Myocardial protection in the intensive care unit

Current Opinion in Critical Care

Volumn 5, Issue 5, 1999, Pages 400-407

  O'Leary, Michael ^a   Davis, Michael ^a   Bihari, David ^a  

^a ST GEORGE HOSPITAL   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0000552942     PISSN: 10705295     EISSN: None     Source Type: Journal    
DOI: 10.1097/00075198-199910000-00011     Document Type: Article

References (74)

1. Parker MM, Shelhamer JH, Bacharach SL, Green MV, Natanson C, Frederick TM: Profound but reversible myocardial depression in patients with septic shock. Ann Intern Med 1984, 100:463-490.
2. Ellrodt AG, Riedinger MD, Kimchi A, Berman DS, Maddahi J, Swan HJ, Murata GH: Left ventricular performance in septic shock: Reversible segmental and global abnormalities. Am Heart J 1985, 110:402-409.
3. Raper R, Sibbald WJ, Driedger AA et al: Relative myocardial depression in normotensive sepsis. J Crit Care 1989, 4:9-18.
4. Kono T, Morita H, Kuriowa T, Onaka H, Takatsuka H, Fujiwara A: Left ventricular wall motion abnormalities in patients with subarachnoid haemorrhage: neurogenic stunned myocardium. J Am Coll Cardiol 1994, 24:636-640.
5. Parker MM, McCarthy KE, Ognibene FP, Parrillo JE: Right ventricular dysfunction and dilatation, similar to left ventricular changes, characterise the cardiac depression of septic shock in humans. Chest 1990, 97:126-131.
6. Cunnion RE, Schaer GL, Parker MM, Natanson C, Parrillo JE: The coronary circulation in human septic shock. Circulation 1986, 73:637-644.
7. Patel J, Movahed A, Reeves WC: Electrocardiographs and segmental wall abnormalities in pancreatitis mimicking myocardial infarction. Clin Cardiol 1994, 17:505-509.
8. Sharkey SW, Shear W, Hodges M, Herzog CA: Reversible myocardial contraction abnormalities in patients with an acute noncardiac illness. Chest 1998, 114:98-105. In this retrospective study, conducted over a-3 year period, the authors identified 22 acutely ill patients hospitalized with a noncardiac illness who demonstrated deep T-wave inversion in the precordial leads of the echocardiogram and presumed new anterior contraction abnormalities on an echocardiogram. The primary diagnoses (n) were: central nervous system injury (6), sepsis (3), acute pulmonary disease (3), drug overdose/metabolic abnormality (7), post noncardiac surgery (3). One patient died from multiple organ failure; of the survivors, 11 patients had a normal echocardiogram at time of hospital discharge, and a further five subsequently were demonstrated to have normal function at outpatient echocardiography. Thirteen patients underwent coronary angiography, of which 10 were normal. The authors comment that the cardiac injury observed in these patients was similar in appearance to myocardial stunning, in that it was predominantly regional and showed progressive recovery. The role of myocardial ischemia and of catecholamines in the etiology of this syndrome is discussed.
9. Braunwald E, Kloner RA: The stunned myocardium; prolonged post-ischaemic ventricular dysfunction. Circulation 1982, 66:1148-49.
10. Kollef MH, Ladenson JH, Eisenberg PR: Clinically recognized cardiac dysfunction: an independent determinant of hospital mortality among critically ill patients. Is there a role for serial measurement of cardiac troponin I? Chest 1997, 111:1340-1347. This study addresses the relation between clinically recognized cardiac dysfunction in critically ill patients and outcome. In addition, the role of unrecognized cardiac injury as a risk factor for mortality, as assessed by measurement of cardiac troponin I, was investigated. Two hundred-sixty patients admitted over a 3-month period were prospectively evaluated for the presence of clinically recognized cardiac dysfunction and had daily measurement of cardiac troponin I. Fifty-five patients were found to have clinically recognized cardiac dysfunction; however, of these 21 had admission diagnoses of congestive heart failure, unstable angina/myocardial infarction, or cardiac arrest. Elevated levels of troponin I were found in 22 of the patients with clinically recognized cardiac dysfunction; it is not clear how many of these came from those patients with admission cardiac diagnoses. Nineteen of the 205 patients without cardiac dysfunction had elevated levels of troponin I, The hospital mortality rate was 45.5% for patients with cardiac dysfunction, compared with 10.2% for those without. The presence of elevated troponin I levels was associated with increased incidence of multiorgan dysfunction and prolonged ICU and hospital stay; however, no significant increase in mortality was found in these patients independent of the presence of clinically recognized cardiac dysfunction. Whereas clinically recognized cardiac dysfunction appears to be an independent determinant of hospital mortality in critically ill patients, the identification of unrecognized cardiac injury using troponin I measurements does not independently contribute to mortality prediction.
