Top

Published in:

Open Access 01-05-2010 | Original Paper

Effects of mild hypothermia on hemodynamics in cardiac arrest survivors and isolated failing human myocardium

Authors: Claudius Jacobshagen, Theresa Pelster, Anja Pax, Wiebke Horn, Stephan Schmidt-Schweda, Bernhard W. Unsöld, Tim Seidler, Stephan Wagner, Gerd Hasenfuss, Lars S. Maier

Published in: Clinical Research in Cardiology | Issue 5/2010

Abstract

Post-cardiac arrest myocardial dysfunction is a common phenomenon after return of spontaneous circulation (ROSC) and contributes to hemodynamic instability and low survival rates after cardiac arrest. Mild hypothermia for 24 h after ROSC has been shown to significantly improve neurologic recovery and survival rates. In the present study we investigate the influence of therapeutic hypothermia on hemodynamic parameters in resuscitated patients and on contractility in failing human myocardium. We analyzed hemodynamic data from 200 cardiac arrest survivors during the hypothermia period. The initial LVEF was 32.6 ± 1.2% indicating a significantly impaired LV function. During hypothermia induction, the infusion rate of epinephrine could be significantly reduced from 9.1 ± 1.3 μg/min [arrival intensive care unit (ICU) 35.4°C] to 4.6 ± 1.0 μg/min (34°C) and 2.8 ± 0.5 μg/min (33°C). The dobutamine and norepinephrine application rates were not changed significantly. The mean arterial blood pressure remained stable. The mean heart rate significantly decreased from 91.8 ± 1.7 bpm (arrival ICU) to 77.3 ± 1.5 bpm (34°C) and 70.3 ± 1.4 bpm (33°C). In vitro we investigated the effect of hypothermia on isolated ventricular muscle strips from explanted failing human hearts. With decreasing temperature, the contractility increased to a maximum of 168 ± 23% at 27°C (n = 16, P < 0.05). Positive inotropic response to hypothermia was accompanied by moderately increased rapid cooling contractures as a measure of sarcoplasmic reticulum (SR) Ca²⁺ content, but can be elicited even when the SR Ca²⁺ release is blocked in the presence of ryanodine. Contraction and relaxation kinetics are prolonged with hypothermia, indicating increased Ca²⁺ sensitivity as the main mechanism responsible for inotropy. In conclusion, mild hypothermia stabilizes hemodynamics in cardiac arrest survivors which might contribute to improved survival rates in these patients. Mechanistically, we demonstrate that hypothermia improves contractility in failing human myocardium most likely by increasing Ca²⁺-sensitivity.

Available only for authorised users

Fredriksson M, Herlitz J, Nichol G (2003) Variation in outcome in studies of out-of-hospital cardiac arrest: a review of studies conforming to the Utstein guidelines. Am J Emerg Med 21:276–281CrossRefPubMed

Nichol G, Thomas E, Callaway CW, Hedges J, Powell JL, Aufderheide TP, Rea T, Lowe R, Brown T, Dreyer J, Davis D, Idris A, Stiell I (2008) Regional variation in out-of-hospital cardiac arrest incidence and outcome. JAMA 300:1423–1431CrossRefPubMed

Ehlenbach WJ, Barnato AE, Curtis JR, Kreuter W, Koepsell TD, Deyo RA, Stapleton RD (2009) Epidemiologic study of in-hospital cardiopulmonary resuscitation in the elderly. N Engl J Med 361:22–31CrossRefPubMed

Nadkarni VM, Larkin GL, Peberdy MA, Carey SM, Kaye W, Mancini ME, Nichol G, Lane-Truitt T, Potts J, Ornato JP, Berg RA, for the National Registry of Cardiopulmonary Resuscitation Investigators (2006) First documented rhythm and clinical outcome from in-hospital cardiac arrest among children and adults. JAMA 295:50–57CrossRefPubMed

Gazmuri RJ, Weil MH, Bisera J, Tang W, Fukui M, McKee D (1996) Myocardial dysfunction after successful resuscitation from cardiac arrest. Crit Care Med 24:992–1000CrossRefPubMed

Laurent I, Monchi M, Chiche JD, Joly LM, Spaulding C, Bourgeois B, Cariou A, Rozenberg A, Carli P, Weber S, Dhainaut JF (2002) Reversible myocardial dysfunction in survivors of out-of-hospital cardiac arrest. J Am Coll Cardiol 40:2110–2116CrossRefPubMed

Ruiz-Bailen M, de guayo HE, Ruiz-Navarro S, az-Castellanos MA, Rucabado-Aguilar L, Gomez-Jimenez FJ, Martinez-Escobar S, Moreno RM, Fierro-Roson J (2005) Reversible myocardial dysfunction after cardiopulmonary resuscitation. Resuscitation 66:175–181CrossRefPubMed

Herlitz J, Ekstrom L, Wennerblom B, Axelsson A, Bang A, Holmberg S (1995) Hospital mortality after out-of-hospital cardiac arrest among patients found in ventricular fibrillation. Resuscitation 29:11–21CrossRefPubMed

Laver S, Farrow C, Turner D, Nolan J (2004) Mode of death after admission to an intensive care unit following cardiac arrest. Intensive Care Med 30:2126–2128CrossRefPubMed

10.

