Experimental evaluation of secondary blood cardioplegia

Reperfusion damage after ischemia may be evidenced by myocardial cell edema, intracellular calcium accumulation, and limited utilization of oxygen. The need for cardioplegic arrest during initial reperfusion to allow oxygen to be used for reversing ischemic damage rather than for electromechanical activity has been propounded by some researchers. Reports of greater postischemic compliance and performance, low postischemic edema, and greater oxygen uptake at a perfusion pressure of 50 mm Hg or lower have been cited. The present study was conducted on 24 pigs having 2-hr cardioplegic arrest, which of 12 underwent normal reperfusion and 12 experienced secondary cardioplegia followed by normal reperfusion. The results showed that in spite of improved high-energy phosphate preservation, the secondary cardioplegia group had higher myocardial edema, less coronary flow, and poorer contractility and compliance at the end of 1 hr of reperfusion. Because of these findings and contradictory results reported by other groups, caution is urged in the clinical extrapolation of the results of such studies pending further investigations.     

Cold blood cardioplegia.

The technique of myocardial protection by means of a cardioplegic solution consisting of cold blood (10 degrees C) with potassium (30 mEq. per liter) is described. A disposable cooling coil is used and a separate pump head for coronary perfusion is avoided. The aortic perfusion cannula can be used for venting of the left ventricle and subsequently for venting of air. This method was used in 125 consecutive patients undergoing coronary revascularization and in 73 consecutive pediatric cardiac surgical procedures with excellent results.     

Safety of prolonged aortic clamping with blood cardioplegia. III. Aspartate enrichment of glutamate-blood cardioplegia in energy-depleted hearts after ischemic and reperfusion injury

This study tests the hypothesis that aspartate enrichment of glutamate-blood cardioplegia improves metabolic and functional recovery after ischemic and reperfusion damage. Ischemic and reperfusion damage were produced in 15 dogs by 45 minutes of aortic clamping at 37 degrees C and 5 minutes of blood reperfusion, before 2 more hours of aortic clamping (simulated operation). Six received multidose blood cardioplegia at 4 degrees C. In nine others, the cardioplegic solution was infused at 37 degrees C for the first 5 minutes, followed by multidose infusions at 4 degrees C. Four received 26 mmol glutamate-enriched cardioplegic solution. In five, the glutamate (13 mmol) cardioplegic solution was enriched with aspartate (13 mmol). Oxygen uptake and ventricular function (stroke work index, left atrial pressure) were measured. These data suggest aspartate enrichment produced the highest oxygen uptake (32 +/- 4 versus 17 +/- 2 ml/100 gm for glutamate and 7 +/- 1 ml/100 gm for 4 degrees C blood cardioplegia). Complete functional recovery occurred in aspartate/glutamate-treated hearts (stroke work index 90% +/- 4%, left atrial pressure 12 +/- 2 mm Hg), whereas recovery was incomplete with both glutamate alone (stroke work index 66% +/- 14%, left atrial pressure 20 +/- 3 mm Hg) and 4 degrees C blood cardioplegia at low cardiac outputs. Eight of 10 hearts not receiving aspartate failed at high cardiac outputs. Aspartate enrichment of glutamate-blood cardioplegia improves recovery after severe ischemic/reperfusion damage by improving oxidative metabolism during cardioplegic infusion and during postischemic work.     

Fluosol cardioplegia results in complete functional recovery: a comparison with blood cardioplegia.

Blood cardioplegia is considered by many to be the preferred solution for myocardial protection. Proposed benefits include the ability to deliver oxygen and the ability to maintain metabolic substrate stores. However, the decreased capacity of blood to release oxygen at hypothermic conditions as well as the presence of deleterious leukocytes, platelets, and complement may limit complete functional recovery. Fluosol is an asanguineous solution with the ability to bind and release oxygen linearly at low temperatures. Neonatal piglet hearts (24 to 48 hours old) were excised and supported on an isolated, blood-perfused working heart model. After baseline stroke-work index was determined, hearts were arrested with either normocalcemic blood cardioplegia (group 1, n = 8) or normocalcemic Fluosol cardioplegia (group 2, n = 8). Cold cardioplegia was administered at 45 mm Hg every 20 minutes for 2 hours. Hearts were then reperfused with whole blood. Functional recovery, expressed as percent of control stroke-work index, was determined 60 minutes after reperfusion at left atrial pressures of 3, 6, 9, and 12 mm Hg. Functional recovery at 60 minutes was similar between group 1 (95%, 93%, 93%, 88%) and group 2 (100%, 94%, 94%, 95%) at left atrial pressures of 3, 6, 9, and 12 mm Hg, respectively. Mean lactate consumption 5 minutes after reperfusion was significantly greater (p = 0.0001) in group 1 (31.8 +/- 6.3 micrograms.min-1 x g-1) than in group 2 (-0.59 +/- 0.1 microgram.min-1 x g-1), indicating superior metabolic recovery in the blood cardioplegia hearts. Edema formation, as determined both by water content (group 1, 81.10%; group 2, 81.63%) and by electron microscopy, was not significantly different between groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adenosine-enhanced ischemic preconditioning provides myocardial protection equal to that of cold blood cardioplegia

