Methylprednisolone fails to preserve pulmonary surfactant and blood-air barrier integrity in a porcine cardiopulmonary bypass model

BACKGROUND: Pulmonary inflammation after cardiac surgery with cardiopulmonary bypass (CPB) has been linked to respiratory dysfunction and ultrastructural injury. Whether pretreatment with methylprednisolone (MP) can preserve pulmonary surfactant and blood-air barrier, thereby improving pulmonary function, was tested in a porcine CPB-model. MATERIALS AND METHODS: After randomizing pigs to placebo (PLA; n = 5) or MP (30 mg/kg, MP; n = 5), animals were subjected to 3 h of CPB with 1 h of cardioplegic cardiac arrest. Hemodynamic data, plasma tumor necrosis factor-alpha (TNF-alpha, ELISA), and pulmonary function parameters were assessed before, 15 min after CPB, and 8 h after CPB. Lung biopsies were analyzed for TNF-alpha (Western blot) or blood-air barrier and surfactant morphology (electron microscopy, stereology). RESULTS: Systemic TNF-alpha increased and cardiac index decreased at 8 h after CPB in PLA (P < 0.05 versus pre-CPB), but not in MP (P < 0.05 versus PLA). In both groups, at 8 h after CPB, PaO2 and PaO2/FiO2 were decreased and arterio-alveolar oxygen difference and pulmonary vascular resistance were increased (P < 0.05 versus baseline). Postoperative pulmonary TNF-alpha remained unchanged in both groups, but tended to be higher in PLA (P = 0.06 versus MP). The volume fraction of inactivated intra-alveolar surfactant was increased in PLA (58 +/- 17% versus 83 +/- 6%) and MP (55 +/- 18% versus 80 +/- 17%) after CPB (P < 0.05 versus baseline for both groups). Profound blood-air barrier injury was present in both groups at 8 h as indicated by an increased blood-air barrier integrity score (PLA: 1.28 +/- 0.03 versus 1.70 +/- 0.1; MP: 1.27 +/- 0.08 versus 1.81 +/- 0.1; P < 0.05). CONCLUSION: Despite reduction of the systemic inflammatory response and pulmonary TNF-alpha generation, methylprednisolone fails to decrease pulmonary TNF-alpha and to preserve pulmonary surfactant morphology, blood-air barrier integrity, and pulmonary function after CPB.     

Myocardial protection with high-dose beta-blockade in acute myocardial ischemia.

OBJECTIVE: The risk of postoperative cardiac dysfunction is markedly increased by emergency coronary artery bypass grafting in the presence of acute myocardial ischemia. High dose beta-blockade during continuous coronary perfusion has been suggested as an alternative to conventional cardioplegia and this technique has been applied successfully in high risk patients for coronary artery bypass grafting (CABG) surgery. This study compared high dose beta-blockade with esmolol to continuous warm blood cardioplegia in a clinically oriented model of acute left ventricular (LV) ischemia and reperfusion. METHODS: Twelve dogs were subjected to 60 min of regional LV ischemia by left anterior descending branch (LAD) ligation. Cardiopulmonary bypass (CPB) and aortic crossclamp were applied after 45 min of ischemia. Thereafter, high dose beta-blockade during continuous coronary perfusion (ESMO, n = 6) or antegrade continuous warm blood cardioplegia (WBC, n = 6) were maintained for 60 min. Myocardial water content (measured from endomyocardial biopsies using a microgravimetric technique), global LV function (preload recruitable stroke work: PRSW), and regional LV function (echocardiographic wall motion score) were determined at baseline and after weaning from CPB. RESULTS: During aortic crossclamp interstitial edema formation was significantly higher in the WBC group with an average water gain of 2.2 +/- 0.49 vs. 0.76 +/- 0.12% in the ESMO group. Thereafter, edema resolved in both groups, but myocardial water gain remained significantly higher in the WBC group at 60 and 120 min post CPB (0.98 +/- 0.19 and 1.13 +/- 0.32% vs. 0.07 +/- 0.25 and 0.04 +/- 0.08%). Global LV function was significantly higher in the ESMO group at 60 and 120 min post CPB (PRSW 103 +/- 6 and 94.7 +/- 4.6% of baseline vs. 85.3 +/- 4.9 and 74.7 +/- 7.6% of baseline). However, regional LV function showed no significant difference between groups. CONCLUSIONS: High-dose beta-blockade during continuous coronary perfusion may allow the surgeon to utilize the advantages of warm heart surgery, while avoiding the interstitial edema formation and temporary cardiac dysfunction associated with continuous warm blood cardioplegia. In high risk patients such as patients with unstable angina or after failed PTCA, high-dose beta-blockade may be an applicable alternative to cardioplegic arrest.     

