Reliability assessment of a cooled intraesophageal balloon to prevent thermal injury during RF cardiac ablation: an agar phantom study

[EN] Cooled Balloon Prevents Thermal Injury During RF Ablation. Introduction: The use of a cooled intraesophageal balloon has recently been proposed to minimize the risk of thermal injury in the esophagus during radiofrequency (RF) ablation of the left atrium. However, the capacity of this device to adequately protect the esophagus under different procedural and anatomical conditions remains unknown. Methods and Results: An agar phantom-based model was built that provided temperature readings not only on the cooled balloon (T-b) but also at a hypothetical point between the esophageal lumen and myocardium at a distance of 2 mm (T2-mm). The RF ablations were conducted considering two anatomical factors (total distance between the electrode and balloon and flow rate around the electrode) and two procedural factors (angle and pressure between the electrode and agar surface). The results show that most of the parameters studied have no significant influence on the temperature measured on the cooled balloon (T-b), the exception being a variation in the flow rate, which was found to influence the temperature. On the other hand, T2-mm was affected to a great extent by all the factors considered, the smallest influence being that of the contact pressure. The results also suggest that when an intraesophageal balloon is employed, the applied power is not a good predictor either of the temperature on the balloon or of the temperature measured at a distance 2 mm away. Conclusion: The results suggest that a cooled intraesophageal balloon provides effective thermal protection of the esophageal lumen. However, under certain circumstances, the temperature reached at a distance 2 mm away could possibly put at risk the integrity of the inner layers of the esophagus. (J Cardiovasc Electrophysiol, Vol. 19, pp. 1188-1193, November 2008).This work was partially supported by the "Plan Nacional de Investigacion Cientifica, Desarrollo e Innovaci on Tecnologica del Ministerio de Educacion y Cienciaa of Spain (TEC 2005-04199/TCM) and by an R&D contract (CSIC-20060633) between Edwards Lifescience Ltd. and the Spanish Council for Scientific Research (CSIC).Lequerica, JL.; Berjano, E.; Herrero, M.; Hornero, F. (2008). Reliability assessment of a cooled intraesophageal balloon to prevent thermal injury during RF cardiac ablation: an agar phantom study. Journal of Cardiovascular Electrophysiology. 19(11):1188-1193. https://doi.org/10.1111/j.1540-8167.2008.01229.xS11881193191

Cooled water-irrigated intraesophageal balloon to prevent thermal injury during cardiac ablation: Experimental study based on an agar phantom

[EN] A great deal of current research is directed to finding a way to minimize thermal injury in the esophagus during radiofrequency catheter ablation of the atrium. A recent clinical study employing a cooling intraesophageal balloon reported a reduction of the temperature in the esophageal lumen. However, it could not be determined whether the deeper muscular layer of the esophagus was cooled enough to prevent injury. We built a model based on an agar phantom in order to experimentally study the thermal behavior of this balloon by measuring the temperature not only on the balloon, but also at a hypothetical point between the esophageal lumen and myocardium (2 mm distant). Controlled temperature (55 degrees C) ablations were conducted for 120 s. The results showed that (1) the cooling balloon provides a reduction in the final temperature reached, both on the balloon surface and at a distance of 2 mm; (2) coolant temperature has a significant effect on the temperature measured at 2 mm from the esophageal lumen (it has a less effect on the temperature measured on the balloon surface) and (3) the pre- cooling period has a significant effect on the temperature measured on the balloon surface (the effect on the temperaturemeasured 2mmaway is small). The results were in good agreement with those obtained in a previous clinical study. The study suggests that the cooling balloon gives thermal protection to the esophagus when a minimum pre- cooling period of 2 min is programmed at a coolant temperature of 5 degrees C or less.We would like to thank the R+D+i Linguistic Assistance Office at the Technical Universityof Valencia for their help in revising this paper. This work was partially financially supported by the ‘Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica del Ministerio de Educación y Ciencia of Spain (TEC 2005-04199/TCM) and by an R&D contract (CSIC-20060633) between Edwards Life science Ltd. and the Spanish Council for ScientificResearch (CSIC).Lequerica, JL.; Berjano, E.; Herrero, M.; Melecio, L.; Hornero, F. (2008). Cooled water-irrigated intraesophageal balloon to prevent thermal injury during cardiac ablation: Experimental study based on an agar phantom. Physics in Medicine and Biology. 53:25-34. https://doi.org/10.1088/0031-9155/53/4/N01S25345

