Warm reperfusion and myocardial protection

BACKGROUND: The aim of this study was to determine whether warm reperfusion improves myocardial protection with cardiac troponin I as the criteria for evaluating the adequacy of myocardial protection. METHODS: One hundred five patients undergoing first-time elective coronary bypass surgery were randomized to one of three cardioplegic strategies of either (1) cold crystalloid cardioplegia followed by warm reperfusion, (2) cold blood cardioplegia followed by warm reperfusion, or (3) cold blood cardioplegia with no reperfusion. RESULTS: The total amount of cardiac troponin I released tended to be higher in the cold blood cardioplegia with no reperfusion group (3.9+/-5.7 microg) than in the cold blood cardioplegia followed by warm reperfusion group (2.8+/-2.7 microg) or the cold crystalloid cardioplegia followed by warm reperfusion group (2.8+/-2.2 microg), but not significantly so. Cardiac troponin I concentration did not differ for any sample in any of the three groups. CONCLUSIONS: Our study showed that the addition of warm reperfusion to cold blood cardioplegia offers no advantage in a low-risk patient group.     

Crystalloid versus cold blood cardioplegia and cardiac troponin I release

BACKGROUND: Cardiac troponin I (CTnI) has been shown to be a marker of myocardial injury. The aim of this study was to compare antegrade crystalloid cardioplegia with antegrade cold blood cardioplegia with warm reperfusion using CTnI release as the criteria for evaluating the adequacy of myocardial protection. METHODS AND RESULTS: Seventy patients were randomly assigned to receive crystalloid or blood cardioplegia. CTnI concentrations were measured in serial venous blood samples drawn just before cardiopulmonary bypass and after aortic unclamping at 6, 9, 12, and 24 hours and daily thereafter for 5 days. ANOVA with repeated measures was performed to test the effect of the type of cardioplegia on CTnI release. The total amount of CTnI released was higher in the crystalloid cardioplegia group than in the blood cardioplegia group (11.2 +/- 8.9 versus 7.8 +/- 8.6 micrograms, P < .02). CTnI concentration was significantly higher in the crystalloid group than in the blood group in the samples drawn at hours 9 and 12. Three patients in each group had ECG evidence of perioperative myocardial infarction. Eight patients in the crystalloid group and five patients in the blood group had CTnI evidence of perioperative myocardial infarction. CTnI release was significantly lower in patients requiring no electrical defibrillation after aortic unclamping. CONCLUSIONS: Cold blood cardioplegia followed by warm reperfusion is beneficial in an unselected group of patients with a preserved left ventricular function undergoing an elective first coronary artery bypass grafting. CTnI allowed the diagnosis of small perioperative necrotic myocardial areas. The need for electrical defibrillation after aortic unclamping was related to a higher release of CTnI. A further study is necessary to determine whether this technique was beneficial because of cold blood cardioplegia, warm reperfusion, or both.     

Homeobox genes in hematopoiesis and leukemogenesis

The effect of cold and warm intermittent antegrade blood cardioplegia, on the intracellular concentration of taurine in the ischaemic/reperfused heart of patients undergoing aortic valve surgery, was investigated. Intracellular taurine was measured in ventricular biopsies taken before institution of cardiopulmonary bypass, at the end of 30 min of ischaemic arrest and 20 min after reperfusion. There was no significant change in the intracellular concentration of taurine in ventricular biopsies taken after the period of myocardial ischaemia in the two groups of patients (from 10.1 +/- 1.0 to 9.6 +/- 0.9 mumol/g wet weight for cold and from 9.3 +/- 1.3 to 10.0 +/- 1.3 mumol/g wet weight for warm cardioplegia, respectively). Upon reperfusion however, there was a fall in taurine in both groups but was only significant (P < 0.05) in the group receiving cold blood cardioplegia (6.9 +/- 0.8 mumol/g wet weight after cold blood cardioplegia versus 8.0 +/- 0.8 mumol/g wet weight following warm blood cardioplegia). Like taurine, there were no significant changes in the intracellular concentration of ATP after ischaemia in the two groups of patients (from 3.2 +/- 0.32 to 2.95 +/- 0.43 mumol/g wet weight for cold and from 2.75 +/- 0.17 to 2.62 +/- 0.21 mumol/g wet weight for warm cardioplegia, respectively). However upon reperfusion there was a significant fall in ATP in both groups with the extent of the fall being less in the group receiving warm cardioplegia (1.79 +/- 0.19 mumol/g wet weight for cold and 1.98 +/- 0.27 mumol/g wet weight for warm cardioplegia, respectively). This work shows that reperfusion following ischaemic arrest with warm cardioplegia reduces the fall in tissue taurine seen after arrest with cold cardioplegia. Accumulation of intracellular sodium provoked by hypothermia and a fall in ATP, may be responsible for the fall in taurine by way of activating the sodium/taurine symport to efflux taurine.     

