Continuous Blood Cardioplegia Research Articles

Normothermic blood cardioplegia. Alternative or adjunct?

Normothermic blood cardioplegia was developed originally to be used during cardioplegic induction and reperfusion as an adjunct for enhancing metabolic reversal of biochemical alterations occurring before, during, and after total myocardial ischemia. This adjunct was introduced clinically after extensive experimental testing. By contrast, continuous normothermic blood cardioplegia without hypothermia was introduced clinically without a scientific infrastructure and has generated great interest because of its simplicity and encouraging early results, but has caused substantial confusion. This report is written to (1) clarify the role of normothermic blood cardioplegia as an adjunct to available hypothermic and antegrade and retrograde methods of myocardial protection, rather than as an alternative to them, (2) call attention to the misconception that continuous coronary perfusion avoids ischemia inasmuch as "unintentional ischemia" may occur despite continuous coronary perfusion, (3) identify theoretic and practical limitations of warm continuous retrograde blood cardioplegia exposed by testing after its clinical introduction, (4) enumerate the unanswered questions posed after clinical use of this method, and (5) focus on the self-imposed inflexibility created by adoption of adversarial positions in regard to cardioprotective strategies that impedes our ability to combine, rationally, the spectrum of approaches to myocardial protection that have evolved from the recognized limitations of individual methods.

Myocardial Protection Era: From Valve Surgery to Heart Transplantation

Myocardial Protection Era: From Valve Surgery to Heart Transplantation

Adenosine in cold blood cardioplegia - a placebo-controlled study

OBJECTIVE Adenosine as an additive in blood cardioplegia is cardioprotective in animal studies, but its clinical role in myocardial protection remains controversial. The aim of this study was to investigate whether the addition of adenosine in continuous cold blood cardioplegia would enhance myocardial protection. METHODS In a prospective double-blind study comparing adenosine 400 μmol l(-1) to placebo in continuous cold blood cardioplegia, 80 patients undergoing isolated aortic valve replacement were randomized into four groups: antegrade cardioplegia with adenosine (n = 19), antegrade cardioplegia with placebo (n = 21), retrograde cardioplegia with adenosine (n = 21) and retrograde cardioplegia with placebo (n = 19). Myocardial arteriovenous differences in oxygen and lactate were measured before, during and after aortic occlusion. Myocardial concentrations of adenine nucleotides and lactate were determined from left ventricular biopsies obtained before aortic occlusion, after bolus cardioplegia, at 60 min of aortic occlusion and at 20 min after aortic occlusion. Plasma creatine kinase (CK-MB) and troponin T were measured at 1, 3, 6, 9, 12 and 24 h after aortic occlusion. Haemodynamic profiles were obtained before surgery and 1, 8 and 24 h after cardiopulmonary bypass. Repeated-measures analysis of variance was used for significance testing. RESULTS Adenosine had no effects on myocardial metabolism of oxygen, lactate and adenine nucleotides, postoperative enzyme release or haemodynamic performance. When compared with the antegrade groups, the retrograde groups showed higher myocardial oxygen uptake (17.3 ± 11.4 versus 2.5 ± 3.6 ml l(-1) at 60 min of aortic occlusion, P < 0.001) and lactate accumulation (43.1 ± 20.7 versus 36.3 ± 23.0 µmol g(-1) at 60 min of aortic occlusion, P = 0.052) in the myocardium during aortic occlusion, and lower postoperative left ventricular stroke work index (27.2 ± 8.4 versus 30.1 ± 7.9 g m m(-2), P = 0.034). CONCLUSIONS Adenosine 400 μmol l(-1) in cold blood cardioplegia showed no cardioprotective effects on the parameters studied. Myocardial ischaemia was more pronounced in patients receiving retrograde cardioplegia.

