Superior protective effect of low-calcium, magnesium-free potassium cardioplegic solution on ischemic myocardium. Clinical study in comparison with St. Thomas' Hospital solution

The protective effect of low-calcium, magnesium-free potassium cardioplegic solution on ischemic myocardium has been assessed in adult patients undergoing heart operations. Postreperfusion recovery of cardiac function and electrical activity was evaluated in 34 patients; 16 received low-calcium, magnesium-free potassium cardioplegic solution (group I) and 18 received St. Thomas' Hospital solution, which is enriched with calcium and magnesium (group II). There were no significant differences between the two groups in age, sex, body weight, and New York Heart Association functional class. Aortic occlusion time (107.3 +/- 46.8 minutes versus 113.6 +/- 44.3 minutes), highest myocardial temperature during elective global ischemia (11.5 degrees C +/- 3.1 degrees C versus 9.3 degrees C +/- 3.2 degrees C), and total volume of cardioplegic solution (44.2 +/- 20.5 ml/kg versus 43.4 +/- 17.6 ml/kg) were also similar in the two groups. On reperfusion, electrical defibrillation was required in four cases (25.5%) in group I and in 15 cases (83.3%) in group II (p less than 0.005), and bradyarrhythmias were significantly more prevalent in group II (6.3% versus 44.4%; p less than 0.05). Serum creatine kinase MB activity at 15 minutes of reperfusion (12.3 +/- 17.0 IU/L versus 42.6 +/- 46.1 IU/L; p less than 0.05) and the dose of dopamine or dobutamine required during the early phase of reperfusion (1.8 +/- 2.5 micrograms/kg/min versus 6.1 +/- 3.3 micrograms/kg/min; p less than 0.0002) were both significantly greater in group II. Postischemic left ventricular function, as assessed by percent recovery of the left ventricular end-systolic pressure-volume relationship in patients who underwent aortic valve replacement alone, was significantly better in group I (160.4% +/- 45.5% versus 47.8% +/- 12.9%; p less than 0.05). Serum level of calcium and magnesium ions was significantly lower in group I. Thus low-calcium, magnesium-free potassium cardioplegic solution provided excellent protection of the ischemic heart, whereas St. Thomas' Hospital solution with calcium and magnesium enabled relatively poor functional and electrical recovery of the heart during the early reperfusion period. These results might be related to differing levels of extracellular calcium and magnesium on reperfusion.     

Comparison of myocardial temperatures with multidose cardioplegia versus single-dose cardioplegia and myocardial surface cooling during coronary artery bypass grafting

Myocardial hypothermia with multidose cardioplegia has not been compared with single-dose cardioplegia and myocardial surface cooling with a cooling jacket in patients having coronary artery bypass grafting. In this study, 20 patients with three-vessel disease undergoing coronary bypass at 28 degrees C with bicaval cannulation, caval tapes, and pulmonary artery venting (4.9 +/- 0.7 grafts per patient) were prospectively randomized equally into group I (multidose cardioplegia) and group II (single-dose cardioplegia with a cooling jacket). The initial dose of cardioplegic solution was 1000 ml. Group I then received 500 ml of cardioplegic solution every 20 minutes, delivered into the aortic root and available grafts. In group II, after the cardioplegic solution had been administered, a cooling jacket covering the right and left ventricles was applied. In both groups temperatures were recorded every 30 seconds at five ventricular sites: (1) right ventricular epicardium; (2) right ventricular myocardium or cavity, 7 mm; (3) left ventricular epicardium; (4) left ventricular myocardium or cavity, 15 mm; and (5) septum, 20 mm. Group mean temperatures at each site at various times were compared within each group and between the two groups by analysis of variance. Aortic crossclamp time was 60.3 +/- 12.1 minutes in group I and 52.8 +/- 7.3 minutes in group II (p = 0.12); cardiopulmonary bypass time was 103.7 +/- 11.1 minutes in group I versus 87.7 +/- 12.7 minutes in group II (p less than 0.01). One minute after the cardioplegic solution was initially given, temperatures between groups at each site were not statistically different, but left ventricular epicardial temperatures within both groups were significantly higher than in the other four sites. Nineteen minutes after administration of the cardioplegic solution, temperatures in group I at all sites were higher than in group II. Similarly, throughout the entire period of aortic crossclamping, mean temperatures (except left ventricular myocardial site), maximum temperatures, and percentage of time all temperatures were 15 degrees C or higher were greater in group I than in group II. The following conclusions can be reached: 1. Initial myocardial cooling with 1000 ml of cardioplegic solution is not significantly limited by coronary artery disease but is suboptimal (16 degrees or 17 degrees C) in the inferior left ventricular epicardium because of continual warming from the aorta and subdiaphragmatic viscera. 2. Without myocardial surface cooling, excessive external myocardial rewarming to 18 degrees to 22 degrees C occurs within 20 minutes at all sites after delivery of the cardioplegic solution.(ABSTRACT TRUNCATED AT 400 WORDS)     

