Leukocyte-depleted blood cardioplegia reduces cardiac troponin T release in patients undergoing coronary artery bypass grafting.

OBJECTIVE: Activated neutrophils have been implicated in reperfusion injury of the myocardium. Leukocyte depletion at reperfusion may contribute to better myocardial protection during cardiac surgery. We tested the efficacy of leukocyte-depleted blood cardioplegia in reducing myocardial injury during coronary artery bypass grafting. METHODS: Subjects were 27 patients undergoing elective coronary artery bypass grafting divided into controls (perfused with nonfiltered blood cardioplegia, n = 12) and those undergoing leukocyte-depleted blood cardioplegia (n = 15). Oxygenated blood mixed with a potassium crystalloid cardioplegic solution was delivered through the aortic root at every 30 minutes during cardiac arrest and terminal warm blood was administered before aortic declamping in both groups. In leukocyte depletion, blood was filtered prior to the mixture with crystalloid solution in the cardioplegic reservoir. RESULTS: Patient profiles did not differ significantly between groups, nor did systemic leukocyte count during or after surgery despite more than 81% removal of leukocytes in cardioplegic delivery. No consistent differences between groups in creatine kinase or creatine kinase-MB were seen up to 18 hours after surgery. Peak troponin T levels were significantly lower in the leukocyte-depleted blood cardioplegia group (0.52 +/- 0.13 ng/ml), however, than in controls (3.85 +/- 0.85 ng/ml). CONCLUSION: We concluded that leukocyte-depleted blood cardioplegia reduces the release of cardiac troponin T in patients undergoing elective coronary artery bypass grafting and may produce better myocardial protection in patients with impaired cardiac function or a damaged myocardium.     

Changes of plasma asymmetric dimethylarginine levels after coronary artery bypass grafting

OBJECTIVES: We investigated whether coronary artery bypass grafting affects plasma asymmetric dimethylarginine (ADMA) concentrations and whether precardioplegic hyperoxia influences ADMA release from the heart. DESIGN: Twenty two patients were randomized into control (n = 11) and hyperoxia (n = 11, ventilated with >96% oxygen before cardiopulmonary bypass) groups. Arterial and coronary sinus blood was sampled before cardioplegia and during early reperfusion. Arterial samples were drawn 60 min after declamping of the aorta, and on the first postoperative day. RESULTS: Baseline arterial values of ADMA were not different between groups (0.59+/-0.18 micro mol/l control, 0.63+/-0.13 micro mol/l hyperoxia group). Negligible release of ADMA into coronary sinus was detected 20 min after cardioplegia. A significant decrease of arterial ADMA was observed by the first postoperative morning (0.42+/-0.16 micro mol/l in control, and 0.38+/-0.07 in hyperoxia group, p < 0.01 compared to baseline). CONCLUSIONS: CABG with cardioplegia is associated with decrease of ADMA by the first postoperative morning. Reperfusion of cardioplegic heart did not result in significant release of ADMA. Pretreatment with hyperoxia had no influence on myocardial release and arterial levels of ADMA.     

Myocardial outflow of prostacyclin in relation to metabolic stress during off-pump coronary artery bypass grafting

BACKGROUND: The metabolic changes, possible myocardial damage, and influence on the vascular endothelium during off-pump coronary artery bypass grafting have been investigated. METHODS: Coronary sinus and arterial blood samples were obtained before coronary arterial occlusion, after 10 minutes of ischemia, and after 1 and 10 minutes of reperfusion in 9 patients who had an anastomosis performed to the left anterior descending coronary artery off-pump bypass RESULTS: The mean ischemic time was 14 +/- 1 minutes. The arteriovenous difference in lactate decreased during ischemia to reach a minimum at 1 minute of reperfusion (-0.15 +/- 0.06 micromol/L compared to 0.21 +/- 10 micromol/L before ischemia; p < 0.01). Myocardial lactate extraction decreased from 14.2 +/- 6.8 micromol/min before ischemia to -10.9 +/- 6.5 micromol/min after 1 minute of reperfusion (p < 0.01). Simultaneously, the arteriovenous difference in 6-keto-PGF(1alpha), the stable metabolite of prostacyclin, decreased from -30 +/- 26 pg/mL to -258 +/- 80 pg/mL at 1 minute of reperfusion (p < 0.05), and the 6-keto-PGF(1alpha) extraction over the heart decreased -556 +/- 466 pg/min to -18,560 +/- 5,683 pg/min (p < 0.01). CONCLUSIONS: The localized myocardial ischemia associated with these procedures causes changes in the myocardium and endothelial influence. Coronary bypass surgery performed on the beating heart may not be superior in preventing cardiac ischemia and endothelial disturbance, compared with conventional bypass surgery.     

