Elevated catecholamines during cardiac surgery: Consequences of reperfusion of the postarrested heart (original) (raw)
Related papers
cardiopulmonary bypass in man Neuronal and adrenomedullary catecholamine release in response to
2000
Cardiopulmonary bypass (CPB) alters systemic hemodynamics and affects several biochemical systems involved in cardiovascular regulation. We investigated the changes in levels of circulating epinephrine (E) and norepinephrine (NE) and related them to events during CPB. Twenty-eight patients undergoing various surgical procedures were studied. Plasma E and NE were determined by radioenzymatic assay at eight stages of the operation. A ninefold increase in arterial E (from 75 + 13 to 708 ± 117.3 pg/mI) occurred from prebypass (stage 1) measurements to the end of aortic cross-clamping (stage 4). The values at stage 4 were signific'antly higher (p < 0.05) than at all other stages. E decreased rapidly, to 360 84.3 pg/ml, rafter myocardial and pulmonary reperfusion (stage 5). Arterial NE increased twofold from stage 1 to stage 4 (from 426 66.9 to 825 84.2, p < 0.05). The increase in NE from initial CPB values (stage 2) to 30 minutes of aortic cross-clamping (stage 3) was associated with an increase in mean blood pressure (r 0.51, p = 0.02). The peak increases in catecholamines occurred when the heart and lungs were'excluded from the circulation, which suggests that either or both contributed to the increase. Because the increase in E was markedly greater than that in NE, the predominant humoral response to CPB appears to be adrenomedullary release of E. This significant increase in catecholamines could jeopardize myocardial protective measures during'CPB. MARKED INCREASES in norepinephrine (NE) and epinephrine (E) concentrations in arterial blood during cardiopulmonary bypass (CPB) have been demonstrated. '-' However, no report describes the temporal increase in NE and E in relation to the abnormal hemodynamic and biochemical events during CPB. Methods Patients Twenty-eight adult patients, 10 female and 18 male, scheduled for elective cardiac surgery were studied using a protocol approved by the institutional review board of'the University of Alabama. The operations performed are shown in table 1. All patients continued to take their usual medications, including propranolol, until the time of surgery. Patients taking a methyldopa were excluded from the study. Table 2 contains demographic variables describing the patient population. Comparison of catecholamines and hemodynamic data from patients with ischemic heart disease (20 patients) and those with combined ischemic and valvular or congenital heart disease revealed no significant alterations in'the response to CPB. Likewise, whether or not patients were taking particular medications (e.g., propranolol or antihypertensive drugs) did not alter the catecholamine or hemodynamic response. Therefore, data from all patients are considered together. Anesthesia All patients were anesthetized by the same physician to ensure a consistent anesthetic approach. Anesthetic
Annals of The New York Academy of Sciences, 1994
Occlusion of the coronary arteries causes adrenergc denervation of the infarcted myocardium and surrounding regions.' Little is known about the extent of functional decline in the surviving adrenergc nerve terminals in the ischemic and non-ischemic portions of the myocardium or about the ability of these nerves to eventually recover full function. Injury and recovery may also be influenced by age and gender. Therefore experiments were performed to assess changes in cardiac adrenergic function after ligation and reperfusion of the left anterior descending artery (LAD) in young (6 months old) and old (24 months old) male and female F344 rats. K+-induced 3H-norepinephrine (NE) release fiom cardiac synaptosomes (SYN) and coronary arteries prepared from these hearts was used to measure adrenergc function.
