Hormonal stress response and hemodynamic stability in patients undergoing endovascular vs. conventional abdominal aortic aneurysm repair.

BACKGROUND AND AIMS: To investigate the effect of two different surgical techniques with different anesthetic modes on intraoperative and postoperative hormonal stress response, hemodynamic stability, fluid loading and renal function in patients scheduled for elective infrarenal abdominal aortic aneurysm (AAA) repair. MATERIALS AND METHODS: Forty consecutive patients scheduled for elective infrarenal AAA repair were allocated without randomizing into two groups: an endovascular (EVAR, n = 20) and a conventional (CAR, n = 20) aneurysm repair group according to aneurysm morphology as determined by preoperative computed tomography and angiography. The EVAR group were operated under spinal anesthesia and the CAR group using general anesthesia with epidural blockade. RESULTS: Patients undergoing CAR showed lower intraoperative mean arterial pressure and significantly higher plasma norepinephrine before aortic cross-clamping and significantly higher lactate after aortic declamping and postoperatively than patients in the EVAR group. Postoperatively, vasopressin and serum cortisol were also significantly higher in the CAR group. Fluid loading and estimated blood loss were more excessive in the CAR group. CONCLUSIONS: Stress response was lower and hemodynamic stability and lower body perfusion superior and renal function also better maintained in patients undergoing EVAR under spinal anesthesia as compared to those undergoing CAR using general anesthesia with epidural blockade.

Anti-inflammatory cytokine response and the development of multiple organ failure in severe sepsis.

BACKGROUND: The production of proinflammatory cytokines activates the systemic inflammatory response in sepsis. Patients also develop a compensatory anti-inflammatory reaction, which may have an important down-regulatory effect on the overactive inflammation. However, the role of this anti-inflammatory response in sepsis is not completely clarified. In this prospective study, we investigated the relationship between the pro- and anti-inflammatory cytokine profiles in severe sepsis and their role in the development of multiple organ failure (MOF). METHODS: Thirty-eight patients meeting the criteria for severe sepsis were studied. MOF was defined as a maximum SOFA score of 10 or higher. Serial measurements of the proinflammatory IL-6 and IL-1beta and the anti-inflammatory IL-10 and IL-1ra were used. The cytokine samples were taken at the onset of sepsis and on the third and fifth day during the ICU period. RESULTS: The initial IL-10 and IL-1ra responses were identical in patients with or without MOF. The anti-inflammatory cytokine levels remained elevated in the MOF patients, whereas in patients without MOF the levels declined. The IL-6/IL-10 ratio was significantly higher in the MOF patients on days 1 and 3 compared with patients without MOF. CONCLUSIONS: We could not demonstrate overproduction of anti-inflammatory IL-10 in MOF patients. On the contrary, the high IL-6/IL-10 ratio indicates that IL-10 deficiency may contribute to the development of MOF in severe sepsis.

Ischemic preconditioning protects right ventricular function in coronary artery bypass grafting patients experiencing angina within 48-72 hours.

BACKGROUND: To test whether ischemic preconditioning (IP) is able to protect the myocardium in recently unstable CABG patients. EXPERIMENTAL DESIGN: prospective, randomised, controlled clinical study. SETTING: University Hospital. PATIENTS: Forty CABG patients with recent unstable angina were randomised into an IP group (n=20) and a control group (n=20). Subgroup was divided based on the time of the most recent ischemia onset before the operation. INTERVENTION: The IP group was preconditioned with 2 cycles of 2-min ischemia followed by 3-min reperfusion before cross clamping. MEASURES: Hemodynamic data were monitored till the 1st POD. Biochemical markers were measured till the 2nd POD. RESULTS: There were no differences in cardiac index (Cl) and right ventricular ejection fraction (RVEF) in patients experiencing angina within 48 hours prior to operation. The percentage changes in CI and RVEF at 1 hour after declamping were significantly better in the IP group in patients experienced angina within 48-72 hours (106% vs 88% of baseline, p=0.027 and 103% vs 81% of baseline, p=0.023). No difference in postoperative cardiac troponin I (CTnI) and CK-MB was found between the IP and controls in either subgroup. CONCLUSIONS: IP has a beneficial effect on global and right ventricular hemodynamic functional recovery in unstable CABG patients experiencing angina within 48-72 hours prior to the operation. However, IP has no additional protective effects in unstable CABG patients who experience angina within 48 hours.