Sodium nitroprusside during coronary artery bypass grafting: evidence for an antiinflammatory action.

BACKGROUND: It was the aim of the present study to investigate whether a nitric oxide donor can reduce systemic inflammation and the cardiac inflammatory response during coronary artery bypass grafting with cardiopulmonary bypass. METHODS: Patients undergoing elective coronary artery bypass grafting (n = 22) were randomly assigned to treatment with either sodium nitroprusside (0.5 microg x kg(-1) x min(-1)) or placebo (controls), both for the first 20 minutes of reperfusion. Interleukin-6 and interleukin-8 levels, the adhesion molecules CD41 and CD62 on platelets and CD41 on monocytes and PMN (as markers for coaggregate formation), CD11b on monocytes and PMN, as well as platelet and leukocyte counts were determined in radial artery and coronary sinus blood before cardiopulmonary bypass and during reperfusion (1, 5, 10, 25, and 35 minutes). RESULTS: A reduction of systemic interleukin-6 levels (15.4+/-3.5 pg/mL, 36.7+/-5.9 pg/mL, and 46.8+/-8.0 pg/mL versus 33.4+/-7.7 pg/mL, 76.7+/-13.2 pg/mL, and 106.0+/-26.5 pg/mL, respectively, at 1, 25, and 35 minutes of reperfusion) and interleukin-8 (29.6+/-4.5 pg/mL versus 54.0+/-9.4, pg/mL, resp., at 35 minutes of reperfusion) resulted from treatment with sodium nitroprusside. No intracardiac production of interleukin-8 in sodium nitroprusside-treated patients (-1.1+/-0.4 pg/mL and -2.8+/-2.2 pg/mL, resp., for the coronary sinus-radial artery difference at 5 and 25 minutes of reperfusion) was observed, whereas cardiac production of interleukin-8 was present in controls (2.5+/-1.5 pg/mL and 5.5+/-2.8 pg/mL, resp.). Retention of platelet/leukocyte coaggregates occurred during coronary passage in controls (coronary sinus-radial artery difference for CD41-positive monocytes at 1 and 10 minutes of reperfusion, -16.3%+/-8.5% and -8.8%+/-2.6%, resp.). This was reduced in sodium nitroprusside-treated patients (with 5.8%+/-5.2% and 0.0%+/-3.2%). Retention of platelets in controls (ratio of coronary sinus to radial artery platelet count at 5 and 10 minutes of reperfusion, 88%+/-6% and 91%+/-5%) was compared to washout in treated patients (108%+/-6% and 113%+/-7%). CONCLUSIONS: In patients undergoing routine coronary artery bypass grafting, administration of sodium nitroprusside during early reperfusion alleviates systemic inflammation and the cardiac inflammatory response.     

Metabolic changes and myocardial injury during cardioplegia: a pilot study.

BACKGROUND: The timing, nature, and severity of both increased cardiac troponin I (cTn-I) levels and myocardial injury during ischemic arrest with cardioplegia are unknown. To define them more accurately, we studied myocardial metabolic activity and the release of markers of myocardial cell injury into the coronary sinus before, during, and after cardioplegia. METHODS: We simultaneously measured creatine kinase, creatine kinase-MB, cTn-I, lactate, phosphate, and blood gases in coronary sinus and systemic arterial blood from 12 patients before cardiopulmonary bypass, after removal of the aortic cross-clamp, and after discontinuation of cardiopulmonary bypass. We also measured coronary sinus flow and transmyocardial fluxes of all analytes and calculated myocardial oxygen consumption, myocardial carbon dioxide production, and myocardial energy expenditure. RESULTS: Myocardial lactate release increased 10-fold after removal of the aortic cross-clamp (p = 0.012) and was accompanied by a surge in myocardial phosphate uptake (p = 0.056). These events were associated with only partial cardioplegia-induced suppression of myocardial oxygen consumption (p = 0.0047), myocardial carbon dioxide production (p = 0.0022), and myocardial energy expenditure (p = 0.0029). Simultaneously, coronary sinus cTn-I levels increased from a mean of 0.76 to 2.43 ng/mL after removal of the aortic cross-clamp, and 2.51 ng/mL after cardiopulmonary bypass (p = 0.014), leading to an increase in arterial cTn-I concentration from 0.18 to 0.98 and 3.01 ng/mL (p = 0.0002). Thus, cTn-I release across the myocardium was absent at baseline, became detectable (p = 0.012) after removal of the aortic cross-clamp, and correlated with cross-clamp and pump times. Similar changes occurred with creatine kinase-MB. CONCLUSIONS: Metabolic myocardial stress occurs during ischemic arrest with cardioplegia and is associated with inadequate suppression of metabolism and with a surge in cTn-I and creatine kinase-MB release, which is maximal after removal of the aortic cross-clamp. These changes are likely to represent structural myocardial cell injury.     