11. Herbert PC, Wells G, Blajchman MA, Marshall J, Martin C, Pagliareffo G, Tweeddale M, Schweitzer I, Yetisir E: A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care: the transfusion requirements in critical care investigators for the Canadian Critical Care Trials Group. N Engl J Med 1999, 340:409-417. Despite some obvious deficiencies, this is an important multi-center, randomized, controlled trial investigating the effect of blood transfusion practice on all-cause 30-day mortality and severity of organ dysfunction in critically ill patients. Patients were eligible for recruitment into the study if they were euvolemic after initial treatment and had hemoglobin concentrations of less than 9.0 g/dl within 72 hours of admission to the ICU. A major criticism of the study is that although over 6,000 patients were assessed for eligibility and 3,206 found eligible, for a variety of medical and administrative reasons only 838 patients actually participated in the study. Patients were randomly allocated to either a liberal transfusion strategy, in which blood transfusion was given to maintain hemoglobin concentrations between 10 and 12 g/dl or a restrictive strategy in which transfusion occurred only if the hemoglobin concentration fell below 7.0 g/dl, and then only sufficient to maintain hemoglobin between 7.0 to 9.0 g/dl. Although 30-day mortality was not different between the two groups (23.3% vs 18.7%, P = 0.11), the rates were significantly lower with the restrictive strategy in patients who were less acutely ill (Acute Physiology and Chronic Health Evaluation II score ≤20) or aged less than 55 years, but not among patients with clinically significant cardiac disease. Unfortunately, the study failed to control for blood transfusion before or after ICU admission. In conclusion, the authors claim that a restrictive strategy for blood transfusion is at least as effective as a more liberal strategy, and may possibly be superior in some patient groups, with the possible exception of patients with acute coronary syndromes.
12. Carson JL, Duff A, Poses RM, Berlin JA, Spence RK, Trout R et al: Effect of anaemia and cardiovascular disease on surgical mortality and morbidity. Lancet 1996, 348:1055-1060.
13. Wells G, Tweedale M, Martin C, Marshall J, Pham B, Blajchman M, Schweitzerl I, Pagliarello G: Does transfusion practice affect mortality in critically ill patients? Transfusion requirements in critical care (TRICC) investigators and the Canadian Critical Care Trials Group. Am J Respir Crit Care Med 1997, 155:1618-1623.
14. Bolli R: Mechanism of myocardial "stunning." Circulation 1990, 82: 723-738.
15. Barilla F, De Vincentis G, Mangieri E, Ciavolella M, Panitteri G, Scopinaro F et al: Recovery of contractility of viable myocardium during inotropic stimulation is not dependent on an increase of myocardial blood flow in the absence of collateral filling. J Am Coll Cardiol 1999, 33:697-704.
16. Schad H, Heimsch W, Eising GP, Mendler N: Effect of dopamine and atrial pacing on stunned myocardium. Eur J Cardiothorac Surg 1998, 13:710-717.
17. LaBruno S, Naim KL, Drzewiecki G, Kedem J: Beta-adrenergic stimulation of reperfused myocardium after 2-hour ischaemia. J Cardiovasc Pharmacol 1998, 32:535-542.
18. Miura H, Morgan DA, Gutterman DD: Oxygen-derived free radicals contribute to neural stunning in the canine heart. Am J Physiol 1997, 273:H1569-H1575.
19. Matsubara T, Dhalla NS: Relationship between mechanical dysfunction and depression of sarcolemmal Ca(2+)-pump activity in hearts perfused with oxygen free radicals. Mol Cell Biochem 1996, 160:179-185.
20. Grupp IL, Jackson TM, Hake P, Grupp G, Szabo C: Protection against hypoxia-reoxygenation in the absence of poly (ADP-ribose) synthetase in isolated working hearts. J Mol Cell Cardiol 1999, 31:297-303.