Cerebellar granule cell GABA(A) receptors studied at the single-channel level: modulation by protein kinase G

BACKGROUND: This study was designed to evaluate the adenosine-triphosphate-sensitive potassium channel opener pinacidil as a blood cardioplegic agent. METHODS: Using a blood-perfused, parabiotic, Langendorff rabbit model, hearts underwent 30 minutes of normothermic ischemia protected with blood cardioplegia (St. Thomas' solution [n = 8] or Krebs-Henseleit solution with pinacidil [50 micromol/L, n = 81) and 30 minutes of reperfusion. Percent recovery of developed pressure, mechanical arrest, electrical arrest, reperfusion ventricular fibrillation, percent tissue water, and myocardial oxygen consumption were compared. RESULTS: The percent recovery of developed pressure was not different between the groups (52.3 +/- 5.9 and 52.8 +/- 6.9 for hyperkalemic and pinacidil cardioplegia, respectively). Pinacidil cardioplegia was associated with prolonged electrical and mechanical activity (14.4 +/- 8.7 and 6.1 +/- 3.9 minutes), compared with hyperkalemic cardioplegia (1.1 +/- 0.6 and 1.1 +/- 0.6 minutes, respectively; p < 0.05). Pinacidil cardioplegia was associated with a higher reperfusion myocardial oxygen consumption (0.6 +/- 0.1 versus 0.2 +/- 0.0 mL/100 g myocardium/beat; p < 0.05) and a higher percent of tissue water (79.6% +/- 0.7% versus 78.6% +/- 1.2%; p < 0.05). CONCLUSIONS: Systolic recovery was not different between groups, demonstrating comparable effectiveness of pinacidil and hyperkalemic warm blood cardioplegia.     

Effects of cold and warm blood cardioplegia assessed by myocardial pH and release of metabolic markers

The optimal temperature of blood cardioplegia remains controversial. Interstitial myocardial pH was monitored online with a probe that was inserted in the anterior wall of the left ventricle. Venous pH, lactate production, and creatine kinase and troponin T release were measured in coronary sinus blood obtained in 14 dogs after ischemic arrest periods of 5, 10, 20, and 40 minutes with warm (n = 7; mean myocardial temperature, 35 degrees +/- 2 degrees C) and cold (n = 7; mean myocardial temperature, 12 degrees +/- 1 degree C) blood cardioplegic protection. Blood cardioplegic solution was delivered at a rate of 100 mL/min during the 10 minutes between each ischemic arrest. The interstitial myocardial pH decreased significantly (p < 0.05) from 7.1 +/- 0.3 to 6.53 +/- 0.3 after ischemia in animals perfused with warm blood cardioplegia and from 7.04 +/- 0.3 to 6.64 +/- 0.1 in those receiving cold blood cardioplegic protection; however, the difference between the groups was not significant (p > 0.05). Lactate production and creatine kinase and troponin T release increased significantly after ischemia, but there was no difference in the changes between the warm and cold blood cardioplegia groups. In conclusion, ischemia caused significant changes in all variables measured, and these changes were directly proportional to the duration of ischemia. However, there was no significant difference (p > 0.05) in the myocardial metabolic changes between the warm and cold blood cardioplegia groups in terms of the duration of ischemic arrest studied.(ABSTRACT TRUNCATED AT 250 WORDS)     

The use of cluster analysis for cell typing

BACKGROUND: Experiments were designed to evaluate the effect of warm blood cardioplegia on endothelium-dependent contraction of the coronary endothelium after cardiac global ischemia and reperfusion. METHOD: Dogs (n = 12 in each group) were exposed to extracorporeal circulation with the body temperature at 37 degrees C (group 1) or 28 degrees C (groups 2 and 3). The ascending aorta was crossclamped for 120 minutes while continuous infusion of warm blood cardioplegec solution (group 1) or intermittent infusion of cold (4 degrees C) crystalloid cardioplegic solution (group 2) was performed via the coronary arteries through the aortic root. Cardioplegic solution was not used in group 3 animals. The heart was then allowed to function for 60 minutes of reperfusion. Reperfused (groups 1, 2, and 3) and control (group 4) coronary arteries were then harvested for study. RESULTS: Perfusate hypoxia caused endothelium-dependent contraction in the arteries of all four groups that could be attenuated by NG-monomethyl-L-arginine (L-NMMA) or L-NMMA plus D-arginine, but not by L-NMMA plus L-arginine or endothelin receptor A and B antagonist PD 145065. The endothelium-dependent contraction results in groups 2 and 3 (75% +/- 4% and 80% +/- 5%, respectively) were significantly greater than those in groups 1 and 4 (15% +/- 3% and 18% +/- 5%, respectively). Scanning electron microscope studies showed that platelet adhesion and aggregation, areas of microthrombi, disruption of endothelial cells, and separation of the intercellular junction could be found in coronary segments from groups 2 and 3, but not in vessels from groups 1 and 4. CONCLUSION: These experiments suggest that global ischemia and reperfusion enhances hypoxia-mediated endothelium-dependent contraction of the coronary endothelium and damages the ultrastructure. These kinds of changes can be prevented by continuous antegrade infusion of warm blood cardioplegic solution during global ischemia.     