The effect of anaesthetics on the myocardium--new insights into myocardial protection

A variety of laboratory and clinical studies clearly indicate that exposure to anaesthetic agents can lead to a pronounced protection of the myocardium against ischaemia-reperfusion injury. Several changes in the protein structure of the myocardium that may mediate this cardioprotection have been identified. Ischaemia-reperfusion of the heart occurs in a variety of clinical situations including transplantations, coronary artery bypass grafting or vascular surgery. Ischaemia may also occur during a stressful anaesthetic induction. Early restoration of arterial blood flow and measures to improve the ischaemic tolerance of the tissue are the main therapeutic options (i.e. cardioplegia and betablockers). There exists increasing evidence that anaesthetic agents interact with the mechanisms of ischaemia-reperfusion injury and protect the myocardium by a 'preconditioning' and a 'postconditioning' mechanism. Hence, the anaesthesiologist may substantially influence the critical situation of ischaemia-reperfusion during surgery by choosing the appropriate anaesthetic agent. This review summarizes the current understanding of the mechanisms of anaesthetic-induced myocardial protection. In this context, three time windows of anaesthetic-induced cardioprotection are discussed: administration (1) during ischaemia, (2) after ischaemia-during reperfusion (postconditioning) and (3) before ischaemia (preconditioning). Possible clinical implications of these interventions will be reviewed.     

Myocardial outflow of calcitonin gene-related peptide in relation to metabolic stress during coronary artery bypass grafting without cardiopulmonary bypass

OBJECTIVE: Because of adverse effects of cardiopulmonary bypass and the prospect of shortening intensive care and hospital stay, coronary artery bypass grafting without cardiopulmonary bypass is gaining increased attention. The impact of the localized myocardial ischemia that is inherent in these procedures has not been thoroughly investigated in human beings. We have investigated metabolic changes, possible myocardial damage, and myocardial outflow of the vasodilator calcitonin gene-related peptide during coronary artery bypass grafting without cardiopulmonary bypass. METHODS: Coronary sinus and arterial blood was sampled before coronary arterial occlusion, after 10 minutes of ischemia, and after 1 and 10 minutes of reperfusion in 9 consecutive patients (mean age 70 +/- 5 years) who had an anastomosis performed to the left anterior descending artery without cardiopulmonary bypass. RESULTS: No perioperative myocardial infarctions occurred. The arteriovenous difference in lactate decreased during ischemia, to reach a minimum after 1 minute of reperfusion (-0.17 +/- 0.25 vs 0.15 +/- 0.25 mmol/L before ischemia; P =.008). Myocardial lactate extraction decreased (from 11.2 +/- 13.6 micromol/min before ischemia to -3.0 +/- 7.0 micromol/min after 1 minute of reperfusion; P =.012), that is, a net production of lactate. The arteriovenous difference in calcitonin gene-related peptide decreased from -0.1 +/- 2.6 pmol/L before ischemia to -30.5 +/- 26.5 pmol/L (P =.008) after 1 minute of reperfusion. CONCLUSIONS: The localized myocardial ischemia associated with these procedures causes metabolic changes in the myocardium, but no myocardial damage. The ischemia-related outflow of calcitonin gene-related peptide indicates that the vasodilating and cardioprotective properties of this peptide that are known from animal studies may be of importance in myocardial ischemia in human beings.     