Esophageal temperature monitoring during radiofrequency catheter ablation: experimental study based on an agar phantom model

[EN] Although previous studies have established the feasibility of monitoring esophageal temperature during radiofrequency cardiac ablation using an esophageal temperature probe (ETP), some questions remain regarding its efficacy. The aims of this study were to study the effect of the location of the ETP on the temperature reached, and to test the characteristics of ETP as used in clinical practice. We constructed an agar phantom to model the thermal and electrical characteristics of the biological tissues (left atrium, esophagus and connective tissue). The ETP was positioned at 6.5 mm from an ablation electrode and at distances of 0, 5, 10, 15, 20 mm from the catheter axis. A thermocouple was located on the probe to measure the actual temperature of the external esophageal layer during the ablations (55 degrees C, 60 s). The mean temperatures reached at the thermocouple were significantly higher than those measured by the ETP (48.3 +/- 1.9 degrees C versus 39.6 +/- 1.1 degrees C). The temperature values measured with the ETP were significantly lower when the probe was located further from the catheter axis ( up to 2.5 degrees C lower when the distance from the probe - catheter axis was 2 cm). The dynamic calibration of the ETP showed a mean value for the time constant of 8 s. In conclusion, the temperature measured by the ETP always underestimates the temperature reached in the thermocouple. This fact can be explained by the distance gap between the thermocouple and probe and by the dynamic response of the ETP. The longer the distance between the ETP and catheter axis, the higher is the temperature difference.We would like to thank the R+D+i Linguistic Assistance Office at the Universidad Politécnica of Valencia for its help in revising this paper. This work was partially supported by the Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica del Ministerio de Educación y Ciencia of Spain (TEC 2005-04199/TCM) and by an R&D contract (CSIC-20060633) between Edwards Lifescience Ltd. and the Spanish Council for Scientific Research (CSIC).Rodriguez, I.; Lequerica, JL.; Berjano, E.; Herrero, M.; Hornero, F. (2007). Esophageal temperature monitoring during radiofrequency catheter ablation: experimental study based on an agar phantom model. Physiological Measurement. 28(5):453-463. https://doi.org/10.1088/0967-3334/28/5/001S453463285Berjano, E. J., & Hornero, F. (2005). What affects esophageal injury during radiofrequency ablation of the left atrium? An engineering study based on finite-element analysis. Physiological Measurement, 26(5), 837-848. doi:10.1088/0967-3334/26/5/020Hong Cao, Vorperian, V. R., Jang-Zem Tsai, Tungjitkusolmun, S., Eung Je Woo, & Webster, J. G. (2000). Temperature measurement within myocardium during in vitro RF catheter ablation. IEEE Transactions on Biomedical Engineering, 47(11), 1518-1524. doi:10.1109/10.880104Cappato, R., Calkins, H., Chen, S.-A., Davies, W., Iesaka, Y., Kalman, J., … Skanes, A. (2005). Worldwide Survey on the Methods, Efficacy, and Safety of Catheter Ablation for Human Atrial Fibrillation. Circulation, 111(9), 1100-1105. doi:10.1161/01.cir.0000157153.30978.67Cummings, J. E., Schweikert, R. A., Saliba, W. I., Burkhardt, J. D., Brachmann, J., Gunther, J., … Natale, A. (2005). Assessment of Temperature, Proximity, and Course of the Esophagus During Radiofrequency Ablation Within the Left Atrium. Circulation, 112(4), 459-464. doi:10.1161/circulationaha.104.509612D‘avila, A., Maldonado, P., Veronese, F., Mendonça, M. L. F., Colafranceschi, A. S., Colle, S., & Saad, E. B. (2005). Accuracy of esophageal temperature measurement and its correlation to microbubbles formation during catheter ablation of atrial fibrillation. Heart Rhythm, 2(5), S9. doi:10.1016/j.hrthm.2005.02.040Doll, N., Borger, M. A., Fabricius, A., Stephan, S., Gummert, J., Mohr, F. W., … Hindricks, G. (2003). Esophageal perforation during left atrial radiofrequency ablation: Is the risk too high? The Journal of Thoracic and Cardiovascular Surgery, 125(4), 836-842. doi:10.1067/mtc.2003.165Gillinov, A. M., Pettersson, G., & Rice, T. W. (2001). Esophageal injury during radiofrequency ablation for atrial fibrillation. The Journal of Thoracic and Cardiovascular Surgery, 122(6), 1239-1240. doi:10.1067/mtc.2001.118041Goldberg, S. N., Ahmed, M., Gazelle, G. S., Kruskal, J. B., Huertas, J. C., Halpern, E. F., … Lenkinski, R. E. (2001). Radio-Frequency Thermal Ablation with NaCl Solution Injection: Effect of Electrical Conductivity on Tissue Heating and Coagulation—Phantom and Porcine Liver