Name: measuring pressure volume loops in the mouse
Uploaded: 2016-05-02T15:00:00.000+00:00
Duration: 9 min 15 s
Description: Watch this Scientific Journal Video about Measuring Pressure Volume Loops in the Mouse at JoVE.com

המחבר מבקש להודות במימון NHLBI (K08 HL102066 ו R01 HL114832).

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	<li>Mozaffarian, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Heart+disease+and+stroke+statistics--2015+update:+a+report+from+the+American+Heart+Association.">Heart disease and stroke statistics--2015 update: a report from the American Heart Association.</a> Circulation. 131 (4), e29-e322 (2015).</li><li>Katz, A. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Influence+of+altered+inotropy+and+lusitropy+on+ventricular+pressure-volume+loops.">Influence of altered inotropy and lusitropy on ventricular pressure-volume loops.</a> J Am Coll Cardiol. 11 (2), 438-445 (1988).</li><li>Kass, D. A., Maughan, W. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=From+&amp;#34;Emax&amp;#34;+to+pressure-volume+relations:+a+broader+view.">From &amp;#34;Emax&amp;#34; to pressure-volume relations: a broader view.</a> Circulation. 77 (6), 1203-1212 (1988).</li><li>Georgakopoulos, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+vivo+murine+left+ventricular+pressure-volume+relations+by+miniaturized+conductance+micromanometry.">In vivo murine left ventricular pressure-volume relations by miniaturized conductance micromanometry.</a> Am J Physiol Heart Circ Physiol. 274 (4 Pt 2), H1416-H1422 (1998).</li><li>Kass, D. A., Hare, J. M., Georgakopoulos, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Murine+cardiac+function:+a+cautionary+tail.">Murine cardiac function: a cautionary tail.</a> Circ Res. 82 (4), 519-522 (1998).</li><li>Feldman, M. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Validation+of+a+mouse+conductance+system+to+determine+LV+volume:+comparison+to+echocardiography+and+crystals.">Validation of a mouse conductance system to determine LV volume: comparison to echocardiography and crystals.</a> Am J Physiol Heart Circ Physiol. 279 (4), H1698-H1707 (2000).</li><li>Baan, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Continuous+measurement+of+left+ventricular+volume+in+animals+and+humans+by+conductance+catheter.">Continuous measurement of left ventricular volume in animals and humans by conductance catheter.</a> Circulation. 70 (5), 812-823 (1984).</li><li>Salo, R. W., Wallner, T. G., Pederson, B. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Measurement+of+ventricular+volume+by+intracardiac+impedance:+theoretical+and+empirical+approaches.">Measurement of ventricular volume by intracardiac impedance: theoretical and empirical approaches.</a> IEEE Trans Biomed Eng. 33 (2), 189-195 (1986).</li><li>Wei, C. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Volume+catheter+parallel+conductance+varies+between+end-systole+and+end-diastole.">Volume catheter parallel conductance varies between end-systole and end-diastole.</a> IEEE Trans Biomed Eng. 54 (8), 1480-1489 (2007).</li><li>Kutty, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Validation+of+admittance+computed+left+ventricular+volumes+against+real-time+three-dimensional+echocardiography+in+the+porcine+heart.">Validation of admittance computed left ventricular volumes against real-time three-dimensional echocardiography in the porcine heart.</a> Exp Physiol. 98 (6), 1092-1101 (2013).</li><li>Kottam, A., Dubois, J., McElligott, A., Henderson, K. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Novel+approach+to+admittance+to+volume+conversion+for+ventricular+volume+measurement.">Novel approach to admittance to volume conversion for ventricular volume measurement.</a> Conf Proc IEEE Eng Med Biol Soc. , 2514-2517 (2011).</li><li>Meyers, T. A., Townsend, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Early+right+ventricular+fibrosis+and+reduction+in+biventricular+cardiac+reserve+in+the+dystrophin-deficient+mdx+heart.">Early right ventricular fibrosis and reduction in biventricular cardiac reserve in the dystrophin-deficient mdx heart.</a> Am J Physiol Heart Circ Physiol. 308 (4), H303-H315 (2015).