Myocardial metabolism and hemodynamics during coronary surgery without cardiopulmonary bypass

BACKGROUND: Although renewed interest has recently been shown in coronary artery bypass grafting without cardiopulmonary bypass, no reports are available on myocardial metabolism and hemodynamics during temporary coronary occlusion and rotation of the contracting heart. METHODS: Changes in myocardial energy metabolism and hemodynamics were monitored in 12 patients undergoing elective coronary artery bypass grafting without cardiopulmonary bypass, and the postoperative efflux of creatine kinase-MB mass and troponin T were also determined. RESULTS: There was a significant increase in myocardial production of ATP degradation products (p = 0.026) and lactate (p = 0.004) during the operation. Myocardial oxygen extraction decreased (p = 0.012) in correlation with use of the short-acting beta-blocker, esmolol (r = -0.71). Apart from a decrease in mean arterial blood pressure (p = 0.002), there were no significant hemodynamic changes during the operation. The overall postoperative troponin T and creatine kinase-MB mass changes remained nonsignificant during the first two postoperative days. One patient had a myocardial infarction, diagnosed by electrocardiography, on the second postoperative day, but otherwise there were no major complications. CONCLUSIONS: Coronary artery bypass grafting without cardiopulmonary bypass seems to be well tolerated as only minor changes in myocardial energy metabolism and hemodynamics are observed during the operation.     

Stimulation of neutrophil activation during coronary artery bypass grafting: comparison of crystalloid and blood cardioplegia

BACKGROUND: During myocardial ischemia, activation of polymorphonuclear neutrophils (PMNs) results in the production of free oxygen radicals, which increase myocardial injury. It has been shown that PMNs also produce nitric oxide. It is not clear whether PMNs become activated as a result of their direct contact with ischemic/reperfused myocardium or if PMN activation and free oxygen radical production are effects of specific stimuli released during coronary artery bypass grafting (CABG). The aim of the current study was to evaluate plasma-mediated neutrophil stimulation and production of superoxide anion (O2) and nitric oxide in patients undergoing CABG, and to verify whether crystalloid and blood cardioplegia can modify such stimulation. METHODS: Coronary sinus, peripheral arterial, and venous plasma samples were collected from 50 patients who underwent CABG and were divided into 2 equal groups which received either crystalloid or blood cardioplegia: directly before myocardial ischemia and aortic cross-clamping; at the beginning of reperfusion after aortic clamp release; and 30 minutes after reperfusion. O2 and nitric oxide production by PMN was evaluated by standard methods. RESULTS: There was a significant (p < 0.05) increase in O2 production by PMN incubated with plasma obtained from the coronary sinus immediately after reperfusion in patients receiving crystalloid cardioplegia compared to blood cardioplegia. No difference was observed in plasma stimulation of nitric oxide production by PMN in the 2 groups of patients at different times during the procedure. CONCLUSIONS: Cardioplegia may affect release of neutrophil-oriented stimuli from ischemic myocardium and modify neutrophil activation during coronary artery bypass grafting.     

Myocardial preservation during coronary surgery with and without cardiopulmonary bypass

BACKGROUND: There is increased interest in coronary artery bypass grafting (CABG) without cardiopulmonary bypass (CPB), although the preservation of the myocardium under such circumstances has not been properly investigated. The aim of this randomized study was to compare the changes in myocardial metabolism during CABG with and without CPB. METHODS: Myocardial energy metabolism and tissue injury during CABG was monitored in a series of 22 patients (11 with and 11 without CPB). RESULTS: The maximum myocardial lactate production was significantly higher (p = 0.02) in the group operated with CPB (0.56 mmol/L) than without it (0.17 mmol/L). A similar phenomenon was seen in the transcardiac pH differences (0.085 and 0.034 with and without CPB, p = 0.007). The postoperative peak values of creatine kinase-MB mass (15.1 vs 6.3 microg/L) and troponin I (13.8 vs 5.2 microg/L) were significantly higher (p < 0.001 and p = 0.008) with than without CPB. CONCLUSIONS: CABG on a beating heart is associated with better myocardial energy preservation and less myocardial damage compared with conventional CABG with CPB and intermittent antegrade mild hypothermic blood cardioplegia.     