A clinical application of histidine buffered cardioplegia

Blood cardioplegia has been widely accepted due to better oxygen delivery, pH buffering and free radical scavenge. We have found that a crystalloid cardioplegia solution formulated to accelerate anaerobic glycolysis with high buffering capacity. To conserve blood cardioplegia, we formulated a crystalloid cardiopletia containing 100 mM histidine for buffering. This cardioplegia (HBS) was compared to cold blood cardioplegia in patients requiring open heart surgery. Eighty patients including HBS (n = 28), and CBC (n = 40) were involved in this study. Left ventricular end-systolic elastance (Emax; mmHg/cm3) was evaluated pre- and postoperatively. Cardiac index and inotropic requirement were also monitored at 1, 3, and 12 hours after cardiopulmonary bypass. There was no death in either group. All hearts returned to previous rhythm in HBS group, whereas total 12 DC cardioversions were requested in 6 patients. Emax was significantly higher in HBS group (5.2 +/- 0.6 mmHg/cm3) than in CBC group (3.4 +/- 0.4 mmHg/cm3). Cardiac index was also significantly higher in HBS group postoperatively than in CBC group with lower inotropic requirements. We conclude that histidine containing crystalloid cardioplegia provides excellent recovery of cardiac performance with lower inotropic requirements in open heart surgery. The ease of use, and lack of blood are other important advantages of this crystalloid cardioplegia.     

How to protect hypertrophied myocardium? A prospective clinical trial of three preservation techniques

Protection of the hypertrophied myocardium during heart surgery is still a controversial matter. We prospectively studied 3 currently available preservation techniques in 60 patients operated on for isolated aortic stenosis. Patients were randomly assigned to one of the following groups: CWB: continuous warm blood cardioplegia ICB: intermittent cold blood with warm blood controlled reperfusion Cryst: intermittent cold crystalloid cardioplegia (SLF11, Biosédra Laboratory, Vernon, France). All groups were matched for age, ejection fraction, NYHA class, aortic valve surface, and operative risk score. There were no deaths. No statistically significant difference was found among the groups in terms of ventilatory support time, ICU stay time, hospitalization or atrial fibrillation occurrence. Blood gases in the coronary sinus at the time of clamp release showed deep acidosis with crystalloid cardioplegia (pH = 7.11 vs 7.39 for CWB and 7.38 for UCB, p < 0.0001) associated with a higher lactate production than in the other groups (1.3 mmol vs 0.5 for CWB and 0.58 for ICB, p < 0.0001). Acidosis was corrected at the end of bypass with no significant differences among groups. CK-MB samples were taken on arrival in ICU, then 6 and 24 hours later. These samples showed much higher levels with cold blood (H6: 70 mcg/l vs 33 for CWB and 45 for Cryst, p = 0.0019). Although the 3 types of cardioplegia may be safely used for isolated aortic stenosis surgery, continuous warm blood cardioplegia appears to be the best choice.     

Controlled reperfusion after lung ischemia: implications for improved function after lung transplantation

