Normothermic Blood Cardioplegia Research Articles

CARD27: Morphologic and functional assessment of beating heart in normothermic ex-situ preservation

Background: Heart transplantation remains the treatment of choice for patients experiencing end-stage heart failure. The emergence of cardiac ex situ machine perfusion not only facilitates the use of donor heart through the avoidance of potentially damaging ischemia during graft storage, it also opens new horizons for more sensitive monitoring of graft quality in the transplant field, and morphologic-functional assessment. Methods: Twenty-five domestic adult pigs, weighing 93.1±13.1kg were selected for this study. Until cardiectomy, all pigs received Principles of Laboratory Animal Care. The pig heart were cannulated, and then connected to the Portable System for Normothermic Ex-Situ HeartPreservation (our made). In the Heart Preservation System (HPS), oxygenated blood is perfused by a centrifugal pump into the aorta, perfusing the coronary arteries. After the end of experiment, (6-14 hour) pig heart was arrested with normothermic blood cardioplegia and disconnected. The pig isolated heart was conditioned with Levosimendan while in the system and hemofiltration was applied in the HPS in order to protect and improve donor heart function. Ex-Situ Heart Perfusion process was accompanied with morphologic-functional assessment such as echocardiography, contrast-enhanced magnetic resonance, thermodilution technique and biochemistry. Results: Mean (SD) ischemic time was 19.2 (±3.3) min. Mean ex vivo perfusion time was 560 (±143) min. Time of sinus rhythm restoration was 2.3 (5.7) min. All isolated hearts had stable perfusion, biochemical, as well as myocardial functional parameters measured by echocardiography and thermodilution technique, and histological characteristics in the perfusion system. MRI structural images showed no infiltrates alterations in myocardium. Mean venous lactate trend are with normal levels at the end of perfusion 1.6 (±0.6). Conclusion: Normothermic Ex-Situ Heart Perfusion provides near to physiologic, reproducible approach to sustain the isolated heart for long period of time. Multiparametric assessment of organ morphology and function is feasible in Ex-Situ Heart Perfusion, and may improve organ assessment, leading to a better selection for transplant.Figure 1. Simplified schema of the experimental design and protocol.

Pediatrik Yaş Grubunda Normotermik Kardiyopulmoner By-Pass ve Normotermik Kan Kardiyoplejisi İle Atriyal Septal Defekt Cerrahisi

Pediatrik Yaş Grubunda Normotermik Kardiyopulmoner By-Pass ve Normotermik Kan Kardiyoplejisi İle Atriyal Septal Defekt Cerrahisi

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.

New technique of local ischemic preconditioning induction without repetitive aortic cross-clamping in cardiac surgery.

BackgroundSeveral studies have demonstrated that local ischemic preconditioning can reduce myocardial ischemia–reperfusion injury in cardiac surgery patients; however, preconditioning has not become a standard cardioprotective intervention, primarily because of the increased risk of atheroembolism during repetitive aortic cross-clamping. In the present study, we aimed to describe and validate a novel technique of preconditioning induction.MethodsPatients undergoing coronary artery bypass grafting (12 women and 78 men; mean age, 56 ± 11 years) were randomized into 3 groups: (1) Controls (n = 30), (2) Perfusion (n = 30), and (3) Preconditioning (n = 30). All patients were operated under cardiopulmonary bypass using normothermic blood cardioplegia. Preconditioning was induced by subjecting the hemodynamically unloaded heart to 2 cycles of 3 min of ischemia and 3 min of reperfusion with normokalemic blood prior to cardioplegia. In the Perfusion group, the heart perfusion remained unaffected for 12 min. Troponin I (TnI) levels were analyzed before surgery, and 12, 24, 48 h, and 7 days after surgery. The secondary endpoints included the cardiac index, plasma natriuretic peptide level, and postoperative use of inotropes.ResultsPreconditioning resulted in a significant reduction in the TnI level on the 7th postoperative day only (0.10 ± 0.05 and 0.33 ± 0.88 ng/ml in Preconditioning and Perfusion groups, respectively, P < 0.05). In addition, cardiac index was significantly higher in the Preconditioning group than in the Control and Perfusion groups just after weaning from cardiopulmonary bypass. The number of patients requiring inotropic support with ≥ 2 agents after surgery was significantly lower in the Preconditioning and Perfusion group than in the Control group (P < 0.05). No complications of the procedure were recorded in the Preconditioning group.ConclusionsThe preconditioning procedure described can be performed safely in cardiac surgery patients. The application of this technique of preconditioning was associated with certain benefits, including improved left ventricular function after weaning from cardiopulmonary bypass and a reduced need for inotropic support. However, the infarct-limiting effect of preconditioning in the early postoperative period was not evident. The procedure does not involve repetitive aortic cross-clamping, thus avoiding possible embolic complications.

