Terminal Cardioplegia Research Articles

Cardioprotection of neonatal heart using normothermic hyperkalaemia: the importance of delivery and terminal cardioplegia

Cardioprotection of immature hearts remains controversial and largely based on the use of hypothermic cardioplegia. Recent clinical trials in pediatric open-heart surgery suggest that normothermic cardioplegic arrest is also cardioprotective. However, the advantages of using normothermic cardioplegia delivered as single- or multi-dose with or without terminal cardioplegia are unknown. This work investigates the efficacy of these techniques and the mechanism(s) underlying their protective effect. Neonatal (7-10 days) rabbit hearts in a working mode were exposed to normothermic global ischemia (60 or 90 min) protected with one of the following cardioplegic (hyperkalaemic buffer) protocols: single-dose, multi-dose infused every 30 min, single-dose or multi-dose with terminal cardioplegia. The extent of functional recovery (e.g., aortic and coronary flow), ischemic stress (e.g., myocardial ATP, lactate) and reperfusion injury (lactate dehydrogenase (LDH) release) were assessed. Recovery following 60 min global ischemia was improved (p < 0.05) by single-dose and multi-dose cardioplegic delivery (from 5% to 60% and 80%, respectively). Improved recovery was augmented by 2 min terminal cardioplegia (to 90% and 97% for single-dose and multi-dose, respectively). Extending ischemia to 90 min with single-dose resulted in 0% recovery that was not improved by 2 min terminal cardioplegia. However, 5 min (not 10 min) terminal cardioplegia significantly improved recovery (32%). Multi-dose followed by 5 min terminal cardioplegia resulted in full recovery. Cardioprotective interventions were associated with a reduction in LDH release and attenuated changes in myocardial metabolites. During normothermic cardioplegic arrest of neonatal heart: (i) multi-dose is superior to single-dose; (ii) terminal cardioplegia confers additional protection to single-dose and multi-dose; and (iii) protection is likely to be due to metabolic preservation.

Myocardial protection with leukocyte depletion in cardiac surgery.

A role of neutrophils in ischemia-reperfusion injury has been focused on as one of the mediating factors of inflammatory reactions. Current studies have reported the efficacy of leukocyte-depletion in reperfusion by using leukocyte removal filter to attenuate reperfusion injury during open heart surgeries. For clinical application, we have introduced leukocyte-depleted terminal blood cardioplegia (LDTC) in adult patients and leukocyte-depleted blood cardioplegia in pediatric patients. The results of elective surgery in noncompromised LDTC did not significantly alter the results in terms of leakage of creatine kinase (CK)-MB, production of malondialdehyde from myocardium, and dopamine dose required at the weaning from cardiopulmonary bypass compared with the whole-blood reperfusion or with terminal cardioplegia alone. In contrast, the results in emergency coronary artery bypass graft (CABG) patients differed significantly between the LDTC group and the other two groups. Leukocyte-depleted reperfusion was also effective in a similar fashion for patients with severe left ventricular hypertrophy caused by chronic aortic valve disease. Leukocyte-depleted blood cardioplegia was useful in pediatric patients. Thus, leukocyte depletion may be beneficial as an adjunct to terminal blood cardioplegia or blood cardioplegia during cardiac surgery to attenuate leukocyte-mediated ischemia-reperfusion injury in patients with compromised hearts, such as those with preoperative ischemic insults, severe left ventricular hypertrophy, and in pediatric patients.