OBJECTIVES: Despite improvements in organ preservation, reperfusion injury remains a major source of morbidity and mortality after lung transplantation. This pilot study was designed to investigate the effects of controlled reperfusion after lung ischemia. METHODS: Twenty adult pigs underwent 2 hours of warm lung ischemia by crossclamping the left bronchus and pulmonary artery. In five (group 1), the clamp was simply removed at the end of ischemia (uncontrolled reperfusion). The 15 other pigs underwent modified reperfusion using blood from the femoral artery to perfuse the lung through the pulmonary artery (pressure 40 to 50 mm Hg) for 10 minutes before removing the pulmonary artery clamp. In five (group 2), the blood was mixed with crystalloid, resulting in a substrate-enriched, hypocalcemic, hyperosmolar, alkaline solution. In five (group 3), the blood was circulated through a leukocyte-depleting filter, and the last five (group 4) underwent reperfusion with both a modified solution and white blood cell filter. Lung function was assessed 60 minutes after reperfusion, and biopsy specimens were taken. RESULTS: Controlled reperfusion with both a white blood cell filter and modified solution (group 4) completely eliminated the reperfusion injury that occurred with uncontrolled reperfusion (group 1), resulting in complete preservation of compliance (98% +/- 1% vs 77% +/- 1%; p < 0.001, and arterial/alveolar ratio (97% +/- 2% vs 27% +/- 2%; p < 0.001); no increase in pulmonary vascular resistance (106% +/- 1% vs 198% +/- 1%; p < 0.001); lowered tissue edema (82.1% +/- 0.4% vs 84.3% +/- 0.2%; p < 0.001), and myeloperoxidase activity (0.18 +/- 0.02 vs 0.35 +/- 0.02 deltaOD/min/mg protein; p < 0.001). In contrast, using either a white blood cell filter or modified solution separately improved but did not avoid the reperfusion injury, resulting in pulmonary function and tissue edema levels that were intermediate between group 1 (uncontrolled reperfusion) and group 4 (white blood cell filter and modified solution). CONCLUSION: After 2 hours of warm pulmonary ischemia, (1) a severe lung injury occurs after uncontrolled reperfusion, (2) controlled reperfusion with either a modified reperfusion solution or white blood cell filter limits, but does not avoid, a lung reperfusion injury, (3) reperfusion using both a modified reperfusate and white blood cell filter results in complete preservation of pulmonary function. We therefore believe surgeons should control the reperfusate after lung transplantation to improve postoperative pulmonary function.     

Intermittent antegrade tepid versus cold blood cardioplegia in elective myocardial revascularization

BACKGROUND: The ideal temperature for blood cardioplegia administration remains controversial. METHODS: Fifty-two patients who required elective myocardial revascularization were prospectively randomized to receive intermittent antegrade tepid (29 degrees C; group T, 25 patients) or cold (4 degrees C; group C, 27 patients) blood cardioplegia. RESULTS: The two cohorts were similar with respect to all preoperative and intraoperative variables. The mean septal temperature was higher in group T (T, 29.6 degrees +/- 1.1 degrees C versus 17.5 degrees +/- 3.0 degrees C; p < 0.0001). After reperfusion, group T exhibited significantly greater lactate and acid release despite similar levels of oxygen extraction (p < 0.05). The creatine kinase-MB isoenzyme release was significantly lower in group T (764 +/- 89 versus 1,120 +/- 141 U x h/L; p < 0.04). Hearts protected with tepid cardioplegia demonstrated significantly increased ejection fraction with volume loading, improvement in left ventricular function at 12 hours, and decreased need for postoperative inotropic support (p < 0.05). The frequency of ventricular defibrillation after cross-clamp removal was lower in this cohort (p < 0.05). There were no hospital deaths, and both groups had similar postoperative courses. CONCLUSIONS: Intermittent antegrade tepid blood cardioplegia is a safe and efficacious method of myocardial protection and demonstrates advantages when compared with cold blood cardioplegia in elective myocardial revascularization.     

Time dependence of endothelium-mediated vasodilation by intermittent antegrade warm blood cardioplegia

BACKGROUND: The technique of intermittent antegrade warm blood cardioplegia (IAWBC) exposes the heart to brief periods of normothermic ischemia. This may impair endothelial function in coronary arteries. METHODS: Three cardioplegic technique were tested in porcine hearts arrested for 32 to 36 minutes and reperfused for 30 minutes: IAWBC, antegrade cold blood cardioplegia (ACBC), and antegrade cold crystalloid cardioplegia (ACCC). In the hearts arrested with IAWBC, three different intervals of ischemia were used: three 10-minute intervals (IAWBC1), two 15-minute intervals (IAWBC2), and one 30-minute interval (IAWBC3). Rings from the coronary arteries were used to evaluate in vitro the contractile responses to U46619 and the relaxant responses to bradykinin, A23187, and sodium nitroprusside. RESULTS: All six groups (treatment groups and control group) displayed similar responses to U46619 (30 nmol/L) and nitroprusside. In the IAWBC1, IAWBC2, AND ACBC groups, endothelium-dependent relaxations to bradykinin and A23187 were preserved compared with controls, whereas those of the ACCC and IAWBC3 groups were significantly impaired (bradykinin: control, 8.72 +/- 0.07; IAWBC1, 8.73 +/- 0.03; IAWBC2, 8.65 +/- 0.05; IAWBC3, 8.30 +/- 0.07 [p < 0.05]; ACBC, 8.50 +/- 0.03; ACCC, 8.25 +/- 0.09 [p < 0.05]; A23187: control, 7.07 +/- 0.08; IAWBC1, 7.07 +/- 0.06; IAWBC2, 7.04 +/- 0.03; IAWBC3, 6.64 +/- 0.01 [p < 0.05]; ACBC, 6.80 +/- 0.05; ACCC, 6.60 +/- 0.08 [p < 0.05]; nitroprusside: control, 6.19 +/- 0.1; IAWBC1, 6.19 +/- 0.07; IAWBC2, 6.03 +/- 0.03; IAWBC3, 6.08 +/- 0.05; ACBC, 6.04 +/- 0.2; ACCC, 6.05 +/- 0.03; all values are expressed as the negative logarithm of the concentration producing 50% of the maximal response). CONCLUSIONS: Myocardial preservation with IAWBC with ischemic intervals of 15 minutes or shorter does not alter the endothelium-dependent relaxation to bradykinin or A23187 in porcine coronary arteries, but these responses are significantly impaired by ACCC and IAWBC with an ischemic interval of 30 minutes.     