The Hypothermia after Cardiac Arrest Study Group (2002) Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 346:549–556CrossRef

11.

Holzer M, Bernard SA, Hachimi-Idrissi S, Roine RO, Sterz F, Mullner M (2005) Hypothermia for neuroprotection after cardiac arrest: systematic review and individual patient data meta-analysis. Crit Care Med 33:414–418CrossRefPubMed

12.

Neumar RW, Nolan JP, Adrie C, Aibiki M, Berg RA, Bottiger BW, Callaway C, Clark RSB, Geocadin RG, Jauch EC, Kern KB, Laurent I, Longstreth WT Jr, Merchant RM, Morley P, Morrison LJ, Nadkarni V, Peberdy MA, Rivers EP, Rodriguez-Nunez A, Sellke FW, Spaulding C, Sunde K, Vanden Hoek T (2008) Post-Cardiac Arrest Syndrome: Epidemiology, Pathophysiology, Treatment, and Prognostication A Consensus Statement From the International Liaison Committee on Resuscitation (American Heart Association, Australian and New Zealand Council on Resuscitation, European Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Asia, and the Resuscitation Council of Southern Africa); the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; and the Stroke Council. Circulation 118:2452–2483CrossRefPubMed

13.

International Liaison Committee on Resuscitation (2005) Proceedings of the 2005 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations. Resuscitation 67:157–341

14.

Storm C, Schefold JC, Kerner T, Schmidbauer W, Gloza J, Krueger A, Jorres A, Hasper D (2008) Prehospital cooling with hypothermia caps (PreCoCa): a feasibility study. Clin Res Cardiol 97:768–772CrossRefPubMed

15.

Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, Smith K (2002) Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 346:557–563CrossRefPubMed

16.

Weisser J, Martin J, Bisping E, Maier LS, Beyersdorf F, Hasenfuss G, Pieske B (2001) Influence of mild hypothermia on myocardial contractility and circulatory function. Basic Res Cardiol 96:198–205CrossRefPubMed

17.

Shattock MJ, Bers DM (1987) Inotropic response to hypothermia and the temperature-dependence of ryanodine action in isolated rabbit and rat ventricular muscle: implications for excitation–contraction coupling. Circ Res 61:761–771PubMed

18.

Langendorff O (1897) Untersuchungen am überlebenden Säugetierherzen. Über den Einfluss von Wärme und Kälte auf das Herz der warmblütigen Tiere. Pflugers Arch 355–400

19.

Sprung J, Stowe DF, Kampine JP, Bosnjak ZJ (1994) Hypothermia modifies anesthetic effect on contractile force and Ca2+ transients in cardiac Purkinje fibers. Am J Physiol 267:H725–H733PubMed

20.

Goetzenich A, Schroth SC, Emmig U, Autschbach R, Pieske B, Rossaint R, Christiansen S (2009) Hypothermia exerts negative inotropy in human atrial preparations: in vitro-comparison to rabbit myocardium. J Cardiovasc Surg (Torino) 50:239–245

21.

Herren T, Gerber PA, Duru F (2009) Arrhythmogenic right ventricular cardiomyopathy/dysplasia: a not so rare “disease of the desmosome” with multiple clinical presentations. Clin Res Cardiol 98:141–158CrossRefPubMed

22.

Nalenz C, Konradi D, Blank R, Rupprecht HJ (2007) 58-year-old patient with cardiac arrest due to coronary spasm. Clin Res Cardiol 96:824–828CrossRefPubMed

23.

Strauss M, Gitt AK, Becker T, Kleemann T, Schiele R, Darius H, Junger C, Senges J, Seidl K (2008) Prehospital cardiac arrest: a marker for higher mortality in patients with acute myocardial infarction and moderately reduced left ventricular function: results from the MITRA plus registry. Clin Res Cardiol 97:748–752CrossRefPubMed

24.

Jung C, Ferrari M, Rodiger C, Fritzenwanger M, Figulla HR (2008) Combined impella and intra-aortic balloon pump support to improve macro- and microcirculation: a clinical case. Clin Res Cardiol 97:849–850CrossRefPubMed

25.