BACKGROUND: We recently described a novel myoprotective protocol-adenosine-enhanced ischemic preconditioning (APC)-that extends the protection of ischemic preconditioning (IPC) by both reducing myocardial infarct size and enhancing postischemic functional recovery in the isolated perfused heart. In the present report the efficacy of APC in the blood-perfused heart was investigated and compared with that of cold blood cardioplegia (CBC). METHODS: Cardiopulmonary bypass was instituted in 21 sheep hearts. The APC hearts (n = 6) received a bolus injection of adenosine through the aortic root at the immediate start of IPC (5 minutes of zero-flow global ischemia, followed by 5 minutes of reperfusion) before 30 minutes of global ischemia and 120 minutes of reperfusion. Nine other hearts received CBC. A control group (n = 6) received IPC only. RESULTS: Infarct size was significantly decreased (p<0.01) in the APC (3.0%+/-0.8%) and CBC (2.6%+/-0.2%) hearts compared with the IPC hearts (16.3%+/-1.6%). The preload recruitable stroke work relation, mean arterial pressure, and the time constant of pressure decay (tau) were significantly preserved (p<0.05) in APC and CBC hearts compared with IPC hearts. No significant differences were observed between APC and CBC hearts. CONCLUSIONS: Use of APC is as effective as CBC in significantly decreasing infarct size and enhancing post-ischemic functional recovery.     

Reperfusion modification with a simplified blood cardioplegia system compared with oxygenated crystalloid cardioplegia

A simplified system was developed for administration of blood cardioplegia with reperfusion modification. This system utilizes a single pass stainless steel coil to eliminate the need for a separate heat exchanger circuit. This system was compared with an oxygenated crystalloid cardioplegia system which was utilized in a manner which allowed warm blood perfusion of the heart for the last three minutes of the crossclamp interval. Both of these systems were compared with regard to mortality, spontaneous defibrillation, myocardial temperature, blood usage and peak CK-MB levels. In this series of patients, no significant advantage of either system could be identified.     

Operative results of acquired valvular disease with blood cardioplegia followed by terminal cardioplegia

Cold blood cardioplegia followed by terminal cardioplegia was employed as a method of myocardial protection for acquired valvular disease. Postoperative clinical results of both cardiac iso-enzyme and cardiac function were discussed from the effect of the myocardial protection. In operative procedures of 62 cases, 30 cases underwent mitral valve replacement and other mitral repair, 17 cases aortic valve replacement, 10 cases double valve replacement and 5 cases modified Bentall operation. Iso-enzymes of Creatine-Kinase (CK) and Lactate-Dehydrogenase (LDH) were measured by the constant time-interval. Cardiac function was estimated in acute postoperative phase and late phase. Hospital mortality was 1.5%. The cause of death was thought to be postoperative Graft Versus Host Disease with skin rash and pancytopenia. Cardiac function during acute phase well recovered in 62 cases of which two cases were controlled with intra-aortic balloon pumping. The values of CK-MB were measured during aortic cross-clamp, 30 min, 3 hours, 6 hours and 24 hours after cross-clamp release. Peak CK-MB value was detected 3 hours or 6 hours in almost cases. In contrast, peak LDH-1 value was detected 24 hours after cross-clamp release. Perioperative myocardial infarction was occurred in one case with modified Bentall operation whose CK-MB value was elevated over 150 IU/L at 3rd hour and 24th hour. However, the cardiac radio-isotope data of this case revealed good cardiac function with left ventricular ejection fraction (LVEF) 76% by cardiac pool imaging in spite of small postero-lateral perfusion defect by Thallium 201 scintigram.(ABSTRACT TRUNCATED AT 250 WORDS)     

Coronary artery bypass graft surgery: clinical comparison of cold blood potassium cardioplegia, warm cardioplegic induction, and secondary cardioplegia

An analysis of myocardial protection was performed in 45 low-risk patients undergoing coronary bypass procedures who were divided into three equal groups with similar preoperative ejection fractions and coronary artery obstructions. Group 1 (N = 15) received cold blood cardioplegia, Group 2 received cold blood cardioplegia and secondary cardioplegia, and Group 3 received cold blood cardioplegia plus warm cardioplegic induction. The aortic cross-clamp time and the number of bypass grafts were similar among the groups. The following variables were measured serially: electrocardiographic changes, serum myocardial-specific isoenzyme of creatine kinase, cardiac output, left ventricular filling pressure, ejection fraction, and left ventricular wall motion. The three methods evaluated were all effective in protecting the myocardium during global myocardial ischemia. Patients who received secondary cardioplegia (Group 2) were more likely to exhibit spontaneous defibrillation (12/15) than those in Group 1 (5/15) or Group 3 (6/15) (p less than 0.05). However, measurements of left ventricular performance and evidence of perioperative myocardial infarction were similar among all three groups. These data suggest that a standard technique of cold potassium cardioplegia alone should be the method of choice in elective, low-risk coronary bypass operations rather than this technique in combination with either of the other two more costly and complex methods evaluated in this study.     

