Design optimization of bidirectional arterial perfusion cannula.

OBJECTIVES: Determine if shortening the covered section of a self-expanding bidirectional arterial cannula, can enhance retrograde flow and thus reduce the risk of lower limb ischemia. METHODS: Outlet pressure vs flow rate was determined for three cannulas types: a 15F self-expanding bidirectional cannula having a covered section of 90 mm, the same cannula but with a shorter covered section of 60 mm, and a Biomedicus cannula as control. The performances of all the cannulas were compared using a computerized flow-bench with calibrated sensors and a centrifugal pump. Water retrograde flow was determined using a tank timer technique. Anterograde and retrograde flow rate versus outlet pressure were determined at six different pump speed. RESULTS: For each of the six pump speed, both bidirectional cannulas, 60-mm covered and 90-mm covered respectively, showed higher performance than Biomedicus cannula control, as demonstrated by higher flow rate and lower pressure. We also observed that for the bidirectional cannula with shorter covered section, i.e. 60 mm coverage, provides enhanced performance as compared to a 90-mm coverage. Finally, the flow rate and the corresponding pressure can be consistently measured by our experimental set-up with low variability. CONCLUSIONS: The new configuration of a shorter covered section in a bidirectional self-expanding cannula design, may present an opportunity to overcome lower leg ischemia during extra-corporal life support with long term peripheral cannulation.

Effect of blood viscosity on the performance of virtually wall-less venous cannulas.

AIM: This study was designed to quantify the influence of blood as test medium compared to water in cannula bench performance assessment. METHODS: An in vitro circuit was set-up with silicone tubing between two reservoirs. The test medium was pumped from the lower reservoir by centrifugal pump to the upper reservoir. The test-cannula was inserted in a silicone tube connected between the lower reservoir and the centrifugal pump. Flow rate and pump inlet-pressure were measured for wall-less versus thin-wall cannula using a centrifugal pump in a dynamic bench-test for an afterload of 40-60 mmHg using two media: blood 10 g/dL and 5.6 g/dL and water 0 g/dL. RESULTS: The wall-less cannula showed significantly higher flows rates as compared to the thin-wall cannula (control), with both hemoglobin concentrations and water. Indeed, for a target volume of 200-250 mL of blood (Hg 10 g/dL) in the upper reservoir, the cannula outlet pressure (P) was -14 ± 14 mmHg versus -18 ± 11 mmHg for the wall-less and control respectively; the cannula outlet flow rate (Q) was 3.91 ± 0.41 versus 3.67 ± 0.45 L/min, respectively. At the same target volume but with a Hg of 5.7 g/dL, P was -16 ± 12 mmHg versus -19 ± 12 mmHg and Q was 4 ± 0.1 versus 4 ± 0.4 L/min for the wall-less cannula and control respectively. Likewise, P and Q values with water were -1 mmHg versus -0.67 ± 0.58 mmHg and 4.17 ± 0.45 L/min versus 4.08 ± 0.47 L/min for the wall-less and control respectively. CONCLUSION: Walls-less cannula showed 5.6% less pump inlet-pressure differences calculated between blood and water, as compared to that of thin-wall cannula (-21 times). Flow differences were 6% and 10% for the walls-less and thin-wall cannula respectively. We conclude that testing the cannula performance with water is a good scenario and can overestimate the flow by a 10%. However, superiority for wall-less is preserved with both water and blood.

New, optimized, dual-lumen cannula for veno-venous ECMO.

