arteriolar tone. PSF decreases with an increase in afferent arteriolar tone. TGF response was measured as a decrease in PSF induced by switching late proximal perfusion from 0,10,20,30 and 40nl/min. Maximal TGF response was 1.3 ± 1.7 mmHg in UNX rats while 8.2 ± 0.9 mmHg in sham-UNX rats indicating a TGF resetting in UNX rats. When CTGF was inhibited with the ENaC blocker Benzamil (1μM), TGF response was 10±1.2 mmHg in UNX rats and 14.8± 1.3 mmHg in sham-UNX rats, indicating the restoration of TGF responses in UNX. We conclude that enhanced CTGF contributes to the TGF resetting after 24 hours of UNX. Enhanced CTGF may be responsible for glomerular damage post UNX.

Wave intensity analysis and assessment of myocardial perfusion abnormalities in patients with hypertrophic cardiomyopathy

Background Coronary perfusion pressure is a combination of proximal perfusion pressure and distal coronary artery pressure resulting from contraction and relaxation of the myocardium and the consequences on the microcirculation. Wave intensity analysis (WIA) defines dominant waves causing coronary filling during the cardiac cycle and allows separation of proximally and distally originating waves.Reduced myocardial perfusion has been shown to predict mortality in hypertrophic cardiomyopathy (HCM), however no study has assessed the relationship between coronary filling patterns and downstream absolute myocardial perfusion.

Thoracoabdominal aortic aneurysm repair using hypothermic cardiopulmonary bypass and circulatory arrest.

Thoracoabdominal aortic aneurysm repair using hypothermic cardiopulmonary bypass and circulatory arrest.

Femoral Cannulation With Long Arterial Cannula in Aortic Dissection

The optimal cannulation site in repair of DeBakey type I aortic dissection is controversial, and malperfusion during cardiopulmonary bypass is facilitated by retrograde flow. We propose the use of a long arterial cannula through the femoral artery to achieve a proximal antegrade perfusion. The tip of the cannula is placed in the true lumen of the distal aortic arch through the common femoral artery (Seldinger technique and transesophageal echography guidance). In 9 patients, there was one case of operative mortality (cardiac death), and no cases of perioperative stroke, bowel ischemia, severe renal failure, or local complications. Proximal perfusion can achieved rapidly and through an easily accessible site.

The Limits of Medial Femoral Condyle Corticoperiosteal Flaps

The medial femoral condyle (MFC) vascularized corticoperiosteal flap has been well described for the treatment of nonunion with minimal bone loss. Recent applications of this donor site as a corticocancellous flap for large intercalary defects bring into question the vascular territory of bone supplied by the descending genicular artery (DGA). This study's purpose is to delineate the proximal extent of periosteal blood supply of the medial column of the femur provided by the DGA system. In 18 cadaveric specimens, the DGA was isolated, measured, and cannulated. Using subtraction techniques of fluoroscopic angiography, the vascular network and proximal-most extent of periosteal perfusion were recorded using radiopaque contrast dye. The DGA branched from the superficial femoral artery 14.2 ± 2.4 cm proximal to the joint line of the knee. The length of the vascular pedicle to its attachment onto the periosteum was 7.7 ± 2.2 cm. All specimens demonstrated a filigree of periosteal vessels dominated by a transverse and a longitudinal branch at the level of the condyle. Proximal perfusion was consistently noted by a large, longitudinal medial metaphyseal periosteal artery. The medial metaphyseal periosteal artery demonstrated that the proximal-most perfusion of the DGA was 13.7 ± 1.3 cm proximal to the joint line. Average femur length was 47.1 ± 3.1 cm. The DGA provided perfusion of 29% ± 2% of the total length of the medial femur. The DGA provides a large and reliable region of periosteal perfusion, suggesting that corticocancellous MFC harvest might provide the benefits of vascularized bone for large, intercalary nonunion defects conventionally treated with fibula flaps. Harvest of MFC osseous flaps extending up to 13.7 cm proximal to the joint line can be perfused from the DGA pedicle. The MFC donor site might, therefore, be a reliable option for vascularized reconstruction of larger bone defects.