Closed-chest cardiopulmonary bypass and cardioplegia: basis for less invasive cardiac surgery

BACKGROUND: We developed a method of closed-chest cardiopulmonary bypass to arrest and protect the heart with cardioplegic solution. This method was used in 54 dogs and the results were retrospectively analyzed. METHODS: Bypass cannulas were placed in the right femoral vessels. A balloon occlusion catheter was passed via the left femoral artery and positioned in the ascending aorta. A pulmonary artery vent was placed via the jugular vein. In 17 of the dogs retrograde cardioplegia was provided with a percutaneous coronary sinus catheter. RESULTS: Cardiopulmonary bypass time was 111 +/- 27 minutes (mean +/- standard deviation) and cardiac arrest time was 66 +/- 21 minutes. Preoperative cardiac outputs were 2.9 +/- 0.70 L/min and postoperative outputs were 2.9 +/- 0.65 L/min (p = not significant). Twenty-one-French and 23F femoral arterial cannulas that allowed coaxial placement of the ascending aortic balloon catheter were tested in 3 male calves. Line pressures were higher, but not clinically limiting, with the balloon catheter placed coaxially. CONCLUSIONS: Adequate cardiopulmonary bypass and cardioplegia can be achieved in the dog without opening the chest, facilitating less invasive cardiac operations. A human clinical trial is in progress.     

Knowledge and perceptions of medical abortion among potential users

Great advances in surgical techniques, perfusion technology and cardiac anesthesia have made heart surgery safer. However, the mayor advance over the past 15 years has been in the field of myocardial protection. Much remains to be done in this field and there is not complete agreement about the different methods of myocardial protection. At the Institute of Cardiac Surgery of Parma a research is developing to concern three different cardioprotective strategies, of which preliminary results are showing. Three groups of patients with the same clinical, surgical, anesthesiological features, who underwent cardiac surgery have been selected. In patients of group A intermittent cold hyperkalemic crystalloid cardioplegia has been used, in those of group B intermittent cold blood cardioplegia and in those of group C intermittent cold blood cardiolegia associated a warm glucose blood cardioplegic reperfusion before aortic unclamping. In all patients enzyme levels (CPK; CPK-MB; LHD; SGOT; SGPT) were measured 12, 24, 72, 120 hours postoperatively; data were collected, also, on spontaneous return to sinus rhythm, perioperative myocardial infarction and the need or not for inotropic agents. All data at first and then those of patients who underwent only coronary rivascularization (75% of patients) were statistically analyzed (one-way Fischer's test). It appears that the use of antegrade cold intermittent blood cardioplegia with reperfusion is more optimal for myocardial protection, how show lower levels of CPK-MB especially in the first postoperative period. In group C remains greater spontaneous resumption of normal sinus rhythm compare to group A and this suggests a best preservation of cellula-integrity and function with use of blood cardioplegia.     