Lam K, Sjauw KD, Henriques JP, Ince C, de Mol BA (2009) Improved microcirculation in patients with an acute ST-elevation myocardial infarction treated with the Impella LP2.5 percutaneous left ventricular assist device. Clin Res Cardiol 98:311–318CrossRefPubMed

26.

Jung C, Rodiger C, Fritzenwanger M, Schumm J, Lauten A, Figulla HR, Ferrari M (2009) Acute microflow changes after stop and restart of intra-aortic balloon pump in cardiogenic shock. Clin Res Cardiol 98:469–475CrossRefPubMed

27.

Pieske B, Maier LS, Bers DM, Hasenfuss G (1999) Ca2+ handling and sarcoplasmic reticulum Ca2+ content in isolated failing and nonfailing human myocardium. Circ Res 85:38–46PubMed

28.

Sossalla S, Wagner S, Rasenack ECL, Ruff H, Weber SL, Schöndube FA, Tirilomis T, Tenderich G, Hasenfuss G, Belardinelli L, Maier LS (2008) Ranolazine improves diastolic dysfunction in isolated myocardium from failing human hearts—role of late sodium current and intracellular ion accumulation. J Mol Cell Cardiol 45:32–43CrossRefPubMed

29.

Mulieri LA, Hasenfuss G, Ittleman F, Blanchard EM, Alpert NR (1989) Protection of human left ventricular myocardium from cutting injury with 2, 3-butanedione monoxime. Circ Res 65:1441–1449PubMed

30.

Hasenfuss G, Pieske B (2002) Calcium cycling in congestive heart failure. J Mol Cell Cardiol 34:951–969CrossRefPubMed

31.

Hasenfuss G, Reinecke H, Studer R, Meyer M, Pieske B, Holtz J, Holubarsch C, Posival H, Just H, Drexler H (1994) Relation between myocardial function and expression of sarcoplasmic reticulum Ca(2+)-ATPase in failing and nonfailing human myocardium. Circ Res 75:434–442PubMed

32.

Blinks JR, Endoh M (1986) Modification of myofibrillar responsiveness to Ca++ as an inotropic mechanism. Circulation 73:III85–III98PubMed

33.

Churcott CS, Moyes CD, Bressler BH, Baldwin KM, Tibbits GF (1994) Temperature and pH effects on Ca2+ sensitivity of cardiac myofibrils: a comparison of trout with mammals. Am J Physiol 267:R62–R70PubMed

34.

Fabiato A, Fabiato F (1978) Effects of pH on the myofilaments and the sarcoplasmic reticulum of skinned cells from cardiac and skeletal muscles. J Physiol 276:233–255PubMed

35.

Henderson AH, Cattell MR (1976) Length-induced changes in activation during contraction. A study of mechanical oscillations in strontium-mediated contractions of cat and frog heart muscle. Circ Res 38:289–296PubMed

36.

Abraham TP, Jones M, Kazmierczak K, Liang HY, Pinheiro AC, Wagg CS, Lopaschuk GD, Szczesna-Cordary D (2009) Diastolic dysfunction in familial hypertrophic cardiomyopathy transgenic model mice. Cardiovasc Res 82:84–92CrossRefPubMed

37.

Kern KB, Berg RA, Hilwig RW, Larson DF, Gaballa MA (2008) Myocardial cytokine IL-8 and nitric oxide synthase activity during and after resuscitation: preliminary observations in regards to post-resuscitation myocardial dysfunction. Resuscitation 77:401–409CrossRefPubMed

38.

McCaul CL, McNamara P, Engelberts D, Slorach C, Hornberger LK, Kavanagh BP (2006) The effect of global hypoxia on myocardial function after successful cardiopulmonary resuscitation in a laboratory model. Resuscitation 68:267–275CrossRefPubMed

39.

Kern KB, Hilwig RW, Berg RA, Rhee KH, Sanders AB, Otto CW, Ewy GA (1997) Postresuscitation left ventricular systolic and diastolic dysfunction: treatment with dobutamine. Circulation 95:2610–2613PubMed

40.

Hettwer S, Panzner-Grote B, Witthaut R, Werdan K (2007) Isolated diastolic dysfunction–diagnostic value of tissue Doppler imaging, colour M-mode and N-terminal pro B-type natriuretic peptide. Clin Res Cardiol 96:874–882CrossRefPubMed

41.

Reil JC, Bohm M (2007) The role of heart rate in the development of cardiovascular disease. Clin Res Cardiol 96:585–592CrossRefPubMed

42.