21. Meldrum DR, Shenkar R, Sheridan BC, Cain BS, Abraham E, Harker AH: Hemorrhage activates myocardial NFκB and increases tumor necrosis factor in the heart. J Mol Cell Cardiol 1997, 29:2849-2854.
22. Gwechenberger M, Mendoza LH, Youker KA, Frangogiannis NG, Smith W, Michael LH, Entman ML: Cardiac myocytes produce interleukin-6 in culture and in viable border zone of reperfused infarctions. Circulation 1999, 99:546-551. This study investigated the effects of TNF-α, IL-1β, lipopolysacharride and post- and pre-ischemic lymph on isolated dog cardiac myocytes. Unstimulated myocytes showed no IL-6 mRNA expression; stimulation with pre-ischemic lymph caused minimal or no IL-6 mRNA expression, whereas TNF-α, IL-1β, lipopolysaccharide and post-ischemic lymph stimulation all caused a strong IL-6 mRNA induction. In a dog model of myocardial ischemia-reperfusion, the authors then demonstrated reperfusion-dependent expression of IL-6 mRNA in cardiac myocytes in the viable border zone of an infarction. This study suggests that the response of cardiac myocytes to several cytokines as well as ischemia-reperfusion is similar, and involves production of IL-6. The potential role of IL-6 in these settings is discussed.
23. Frangogiannis NG, Lindsey ML, Michael LH, Youker KA, Bressler RB, Mendoza LH, Spengler RN, Smith W: Resident cardiac mast cells degranulate and release pre-formed TNF-α initiating the cytokine cascade in experimental canine myocardial ischemia/reperfusion. Circulation 1998, 98:699-710.
24. Meldrum DR, Dinarello CA, Shames BD, Cleveland JC, Cain BS, Banerjee A, Meng X, Harken AH: Ischemic preconditioning decreases postischemic myocardial tumor necrosis factor-α production: Potential ultimate effector mechanism of preconditioning. Circulation 1998 [suppl], 98:214-219. This study describes the effect of transient ischaemia/reperfusion and/or adenosine pre-treatment on TNF-α production and function in isolated, perfused rat hearts. The results showed that both preconditioning and adenosine treatment reduced TNF-α production and improved cardiac function, and it is suggested that TNF-α may be the distal effector mechanism of preconditioning. The discussion constitutes an excellent review of the current understanding of the role of TNF-α in ischemic myocardial dysfunction.
25. Grinwald PM: Calcium uptake during post-ischaemic reperfusion in the isolated rat heart: influence of extracellular sodium, J Mol Cell Cardiol 1982, 14:359-365.
26. Zaloga GP, Roberts PR, Nelson TE: Carnosine: a novel peptide regulator of intracellular calcium and contractility in cardiac muscle. New Horiz 1996, 4:26-35.
27. Edwards RJ, Marber MS: Myocardial preconditioning: mechanisms and man. Int J Clin Pract 1998, 52:395-401. A comprehensive state-of-the-art review of current concepts of myocardial preconditioning with 103 references.
28. Gho BC, Schoemaker RG, van den Doel MA, Duncker DJ, Verdouw PD: Myocardial protection by brief ischaemia in noncardiac tissue. Circulation 1996, 94:2130-2200.
29. Pell TJ, Baxter GF, Yellon DM, Drew GM: Renal ischaemia preconditions myocardium: role of adenosine receptors and ATP-sensitive potassium channels. Am J Physiol 1999, 275:H1542-H1547. Rabbits were subjected to laparotomy and 10-minute occlusion of the left renal artery or sham anaesthesia. Subsequently, the left coronary artery was occluded for 30 minutes and then reperfused for 2 hours. Preconditioning with renal ischemia limited the infarct-to-risk ratio from 32.7 ± 4% in controls to 17.8 ± 3%, P = 0.002, Protection was abolished by pretreatment with both the nonselective adenosine receptor antagonist B-(p-sulfophenyl) theophylline and the ATP-sensitive potassium channel blocker 5-hydrosydecanoate. Neither substance affected infarct-to-risk ratios in control animals. Myocardial preconditioning by distant organ ischemia appears to involve both adenosine receptors and KATP channels.
30. Parratt JR, Veigh A, Zeitlin IJ, Ahmad M, Oldroyd K, Kaszala K, Papp JG: Bradykinin and endothelial-cardiac myocyte interactions in ischaemic preconditioning. Am J Cardiol 1997, 80:124A-131A.
