The effect of supplementing hypothermic crystalloid cardioplegia with catalase plus allopurinol in the isolated rabbit heart

The effect of adding allopurinol and catalse to hypothermic cardioplegia for ischemic-reperfusion injury was investigated in the isolated rabbit heart. Hearts were divided into two groups, namely: Group C (n=7), which received a hypothermic crystalloid cardioplegic solution alone (4°C), and group T (n=7), which received the hypothermic cardioplegic solution with allopurinol (148 mol/L)¹³ and catalase (37 nmol/L).¹² The cardioplegic solution was infused continuously into the isolated hearts, which had been placed in ice-cold saline, during a 12 h preservation. Subsequently, the hearts were mounted on a noncirculating, nonpulsatile perfusion circuit using Krebs-Henseleit buffer solution at 37°C for 1 h at a constant perfusion pressure of 75 mm Hg. The left ventricular developed pressure (LVDP), maximum rate of pressure change (max dp/dt), and percent recovery of coronary flow were higher, while the creatine phosphokinase concentration and left ventricular end diastolic pressure (LVEDP) were lower in group T. The tissue malondialdehyde concentration and water content were similar in both groups. Thus, cardiac function after a 12 h preservation was enhanced by the added combination of allopurinol and catalase to the cardioplegic solution, supporting its role in the prevention of free radical reperfusion injury in cardiac preservation.     

Age-related changes in the efficacy of crystalloid cardioplegia

Recent work has shown that multi-dose St. Thomas' Hospital cardioplegia solution (STHC) may not provide reliable protection of the neonatal myocardium. We have used an isolated working heart model to study the age-related development of this observation. Sets of eight hearts from 2-, 4-, 6-, and 8-week-old rabbits were subjected to 90 min of ischemia at 10 degrees C. STHC was infused at 30-min intervals in a dose of 10 ml/kg. There were no differences in the preservation of ATP stores during ischemia among the groups. The percentage recovery of preischemic mean aortic pressure, left atrial pressure, and heart rate were not different among groups, but the percentage recovery of aortic flow (AF) (expressed as means +/- standard error of the mean) was significantly lower in the 2- and 4-week hearts (44.1 +/- 8.2 and 66.2 +/- 7.7%) than in the 6- and 8-week hearts (93.0 +/- 6.4 and 97.6 +/- 4.7%). We have confirmed that the use of multi-dose STHC impairs recovery of ventricular function in the neonatal rabbit heart. This effect, however, diminishes rapidly as the immature animal develops and is not present by 6 weeks of age. Additional experimentation is necessary to identify those aspects of the developing myocardium that account for these observations.     

Blood cardioplegia: a review and comparison with crystalloid cardioplegia.

The Oxford International Symposium on myocardial preservation provided an appropriate milestone and impetus to survey one aspect of operative myocardial preservation, namely blood cardioplegia, and to contrast it with the more popular crystalloid cardioplegia. This review is by no means complete or exhaustive but represents my best effort to summarize important information that has accumulated in the literature as blood cardioplegia, and our understanding of it, has evolved. It is appropriate to compare blood and crystalloid cardioplegia with respect to biochemical and physiological differences. Clinical comparison has been limited, for the most part, to randomized studies, and a number of differences and details of clinical management of the two techniques have been omitted, either because they seemed unimportant or there was no good information that would allow an objective comparison of their significance. Hopefully, the reader will recognize the intent to focus on meaningful differences and similarities between the two techniques and to present them fairly.     