Leukocyte Depletion Attenuates Reperfusion Injury in Patients With Left Ventricular Hypertrophy

Reperfusion injury can occur after a long period of aortic cross-clamping in patients with left ventricular hypertrophy during open-heart surgery, even with the most up-to-date techniques of myocardial protection. In the present study, we examined whether leukocyte depletion as an adjunct to terminal blood cardioplegia (LDTC) attenuates reperfusion injury in patients with left ventricular hypertrophy (LV mass, >300 g; left ventricular end-systolic volume index, >100 mL/m2) in a group of 30 patients undergoing aortic valve replacement. We used basic cold potassium crystalloid cardioplegic solution. Terminal blood cardioplegic solution (TC) or LDTC was accomplished by mixing a cold potassium crystalloid cardioplegic solution with warm arterial blood obtained through cardiopulmonary bypass and administered to the aortic root for the first 10 minutes of reperfusion. During delivery of LDTC, warm arterial blood was passed through a leukocyte-removal filter. Patients were randomized into one of three groups for reperfusion: whole blood (WB) (n=10), TC (n=10), and LDTC (n=10). Left ventricular biopsies were obtained before ischemia, at the end of ischemia, and 15 minutes after reperfusion. Semiquantitative scoring for ultrastructural alterations indicated that the LDTC group achieved significantly better recoveries of both scores at reperfusion for myocyte damage and for endothelial cell damage of capillaries than did the WB and TC groups. The LDTC group had significantly fewer neutrophils adhering to endothelial cells at reperfusion and a lower level of malondialdehyde derived from myocardium than did the WB and TC groups. Regarding the clinical data, the LDTC group had a lower maximum creatine kinase-MB, a higher percentage of spontaneous defibrillation, a lower pulmonary capillary wedge pressure, and a lower requirement for dopamine that did the WB group, whereas the TC group failed to do better than the WB group. These results demonstrate that leukocyte-depleted reperfusion is potentially beneficial as an adjunct to terminal cardioplegia during cardiac surgery to attenuate reperfusion injury in patients with left ventricular hypertrophy.

Evaluation of leukocyte-depleted terminal blood cardioplegic solution in patients undergoing elective and emergency coronary artery bypass grafting

Leukocyte depletion at reperfusion may have a role in myocardial protection when combined with terminal cardioplegia. We applied this method in a selected group of 68 patients with coronary artery bypass grafting either for elective surgical procedures (n = 38) or emergency surgical procedures with the use of a preoperative intraaortic balloon pump (n = 30) because of developing acute myocardial infarction. Basic cold potassium crystalloid cardioplegic solution was used. During delivery of leukocyte-depleted terminal cardioplegic solution, warm arterial blood delivered from cardiopulmonary bypass was passed through a leukocyte removal filter, mixed with potassium crystalloid cardioplegic solution, and administered to the aortic root for the first 10 minutes of reperfusion. Patients were randomized into three groups for reperfusion: whole blood, terminal cardioplegic solution, and leukocyte-depleted terminal cardioplegic solution reperfusion groups. In elective coronary artery bypass grafting, no significant difference was found in the clinical data. However, in emergency coronary artery bypass grafting, the leukocyte-depleted terminal cardioplegic solution group (n = 10) showed significantly lower peak creatine kinase MB levels (leukocyte-depleted terminal cardioplegic solution versus terminal cardioplegic solution versus whole blood: 27 +/- 11, 56 +/- 13, 74 +/- 18, respectively; p < 0.05) and maximum dopamine doses required at the weaning of cardiopulmonary bypass (6.3 +/- 1.1 versus 11.2 +/- 3.3 versus 9.2 +/- 2.2; p < 0.05) than did the terminal cardioplegic solution (n = 10) and whole blood groups (n = 10). Moreover, the leukocyte-depleted terminal cardioplegic solution group showed significantly lower difference of malondialdehyde between arterial and coronary sinus blood (0.15 +/- 0.09 versus 0.36 +/- 0.06 versus 0.06 +/- 0.12 nmol/ml, p < 0.05) than did the terminal cardioplegic solution or whole blood groups. These results showed that leukocyte-depleted terminal blood cardioplegic solution may have a role in attenuating reperfusion injury in patients with critical conditions such as preoperative myocardial ischemic injury.