OBJECTIVE: The present study was designed to assess in vivo a new, optimized, virtually wall-less, dual-lumen, bi-caval cannula for veno-venous ECMO in comparison to a commercially available cannula. METHODS: Veno-venous extracorporeal membrane oxygenation (ECMO) was carried out in a bovine study (n=5, bodyweight 75±5kg). Following systemic heparinization, ECMO was established in a trans-jugular fashion through a calibrated 23F orifice, using a new, optimized, virtually wall-less, dual-lumen, bi-caval 24F cannula (Smartcanula LLC, Lausanne, Switzerland) versus a commercially available 23F bi-caval, dual-lumen control cannula (Avalon Elite®, Maquet, Rastatt, Germany) in a veno-venous ECMO setup. Veno-venous ECMO was initiated at 500 revolutions per minute (RPM) and increased by incremental steps of 500 RPM up to 2500 RPM. Catheter outlet pressure, catheter inlet pressure, oxygen saturation and pump flow were recorded at each stage. RESULTS: Mean flow accounted for 0.37±0.04 L/min for wall-less versus 0.29± 0.07 L/min for control at 500 RPM, 0.97±0.12 versus 0.67±0.06 at 1000 RPM, 1.60±0.14 versus 1.16±0.08 at 1500 RPM, 2.31±0.13 versus 1.52±0.13 for 2000 RPM and 3.02±0.5 versus 2.11±0.18 (p<0.004). The mean venous suction required was 19±8 mmHg for wall-less versus 20±3 mmHg for control at 500 RPM, 7±3 versus 9±4 for 1000 RPM, -11±10 versus -12±8 at 1500 RPM, -39±15 versus -49±10 for 2000 RPM and -60±28 versus -94±7 for 2500 RPM. The mean venous injection pressure accounted for 29±7 mmHg for wall-less versus 27±5 mmHg for control at 500 RPM, 50±6 versus 61±7 at 1000 RPM, 89±10 versus 99±17 for 1500 RPM, 142±14 versus 161±9 at 2000 RPM and 211±41 versus 252 ±3 for 2500 RPM. CONCLUSION: Compared to the commercially available control cannula, the new, optimized, virtually wall-less, dual-lumen, bi-caval 24F cannula allows for significantly higher blood flows, requires less suction and results in lower injection pressures in vivo.

New, Virtually Wall-less Cannulas Designed for Augmented Venous Drainage in Minimally Invasive Cardiac Surgery.

OBJECTIVE: Inadequate venous drainage during minimally invasive cardiac surgery becomes most evident when the blood trapped in the pulmonary circulation floods the surgical field. The present study was designed to assess the in vivo performance of new, thinner, virtually wall-less, venous cannulas designed for augmented venous drainage in comparison to traditional thin-wall cannulas. METHODS: Remote cannulation was realized in 5 bovine experiments (74.0 ± 2.4 kg) with percutaneous venous access over the wire, serial dilation up to 18 F and insertion of either traditional 19 F thin wall, wire-wound cannulas, or through the same access channel, new, thinner, virtually wall-less, braided cannulas designed for augmented venous drainage. A standard minimal extracorporeal circuit set with a centrifugal pump and a hollow fiber membrane oxygenator, but no in-line reservoir was used. One hundred fifty pairs of pump-flow and required pump inlet pressure values were recorded with calibrated pressure transducers and a flowmeter calibrated by a volumetric tank and timer at increasing pump speed from 1500 RPM to 3500 RPM (500-RPM increments). RESULTS: Pump flow accounted for 1.73 ± 0.85 l/min for wall-less versus 1.17 ± 0.45 l/min for thin wall at 1500 RPM, 3.91 ± 0.86 versus 3.23 ± 0.66 at 2500 RPM, 5.82 ± 1.05 versus 4.96 ± 0.81 at 3500 RPM. Pump inlet pressure accounted for 9.6 ± 9.7 mm Hg versus 4.2 ± 18.8 mm Hg for 1500 RPM, -42.4 ± 26.7 versus -123 ± 51.1 at 2500 RPM, and -126.7 ± 55.3 versus -313 ± 116.7 for 3500 RPM. CONCLUSIONS: At the well-accepted pump inlet pressure of -80 mm Hg, the new, thinner, virtually wall-less, braided cannulas provide unmatched venous drainage in vivo. Early clinical analyses have confirmed these findings.

A Model of Anterograde Oxygenated Lung Blood Flow in Acardia.

In extreme situations such as hyperacute rejection of heart transplant or major heart trauma, heart explantation and extracorporeal membrane oxygenation (ECMO) hemodynamic support might be the only means for survival. In our previous model of acardia, pulmonary artery (PA) was clamped and did not receive any anterograde blood flow. A model of anterograde PA perfusion might be necessary to avoid ischemic pulmonary damage in prolonged ECMO in acardia. The aim of this study was to describe the surgical technique and to determine the feasibility of an anterograde lung perfusion in acardia through the anastomosis of the right internal mammary artery (RIMA) to the PA. A venoarterial cardiopulmonary bypass was established in three pigs (72 ± 2.6 kg) by the transjugular insertion to the caval axis of a double-staged cannula with carotid artery return. Heart was excised and ECMO was established as previously reported. Right internal mammary artery was harvested and after measurement of its output (93.3 ± 5.8 ml/min, representing 2.17% ± 0.15% of total pump flow), it was anastomosed to PA. Right internal mammary artery anastomosis to PA is a feasible, safe, and easy to perform maneuver assuring an anterograde lung perfusion in acardia.