Hypoplastic Left Heart Syndrome and Aortic Atresia-Mitral Stenosis Variant: Role of Myocardial Protection Strategy and Impact of Ventriculo-coronary Connections After Stage I Palliation

Aortic atresia-mitral stenosis (AA-MS) has been implicated as a determinant of outcome after Stage-1 palliation (S1P) in hypoplastic left heart syndrome (HLHS).Studies evaluating the association of AA-MS with ventriculo-coronary connections (VCC) and mortality report conflicting results. The significance of VCC, myocardial protection, and shunt strategy after S1P has yet to be determined. Between January 2005 and July 2009, 100 neonates with HLHS underwent S1P. Mitral and aortic valves and presence of VCC were assessed. Antegrade continuous cold blood cardioplegia was administered throughout the vast extent of the neo-aortic reconstruction. A right ventricle-to-pulmonary shunt was used for an ascending aortic diameter of 0.6 mm/kg or less. Survival analysis was performed to determine predictors and assess impact of AA-MS and VCC on hospital and interstage mortality. Twenty-seven (of 100) patients had AA-MS. The mean age and weight at S1P were 6.5 ± 2.8 days and 3.09 ± 0.47 kg, respectively. VCC were found in 56% of AA-MS. Twenty-two had Norwood-Sano, 3 had classic Norwood, and 2 had hybrid S1P. VCC were associated with AA-MS, endocardial fibroelastosis, and ascending aortic size <2 mm (P < 0.05) but not higher mortality (P = ns). Operative and interstage survival for AA-MS after S1P was 85.2 and 71%, respectively (not statistically different compared to all other subtypes; P = ns). Actuarial survival after S1P at 1, 3, 6, 12, and 36 months was 92.9 ± 4.9, 78.6 ± 7.8, 75 ± 8.2, 71.3 ± 8.3, and 71.3 ± 8.3%, respectively. Intact atrial septum and post-S1P renal dysfunction (P < 0.05) were independent predictors of hospital and interstage mortality. In patients with HLHS, AA-MS carries no survival disadvantage after S1P during the hospital and interstage period regardless of VCC. Intact atrial septum and post-S1P renal dysfunction predict early and interstage mortality. Myocardial protection and shunt strategy might influence the outcome in this HLHS variant.

Myocardial energy metabolism and functional recovery in coronary bypass surgery: A comparative study between continuous retrograde warm and mild hypothermic blood cardioplegia

The optimal temperature for delivery of continuous retrograde blood cardioplegia is not known. Twenty-two patients admitted to the hospital for elective coronary artery bypass grafting were randomized into the warm (37°) and mild hypothermic (28°C) cardioplegia groups. Changes in myocardial energy metabolism during cardiopulmonary bypass, postoperative efflux of the creatine kinase MB isoform (CK-MB), functional hemodynamic recovery, and postoperative complications were followed. During aortic cross-clamp, the average oxygen consumption was higher in the warm than in the mild hypothermic group (3.4±0.4 vs 2.4±0.3 ml/minute,p=0.06), as was the average transcardiac (outflow-inflow) pCO2-difference (1.1±0.1 vs 0.7±0.1 kPa,p=0.02). The average transcardiac pH-difference during aortic cross-clamp was lower in the warm group (−0.08±0.01 vs −0.06±0.01 U,p=0.02), reflecting more profound tissue acidosis. In accordance with this, warm hearts produced more lactate, especially towards the end of the aortic cross-clamp period (p=0.001). The net efflux of adenosine and its degradation products was more prominent during warm than during mild hypothermic cardioplegia (p=0.016), indicating less degradation of high energy adenylates in the hypothermic group. The functional hemodynamic recovery during the first postoperative day was similar in both patient groups, although the myocardial injury estimated as postoperative leakage of CK-MB was less extensive in the hypothermic group (p=0.011). There were no major differences in the postoperative complications between the study groups. We conclude that continuous retrograde mild hypothermic blood cardioplegia offers better myocardial protection during coronary bypass surgery than does continuous retrograde warm cardioplegia. The clinical significance of this should be tested in a larger series of patients, especially those with recent myocardial infarction, unstable angina, or severely depressed left ventricular function.

Heat Shock Proteins and Myocardial Protection during Cardiopulmonary Bypass

This prospective randomized study investigated the effects of two different cardioplegia techniques on myocardial heat shock protein 70 (HSP70) mRNA levels. Patients undergoing elective coronary artery bypass grafting with cardiopulmonary bypass (CPB) were divided into two equal groups. All patients received the same anaesthesia. Myocardial preservation was achieved by delivering intermittent antegrade isothermic blood cardioplegia in one group and antegrade plus continuous retrograde isothermic blood cardioplegia in the other. Biopsies for measurement of HSP70 mRNA levels were taken from the right atria before surgical manipulation of the heart, and later from the same place following CPB. HSP70 mRNA levels were evaluated using quantitative real-time reverse transcription-polymerase chain reaction. Crossing-point values for HSP70 and β-actin were used to evaluate up-regulation. There was a significant increase in HSP70 mRNA levels in response to CPB in both groups, but no significant between-group difference in HSP70 up-regulation. Further investigation is required to evaluate the correlation between the level of HSP induction and the degree of myocardial protection in more heterogeneous groups of patients.