31. Imagawa J, Yellon DM, Baxter GF: Pharmacological evidence that inducible nitric oxide synthase is a mediator of delayed preconditioning. Br J Pharmacol 1999, 126:701-708. This carefully conducted animal study investigated the effect of blockade of iNOS on size of infarct following 30-minute coronary occlusion, performed 48 hours after four 5-minute coronary artery occlusions. Both dexamethasone and aminoguanidine (iNOS inhibitors) abolished the delayed protection afforded by ischemic preconditioning. The authors concluded that induction of iNOS following brief periods of coronary occlusion is associated with increased myocardial tolerance to infarction at 48 hours.
32. Meldrum DR, Cleveland JC Jr, Rowland RT, Bannerjee A, Harken AH, Meng X: Early and delayed preconditioning: differential mechanisms and additive protection. Am J Physiol 1997, 273:H725-H733.
33. Bluhm WF, Martin JL, Mestril R, Dillmann WH: Specific heat shock proteins protect microtubules during simulated ischaemia in cardiac myocytes. Am J Physiol 1998, 275:H2243-H2249.
34. Rowland RT, Meng X, Cleveland JC, Meldrum DR, Harken AH, Brown JM: Cardioadaption induced by cyclic ischaemic preconditioning is mediated by translational regulation of de novo protein synthesis. J Surg Res 1997, 71:155-160.
35. Cunnion RE: Myocardial depressant substance. In: Septic shock in humans: Advances in the understanding of pathogenesis, cardiovascular dysfunction and therapy. Parillo JE (moderator). Ann Intern Med 1990, 113:237-239.
36. Werdan K, Muller U, Reithmann C, Pfeifer A, Hallstrom S, Koidl B, Schlag G: Mechanisms in acute septic cardiomyopathy: evidence from isolated myocytes. Basic Res Cardiol 1991, 86:411-421.
37. O'Leary M, Ferguson C, Hinds C, Coakley J, Preedy V: Heart protein synthesis after cecal ligation and puncture in the rat. Shock 1999, 11(suppl):12.
38. Lang CH, Fan J, Cooney R, Vary TC: IL-1 receptor antagonist attenuates sepsis-induced alterations in the IGF system and protein synthesis. Am J Physiol 1996, 270:E430-E437.
39. Timmins AC, Cotterill AM, Hughes SC, Holly JM, Ross RJ, Blum W, Hinds CJ: Critical illness is associated with low circulating concentrations of insulin-like growth factors I and II, alterations in insulin-like growth factor binding proteins, and induction of an insulin-like growth factor binding protein 3 protease. Crit Care Med 1996, 24:1460-1466.
40. Macallan DC, Griffin GE: Cardiac muscle protein gene expression in the septic rat. Clin Sci (Colch) 1994, 87:539-546.
41. Khogali SE, Harper AA, Lyall JA, Rennie MJ: Effects of L-glutamine on post-ischaemic cardiac function: protection and rescue. J Moll Cell Cardiol 1998, 30:819-827. In this study, isolated perfused working rat hearts were subjected to 20 minutes of normothermic low-flow ischemia, Ischemia-reperfusion was shown to significantly depress cardiac output and cause significant diminutions of myocardial ATP, glutamate and phosphocreatine, and a rise in myocardial lactate. Both the changes in cardiac output and in myocardial metabolites could be abolished by addition of glutamine throughout the perfusion period (ie, commencing pre-ischemia) at 1.25 mM, and by post-ischemic treatment with glutamine at 2.5 mM. These levels are considerably above the normal plasma glutamine concentrations of 0.4-0.6 mM, and suggest a role for glutamine substitution in cardiac protection and rescue.
42. Ehrenfried JA, Chen J, Li J, Evers BM: Glutamine-mediated regulation of heat shock protein expression in intestinal cells. Surgery 1995, 118:352-357.
43. Cittadini A, Stromer H, Vatner DE, Grossman JD, Katz SE, Clark R, Morgan JP, Douglas PS: Consequences of growth hormone deficiency on cardiac structure, function and beta-adrenergic pathway: studies in mutant dwarf rats. Endocrinology 1997, 138:5161-5169.
44. De Gennaro Colonna V, Rossoni G, Bernareggi M, Muller EE, Berti F: Cardiac ischemia and impairment of vascular endothelium function in hearts from growth hormone-deficient rats: protection by hexarelin. Eur J Pharmacol 1997, 334:201-207.