Efficacy of crystalloid cardioplegia against immature myocardium

Previous reports have not suggested a critical answer for the question, if the efficacy of crystalloid cardioplegic (St' Thomas Hospital) solution against immature myocardium was the same as that against mature myocardium, or not. The author in this study, therefore, investigated 72 isolated puppy (2-4 weeks old) hearts dividing them at random into three groups according to the different doses to be administered, namely, Group A: single-dose of 10 ml/kg of cardioplegia; Group B: multiple-dose of cardioplegia with the initial dose of 10 ml/kg followed by 5 ml/kg every 20 minutes; and Group C: no use of cardioplegia. They were subjected to 120 minutes of ischemic arrest at 15 degrees C and subsequent 30 minutes of reperfusion. Ultrastructural changes of the myocardium were studied systematically and, in particular, semiquantification was carried out on mitochondria. Gravimetric and high energy phosphate (HEP) content of myocardium, and recovery of left ventricular end-systolic pressure volume ratio (Emax), spontaneous defibrillation ratio were also studied. Electron microscopic study showed that ischemic myocardial change with global ischemia was severer and more frequent in Group C as compared to Groups A and B, which coincided with less HEP content in Group C. Intracellular rarefaction following global ischemia was less frequent in Group A than in Group B or C, which corresponded to the result of gravimetric myocardial water content study. Spontaneous defibrillation in Group C was evidently prolonged, although there was no significant difference in the left ventricular function among the groups. The author should recommend single-dose administration of cardioplegia with topical cooling against immature myocardium, because this cardioplegia was effective in either single- or multiple-dose, and intracellular myocardial edema was lesser in the case of single-dose than in multiple-dose.     

Protection of the immature heart. Temperature-dependent beneficial or detrimental effects of multidose crystalloid cardioplegia in the neonatal rabbit heart

There are conflicting reports of the detrimental or beneficial effects of hypothermic cardioplegia in the immature heart. We therefore investigated the temperature-dependence of myocardial protection and the ability of single-dose and multidose infusions of cardioplegic solution to protect the immature heart during hypothermic ischemia. Isolated, working hearts (n = 6 per group) from neonatal rabbits (aged 7 to 10 days) were perfused aerobically (37.0 degrees C) for 20 minutes before infusion (2 minutes) with either perfusion fluid (noncardioplegia control) or St. Thomas' Hospital cardioplegic solution and ischemic arrest (for 4, 6, and 18 hours) at various temperatures between 10.0 degrees and 30.0 degrees C. Hearts arrested with cardioplegic solution received either one preischemic infusion only (single-dose cardioplegia) or repeated infusions at intervals of 60 or 180 minutes (multidose cardioplegia). Ischemic arrest with single-dose cardioplegia for 4 hours at 10.0 degrees, 20.0 degrees, 22.5 degrees, 25.0 degrees, 27.5 degrees, and 30.0 degrees C resulted in 96.0% +/- 4.3%, 96.6 +/- 2.5%, 87.0% +/- 3.8%, 71.8% +/- 10.0% (p less than 0.05 versus 10.0 degrees C group), 35.1% +/- 10.3% (p less than 0.01 versus 10.0 degrees C group), and 3.0% +/- 1.9% (p less than 0.04 versus 10.0 degrees C group) recovery of preischemic cardiac output, respectively. With 6 hours of ischemia at 20.0 degrees C, single-dose cardioplegia significantly (p less than 0.01) increased the recovery of cardiac output from 20.9% +/- 13.1% (control) to 76.4% +/- 4.4%, whereas multidose cardioplegia (infusion every 60 minutes) further increased recovery to 97.8% +/- 3.8% (p less than 0.01 versus control and single-dose cardioplegia). In contrast, after 6 hours of ischemia at 10.0 degrees C, cardiac output recovered to 93.4% +/- 1.2% (control) and 92.3% +/- 3.1% (single-dose cardioplegia), whereas multidose cardioplegia reduced recovery to 76.9% +/- 2.2% (p less than 0.01 versus both groups). This effect was confirmed after 18 hours of ischemia at 10.0 degrees C; single-dose cardioplegia significantly increased the recovery of cardiac output from 24.5% +/- 10.9% (control) to 62.9% +/- 13.3% (p less than 0.05), whereas multidose cardioplegia reduced recovery to 0.8% +/- 0.4% (p less than 0.01 versus single-dose cardioplegia) and elevated coronary vascular resistance from 8.90 +/- 0.56 mm Hg.min/ml (control) to 47.83 +/- 9.85 mm Hg.min/ml (p less than 0.01). This effect was not reduced by lowering the infusion frequency (from every 60 to every 180 minutes).(ABSTRACT TRUNCATED AT 400 WORDS)     

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.)     