The role of leukocyte depleting filters in heart transplantation: early outcomes in prospective, randomized clinical trial.

OBJECTIVE: Leukocyte-mediated reperfusion injury to cardiac allograft in the perioperative period is most likely associated with the early and late mortality after heart transplantation (Htx). Our aim is to determine the efficacy and safety of using leukocyte-depleting filters in a cardiopulmonary bypass (CPB) and secondary blood cardioplegia (SBC) circuit in Htx. METHODS: A prospective, randomized trial was performed in 40 patients undergoing orthotopic Htx. These patients were divided into two groups, to be treated with either leukocyte-depleted (LD) reperfusion (n=20) in the LD group, or whole blood reperfusion (n=20) in the Control group. The SBC was used in both groups. RESULTS: Intraoperatively, the LD group presented the reduced markers of reperfusion injury. The course of the creatine kinase MB (CK-MB) releases was significantly lower in the LD group (p<0.05). The LD hearts showed better spontaneous rhythm resumption (60% vs 10%; p<0.001), and lower need for isoprenaline (0.02+/-0.01 microg/(kg min) vs 0.03+/-0.02 microg/(kg min); p<0.05) and epicardial pacing (25% vs 60%; p<0.05) for weaning off CPB. Postoperatively, lower and shorter need for inotropic support (48+/-46, median=35 h vs 131+/-68, median=109 h; p<0.001), shorter temporary epicardial pacing (6+/-14, median=0 h vs 25+/-52, median=1 h; p<0.01), and lower 24-h chest drainage (551+/-274, median=500 ml vs 973+/-836, median=665 ml; p<0.05) in the LD group contributed to the shorter mechanical ventilation time (8+/-3, median=7.5 h vs 14+/-12, median=8.5 h; p<0.05) and the shorter stay at an intensive care unit (ICU) (70+/-24 h vs 116+/-73 h; p<0.05). The 30-day mortality was zero in both groups. CONCLUSIONS: The use of leukocyte depleting filters in heart transplantation is an effective, easy and safe method of myocardial protection, reducing significant myocardial reperfusion injury and improving posttransplant graft functional recovery.     

Cardiac interleukin-6 release and myocardial recovery after aortic crossclamping. Crystalloid versus blood cardioplegia

BACKGROUND: Pro-inflammatory cytokines may play an important role in patient response to cardiopulmonary bypass (CPB). Since the myocardium is proposed to be a major source of cytokines, we studied the influence of the cardiolpegia type on interleukin-6 release and early myocardial recovery. METHODS: Experimental design: prospective, randomized study. Setting: university hospital, operative and intensive care. Patients: 20 consecutive patients (3 females) scheduled for elective coronary artery bypass grafting (CABG), mean age 62.8+/-5 years, history of myocardial infarction 11/20, left ventricular ejection fraction 62.9+/-15%. Interventions: patients were operated on using randomly either cold blood cardioplegia (B, n = 10) or cold crystalloid cardioplegia (C, n = 10). Measures: plasma levels of interleukin-6 (IL-6) were measured prior to CPB, after aortic declamping, after CPB, 1 hour, 6 hours and 12 hours postoperatively. RESULTS: Groups were comparable with respect to demographic data, left ventricular function, number of grafts, CPB and aortic crossclamp time. Group B patients demonstrated significant lower IL-6 levels after 1 hour (210+/-108 vs. 578+/-443 pg/ml), 6 hours (204+/-91 vs. 1210+/-671 pg/ml) and 12 hours (174+/-97 vs. 971+/-623 pg/ml). Post-CPB cardiac index was superior in group B (3.9+/-0.3 vs. 3.2+/-0.3 l/min/m2, p<0.05) with similar doses of inotropes. Group B patients could earlier be weaned off respirator (10+/-4 vs. 13+/-4 hours, p<0.05) and showed minor blood loss (635+/-211 vs. 918+/-347 ml, p<0.05). CONCLUSIONS: Inflammatory response to CPB is associated with delayed myocardial recovery. The use of blood cardioplegia may attenuate inflammatory reactions.     