</li><li>Townsend, D., Yasuda, S., Li, S., Chamberlain, J. S., Metzger, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Emergent+dilated+cardiomyopathy+caused+by+targeted+repair+of+dystrophic+skeletal+muscle.">Emergent dilated cardiomyopathy caused by targeted repair of dystrophic skeletal muscle.</a> Mol Ther. 16 (5), 832-835 (2008).</li><li>Townsend, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Systemic+administration+of+micro-dystrophin+restores+cardiac+geometry+and+prevents+dobutamine-induced+cardiac+pump+failure.">Systemic administration of micro-dystrophin restores cardiac geometry and prevents dobutamine-induced cardiac pump failure.</a> Mol Ther. 15 (6), 1086-1092 (2007).</li><li>Strakova, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dystrobrevin+increases+dystrophin's+binding+to+the+dystrophin-glycoprotein+complex+and+provides+protection+during+cardiac+stress.">Dystrobrevin increases dystrophin's binding to the dystrophin-glycoprotein complex and provides protection during cardiac stress.</a> J Mol Cell Cardiol. 76, 106-115 (2014).</li><li>Yasuda, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dystrophic+heart+failure+blocked+by+membrane+sealant+poloxamer.">Dystrophic heart failure blocked by membrane sealant poloxamer.</a> Nature. 436 (7053), 1025-1029 (2005).</li><li>Townsend, D., Daly, M., Chamberlain, J. S., Metzger, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Age-dependent+dystrophin+loss+and+genetic+reconstitution+establish+a+molecular+link+between+dystrophin+and+heart+performance+during+aging.">Age-dependent dystrophin loss and genetic reconstitution establish a molecular link between dystrophin and heart performance during aging.</a> Mol Ther. 19 (10), 1821-1825 (2011).</li><li>Townsend, D., Yasuda, S., McNally, E., Metzger, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Distinct+pathophysiological+mechanisms+of+cardiomyopathy+in+hearts+lacking+dystrophin+or+the+sarcoglycan+complex.">Distinct pathophysiological mechanisms of cardiomyopathy in hearts lacking dystrophin or the sarcoglycan complex.</a> FASEB J. 25 (9), 3106-3114 (2011).</li><li>Pacher, P., Nagayama, T., Mukhopadhyay, P., B&#225;tkai, S., Kass, D. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Measurement+of+cardiac+function+using+pressure-volume+conductance+catheter+technique+in+mice+and+rats.">Measurement of cardiac function using pressure-volume conductance catheter technique in mice and rats.</a> Nat Protoc. 3 (9), 1422-1434 (2008).</li><li>Zhang, B., Davis, J. P., Ziolo, M. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cardiac+Catheterization+in+Mice+to+Measure+the+Pressure+Volume+Relationship:+Investigating+the+Bowditch+Effect.">Cardiac Catheterization in Mice to Measure the Pressure Volume Relationship: Investigating the Bowditch Effect.</a> J Vis Exp. (100), e52618-e52618 (2015).</li><li>Barnabei, M. S., Palpant, N. J., Metzger, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Influence+of+genetic+background+on+ex+vivo+and+in+vivo+cardiac+function+in+several+commonly+used+inbred+mouse+strains.">Influence of genetic background on ex vivo and in vivo cardiac function in several commonly used inbred mouse strains.</a> Physiol Genomics. 42A (2), 103-113 (2010).</li><li>Guo, X., Kono, Y., Mattrey, R., Kassab, G. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Morphometry+and+strain+distribution+of+the+C57BL/6+mouse+aorta.">Morphometry and strain distribution of the C57BL/6 mouse aorta.</a> Am J Physiol Heart Circ Physiol. 283 (5), H1829-H1837 (2002).</li><li>Weiss, R. M., Ohashi, M., Miller, J. D., Young, S. G., Heistad, D. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Calcific+aortic+valve+stenosis+in+old+hypercholesterolemic+mice.">Calcific aortic valve stenosis in old hypercholesterolemic mice.</a> Circulation. 114 (19), 2065-2069 (2006).</li><li>Palpant, N. J., Day, S. M., Herron, T. J., Converso, K. L., Metzger, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Single+histidine-substituted+cardiac+troponin+I+confers+protection+from+age-related+systolic+and+diastolic+dysfunction.">Single histidine-substituted cardiac troponin I confers protection from age-related systolic and diastolic dysfunction.</a> Cardiovasc Res. 80 (2), 209-218 (2008).