Myocardial Protection Era: From Valve Surgery to Heart Transplantation

Myocardial Protection Era: From Valve Surgery to Heart Transplantation

Successful Use of Hirudin During Cardiac Surgery Using Minimized Extracorporeal Circulation in Patients With Heparin-Induced Thrombocytopenia

In this case series, we describe our successful use of a reduced hirudin dosage as an anticoagulant during cardiac surgery using minimized extracorporeal circulation in patients with heparin-induced thrombocytopenia.

Left Ventricular Function After Cardiopulmonary Bypass Is Related to the Length-Dependent Regulation of Myocardial Function: In Response

We thank Drs. de Hert and Van der Linden for their insightful comments on our article (1) and we would like to respond on some of the issues brought forward. The aim of our study was two-fold: first, to describe our approach to quantify perioperative LV function, and second, to obtain a reference data set for future studies in patients undergoing cardiac surgery. The comments of de Hert and Van der Linden focus on the latter aspect of our study. We fully agree that the published literature indicates a substantial variability in recovery of LV function after cardiopulmonary bypass, and we acknowledge the extensive list of possible factors influencing this variable outcome. In fact, this is exactly the reason why we felt it was necessary to generate a data set that would be applicable to the anesthetic and cardioprotective approach followed in our institute. Specifically, we use low-dose target-controlled infusion of propofol, remifentanil, and sufentanil, and intermittent antegrade warm-blood cardioplegic arrest during normothermic cardiopulmonary bypass. The metabolic advantages of this approach have already been published, but few data are available on the acute hemodynamic effects. Our study was performed in patients with relatively preserved LV function undergoing elective CABG, to ensure that the possible changes in LV function could be contributed mainly to the effects of anesthesia and cardioplegic arrest, rather than to the surgical intervention. This selection may partly explain the preserved postoperative systolic function in our patient group. However, de Hert et al. studied a similar patient group and reported a more variable outcome that could not be explained by preoperative LV function (2). Therefore, differences in anesthesia and cardioplegic approaches between our study and the studies by de Hert et al. may need to be considered. One such difference is the use of normothermic arrest with blood cardioplegia in our study, whereas the studies of de Hert et al. included the use of hypothermia and crystalloid cardioplegia. This may be important because recent studies indicate less myocardial cell damage after normothermic blood cardioplegia (3). Furthermore, the use of propofol in both studies may not be comparable, because hypothermia has an important influence on propofol pharmacokinetics (4). However, we certainly agree that extrapolation of our findings to patients with poor baseline LV function and prolonged cardiac arrest should be done with caution. But despite this, we would still conclude that the new data provided by our study constitute valuable background information when interpreting the acute hemodynamic effects of complex surgical interventions such as LV reconstruction in heart failure patients in whom the same anesthesia and cardioplegia approach is used. Sven A. F. Tulner Robert J. M. Klautz Gerda L. van Rijk-Zwikker Frank H. M. Engbers Jeroen J. Bax Jan Baan Ernst E. van der Wall Robert A. Dion Paul Steendijk

658. Different Regulation of Atrial and Ventricular HSP70 mRNA Expression during Warm Blood Cardioplegic Arrest in Rats

Objectives: Normothermic blood cardioplegia (CWBCP) is considered as non-ischemic cardioprotection. Heat shock protein (HSP70) and creatine kinase (MCK) are markers of myocardial integrity and ischemia. We hypothesized that changes occur in atrial(A) and in ventricular(V) mRNA expression during CWBCP arrest and that A and V respond differently.