Stimulation of neutrophil integrin expression during coronary artery bypass grafting: comparison of crystalloid and blood cardioplegic solutions

OBJECTIVES: This study was designed (1) to evaluate the influence of plasma obtained from patients undergoing coronary artery bypass grafting on L-selectin, CD11b, and CD18 expression on human neutrophils and (2) to determine the influence of the use of crystalloid or blood cardioplegia during bypass grafting on plasma-mediated expression of adhesion molecules on polymorphonuclear neutrophils.Patients and methods: Patients undergoing coronary artery bypass grafting were divided into 2 groups to receive crystalloid or blood cardioplegic solutions. Peripheral vein, radial artery, and coronary sinus blood samples were drawn at aortic crossclamping, aortic crossclamp release, and 30 minutes after reperfusion. Human neutrophils were incubated with patients' plasma, and the expression of CD11b, CD18, and L-selectin was determined with flow cytometry. RESULTS: In patients receiving crystalloid cardioplegic solutions, plasma samples collected from the coronary sinus at aortic clamp release and 30 minutes thereafter induced significantly higher expression of neutrophil CD11b and CD18 than plasma samples obtained from a peripheral vein or artery at the same time points. The expression of L-selectin on polymorphonuclear neutrophils was significantly reduced with plasma obtained 30 minutes after reperfusion as compared with samples collected at aortic crossclamp release. In the group receiving blood cardioplegia, no significant differences in CD11b, CD18, or L-selectin expression were found. CONCLUSIONS: (1) Ischemia/reperfusion after coronary artery bypass grafting is associated with the release of factors capable of neutrophil activation from myocardium into the circulating blood. (2) The release of soluble stimuli for neutrophils during bypass grafting may be modified by the cardioplegic solution.     

Does interruption of normothermic cardioplegia have adverse effects on myocardium? A retrospective and prospective clinical evaluation

A total of 154 patients who underwent isolated coronary revascularization (coronary artery bypass grafting) using retrograde, near-continuous, warm cardioplegia for myocardial protection, were arbitrarily divided into three groups according to the cumulative cardioplegic interruption (i.e. the sum total of all the short cardioplegic interruption periods, expressed as a percentage of the cardiac arrest period). Group 1 (39 patients) had <20% interruption (mean(s.e.m.) 12.5(0.01)%), group 2 (82 patients) had 20–39% interruption (mean(s.e.m.) 30.1(0.01)%) and group 3 (33 patients) had >40% interruption (mean(s.e.m.) 45.4(0.01)%). The three groups were comparable except for longer clamp time in group 3 and a tower cardiac index in group 1. The mean number and duration of cardioplegic interruptions and reperfusions and multiple clinical outcomes were recorded. Clinical outcomes (Q) wave perioperative infarction, use of an intra-aortic balloon pump, mortality, and length of stay in the intensive care unit and hospital) were the same in all groups despite significant differences in percent, number and duration of interruption and reperfusion as well as cardiac arrest. The only significant differences found were in the level of creatine kinase-MB (CK-MB) and use of inotropes after surgery, both being higher in group 1 than in groups 2 and 3 (which is the opposite of what would be expected). Intraoperative hemodynamic (cardiac index and left ventricular ejection fraction) and metabolic evaluations (CK-MB, lactate production and oxygen extraction) in 22 additional patients who underwent coronary artery bypass grafting showed no significant differences between two groups having <30% versus >30% cumulative cardioplegic interruption. It is concluded that warm cardioplegic interruption as used clinically has no adverse effects on the myocardium in patients undergoing coronary revascularization. Warm retrograde near-continuous blood cardioplegia is an effective method of myocardial protection.     

Relationship between hemodynamics and cardiac metabolism in the reperfusion period following hypothermic global ischemia

Ten mongrel dogs were subjected to hypothermic ischemic cardioplegia for two hours followed by 30 minutes of reperfusion to characterize the relationship between hemodynamic parameters during reperfusion and the recovery of high energy store of the post-ischemic left ventricular myocardium. Dogs were anesthetized with intravenous pentobarbital 30 mg/kg, and standard cardiopulmonary bypass was instituted with the flow rate of 80 ml/min/kg and perfusion pressure around 80 mmHg. Ischemic cardioplegia was obtained by cross-clamping of the aorta for 2 hours under 20°C of myocardial temperature. After termination of cardioplegia, the heart was rewarmed by the support of cardiopulmonary bypass with the flow rate of 80 ml/min/kg until the myocardial temperature reached 36 °C. Hemodynamic parameters were measured throughout the experiment and myocardial adenosine triphosphate (ATP) and creatine phosphate (CP) were measured at the end of experiment. Correlation was significant between myocardial ATP and coronary blood flow and myocardial oxygen consumption. However, myocardial creatine phosphate correlated poorly to coronary blood flow, myocardial oxygen consumption and other hemodynamic parameters. These results indicate that the recovery of myocardial high energy store is partly related to coronary blood flow and myocardial oxygen consumption, but other parameters are probably involved in the process of early recovery of the myocardium from ischemic cardioplegia. This study was supported in part by a Grant from the Japan Heart Foundation for 1979.     