Adrenocortical function and multiple organ failure in severe sepsis.

BACKGROUND: Some patients with severe sepsis may have relative adrenocortical insufficiency, although not all studies confirm this finding. Corticosteroids play an important role in controlling excessive immune response, and they may reduce the severity of organ dysfunction in critical illness. In this prospective study, we investigated the incidence of adrenal insufficiency in severe sepsis and its relation to the development of multiple organ failure. METHODS: Forty-one patients meeting the criteria for severe sepsis were studied. A short ACTH stimulation test was carried out within 24 h of the diagnosis of sepsis. Peak serum cortisol level < 680 nmol/L and a rise of less than 260 nmol/L were used as the criteria for relative adrenocortical insufficiency. RESULTS: Relative adrenocortical insufficiency was detected in six patients. Duration of the ICU stay (P = 0.002) and mechanical ventilation (P = 0.024) were significantly longer in patients with impaired adrenal function. In the survivors, SOFA scores were significantly higher in patients with impaired adrenal function. The plasma ACTH levels were normal in most of the patients with relative adrenal insufficiency, whereas most patients with normal adrenal function had extremely low plasma ACTH levels. CONCLUSION: The ICU stay was longer and multiple organ failure more severe in patients with impaired adrenocortical function. There was a clear dissociation between ACTH and cortisol levels in AAR patients. This finding suggests that the integrity of the hypothalamic-pituitary-adrenal axis may be impaired in severe sepsis.

The influence of anaesthesia and surgery on the circadian rhythm of melatonin.

BACKGROUND: Operations are typically associated with sleep and other circadian rhythm disturbances. The present study was set up to evaluate the influence of spinal and general anaesthesia associated with knee surgery on the circadian rhythm of melatonin, which has sleep inducing properties. Previously this context has been studied only in some invasive operations and it might be that general anaesthesia induces more disturbances on circadian rhythm of melatonin than operations done with patients awake. METHODS: The circadian secretion pattern of melatonin was monitored during the pre- and postoperative evenings, nights and mornings to clarify possible anaesthesia/surgery-induced changes in the nocturnal secretion of melatonin and in the phase of the melatonin rhythm. The study included 20 patients scheduled for minor orthopaedic operations. The patients were randomised to receive either spinal or general anaesthesia. Melatonin was measured from evening and morning saliva samples radioimmunologically. The nocturnal urine before and after surgery was radioimmunologically examined for 6-hydroxymelatonin sulphate. RESULTS: Melatonin secretion evaluated from the saliva samples was significantly diminished during the first postoperative evening as compared with that during the preoperative evening (P<0.001). There was also a significant decline of 26% (P<0.05) in postoperative 6-hydroxymelatonin sulphate excretion. There was no significant difference in melatonin secretion between the spinal and general anaesthesia groups. CONCLUSION: Our findings suggest that anaesthesia in conjunction with surgery acutely disturbed the normal circadian rhythm of melatonin by delaying the onset of nocturnal melatonin secretion.

The protective effects of preconditioning decline in aged patients undergoing coronary artery bypass grafting.