Connecting tubule glomerular feedback (CTGF) antagonizes tubuloglomerular feedback (TGF) in vivo

We recently described that there is crosstalk between the connecting tubule (CNT) and the Af‐Art that causes dilation. CTGF is mediated by CNT Na transport via epithelial Na channels (ENaC). We hypothesized that CTGF opposes TGF. We performed renal micropuncture studies in male rats. We induced TGF by increasing late proximal perfusion rate (0, 10, 20, 40, 80 nL/min). Stop‐flow pressure (PSF) was used as an index of TGF response. First, we showed that TGF was reversible and reproducible. Next, we tested whether inhibition of CTGF with benzamil (ENaC inhibitor; 1 μM) potentiated TGF. In control, high flow (80 nL/min) increased PSF indicating that CTGF increased Af‐Art dilatation. CTGF inhibition with benzamil potentiated the TGF response, especially at high flow rates. When NaCl transport in the distal tubule was inhibited with hydrochlorothiazide (HCTZ, 1 mM) to increase delivery of Na to the CNT, benzamil potentiated the TGF response at lower (20 nL/min) flow rates (Table). We conclude that CTGF antagonizes the vasoconstrictor effect of TGF. Perfusion rate (nL/min) 0 10 20 40 80 Control PSF (n=5) 39.6 ± 0.8 39.2 ± 0.6 36.4 ± 0.8 32.4 ± 0.9 34.2 ± 0.8† Benzamil PSF 39.1 ± 0.8 38.7 ± 0.7 35.7 ± 0.9 30.1 ± 0.8** 30.1 ± 0.7*** HCTZ PSF (n=4) 40.0 ± 0.6 40.3 ± 0.6 37.4 ± 0.5 33.5 ± 0.8 35.5 ± 0.8† HCTZ+Benzamil PSF 39.8 ± 0.4 39.9 ± 0.5 35.8 ± 0.4# 31.0 ± 0.6# 30.9 ± 0.6# p &lt; 0.01 and p &lt; 0.001 vs. control; p &lt; 0.05 vs. HCTZ; p &lt; 0.001 40 vs. 80 nL/min Source of Funding: This study was supported by NIH Grants HL028982 and HL088036.

Carbon monoxide inhibits tubuloglomerular feedback in vivo by activation of soluble guanylyl cyclase

We have previously shown in vitro that carbon monoxide (CO) inhibits tubuloglomerular feedback (TGF), but how this happens is not known. We hypothesized that CO in vivo inhibits TGF by activating the soluble guanylyl cyclase (sGC)/cyclic guanosine 3′, 5′‐monophosphate (cGMP) system. Renal micropuncture studies were performed in male Sprague Dawley rats. TGF was induced by increasing late proximal perfusion rate (0, 10, 20, 30, 40 nL/min) while measuring stop‐flow pressure (PSF) as an index of single nephron glomerular filtration. We measured the effect of a CO‐donor, CORM‐3 (50 μM) on PSFmax with and without inhibition of sGC using the sGC inhibitor LY83583 (1 μM). First, we demonstrated that the PSF response to increased tubular perfusion rate was reversible and reproducible. Next, we found CORM‐3 blunted the TGF response, as the maximum change in PSF was 6.9 ± 0.2 mmHg in controls, but only 3.9 ± 0.4 mmHg in CORM‐3 treated tubules (p &lt; 0.001). However, with addition of LY83583 to the perfusate, the effect of CORM‐3 was eliminated. Addition of LY83583 potentiated the TGF response by 28% (8.4 ± 0.3 mmHg, p &lt; 0.001), and it also reversed the blunting effect of CORM‐3 (8.3 ± 0.4 mmHg, p &lt; 0.001) to a similar extent. From these data, we conclude that inhibition of TGF by CO in vivo is mediated by activation of the sGC/cGMP system. This study was supported by National Institutes of Health Grant HL‐090550.