The antioxidant N-acetylcysteine preserves myocardial function and diminishes oxidative stress after cardioplegic arrest

OBJECTIVE: Oxidative stress contributes to myocardial ischemia-reperfusion injury. We hypothesized that administration of the antioxidant N-acetylcysteine would have beneficial effects on myocardial function after cardiopulmonary bypass and cardioplegic arrest. METHODS: Anesthetized dogs (n = 18) were instrumented with myocardial ultrasonic crystals and a left ventricular micromanometer. Systolic function was measured by preload recruitable stroke work. Myocardial tissue water was determined by microgravimetry. Treated animals received 100 mg.kg(-1) N-acetylcysteine 10 minutes before initiation of cardiopulmonary bypass followed by 20 mg.kg(-1).h(-1) continuous infusion until 1 hour after cardiopulmonary bypass. After baseline, cardiopulmonary bypass and 2-hour crystalloid cardioplegic arrest was initiated, then reperfusion/rewarming for 40 minutes and separation from cardiopulmonary bypass. Myocardial function parameters and myocardial tissue water were measured at 30, 60, and 120 minutes after cardiopulmonary bypass. Oxidative stress was measured by 8-isoprostane concentrations in the coronary sinus plasma. RESULTS: Preload recruitable stroke work did not decrease from baseline in the N-acetylcysteine group and was significantly greater in N-acetylcysteine group compared with controls at 30 (104% +/- 9% vs 80% +/- 4%; P <.05) and 120 minutes (98% +/- 7% vs 79% +/- 4%; P <.05) after cardiopulmonary bypass. Concentrations of 8-isoprostane in the coronary sinus plasma of the control dogs were significantly higher 30 minutes after cardiopulmonary bypass compared with baseline but were unchanged in the N-acetylcysteine group. Myocardial edema resolution was significantly greater in the N-acetylcysteine group at 30 minutes after cardiopulmonary bypass compared with control (-2.5% +/- 0.7% vs -0.3% +/- 0.5% myocardial tissue water; P <.05). CONCLUSIONS: Administration of the antioxidant N-acetylcysteine preserves systolic function and enhances myocardial edema resolution after cardiopulmonary bypass/cardioplegic arrest. Furthermore, oxidative stress was significantly reduced in the treated animals. Therefore, our findings support the hypothesis that oxidative stress is the main cause for myocardial dysfunction after ischemia-reperfusion.     

High myocardial lactate concentration is associated with poor myocardial function prior to cardiopulmonary bypass

AIM: This study was designed to analyse the relationship between myocardial lactate--determined by microdialysis--and hemodynamics during coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). METHODS: Twenty consecutive patients with coronary artery disease were enrolled for this prospective, observational study. Microdialysis measurements were performed in the apical region of the heart during periods of 15 to 20 min before, during, and after CPB; hemodynamics and plasma lactate concentrations were determined correspondingly. Correlation analysis revealed a relationship between myocardial lactate concentration and right ventricular ejection fraction at baseline (Spearman's r: 0.6; P=0.02). Patients were thus grouped according to the myocardial lactate concentration at baseline into a high-lactate group (2.5+/-0.7 mmol.l(-1), n=10) and low-lactate group (0.9+/-0.5 mmol.l(-1), n=10). RESULTS: Preoperative left ventricular ejection fraction was not different between the groups (high-lactate group: 53+/-16%; low-lactate group: 57+/-15%; P=n.s.) Patients in the high-lactate-group had a lower stroke volume index (P=0.005) and right ventricular ejection fraction (P=0.04) before, and higher central venous and pulmonary artery pressures (P<0.01) after CPB. Plasma lactate was significantly higher during CPB in the high-lactate-group (P<0.05). No correlation was observed between myocardial and plasma lactate. Six patients in the high-lactate but none in the low-lactate-group needed inotropic support after weaning from CPB (P=0.01). CONCLUSIONS: These data are suggestive of an association between subtle myocardial ischemia--detected by microdialysis--and perioperative myocardial dysfunction in patients undergoing CABG. The microdialysis technique may be a valuable adjunct for monitoring myocardial metabolism during cardiac surgery.     

Plasma and urinary cytokine homeostasis and renal dysfunction during cardiac surgery

BACKGROUND: Cardiac surgery induces changes in plasma cytokines. Proinflammatory cytokines have been associated with a number of renal diseases. The proinflammatory cytokines interleukin 8 (IL-8), tumor necrosis factor alpha (TNFalpha), and interleukin 1beta (IL-1beta) are smaller than the antiinflammatory cytokines interleukin 10 (IL-10), interleukin 1 receptor antagonist (IL-1ra), and TNF soluble receptor 2 (TNFsr2), and thus undergo glomerular filtration more readily. Accordingly, this study investigated the relation between plasma and urinary cytokines and proximal renal dysfunction during cardiac surgery. METHODS: Twenty patients undergoing coronary artery bypass grafting with cardiopulmonary bypass (CPB) were studied. Blood and urine samples were analyzed for proinflammatory and antiinflammatory cytokines. Proximal tubular dysfunction was measured using urinary N-acetyl-beta-d-glucosaminidase (NAG)/creatinine and alpha1-microglobulin/creatinine ratios. RESULTS: Plasma IL-8, IL-10, IL-1ra, and TNFsr2 values were significantly elevated compared with baseline. Urinary IL-1ra and TNFsr2 were significantly elevated. Urinary NAG/creatinine and alpha1-microglobulin/creatinine ratios were also elevated. Plasma TNFalpha at 2 h correlated with urinary NAG/creatinine ratio at 2 and 6 h (P < 0.05) and with urinary IL-1ra at 2 h (P < 0.05). Plasma IL-8 at 2 h correlated with NAG/creatinine at 6 h (P < 0.05). Urinary IL-1ra correlated with urinary NAG/creatinine ratio after cross-clamp release and 2 and 6 h after CPB (P < 0.05). CONCLUSIONS: Cardiac surgery using CPB leads to changes in plasma and urinary cytokine homeostasis that correlate with renal proximal tubular dysfunction. This dysfunction may be related to the renal filtration of proinflammatory mediators. Renal autoprotective mechanisms may involve the intrarenal generation of antiinflammatory cytokines.     