Induced fibrillation is equally effective as crystalloid cardioplegia in the protection of fetal myocardial function

BACKGROUND: Fetal cardiac intervention represents a potential advance in the treatment of congenital cardiac lesions that increase in complexity during development. Prenatal repair of a primary defect might prevent pathologic blood-flow patterns that can result in hypoplasia of a cardiac chamber or great vessel. However, strategies to optimize fetal myocardial protection have not been studied. A biventricular working fetal heart preparation was used to evaluate the cardioprotective properties of induced fibrillation and crystalloid cardioplegia. METHODS: Hearts from 16 fetal lambs at 115 to 125 days' gestation were harvested and perfused with Krebs-Henseleit solution. The descending aorta was ligated distal to the ductal insertion and the branch pulmonary arteries were ligated to simulate the parallel circulation of the fetus. Hearts were arrested with normothermic fibrillation (n = 8) or hypothermic crystalloid cardioplegia (n = 8) before reperfusion with Krebs-Henseleit solution. Baseline and postarrest myocardial function measurements were obtained from analysis of pressure-dimension relationships. RESULTS: Fibrillatory and cardioplegic arrest were equally effective at preserving postarrest systolic function (left ventricle, 70% +/- 5% vs 68% +/- 15%, P =.52; right ventricle, 68% +/- 4.5% vs 65% +/- 4.5%, P =.26) and preventing increased diastolic stiffness (left ventricle, 32% +/- 5.3% vs 38% +/- 11%, P =.24; right ventricle, 25% +/- 3.3% vs 27% +/- 2.1%, P =.46). Myocardial water content was unchanged in hearts arrested with fibrillation and cardioplegia (84% +/- 1.5% vs 83.7% +/- 0.9%, P =.71). CONCLUSIONS: Normothermic fibrillation and hypothermic crystalloid cardioplegia provide equal protection of the fetal myocardium. In the setting of diminished fetal myocardial reserve and because of the limited ability to manipulate the surrounding temperature in the fetus, normothermic fibrillation may be preferable for in utero repairs of selected congenital heart defects.     

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.     

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.     

Antegrade crystalloid cardioplegia vs antegrade/retrograde cold and tepid blood cardioplegia in CABG.

BACKGROUND: This study evaluated the myocardial protective strategies in isolated coronary bypass surgeries. METHODS: One hundred and twenty-eight patients were prospectively randomized to 3 techniques of myocardial protection; group I (n = 47) antegrade/retrograde tepid blood cardioplegia, group II (n = 40) antegrade/retrograde cold blood cardioplegia with topical cooling, group III (n = 41) antegrade crystalloid cardioplegia with topical cooling. RESULTS: The incidence of spontaneous defibrillation was significantly higher in group I (p < 0.001) while the incidence of low cardiac output was not different between the 3 groups. The incidence of ventricular arrhythmia was higher in group III (p < 0.016 group III vs I). There was no significant statistical difference in hemodynamic recovery between the 3 groups. CK-MB levels were significantly lower in group I versus the other 2 groups, (p = 0.0013, 0.04). Acid release and oxygen extraction were higher in group II than in group I (p = 0.06) during cardioplegia and reperfusion. Lactate release was less in group I at the release of aortic cross-clamp, and reperfusion. There was no significant difference between the 3 groups in ICU stay, ventilation time, or hospital complications. CONCLUSIONS: Tepid blood cardioplegia showed superiority in metabolic and functional recovery, whereas crystalloid cardioplegia had the highest incidence of postoperative arrhythmias. There was no significant statistical difference between the 3 groups in hospital mortality and morbidity.     

Protection of the hypertrophied myocardium by crystalloid cardioplegia.