45. Cittadini A, Grossman JD, Napoli R, Katz SE, Stromer H, Smith RJ, Clark R, Morgan JP, Douglas PS: Growth hormone attenuates early left ventricular remodeling and improves cardiac function in rats with large myocardial infarction. J Am Coll Cardiol 1997, 29:1109-1016.
46. Ross R, Miell J, Freeman E, Jones J, Matthews D, Preece M, Buchanan C: Critically-ill patients have high basal growth hormone levels with attenuated oscillatory activity associated with low levels of insulin-like growth factor-1. Clin Endocrinol 1991, 35:47-54.
47. Todd GL, Baroldi G, Pieper GM, Clayton FC, Eliot RS: Experimental catechalamine-induced myocardial necrosis. II. Temporal development of isoproterenol-induced contraction band lesions correlated with ECG, hemodynamic, and biochemical changes. J Mol Cell Cardiol 1985, 17:647-656.
48. Novitzky D, Wicomb WN, Cooper DK, Rose AG, Reinhart B: Prevention of myocardial injury during brain death by total cardiac sympathectomy in the Chacma baboon. Ann Thorac Surg 1986, 41:520-24.
49. Timmins AC, Hayes M, Yau E, Watson JD, Hinds CJ: The relationship between cardiac reserve and survival in critically ill patients receiving treatment aimed at achieving supranormal oxygen delivery and consumption. Postgrad Med J 1992 [suppl], 68:S34-S40.
50. Hayes MA, Timmins AC, Yau EHS, Palazzo M, Hinds CJ, Watson D: Elevation of systemic oxygen delivery in the treatment of critically ill patients. N Engl J Med 1994, 330:1717-1722.
51. Vincent JL, Bihari D: Elevation of systemic oxygen delivery in the treatment of critically ill patients. N Engl J Med 1994, 331:1160-1162.
52. Erdmann D: The effect of positive inotropes on the failing human myocardium. Cardiology 1997 [suppl], 2:7-11.
53. Kawahira Y, Sawa Y, Nishimura M, Sakakida S, Udea H, Kaneda Y, Matsuda H: In vitro transfer of a beta-2-adrenergic receptor gene into the pressure-overloaded rat heart enhances cardiac response to beta-adrenergic agonist. Circulation 1998, 98(suppl)II:262-267.
54. Gottlieb SS, McCarter RJ, Vogel RA: Effect of beta-blockade on mortality among high-risk and low-risk patients after myocardial infarction. N Eng J Med 1998, 339:489-497. That β-blockers improve survival following myocardial infarction is undisputed, yet many physicians remain reluctant to administer these agents to many patients, including the elderly, those with chronic lung disease, and those with left ventricular dysfunction. These authors have retrospectively reviewed the medical records of 201,752 patients with myocardial infarction. Thirty-four percent received β-blockers, with fewer in those who were very old, black, had a low ejection fraction, heart failure, COPD, elevated serum creatinine, or type I diabetes mellitus. Nonetheless, mortality was lower in every subgroup of patients treated with β-blockers than in untreated patients. Those patients treated with β-blockers who had specific risk factors traditionally cautioning β-blocker therapy had lower mortality reductions than other groups; however, because these patients had higher mortality rates overall, the absolute reduction in mortality was the same or greater than that among patients with no specific risk factors. The authors concluded that, following myocardial infarction, patients with conditions often considered contraindications to β-blockade also benefit from therapy. Despite the size of this study, this conclusion should be accepted with some caution, however. It is a retrospective study and is thus subject to the bias that there might have been important factors present in patients in the "risk-factor" groups not treated with β-blockers which were obvious only to the treating physician at the time, yet were associated with both the clinical decision not to prescribe a β-blocker and the subsequent early mortality.
55. Packer M, Bristow MR, Cohn JN, Colucci WS, Fowler MB, Gilbert EM, Shusterman NH: The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. N Engl J Med 1996, 334:1349-1355.
56. Cleland JGF, Swedberg K: Carvedilol for heart failure - with care. Lancet 1996, 1199-1201.
57. Pfeffer MA, Braunwald E, Moye LA, Basta L, Brown EJ Jr, Cuddy TE, et al: Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction: results of the survival and ventricular enlargement trial: The SAVE investigators. N Engl J Med 1992;327:669-677.