Effect of Partial Oxygen Supply on Mitochondrial Electron Transport System During Complete Cardiac Ischemia

During complete ischemia we assessed myocardial utilization of the small amount of oxygen available. We also determined whether blood cardioplegia has any advantage over crystalloid cardioplegia in this setting. Patients with preserved left ventricular myocardial function and without anterolateral wall infarct or aneurysm were included to the study. Intermittent cold blood and crystalloid cardioplegia were used in 10 patients (group BC) and 9 patients (group CC), respectively. From myocardial biopsies, obtained before and after ischemia, complete electron transport system (ETS) enzyme activities (NDH, SDH, NCCR, SCCR, and COX) and lactate content were analyzed. Biochemical and hemodynamic analyses also were done. Myocardial and blood temperatures were monitored. Ischemic time was longer in group CC (p < 0.05). There were no important differences in biochemical and hemodynamic variables between the two groups. In addition, there was no difference in NDH and SDH activities as well as COX/SCCR and COX/RS-NCCR ratios between the two groups before and after ischemia. After Ischemia, RS-NCCR in group CC and SCCR and COX activities in both groups were lower than the control. For all enzymes, activity change ratios were not different between groups. Myocardial lactate content was increased in both groups after ischemia. However, the increase in group BC was less (p < 0.01). Based on our findings, we believe that the superiority of blood cardioplegia over crystalloid cardioplegia does not depend on oxygen content, but on other factors such as buffering and free oxygen radical scavenger effects among others. However, with the warm and continuous blood cardioplegia technique, oxygen content might be more important.

Leucocyte-depleted Blood Cardioplegia

The effect of the depletion of leucocytes from cardioplegic and initial myocardial reperfusion blood on the inflammatory response and myocardial protection in patients with unstable angina undergoing cardiopulmonary bypass (CPB) was studied. Patients were allocated randomly to a leucocyte-depleted (LD) group or a control group. The LD group received continuous retrograde LD isothermic blood cardioplegia and the control group received isothermic blood cardioplegia. Blood samples were collected at seven time-points before, during and after the procedure. Total leucocyte counts of cardioplegia blood in the LD group were significantly lower than in the control group, but systemic leucocyte and neutrophil counts after CPB did not differ between the groups. The levels of adhesion molecules, cytokines, elastase and malondialdehyde were significantly increased after CPB in both groups and reached peak values 2-6 h after surgery; no other significant differences were found. LD cardioplegia and myocardial reperfusion did not attenuate the endothelial and neutrophil-mediated components of the CPB-induced inflammatory response, which may lead to myocardial reperfusion injury.

Continuous retrograde blood cardioplegia ensures prolonged aortic cross-clamping time without increasing the operative risk

The aim of this study was to assess whether the continuous retrograde blood cardioplegia ensures prolonged aortic cross-clamping time without increasing the operative risk. From 1996 to 2003, 204 consecutive patients who had cardiac procedure requiring aortic cross-clamping time > or = 150 min, were prospectively included in this study: low risk group (EuroSCORE < or = 2) 50 patients, medium risk group (EuroSCORE 3-5) 68 patients, high risk group (EuroSCORE > or = 6) 86 patients. The myocardial protection associated induction of cardiac arrest by antegrade injection of hyperkalemic warm blood, continuous retrograde intermediate lukewarm (20 degrees C) blood cardioplegia, retrograde warm blood reperfusion and systemic normothermia. The mean aortic clamping time was 187+/-45 min (range 150-436 min). The mean cardiopulmonary bypass time was 245+/-73 min (range 168-653 min). The operative mortality was 8.3% (17 patients). The mean predicted mortality of the population studied (EuroSCORE logistic method) was 8.4%+/-12 (range 0.87%-76.15%) with a 95% confidence interval of 6.7% to 10%. The observed mortality was not different from the predicted mortality. Continuous retrograde intermediate lukewarm blood cardioplegia associated with systemic normothermia allows prolonged aortic clamping time for complex intervention without increase of operative mortality and morbidity.