Serum Myoglobin/Carbonic Anhydrase III Ratio in the Diagnosis of Perioperative Myocardial Infarction During Coronary Bypass Surgery

Objective- The purpose of the present study was to evaluate the usefulness of the myoglobin/carboanhydrase III (Myo/CAIII) ratio in the diagnosis of peri operative myocardial infarction during coronary artery bypass surgery.Design- Thirty patients undergoing elective coronary artery bypass grafting (CABG) were included in the series. The patients were randomized in two groups: One received conventional normothermic retrograde blood cardioplegia, while the other was subjected to a 5-min period of ischemic preconditioning before cardioplegia. Biochemical markers for myocardial and skeletal muscle injury were measured in serial blood samples taken postoperatively from 4 h after aortic declamp.Results- Three patients were diagnosed to have suffered from peri operative myocardial infarction on the basis of significant elevations of troponin T and creatine kinase MB-isoenzyme (CK-MB) concentrations. In these particular patients the Myo/CAIII ratio Increased rapidly after aortic declamping. In uncomplicated patients, the median value of the Myo/CAIII ratio remained within normal limits. There was a Positive correlation between the net output of lactate during the aortic cross-clamping period and post-perative Myo/CAIII ratio. The Myo/CAIII ratio proved to be a more specific indicator for myocardial damage than myoglobin alone. The Myo/CAIII ratio was higher in the preconditioning group than in the Control group.Conclusion- Myo/CAIII ratio is a sensitive and specific marker for perioperative myocardial infarction Increasing rapidly after aortic declamping. This ratio could also be used when assessing the extent of ischemic myocardial injury and comparing different Surgical and cardioprotective techniques.

Fast track as a routine for open heart surgery.

Evaluation of thoracic epidural analgesia (TEA), normothermic cardiopulmonary bypass (CPB) and normothermic blood cardioplegia as a routine procedure for fast track open heart surgery. Consecutive patients (n=250, age 36--81 years, mean 63, M/F, ratio=4) were subjected to the combination of general anaesthesia using ultra-short acting opiates, TEA, normothermic CBP, normothermic whole blood cardioplegia. Operative procedures included coronary artery bypass grafting (CABG), valve replacement, combined CABG and valves, aortic aneurysm and Maze III. LVEF ranged 20--76%. Eighty percent were in Tuman score 0--5 and 20% in score >5. All patients were extubated within 10 min after skin closure. There was one myocardial infarction. Four percent were shortly treated with cathecholamines. Postoperative atrial fibrillation was noticed in 9.6%. Four transient cerebral ischemic events were encountered. No neurological disturbance related to the use of TEA was seen. Seven patients were reoperated because of bleeding. Blood transfusion was given to 6.4% of the patients. Mortality was 0.8%. The combined methods provides a way for routine immediate postoperative extubation, with low morbidity and short hospital stay.

Myocardial protection during antegrade versus retrograde cardioplegia

Background. It has been suggested that the right ventricular myocardium is suboptimally protected during retrograde blood cardioplegia. Methods. Twenty patients undergoing an elective coronary bypass procedure were randomized to receive antegrade or retrograde mild hypothermic blood cardioplegia. Transventricular differences in oxygen extraction, lactate production, and pH were monitored during aortic cross-clamping, and myocardial biopsy specimens were taken from both ventricles before cannulation and 15 minutes after aortic declamping for analysis of adenine nucleotides and their breakdown products. The extent of myocardial injury was estimated by monitoring postoperative leakage of troponin T and the MB isoenzyme of creatine kinase. Hemodynamic recovery and postoperative complications were noted. Results. The preoperative characteristics of the two groups were similar. Oxygen extraction and lactate production in the right ventricular myocardium were higher in the retrograde group. In this group, the right ventricle also extracted more oxygen and produced more lactate and acid than did the left ventricle. Tissue levels of adenine nucleotides tended to decrease in both ventricles during operation, with no differences between them. The level of adenosine catabolites did increase somewhat in the right ventricular myocardium of the retrograde cardioplegia group after aortic declamping. There was a tendency for more prominent efflux of troponin T and the MB isoenzyme of creatine kinase in the retrograde group. Nevertheless, the postoperative course was uneventful in both groups. Conclusions. Retrograde mild hypothermic blood cardioplegia leads to metabolic changes compatible with right ventricular ischemia. Nevertheless, tissue levels of high-energy phosphates are well preserved, and the postoperative course seems to be unproblematic. Care should be taken when retrograde normothermic blood cardioplegia is provided for patients with right ventricular hypertrophy, poor right ventricular function, or severe preoperative myocardial ischemia.