</li><li>Palpant, N. J., D'Alecy, L. G., Metzger, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Single+histidine+button+in+cardiac+troponin+I+sustains+heart+performance+in+response+to+severe+hypercapnic+respiratory+acidosis+in+vivo.">Single histidine button in cardiac troponin I sustains heart performance in response to severe hypercapnic respiratory acidosis in vivo.</a> FASEB J. 23 (5), 1529-1540 (2009).</li><li>Palpant, N. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cardiac+disease+in+mucopolysaccharidosis+type+I+attributed+to+catecholaminergic+and+hemodynamic+deficiencies.">Cardiac disease in mucopolysaccharidosis type I attributed to catecholaminergic and hemodynamic deficiencies.</a> Am J Physiol Heart Circ Physiol. 300 (1), H356-H365 (2011).</li><li>Townsend, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diastolic+dysfunction+precedes+hypoxia-induced+mortality+in+dystrophic+mice.">Diastolic dysfunction precedes hypoxia-induced mortality in dystrophic mice.</a> Physiol Rep. 3 (8), e12513 (2015).</li><li>Schm&#228;hl, D., Port, R., Wahrendorf, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+dose-response+study+on+urethane+carcinogenesis+in+rats+and+mice.">A dose-response study on urethane carcinogenesis in rats and mice.</a> Int J Cancer. 19 (1), 77-80 (1977).</li><li>Freeman, G. L., Little, W. C., O'Rourke, R. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+effect+of+vasoactive+agents+on+the+left+ventricular+end-systolic+pressure-volume+relation+in+closed-chest+dogs.">The effect of vasoactive agents on the left ventricular end-systolic pressure-volume relation in closed-chest dogs.</a> Circulation. 74 (5), 1107-1113 (1986).</li><li>Reyes, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Enhancement+of+contractility+with+sustained+afterload+in+the+intact+murine+heart:+blunting+of+length-dependent+activation.">Enhancement of contractility with sustained afterload in the intact murine heart: blunting of length-dependent activation.</a> Circulation. 107 (23), 2962-2968 (2003).</li><li>Segers, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Conductance+catheter-based+assessment+of+arterial+input+impedance,+arterial+function,+and+ventricular-vascular+interaction+in+mice.">Conductance catheter-based assessment of arterial input impedance, arterial function, and ventricular-vascular interaction in mice.</a> Am J Physiol Heart Circ Physiol. 288 (3), H1157-H1164 (2005).</li><li>Townsend, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chronic+administration+of+membrane+sealant+prevents+severe+cardiac+injury+and+ventricular+dilatation+in+dystrophic+dogs.">Chronic administration of membrane sealant prevents severe cardiac injury and ventricular dilatation in dystrophic dogs.</a> J Clin Invest. 120 (4), 1140-1150 (2010).</li><li>Sato, T., Shishido, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=ESPVR+of+in+situ+rat+left+ventricle+shows+contractility-dependent+curvilinearity.">ESPVR of in situ rat left ventricle shows contractility-dependent curvilinearity.</a> Am J Physiol Heart Circ Physiol. 274 (5 Pt 2), H1429-H1434 (1998).</li><li>Sunagawa, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+coronary+arterial+pressure+on+left+ventricular+end-systolic+pressure-volume+relation+of+isolated+canine+heart.">Effects of coronary arterial pressure on left ventricular end-systolic pressure-volume relation of isolated canine heart.</a> Circ Res. 50 (5), 727-734 (1982).</li><li>Cingolani, H. E., P&#233;rez, N. G., Cingolani, O. H., Ennis, I. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Anrep+effect:+100+years+later.">The Anrep effect: 100 years later.</a> Am J Physiol Heart Circ Physiol. 304 (2), H175-H182 (2013).</li><li>Baan, J., van der Velde, E. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sensitivity+of+left+ventricular+end-systolic+pressure-volume+relation+to+type+of+loading+intervention+in+dogs.">Sensitivity of left ventricular end-systolic pressure-volume relation to type of loading intervention in dogs.</a> Circ Res. 62 (6), 1247-1258 (1988).</li><li>Rankin, J. S., Olsen, C. O., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+effects+of+airway+pressure+on+cardiac+function+in+intact+dogs.">The effects of airway pressure on cardiac function in intact dogs.</a> Circulation. 66 (1), 108-120 (1982).</li></ol>