Catecholamines in coronary sinus and peripheral plasma during pacing- induced angina in man
Circulation, 1979
Subscriptions: Information about subscribing to Circulation is online at by guest on July 9, 2011 http://circ.ahajournals.org/ Downloaded from CATECHOLAMINE RESPONSE TO ANGINA/Schwartz et al. 32. Palacious 1, Johnson RA, Newell JB, Powell WJ Jr: Left ventricular end-diastolic pressure volume relationships with experimental acute global ischemia. Circulation 53: 428, 1976 33. Forrester JS, Diamond G, Parmley WW, Swan HJC: Early increase in left ventricular compliance after myocardial infarction. J Clin Invest 51: 598, 1972 34. Tyberg JV, Forrester JS, Wyatt HL, Goldner SJ, Parmley WW, Swan HJC: An analysis of segmental ischemic dysfunction utilizing the pressure-length loop. Circulation 49: 748, 1974 35. Theroux P, Ross J Jr, Franklin D, Kemper WS, Sasayama S: Regional myocardial function in the conscious dog during acute coronary occlusion and responses to morphine, propranolol, nitroglycerin, and lidocaine. Circulation 53: 302, 1976 36. Theroux P, Ross J Jr, Franklin D, Covell JW, Bloor CM, Sasayama S: Regional myocardial function and dimensions early and late after myocardial infarction in the unanesthetized dog. Circ Res 40: 158, 1977 37. Crozatier B, Ashraf M, Franklin D, Ross J Jr: Sarcomere length in experimental myocardial infarction: evidence for sarcomere overstretch in dyskinetic ventricular regions. J Mol Cell Cardiol 9: 785, 1977 38. Theroux P, Franklin D, Ross J Jr, Kemper WS: Regional myocardial function during acute coronary artery occlusion and its modification by pharmacologic agents in the dog. Circ Res 35: 896, 1974 39. Waters DD, Da Luz P, Wyatt HL, Swan HJC, Forrester JS: Early changes in regional and global left ventricular function induced by graded reductions in regional coronary perfusion. Am frequently during pacing-induced angina, cannot be demonstrated during exercise-induced angina, since metabolic evidence of ischemia is obscured by elevated arterial lactate concentrations."' 12 In relationship to anaerobic glycolysis, a decrease of myocardial tissue content of high-energy phosphates, ATP and CP, has been demonstrated.'13-5 An increase in myocardial tissue content'517, 37 and a coronary venous release of the diffusible ATP catabolites adenosine, inosine and hypoxanthine, have been shown19 20 22 23 in animals after temporary coronary occlusion. 43 by guest on July 9, 2011
Decreased Catecholamine Degradation Associates with Shock and Kidney Injury after Cardiac Surgery
Journal of the American Society of Nephrology, 2009
Enzymatic pathways involving catechol-O-methyltransferase (COMT) catabolize circulating catecholamines. A G-to-A polymorphism in the fourth exon of the COMT gene results in a valine-to-methionine amino acid substitution at codon 158, which leads to thermolability and low ("L"), as opposed to high ("H"), enzymatic activity. We enrolled 260 patients postbypass surgery to test the hypothesis that COMT gene variants impair circulating catecholamine metabolism, predisposing to shock and acute kidney injury (AKI) after cardiac surgery. In accordance with the Hardy-Weinberg equilibrium, we identified 64 (24.6%) homozygous (LL), 123 (47.3%) heterozygous (HL), and 73 (28.1%) homozygous (HH) patients. Postoperative catecholamines were higher in homozygous LL patients compared with heterozygous HL and homozygous HH patients (P Ͻ 0.01). During their intensive care stay, LL patients had both a significantly greater frequency of vasodilatory shock (LL: 69%, HL: 57%, HH: 47%; P ϭ 0.033) and a significantly longer median duration of shock (LL: 18.5 h, HL: 14.0 h, HH: 11.0 h; P ϭ 0.013). LL patients also had a greater frequency of AKI (LL: 31%, HL: 19.5%, HH: 13.7%; P ϭ 0.038) and their AKI was more severe as defined by a need for renal replacement therapy (LL: 7.8%, HL: 2.4%, HH: 0%; P ϭ 0.026). The LL genotype associated with intensive care and hospital length of stay (P Ͻ 0.001 and P ϭ 0.002, respectively), and we observed a trend for higher mortality. Cross-validation analysis revealed a similar graded relationship of adverse outcomes by genotype. In summary, this study identifies COMT LL homozygosity as an independent risk factor for shock, AKI, and hospital stay after cardiac surgery. (ClinicalTrials.gov number, NCT00334009) Shock and acute kidney injury (AKI) are associated with increased mortality after cardiac surgery. 