Continuous retrograde blood cardioplegia

We present a technique of myocardial protection using retrograde cold blood cardioplegia. This safe and simple method allows excellent continuous and homogeneous cooling of the heart during the ischemic period in all types of open heart operations.     

Polarized arrest with warm or cold adenosine/lidocaine blood cardioplegia is equivalent to hypothermic potassium blood cardioplegia

BACKGROUND: Hypothermic depolarizing hyperkalemic (K + 20 mEq/L) blood cardioplegia is the "gold standard" in cardiac surgery. K + has been associated with deleterious consequences, eg, intracellular calcium overload. This study tested the hypothesis that elective arrest in a polarized state with adenosine (400 micromol/L via adenosine triphosphate-sensitive potassium channel opening) and the Na + channel blocker lidocaine (750 micromol/L) as the arresting agents in blood cardioplegia provides cardioprotection comparable to standard hypothermic K + -blood cardioplegia. METHODS: Anesthetized dogs were placed on cardiopulmonary bypass and assigned to 1 of 3 groups receiving antegrade cardioplegia delivered every 20 minutes for 1 hour of arrest: cold (10 degrees C) K + -blood cardioplegia (n = 6), cold (10 degrees C) adenosine/lidocaine blood cardioplegia (n = 6), or warm (37 degrees C) adenosine/lidocaine blood cardioplegia (n = 6). After an hour of arrest, cardiopulmonary bypass was discontinued, and reperfusion was continued for 120 minutes. RESULTS: Time to arrest was longer with cold and warm adenosine/lidocaine blood cardioplegia (175 +/- 19 seconds and 143 +/- 19 seconds, respectively) compared with K + -blood cardioplegia (27 +/- 2 seconds; P < .001). Postcardioplegia left ventricular systolic function (slope of the end-systolic pressure/dimension relationship) was comparable among the 3 groups (K + -blood cardioplegia, 15.2 +/- 2.1 mm Hg/mm; cold adenosine/lidocaine blood cardioplegia, 15.9 +/- 3.4 mm Hg/mm; warm adenosine/lidocaine blood cardioplegia, 14.1 +/- 2.8 mm Hg/mm; P = .90). Plasma creatine kinase activity in cold and warm adenosine/lidocaine blood cardioplegia was similar to that in K + -blood cardioplegia at 120 minutes of reperfusion (cold adenosine/lidocaine blood cardioplegia, 11.5 +/- 2.1 IU/g protein; warm adenosine/lidocaine blood cardioplegia, 10.1 +/- 0.9 IU/g protein; K + -blood cardioplegia, 7.6 +/- 0.8 IU/g protein; P = .17). Postcardioplegia coronary artery endothelial function was preserved in all groups. CONCLUSIONS: Intermittent polarized arrest with warm or cold adenosine/lidocaine blood cardioplegia provided the same degree of myocardial protection as intermittent hypothermic K + -blood cardioplegia in normal hearts.     

Adenosine with cold blood cardioplegia during coronary revascularization

OBJECTIVE: To investigate whether adenosine in association with blood cardioplegia results in more rapid cardiac arrest or improved myocardial protection. DESIGN: A prospective, randomized, placebo-controlled double-blind clinical study. SETTING: Operative and intensive care units in a university hospital, Finland. PARTICIPANTS: Forty patients undergoing primary, elective coronary revascularization. INTERVENTION: Adenosine as a bolus dose, 12 mg intravenously, was given immediately before the induction of blood cardioplegia. MEASUREMENTS AND MAIN RESULTS: There were nonsignificantly higher serial serum values of CK (MB) (p = 0.33), troponin-T (p = 0.23), and troponin-I (p = 0.10) in the adenosine group. There were no differences between the groups in arrest time, blood pressure decrease, or lactate extraction. CONCLUSIONS: The adenosine regimen used in this study did not cause more rapid arrest with blood cardioplegia. The effect on cardioprotection was insignificant.     