The author has nothing to disclose.

ישנם שלושה שלבים קריטיים בהליך זה: 1) את המיקום של הטובוס ואוורור המתאים, 2) המיקום של קטטר IV הצוואר, ו -3) את המיקום הנכון של הקטטר PV בחדר השמאלי. קביעת קצב הנשימה המתאימה היא חלק חשוב של מתן תמיכה נשימתית. עכברים מודעים בדרך כלל לשמור על אוורור המכתשית עם נשימות שטחיות מה...

מחלות לב וכלי דם ממשיכה להיות גורם משמעותי לתמותה ותחלואה בעולם 1. מחלות של הלב להציב אתגרים קשים במיוחד בפיתוח טיפולים חדשים. התקדמות בגנטיקה לספק לאפשרות לזהות מספר רב של תורמים גנטיים פוטנציאל להתפתחות של מחלות לב. האופי האינטגרטיבי של מערכת הלב וכלי הדם מחייב המטרות הגנטיות הללו להיות מאומתים במודלים של בעלי חיים ללא פגע. הגמישות הגנטית והעלויות נמוכים דיור של העכבר הביאו אותו לקדמה עבור הערכת התפקיד הפיזיולוגי של גן מסוים. גודלו הקטן של העכבר מציבה מספר אתגרים ייחודיים להערכת תפקוד הלב. ישנן שיטות שיכולות לספק מידע לגבי תפקוד הלב, אבל רק מדידה בו זמנית של הלחץ חדרית ונפח מאפשר בנפח הלחץ (PV) ניתוח הלולאה של פונקציה חדרית. PV לולאות כלתפקוד לב ow להיות מנותח עצמאי של הקשר בינו לבין כלי הדם; גורם חשוב בקביעת התפקיד הפונקציונלי של מרכיב גנטי מסוים. הערכת לולאות לחצו-נפח נעשתה שימוש הוא בניסוי קליני במשך שנים רבות ספרות ענפה שקיימת לגבי הניתוח של נתונים אלה קובע 2,3. התאמת טכנולוגית לולאת PV העכבר כבר התקדמות חשובה להבנת פיזיולוגית murine לב 4-6. טכנולוגיות PV לולאת צנתר מבוסס זוג מתמר לחץ והשימוש מוליך להעריך נפח חדרית. היקף חדרית נקבע על ידי בחינת שינויי שדה חשמלי שנוצר על ידי קטטר. מודלי שיטה זו החדר כמו גליל, הגובה אשר מוגדר על ידי המרחק בין האלקטרודות על הקטטר ואת הרדיוס מחושבים הולכה של שדה חשמלי דרך הדםהחדר 7-9. אות מוליכות נמדדת הקטטר יש שני מרכיבים. הראשונה היא ההולכה דרך הדם; זה משתנה עם הנפח של החדר ומהווה האות העיקרית המשמשת לקביעת נפח חדרית. המרכיב השני נובע הולכה דרך ולאורך הקיר של החדר. זה נקרא מוליכות במקביל וצריך להסיר על מנת לקבוע את עוצמת קול חדרית המוחלטת. ישנן שתי מערכות זמינות מסחרית לאיסוף נתונים לחצו-נפח ששמש למחקר במעבדה לבין השיטה הנהוגה לחישוב ולהסיר מוליכות המקבילי ההבדל העיקרי ביניהם 6,10,11. צנתרים מוליכים דרש הזרקת סליין היפרטוני לחישוב מוליכות במקביל. הזרקה זה זמני משנה את המוליכות של דם החדר, בעוד המוליכות של הקיר נשארה קבועות. מנתונים אלה ניתן לקבוע אתרכיב של אות מוליכות שמקורה בדם ומה מגיע מקיר חדרית. גישה זו מניחה כי מוליכות במקביל אינן משתנות במהלך מחזור הלב. שיטת הקבלה מסתמכת על שינויים בשלב בתחום החשמל כדי להעריך את התרומה של קיר החדר לאות ההיקף הכולל. שיטה זו מסתמכת על מגוון של קבועים מראש עבור המוליכות של הדם לשריר הלב כדי לקבוע את עוצמת הקול הסופי, אבל עושה צעדים רציפים של מוליכות במקביל במהלך מחזור הלב. שתי מערכות אלה לספק הערכה טובה של נפח חדר השמאלי ואת ההבדלים ביניהם הם לא עשויים להיות משמעותיים מבחינה פיזיולוגית. המודל הגלילי של החדר והנחות אחרות העושה גישות אלה מבוססות קטטר לא מדויקות ככל שיטות אחרות, אך נתונים אלה הניתנים על בסיס פעימה אחרת פעימה כי הוא חיוני להערכת צעדים עצמאיים עומס של תפקוד לב. ההליך המתואר כאן משמש במעבדה שלי ספק נתונים עבור מספר רב של מחקרים הבוחנים את מנגנוני pathophysiological הבסיסיים של קרדיומיופתיה דיסטרופי 12-18. ההליך המתואר להלן הוא אחד משני שניתן להשתמש בהם כדי לקבל נתונים לולאה PV. בעוד רבים מן העקרונות חלים גם גישה, פרוטוקול זה יתמקד בגישת פסגה פתוח חזה; פרוטוקול החזה סגור כבר מפורט במקומות אחרים 19,20. בעוד הליך יתוארו בפירוט, עקרונות העל חשובים כדי לחשוף את הלב עם נזק מינימלי או ללב או לריאות. לאורך כל הפרוטוקול זה חשוב לזכור כי מדובר בהליך בלתי-הישרדות כי לאחר חשיפה טובה של הלב יש חשיבות קריטית עבור המיקום הנכון של הקטטר.

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measuring pressure volume loops in the mouse

הבנת הגורמים וההתקדמות של מחלת לב מהווה אתגר משמעותי לקהילה ביו. הגמישות הגנטית של העכבר מספקת פוטנציאל גדול כדי לחקור תפקוד לב ברמה המולקולרית. גודלו הקטן של העכבר עושה להציג כמה אתגרים בכל הקשור בביצוע phenotyping הלב מפורט. מזעור פיתוחים אחרים טכנולוגיה הפכו שיטות רבות של הערכה לבבית אפשרית העכבר. מבין אלה, אוסף סימולטני של נתונים בלחץ ונפח מספק תמונה מפורטת של תפקוד לב שאינו זמינה דרך כל אפנות אחרות. הנה נוהל מפורט לאיסוף נתוני לולאה לחץ-נפח מתואר. כולל דיון של העקרונות שבבסיס המדידים ואת המקורות הפוטנציאליים של שגיאה. ניהול הרדמה וגישות כירורגית נדונים בפירוט רב כפי שהם שניהם קריטי מדידה המודינמי באיכות גבוהה בהשגהים. עקרונות של פיתוח פרוטוקול המודינמי ואת ההיבטים הרלוונטיים של ניתוח נתונים גם מופנים.

לפי אמנה, נפח הוא זמם על ציר ה- X ואת הלחץ על ציר Y כמו באיור 1. הלולאות לחצו-הנפח כתוצאה מלחץ התוויית נגד נפח צריך להיות דומה מלבן, את הקצוות האנכיים המייצגים שינויי isovolumic בלחץ (כלומר, כאשר הן המיטרלי שסתומי עורקים סגורים). האופקי התחתון מי...