Increasing the colloid osmotic pressure of cardiopulmonary bypass prime and normothermic blood cardioplegia minimizes myocardial oedema and prevents cardiac dysfunction

Our recent work demonstrated that normothermic continuous antegrade blood cardioplegia results in cardiac dysfunction related to myocardial oedema. This oedema was partially due to increased myocardial microvascular fluid filtration induced by crystalloid hemodilution. We hypothesized that increasing the colloid osmotic pressure of blood cardioplegia would stop fluid filtration into the cardiac interstitium, thus preventing myocardial oedema and cardiac dysfunction. Methods: We determined myocardial water content in six dogs by microgravimetry and myocardial lymph flow from the major prenodal cardiac lymphatic. Preload recruitable stroke work was derived from sonomicrometry and micromanometry. The dogs were subjected to normothermic cardiopulmonary bypass primed with 6% hetastarch and 1 h of normothermic continuous antegrade blood cardioplegia (4:1 blood:6% hetastarch colloid osmotic pressure 21±2 mmHg) delivered at 50 mmHg perfusion pressure. Results: We found that despite increased colloid osmotic pressure, a small but significant increase in myocardial water content still occurred during blood cardioplegia. As myocardial lymph flow virtually ceased during cardioplegia, myocardial microvascular filtration must have been present. However, increased myocardial lymph flow following cardioplegia resulted in complete oedema resolution associated with normal left ventricular performance post-cardiopulmonary bypass. Conclusions: Our data show that the plegic myocardium is prone to oedema formation because of both relatively enhanced fluid filtration and lymph flow cessation. We conclude that increasing the colloid osmotic pressure of normothermic blood cardioplegia minimizes myocardial oedema, thus preventing post-cardiopulmonary bypass cardiac dysfunction.

Cardiac troponin I as an early marker of myocardial damage after coronary bypass surgery.

To evaluate the performance of cardiac specific markers, cardiac troponin I (cTnI) and CK-MB by mass assay (CK-MB mass), for the early diagnosis of myocardial ischemia and/or infarction after coronary bypass surgery. Prospective clinical, electrocardiograpic and biologic follow-up of 117 patients undergoing isolated coronary surgery with the use of intermittent anterograde normothermic blood cardioplegia. Blood samples for biochemical analysis were drawn before surgery (T0) and at 2 (T1), 6 (T2), 10 (T3) and 20 h (T4) after aortic cross-clamp release. Without knowledge of the biochemical data, patients were classified according to the electrocardiographic evolution into two groups: group 1, uneventful recovery and group 2, evidence of ischemia/infarction based on continuous ST-T segment monitoring and 12-lead ECG. No patients had abnormal markers at T0. At T1, although both markers were elevated, no difference was noted between the two groups. At T2, 6 h after surgery, cTnI and CK-MB mass levels were significantly higher in group 2 than in group 1 (median = 17 microg/l, Interquartile Range (IR): 14.7-27.3 vs. 3.1 microg/l, IR 1.9-5.3 for cTnI and median 42.5 microg/l, IR: 27.1-95.7 vs. 13.6 microg/l, IR: 9.5-18.5 for CK-MB mass). A receiver operating characteristic (ROC) curve analysis shows that a cTnI value of 13.1 microg/ml has 100% specificity and 90% sensitivity to separate both groups, whereas a value of 33.2 microg/ml for CK-MB mass has a specificity of 100% and a sensitivity of 73%. At T3 and T4, the same difference was noted between the groups. cTnI values in all six patients with a Q-wave infarction were > or = 20 ng/ml, whereas only one of five patients with prolonged ischemia had cTnI level > 20 ng/ml. As soon as 6 h postoperatively, cTnI and CK-MB by mass assay were able to separate those patients with an uneventful recovery from those with significant ischemia. This is particularly useful in frequent cases when the ECG is difficult to interpret.