Therapeutic implications of thymic uptake of radioiodine in thyroid carcinoma

BACKGROUND: NPC18915, a member of new antiinflammatory agent called nactins (neutrophil activation inhibitors), has been shown to reduce reperfusion injury in rat lung transplantation at high dosage. In vitro studies have demonstrated effectiveness of this compound even at low dosage. We hypothesized that this compound ameliorates lung ischemia reperfusion injury even at low dosage levels if administration is optimally timed. The aim of this study was to determine the efficacy and the best timing for administration of low-dose NPC18915. METHODS: Forty syngeneic rat left lung transplantations were performed. All isografts were flushed with low-potassium dextran-1% glucose solution 20 ml and preserved for 18 hours at 4 degrees C. Animals were divided into four groups. Group I animals (n = 10) served as control subjects. In groups II (n = 10), III (n = 10), and IV (n = 10), NPC18915 (0.04 mg) was added to the flush solution and was administered intravenously (0.4 mg/kg) immediately before reperfusion (group II) and 60 minutes (group III) and 120 minutes (group IV) after reperfusion. Pulmonary function was assessed 24 hours after reperfusion. RESULTS: In group III, oxygenation improved in comparison to group I (247.2 +/- 59.8 versus 76.6 +/- 16.0 mm Hg, p < 0.002). Wet-to-dry weight ratio and graft myeloperoxidase activity were significantly improved (group III versus group I, 6.02 +/- 0.21 versus 7.19 +/- 0.41, p = 0.013) (group III versus group I, 0.093 +/- 0.019 versus 0.207 +/- 0.023 delta optical density/min/mg, p < 0.002). There were no significant differences in CD11b expression. CONCLUSION: These data suggest that delayed administration of NPC18915, 60 minutes after reperfusion, dramatically improves pulmonary graft function.     

Protective effect of preservation of canine pancreas by the two-layer (University of Wisconsin solution/perfluorochemical) method against rewarming ischemic injury during implantation

Rewarming ischemia during implantation severely compromises posttransplant pancreas graft survival because the graft has already been subjected to warm and cold ischemia before implantation. The purpose of this study was to examine whether preservation of the pancreas graft by the two-layer method ameliorates rewarming ischemic injury of the graft during implantation using a canine model. After flushing with cold University of Wisconsin solution (UW), the pancreas grafts were preserved by the two-layer (UW/perfluorochemical [PFC]) method (group 1) or simple cold storage in UW (group 2) for 24 hr and then autotransplanted. In control, the pancreas grafts were flushed out with cold UW and immediately autotransplanted without preservation (group 3). After completion of vascular anastomosis, vascular clamp was not released until 90, 120, or 150 min of rewarming ischemia, including anastomosis time, had elapsed. After 90 min of rewarming ischemia, graft survival rates were 5/5, 100%, 5/5, 100%, and 5/5, 100%, in groups 1, 2, and 3, respectively. After 120 min, all the grafts in groups 2 and 3 failed (0/5, 0%, and 0/5, 0%, respectively); however, all the grafts in group 1 survived (5/5, 100%). Even after 150 min, 1 of 3 grafts in group 1 survived (1/3, 33%). After 24 hr preservation, tissue ATP levels of the grafts in group 1 were about 2-fold the reference values before harvesting (8.23 +/- 0.72 vs. 4.44 +/- 0.49 mumol/g dry weight, P < 0.05) and significantly higher compared with group 2 (8.23 +/- 0.72 vs. 1.76 +/- 0.52 mumol/g dry weight, P < 0.01). After 120 min of rewarming ischemia, tissue ATP levels in group 1 were 84% of the reference values and significantly higher compared with group 2 (3.75 +/- 0.25 vs. 1.57 +/- 0.48 mumol/g dry weight, P < 0.05). Two hours after reperfusion, ATP levels in group 1 were 42% of reference values but significantly higher compared with group 2 (1.86 +/- 0.36 vs. 1.03 +/- 0.18 mumol/g dry weight, P < 0.05). We conclude that the two-layer (UW/PFC) method ameliorates rewarming ischemic injury of the pancreas graft during implantation by increasing tissue ATP contents during preservation and consequently maintaining tissue ATP levels during implantation.     

Dichotomy of ischemic preconditioning: improved postischemic contractile function despite intensification of ischemic contracture