Beta-blockade versus Buckberg blood-cardioplegia in coronary bypass operation.

OBJECTIVE: Continuous perfusion of the coronary arteries with beta-blocker (esmolol)-enriched normothermic blood during cardiac surgery has been suggested as an alternative technique for myocardial protection. The aim of the present study was to compare the beta-blocker technique to Buckberg's blood cardioplegia during coronary artery bypass grafting (CABG). METHODS: Sixty patients with coronary artery disease were randomly assigned to either the esmolol group (ES, n = 30) or the blood cardioplegia group (BC, n = 30). During aortic crossclamp ES patients received continuous normothermic coronary perfusion with esmolol-enriched blood. Hearts of the BC group were protected by antegrade cold blood cardioplegia according to Buckberg. We measured left ventricular (LV) contractility using TEE (fractional area of contraction, FAC) and hemodynamic parameters prior to cannulation for cardiopulmonary bypass (CPB), after decannulation, and 4 h postoperatively. Myocardial lactate release was measured prior to aortic cross-clamp, during cross-clamp, and after decannulation. LV biopsies for determination of heat-shock protein (HSP-70), actin pattern and intercellular adhesion-molecule (ICAM-I) as indicators for structural changes were collected prior CPB, at the end of the aortic cross-clamp period, and prior to weaning off CPB. RESULTS: There was no significant difference between both groups with respect to grafts and cross-clamp time. ES hearts did not release lactate during cross-clamp. In contrast, BC hearts released significant amounts of lactate. Post CPB FAC and hemodynamics under similar inotropic stimulation showed no difference between groups, whereas at 4 h post CPB measurements showed slightly better values in the ES group: cardiac index: ES: 2.9+/-0.1 (SEM) versus BC: 2.6+/-0.1 L/min per m2 (P < 0.05); FAC: ES: 55+/-3 versus BC: 48+/-3% (P < 0.05). HSP-70 and actin pattern showed no difference between groups; however, ICAM-I showed a significantly higher degree of structural changes in BC hearts: 18+/-2 versus ES: 11+/-1% (P < 0.05). CONCLUSION: Our data demonstrate that application of the beta-blocker technique during routine CABG was associated with slightly better functional recovery and less structural myocardial alteration as compared with intermittent cold blood cardioplegia, however, both techniques provided equivalent myocardial protection in terms of patient outcome. Future studies are required to investigate if myocardial ischemia minimization by use of the beta-blocker technique may be beneficial in compromized hearts.     

Inhibition of phosphodiesterase type III before aortic cross-clamping preserves intramyocardial cyclic adenosine monophosphate during cardiopulmonary bypass

Inotropes are often used to treat myocardial dysfunction shortly after cardiopulmonary bypass (CPB). beta-Adrenergic agonists improve contractility, in part by increasing cyclic adenosine monophosphate (cAMP) production, whereas phosphodiesterase type III inhibitors prevent its breakdown. CPB is associated with abnormalities at the beta-receptor level and diminished adenyl cyclase activity, both of which tend to decrease cAMP. These effects may be increased in the presence of preexisting myocardial dysfunction. We tested the hypothesis that inhibition of phosphodiesterase type III before global myocardial ischemia and pharmacologic arrest results in the preservation of intramyocardial cAMP concentration during CPB. Twenty adult patients undergoing coronary artery bypass grafting with CPB were studied. After CPB was instituted, a myocardial biopsy was obtained from the apex of the left ventricle. Patients were randomized to receive either placebo or milrinone (50 micro/kg) through the bypass pump 10 min before aortic cross-clamping. Another myocardial biopsy was performed adjacent to the left ventricular apex just before weaning from CPB. Myocardial cAMP concentration was determined by radioimmunoassay. Myocyte protein content was determined by the Bradford method by using a commercial kit. There were no significant demographic differences between the groups; however, patients in the Milrinone group had a lower left ventricular ejection fraction than placebo (41% +/- 13% vs 53% +/- 7%; P < 0.05). Patients who received milrinone had larger cAMP concentrations at the end of CPB compared with placebo (21 +/- 12.5 pmol/mg protein versus 12.8 +/- 2.2 pmol/mg protein; P < 0.05). The administration of milrinone before aortic cross-clamping is associated with increased intramyocardial cAMP concentration at the end of CPB. IMPLICATIONS: The administration of a single dose of milrinone before aortic cross-clamping resulted in significantly larger intramyocardial cyclic adenosine monophosphate concentration in myocardial biopsy specimens compared with controls.     