Cardioplegia sangüínea normotérmica intermitente anterógrada: II. Com e sem aminoácidos: estudo comparativo em coelhos

0bjetivos: Investigar se a adição de aspartato e glutamato à solução cardioplégica sangüínea normotérmica, infundida de forma intermitente, acrescentaria benefício a esta técnica de proteção miocárdica. Material e Métodos: Estudaram-se 32 coelhos da raça Nova Zelândia, divididos em grupos Experimental e Controle. O estudo constou de 2 fases: Fase I: Estudo metabólico após isquemia sem reperfusão, Fase II: Estudo metabólico e funcional após reperfusão. A reperfusão foi realizada utilizando-se um sistema de perfusão parabiótica. Determinou-se o glicogênio miocárdico e a respiração mitocondrial no miocárdio ventricular, imediatamente ao final do período de infusão intermitente das soluções cardioplégicas (Fase I) e após reperfusão (Fase II), durante a qual analisou-se, também, a função ventricular esquerda (dP/dtmax). Resultados: Detectou-se queda significativa nos níveis de glicogênio miocárdico, de 53% e 58%, nos grupos com e sem aminoácidos, respectivamente, na fase sem reperfusão. Após reperfusão, não houve diferenças significativas nos níveis de glicogênio miocárdico entre os grupos experimentais e entre estes e seus respectivos controles. A análise da respiração mitocondrial não mostrou diferença significativa entre os grupos experimentais, nem entre cada grupo experimental e seu controle, quer seja com ou sem reperfusão. Quanto à função ventricular, os resultados da dP/dtmax não mostraram diferença significativa em relação aos controles, nem entre os grupos experimentais. Conclusões: A adição de aspartato e glutamato à solução cardioplégica sangüínea a 37°C, infundida anterogradamente e de forma intermitente, não acrescentou benefícios a este método de proteção miocárdica em corações normais de coelhos.

Cardioplegia sangüínea normotérmica intermitente anterógrada: estudo experimental em coelhos

Objetivos: Investigar a proteção miocárdica proporcionada pela infusão anterógrada intermitente, durante 60 minutos, de solução cardioplégica sangüínea a 37°C, em corações normais isolados de coelhos. Material e Métodos: Foram estudados 32 coelhos da raça Nova Zelândia, divididos em grupos, Experimental e Controle. O estudo foi realizado em 2 fases: Fase I: Estudo metabólico após isquemia sem reperfusão, Fase II: Estudo metabólico e funcional após reperfusão. A reperfusão foi realizada utilizando-se um sistema de perfusão parabiótica. Determinou-se o glicogênio miocárdico e a respiração mitocondrial no miocárdio ventricular, imediatamente ao final do período de infusão intermitente da solução cardioplégica (Fase I) e após reperfusão sangüínea (Fase II), durante a qual analisou-se, também, a função ventricular esquerda (dP/dtmax). Resultados: Detectou-se queda significativa nos níveis de glicogênio miocárdico de 58% em relação ao controle, ao final do período de infusão (Fase I). Na fase com reperfusão (Fase II), as diferenças no glicogênio miocárdico entre o grupo experimental e seu controle não foram significativas. A análise da respiração mitocondrial não mostrou diferenças significativas entre os grupos experimentais e seus controles, quer seja nas fases com ou sem reperfusão. Os valores da dP/dtmax, na Fase II foram de 903,39 ± 113,46 mmHg/s e 1.043 ± 256,94 mmHg/s, para o grupo experimental e controle, respectivamente. A diferença entre os valores não foi significativa. Conclusões: A infusão anterógrada intermitente a cada 20 minutos, durante 60 minutos, de solução cardioplégica sangüínea a 37°C, mostrou-se um método eficaz de proteção miocárdica em corações normais de coelhos.