Biochemical indicators of myocardial ischaemia during coronary artery bypass grafting

Metabolic indicators of myocardial ischaemia were measured in coronary sinus blood in six patients undergoing coronary artery bypass grafting (CABG). Five arterial and coronary sinus blood samples were taken in each case--one before cardiopulmonary bypass (CPB), and three during and one after CPB. Moderate hypothermia with topical cardiac cooling and cold cardioplegia were used. Myocardial infarction occurred perioperatively in two patients. Myocardial lactate production was not found before CPB in any patient, but it was common during CPB. Adenosine, inosine and hypoxanthine were released into the coronary sinus blood, but their release did not correlate significantly with lactate production. Myocardial noradrenaline production showed positive correlation with lactate levels (p less than 0.05). Release of adrenaline from the myocardium during CABG was also demonstrated. Myocardial catecholamine production was especially seen in the patients with myocardial infarction. Myocardial catecholamine release seemed to be the most sensitive of the studied biochemical indicators of myocardial ischaemia during CABG.     

Does warm antegrade intermittent blood cardioplegia really protect the heart during coronary surgery?

OBJECTIVE: Intermittent antegrade blood cardioplegia (IABC) has been standardized as a routine technique for myocardial protection in coronary surgery. However, if the myocardium is known to tolerate short periods of ischemia during hypothermic arrest, it may be less tolerant of warm ischemia, so the optimal cardioplegic temperature of intermittent antegrade blood cardioplegia is still controversial. The aim of this study was to compare the effects of warm intermittent antegrade blood cardioplegia and cold intermittent antegrade blood cardioplegia on myocardial pH and different parameters of the myocardial metabolism. METHODS: Thirty patients undergoing first-time isolated coronary surgery were randomly allocated into two groups: group 1 (15 patients) received warm (37 degrees C) intermittent antegrade blood cardioplegia and group 2 (15 patients) received cold (4 degrees C) intermittent antegrade blood cardioplegia. The two randomization groups had similar demographic and angiographic characteristics. Total duration of cardiopulmonary bypass (108+/-17 and 98+/-21 min) and of aortic cross-clamping (70+/-13 and 65+/-15 min) were similar. The cardioplegic solutions were prepared by mixing blood with potassium and infused at a flow rate of 250 ml/min for a concentration of 20 mEq/l during 2 min after each anastomosis or after 15 min of ischemia. Intramyocardial pH was continuously measured during cardioplegic arrest by a miniature glass electrode and values were corrected by temperature. Myocardial metabolism was assessed before aortic clamping (pre-XCL), 1 min after removal of the clamp (XCL off) and 15 min after reperfusion (Rep) by collecting coronary sinus blood samples. All samples were analyzed for lactate, creatine kinase (MB fraction), myoglobin and troponin I. Creatine kinase and troponin I were also daily evaluated in peripheral blood during 6 days post-operatively. RESULTs: The clinical outcomes and the haemodynamic parameters between the two groups were identical. In group 1, XCL off and Rep were associated with higher coronary sinus release of lactate (5.5 +/- 1.8 and 2.2 +/- 0.5 mmol/l) than in group 2 (2.0 +/- 0.7 and 1.6 +/- 0.3 mmol/l, P < 0.05). Mean intramyocardial pH was lower in group 1 (7.23 +/- 0.08) than in group 2 (7.65 +/- 0.30, P < 0.05). There were no significant differences between the two groups with respect of creatine kinase (MB fraction) either after Rep or during the post-operative period. Lower coronary sinus release of myoglobin was detected at Rep in group 1 (170 +/- 53 microg/l) than in group 2 (240 +/- 95 microg/l, P < 0.05). At day 1, a lower release of troponin I was found in group 1 (0.11 +/- 0.07 g/ml) compared to group 2 (0.17 +/- 0.07 ng/ml, P < 0.05). CONCLUSION: With regards to similar clinical and haemodynamic results, myocardial protection induced by warm IAEX is associated with more acidic conditions (intramyocardial pH and lactate release) and less myocardial injury (myoglobin and troponin I release) than cold intermittent antegrade blood cardioplegia during coronary surgery.     