OBJECTIVE: We sought to investigate the effects of myocardial ischemic preconditioning in adult and aged patients undergoing coronary artery bypass grafting. METHODS: Eighty patients with 3-vessel disease undergoing coronary artery bypass grafting were randomized into one of the following groups: adult ischemic preconditioning, adult control, aged ischemic preconditioning, and aged control. Hemodynamic data and cardiac troponin I values were compared between the groups. The ischemic preconditioning groups received 2 periods of 2 minutes of ischemia, followed by 3 minutes of reperfusion. The Student t test, chi(2) test, and analysis of variance for repeated measures were used for the statistical analysis. RESULTS: The baseline for right ventricular ejection fraction and cardiac index was similar. Right ventricular ejection fraction was depressed after the operation in all groups. Ischemic preconditioning significantly improved the recovery of right ventricular ejection fraction and cardiac index after the operation in adult patients (P =.013 and.001, respectively), but in the aged group there was no difference in the changes of ejection fraction and cardiac index (P =.232 and.889, respectively). The cardiac troponin I value in the adult patients subjected to ischemic preconditioning was lower than that in the adult control subjects (P =.046), but in aged patients undergoing ischemic preconditioning, the value was similar to that in aged control subjects (P =.897). Ischemic preconditioning also resulted in a shorter postoperative mechanical ventilation time and in less inotropic use in the adult group. CONCLUSION: Ischemic preconditioning protects the heart from ischemic reperfusion injury in adult patients undergoing coronary artery bypass grafting. The beneficial effects of ischemic preconditioning are manifested as a better recovery of right ventricular and global hemodynamic function, cellular viability, and surgical outcome. The protective effect of ischemic preconditioning is diminished in aged patients undergoing coronary bypass.

Inflammatory cytokines and soluble receptors after coronary artery bypass grafting.

Much interest has been focused on the overexpression of proinflammatory cytokines, but studies on their soluble receptors are rare. For a comprehensive picture of cytokine activation in cardiac surgery, a combination of cytokines and the corresponding soluble receptor concentration should be determined. Blood samples were collected from the radial artery and coronary sinus perioperatively in ten patients undergoing coronary artery bypass grafting with cardiopulmonary bypass. TNF-alpha, IL-6, sTNFRI, sTNFRII, and sIL-6R levels in the plasma were determined. Systemic TNFRI, TNFRII and IL-6 increased significantly after reperfusion to the myocardium, while perioperative systemic sIL-6r levels were similar. Arterial and sinus levels of TNFRI, TNFRII and sIL-6r were similar before cardiopulmonary bypass. Five minutes after reperfusion to the myocardium, higher sinus TNFRI and TNFRII and lower sinus sIL-6R levels were observed as compared to the arterial levels. The myocardium release of sTNFRI (r=0.57, P=0.089) and sTNFRII (r=0.64, P=0.047) positively correlated with the change of cardiac index after cardiopulmonary bypass. Myocardium releases sTNFRI and sTNFRII after ischaemic-reperfusion injury, and this may be of benefit to cardiac performance. sIL-6R is constantly being produced in areas other than the myocardium, while sIL-6R levels are reduced by consumption in the myocardium after ischaemic-reperfusion injury.

Cardioprotective effect of adenosine pretreatment in coronary artery bypass grafting.

OBJECTIVE: There are several reports of the use of adenosine as a cardioprotective agent during cardiac surgery. Adenosine treatment might affect neutrophils and inflammatory mediators. The present prospective randomized study was designed to investigate the effect of adenosine pretreatment on myocardial recovery and inflammatory response in patients undergoing elective coronary artery bypass surgery. DESIGN: A prospective, randomized, controlled study. SETTING: Operative unit and ICU in a university hospital in Finland. PATIENTS: Thirty male patients undergoing primary, elective coronary revascularization. INTERVENTIONS: Patients in the adenosine group received a 7-min infusion of adenosine (total, 650 microg/kg) before the initiation of cardiopulmonary bypass. MEASUREMENTS: Postoperative creatine kinase (CK)-MB release and hemodynamics were recorded. Perioperative leukocyte and cytokine release were measured. RESULTS: Adenosine pretreatment resulted in less CK-MB release and an improved postbypass cardiac index. Similar leukocyte counts and cytokine responses were seen in both groups perioperatively. Neutrophil counts were similar between the groups before and after myocardial ischemia when measured simultaneously in arterial and coronary sinus blood. CONCLUSIONS: The present results support the hypothesis that adenosine pretreatment is cardioprotective in humans, but the present dose failed to regulate the inflammatory responses after coronary artery bypass grafting.