Recent Developments in Myocardial Protection: Retrograde Cardioplegia

In recent years there has been increasing use of coronary sinus perfusion to deliver cardioplegic solutions during open-heart surgery. This has been aided by advances in coronary sinus catheter design and by easier methods of cannula insertion. Coronary sinus perfusion has been used with both intermittent crystalloid and blood cardioplegia and has recently evolved to include retrograde continuous normothermic blood cardioplegia. Coronary sinus perfusion has several advantages including safety, ease of use (with a single cannula placed out of the operative field), usefulness in patients with significant aortic regurgitation, redo coronary artery bypass graft surgery, and acute myocardial infarction. However, there are continuing concerns about the distribution of retrograde perfusion, preservation of right ventricular function, dislodgment of the coronary sinus catheter (and resulting ischemia during surgery), and damage to the coronary sinus.

Endothelial effects of hemostatic devices for continuous cardioplegia or minimally invasive operations

Improvements in myocardial protection may include the continuous delivery of normothermic blood cardioplegia. Technical aids are required for optimal visualization of the operative field during the performance of coronary anastomoses if cardioplegia is to be given continuously or during minimally invasive operations. However, the effects of the different hemostatic devices on coronary endothelial function are unknown. We compared the effects on endothelial function of two commonly used hemostatic techniques, coronary clamping and gas jet insufflation, with those of a technique using extravascular balloon occlusion to mimic systolic luminal closure by the surrounding myocardium. The three techniques were applied for 15 minutes on porcine epicardial coronary arteries from explanted hearts. For coronary clamping, standard bulldog clamps were used. Gas jet insufflation was applied by blowing oxygen (12 L/min) tangentially at a 45-degree angle 1 cm away from a 3-mm arteriotomy. Extravascular balloon occlusion was achieved with a needle-tipped silicone loop, the midportion of which, once positioned beneath the coronary artery, was inflated to push a myocardial "cushion" against the back of the vessel until its occlusion. Control rings were taken from the same coronary artery. The endothelial function of control and instrumented arterial rings was then studied in organ chambers filled with modified Krebs-Ringer bicarbonate solution. Contractions to potassium chloride and prostaglandin F2 alpha and endothelium-independent relaxation to sin-1, a nitric oxide donor, were unaffected in all groups. Endothelium-dependent relaxation to serotonin was impaired after clamping and preserved after gas jet insufflation and extravascular balloon occlusion. Maximal endothelium-dependent relaxation to serotonin was as follows: for coronary clamping, 63% +/- 6% versus 87% +/- 3% in controls; for gas jet insufflation, 67% +/- 12% versus 88% +/- 7%; and for extraluminal balloon occlusion, 79% +/- 6% versus 85% +/- 5%. Whereas commonly used hemostatic devices may impair endothelial function, extravascular balloon occlusion appears to achieve effective hemostasis while preserving endothelial integrity.

Normotherm continuous blood cardioplegia for 4 hours in an in vivo pig model.

Warm, continuous blood cardioplegia should theoretically maintain cardiac arrest for hours without ischaemic or hypothermic injury. In the absence of in vivo studies of myocardial metabolism and ultrastructural and/or functional preservation during and after more than 2 hours of cardiac arrest and after weaning from bypass, we devised a porcine model with a closed extracorporeal circuit for the heart alone. Normothermic blood cardioplegia was administered antegrade and recirculated for 2 or 4 hours, each in seven pigs. After aortic declamping all were successfully weaned from bypass and reperfused for 1 hour. Thereafter we found no significant intergroup difference in haemodynamic characteristics (average fall in mean arterial pressure 31.7 +/- 3.2% and 26.9 +/- 2.6%) or blood analyses. After 5 and 60 minutes of cardiac arrest there was minimal lactate production (5.7 +/- 10.7 and 0.5 +/- 10.5 nmol/l, respectively), whereas in the remainder of the arrest period there was lactate uptake, indicating aerobic heart metabolism. Our setup avoids systemic hyperkalaemia, gives good cardiac protection with no deterioration between 2 and 4 hours and is well suited for studies on the quiescent, blood-perfused oxygenated heart.