&lt;![CDATA[Myocardial metabolism after hypothermic retrograde continuous blood cardioplegia with anterograde warm cardioplegic induction]]&gt;

&lt;![CDATA[Myocardial metabolism after hypothermic retrograde continuous blood cardioplegia with anterograde warm cardioplegic induction]]&gt;

Metabolismo miocárdico após cardioplegia sangüínea hipotérmica retrógrada contínua com indução anterógrada normotérmica

OBJECTIVE: To determinate the alterations suffering by myocardium in the hypothermic retrograde continuous blood cardioplegia with antegrade warm cardioplegic induction. METHOD: A metabolic analysis of hypothermic retrograde continuous blood cardioplegia with antegrade warm cardioplegic induction was performed in a prospective study of 15 patients scheduled for elective coronary artery bypass grafting. Arterial and coronary sinus blood samples were simultaneously taken: before establishing cardiopulmonary bypass, after anterograde warm cardioplegic induction, when the aortic clamp was removed and 10, 30 and 60 minutes after reperfusion to analyze the oxygen content and lactate concentration. Four transmural left ventricular biopsy samples were obtained: before aortic clamping, immediately after the initial cardioplegia bolus, immediately before aortic declamping and 30 minutes after reperfusion to analyze the levels of ATP, ADP, AMP and lactate in the myocardium. The CK-MB isoenzyme was analysed in venous blood samples. RESULTS: There were no mortalities in the group. Inotropic support was not necessary in any patients and no peri- or post-operative myocardial infarction was detected. There was a decrease in the arterial-venous extraction of oxygen and lactate in the heart during reperfusion, a partial recovery occurred at 60 minutes of reperfusion. The levels of ATP and the other nucleotides in the myocardium were maintained during aortic clamping, but these levels decreased during the first 30 minutes of reperfusion. The lactate accumulated in the heart muscle during aortic clamping with a decrease occurring during reperfusion. CONCLUSIONS: From a metabolic point of view the method could not avoid an anaerobic metabolism during cross-clamping and only after 60 minutes of reperfusion there was a satisfactory metabolic recovery. These alterations are probably a reflection of cellular ischemic injury that occurs during cross-clamping and they seem to be of transitory effect. A better myocardium protection was observed with the addiction of anterograde warm induction cardioplegia.

Continuous cold blood cardioplegia improves myocardial protection: a prospective randomized study

Background To assess the influence on myocardial protection of the rate of infusion (continuous vs intermittent) of cold blood cardioplegia administered retrogradely during prolonged aortic cross-clamping. The end-points were ventricular performance and biochemical markers of ischemia. Methods Seventy patients undergoing myocardial revascularization for three-vessel disease were prospectively randomized to receive intermittent or continuous retrograde cold blood cardioplegia. Hemodynamic measurements were obtained using a rapid-response thermodilution catheter and included right ventricular ejection fraction, cardiac output, left and right ventricular stroke work index, and systemic and pulmonary vascular resistance. Blood samples were obtained from the coronary sinus before cross-clamp application and immediately after cross-clamp removal for determinations of lactate and hypoxanthine. Results The left ventricular stroke work index trend was significantly superior ( p = 0.038) by repeated-measures analysis in continuous cardioplegia. Other hemodynamic measurements revealed a similar trend. The need for postoperative inotropic drugs support was reduced in continuous cardioplegia. The release of lactate in the coronary sinus after unclamping was 2.30 ± 0.12 mmol/L after intermittent cardioplegia and 1.97 ± 0.09 mmol/L after continuous cardioplegia ( p = 0.036). The release of hypoxanthine was 20.47 ± 2.74 μmol/L in intermittent cardioplegia and 11.77 ± 0.69 μmol/L in continuous cardioplegia ( p = 0.002). Conclusions Continuous cold blood cardioplegia results in improved ventricular performance and reduced myocardial ischemia in comparison with intermittent administration.