Study. Radiology, 219(1), 157-165. doi:10.1148/radiology.219.1.r01ap27157YEN HO, S., SANCHEZ-QUINTANA, D., CABRERA, J. A., & ANDERSON, R. H. (1999). Anatomy of the Left Atrium:. Journal of Cardiovascular Electrophysiology, 10(11), 1525-1533. doi:10.1111/j.1540-8167.1999.tb00211.xHORNERO, F., & BERJANO, E. J. (2006). Esophageal Temperature During Radiofrequency-Catheter Ablation of Left Atrium: A Three-Dimensional Computer Modeling Study. Journal of Cardiovascular Electrophysiology, 17(4), 405-410. doi:10.1111/j.1540-8167.2006.00404.xJain, M. K., & Wolf, P. D. (2000). In Vitro Temperature Map of Cardiac Ablation Demonstrates the Effect of Flow on Lesion Development. Annals of Biomedical Engineering, 28(9), 1066-1074. doi:10.1114/1.1310218Kuwahara, T., Takahashi, A., Yokoyama, Y., Kobori, A., Sato, A., Iesaka, Y., … Aonuma, K. (2005). Importance of esophageal temperature monitoring for the avoidance of esophageal injury during circumferential left atrial ablation. Heart Rhythm, 2(5), S156. doi:10.1016/j.hrthm.2005.02.487Lemola, K., Sneider, M., Desjardins, B., Case, I., Han, J., Good, E., … Oral, H. (2004). Computed Tomographic Analysis of the Anatomy of the Left Atrium and the Esophagus. Circulation, 110(24), 3655-3660. doi:10.1161/01.cir.0000149714.31471.fdLobo, S. M., Afzal, K. S., Ahmed, M., Kruskal, J. B., Lenkinski, R. E., & Goldberg, S. N. (2004). Radiofrequency Ablation: Modeling the Enhanced Temperature Response to Adjuvant NaCl Pretreatment. Radiology, 230(1), 175-182. doi:10.1148/radiol.2301021512Meade, T., Razavi, M., Yang, D., Delapasse, S., Donsky, A., Ai, T., … Cheng, J. (2005). Real-time esophageal thermal profile during posterior left atrial radiofrequency ablation. Heart Rhythm, 2(5), S236. doi:10.1016/j.hrthm.2005.02.738Pappone, C., Oral, H., Santinelli, V., Vicedomini, G., Lang, C. C., Manguso, F., … Morady, F. (2004). Atrio-Esophageal Fistula as a Complication of Percutaneous Transcatheter Ablation of Atrial Fibrillation. Circulation, 109(22), 2724-2726. doi:10.1161/01.cir.0000131866.44650.46PERZANOWSKI, C., TEPLITSKY, L., HRANITZKY, P. M., & BAHNSON, T. D. (2006). Real-Time Monitoring of Luminal Esophageal Temperature During Left Atrial Radiofrequency Catheter Ablation for Atrial Fibrillation: Observations About Esophageal Heating During Ablation at the Pulmonary Vein Ostia and Posterior Left Atrium. Journal of Cardiovascular Electrophysiology, 17(2), 166-170. doi:10.1111/j.1540-8167.2005.00333.xPiorkowski, C., Hindricks, G., Schreiber, D., Tanner, H., Weise, W., Koch, A., … Kottkamp, H. (2006). Electroanatomic reconstruction of the left atrium, pulmonary veins, and esophagus compared with the «true anatomy» on multislice computed tomography in patients undergoing catheter ablation of atrial fibrillation. Heart Rhythm, 3(3), 317-327. doi:10.1016/j.hrthm.2005.11.027REDFEARN, D. P., TRIM, G. M., SKANES, A. C., PETRELLIS, B., KRAHN, A. D., YEE, R., & KLEIN, G. J. (2005). Esophageal Temperature Monitoring During Radiofrequency Ablation of Atrial Fibrillation. Journal of Cardiovascular Electrophysiology, 16(6), 589-593. doi:10.1111/j.1540-8167.2005.40825.xSánchez-Quintana, D., Cabrera, J. A., Climent, V., Farré, J., de Mendonça, M. C., & Ho, S. Y. (2005). Anatomic Relations Between the Esophagus and Left Atrium and Relevance for Ablation of Atrial Fibrillation. Circulation, 112(10), 1400-1405. doi:10.1161/circulationaha.105.551291SCANAVACCA, M. I., D’ÁVILA, A., PARGA, J., & SOSA, E. (2004). Left Atrial-Esophageal Fistula Following Radiofrequency Catheter Ablation of Atrial Fibrillation. Journal of Cardiovascular Electrophysiology, 15(8), 960-962. doi:10.1046/j.1540-8167.2004.04083.xSolazzo, S. A., Liu, Z., Lobo, S. M., Ahmed, M., Hines-Peralta, A. U., Lenkinski, R. E., & Goldberg, S. N. (2005). Radiofrequency Ablation: Importance of Background Tissue Electrical Conductivity—An Agar Phantom and Computer Modeling Study. Radiology, 236(2), 495-502. doi:10.1148/radiol.2362040965Teplitsky, L., Perzanowski, C., Durrani, S., Berman, A. E., Hranitzky, P., & Bahnson, T. D. (2005). Radiofrequency catheter ablation for atrial fibrillation produces delayed and long lasting elevation of luminal esophageal temperature independent of lesion duration and power. Heart Rhythm, 2(5), S8-S9. doi:10.1016/j.hrthm.2005.02.038Tsao, H.-M., Wu, M.-H., Higa, S., Lee, K.-T., Tai, C.-T., Hsu, N.-W., … Chen, S.-A. (2005). Anatomic Relationship of the Esophagus and Left Atrium. Chest, 128(4), 2581-2587. doi:10.1378/chest.128.4.2581Wittkampf, F. H. M., Nakagawa, H., Yamanashi, W. S., Imai, S., & Jackman, W. M. (1996). Thermal Latency in Radiofrequency Ablation. Circulation, 93(6), 1083-1086. doi:10.1161/01.cir.93.6.108