Myocardial lactate production is not involved in the ischemic preconditioning mechanism in coronary artery bypass graft surgery patients.

OBJECTIVE: To study the relationship between ischemic preconditioning (IP) and lactate production and their impact on coronary artery bypass graft surgery patients. DESIGN: Prospective, randomized, controlled study. SETTING: University hospital. PARTICIPANTS: Eighty 3-vessel disease coronary artery bypass graft surgery patients with stable and unstable angina pectoris. INTERVENTIONS: The IP patients were preconditioned with 2 periods of 2-minute ischemia followed by 3-minute reperfusion before aortic cross-clamping. MEASUREMENTS AND MAIN RESULTS: The cardiac index (CI) after surgery was significantly higher in the IP group than in controls among stable patients (p = 0.013). IP was not effective in CI recovery in unstable patients. The baseline values of lactate production were 11.6%, 20.3%, -7.0%, and -2.9% in stable IP, stable control, unstable IP, and unstable control patients. Compared with baseline, lactate production increased significantly after the IP protocol (39.0% and 47.5% in the stable and unstable patients), and operation (47.5%, 31.7%, 35.4%, and 35.6% in stable IP, stable control, unstable IP, and unstable control patients) but not after 10 minutes of cardiopulmonary bypass (29.7% and 19.0% in the stable and unstable patients). There were no differences among the groups in lactate production after the operation. Lactate production after the IP protocol was negatively associated with CI recovery after surgery in the IP patients (p = 0.026). CONCLUSION: The IP effects do not include modulation of lactate production. IP induces lactate production, but it seems not to be involved in the triggering process.

Anti-inflammatory effects of 17beta-estradiol pretreatment in men after coronary artery surgery.

OBJECTIVE: To investigate the anti-inflammatory and hemodynamic effects of 17beta-estradiol in men undergoing elective coronary artery bypass graft surgery (CABG). DESIGN: Prospective, randomized, controlled. SETTING: Operating room and intensive care unit in a university hospital. PARTICIPANTS: Twenty-one men undergoing primary, elective CABG surgery. INTERVENTION: 17beta-estradiol, 2mg, was given orally twice in 14 hours before the operation. MEASUREMENTS AND MAIN RESULTS: Leukocyte counts, plasma myeloperoxidase, tumor necrosis factor-alpha, interleukin (IL)-6, IL-8, and IL-10 were measured perioperatively. Leukocyte counts were lower in the 17beta-estradiol group than in controls at 6 hours (11.4 +/- 2.0 hours v 15.5 +/- 4.7 hours x 10(9)/L) and 20 hours (11.6 +/- 1.9 hours v 13.6 +/- 2.5 hours x 10(9)/L) after reperfusion (p = 0.03). The release of myeloperoxidase was lower in the 17beta-estradiol group than in controls (5 minutes; 634.4 +/- 213.1 microg/mL v 773.1 +/- 209.3 microg/mL; 4 hours, 305.0 +/- 108.0 microg/mL v 441.3 +/- 191.6 microg/mL; p = 0.02). Systemic vascular resistance index was lower just after cardiopulmonary bypass, and cardiac index was higher postoperatively in the 17beta-estradiol group as compared with controls. CONCLUSION: Pretreatment with 17beta-estradiol can limit leukocyte activation in men after CABG surgery.

Distinct expression of type XIII collagen in neuronal structures and other tissues during mouse development.