Huang L, Weil MH, Tang W, Sun S, Wang J (2005) Comparison between dobutamine and levosimendan for management of postresuscitation myocardial dysfunction. Crit Care Med 33:487–491CrossRefPubMed

43.

Felker GM, O’Connor CM (2001) Inotropic therapy for heart failure: an evidence-based approach. Am Heart J 142:393–401CrossRefPubMed

44.

Packer M, Carver JR, Rodeheffer RJ, Ivanhoe RJ, DiBianco R, Zeldis SM, Hendrix GH, Bommer WJ, Elkayam U, Kukin ML (1991) Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group. N Engl J Med 325:1468–1475PubMedCrossRef

45.

Overgaard CB, Dzavik V (2008) Inotropes and vasopressors: review of physiology and clinical use in cardiovascular disease. Circulation 118:1047–1056CrossRefPubMed

46.

Miki T, Liu GS, Cohen MV, Downey JM (1998) Mild hypothermia reduces infarct size in the beating rabbit heart: a practical intervention for acute myocardial infarction? Basic Res Cardiol 93:372–383CrossRefPubMed

47.

Kuhn LA, Apter R, Weinrauch H, Jacobson TE, Meltzer L (1963) Hemodynamic and metabolic effects of skin and blood-stream cooling in experimental myocardial infarction with shock. Am J Cardiol 12:795–801CrossRefPubMed

48.

Schmidt-Schweda S, Ohler A, Grothe A, Pieske B (2004) Mild hypothermia in cardiogenic shock (COOL-SHOCK). Eur Heart J 25(Suppl 1):653–654

49.

Lewis ME, Al-Khalidi AH, Townend JN, Coote J, Bonser RS (2002) The effects of hypothermia on human left ventricular contractile function during cardiac surgery. J Am Coll Cardiol 39:102–108CrossRefPubMed

50.

Vasquez A, Kern KB, Hilwig RW, Heidenreich J, Berg RA, Ewy GA (2004) Optimal dosing of dobutamine for treating post-resuscitation left ventricular dysfunction. Resuscitation 61:199–207CrossRefPubMed

51.

Adrie C, dib-Conquy M, Laurent I, Monchi M, Vinsonneau C, Fitting C, Fraisse F, nh-Xuan AT, Carli P, Spaulding C, Dhainaut JF, Cavaillon JM (2002) Successful cardiopulmonary resuscitation after cardiac arrest as a “sepsis-like” syndrome. Circulation 106:562–568CrossRefPubMed

52.

Karimova A, Pinsky DJ (2001) The endothelial response to oxygen deprivation: biology and clinical implications. Intensive Care Med 27:19–31CrossRefPubMed

53.

Debrunner M, Schuiki E, Minder E, Straumann E, Naegeli B, Mury R, Bertel O, Frielingsdorf J (2008) Proinflammatory cytokines in acute myocardial infarction with and without cardiogenic shock. Clin Res Cardiol 97:298–305CrossRefPubMed

54.

Reinhart K, Brunkhorst FM, Bone HG, Gerlach H, Grundling M, Kreymann G, Kujath P, Marggraf G, Mayer K, Meier-Hellmann A, Peckelsen C, Putensen C, Stuber F, Quintel M, Ragaller M, Rossaint R, Weiler N, Welte T, Werdan K (2006) Diagnosis and therapy of sepsis. Clin Res Cardiol 95:429–454CrossRefPubMed

Title: Effects of mild hypothermia on hemodynamics in cardiac arrest survivors and isolated failing human myocardium
Authors: Claudius Jacobshagen
Theresa Pelster
Anja Pax
Wiebke Horn
Stephan Schmidt-Schweda
Bernhard W. Unsöld
Tim Seidler
Stephan Wagner
Gerd Hasenfuss
Lars S. Maier
Publication date: 01-05-2010
Publisher: Springer-Verlag
Published in: Clinical Research in Cardiology / Issue 5/2010
Print ISSN: 1861-0684
Electronic ISSN: 1861-0692
DOI: https://doi.org/10.1007/s00392-010-0113-2

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Effects of mild hypothermia on hemodynamics in cardiac arrest survivors and isolated failing human myocardium

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 5/2010

The corrected QT interval in 24 h ECGs in neonates

Intrathoracic impedance monitoring detecting pneumonia

The risk of non-sustained ventricular tachycardia after percutaneous alcohol septal ablation in patients with hypertrophic obstructive cardiomyopathy

Prognostic value of galectin-3, a novel marker of fibrosis, in patients with chronic heart failure: data from the DEAL-HF study

Percutaneous successful closure of dual atrial septal defect with two Amplatzer septal occluder devices

Utility of NT-pro-BNP in patients undergoing transapical aortic valve replacement

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page