Black-box modeling to estimate tissue temperature during radiofrequency catheter cardiac ablation: feasibility study on an agar phantom model

This is an author-created, un-copyedited versíon of an article published in Physiological Measurement. IOP Publishing Ltd is not responsíble for any errors or omissíons in this versíon of the manuscript or any versíon derived from it. The Versíon of Record is available online at http://doi.org/10.1088/0967-3334/31/4/009[EN] The aim of this work was to study linear deterministic models to predict tissue temperature during radiofrequency cardiac ablation (RFCA) by measuring magnitudes such as electrode temperature, power and impedance between active and dispersive electrodes. The concept involves autoregressive models with exogenous input (ARX), which is a particular case of the autoregressive moving average model with exogenous input (ARMAX). The values of the mode parameters were determined from a least-squares fit of experimental data. The data were obtained from radiofrequency ablations conducted on agar models with different contact pressure conditions between electrode and agar (0 and 20 g) and different flow rates around the electrode (1, 1.5 and 2 L min¿1). Half of all the ablations were chosen randomly to be used for identification (i.e. determination of model parameters) and the other half were used for model validation. The results suggest that (1) a linear model can be developed to predict tissue temperature at a depth of 4.5 mm during RF cardiac ablation by using the variables applied power, impedance and electrode temperature; (2) the best model provides a reasonably accurate estimate of tissue temperature with a 60% probability of achieving average errors better than 5 °C; (3) substantial errors (larger than 15 °C) were found only in 6.6% of cases and were associated with abnormal experiments (e.g. those involving the displacement of the ablation electrode) and (4) the impact of measuring impedance on the overall estimate is negligible (around 1 °C).This work was supported by the 'Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica del Ministerio de Educacion y Ciencia' of Spain (TEC200801369/ TEC) and by an R&D contract (CSIC-20060633) between Edwards Lifescience Ltd and the Spanish National Research Council (CSIC). The English revision and correction of this paper was funded by the Universidad Politecnica de Valencia, Spain. We thank L Melecio for his invaluable technical support in conducting the experiments.Blasco-Giménez, R.; Lequerica, JL.; Herrero, M.; Hornero, F.; Berjano, E. (2010). Black-box modeling to estimate tissue temperature during radiofrequency catheter cardiac ablation: feasibility study on an agar phantom model. Physiological Measurement. 31(4):581-594. https://doi.org/10.1088/0967-3334/31/4/009S581594314Hong Cao, Tungjitkusolmun, S., Young Bin Choy, Jang-Zern Tsai, Vorperian, V. R., & Webster, J. G. (2002). Using electrical impedance to predict catheter-endocardial contact during RF cardiac ablation. IEEE Transactions on Biomedical Engineering, 49(3), 247-253. doi:10.1109/10.983459Hong Cao, Vorperian, V. R., Jang-Zem Tsai, Tungjitkusolmun, S., Eung Je Woo, & Webster, J. G. (2000). Temperature measurement within myocardium during in vitro RF catheter ablation. IEEE Transactions on Biomedical Engineering, 47(11), 1518-1524. doi:10.1109/10.880104Hamner, C. E., Potter, D. D., Cho, K. R., Lutterman, A., Francischelli, D., Sundt, T. M., & Schaff, H. V. (2005). Irrigated