BACKGROUND: Acceleration of ischemic contracture is conventionally accepted as a predictor of poor postischemic function. Hence, protective interventions such as cardioplegia delay ischemic contracture and improve postischemic contractile recovery. We compared the effect of ischemic preconditioning and cardioplegia (alone and in combination) on ischemic contracture and postischemic contractile recovery. METHODS AND RESULTS: Isolated rat hearts were aerobically perfused with blood for 20 minutes before being subjected to zero-flow normothermic global ischemia for 35 minutes and reperfusion for 40 minutes. Hearts were perfused at a constant pressure for 60 mm Hg and were paced at 360 beats per minute. Left ventricular developed pressure and ischemic contracture were assessed with an intraventricular balloon. Four groups (n=8 hearts per group) were studied: control hearts with 35 minutes of unprotected ischemia, hearts preconditioned with one cycle of 3 minutes of ischemia plus 3 minutes of reperfusion before 35 minutes of ischemia, hearts subjected to cardioplegia with St Thomas' solution infused for 1 minute before 35 minutes of ischemia, and hearts subjected to preconditioning plus cardioplegia before 35 minutes of ischemia. After 40 minutes of reperfusion, each intervention produced a similar improvement in postischemic left ventricular development pressure (expressed as a percentage of its preischemic value: preconditioning, 44 +/- 2%; cardioplegia, 53 +/- 3%; preconditioning plus cardioplegia, 54 +/- 4% and control, 26 +/- 6%, P<.05). However, preconditioning accelerated whereas cardioplegia delayed ischemic contracture; preconditioning plus cardioplegia gave an intermediate result. Thus, times to 75% contracture were as follows: control, 14.3 +/- 0.4 minutes; preconditioning, 6.2 +/- 0.3 minutes; cardioplegia 23.9 +/- 0.8 minutes; and preconditioning plus cardioplegia 15.4 +/- 2.4 minutes (P<.05 preconditioning and cardioplegia versus control). In additional experiments, using blood- and crystalloid-perfused hearts, we describe the relationship between the number of preconditioning cycles and ischemic contracture. CONCLUSIONS: Although preconditioning accelerates, cardioplegia delays, and preconditioning plus cardioplegia has little effect on ischemic contracture, each affords similar protection of postischemic contractile function. These results question the utility of ischemic contracture as a predictor of the protective efficacy of anti-ischemic interventions. They also suggest that preconditioning and cardioplegia may act through very different mechanisms.     

The effect of coenzyme Q10 and cold cristalloid cardioplegia on hypothermic global ischemia

Coenzyme Q10 (CoQ10, ubiquinone) has been shown to be protective against myocardial ischemia/reperfusion induced injury. The purpose of this study was to investigate the effect of CoQ10 added to cold cristalloid cardioplegia on hypothermic ischemia and normothermic reperfusion using an isolated working rat heart. Hearts (n = 6-9/group) from male Wistar rats were aerobically (37 degrees C) perfused (20 min) with bicarbonate buffer. This was followed by a 3-min infusion of St. Thomas' Hospital cardioplegic solution containing various concentrations of CoQ10 (0, 1, 3, 6, 12, and 58 mumol/L). Hearts were then subjected to 180 min of hypothermic (20 degrees C) global ischemia and 35 min of normothermic (37 degrees C) reperfusion (15 min Langendorff, 20 min working). Ventricular fibrillation (Vf) upon reperfusion was irreversible in the 12 and 58 mumol/ L CoQ10 groups (4/6 and 3/6, respectively). In the hearts which Vf upon reperfusion was not irreversible, the percent recovery of aortic flow (%AF) was 43.3 +/- 5.4% (n = 9) in the control group versus 31.6 +/- 7.7% (n = 6), 38.0 +/- 12.0% (n = 6), 27.2 +/- 6.9% (n = 6), 31.3% (n = 2), and 30.4 +/- 14.2% (n = 3) in the 1, 3, 6, 12, and 58 mumol/L CoQ10 groups, respectively. Creatine kinase leakage during Langendorff reperfusion tended to be greater in the 12 and 58 mumol/L CoQ10 groups than in the control group. Thus, CoQ10 in the cold cristalloid cardioplegic solution induced irreversible Vf upon reperfusion and failed to improve functional recoveries following hypothermic global ischemia.     

Adenosine-enhanced ischemic preconditioning provides enhanced postischemic recovery and limitation of infarct size in the rabbit heart

OBJECTIVE: The purpose of this study was to determine the effect of an intracoronary bolus injection of adenosine used in concert with ischemic preconditioning on postischemic functional recovery and infarct size reduction in the rabbit heart and to compare adenosine-enhanced ischemic preconditioning with ischemic preconditioning and magnesium-supplemented potassium cardioplegia. METHODS: New Zealand White rabbits (n = 36) were used for Langendorff perfusion. Control hearts were perfused at 37 degrees C for 180 minutes; global ischemic hearts received 30 minutes of global ischemia and 120 minutes of reperfusion; magnesium-supplemented potassium cardioplegic hearts received cardioplegia 5 minutes before global ischemia; ischemic preconditioned hearts received 5 minutes of zero-flow global ischemia and 5 minutes of reperfusion before global ischemia; adenosine-enhanced ischemic preconditioned hearts received a bolus injection of adenosine just before the preconditioning. To separate the effects of adenosine from adenosine-enhanced ischemic preconditioning, a control group received a bolus injection of adenosine 10 minutes before global ischemia. RESULTS: Infarct volume in global ischemic hearts was 32.9% +/- 5.1% and 1.03% +/- 0.3% in control hearts. The infarct volume decreased (10.23% +/- 2.6% and 7.0% +/- 1.6%, respectively; p < 0.001 versus global ischemia) in the ischemic preconditioned group and control group, but this did not enhance postischemic functional recovery. Magnesium-supplemented potassium cardioplegia and adenosine-enhanced ischemic preconditioning significantly decreased infarct volume (2.9% +/- 0.8% and 2.8% +/- 0.55%, respectively; p < 0.001 versus global ischemia, p = 0.02 versus ischemic preconditioning and p = 0.05 versus control group) and significantly enhanced postischemic functional recovery. CONCLUSIONS: Adenosine-enhanced ischemic preconditioning is superior to ischemic preconditioning and provides equal protection to that afforded by magnesium-supplemented potassium cardioplegia.     