1,2 Cardiopulmonary bypass represents a common clinical setting of sympathetic nervous system activation and cardiovascular instability. Postoperative hypotension and vasodilation with increased requirements for catecholamines occur despite adequate intravascular filling, cardiac output, and increased plasma catecholamine concentrations. 1,3 High circulating catecholamine levels may contribute to persistent vasodilatation via ␣-adrenoceptor downregulation and desensitization, 4 depression of vasopressin synthesis, and adenosine triphosphate-sensitive potassium channel activation in vascular smooth muscle cells. 5 Circulating catecholamines
Circulation Research, 1993
The effect of myocardial ischemia and its major metabolic changes, such as anoxia, acidosis, and hyperkalemia, on exocytotic noradrenaline release was investigated in rat, guinea pig, and human cardiac tissue. Noradrenaline release was evoked by electrical field stimulation, and the effect of each experimental intervention on stimulation-evoked noradrenaline release (S2) was intraindividually compared with the release induced by a control stimulation (S1). In perfused hearts, 10 minutes of global ischemia caused a reduction of noradrenaline overflow in rat hearts (mean S2/S1, 0.31), whereas the overflow was increased in guinea pig hearts (S2/S1, 1.89). This species-dependent effect may be caused by quantitatively different responses to facilitating and suppressing factors of noradrenaline release in both species. Anoxia and substrate-free perfusion increased noradrenaline overflow in guinea pig hearts (S2/S1, 2.40) but had no significant effect in rat hearts (S2/S1, 0.75). Acidosis (pH 6.0) resulted in a suppression of noradrenaline release in rat hearts (S2/Si, 0.16), whereas it had only a minor inhibiting effect in guinea pig hearts (S2/S1, 0.67). Hyperkalemia had a comparable effect in both species (S2/Sl at 15 mmol/L K', 1.17 in rat and 1.14 in guinea pig; and S2/Sl at 20 mmol/L K', 0.64 in rat and 0.41 in guinea pig). To obtain results regarding the modulation of noradrenaline release in human myocardium, human atrial tissue was incubated, and the effect of anoxia, acidosis, and hyperkalemia on stimulation-evoked noradrenaline release was investigated. Anoxia had a moderate facilitating effect on stimulation-evoked noradrenaline release (S2/S1, 1.20), whereas acidosis (S2/S1, 0.35) and hyperkalemia resulted in a suppression (S2/SI at 15 mmol/L K', 0.63; and S2/Sl at 20 mmol/L K', 0.03). When the same studies were performed in incubated rat and guinea pig atrial tissue, stimulation-evoked noradrenaline release was modulated by the same metabolic factors as in perfused hearts. In conclusion, stimulation-evoked noradrenaline release in ischemic myocardium is determined by facilitating and suppressing factors in guinea pig, rat, and human cardiac tissue. In human hearts, the suppressing factors dominate even more than in rat hearts, whereas in guinea pig hearts, the facilitating factors outweigh the suppressing factors during early myocardial ischemia. (Circulation Research 1993;73:496-502) KEY WoRDs * acidosis * energy metabolism * myocardial ischemia * K' * noradrenaline release
Ca2+ sensitizer superior to catecholamine during myocardial stunning?☆
European Journal of Cardio-Thoracic Surgery, 2008
Background: After open-chest cardiac surgery, ventricular function remains depressed (myocardial stunning). Catecholamines (epinephrine) improve ventricular function by increasing the intracellular Ca 2+ concentration. In parallel, the oxygen consumption is increased, so that the hitherto intact myocardium can be jeopardized. In the very insufficient ventricle, epinephrine can even become ineffective. Since Ca 2+ sensitizers provide another therapeutic avenue, the effects of epinephrine and levosimendan on postischemic hemodynamics were investigated. Methods: After hemodynamic steady state, isolated, blood (erythrocyte-enriched Krebs-Henseleit solution)-perfused rabbit hearts were subjected to 25 min normothermic, no-flow ischemia and 20 min