Radiofrequency Ablation With Transmurality Feedback Reliably Produces Cox Maze Lesions In Vivo. The Annals of Thoracic Surgery, 80(6), 2263-2270. doi:10.1016/j.athoracsur.2005.06.017HARTUNG, W. M., BURTON, M. E., DEAM, A. G., WALTER, P. F., McTEAGUE, K., & LANGBERG, J. J. (1995). Estimation of Temperature During Radiofrequency Catheter Ablation Using Impedance Measurements. Pacing and Clinical Electrophysiology, 18(11), 2017-2021. doi:10.1111/j.1540-8159.1995.tb03862.xDing Sheng He, Bosnos, M., Mays, M. Z., & Marcus, F. (2003). Assessment of myocardial lesion size during in vitro radio frequency catheter ablation. IEEE Transactions on Biomedical Engineering, 50(6), 768-776. doi:10.1109/tbme.2003.812161KO, W.-C., HUANG, S. K. S., LIN, J.-L., SHAU, W.-Y., LAI, L.-P., & CHEN, P. H. (2001). New Method for Predicting Efficiency of Heating by Measuring Bioimpedance During Radiofrequency Catheter Ablation in Humans. Journal of Cardiovascular Electrophysiology, 12(7), 819-823. doi:10.1046/j.1540-8167.2001.00819.xLabonte, S. (1994). Numerical model for radio-frequency ablation of the endocardium and its experimental validation. IEEE Transactions on Biomedical Engineering, 41(2), 108-115. doi:10.1109/10.284921Lai, Y.-C., Choy, Y. B., Haemmerich, D., Vorperian, V. R., & Webster, J. G. (2004). Lesion Size Estimator of Cardiac Radiofrequency Ablation at Different Common Locations With Different Tip Temperatures. IEEE Transactions on Biomedical Engineering, 51(10), 1859-1864. doi:10.1109/tbme.2004.831529Lequerica, J. L., Berjano, E. J., Herrero, M., Melecio, L., & Hornero, F. (2008). A cooled water-irrigated intraesophageal balloon to prevent thermal injury during cardiac ablation: experimental study based on an agar phantom. Physics in Medicine and Biology, 53(4), N25-N34. doi:10.1088/0031-9155/53/4/n01Mattingly, M., Bailey, E. A., Dutton, A. W., Roemer, R. B., & Devasia, S. (1998). Reduced-order modeling for hyperthermia: an extended balanced-realization-based approach. IEEE Transactions on Biomedical Engineering, 45(9), 1154-1162. doi:10.1109/10.709559PILCHER, T. A., SANFORD, A. L., SAUL, J. P., & HAEMMERICH, D. (2006). Convective Cooling Effect on Cooled-Tip Catheter Compared to Large-Tip Catheter Radiofrequency Ablation. Pacing and Clinical Electrophysiology, 29(12), 1368-1374. doi:10.1111/j.1540-8159.2006.00549.xRodríguez, I., Lequerica, J. L., Berjano, E. J., Herrero, M., & Hornero, F. (2007). Esophageal temperature monitoring during radiofrequency catheter ablation: experimental study based on an agar phantom model. Physiological Measurement, 28(5), 453-463. doi:10.1088/0967-3334/28/5/001SCHUMACHER, B., EICK, O., WITTKAMPF, F., PEZOLD, C., TEBBENJOHANNS, J., JUNG, W., & LUDERITZ, B. (1999). Temperature Response Following Nontraumatic Low Power Radiofrequency Application. Pacing and Clinical Electrophysiology, 22(2), 339-343. doi:10.1111/j.1540-8159.1999.tb00448.xTeixeira, C. A., Ruano, A. E., Ruano, M. G., Pereira, W. C. A., & Negreira, C. (2006). Non-invasive temperature prediction of in vitro therapeutic ultrasound signals using neural networks. Medical & Biological Engineering & Computing, 44(1-2), 111-116. doi:10.1007/s11517-005-0004-2Teixeira, C. A., Ruano, M. G., Ruano, A. E., & Pereira, W. C. A. (2008). A Soft-Computing Methodology for Noninvasive Time-Spatial Temperature Estimation. IEEE Transactions on Biomedical Engineering, 55(2), 572-580. doi:10.1109/tbme.2007.90102