Efficacy of esmolol as a myocardial protective agent during continuous retrograde blood cardioplegia

Objective: Esmolol, an ultra-short-acting β-blocker, is known to attenuate myocardial ischemia-reperfusion injury. The aim of this study was to compare the effects of esmolol and potassium on myocardial metabolism during continuous normothermic retrograde blood cardioplegia. Methods: Forty-one patients operated on for isolated aortic valve stenosis were randomly assigned to continuous coronary infusion with either potassium or esmolol during cardiopulmonary bypass. Myocardial metabolism was assessed by measuring the transmyocardial gradient of oxygen content indexed to left ventricular mass of glucose, lactate, and nitric oxide. To do so, blood samples were simultaneously withdrawn upstream (in the cardioplegia line) and downstream of the myocardium (in the left coronary ostium) 10 and 30 minutes after aortic crossclamping. Results: Although the cardioplegia flow rate and pressure were similar, esmolol markedly reduced the transmyocardial gradient of oxygen content indexed to left ventricular mass compared with potassium: 13 ± 6 vs 20 ± 6 mL of oxygen per liter of blood per 100 g of myocardium, respectively, at 10 minutes and 16 ± 8 vs 24 ± 8 mL of oxygen per liter of blood per 100 g of myocardium, respectively, at 30 minutes (P = .009). Coronary glucose and lactate transmyocardial gradients were similar in both groups, indicating adequate myocardial perfusion in all patients at all times. In addition, during retrograde cardioplegia, esmolol showed a lower nitric oxide release compared with that caused by potassium (39 ± 49 μmol × L−1 for potassium vs 14 ± 8 μmol × L−1 for esmolol at 10 minutes and 39 ± 47 μmol × L−1 for potassium vs 6 ± 8 μmol × L−1 for esmolol at 30 minutes, P = .05). However, hemodynamic parameters and plasma troponin I levels remained unchanged postoperatively between the 2 types of cardioplegia. Conclusion: Esmolol provides potent myocardial protection in hypertrophied hearts, at least in part, by reducing myocardial oxygen metabolism.J Thorac Cardiovasc Surg 2003;125:1022-9

Continuous Tepid Blood Cardioplegia Can Preserve Coronary Endothelium and Ameliorate the Occurrence of Cardiomyocyte Apoptosis

In modern cardiac surgery, crystalloid or blood cardioplegic solutions have been used widely for myocardial protection; however, ischemia does occur during protection with intermittent infusion of cold crystalloid or blood cardioplegic solutions. The present study was designed to evaluate the effect of different cardioplegic methods on myocardial apoptosis and coronary endothelial injury after global ischemia, cardiopulmonary bypass (CPB), and reperfusion in anesthetized open-chest dogs. The dogs were classified into five groups to identify the injury of myocardium and coronary endothelium: group 1, normothermic CPB without cardiac arrest; group 2, hypothermic CPB with continuous tepid blood cardioplegia, and with cardiac arrest; group 3, hypothermic CPB with intermittent cold blood cardioplegia, and with cardiac arrest; group 4, hypothermic CPB with intermittent cold crystalloid cardioplegia, and with cardiac arrest; and group 5, sham-operated control group. During CPB, cardiac arrest was achieved with different cardioplegia solutions for 60 min, followed by reperfusion for 4 h before the myocardium and coronary arteries were harvested. Coronary arteries were harvested immediately and analyzed by scanning electron microscopy. Cardiomyocytic apoptosis was detected using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling, Western blot, and DNA ladder methods. Regardless of the detection method used, significantly higher percentages of apoptotic cardiomyocytes were found in group 3 and group 4 than in other groups. Expression of caspase-3 correlated with increased apoptosis. Scanning electron microscopy revealed severe endothelial injury of coronary arteries in group 3 and group 4. These results point to an important explanation for the difference in cardiac recovery after hypothermic ischemia and arrest with various cardioplegic solutions.