Study of efficacies of leukocyte-depleted terminal blood cardioplegia in 24-hour preserved hearts

To evaluate the effect of leukocyte-depleted terminal blood cardioplegia on prolonged preservation, 41 canine hearts were stored in modified Collins' solution and transplanted heterotopically. Hearts were transplanted soon after harvesting in group 1 and after 24-hour preservation in groups 2, 3, and 4. Blood cardioplegia was applied just before aortic unclamping in groups 3 and 4; group 3 received simple blood cardioplegia and group 4 received leukocyte-depleted cardioplegia. The percentage of the preload recruitable stroke work and diastolic compliance after transplantation compared with the preharvesting value in group 4 did not differ from those in group 1, but the percentage of the preload recruitable stroke work in groups 2 and 3 was significantly lower than that in groups 1 and 4. The percentage of diastolic compliance in groups 2 and 3 was significantly higher than that in groups 1 and 4. Coronary blood flow 40 minutes after aortic unclamping in group 4 did not differ from that in group 1, but was significantly higher than the blood flows in groups 2 and 3. Significant production of malondialdehyde was detected during terminal blood cardioplegia and 10 minutes after aortic unclamping in groups 2 and 3, but never in groups 1 and 4. After leukocyte-depleted terminal cardioplegia, the myocardial adenosine triphosphate content increased to the preharvesting value in group 4. Our results suggest that leukocyte-depleted terminal blood cardioplegia may be effective in replenishing the energy-depleted myocardium and reducing reperfusion injury, resulting in adequate cardiac function.

Role of amino acids and enhancement cardioplegia in routine myocardial protection: Experimental results

The purpose of this study was to determine the effects of the addition of amino acids to blood cardioplegic solution and the value of terminal cardioplegia enhancement techniques in routine myocardial protection. Forty-five open-chest adult dogs were instrumented with sonomicrometry crystals to measure left ventricular long axis, midequatorial short axis, and wall thickness. The aorta was clamped for 120 minutes of cardiopulmonary bypass. Animals were randomly separated into four myocardial protection groups: (1) blood cardioplegic solution with amino acids and no terminal cardioplegia (n = 12); (2) blood cardioplegic solution with amino acids and warm amino acid terminal cardioplegia (n = 11); (3) blood cardioplegic solution with amino acids and cold amino acid terminal cardioplegia (n = 12); and (4) blood cardioplegic solution plus cold terminal cardioplegia (no amino acids, n = 10). Data for preload recruitable stroke work were obtained by inflow occlusion before bypass (baseline) and at 30 and 60 minutes after reperfusion and analyzed for changes in x-intercept and slope. A significant rightward shift in x-intercept did not occur in any group. When cardiac function was expressed as a percentage of baseline preload recruitable stroke work slope, improved functional recovery was seen at both 30 and 60 minutes in groups 2 (88.6% and 91.8%), 3 (85.8% and 86.9%), and 4 (88.6% and 92.6%) compared with group 1 (77.3% and 79.2%, p < 0.05). No significant difference was found in the degree of functional recovery among groups 2, 3, and 4. These results suggest that for myocardial protection of 2 hours in nonischemic hearts, a terminal dose of blood cardioplegic solution before unclamping is beneficial, but this positive effect is independent of amino acid supplementation and temperature.

Prevention of postischemic reperfusion injury: The improvement of myocardial tissue blood flow after ischemia by terminal Nicorandil-Mg cardioplegia