Assessment of Hyperbolic Heat Transfer Equation in Theoretical Modeling for Radiofrequency Heating Techniques

Theoretical modeling is a technique widely used to study the electrical-thermal performance of different surgical procedures based on tissue heating by use of radiofrequency (RF) currents. Most models employ a parabolic heat transfer equation (PHTE) based on Fourier’s theory, which assumes an infinite propagation speed of thermal energy. We recently proposed a one-dimensional model in which the electrical-thermal coupled problem was analytically solved by using a hyperbolic heat transfer equation (HHTE), i.e. by considering a non zero thermal relaxation time. In this study, we particularized this solution to three typical examples of RF heating of biological tissues: heating of the cornea for refractive surgery, cardiac ablation for eliminating arrhythmias, and hepatic ablation for destroying tumors. A comparison was made of the PHTE and HHTE solutions. The differences between their temperature profiles were found to be higher for lower times and shorter distances from the electrode surface. Our results therefore suggest that HHTE should be considered for RF heating of the cornea (which requires very small electrodes and a heating time of 0.6 s), and for rapid ablations in cardiac tissue (less than 30 s)

Global urban environmental change drives adaptation in white clover

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale

Nuevo péptido inhibidor del intercambiador NA4+H+ (pinhe), y sus aplicaciones.