New Dual Lumen Self-Expanding Catheter Design Requiring Less Suction.

Contribution of venovenous extracorporeal membrane oxygenation (v-v ECMO) to gas transfer is flow dependent. Catheter design is a key factor for optimal pressure/flow rate relationship. This study was designed for the assessment of a new self-expanding dual lumen catheter design versus the current standard. Outlet pressure/flow rate and inlet pressure/flow rate for a new Smart catheter with self-expanding dual lumen design constricted to 27 F with 5 mm long constrictor corresponding to the percutaneous path versus Avalon 27 F catheter (control) were compared on a flow bench with a Biomedicus centrifugal pump. Flow, pump inlet pressure and outlet pressure were determined at 500, 1,000, 1,500, 2,000, and 2,500 revolutions per minute (RPM). At 500 RPM and with a 5 mm long constrictor (1,000; 1,500; 2,000; and 2,500 RPM), catheter outlet pressure values were -0.13 ± 0.07 mm Hg (-2.55 ± 0.06; -7.38 ± 0.14; -15.03 ± 0.44; -26.46 ± 0.39) for self-expanding versus -2.93 ± 0.23* (-10.60 ± 0.14; -22.74 ± 0.34; -38.43 ± 0.41; -58.25 ± 0.40)*: p < 0.0001* for control. The flow values were 0.61 ± 0.01 L/min (1.64 ± 0.03, 2.78 ± 0.02; 4.07 ± 0.04; 5.37 ± 0.02) for self-expanding versus 1.13 ± 0.06*; (2.19 ± 0.04; 3.30 ± 0.03; 4.30 ± 0.03; 5.30 ± 0.03)*: p < 0.0001* for control. The corresponding catheter inlet flow rates of the self-expanding catheter were slightly more than that of the control. For the given setup, our evaluation demonstrated that the new dual lumen self-expanding catheter requires lower catheter outlet pressures for higher flows as compared to the current standard.

Venous cannula performance assessment in a realistic caval tree model.

OBJECTIVES: A new caval tree system was designed for realistic in vitro simulation. The objective of our study was to assess cannula performance for virtually wall-less versus standard percutaneous thin-walled venous cannulas in a setting of venous collapse in case of negative pressure. METHODS: For a collapsible caval model, a very flexible plastic material was selected, and a model with nine afferent veins was designed according to the anatomy of the vena cava. A flow bench was built including a lower reservoir holding the caval tree, built by taking into account the main afferent vessels and their flow provided by a reservoir 6 cm above. A cannula was inserted in this caval tree and connected to a centrifugal pump that, in turn, was connected to a reservoir positioned 83 cm above the second lower reservoir (after-load = 60 mmHg). Using the same pre-load, the simulated venous drainage for cardiopulmonary bypass was realized using a 24 F wall-less cannula (Smartcanula) and 25 F percutaneous cannula (Biomedicus), and stepwise increased augmentation (1500 RPM, 2000 and 2500 RPM) of venous drainage. RESULTS: For the thin wall and the wall-less cannulas, 36 pairs of flow and pressure measurements were realized for three different RPM values. The mean Q-values at 1500, 2000 and 2500 RPM were: 3.98 ± 0.01, 6.27 ± 0.02 and 9.81 ± 0.02 l/min for the wall-less cannula (P <0.0001), versus 2.74 ± 0.02, 3.06 ± 0.05, 6.78 ± 0.02 l/min for the thin-wall cannula (P <0.0001). The corresponding inlet pressure values were: -8.88 ± 0.01, -23.69 ± 0.81 and -70.22 ± 0.18 mmHg for the wall-less cannula (P <0.0001), versus -36.69 ± 1.88, -80.85 ± 1.71 and -101.83 ± 0.45 mmHg for the thin-wall cannula (P <0.0001). The thin-wall cannula showed mean Q-values 37% less and mean P values 26% more when compared with the wall-less cannula (P <0.0001). CONCLUSIONS: Our in vitro water test was able to mimic a negative pressure situation, where the wall-less cannula design performs better compared with the traditional thin-wall cannula.

Late removal of retrievable caval filters.