Watch this Scientific Journal Video about Measuring Pressure Volume Loops in the Mouse at JoVE.com

Measuring Pressure Volume Loops in the Mouse

כתב יד זה מתאר פרוטוקול מפורט לאיסוף נתונים לחץ-נפח מהעכבר.

מדידת לולאות נפח לחץ העכבר

Understanding the causes and progression of heart disease presents a significant challenge to the biomedical community. The genetic flexibility of the ...

measuring-pressure-volume-loops-in-the-mouse

Research

JoVE Journal

Biology

16.3K Views.  University of Minnesota.  כתב יד זה מתאר פרוטוקול מפורט לאיסוף נתונים לחץ-נפח מהעכבר. 

Video: Measuring Pressure Volume Loops in the Mouse

Measuring Left Ventricular Pressure in Late Embryonic and Neonatal Mice

Blood pressure increases significantly during embryonic and postnatal development in vertebrate animals. In the mouse, blood flow is first detectable around embryonic day (E) 8.51. Systolic left ventricular (LV) pressure is 2 mmHg at E9.5 and 11 mmHg at E14.52. At these mid-embryonic stages, the LV is clearly visible through the chest wall for invasive pressure measurements because the ribs and skin are not fully developed. Between E14.5 and birth (approximately E21) imaging methods must be used to view the LV. After birth, mean arterial pressure increases from 30 - 70 mmHg from postnatal day (P) 2 - 353. Beyond P20, arterial pressure can be measured with solid-state catheters (i.e. Millar or Scisense). Before P20, these catheters are too big for developing mouse arteries and arterial pressure must be measured with custom pulled plastic catheters attached to fluid-filled pressure transducers3 or glass micropipettes attached to servo null pressure transducers4.
Our recent work has shown that the greatest increase in blood pressure occurs during the late embryonic to early postnatal period in mice5-7. This large increase in blood pressure may influence smooth muscle cell (SMC) phenotype in developing arteries and trigger important mechanotransduction events. In human disease, where the mechanical properties of developing arteries are compromised by defects in extracellular matrix proteins (i.e. Marfan's Syndrome8 and Supravalvular Aortic Stenosis9) the rapid changes in blood pressure during this period may contribute to disease phenotype and severity through alterations in mechanotransduction signals. Therefore, it is important to be able to measure blood pressure changes during late embryonic and neonatal periods in mouse models of human disease.
We describe a method for measuring LV pressure in late embryonic (E18) and early postnatal (P1 - 20) mice. A needle attached to a fluid-filled pressure transducer is inserted into the LV under ultrasound guidance. Care is taken to maintain normal cardiac function during the experimental protocol, especially for the embryonic mice. Representative data are presented and limitations of the protocol are discussed.

Measuring left ventricular pressure (LV) in embryonic and neonatal mice is described. Pressure is measured by inserting a needle connected to a fluid-filled transducer into the LV under ultrasound guidance. Care must be taken to maintain normal cardiac function during the experimental protocol.

מדידת לחץ חדרית השמאל עכברים עובריים ילודים המאוחרת

Blood pressure increases significantly during embryonic and postnatal development in vertebrate animals. In the mouse, blood flow is first detectable ...

Bioengineering

Right Ventricular Systolic Pressure Measurements in Combination with Harvest of Lung and Immune Tissue Samples in Mice

The function of the right heart is to pump blood through the lungs, thus linking right heart physiology and pulmonary vascular physiology. Inflammation is a common modifier of heart and lung function, by elaborating cellular infiltration, production of cytokines and growth factors, and by initiating remodeling processes 1.
Compared to the left ventricle, the right ventricle is a low-pressure pump that operates in a relatively narrow zone of pressure changes. Increased pulmonary artery pressures are associated with increased pressure in the lung vascular bed and pulmonary hypertension 2. Pulmonary hypertension is often associated with inflammatory lung diseases, for example chronic obstructive pulmonary disease, or autoimmune diseases 3. Because pulmonary hypertension confers a bad prognosis for quality of life and life expectancy, much research is directed towards understanding the mechanisms that might be targets for pharmaceutical intervention 4. The main challenge for the development of effective management tools for pulmonary hypertension remains the complexity of the simultaneous understanding of molecular and cellular changes in the right heart, the lungs and the immune system.
Here, we present a procedural workflow for the rapid and precise measurement of pressure changes in the right heart of mice and the simultaneous harvest of samples from heart, lungs and immune tissues. The method is based on the direct catheterization of the right ventricle via the jugular vein in close-chested mice, first developed in the late 1990s as surrogate measure of pressures in the pulmonary artery5-13. The organized team-approach facilitates a very rapid right heart catheterization technique. This makes it possible to perform the measurements in mice that spontaneously breathe room air. The organization of the work-flow in distinct work-areas reduces time delay and opens the possibility to simultaneously perform physiology experiments and harvest immune, heart and lung tissues.
The procedural workflow outlined here can be adapted for a wide variety of laboratory settings and study designs, from small, targeted experiments, to large drug screening assays. The simultaneous acquisition of cardiac physiology data that can be expanded to include echocardiography5,14-17 and harvest of heart, lung and immune tissues reduces the number of animals needed to obtain data that move the scientific knowledge basis forward. The procedural workflow presented here also provides an ideal basis for gaining knowledge of the networks that link immune, lung and heart function. The same principles outlined here can be adapted to study other or additional organs as needed.