Type XIII collagen is a type II transmembrane protein found in adhesive structures of mature tissues. We describe here its expression and spatio-temporal localization during mouse fetal development. Type XIII collagen mRNAs were expressed at a constant rate during development, with an increase of expression towards birth. Strong type XIII collagen expression was detected in the central and peripheral nervous systems of the developing mouse fetus in mid-gestation. Cultured primary neurons also expressed this collagen, and it was found to enhance neurite outgrowth. The results suggest that type XIII collagen is a new member among the proteins involved in nervous system development. Strong expression during early development was also detected in the heart, with localization to cell-cell contacts and accentuation in the intercalated discs perinatally. During late fetal development, type XIII collagen was observed in many tissues, including cartilage, bone, skeletal muscle, lung, intestine and skin. Clear developmental shifts in expression suggest a role in endochondral ossification of bone and the branching morphogenesis in the lung. Notable structures lacking type XIII collagen were the endothelia of most blood vessels and the endocardium. Its initially unique staining pattern began to concentrate in the same adhesive structures where it exists in adult tissues, and started to resemble that of the beta1 integrin subunit and vinculin during late intrauterine development and in the perinatal period.

Cytokine responses in patients undergoing coronary artery bypass surgery after ischemic preconditioning.

OBJECTIVE: The release of proinflammatory cytokines has been shown to be associated with the development of complications after coronary artery bypass grafting with cardiopulmonary bypass. The purpose of the present study was to establish whether ischemic preconditioning (IP) could limit inflammatory cytokines release in patients undergoing elective coronary artery bypass surgery. METHODS: Twenty-two patients with multiple-vessel coronary artery disease and stable angina admitted for first-time elective coronary artery bypass surgery were randomized into control or ischemic preconditioning groups. Patients in the IP group were exposed to two cycles of two-minute myocardial ischemia, followed by three minutes of reperfusion, at the beginning of the revascularization operation, before the cross-clamping and ischemic period used for coronary artery bypass graft anastomosis. Peripheral plasma levels of TNF-alpha, IL-6, IL-8 and IL-10 were measured perioperatively. RESULTS: Significant elevation of IL-6, IL-8 and IL-10 were observed in both groups after reperfusion. Ischemic preconditioning has no effect on cytokine release in the early stage after reperfusion. Arterial blood IL-6 levels in the preconditioning group were significantly lower than in controls at 20 h after declamping (52.93 +/- 9.79 vs 96.04 +/- 17.56 pg/ml, p < 0.05). CONCLUSIONS: The results indicate that ischemic preconditioning results in no effect on systemic inflammatory cytokine release in the early stage but a delayed reduction in IL-6 levels at 20 h after reperfusion.

Effects of hypertonic 75 mg/ml (7.5%) saline on extracellular water volume when used for preloading before spinal anaesthesia.

BACKGROUND: Prevention of hypotension during spinal anaesthesia is commonly achieved using fluid preloading. This may result in a substantial amount of excess free water retained in the body after spinal anaesthesia. We aimed to evaluate the effects of 7.5% hypertonic saline on extracellular water volume and haemodynamics when used for fluid preloading before spinal anaesthesia. METHODS: This randomised double-blind study evaluated the effects of 75 mg/ml (7.5%) hypertonic saline (HS) on extracellular water volume and haematocrit in patients undergoing arthroscopy or other lower limb surgery under spinal anaesthesia. Amounts of 1.6 ml/kg of HS (20 patients) or 13 ml/kg of 9 mg/ml normal saline (20 patients) were administered for preloading before spinal anaesthesia with a 10 mg dose of 0.5% hyperbaric bupivacaine. Etilefrine was administered in order to maintain mean arterial pressure (MAP) at >or=80% of its baseline value. Whole-body impedance cardiography-derived cardiac index (CI) and extracellular water (ECW) were measured. RESULTS: There were no significant differences in demographic data or in the number of blocked segments. ECW remained similar in both groups despite the much smaller amount of infused free water in the HS group. There were no significant differences between the groups in CI values during the study. The amount of etilefrine administered was similar in the treatment groups. Dilution of haematocrit was also similar in both groups. CONCLUSION: Hypertonic 75 mg/ml (7.5%) saline is an alternative for preloading before spinal anaesthesia in situations where excess free water administration is not desired. It is effective in small doses of 1.6 ml/kg, which increase the extracellular water, plasma volume and cardiac output, and thus maintain haemodynamic stability during spinal anaesthesia.