The advent of retrievable caval filters was a game changer in the sense, that the previously irreversible act of implanting a medical device into the main venous blood stream of the body requiring careful evaluation of the pros and cons prior to execution suddenly became a "reversible" procedure where potential hazards in the late future of the patient lost most of their weight at the time of decision making. This review was designed to assess the rate of success with late retrieval of so called retrievable caval filters in order to get some indication about reasonable implant duration with respect to relatively "easy" implant removal with conventional means, i.e., catheters, hooks and lassos. A PubMed search (www.pubmed.gov) was performed with the search term "cava filter retrieval after 30 days clinical", and 20 reports between 1994 and 2013 dealing with late retrieval of caval filters were identified, covering approximately 7,000 devices with 600 removed filters. The maximal duration of implant reported is 2,599 days and the maximal implant duration of removed filters is also 2,599 days. The maximal duration reported with standard retrieval techniques, i.e., catheter, hook and/or lasso, is 475 days, whereas for the retrievals after this period more sophisticated techniques including lasers, etc. were required. The maximal implant duration for series with 100% retrieval accounts for 84 days, which is equivalent to 12 weeks or almost 3 months. We conclude that retrievable caval filters often become permanent despite the initial decision of temporary use. However, such "forgotten" retrievable devices can still be removed with a great chance of success up to three months after implantation. Conventional percutaneous removal techniques may be sufficient up to sixteen months after implantation whereas more sophisticated catheter techniques have been shown to be successful up to 83 months or more than seven years of implant duration. Tilting, migrating, or misplaced devices should be removed early on, and replaced if indicated with a device which is both, efficient and retrievable.

Performance increase in venous drainage for mini-invasive heart surgery: superiority of self-expanding cannulas.

OBJECTIVE: Originally, the Smartcanula principle (collapsed insertion and expansion in situ) was developed for venous drainage by gravity. However, in minimally invasive surgery, augmentation with either constrained force vortex pumps or vacuum is often used. The current study was set up to assess whether smaller diameters of self-expanding venous cannulas are sufficient in conjunction with venous drainage augmentation resulting in smaller access orifices. METHODS: To evaluate cannulas intended for cardiopulmonary bypass, an in vitro circuit was set up with silicone tubing between the test cannula encased in a lower reservoir, the centrifugal pump, and after an upper reservoir. Afterload was set arbitrarily at 60 mm Hg using a centrifugal pump. The pressure value was measured using Millar pressure transducers. Flow rate (Q) was measured using an ultrasonic flow meter calibrated with volume tank and timer. Revolutions per minute of the centrifugal pump were calibrated with a stroboscope. Data display and data recording were controlled using a Lab View application. Self-expanding (24F Smartcanula) and control (25F Biomedicus) cannulas were used. RESULTS: Sixty measurements were recorded. At pump speed of 1500, 1570, 2000, 2500, and 3000 rpm, the Q values were 3.6, 5.2, 6.6, 9.3, and 11.8 L/min for the 24F self-expanding cannula and 3, 4.3, 5.4, 7.5, and 9.3 L/min for the control cannula. The pressure values were 3.6, -5.4, -15.9, -45.3, and 80.6 mm Hg. Biomedicus 25F showed Q values from 16% to 19% less as compared with 24F Smartcanula. The pressure values were 6, 7, 4, 2, and 2 times more as compared with 24F Smartcanula. CONCLUSIONS: Our experimental evaluation demonstrated the superior performance of the Smartcanula with its self-expanding design in comparison with the reference commercially available standard cannulas. The Smartcanula with its small diameter is particularly welcome for minimally invasive surgery.

Caval collapse during cardiopulmonary bypass: a reproducible bench model.