Patients with left ventricular hypertrophy (LVH) have a worse outcome after cardiac surgery than those without hypertrophy. We studied protection of hearts with LVH in an isolated rat heart model using multidose, cold, oxygenated cardioplegia. LVH was produced by banding the abdominal aorta in young rats. Six weeks after banding, this produced a 31% increase in the left ventricular dry weight/body weight ratio compared to two age-matched control groups comprising sham-operated and nonoperated animals. The recovery of cardiac output after arrest was higher in LVH (82 +/- 4% of prearrest) than in sham-operated (69 +/- 4%) or nonoperated (66 +/- 3%) control groups. The improved functional recovery in LVH occurred although there were no differences among the groups in myocardial adenosine triphosphate (ATP) and phosphocreatine (PCr) prior to arrest, at the end of arrest, or after reperfusion. Glycogen levels were also similar among the three groups prior to arrest and after reperfusion but were highest in LVH after arrest. Myocardial oxygen consumption (MVO2) and efficiency, expressed as cardiac output/MVO2, were similar among the groups prior to arrest. Myocardial efficiency after reperfusion declined in all groups but was best preserved in LVH. We also compared the sensitivity of hypertrophied and control hearts to the deleterious effects of calcium in cardioplegia. Calcium in the cardioplegia increased myocardial lactate production during arrest in a dose-related fashion and depressed myocardial levels of ATP, PCr, and glycogen at end arrest in all groups. Cardiac output recovery was also depressed by calcium but was still best in LVH. We conclude that the hypertrophied myocardium is well protected by standard cardioplegia and that calcium in cardioplegia does not preferentially depress recovery in LVH.     

Papaverine hydrochloride as an adjunct to asanguinous cardioplegia, is it beneficial?

Papaverine hydrochloride was added to a standard asanguinous cardioplegic solution to study its effect on cardioplegic distribution by evaluating coronary resistance, myocardial temperature, and postoperative enzyme changes. Seventeen patients were randomized into a control group (8 patients) and a papaverine group (9 patients). All patients received 300 cc of a standard asanguinous cardioplegic solution into the aortic root after systemic cooling to 28 degrees C and measurement of septal temperature (To). The duration of infusion (t1), root pressure (p1), and septal temperature (T1) were recorded. All patients received a subsequent infusion of 200 cc of cardioplegia to which had been added either 10 cc normal saline (control group) or 1 mg papaverine hydrochloride in 10 cc normal saline (papaverine group). Time of infusion, root pressure, and septal temperature (t2, p2, T2) were recorded. Coronary resistance was calculated. Postoperative CPK and CPK-MB were recorded and compared. Mean high CPK in the papaverine group was 163 units and 182 units in the control group. There was no statistically significant difference in any parameter between groups. This study, in contradistinction to experience with animal research models, failed to demonstrate any significant value in adding papaverine hydrochloride to standard cardioplegic solutions.     

Effect of glutathion pretreatment on hypothermic ischemic cardioplegia

Glutathion (GSH) plays an important role in maintenance of the redox state of the myocardium and acts as the membrane stabilizer. Seventeen patients who underwent cardiac surgery were subjected to cardiopulmonary bypass (CPB) and ischemic cardioplegia. The effect of GSH on ischemic myocardium was evaluated by serum lysosomal enzymes (acid phosphatase, beta-glucuronidase), isoenzymes of creatine phosphokinase (MB-CPK) and aspartate aminotransferase (m-GOT). Standard CPB was instituted and systemic hypothermia was employed. GSH was administered to 8 patients in a dose of 200 mg/kg i.v. prior to institution of CPB. Mixed venous blood was sampled before administration of GSH, 10 min after institution of CPB and 0, 1, 6, 24 and 48 hr of reperfusion period following cardioplegia. Activity of acid phosphatase and beta-glucuronidase were significantly suppressed in the GSH-treated group compared to the non-treated group at 24 hours of reperfusion and immediately after aortic unclamping, respectively. Serum MB-CPK levels remained stable during reperfusion, but in the non-treated group, the level increased significantly at 6 hours of reperfusion. Increment of serum m-GOT levels was significantly suppressed at 1, 6 and 24 hours of reperfusion, compared to the non-treated group. These data suggest that pretreatment of GSH can protect the myocardium subjected to CPB from ischemic insult.     