We evaluated the preventive effect of postischemic reperfusion injury by Nicorandil-Mg cardioplegia given just prior to reperfusion as "terminal cardioplegia." Twenty seven dogs were placed on cardiopulmonary bypass and the aorta was cross-clamped for 90 min under hypothermic (17-19 degrees C) cardioplegic arrest. The canine hearts were divided into three groups: in group A (n = 10) the hearts reperfused without any treatment; in group B (n = 9) the hearts received coronary perfusion with Nicorandil-Mg solution (Nic, 8 mg/l; Mg, 20 mEq/l; glucose, 50 g/l) for 2 min just prior to reperfusion; and in group C (n = 8) the hearts received coronary perfusion with Nicorandil-Mg free solution (glucose, 50 g/l). During and after ischemia, the myocardial tissue PCO2 (t-PCO2) was continuously monitored by an ion-sensitive field effective transistor (ISFET) sensor. In addition, the myocardial tissue blood flow (TBF), oxygen consumption, and lactate flux were then calculated at 5, 10, 20, and 40 min of reperfusion. In the initial reperfusion period, Group B showed an improved TBF compared to group A and C (at 5 min, group B was 42.7 +/- 11.9; group A was 29.4 +/- 11.2, P < 0.025; and group C was 33.9 +/- 9.2% of the preischemic control level, P < 0.05). T-PCO2 in group B was significantly decreased at 5 min of reperfusion (group B, 127.5 +/- 22.5-->42.5 +/- 9.7; group A, 117.5 +/- 23.0-->85.2 +/- 17.4, P < 0.001; group C, 122.3 mmHg-->68.2 +/- 18.7 mmHg, P < 0.01), and group B had a better metabolic recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

重症開心術症例における再潅流障害に対する心筋保護上の対策： Ｔｅｒｍｉｎａｌ ｃａｒｄｉｏｐｌｅｇｉａ法における白血球除去併用の有用性に関する検討

重症開心術症例における再潅流障害に対する心筋保護上の対策： Ｔｅｒｍｉｎａｌ ｃａｒｄｉｏｐｌｅｇｉａ法における白血球除去併用の有用性に関する検討

The effect of prostaglandin E1 on heart preservation.

The purpose of this study was to investigate the effect of prostaglandin E1 on rabbit heart preservation. The hearts were arrested with cardioplegia (CP) solution, followed by intracoronary infusion of Euro-Collins (E-C) solution. They were immersed in E-C solution at 4 degrees C for 9 hr, flushed with terminal warm CP solution, and reperfused with oxygenated Tyrodes' solution at 80 mmHg for 90 min. Eighteen rabbits (Kabushikigaishya BioTec Japanese white) were divided into 3 groups. Group I served as the control. In groups II and III, 200 ng/kg/min of PGE1 was given for 30 min before the heart was removed and 5 micrograms was added to the initial CP solution. In group III, 5 micrograms was also added to both E-C solutions and to the terminal CP solution. The values of CPK and LDH in the terminal CP solution and in the coronary effluent in groups II and III were lower, and coronary flow after reperfusion in group III was significantly greater at 5 min and from 60 min until the end of the experiment. Left ventricular maximum dP/dt at each end-diastolic pressure was significantly higher than control in groups II and III. The values of the wet/dry ratio of reperfused hearts in groups II and III were significantly lower than in the control. In conclusion, treatment with PGE1 before heart extraction and the addition of PGE1 to both E-C solutions and to the terminal CP solution contributed to superior left ventricular function after reperfusion, by improving preservation and reducing interstitial edema.

Accelerated myocardial metabolic and functional recovery with terminal nicorandil-Mg cardioplegia in heart transplantation

Cardiac reperfusion injury after heart transplantation or cardiopulmonary bypass has been difficult to control due to the variable degree of myocardial damage with respect to the length of ischemia and the complexity of the surgical procedure. Here, we evaluated the myocardial metabolic and functional recovery of hearts infused with a nicorandil vasodilator-magnesium (Mg) solution just prior to reperfusion (terminal cardioplegia). Donor hearts (20 dogs) were removed and immersed in a 4 degrees C water bath containing 20 mEq/l KCL-5% glucose for 6 hours, and then were transplanted to recipient dogs. Orthotopically transplanted dog hearts were either reperfused without any further treatment or received a terminal cardioplegic solution containing 8 mg/l nicorandil, 30 mEq/l Mg, and 50 g/l glucose, which was infused at a pressure of 75 cm H2O for 2 minutes. During the reperfusion period, myocardial tissue PCO2 (t-PCO2) and calcium ion (t-Ca) were continuously monitored by an ISFET (ion-sensitive field effect transistor) sensor. Myocardial oxygen consumption and lactate flux were calculated/monitored at 5, 10, 20 and 40 minutes of reperfusion. Thereafter, myocardial function was evaluated at 45 minutes of reperfusion using LVSWI. Just after reperfusion, the treatment group (group B, n = 10) had a significantly greater coronary flow than the control group (Group A, n = 10, 35.0 +/- 10.1; group B, 47.4 +/- 8.5 ml/100 g/min, p less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)