58. Ball SG, Acute Infarction Ramipril Efficacy (AIRE) Study Investigators, Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction and clinical evidence of heart failure. Lancet 1993;342:821-828.
59. Matoba S, Tatsumi T, Keira N, Kawahara A, Akashi K, Kobara M, et al: Cardioprotective effect of angiotensin-converting enzyme inhibition against hypoxia/ reoxygenation injury in cultured rat cardiac myocytes. Circulation 1999, 99:817-822. The benefit of long-term ACE inhibition after myocardial infarction is well established. It is also known that ACE inhibitors can protect the myocardium against ischaemia/reperfusion injury. This study attempted to characterize the mechanism of this protection by examining cultured rat cardiac myocytes. It demonstrated that an accumulation of bradykinin and the production of nitric oxide induced by constitutive nitric oxide synthase was responsible for this production. It did this by showing the protective effects of ACE-inhibition could be blocked using Hoe 140 (a bradykinin B2 receptor antagonist) and methylene blue (a soluble guanylate cyctase inhibitor).
60. Bartels GL, van den Heuvel AFM, van Veldhuisen DJ, van der Ent M, Remme WJ: Acute anti-ischaemic effects of perindoprilat in men with coronary artery disease and their relation with left ventricular function. Am J Cardiol 1999, 83:332-336.
61. Frazier OH, Benedict CR, Radovancevic B, Bick RJ, Capek P, Springer WE et al: Improved left ventricular function after chronic left ventricular unloading. Ann Thorac Surg 1996, 62:675-681.
62. Levin HR, Chen JM, Oz MC, Catanese KA, Krum H, Golsmith RL et al: Potential of left ventricular assist devices as outpatient therapy while awaiting transplantation. Ann Thorac Surg 1994, 58:1515-1520.
63. James KB, McCarthy PM, Thomas JD, Vargo R, Hobbs RE, Sapp S, Bravo E et al: Effect of the implantable left ventricular assist device on neuroendocrine activation in heart failure. Circulation 1995 [suppl], 92 S191-S195.
64. Goldstein DJ, Moazami N, Seldomridge JA, et al. Circulatory resuscitation with left ventricular assist device support reduces interleukins 6 and 8 levels. Ann Thorac Surg 1997, 63:971-974.
65. Dipla K, Mattiello JA, Jeevanandam V, Houser SR, Margulies KB: Myocyte recovery after mechanical circulatory support in humans with end-stage heart failure. Circulation 1998, 97:2316-2322.
66. Mancini DM, Beniaminovitz A, Levin H, Catanese K, Flannery M, DiTullio M et al: Low incidence of myocardial recovery after left ventricular assist device implantation in patients with chronic heart failure. Circulation 1998, 98:2383-2389.
67. Nanas JN, Moulopoulos SD: Counterpulsation: historical background, technical improvements, haemodynamic and metabolic effects. Cardiology 1994, 84:156-167.
68. Shayani V, Watson WC, Mansour MA, Thomas N, Pickleman J: Intra-aortic balloon counterpulsation in patients with severe cardiac dysfunction undergoing abdominal operations. Arch Surg 1998, 133:632-635.
69. Ruffolo RR Jr, Feuerstein GZ, Ohlstein EH: Recent observations with β-adrenoreceptor blockade: beneficial effects in hypertension and heart failure. Am J Hypertens 1998, 11:9S-14S.
70. Fuerstein GZ, Bril A, Ruffolo RR Jr: Protective effects of carvedilol in the myocardium. Am J Cardiol 1997, 80:41L-45L.
71. Brunvand H, Kvitting PM, Rynning SE, Berge RK, Grong K: Carvedilol protects against lethal reperfusion injury through antiadrenergic mechanisms. J Cardiovasc Pharmacol 1996, 28:409-417.
72. Unger T, Culman J, Gohlke P: Angiotensin II receptor blockade and end-organ protection: pharmacological rationale and evidence. J Hypertens 1998 (suppl), 16:S3-S9.
73. Meissner A, Weber TP, Van Aken H, et al: Clonidine improves recovery from myocardial stunning in conscious chronically instrumented dogs. Anesth Analg 1998, 87:1009-1014.
74. Goldschmidt M, Landzberg BR, Frishman WH: Nicorandil: a potassium channel opening drug for treatment of ischaemic heart disease. J Clin Pharmacol 1996, 36:559-572.