The crystalloid cardioplegia: advantages with a word of caution

Technical success and absence of iatrogenic injury from inadequate myocardial protection are the foremost targets of every cardiac surgical procedure. The current trends of pediatric cardiac surgery are aimed to achieve definitive repair of complex cardiac defects at birth as to avoid the risks related with palliative surgery and to reduce the long term impact of the untreated defect on the cardiac function. Thus, even newborn patients are exposed to a prolonged time of myocardial ischemia. The aim of this paper is to describe the impact of crystalloid HKT Custodiol cardioplegia infusion on myocardial protection in the early and late outcome of newborn patients who underwent arterial switch operation (ASO) for transposition of the great arteries (TGA).     

Verapamil crystalloid cardioplegia: an experimental evaluation of dose-response relationships

Calcium channel blockers have been advocated as agents which enhance myocardial protection during ischemia and reperfusion. Unfortunately, while cellular integrity is preserved, myocardial function is depressed as a result of the negative inotropic effects of these agents. In order to assess the efficacy of verapamil cardioplegia, 25 isolated perfused rabbit hearts were studied. A model of normothermic ischemic arrest was utilized, employing either verapamil-free crystalloid cardioplegia or cardioplegia containing verapamil in concentrations of 0.5, 1.0, or 5.0 mg/liter. All three verapamil-treated groups demonstrated increased postischemic left ventricular developed pressure and improved postischemic compliance when compared with the untreated group (P less than 0.05). However, myocardial function was significantly depressed at 15 min of reperfusion in the 1.0 and 5.0 mg/liter verapamil-treated groups when compared with the 0.5 ml/liter group (P less than 0.05). These data suggest that the addition of verapamil to crystalloid cardioplegia results in enhanced myocardial function while minimizing the early reperfusion depression associated with higher dose therapy.     

High-volume crystalloid cardioplegia. An improved method of myocardial preservation

Controlled metabolic studies were used to gauge the relative efficacy of three cardioplegic techniques in 41 patients undergoing multiple coronary artery bypass grafts. Normal-volume (1,946 +/- 155 ml) crystalloid cardioplegia (NVCC) (14 patients) was compared to high-volume (4,961 +/- 282 ml) crystalloid cardioplegia (HVCC) (14 patients) and to blood cardioplegia (BC) (1,672 +/- 127 ml) (13 patients). Measurements of coronary blood flow, coronary vascular resistance, coronary arteriovenous oxygen difference, myocardial oxygen consumption and extraction, and myocardial lactate and potassium extraction and release were all measured in the isolated, vented, paced, beating heart, before and for 20 minutes after a 1 hour arrest interval during which revascularization was completed. Additionally, during administration of the cardioplegic solution, infusion flow rate, myocardial oxygen consumption and extraction, and lactate and potassium release and uptake were noted. The results indicate that during cardioplegic administration, myocardial oxygen consumption is 1 ml O2/min with crystalloid infusion and 2.6 ml O2/min during BC infusion. The volume of crystalloid solution administered contributed to increased oxygen utilization during HVCC compared to NVCC, whereas BC promoted the highest oxygen utilization of the three groups. Potassium absorption was nearly three times greater during BC than during crystalloid administration. During myocardial reperfusion, oxygen extraction was maintained at prearrest levels only in the HVCC group. Following both NVCC and BC, oxygen extraction was depressed during the first 5 minutes of reperfusion, and the difference between the latter two groups and HVCC was significant (p less than 0.01). The rapid recovery in normal metabolic function seen with HVCC allows early discontinuation of cardiopulmonary bypass without myocardial metabolic depression.