Leukocyte depleted terminal cardioplegia in the severely hypertrophied and failing heart

Leukocyte depleted terminal cardioplegia in the severely hypertrophied and failing heart

The Effect of Substrate Enhanced Cardioplegia on Postbypass Electrical and Hemodynamic Recovery

Substrate enhanced terminal cardioplegia increases metabolic activity which may enhance recovery in the post cardiotomy patient. Twenty-eight consecutive low risk patients requiring coronary artery bypass grafting were randomly assigned to receive either a dose of warm aspartate glutamate enriched terminal cardioplegia or reperfusion with unmodified pump blood. There were no significant differences between patient groups in prebypass parameters. Bypass indices did not vary between groups other than total cardioplegia volume administered (2364±578 cc mean±SD in the non-aspartate glutamate group, vs 2828±579 cc in the aspartate glutamate group, p&lt;.05). Patients in the aspartate glutamate group received less defibrillatory shocks with lower total Joule wattage, and were paced less than the non-aspartate glutamate hearts. There were no significant differences in the use of inotropes or antiarrhythmics, nor did cardiac index or systemic vascular resistance differ between groups over the first several postoperative days. Therefore, in low risk patients undergoing coronary artery bypass grafting, the routine use of substrate enriched terminal cardioplegia resulted in a more rapid return to electrical activity, but failed to improve immediate postoperative hemodynamic recovery.

重症弁膜症例に対するｌｅｕｋｏｃｙｔｅ ｄｅｐｌｅｔｅｄ ｔｅｒｍｉｎａｌ ｃａｒｄｉｏｐｌｅｇｉａの有用性に関する臨床的検討

重症弁膜症例に対するｌｅｕｋｏｃｙｔｅ ｄｅｐｌｅｔｅｄ ｔｅｒｍｉｎａｌ ｃａｒｄｉｏｐｌｅｇｉａの有用性に関する臨床的検討

Terminal magnesium cardioplegia: Protective effect in the isolated rat heart model using calcium accentuated ischemic damage

We have developed a modified isolated working rat heart model to study the effect of potassium and magnesium cardioplegia given just prior to reperfusion, “terminal cardioplegia,” on preservation of aortic flow following a standard ischemic insult. The model incorporates a short-term calcium challenge at the beginning of reperfusion to accentuate ischemic injury. All hearts were given initial potassium cardioplegia and subjected to 30 min of normothermic ischemia. Terminal cardioplegia was given for the 2 min prior to reperfusion. Calcium-challenged hearts were reperfused initially with calcium-enriched reperfusate and then switched to standard reperfusate. Aortic flow prior to and 60 min after ischemia was used to determine functional protection. Hearts recovered 82 ± 3% of preischemic aortic flow when reperfused with normocalcemic reperfusate. When the initial reperfusate was enriched with calcium, aortic flow was only 43 ± 4% of control. Hearts given terminal magnesium cardioplegia and then challenged with calcium-enriched reperfusate recovered 79 ± 4% of control aortic flow. Hearts given terminal potassium cardioplegia recovered only 53 ± 5% of control aortic flow when challenged with calcium-enriched initial reperfusate. Our results indicate that the recovery of aortic flow is significantly reduced by short-term postischemic calcium challenge. This damage is blocked by terminal magnesium cardioplegia, but not by terminal potassium cardioplegia.