OBJECTIVES: During open heart surgery, so-called atrial chatter, a phenomenon due to right atria and/or caval collapse, is frequently observed. Collapse of the cava axis during cardiopulmonary bypass (CPB) limits venous drainage and may result downstream in reduced pump flow on (lack of volume) and upstream in increased after-load (stagnation), which in turn may both result in reduced or even inadequate end-organ perfusion. The goal of this study was to reproduce venous collapse in the flow bench. METHODS: In accordance with literature for venous anatomy, a caval tree system is designed (polyethylene, thickness 0.061 mm), which receives venous inflow from nine afferent veins. With water as medium and a preload of 4.4 mmHg, the system has an outflow of 4500 ml/min (Scenario A). After the insertion of a percutaneous venous cannula (23-Fr), the venous model is continuously served by the afferent branches in a venous test bench and venous drainage is augmented with a centrifugal pump (Scenario B). RESULTS: With gravity drainage (siphon: A), spontaneously reversible atrial chatter can be generated in reproducible fashion. Slight reduction in the outflow diameter allows for generation of continuous flow. With augmentation (B), irreversible collapse of the artificial vena cava occurs in reproducible fashion at a given pump speed of 2300 ± 50 RPM and a pump inlet pressure of -112 mmHg. Furthermore, bubbles form at the cannula tip despite the fact that the entire system is immersed in water and air from the environment cannot enter the system. This phenomenon is also known as cavitation and should be avoided because of local damage of both formed blood elements and endothelium, as well embolization. CONCLUSIONS: This caval model provides a realistic picture for the limitations of flow due to spontaneously reversible atrial chatter vs irreversible venous collapse for a given negative pressure during CPB. Temporary interruption of negative pressure in the venous line can allow for recovery of venous drainage. This know-how can be used not only for testing different cannula designs, but also for further optimizing perfusion strategies.

Prevention of caval collapse during venous drainage for CPB.

A new plastic self-expanding Smartcanula (Smartcanula LLC, Lausanne, Switzerland) is designed for central insertion and prevention of caval collapse. The objective of our work is to assess the influence of the new design on atrial chatter. Caval collapse over the entire caval axis, right atrial, hepatic, renal vein, and iliac vein is realized in drainage tubes with holes at 5 cm distance intervals. Smartcanulas with various lengths (26 cm [= right atrial], 34 cm [= hepatic], 43 cm [= renal], and 53 cm [= iliac]) versus two-stage cannulas are compared. Pressure drop (ΔP) is measured using Millar pressure-transducers. Flow rate (Q) is measured using an ultrasonic flow meter. Cannula resistance is defined as the ΔP/Q ratio. Data display and recording are controlled using LabView virtual instruments. At an 88 cm height differential, Q values are 8.69 and 6.8 l/min, and ΔP/Q ratios are 0.63 and 1.28 for the 26-cm Smartcanula and the reference cannula, respectively. The 34-cm Smartcanula showed 8.89 l/min and 0.6 ΔP/Q ratio vs. 7.59 l/min and 0.9 for the control cannula (P < 0.05). The 43-cm and 53-cm Smartcanulas showed Q values of 9.04 and 8.81 l/min, respectively, and ΔP/Q2 ratio of 0.6. The Smartcanula outperforms the two-stage cannula, and direct cannula insertion without guide wire is effective.

Characterizing the impact of minor cannula design modification.

OBJECTIVE: Bench evaluation of the hydrodynamic behavior of venous cannulas is a valuable technique for the analysis of their performance during cardiopulmonary bypass (CPB). The aim of this study was to investigate the effect of the internal diameter of the extracorporeal connecting tube of venous cannulas on flow rate (Q), pressure drop (delta P), and cannula resistance (delta P/Q²) values, using a computer assisted test bench. METHODS: An in vitro circuit was set up with silicone tubing between the test cannula encased in a movable reservoir, and a static reservoir. The delta P, defined as the difference between the drainage pressure and the preload pressure, was measured using high-fidelity Millar pressure transducers. Q was measured using an ultrasonic flowmeter. Data display and data recording were controlled using virtual instruments in a stepwise fashion. RESULTS: The 27 F smartcanula® with a 9 mm connecting tube diameter showed 17% less resistance compared to that with an 8 mm connecting tube diameter. Q values were 7.22±0.1 and 7.81±0.04 L/min for cannulas with 8 mm and 9 mm connecting tube diameters, respectively. The delta P/Q² ratio values were 72% lower for the Medtronic cannula with a 9 mm connecting tube diameter compared to that with an 8 mm connecting tube diameter. Q values for the Medtronic cannula were 3.94±0.23 and 6.58±0.04 L/min with 8 mm and 9 mm connecting tube diameters, respectively. The 27 F smartcanula® showed 13% more flow rate compared to the 28 F Medtronic cannula using the unpaired Student t-test (p<0.0001). CONCLUSIONS: Our results demonstrated that Q was increased but delta P and delta P/Q² values were significantly decreased when the connecting tube diameter was increased for venous cannulas. The connecting tube diameter significantly affected the resistance to liquid flow through the cannula. Smartcanulas® outperform Medtronic cannulas.

Renal endothelin receptor type B upregulation in rats with low or high renin hypertension.