Effect of ischaemic preconditioning, cardiopulmonary bypass and myocardial ischaemic/reperfusion on free radical generation in CABG patients.

OBJECTIVE: To investigate the free radicals (FR) generation after ischaemic preconditioning and cardiopulmonary bypass and during reperfusion in CABG patients, and the role of ischaemic preconditioning. METHODS: Forty-three CABG patients were randomised into an ischaemic preconditioning and a control group. The protocol for ischaemic preconditioning was two cycles of 2-min ischaemia followed by 3-min reperfusion. Free radicals were measured using electron spin resonance spectroscopy. Global and right heart functions were collected. RESULTS: The free radicals generation in coronary sinus blood in the ischaemic preconditioning group was 9.7 and 16.6% after the ischaemic preconditioning protocol and 10 min after declamping, 6.8 and 13.3% in the controls. The free radicals in arterial samples were, respectively, 21, 14, 10 and 9% at 10 min, 1, 2 and 24 h after reperfusion. Cardiac index (CI) and right ventricular ejection fraction (RVEF) were improved by ischaemic preconditioning. CONCLUSION: Both ischaemic preconditioning and cardiopulmonary bypass induced free radicals generation. Although ischaemic preconditioning had no effect on free radicals generation after the operation, it protected against postoperative stunning.

Pump prime aprotinin fails to limit proinflammatory cytokine release after coronary artery bypass surgery.

BACKGROUND: The purpose of this study was to establish whether pump prime aprotinin could limit the cytokine responses in patients undergoing elective coronary artery bypass surgery. METHODS: Twenty-one patients admitted for first-time elective coronary artery bypass surgery were randomized into control or aprotinin groups. Patients in the aprotinin group received 280 mg aprotinin in the pump prime. Leukocyte count, creatine kinase cardiac isoenzyme (CK-MB), cytokine production and postoperative blood loss were analyzed perioperatively and compared with preoperative values. RESULTS: The peak level of leukocyte count was lower in the aprotinin group than in controls (9.3 +/- 0.58 vs 11.2 +/- 0.68 x 10(9)/L, p = 0.01). Interleukin (IL)-6 and IL-8 did not differ significantly between the groups throughout the study period. Plasma IL-10 levels were higher in the controls than in the aprotinin group at 5 min (49.6 +/- 24.9 vs 8.13 +/- 2.8 pg/ml, p = 0.01) after reperfusion. CONCLUSION: Pump prime aprotinin fails to limit proinflammatory cytokine response in circulating blood.

Cytokine responses and myocardial injury in coronary artery bypass grafting.

OBJECTIVE: Cardiopulmonary bypass is acknowledged to be one of the major causes of a complex systemic inflammatory response after cardiac surgery, and it may contribute to postoperative complications and even multiple organ dysfunction. We here compared the cytokine responses and the degree of myocardial injury after coronary artery bypass grafting with or without cardiopulmonary bypass. METHODS: Nine patients underwent off-pump revascularization and 13 with cardiopulmonary bypass. Plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-8 and IL-10 were measured before anesthesia induction, and 5 min, 1, 4, and 20 h after reperfusion to the myocardium. Levels of the MB isoenzyme of creatine kinase (CK-MB) were also measured after the operation. RESULTS: Levels of TNF-alpha were low in both groups. A delayed elevation of IL-6 was noted in the off-pump group. IL-8 and IL-10 levels were significantly higher in the CPB than in the off-pump patients after reperfusion (p=0.006 and 0.001 respectively). Postoperative CK-MB levels were significantly higher in the CPB than in the off-pump group (p=0.001). Cytokine levels correlated with CK-MB values. CONCLUSION: The results indicated that off-pump revascularization was associated with reduced cytokine responses and less severe myocardial injury. The degree of myocardial injury, as defined by CK-MB release, correlated with cytokine release. Intervention designed to reduce cytokine responses in cardiac surgery may be advantageous for patients with severe comorbidity.