Improved myocardial protection with blood and crystalloid cardioplegia

Although the results of coronary artery bypass surgery have been excellent, recent studies have demonstrated transient alterations in myocardial function and metabolism in spite of apparently adequate cardioplegic protection. Blood cardioplegia may provide better protection than crystalloid cardioplegia, but clinical studies remain inconclusive. Critical coronary stenoses limit cardioplegic delivery, and myocardial protection would be improved with either blood or crystalloid cardioplegia if the solution could be delivered beyond the coronary stenosis. The construction of proximal as well as distal anastomoses during a prolonged cross-clamp period permits more uniform cardioplegic delivery and immediate reperfusion when the cross clamp is released. This technique was used in a prospective randomized trial comparing blood and crystalloid cardioplegia. The long cross-clamp technique eliminated temperature gradients induced when cardioplegia was delivered into the aortic root. The technique of cardioplegic delivery may be as important as the solution used for cardioplegic protection. (J VASC SURG 1984;1:656-9.)     

Prevention of myocardial electrical activity during ischemic arrest with verapamil cardioplegia

The effect of potassium cardioplegia and potassium cardioplegia containing verapamil hydrochloride on myocardial preservation and electrical activity during prolonged aortic occlusion was examined in 40 adult mongrel dogs. Twenty-four animals (Group 1) received potassium cardioplegia, and 16 animals (Group 2) received potassium verapamil cardioplegia. Potassium or potassium verapamil cardioplegia, 10 ml per kilogram of body weight, was administered after application of the aortic cross-clamp and at 30-minute intervals during the 90-minute arrest. Myocardial temperature was maintained within a range of 8 degrees to 10 degrees C with topical ice saline solution, and electrical activity was monitored with specially designed plunge electrodes. Plunge electrode activity was recorded from the myocardium during arrest in 16 of the 24 animals in Group 1; no electrical activity was present in the animals in Group 2 (p less than .001). The addition of verapamil to potassium cardioplegia increased the tolerance of the myocardium to prolonged ischemia and resulted in less depletion of high-energy phosphate stores and better preservation of mitochondrial ultrastructure and left ventricular function. These data suggest that verapamil augments the preservation provided by potassium cardioplegia by initiating and maintaining a more complete electrical arrest.     

Myocardial oxygen tension during surgical revascularization. A clinical comparison between blood cardioplegia and crystalloid cardioplegia.

OBJECTIVE: The aim of this study was to assess the effect of cardioplegic solutions on myocardial oxygenation during surgical revascularization. METHODS: In 30 patients, randomized to receive crystalloid (CC) or blood (BC) cardioplegia, myocardial oxygen tension was measured continuously by polarography. RESULTS: The two groups were comparable in terms of patients' age, sex, pre-operative ejection fraction, coronary disease, perfusion time, and aorta cross-clamping time. However, the BC group required 22% more of cardioplegic solution to stop electrical activity of the heart. Throughout the pre- and post-cardiac arrest periods, oxygen tension between the two groups was similar. At the end of the observation (4th day), myocardial oxygenation increased over 200% in relation to the values before revascularization. During the first infusion of cardioplegia, oxygen tension in the CC group was lower compared to the BC group (0.1 mmHg vs 1.3 mmHg; P<0.05) being the only significant difference between the two groups during cardiac arrest. Throughout the cardiac arrest, myocardial oxygen tension was close to zero regardless of the type of cardioplegia used. Post-operatively, addition of oxygen to the respiratory air increased myocardial oxygenation by over 17% resulting in a positive correlation (r=0.94; P<0.05) between myocardial oxygen tension and peripheral saturation. CONCLUSIONS: In conclusion, the differences in myocardial oxygen tension between the CC and BC groups are trivial. Thus, any potential beneficial effect of blood cardioplegia compared to crystalloid cardioplegia must be due to other circumstances than its oxygen carrying capacity. An important observation is a significant increase in myocardial oxygenation during oxygen supplement to the respiratory air.     

Experience with warm blood cardioplegia in 480 patients

From 1 March 1992 too 31 July 1993 (17 months), 480 consecutive patients underwent various open-heart procedures under anterograde (83 patients) or retrograde (397 patients) continuous warm blood cardioplegia. Some 352 patients (73.3%) had isolated coronary artery bypass grafts (CABG) and 117 (24.3%) had valve replacement either isolated (96) or in combination with other operations (21). Two patients had CABG and ventricular aneurysmectomy, eight had correction of congenital defects, and one had resection of left atrial myxoma. The 30-day postoperative mortality rate was 2.9% (14 deaths). In four patients the cause of death was not cardiogenic. An intra-aortic balloon was used in 11 patients following CABG (3.1%) with six survivors. Perforation of the coronary sinus occurred in one patient. Perioperative myocardial infarction was observed in 5.6% of patients after CABG. No myocardial infarction occurred after valve replacement. Phrenic nerve injury and wound infection were not observed. These results indicate that warm blood cardioplegia, especially when delivered retrogradely, provides excellent myocardial protection of both ventricles during various open-heart procedures.