Fecha de solicitud: 15.07.2003.- Titulares: Consejo Superior de Investigaciones Científicas (CSIC).- Universidad de Valencia.- Universidad Miguel Hernández.[EN]The invention relates to a peptide (PINHE) comprising 28 amino acids, which is obtained by fractionation and purification of the supernatant of the culture of Haloferax gibbonsii alicante SPH7. PINHE acts as a natural physiological inhibitor of the Na/H exchanger in eukaryotes. Moreover, PINHE is active in wide ranges of saline concentrations, temperature and pH as well as being trypsin resistant and pronase sensitive. Owing to the reversible action of said peptide on the Na/H exchanger, it can be used (1) for the treatment or prophylaxis of pathologies such as cardiovascular, renal, cerebral and metabolic diseases, pathological proliferative processes, hyperproduction of hydrochloric acid, etc. and (2) for other diseases or pathologies associated with a post-ischemic reperfusion lesion and ischemia caused by hyperactivity of the NHE, such as ischemias caused by primary or secondary vascular alterations in different tissues, by post-infarction reperfusion, by an organ or tissue transplant, etc. The inventive peptide can also be used as a contraceptive (in male mammals), an antibiotic or an immunoregulatory agent and in plants as a saline stress modulator. [ES]La presente invención describe un péptido (PINHE) constituido por 28 aminoácidos obtenido por fraccionamiento y purificación del sobrenadante del cultivo de Haloferax gibbonsii alicante SPH7. El PINHE actúa como inhibidor fisiológico natural del intercambiador Na+/H+ en eucariotas. Es activo en rangos amplios de concentraciones salinas, temperatura y pH, resistente a tripsina y sensible a pronasa. De su acción reversible sobre el intercambiador Na+/H+ se deriva: (1) su uso para el tratamiento o profilaxis de patologías como enfermedades cardiovasculares, renales, cerebrales, metabólicas, procesos proliferativos patológicos, hiperproducción de ácido clorhídrico, etc., (2) en otras enfermedades o patologías que cursen con isquemia y lesión por reperfusión post-isquémica debida a la hiperactividad del NHE como isquemias por alteraciones vasculares primarias o secundarias en diversos tejidos, por reperfusión post-infarto, por transplante de órganos o tejidos, etc. También como contraceptivo (en mamíferos macho), antibiótico o agente inmunorregulador, y en plantas como modulador del estrés salino.Peer reviewe

Una halocina que actúa sobre el intercambiador Na+/H+ de Haloarchaea como un nuevo tipo de inhibidor de NHE de mamíferos

10 páginas, 3 figuras.[EN]: The capability of halocin H6 (a bacteriocin-like protein produced by haloarchaeaHaloferax gibbonsii) to inhibit Na+/H+ exchange (NHE) in mammalian cells and its cardio-protective efficacy on the ischemic and reperfused myocardium were evaluated in the present study. H6 inhibits NHE activity (measured by a flow cytometry method) in a dose-dependent form of cell lines of mammalian origin (HEK293, NIH3T3, Jurkat and HL-1) as well as in primary cell culture from human skeletal muscle (myocytes and fibroblasts).In vivo, an ischemia-reperfusion model in dogs by coronary arterial occlusion was used (two hours of regional ischemia and three hours of reperfusion). In animals treated with halocin H6 there was a significant reduction of premature ventricular ectopic beats and infarct size, whereas blood pressure and heart rate remained unchanged. Up to date, halocin H6 is the only described biological molecule that exerts a, specific inhibitory activity in NHE of eukaryotic cells.[ES]: En el presente trabajo se evalúa la capacidad de la halocina H6 (una proteína tipo bacteriocina producida por la haloarchaea Haloferax gibbonsii) para inhibir el intercambiador Na+/H+ (NHE) de células de mamífero y su posible eficacia cardioprotectora frente a los daños causados por isquemia-reperfusión del miocardio. En experimentos in vitro H6 inhibe la actividad de NHE (determinada por citometría de flujo) de forma dosis-dependiente tanto en líneas celulares de mamíferos (HEK293, NIH3T3, Jurkat y HL-1) como en cultivos primarios de miocitos y fibroblastos aislados de músculo esquelético humano. En experimentos in vivo se utilizó un modelo de isquemia- reperfusión en perros por oclusión de la arteria coronaria (dos horas de isquemia y tres de reperfusión). En animales tratados con halocina H6 se produjo una disminución significativa a nivel estadístico, tanto del número de latidos ectópicos ventriculares como del tamaño del infarto, mientras que no se produjeron cambios tanto en la presión sanguínea como en el ritmo cardíaco. Hasta la fecha la halocina H6 es la única molécula biológica descrita que ejerce una actividad inhibidora específica sobre el NHE de células eucariotas.M. Dolz held a fellowship of CSIC-Bancaja Foundation. This work was supported in part by Spanish Council for Scientific Research (CSIC- 2001551).Peer reviewe