Myocardial protective effect of FR167653; a novel cytokine inhibitor in ischemic-reperfused rat heart.

OBJECTIVES: In this study, a newly synthesized cytokine inhibitor FR167653 was investigated using a rat heart ischemia-reperfusion model to prove its myocardial protective effect and its role in the inhibition of cytokine production in ischemic myocardium. METHODS: Studies were performed with isolated, Langendorff-perfused Lewis rat hearts (n=80) which were either treated with FR167653 or untreated, as the control group, and subjected to ischemia-reperfusion. RESULTS: Reperfusion followed by 30min of 37 degrees C ischemia induced marked myocardial cytokine expression and activated p38MAPK. FR167653 administered before ischemia and during reperfusion significantly reduced ischemia-activated myocardial TNFalpha mRNA expression (190+/-97 vs. 4805+/-3017, P=0.024) as well as TNFalpha production (0 vs. 9.6+/-2.5 ng/ml, P<0.05) and also inhibited p38 MAPK activation. Its administration improved recovery of cardiac contractile function during reperfusion: LVDP (130+/-18 vs. 82+/-21 mmHg (P=0.002)), max/min dP/dt (2812+/-328/-2283+/-216 vs. 1520+/-424/-1325+/-237 mmHg/s, P=0.003). CPK leakage was significantly reduced in FR167653 treated hearts versus untreated hearts (54+/-6 vs. 0.5+/-0.1, P<0.05) and reduction of coronary flow was improved (110+/-13 vs. 77+/-11%) 1h after beginning of reperfusion (P<0.05). Moreover, FR administration attenuated the number of TUNEL positive cardiomyocytes (3+/-1 vs. 9+/-2%). CONCLUSION: These data demonstrated positive inotropic and antiapoptotic effects of a newly synthesized compound (FR167653) of cytokine inhibitors and its inhibitory effect on myocardial TNFalpha production and p38 MAPK activation in ischemic-reperfused rat heart. This suggested that cytokine inhibition is significant as a method for myocardial protection against ischemia-reperfusion injury.     

Promoting angiogenesis protects severely hypertrophied hearts from ischemic injury

BACKGROUND: Myocardial hypertrophy is associated with progressive contractile dysfunction, increased vulnerability to ischemia-reperfusion injury, and is, therefore, a risk factor in cardiac surgery. During the progression of hypertrophy, a mismatch develops between the number of capillaries and cardiomyocytes per unit area, suggesting an increase in diffusion distance and the potential for limited supply of oxygen and nutrients. We hypothesized that promoting angiogenesis in hypertrophied hearts increases microvascular density, thereby improves tissue perfusion and substrate availability, maintains myocardial function, and improves postischemic recovery. METHODS: Left ventricular hypertrophy was created in 10-day-old rabbits by aortic banding and progression was monitored by echocardiography. At 4 weeks (compensated hypertrophy), 2 microg of vascular endothelial growth factor (VEGF) or placebo was administered intrapericardially. After 2 weeks, microvascular density, coronary flow (CF), and glucose uptake (GU) were measured. Tolerance to ischemia was determined by cardiac function measurements before and after ischemia-reperfusion using an isolated heart preparation. RESULTS: Microvascular density increased significantly following VEGF treatment (1.43 +/- 0.08/nuclei/field vs 1.04 +/- 0.06/nuclei/field untreated hypertrophy). Concomitantly, there was an increase in CF (7 +/- 0.5 vs 5 +/- 0.4 mL/min/g) and GU (1.24 +/- 0.2 vs 0.69 +/- 0.2 micromoles/g/30 minutes; p 相似文献   

Inhibition of NFkappaB activation with curcumin attenuates plasma inflammatory cytokines surge and cardiomyocytic apoptosis following cardiac ischemia/reperfusion