Appraising the pathophysiologic impact of coronary collaterals as measured by fractional flow reserve on symptoms and signs of myocardial ischemia

The purpose of coronary revascularization in stable patients is anginal relief, yet there is no linear relationship between stenosis severity and clinical significance. A major factor in this complex lesion-myocardium interaction is collateral flow. We aimed to define which collateral flow cut-offs separate asymptomatic from symptomatic patients during coronary occlusion. Patients undergoing percutaneous transluminal coronary angioplasty for a single stenotic lesion were selected, collaterals were appraised angiographically, and fractional flow reserve was used during prolonged balloon occlusion to measure collateral flow index (FFRcoll). Changes in anginal symptoms, ST-T segment, and left ventricular wall motion were appraised before and during/shortly after balloon dilation. Receiver-operating-characteristic curves and area under the curve were computed to identify the most appropriate FFRcoll cut-offs. Twenty consecutive patients were enrolled. At baseline, 10 patients had angiographic evidence of collaterals, whereas 10 had no angiographic evidence of collateral flow distal to the target lesion. FFRcoll had an excellent discriminatory performance for the presence of angiographic collaterals (area under the curve = 0.90, P = 0.003), a good discriminatory performance for the occurrence of angina (area under the curve = 0.80, P = 0.025), and a trend toward a good discriminatory performance for the occurrence of asynergy (area under the curve = 0.81, P = 0.06). On the basis of receiver-operating-characteristic curves, an FFRcoll cut-off greater than 0.26 could reliably distinguish patients with adequate collaterals (sensitivity = 0.90, specificity = 0.80), whereas a greater than 0.41 cut-off distinguished patients having angina or wall motion abnormalities from those remaining asymptomatic. This study shows that distal collateral pressure greater than 41% of proximal perfusion pressure protects from anginal symptoms or regional systolic dysfunction during coronary occlusion, whereas a greater than 26% cut-off is more appropriate to identify angiographically evident collaterals ensuring distal myocardial viability.

Functional Assessment at the Buttock Level of the Effect of Aortobifemoral Bypass Surgery

Little is known about the prevalence of proximal (hip, buttock, lower back) claudication after aortobifemoral bypass (AF2B) grafting and its hemodynamic effects at the buttock level. Forty-eight patients performed a treadmill test before and within 6 months after AF2B. The San Diego Claudication Questionnaire and the chest-corrected decrease from rest of transcutaneous oxygen pressure on buttocks were used to study exercise-induced proximal claudication and regional pelvic blood flow impairment. A decrease from rest of transcutaneous oxygen pressure value <-15 mm Hg was used to indicate regional blood flow impairment (RBFI). Patients had the following characteristics: 39 were men and 9 were women, 60 +/- 9 years, lowest ankle-to-brachial index (ABI) of 0.55 +/- 0.18 and maximal walking distance (MWD) on treadmill of 188 +/- 192 m at inclusion. ABI and MWD were significantly improved after surgery at 0.83 +/- 0.19 and 518 +/- 359 m (P < 0.0001). Unilateral or bilateral RBFI at the buttocks was found in 39 versus 29 patients before and after AF2B, respectively. Proximal claudication with underlying RBFI on one or both sides on treadmill were observed in 29 patients before AF2B, and in 9 of 26 (41%) versus 6 of 22 (23%) patients in end-to-end versus end-to-side proximal aorto-graft anastomosis of the AF2B, respectively (P < 0.05). A significant increase in MWD and ABI, but little improvement of proximal perfusion is observed after surgery, a finding that is expected from the absence of hypogastric artery revascularization. The prevalence of proximal claudication and proximal blood flow impairment is higher in case of end-to-end when compared with end-to-side proximal aorto-graft anastomosis, confirming the role of collaterals such as lumbar arteries in the buttock circulation during exercise in patients suffering from peripheral arterial disease. Proximal claudication on treadmill early after surgery affects almost one third of the patients and must not be underestimated among patients receiving AF2B. Attempts at hypogastric artery revascularization, if possible, might be preferable to decrease the risk of proximal claudication after AF2B.

Making sense of the sensor: Mysteries of the macula densa

Increases in luminal NaCl concentration at the macula densa (MD), the sensing element, activate tubuloglomerular feedback (TGF). MD cell volume increases when increments are isosmotic and shrinks if osmolality increases. This interesting finding introduces additional complexity to the role of the MD in TGF.