OBJECTIVES: To evaluate the role of endothelin-1 (ET-1) in hypertension, we investigated density and distribution of ETA and ETB receptors in hearts and kidneys of deoxycorticosterone acetate (DOCA)-salt and 1 kidney -- 1 clip (1K1C) hypertensive rats. METHODS: Five groups of uninephrectomized Wistar rats were put on a low salt diet. Three groups of rats drank tap water and two groups received saline. One group of each regimen received DOCA subcutaneously and two corresponding groups without DOCA served as controls. The fifth group of rats had the renal artery clipped to induce 1K1C hypertension. At 6 weeks, mean arterial pressure (MAP) was recorded and membrane binding assays using 125I-ET-1 were carried out. RESULTS: MAP was increased from control 122 +/- 3 to 155 +/- 6 and 218 +/- 11 mmHg in DOCA-salt and 1K1C rats, respectively, and cardiac weight index was increased. ETA receptors were predominantly expressed in the heart, whereas ETB receptors were predominant in the kidney. In the kidneys, the density of the ETB receptor subtype was upregulated in DOCA-salt and 1K1C rats from 160 +/- 8 to 217 +/- 12 and 190 +/- 2 fmol/mg (P < 0.05), respectively, and ETA tended to be downregulated (P = 0.057). Plasma renin activity was decreased in DOCA-salt rats from 17 +/- 3 to 0.17 +/- 0.01 ng/ml per h and increased in 1K1C rats on low salt diet to 30 +/- 5 ng/ml per h. CONCLUSIONS: Since ETB is the predominant endothelin receptor in the kidneys, upregulation of the ETB receptor mediating vasodilation and downregulation of the ETA receptor mediating vasoconstriction would be compatible with a mainly renal counter-regulatory effect of endothelin-1 to hypertension. Both low and high renin models of hypertension may be affected.

Volume expansion enhances plasma endothelin-1.

We hypothesized that acute volume expansion by saline infusion triggers the release of endothelin-1. Bolus intravenous saline infusion (8 mL/min) in six groups of conscious Wistar rats and spontaneously hypertensive rats did not change mean arterial pressure or heart rate (n = 8 to 12). At 1 min after infusion, the plasma endothelin-1 level was significantly increased in Wistar rats and in spontaneously hypertensive rats by 42% and 61%, respectively (unpaired data). In 12 Wistar rats, the endothelin-1 level increased from 0.68 +/- 0.13 to 1.19 +/- 0.17 fmol/mL (mean +/- SEM, P <.0001, paired data). Thus, acute volume load by rapid saline infusion increases plasma endothelin-1 levels. Vasoconstriction induced by endothelin-1 may counteract enhanced circumferential stretch created by volume expansion.

Measurement of plasma endothelin-1 in experimental hypertension and in healthy subjects.

BACKGROUND: Endothelin-1 is an endothelium-derived potent vasoconstrictor peptide of 21 amino acids. To establish reference values in different models of hypertension and in human subjects an assay for plasma immunoreactive endothelin-1 (ET-1) was optimized. METHODS: ET-1 is extracted by acetone from 1 mL of plasma and subjected to a sensitive enzyme-linked immunosorbent assay. RESULTS: The detection limit for plasma ET-1 is 0.05 fmol/mL. Mean recoveries of the 1, 2, 5, and 10 fmol of ET-1 added to 1 mL of plasma were 66%, 75%, 85%, and 92%, respectively. Within- and between-assay coefficients of variation were < or =12% and < or =10%, respectively. Assay accuracy was demonstrated by consistent recoveries of added ET-1 over the entire physiologic range of plasma concentrations and by the linearity of ET-1 concentrations measured in serially diluted plasma extracts (r = 0.99). No ET-1 was detected when albumin buffer was extracted instead of plasma. Using this method, we found increased ET-1 levels in plasma of three experimental rat models of hypertension: stroke prone spontaneously hypertensive rats (SP-SHR), deoxycorticosterone acetate-salt hypertensive rats, and one kidney-one clip hypertensive rats. In contrast, plasma ET-1 levels of SHR were half those of normotensive Wistar rats. In two kidney-one clip hypertensive rats, plasma ET-1 concentrations were not different from those found in sham-operated control rats. Plasma ET-1 concentrations of 37 healthy men were 0.85 +/- 0.26 fmol/ml (mean +/- SD). CONCLUSIONS: The present assay reliably measures ET-1 levels in rat and human plasma. It allows to discriminate between different forms of hypertension with high or low circulating levels of ET-1.