Myocardial protection in normal and hypoxically stressed neonatal hearts: the superiority of blood versus crystalloid cardioplegia

OBJECTIVES: Blood cardioplegia predominates in the adult because it provides superior myocardial protection, especially in the ischemically stressed heart. However, the superiority of blood over crystalloid cardioplegia in the pediatric population is unproved. Furthermore, because many pediatric hearts undergo a preoperative stress such as hypoxia, it is important to compare the different methods of protection in both normal and hypoxic hearts. METHODS: Twenty neonatal piglets were supported by cardiopulmonary bypass and subjected to 70 minutes of cardioplegic arrest. Of 10 nonhypoxic hearts, five (group 1) were protected with blood cardioplegia and five (group 2) with crystalloid cardioplegia (St. Thomas' Hospital solution). Ten other piglets underwent 60 minutes of ventilator hypoxia (inspired oxygen concentration 8% to 10%) before cardioplegic arrest. Five (group 3) were then protected with blood cardioplegia and the other five (group 4) with crystalloid cardioplegia. Myocardial function was assessed by means of pressure volume loops and expressed as a percentage of control. Coronary vascular resistance was measured with each infusion of cardioplegic solution. RESULTS: No difference was noted between blood (group 1) or crystalloid cardioplegia (group 2) in nonhypoxic hearts regarding systolic function (end-systolic elastance 104% vs 103%), diastolic stiffness (156% vs 159%), preload recruitable stroke work (102% vs 101%), or myocardial tissue edema (78.9% vs 78.9%). Conversely, in hearts subjected to a hypoxic stress, blood cardioplegia (group 3) provided better protection than crystalloid cardioplegia (group 4) by preserving systolic function (end-systolic elastance 106% vs 40%; p < 0.05) and preload recruitable stroke work (103% vs 40%; p < 0.05); reducing diastolic stiffness (153% vs 240%; p < 0.05) and myocardial tissue edema (79.6% vs 80.1%); and preserving vascular function, as evidenced by unaltered coronary vascular resistance (p < 0.05). CONCLUSION: This study demonstrates that (1) blood or crystalloid cardioplegia is cardioprotective in hearts not compromised by preoperative hypoxia and (2) blood cardioplegia is superior to crystalloid cardioplegia in hearts subjected to the preoperative stress of acute hypoxia.     

Ischemic preconditioning prior to myocardial protection with cold blood cardioplegia in coronary surgery

OBJECTIVE: Encouraging results on myocardial preconditioning in experimental models of infarction, stunning or prolonged ischemia raise the question whether preconditioning techniques may enhance conventional cardioplegic protection used for routine coronary surgery. METHODS: A prospective clinical trial was conducted to investigate the effect of additional ischemic normothermic preconditioning prior to cardioplegic arrest applying cold blood cardioplegia in patients scheduled for routine coronary surgery (3 vessel disease, left ventricular ejection fraction > 50%). Two cross clamp periods of 5 min with the hearts beating in sinus rhythm were applied followed by 10 min of reperfusion, each (n = 7, group I). Inducing moderate hypothermia cold blood cardioplegia was delivered antegradely. In control groups, cold intermittent blood cardioplegia (n = 7, group II) was used alone. Coronary sinus effluents were analyzed for release of creatine kinase (CK), CK-MB, lactate, and troponin T at 1, 3, 6, 9, and 12 h. In addition, postoperative catecholamine requirements were monitored. RESULTS: The procedure was tolerated well, and no perioperative myocardial infarction in any of the groups studied occurred. Concentrations of lactate tended to be higher in group I, but this difference was not significant. In addition, no significant differences for concentrations of CK, CK-MB, and troponin T were found. Following ischemic preconditioning an increased dosage of dopamine was required within the first 12 h postoperatively (group I: 2.63 +/- 1.44 microg/kg/min, group II: 0.89 +/- 1.06 microg/kg/min). CONCLUSIONS: Combining ischemic preconditioning and cardioplegic protection with cold blood cardioplegia does not appear to ameliorate myocardial protection when compared to cardioplegic protection applying cold blood cardioplegia alone. Inversely, contractile function seemed to be impaired when applying this protocol of ischemic preconditioning.