Relation of Cytokines to Vasodilation after Coronary Artery Bypass Grafting

Hemodynamic instability is frequent after coronary surgery. The present study tested the hypothesis that inflammation, as determined by circulating cytokine levels, may contribute to the difficulty of controlling arterial blood pressure after coronary artery bypass grafting. A group of 44 male patients undergoing elective coronary artery bypass grafting with cardiopulmonary bypass were studied. Plasma levels of tumor necrosis factor-, interleukin-6 (IL-6), IL-8, and IL-10 were measured before anesthesia induction, 5 minutes and 1 hour after reperfusion to the myocardium, and 2 and 18 hours after arriving in the intensive care unit (ICU). The 29 patients who did not need a vasopressor (norepinephrine) during their ICU stay were designated group I. They were compared to group II, which consisted of 15 patients who required a pressor agent in the ICU. Although no significant differences between groups were found regarding their hemodynamic variables, IL-6 and IL-8 levels were higher in the patients who used a pressor agent in the ICU. The norepinephrine dosage used in the ICU correlated with plasma IL-8 levels 2 hours after arriving in the ICU (r = 0.56, p = 0.031). Circulating IL-6 levels in group II were significantly higher than those in group I 2 hours after arriving in the ICU (126.5 ± 90.5 vs. 66.5 ± 48.2 pg/ml; p < 0.05). The mean IL-8 levels were higher in group II at 5 minutes (34.9 ± 25.7 vs. 17.3 ± 11.3 pg/ml) and 1 hour (38.6 ± 30.5 vs. 22.4 ± 16.7 pg/ml) after reperfusion, and 2 hours (33.0 ± 21.6 vs. 22.8 ± 16.7 pg/ml) after arriving in the ICU (p = 0.036). Postoperative vasodilation was associated with increased circulating IL-8 levels. Strategies that modulate cytokine responses may improve hemodynamic stability after coronary artery bypass grafting.     

Bypass graft material and myocardial protective procedure in combined coronary artery bypass grafting and valve surgery.

OBJECTIVE: The aortic cross clamping time is prone to be longer when coronary artery bypass grafting (CABG) is combined with valve surgery. Therefore, the myocardium that is revascularized by in-situ internal thoracic artery graft is at risk to ischemia, and, myocardial protection is especially important in such operation. In this study, the effect of myocardial preservation of combined antegrade, retrograde and terminal warm blood cardioplegia during combined valve surgery and CABG using the internal thoracic artery as a bypass conduit was evaluated. METHODS: From November 1992 to August 1999, 15 patients received combined CABG and valve surgery. Among these 15 patients, 13 patients who did not need hemodialysis were divided into 2 groups, and a comparative study was done. In Group I (n = 5), only the saphenous vein graft was employed for combined CABG and valve surgery, and myocardial protection was done by combined antegrade and terminal warm blood cardioplegia. In Group II (n = 8), at least 1 in-situ internal thoracic artery graft was employed for CABG and valve surgery, and myocardial protection was done by combined antegrade, retrograde and terminal warm blood cardioplegia. RESULTS: Despite longer aortic cross clamping time in Group II, the peak creatine kinase-MB of Group II was significantly lower. In addition, the postoperative administration of dopamine tended to be less in Group II. CONCLUSION: Myocardial protection by combined antegrade, retrograde and terminal warm blood cardioplegia may be an effective adjunct to combined valve surgery and CABG employing the in-situ internal thoracic artery graft.     

IL-8 concentration in coronary sinus blood during early coronary reperfusion after ischemic arrest.