A specific and rapid protocol to simultaneously investigate right heart function, lung inflammation, and the immune response is described as a learning tool. Video and figures describe physiology and microdissection techniques in an organized team-approach that is adaptable to be used for small to large sized studies.

מדידות נכונות חדרית סיסטולי לחץ בשילוב עם קציר של ריאה ודגימות רקמה חיסוניות בעכברים

The function of the right heart is to pump blood through the lungs, thus linking right heart physiology and pulmonary vascular physiology. Inflammation is ...

Immunology and Infection

Measuring Blood Pressure in Mice using Volume Pressure Recording, a Tail-cuff Method

The CODA 8-Channel High Throughput Non-Invasive Blood Pressure system measures the blood pressure in up to 8 mice or rats simultaneously. The CODA tail-cuff system uses Volume Pressure Recording (VPR) to measure the blood pressure by determining the tail blood volume. A specially designed differential pressure transducer and an occlusion tail-cuff measure the total blood volume in the tail without the need to obtain the individual pulse signal. Special attention is afforded to the length of the occlusion cuff in order to derive the most accurate blood pressure readings. VPR can easily obtain readings on dark-skinned rodents, such as C57BL6 mice and is MRI compatible. The CODA system provides you with measurements of six (6) different blood pressure parameters; systolic and diastolic blood pressure, heart rate, mean blood pressure, tail blood flow, and tail blood volume. Measurements can be made on either awake or anesthetized mice or rats. The CODA system includes a controller, laptop computer, software, cuffs, animal holders, infrared warming pads, and an infrared thermometer. There are seven different holder sizes for mice as small as 8 grams to rats as large as 900 grams.

The CODA 8-Channel High Throughput Non-Invasive Blood Pressure system measures the blood pressure in up to 8 mice or rats simultaneously. This tail-cuff system uses Volume Pressure Recording (VPR) to measure the blood pressure by determining the tail blood volume.

מדידת לחץ דם בעכברים באמצעות לחץ נפח הקלטה, שיטת זנב השרוול

The CODA 8-Channel High Throughput Non-Invasive Blood Pressure system measures the blood pressure in up to 8 mice or rats simultaneously. The CODA ...

Catheterization of Intestinal Loops in Ruminants

The intestine is a complex structure that is involved not only in absorption of nutrients, but also acts as a barrier between the individual and the outside world. As such, the intestine plays a pivotal role in immunosurveillance and protection from enteric pathogens. Investigating intestinal physiology and immunology commonly employs 'intestinal loops' as an experimental model. The majority of these loop models are non-recovery surgical procedures that study short-term (&lt;24 hr) changes in the intestine (1-3). We previously created a recovery intestinal loop model to specifically measure long-term (&lt;6 mo) immunological changes in the intestine of sheep following exposure to vaccines, adjuvants, and viruses (4). This procedure localized treatments to a specific 'loop', allowing us to sample this area of the intestine. A significant drawback of this method is the single window of opportunity to administer treatments (i.e. at the time of surgery). Furthermore, samples of both the intestinal mucosa and luminal contents can only be taken at the termination of the project. Other salient limitations of the above model are that the surgical manipulation and requisite post-operative measures (e.g. administration of antibiotics and analgesics) can directly affect the treatment itself and/or alter immune function, thereby confounding results. Therefore, we modified our intestinal loop model by inserting long-term catheters into the loops. Sheep recover fully from the procedure, and are unaffected by the exteriorized catheters. Notably, the establishment of catheters in loops allows us to introduce multiple treatments over an extended interval, following recovery from surgery and clearance of drugs administered during surgery and the post-operative period.

We describe a novel surgical method for catheterizing 'intestinal loops' within the ileum of sheep. Once animals have recovered from surgery and have cleared antibiotics and analgesics, multiple treatments can be deposited directly in loops via the catheters.

צנתור של לולאות מעיים של מעלי גירה

The intestine is a complex structure that is involved not only in absorption of nutrients, but also acts as a barrier between the individual and the ...

Measurement of the Pressure-volume Curve in Mouse Lungs

In recent decades the mouse has become the primary animal model of a variety of lung diseases. In models of emphysema or fibrosis, the essential phenotypic changes are best assessed by measurement of the changes in lung elasticity. To best understand specific mechanisms underlying such pathologies in mice, it is essential to make functional measurements that can reflect the developing pathology. Although there are many ways to measure elasticity, the classical method is that of the total lung pressure-volume (PV) curve done over the whole range of lung volumes. This measurement has been made on adult lungs from nearly all mammalian species dating back almost 100 years, and such PV curves also played a major role in the discovery and understanding of the function of pulmonary surfactant in fetal lung development. Unfortunately, such total PV curves have not been widely reported in the mouse, despite the fact that they can provide useful information on the macroscopic effects of structural changes in the lung. Although partial PV curves measuring just the changes in lung volume are sometimes reported, without a measure of absolute volume, the nonlinear nature of the total PV curve makes these partial ones very difficult to interpret. In the present study, we describe a standardized way to measure the total PV curve. We have then tested the ability of these curves to detect changes in mouse lung structure in two common lung pathologies, emphysema and fibrosis. Results showed significant changes in several variables consistent with expected structural changes with these pathologies. This measurement of the lung PV curve in mice thus provides a straightforward means to monitor the progression of the pathophysiologic changes over time and the potential effect of therapeutic procedures.