BACKGROUND: Following cardiopulmonary bypass (CPB) and cardiac global ischemia and reperfusion, pro-inflammatory cytokines are activated and cause cardiomyocytic injury. Nuclear factor (NF)-kappaB is involved in regulating inflammatory signal transduction. Curcumin inhibits NF-kappaB activation and blocks the inflammatory responses. We studied whether curcumin could decrease myocardial ischemia/reperfusion injury with cardioplegia during CPB and attenuate the appearance of apoptosis of cardiomyocytes. MATERIALS AND METHODS: Rabbits received normal saline (group 1) or curcumin (70 mum/kg, group 2; 100 mum/kg, group 3) injection 2 h before CPB. Total CPB was initiated and cold (4 degrees C) antegrade intermittent crystalloid cardioplegia was delivered every 20 min for 60 min of cardiac arrest. Rabbits were weaned from CPB and reperfused for 4 h. Blood was sampled at various time points and then the reperfused hearts were harvested. RESULTS: Postoperative elevation of plasma levels of interleukin (IL)-8 (14.5, 0.9, 2.9 times over baseline in groups 1-3, respectively, P < 0.05), IL-10 (201.1, 6.0, 14.9 times over baseline in groups 1-3, respectively, P < 0.05), TNF-alpha (9.4, 3.1, 3.9 times over baseline in groups 1-3, respectively, P < 0.05), and cardiac troponin I (141.2, 14.9, 15.0 times over baseline) significantly decreased in the curcumin groups. Appearance of apoptotic cardiomyocytes significantly decreased in the curcumin groups (5.69 +/- 1.64, 1.51 +/- 0.41, 2.43 +/- 0.49 per 1000 nuclei in groups 1-3, respectively, P < 0.01). The activation of neutrophil in the myocardium, which was measured using myocardial myloperoxidase activity assay, was significantly attenuated in the curcumin group. There was a significant increase in apoptosis-related cleavage fragments of caspase-3 and poly-ADP-ribose polymerase in group 1 compared to the other groups. CONCLUSIONS: Curcumin, an inhibitor of NF-kappaB, ameliorated the surge of pro-inflammatory cytokines during CPB and decreased the occurrence of cardiomyocytic apoptosis after global cardiac ischemia/reperfusion injury.     

Myocardial metabolic monitoring with the microdialysis technique during and after open heart surgery

BACKGROUND: Post-operative ischemia after coronary artery bypass grafting (CABG) is well described but effective intervention requires immediate diagnosis. One possible way of increasing efficacy of peri-operative myocardial monitoring is using the microdialysis technique. METHODS: In 30 patients undergoing routine CABG, a microdialysis catheter was inserted in the left heart in an area of abnormal ventricular contraction. A second catheter was placed in normal tissue of the right ventricle. Microdialysis measurements were performed at time intervals before, during and 24 h after cardiopulmonary bypass (CPB) and retrospectively compared with standard clinical monitoring and clinical course. RESULTS: During CPB, both ventricles showed signs of poor tissue oxygenation. Glycerol was significantly higher in the left myocardium (146 +/- 67 vs. 72 +/- 36 micromol/l) and the glucose/lactate ratio (GLR), as a marker of nutritional disorder of the right ventricle (41 +/- 15% vs. 67 +/- 17%, P < 0.05), had significantly better values at this time point. Myocardial lactate concentrations were significantly higher in the dyskinetic segments (2.82 +/- 0.81 vs. 1.5 +/- 0.81 microM). During this period, no abnormal clinical standard monitoring results were observed. Post-operative significantly increased lactate/pyruvate ratios of three patients were clinically associated with peri-operative myocardial infarction (108 +/- 67 vs. 38 +/- 9, P < 0.05). The lactate/pyruvate ratio started rising before any other standard monitoring tools showed abnormal values. CONCLUSIONS: Peri-operative microdialytic measurements of parameters related to ischemia can be safely performed in a clinical setting, resulting in faster and more reliable detection of ongoing or new ischemia.     

Heparin influences human platelet behavior in cardiac surgery with or without cardiopulmonary bypass

The objective was to investigate whether the platelet dysfunction in cardiac surgery is caused by hemodilution or by shear stress due to cardiopulmonary bypass (CPB). Platelet count and function were prospectively analyzed in two groups of patients undergoing cardiac surgery either with or without CPB (n = 40). In the first study (n = 20; 10 patients with and 10 without CPB), platelet counts were assessed at seven time points. In the second study (n = 20; 10 patients with and 10 without CPB), platelet function was studied with platelet aggregometry at different points during surgery: (a) after induction of anesthesia; (b) after sternotomy; and (c) 1 h after heparin. In the first study, the CPB group showed a significant decrease in platelet count starting after sternotomy (230 +/- 34 vs. 182 +/- 25, P < 0.05) and a maximum decrease at day 1 postoperative (96 +/- 34, P < 0.05). A similar observation was made in the non-CBP group. In the second study, a significant decrease of ADP (54 +/- 13% vs. 38 +/- 9%, P < 0.05), AA (76 +/- 16% vs. 22 +/- 14%, P < 0.05), and Collagen (66 +/- 13% vs. 37 +/- 11%, P < 0.05) induced platelet aggregation was observed at MOMENT d compared to the beginning of surgery in the CPB group. In the non-CBP group a significant decrease was observed in AA-induced platelet aggregation at MOMENT d (83% +/- 4 vs. 44% +/- 14, P < 0.05). The reduction in platelet count is similar with or without cardiopulmonary bypass and is due to pure hemodilution. Platelet function reduces significantly after heparin administration. Hemodilution and predominantly heparin are the causes of platelet dysfunction after cardiac surgery.     