Effects of hypertonic saline (7.5%) on extracellular fluid volumes compared with normal saline (0.9%) and 6% hydroxyethyl starch after aortocoronary bypass graft surgery.

OBJECTIVE: To compare the effects of hypertonic (7.5%) saline (HS), normal (0.9%) saline (NS), and 6% hydroxyethyl starch (HES) on extracellular fluid volumes in the early postoperative period after cardiopulmonary bypass. DESIGN: A prospective, randomized, double-blind study. SETTING: University teaching hospital. PARTICIPANTS: Forty-eight patients scheduled for elective coronary artery bypass graft surgery. INTERVENTIONS: Patients were randomly allocated to receive 4 mL/kg of HS, NS, or HES during 30 minutes when volume loading was needed during the postoperative rewarming period in the intensive care unit. Plasma volume was measured using a dilution of iodine-125-labeled human serum albumin. Extracellular water and cardiac output were measured by whole-body impedance cardiography. MEASUREMENTS AND MAIN RESULTS: Plasma volume had increased by 19 +/- 7% in the HS group and by 10 +/- 3% in the NS group (p = 0.001) at the end of the study fluid infusion. After 1-hour follow-up time, the plasma volume increase was greatest (23 +/- 8%) in the group receiving HES (p < 0.001). The increase of extracellular water was greater than the infused volume in the HS and HES groups at the end of the infusion. One-hour diuresis after the study infusion was greater in the HS group (536 +/- 280 mL) than in the NS (267 +/- 154 mL, p = 0.006) and HES groups (311 +/- 238 mL, p = 0.025). CONCLUSION: The effect of HS on plasma volume was short-lasting, but it stimulated excretion of excess body fluid accumulated during cardiopulmonary bypass and cardiac surgery. HS may be used in situations in which excess free water administration is to be avoided but the intravascular volume needs correction.

Effect of ischemic preconditioning on myocardial protection in coronary artery bypass graft patients : can the free radicals act as a trigger for ischemic preconditioning?

OBJECTIVE: To investigate the interrelationship of free radicals (FRs), ischemic preconditioning (IP), and hemodynamic function in coronary artery bypass graft (CABG) patients. DESIGN: Prospective, randomized, and controlled clinical study. PATIENTS: Forty CABG patients were randomized into an IP group (n = 20) and a control group (n = 20). INTERVENTION: The IP group was preconditioned with two cycles of two-min ischemia followed by 3-min reperfusion before cross-clamping. MEASUREMENT AND RESULTS: FR content in coronary sinus blood was measured directly using alpha-phenyl-N-tert-butylnitrone-electron spin-trapped spectroscopy. A small amount of FRs was generated after the IP protocol (5.6% above the baseline) but not in control subjects. A larger amount was generated 10 min after declamping in both groups (8.4% in IP protocol and 7.7% in control subjects). Hemodynamic function recovered better in the IP group at 1 h and 6 h after declamping. There was a significant negative correlation between FR generation after declamping and left ventricular stroke work index (LVSWI) at 1 h and 6 h after declamping (r = -0.71 and - 0.59, respectively) in the control subjects but not in the IP group. There was a significant positive correlation between FR generation after the IP protocol and cardiac index at 1 h and 6 h (r = 0.50 and 0.61, respectively) and LVSWI at 1 h and 6 h (r = 0.56 and 0.54, respectively) after declamping in the IP group but not in the control subjects. CONCLUSION: FR generation after the operation correlates with ventricular functional depression in CABG patients. IP protects the stunning heart but does not alter FR generation. The association of better hemodynamic recovery after CABG with FR generation during the IP period suggests that FRs might act as one of the triggers for IP.