Continuous retrograde blood cardioplegia is associated with lower hospital mortality after heart valve surgery

Objective: Myocardial preservation studies comparing blood and crystalloid cardioplegia techniques were almost exclusively performed on patients undergoing coronary bypass, and they were unable to show a difference in hospital mortality. We investigated possible factors, including cardioplegia techniques, influencing hospital mortality in patients undergoing cardiac valve surgery. Methods: We evaluated hospital mortality in 1098 consecutive patients undergoing cardiac valve surgery by using a multivariate logistic regression with propensity score balancing of the groups. In 25% of the patients, multiple valve or Bentall procedures were performed, and in 46% of all patients, coronary bypass grafting was associated with valve surgery. A first cohort of 504 consecutive patients were operated on by using single-shot antegrade cold crystalloid cardioplegia, and a second cohort of 594 patients were operated on by using continuous retrograde cold blood cardioplegia. Results: After correction for patient-related and operative risk factors, lower hospital mortality was found in patients who received retrograde blood cardioplegia (P =.020). The odds ratio of in-hospital death when using blood cardioplegia was 0.44 (95% confidence interval, 0.22-0.88). Further predictors of hospital mortality were age, advanced New York Heart Association functional class, cardiopulmonary bypass time, reoperation, active endocarditis, and renal failure. Conclusions: This study shows that continuous retrograde blood cardioplegia is associated with lower hospital mortality in heart valve operations.J Thorac Cardiovasc Surg 2003;125:121-5

Continuous antegrade blood cardioplegia: cold vs. tepid.

Continuous antegrade blood cardioplegia (CABCP) is used at different temperatures. We investigated the consequences of CABCP at 6 degrees C (COLD) vs. 28 degrees C (TEPID). Anesthetized open-chest pigs (25 +/- 2 kg) were placed on cardiopulmonary bypass (CPB). The hearts were arrested for 30 min by 6 degrees C cold or 28 degrees C tepid CABCP (n = 8 each). After an initial 3 min antegrade application of high potassium (20 mEq) cold (6 degrees C) blood cardioplegia, the hearts were arrested for a subsequent 27 min by normokalemic blood delivered antegrade at either 6 degrees C or 28 degrees C. After this, the hearts underwent perfusion with warm systemic blood for an additional 30 min on CPB. Biochemical cardiac data (MVO2 [ml/min/100 g], release of creatine kinase [CK U/min/100 g] and lactate [mg/min/100 g]) were measured during CPB. Total tissue water content (%) and left ventricular stroke work index (SWI g x m/kg) were determined 30 min after discontinuation of CPB and compared to pre-CPB controls. Cold CABCP kept all hearts continuously arrested. The COLD hearts showed no biochemical or functional disturbance. The TEPID hearts intermittently fibrillated and required additional high potassium BCP shots. The TEPID hearts showed a marked CK leakage (2.6 +/- 0.4 vs. 0.7 +/- 0.4), lactate production (4.0 +/- 1.6 vs. extraction from the COLD group) despite the non-ischemic protocol, an impaired initial oxygen consumption (4.2 +/- 1.3 vs. 7.1 +/- 1.6) at the end of cardiac arrest, the formation of myocardial edema (79.5 +/- 1.0 vs. 77.0 +/- 0.8), and a depressed recovery of SWI (0.69 +/- 0.15 degrees vs. 1.41 +/- 0.13). *p < 0.05 for comparison of TEPID vs. COLD hearts using Student's t-test for unpaired data; degrees p < 0.05 for intergroup-comparison of TEPID vs. COLD vs. controls using ANOVA adjusted for repeated measures. Uninterrupted cardioplegia can be safely performed with cold normokalemic CABCP. In contrast, tepid normokalemic CABCP leads to fibrillation, jeopardizes the heart, and should be avoided.UND

酸化ストレスよりみた逆行性持続的血液心筋保護法における至適潅流温度の臨床的検討

酸化ストレスよりみた逆行性持続的血液心筋保護法における至適潅流温度の臨床的検討

Both Glucose-Insulin-Potassium and Glutamine in Warm Blood Cardioplegia Increase the Rates of Myocardial Glucose and Free Fatty Acid Oxidation