Systemic coronary surgery in the beating heart. Experience in 250 cases

OBJECT: To report our recent experience with off-pump coronary artery revascularization in multi-vessel disease. METHODS: Between October 1996 and August 1998, 250 off-pump (OP) procedures were completed at the Montreal Heart Institute, representing more than 90% of all procedures done during the same time frame (97% for 1998). These patients have been compared to 1870 patients operated upon under cardiopulmonary bypass during the years 1995-1996 (CPB). RESULTS: Mean age, sexe distribution, and preoperative risk factors were comparable for both groups. On average 2.89 +/- 0.8 and 2.84 +/- 0.6 grafts/patient were completed in OP and CPB groups respectively. A majority (70%) of patients had either a triple or quadruple bypass. Coronary anastomoses were achieved with myocardial mechanical stabilization and heart "verticalization". Ischemic time was shorter in the OP group (29.8 +/- 0.9 vs 45 +/- 0.4 min, p < 0.05). Similarly, need for transfusion was significantly less (OP: 34 vs CPB: 66%, p < 0.005). Use of postoperative intra-aortic counterpulsation as well as the raise of CK-MB were lesser in the OP group. Operative mortality (OP: 1.6%, vs CPB: 2%, p = ns) and perioperative myocardial infarction rate (OP: 3.6% vs CPB: 4.2) were comparable for both groups. CONCLUSION: Off-pump complete coronary artery revascularization is an acceptable alternative to conventional surgery in a majority of patients with good results given progressive experience, rigorous technique, and adequate coronary artery stabilization.     

Hyperoxic ventilation at the critical hematocrit: effects on myocardial perfusion and function

BACKGROUND: Hemodilution reduces hematocrit (Hct) and blood oxygen content. Tissue oxygenation is mainly preserved by increased cardiac output. As myocardial O2-demands increase, coronary vasodilatation becomes necessary to increase myocardial blood flow. Myocardial ischemia occurs at a critical Hct-value (Hctcrit), with accompanying exhaustion of coronary reserve. Hyperoxic ventilation is known to both reverse peripheral tissue hypoxia at Hctcrit and also to induce coronary vasoconstriction. This study aimed to determine whether hyperoxic ventilation at Hctcrit further exacerbates myocardial ischemia and dysfunction. METHODS: Nine anesthetized pigs ventilated on room air were hemodiluted by 1:1 exchange of blood with pentastarch (6%HES) to Hctcrit, defined as onset of myocardial ischemia (ECG changes). At Hctcrit, hyperoxic ventilation was started. Measurements were performed at baseline, at Hctcrit, and after 15 min of hyperoxic ventilation. We determined myocardial blood flow (microsphere method), arterial O2-content, subendocardial O2-delivery and myocardial function (left ventricular pressure increase). RESULTS: At Hctcrit 7 (6;8)%, O2-content was reduced [3.7 (3.1;3.9) ml dl(-1)]. Despite a compensatory increase of myocardial blood flow [531 (449;573), ml min(-1)100 g(-1)], all pigs displayed myocardial ischemia and compromised myocardial function (P < 0.05). Hyperoxic ventilation produced increased coronary vascular resistance secondary to vasoconstriction, and reduced myocardial blood flow [426 (404;464), ml min(-1)100 g(-1); P < 0.05]. Myocardial oxygenation was found to be maintained by increased O2-content [4.4 (4.2;4.8), ml dl(-1); P < 0.05], the contribution of dissolved O2 to subendocardial O2-delivery increased (32 vs. 8%; P < 0.05), which preserved myocardial function. CONCLUSION: Hyperoxic ventilation at Hctcrit is followed by coronary vasoconstriction and reduction of coronary blood flow. However, myocardial oxygenation and function is maintained, as increased O2-content (in particular dissolved O2) preserves myocardial oxygenation.     