Intermittent Warm Blood Cardioplegia

Warm heart surgery implies continuous perfusion with normothermic blood cardioplegia. Interruption of cardioplegia, however, facilitates construction of distal coronary anastomoses and is the method practiced by many surgeons. To determine whether intermittency is harmful, we present results from 720 coronary bypass patients, protected with intermittent antegrade warm blood cardioplegia, that were derived from a previous study of normothermic versus hypothermic cardioplegia. Mean +/- SD age was 60.8 +/- 9.0 years; 27% of cases were urgent; 16% of patients had > 50% left main stenosis, and 19% had grade III or IV ventricles. A mean of 3.2 +/- 0.9 grafts was constructed. The average aortic cross-clamp time was 61.8 +/- 22.2 minutes. The longest single time off cardioplegia (LTOC) averaged 11.4 +/- 4.0 minutes per patient. The cumulative time off cardioplegia as a percentage of the cross-clamp time (PTOC) was 48.2 +/- 18.6% per patient. LTOC and PTOC were divided into quartiles (LTOC, < 10, 10 to 11, 12 to 13, and > 13 minutes; PTOC, < 36%, 36% to 49%, 50% to 62%, and > 62%) and related to the prespecified composite outcome of mortality, myocardial infarction according to serial CK-MB sampling, and low-output syndrome (LOS). Longer LTOC was harmful (event rates per quartile, 13.5%, 10.3%, 10.9%, and 19.0%; P = .046), whereas longer PTOC was protective (16.1%, 17.2%, 9.4%, and 10.6%; P = .07). Stepwise logistic regression was performed, controlling for demographic and angiographic predictors. In the multivariate models, LTOC remained detrimental (P = .07) and PTOC remained beneficial (P = .053). Additional modeling after entering surgeon identity (P < .001) into the risk equation eliminated the PTOC effect, whereas LTOC remained predictive of adverse outcomes (P = .053; odds ratio, 1.06; 95% CI, 1.00, 1.13). The data indicate that a reasonable margin of safety exists with intermittent, antegrade warm blood cardioplegia. Repeated interruptions of warm blood cardioplegia are unlikely to lead to adverse clinical results if single interruptions are < or = 13 minutes.

Antegrade and retrograde continuous warm blood cardioplegia: A 31P magnetic resonance study

Retrograde normothermic blood cardioplegia has been shown to provide myocardial protection during certain bypass procedures. However, a number of animal studies have shown less than optimal myocardial protection with this technique. Isolated, beating porcine hearts were perfused antegradely (aortic root pressure = 75 to 95 mm Hg) for 30 minutes. Arrest was induced and maintained for 60 minutes with high K+ blood cardioplegia delivered either antegradely (n = 8) or retrogradely (n = 8) (coronary sinus pressure = 35 to 55 mm Hg). Perfusate was switched to normokalemic blood for recovery of sinus rhythm (30 minutes). Intracellular pH, creatine phosphate, inorganic phosphate, and adenosine triphosphate were monitored continuously and noninvasively with phosphorus 31 magnetic resonance spectroscopy throughout the experiment, and functional variables (rate-pressure product and the positive and negative first derivatives of left ventricular pressure) were assessed concurrently. Antegrade cardioplegia maintained high-energy metabolites, intracellular pH, and myocardial function. Retrograde normothermic blood cardioplegia resulted in an increase in inorganic phosphate (197% +/- 15% of control) and a decrease in creatine phosphate (51% +/- 6% of control). There was no significant difference in myocardial function between the two groups (p > 0.05). The magnetic resonance spectroscopy data indicate ischemia occurred within 2 minutes of the initiation of retrograde perfusion. This study suggests that retrograde normothermic blood cardioplegia causes a transition of the myocardium to ischemic metabolism in the normal porcine heart.