Here we present a protocol to simply and reliably measure the lung pressure-volume curve in mice, showing that it is sufficiently sensitive to detect phenotypic parenchymal changes in two common lung pathologies, pulmonary fibrosis and emphysema. This metric provides a means to quantify the lung&#8217;s structural changes with developing pathology.

מדידה של עקומת לחץ-נפח ריאות עכבר

In recent decades the mouse has become the primary animal model of a variety of lung diseases. In models of emphysema or fibrosis, the essential ...

Medicine

Cardiac Catheterization in Mice to Measure the Pressure Volume Relationship: Investigating the Bowditch Effect

Animal models that mimic human cardiac disorders have been created to test potential therapeutic strategies. A key component to evaluating these strategies is to examine their effects on heart function. There are several techniques to measure in vivo cardiac mechanics (e.g., echocardiography, pressure/volume relations, etc.). Compared to echocardiography, real-time left ventricular (LV) pressure/volume analysis via catheterization is more precise and insightful in assessing LV function. Additionally, LV pressure/volume analysis provides the ability to instantaneously record changes during manipulations of contractility (e.g., &#946;-adrenergic stimulation) and pathological insults (e.g., ischemia/reperfusion injury). In addition to the maximum (+dP/dt) and minimum (-dP/dt) rate of pressure change in the LV, an accurate assessment of LV function via several load-independent indexes (e.g., end systolic pressure volume relationship and preload recruitable stroke work) can be attained. Heart rate has a significant effect on LV contractility such that an increase in the heart rate is the primary mechanism to increase cardiac output (i.e., Bowditch effect). Thus, when comparing hemodynamics between experimental groups, it is necessary to have similar heart rates. Furthermore, a hallmark of many cardiomyopathy models is a decrease in contractile reserve (i.e., decreased Bowditch effect). Consequently, vital information can be obtained by determining the effects of increasing heart rate on contractility. Our and others data has demonstrated that the neuronal nitric oxide synthase (NOS1) knockout mouse has decreased contractility. Here we describe the procedure of measuring LV pressure/volume with increasing heart rates using the NOS1 knockout mouse model.

This article describes the measurement of murine left ventricular function via pressure/volume analysis at different heart rates.

צנתור לב בעכברים כדי למדוד את יחסי נפח לחץ: חקירת אפקט Bowditch

Animal models that mimic human cardiac disorders have been created to test potential therapeutic strategies. A key component to evaluating these ...

Biventricular Assessment of Cardiac Function and Pressure-Volume Loops by Closed-Chest Catheterization in Mice

Assessment of cardiac function is essential to conduct cardiovascular and pulmonary-vascular preclinical research. Pressure-volume loops (PV loops) generated by recording both pressure and volume during cardiac catheterization are vital when assessing both systolic and diastolic cardiac function. Left and right heart function are closely related, reflected in ventricular interdependence. Thus, recording biventricular function in the same animal is important to get a complete assessment of cardiac function. In this protocol, a closed chest approach to cardiac catheterization consistent with the way catheterization is performed in patients is adopted in mice. While challenging, the closed chest strategy is a more physiological approach, because opening the chest results in major changes in preload and afterload that create artifacts, most notably a fall in systemic blood pressure. While high-resolution echocardiography is used to assess rodents, cardiac catheterization is invaluable, particularly when assessing diastolic pressures in both ventricles.
Described here is a procedure to perform invasive, closed chest, sequential left and right ventricular pressure-volume (PV) loops in the same animal. PV loops are acquired using&#160;admittance technology with a mouse pressure-volume catheter and pressure-volume system acquisition. The procedure is described, beginning with the neck dissection, which is required to access the right jugular vein and the right carotid artery, to the insertion and positioning of the catheter, and finally the data acquisition. Then, the criteria required to ensure the acquisition of high-quality PV loops are discussed. Finally, the analysis of the left and right ventricular PV loops and the different hemodynamic parameters available to quantify systolic and diastolic ventricular function are briefly described.

Presented here is a protocol to assess biventricular heart function in mice by generating pressure-volume (PV) loops from the right and left ventricle in the same animal using closed chest catheterization. The focus is on the technical aspect of surgery and data acquisition.

הערכה דו-חדרית של תפקוד הלב ולולאות נפח לחץ על ידי צנתור חזה סגור בעכברים

Assessment of cardiac function is essential to conduct cardiovascular and pulmonary-vascular preclinical research. Pressure-volume loops (PV loops) ...