Optimal myocardial protection strategy for coronary artery bypass grafting without cardioplegia: prospective randomised trial

Although hypothermia and ischaemic preconditioning (IP) are independently recognised mechanisms of cardioprotection, interactions between myocardial temperature and preconditioning have not been investigated. Therefore, this study explored the possibility of inducing IP during hypothermia and quantifying its effects at two temperature regimens commonly used in clinical practice. One hundred and four patients undergoing coronary artery bypass grafting (CABG) with intermittent cross-clamping and ventricular fibrillation were randomised to four groups: N=normothermia (36.5+/-0.5 degrees C); NP=normothermia+preconditioning, H=hypothermia (31.5+/-0.5 degrees C), HP=hypothermia+preconditioning. The primary outcome measure was release of cardiac Troponin I (cTnI), measured at 6 time points from pre- to 72 h after the end of CPB. There were no hospital deaths and no significant differences in pre- and intra-operative variables (P>or=0.05). There were significant differences in cTnI release between all groups, as follows: N: 117+/-12 microg/l (P相似文献   

Does Off‐Pump Revascularization Reduce Coronary Endothelial Dysfunction?

BACKGROUND: Off-pump coronary revascularization (OPCAB) has been shown to reduce markers of acute inflammation but its effect on coronary endothelial function is unknown. This experimental study sought to determine whether OPCAB reduces endothelial dysfunction, compared to standard cardiopulmonary bypass (CPB) with and without the anticomplement agent soluble complement receptor-1 (sCR(1)). METHODS: In 10 pigs, OPCAB was simulated by snaring the left anterior descending (LAD) artery for 15 minutes followed by 3 hours of reperfusion. On-pump revascularization was simulated in 20 pigs by 15 minutes of LAD occlusion on CPB with cold blood cardioplegic arrest followed by 3 hours of reperfusion. Ten of these animals received sCR(1) (10 mg/kg) prior to CPB. Inflammatory response was monitored by percent (%) lung water increase, wall motion scores (WMS) with transthoracic echocardiography where 4 = normal to -1 = dyskinesia, and endothelial function in the distal LAD with bradykinin-induced coronary artery relaxation using organ chamber methodology. RESULTS: OPCAB had no effect on lung edema (% increase = 1.7 +/- 1.4 OPCAB vs. 3.4 +/- 0.5 CPB vs. 2.3 +/- 0.9 CPB + sCR(1)) and failed to prevent wall motion changes (WMS = 2.65 +/- 0.08 OPCAB vs. 2.70 +/- 0.04 CPB vs. 3.10 +/- 0.07* CPB + sCR(1), *p < 0.01) and coronary endothelial dysfunction (% relaxation = 41 +/- 9 OPCAB vs. 40 +/- 9 CPB vs. 78 +/- 8** CPB + sCR(1), **p < 0.001), which was best preserved with sCR(1). CONCLUSIONS: This study suggests that agents which directly inhibit complement activation such as sCR(1) are more important in preventing endothelial dysfunction during coronary revascularization than merely avoiding CPB.     

Myocardial revascularization with and without cardiopulmonary bypass in multivessel disease: impact of strategy on midterm outcome

BACKGROUND: In a previous study, we demonstrated that patients with multivessel disease benefit during the first postoperative month from elimination of cardiopulmonary bypass (CPB). We evaluated the midterm results of the same patients excluding the first postoperative month from the analysis. METHODS: From May 1997 to November 2000, 1,802 patients with multivessel disease survived the first postoperative month; 906 were operated on without (group A) and 896 with (group B) CPB. Follow-up ranged from 23 to 65 months (mean, 42 +/- 12 months). Four-year actuarial freedom from the following events was evaluated: death from any cause; cardiac death; acute myocardial infarction (AMI) in any territory; AMI in a grafted area; redo percutaneous transluminal coronary angioplasty (PTCA); redo PTCA in a target vessel; cardiac events (death from a cardiac cause, acute myocardial infarction on grafted vessel, redo PTCA on target vessel); and any event. RESULTS: No statistical difference was found between groups A and B with regard to freedom from any death (95.3 +/- 0.8 vs 95.7 +/- 0.7, p = 0.5160); from cardiac death (97.3 +/- 0.6 vs 97.5 +/- 0.6, p = 0.5345); from AMI (98.4 +/- 0.4 vs 98.7 +/- 0.4, p = 0.4655); from AMI in a grafted area (98.9 +/- 0.4 vs 98.7 +/- 0.4, p = 0.9374); from redo PTCA (97.9 +/- 0.5 vs 97.7 +/- 0.6, p = 0.8485); from redo PTCA in a grafted area (98.7 +/- 0.4 vs 98.5 +/- 0.5, p = 0.8774); from target cardiac events (95.8 +/- 0.7 vs 95.9 +/- 0.8, p = 0.6070); and from any event (92.9 +/- 0.9 vs 93.4 +/- 1.0, p = 0.3721). CONCLUSIONS: After exclusion of the first postoperative month, myocardial revascularization without CPB has midterm results similar to myocardial revascularization with CPB. In particular, failure of revascularization does not depend on intraoperative strategy.