Objective -- We wanted to assess the effect of glucose-insulin-potassium (GIK) and glutamine on the oxidative metabolism during and after prolonged warm continuous blood cardioplegia (WB). Design -- WB was given to 21 pigs divided into three equally sized groups: WB (control), WB and GIK, or WB and glutamine. Oxidation rates of radiolabeled glucose ( 14 C) and free fatty acid (FFA) ( 3 H) were assessed before, during, and at 30 and 60 min after 3 h of cardiac arrest with WB. Results -- During standstill the substrate oxidation dropped markedly (<60%), glucose oxidation was highest in the WB + GIK group ( p < 0.05) and FFA oxidation highest in the WB + glutamine group (NS). During recovery the GIK group had an elevated glucose oxidation (47 and 40% vs WB at 30 and 60 min recovery, respectively - p < 0.05). Following 30 min recovery the addition of GIK suppressed FFA oxidation some 60%. Glutamine increased the oxidation of both glucose (30%) and FFA (150%) following 60 min recovery ( p < 0.05). During the whole recovery phase the relative FFA oxidation was significantly lowered in the GIK group. There were no differences between the groups regarding arterial levels or uptake of substrates, except for a higher myocardial oxygen consumption (MVO 2 ) during cardioplegia in the glutamine group. All the hearts performed similarly. Conclusion -- Addition of GIK or glutamine to the well-perfused and oxygenated heart during WB led to a postcardioplegic increase in oxidative metabolism and MVO 2 . GIK resulted in a significant metabolic shift from FFA to glucose.

Cardiac dysfunction and inefficiency after substrate-enriched warm blood cardioplegia.

The study assessed the outcome after prolonged warm continuous antegrade blood cardioplegia (WCBC) with substrate enrichment, in terms of mechanical performance and mechanoenergetic efficiency. WCBC was given for 3 h to three groups of pigs on cardiopulmonary bypass; WCBC alone (n=7), WCBC+glucose and insulin (+GIK, n=7) and WCBC+L-glutamine (+GLN, n=7). Cardiac systolic and diastolic function, pressure-volume area (PVA) and myocardial oxygen consumption (MVO(2)) were assessed before, and twice after WCBC using pressure-conductance catheter, coronary flow-probes and O(2)-content difference. In the WCBC, +GIK and +GLN groups respectively, the following parameters decreased after WCBC compared to baseline: left ventricular developed pressure by 26, 19 and 25% (P<0.001); dP/dt(max) by 36, 37 and 34% (P<0.001); preload recruitable stroke work by 35, 41 and 28% (P<0.001); mechanoenergetic efficiency (PVA/MVO(2)) by 44, 41 and 22% (P<0.001). End-diastolic stiffness increased early after WCBC in the WCBC and +GLN groups, while it was unchanged in the +GIK group (P=0.032). Despite continuous aerobic conditions and additional substrates, post-WCBC cardiac contractile function and mechanoenergetic efficiency was severely depressed. The results demonstrate the hazards of sustained normothermic hyperkalemic perfusion.

Cardioplegia and ischemia in the canine heart evaluated by 31P magnetic resonance spectroscopy

Background. Warm continuous blood cardioplegia provides excellent protection, but must be interrupted by ischemic intervals to aid visualization. We hypothesized that (1) as ischemia is prolonged, the reduced metabolic rate offered by cooling gives the advantage to hypothermic cardioplegia; and (2) prior cardioplegia mitigates the deleterious effects of normothermic ischemia. Methods. Isolated cross-perfused canine hearts underwent cardioplegic arrest followed by 45 minutes of global ischemia at 10°C or 37°C, or 45 minutes of normothermic ischemia without prior cardioplegia. Left ventricular function was measured at baseline and during 2 hours of recovery. Metabolism was continuously evaluated by phosphorus-31 magnetic resonance spectroscopy. Results. Adenosine triphosphate was 71% ± 4%, 71% ± 7%, and 38% ± 5% of baseline at 30 minutes, and 71% ± 4%, 48% ± 5%, and 39% ± 6% at 42 minutes of ischemia in the cold ischemia, warm ischemia, and normothermic ischemia without prior cardioplegia groups, respectively. Left ventricular systolic function, left ventricular relaxation, and high-energy phosphate levels recovered fully after cold cardioplegia and ischemia. Prior cardioplegia delayed the decline in intracellular pH during normothermic ischemia initially by 9 minutes, and better preserved left ventricular relaxation during recovery, but did not ameliorate the severe postischemic impairment of left ventricular systolic function, marked adenosine triphosphate depletion, and creatine phosphate increase. Left ventricular distensibility decreased in all groups. Conclusions. When cardioplegia is followed by prolonged ischemia, better protection is provided by hypothermia than by normothermia. Prior cardioplegia confers little advantage on recovery after prolonged normothermic ischemia but delays initial ischemic metabolic deterioration, which would contribute to the safety of brief interruptions of warm cardioplegia.