reperfusion. Heart rate (HR), cardiac output (CO), left ventricular pressure (LVP), coronary blood flow (CBF), and arterio-venous oxygen difference (AVDO 2) were recorded during reperfusion and after administration of either epinephrine (n = 16; 0.03 mmol), or levosimendan (n = 11; 0.75 mmol) or epinephrine plus levosimendan (n = 5). Results: Epinephrine increased HR (19%, p = 0.01) and improved hemodynamics in terms of CO (62%, p = 0.0006), stroke volume SV (46%, p = 0.02), stroke work W (158%, p = 0.01), LVP max (58%, p = 0.0001), maximal pressure increase dP/dt max (140%, p = 0.0004), minimal pressure increase dP/dt min (104%, p = 0.0002), LVP ed (À26%, p = 0.02), and increased coronary resistance CR (31%, p = 0.05). Epinephrine impaired hemodynamics in terms of AVDO 2 (+63%, p = 0.003), myocardial oxygen consumption MVO 2 (+67%, p = 0.0003) and MVO 2 /beat (+36%, p = 0.01). External efficiency h was increased by 92% (p = 0.02). Levosimendan in postischemic hearts increased HR (32%, p = 0.009) and improved hemodynamics in terms of CO (85%, p = 0.01), SV (44%, p = 0.03), W (115%, p = 0.04), LVP max (95%, p = 0.04), dP/dt max (133%, p = 0.009), dP/dt min (121%, p = 0.007), LVP ed (À63%, p = 0.0006), and CR (À17%; n.s., p = 0.1). It altered hemodynamics in terms of AVDO 2 (+7.0%; n.s., p = 0.3) and MVO 2 (+32%, p = 0.007) and MVO 2 /beat (+2.3%; n.s., p = 0.4). External efficiency was increased by 307% (p = 0.04). In five additional extremely dysfunctional rabbit hearts, epinephrine was ineffective. Additional levosimendan increased hemodynamics in terms of HR (56%; n.s., p = 0.1), CO (159%, p = 0.04), SV (89%, p = 0.03), W (588%, p = 0.02), LVP max (168%, p = 0.03), dP/dt max (102%, p = 0.005), dP/dt min (78%, p = 0.006), LVP ed (À98%, p = 0.0006), and CR (À50%, p = 0.02). It altered hemodynamics in terms of AVDO 2 (À11%; n.s., p = 0.05), MVO 2 (+131%, p = 0.04) and MVO 2 /beat (+171%, p = 0.03). External efficiency was increased by 212% (p = 0.04). Conclusion: In contrast to epinephrine, levosimendan improves ventricular function without increasing oxygen demand, thereby considerably improving external efficiency. Even during epinephrine resistance in extremely dysfunctional hearts, levosimendan successfully improves ventricular function.
Veterinary Surgery, 1989
Peripheral vasoconstriction and plasma catecholamine concentrations were studied in 37 dogs after cervical disc fenestration and salivary gland excision, laparotomy for intestinal anastomoses and cystotomy, or laparotomy for repair of diaphragmatic rupture, gastrotomy, and pyloromyotomy. Meperidine (4.4 mg/kg) was administered before extubation of 12 dogs undergoing laparotomy. Heart rate, respiratory frequency, indirect blood pressure, rectal temperature, toe web temperature, and plasma concentrations of epinephrine and norepinephrine were determined before induction of anesthesia, after intubation, after extubation, at sternal recumbency, and at standing. All dogs were hypothermic during surgery. After surgery, peripheral hypothermia (large rectal-toe web temperature gradients) increased from a mean of 4.6OC after intubation to a mean of 10.4OC when the dogs initially stood. Heart and respiratory rates and blood pressures during recovery were similar to those before anesthesia. Mean plasma catecholamine concentrations were neither significantly higher during recovery than before surgery nor were they increased in any surgical group, including the dogs not treated with meperidine. After anesthesia, 15% of the epinephrine and 12% of the norepinephrine samples were more than two standard deviations above the mean of the preanesthetic concentrations of all dogs. The ratio of all dogs with an epinephrine,concentration more than two standard deviations above the mean of baseline epinephrine concentrations was greater at sternal recumbency than before anesthesia and the ratio of dogs with an increased epinephrine concentration at sternal recumbency was greater in the laparotomy dogs (9 of 24) than in the cervical surgery dogs (0 of 12). Decreased peripheral blood flow during recovery from anesthesia appears to be a homeostatic attempt of conserving body heat to correct the hypothermia produced by anesthesia and peripheral vasodilation.