Cardiac Response to &#946;-Adrenergic Stimulation Determined by Pressure-Volume Loop Analysis

Determination of the cardiac function is a robust endpoint analysis in animal models of cardiovascular diseases in order to characterize effects of specific treatments on the heart. Due to the feasibility of genetic manipulations the mouse has become the most common mammalian animal model to study cardiac function and to search for new potential therapeutic targets. Here we describe a protocol to determine cardiac function&#160;in vivo using pressure-volume loop measurements and analysis during basal conditions and under &#946;-adrenergic stimulation by intravenous infusion of increasing concentrations of isoproterenol. We provide a refined protocol including ventilation support taking into account the positive end-expiratory pressure to ameliorate negative effects during open-chest measurements, and potent analgesia (Buprenorphine) to avoid uncontrollable myocardial stress evoked by pain during the procedure. All together the detailed description of the procedure and discussion about possible pitfalls enables highly standardized and reproducible pressure-volume loop analysis, reducing the exclusion of animals from the experimental cohort by preventing possible methodological bias.

Here we describe a cardiac pressure-volume loop analysis under increasing doses of intravenously infused isoproterenol to determine the intrinsic cardiac function and the &#946;-adrenergic reserve in mice. We use a modified open-chest approach for the pressure-volume loop measurements, in which we include ventilation with positive end-expiratory pressure.

תגובת לב לגירוי β-אדנרגיות שנקבע על ידי ניתוח לולאת נפח לחץ

Determination of the cardiac function is a robust endpoint analysis in animal models of cardiovascular diseases in order to characterize effects of ...

Cardiac Pressure-Volume Loop Analysis Using Conductance Catheters in Mice

Cardiac pressure-volume loop analysis is the &#8220;gold-standard&#8221; in the assessment of load-dependent and load-independent measures of ventricular systolic and diastolic function. Measures of ventricular contractility and compliance are obtained through examination of cardiac response to changes in afterload and preload. These techniques were originally developed nearly three decades ago to measure cardiac function in large mammals and humans. The application of these analyses to small mammals, such as mice, has been accomplished through the optimization of microsurgical techniques and creation of conductance catheters. Conductance catheters allow for estimation of the blood pool by exploiting the relationship between electrical conductance and volume. When properly performed, these techniques allow for testing of cardiac function in genetic mutant mouse models or in drug treatment studies. The accuracy and precision of these studies are dependent on careful attention to the calibration of instruments, systematic conduct of hemodynamic measurements and data analyses. We will review the methods of conducting pressure-volume loop experiments using a conductance catheter in mice.

Cardiac pressure-volume loop analysis is the most comprehensive way to measure cardiac function in the intact heart. We describe a technique to perform and analyze cardiac pressure volume loops, using conductance catheters.

לחץ-נפח לב ניתוח לולאה באמצעות מוליכות קטטרים בעכברים

Cardiac pressure-volume loop analysis is the &#8220;gold-standard&#8221; in the assessment of load-dependent and load-independent measures of ventricular ...

חקירת ביצועי לב תלויי HR באמצעות פרוטוקול קצב פרוזדורים

A Pacing-Controlled Procedure for the Assessment of Heart Rate-Dependent Diastolic Functions in Murine Heart Failure Models

Heart failure with preserved ejection fraction (HFpEF) is a condition characterized by diastolic dysfunction and exercise intolerance. While exercise-stressed hemodynamic tests or MRI can be used to detect diastolic dysfunction and diagnose HFpEF in humans, such modalities are limited in basic research using mouse models. A treadmill exercise test is commonly used for this purpose in mice, but its results can be influenced by body weight, skeletal muscle strength, and mental state. Here, we describe an atrial-pacing protocol to detect heart rate (HR)-dependent changes in diastolic performance and validate its usefulness in a mouse model of HFpEF. The method involves anesthetizing, intubating, and performing pressure-volume (PV) loop analysis concomitant with atrial pacing. In this work, a conductance catheter was inserted via a left ventricular apical approach, and an atrial pacing catheter was placed in the esophagus. Baseline PV loops were collected before the HR was slowed with ivabradine. PV loops were collected and analyzed at HR increments ranging from 400 bpm to 700 bpm via atrial pacing. Using this protocol, we clearly demonstrated HR-dependent diastolic impairment in a metabolically induced HFpEF model. Both the relaxation time constant (Tau) and the end-diastolic pressure-volume relationship (EDPVR) worsened as the HR increased compared to control mice. In conclusion, this atrial pacing-controlled protocol is useful for detecting HR-dependent cardiac dysfunctions. It provides a new way to study the underlying mechanisms of diastolic dysfunction in HFpEF mouse models and may help develop new treatments for this condition.

מחבר זרקור: חקירת תפקוד לב תלוי HR במודלים של עכברים באמצעות גישה חדשנית לקצב פרוזדורים 

The present protocol describes obtaining the pressure-volume relationship through transesophageal pacing, which serves as a valuable tool in evaluating diastolic function&#160;in mouse models of heart failure.