OBJECTIVE: Activation of the inflammatory response is an important factor contributing to complications of cardiopulmonary bypass. Increased level of proinflammatory cytokine - IL-8 has been reported during coronary artery bypass grafting (CABG) operations with the use of cardiopulmonary bypass. The aim of this study was to find out whether the heart is the main source of IL-8 during early coronary reperfusion. METHODS: IL-8 concentration in coronary sinus before clamping and 5, 10, and 15 min after declamping of the aorta as well as in radial artery blood before clamping and 10 min after declamping of the aorta, was assessed in 30 patients undergoing CABG surgery. RESULTS: We observed increase in IL-8 concentration in coronary sinus blood after declamping of the aorta, however no difference between coronary sinus and arterial blood concentration was noted. The median value of IL-8 concentration in coronary sinus blood was 1.85 pg/ml before ischemia and 15.4, 20.3, and 29.3 pg/ml in 5, 10 and 15 min after aortic declamping, respectively. Our additional finding was that there was a negative correlation between IL-8 level and hemoglobin saturation with oxygen in coronary sinus blood 10 min after coronary reperfusion. CONCLUSIONS: We conclude that the heart is not the main source of IL-8 in early coronary reperfusion, although coronary reperfusion induces its release.     

Elevated coronary endothelin-1 but not Nitric Oxide in diabetics during CABG

Background. After coronary artery bypass grafting procedures, a higher incidence of morbidity and mortality has been reported in diabetic patients. We tested whether coronary artery bypass grafting in diabetics affects the endothelin-1 and nitric oxide coronary effluent profile during reperfusion.

Methods. Twenty-one consecutive patients (9 with type II diabetes mellitus, 12 non-diabetics) underwent coronary artery bypass grafting by one surgeon. The two groups did not differ in preoperative ejection fraction, Parsonnet score, number of vessels bypassed, or cross-clamp time. Each patient was treated in the same intraoperative manner with single atrial, aortic, and antegrade and retrograde cardioplegia (CPL) cannulas. Cold CPL arrest was by antegrade and retrograde infusion of modified Buckberg CPL solution. Warm CPL solution was infused before reperfusion. Coronary sinus blood samples were obtained for estimation of endothelin-1 and nitrite plus nitrate before CPL arrest and at 1 and 15 minutes after each of 2 reperfusion periods.

Results. In diabetics, endothelin-1 was significantly increased at all reperfusion times as compared with non-diabetics. Nitrite plus nitrate levels were significantly higher in patients with diabetes than in those without, but did not change with time in either of the groups.

Conclusions. Reperfusion after CPL during coronary artery bypass grafting procedure can trigger the release of endothelin-1 in patients with diabetes mellitus. This may favor increased vascular tone or positive inotropic responses after coronary artery bypass grafting and may contribute to significant cardiovascular consequences in diabetic patients.     

On-pump versus off-pump coronary artery bypass grafting: more heat-shock protein 70 is released after on-pump surgery

Objectives: The use of cardiopulmonary bypass in coronary artery bypass grafting (CABG) may contribute to the postoperative inflammatory response. The molecular chaperone heat-shock protein (HSP) 70 may be induced by ischemia, and has been detected both in the myocardium and in the circulation after CABG. In vitro, extracellular HSP70 may activate both innate and adaptive immunity. Hypothesizing that use of cardiopulmonary bypass (CPB) leads to more circulating HSP70, we explored the release of it in 10 patients undergoing CABG with the use of CPB, and in 10 patients undergoing off-pump surgery CABG (OPCAB). Methods: Blood samples were taken preoperatively, twice peroperatively, 2 and 6 h postoperatively and the next day. Serum analyses were performed by means of immunoassays. Results: We detected a significant difference in postoperative circulating HSP70 between on-pump and off-pump patients (median peaks of 2849 and 756 pg/ml, respectively, P<0.01, 2 h postoperatively). Interleukin-6 and -8 increased in all patients, without significant differences between the groups. Serum interleukin-10 increased at the end of the operation in 7 of 10 patients operated with cardiopulmonary bypass (median 51.7 pg/ml), but in none of the off-pump patients. Furthermore, in the first group, interleukin-10 correlated with the HSP70 concentration at the end of the operation, r=0.75, P<0.05. Serum markers of myocardial damage were higher in conventional than off-pump patients on day 1 postoperatively: median cardiac Troponin T was 0.358 and 0.126 μg/l, respectively, P<0.01. Correspondingly, median creatine kinase-MB was 23.6 and 7.8 μg/l in on-pump and off-pump patients, respectively, P<0.01. Peak HSP70 correlated with both Troponin T and creatine kinase-MB measured on day 1. Conclusions: Significantly more HSP70 was released into the circulation following conventional than following off-pump CABG. Circulating HSP70 may indicate cellular stress or damage. Furthermore, HSPs are suggested as immunoregulatory agents, and may be important in the host defence postoperatively.