Rapid cooling contracture of the myocardium. The adverse effect of prearrest cardiac hypothermia

Hypothermic total circulatory arrest for repair of congenital heart lesions in neonates requires a period of rapid core cooling on cardiopulmonary bypass during which the myocardium is also exposed to hypothermic perfusion. Myocardial hypothermia in the nonarrested state results in an increase in contractility due to elevation of intracellular calcium levels. This study was designed to test the hypothesis that rapid myocardial cooling before cardioplegic ischemic arrest results in damage, with impaired recovery during reperfusion. Two groups of 10 rabbit hearts were perfused on an isolated Langendorff apparatus. Group N (normothermia) was perfused at 37 degrees C before 2 hours of cardioplegic ischemic arrest at 10 degrees C. Group C (cooling) was perfused at 15 degrees C in the unarrested state for 20 minutes before the same cardioplegic arrest conditions as group N. Left ventricular isovolumic pressure measurements, biochemical measurements from right ventricular biopsy specimens, and ventricular necrosis as defined by tetrazolium staining were used to compare the groups at 30 and 60 minutes of normothermic reperfusion. Developed pressure at a constant volume was preserved in group N at 90.7 +/- 4.5 mm Hg versus 76.9 +/- 6.3 in group C after reperfusion (p less than 0.05). Diastolic compliance showed significant deterioration in group C, with marked elevation of diastolic pressure during reperfusion (group N = 6.8 +/- 2.5 mm Hg versus group C = 38.9 +/- 6.1 after reperfusion; p less than 0.001). Adenosine triphosphate levels were significantly higher in group N both at end-ischemia and after reperfusion versus group C (group N = 17.0 +/- 1.1 nmol/mg protein versus group C = 7.7 +/- 1.0 after reperfusion; p less than 0.001). Group N had 0.4% +/- 0.4% necrosis of ventricular mass versus 19.3% +/- 2.2% with prearrest cooling in group C (p less than 0.0001). These results indicate that, when combined with cardioplegic ischemic arrest, rapid myocardial cooling in the unarrested state results in significant damage. The mechanism may be related to the cytosolic calcium loading effect of hypothermia that is not relieved during the subsequent period of cardioplegic arrest. Although hypothermia is an essential component to ischemic preservation, rapid cooling contracture can adversely influence cardioplegic myocardial protection.     

Adverse effect of prearrest hypothermia in immature hearts: rate versus duration of cooling.

It has been suggested that rapid cooling before the induction of arrest may be harmful to the newborn myocardium. The objective of this study was twofold: (1) to evaluate whether prearrest rapid cooling is indeed detrimental to myocardial recovery and (2) if so, to evaluate whether the adverse effect of prearrest hypothermia is dependent on the rate of cooling or the total duration of cold perfusion. After an initial stabilization period isolated Langendorff hearts (n = 5 per group) from neonatal piglets (5 to 7 days old) were randomized to four groups: group 1, 5 minutes of rapid cooling to 15 degrees C; group 2, 20 minutes of slow cooling to 15 degrees C; group 3 and group 4, rapid and slow cooling, respectively, with the addition of St. Thomas cardioplegic solution. All groups were then subjected to 2 hours of ischemia at 15 degrees C followed by 30 minutes of reperfusion at 38.5 degrees C. Post-ischemic recovery of left ventricular developed pressure was significantly greater in group 1 versus group 2 (80% +/- 3% versus 61% +/- 2%; p less than 0.05) and in the presence of cardioplegia, group 3 versus group 4 (72% +/- 3% versus 57% +/- 3%; p less than 0.05). The increase in left ventricular end-diastolic pressure was significantly less in group 1 versus group 2 (8% +/- 5% versus 33% +/- 7%; p less than 0.01). Myocardial adenosine triphosphate content recovery correlated with ventricular recovery.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of antegrade cardioplegic infusion with simultaneously controlled coronary sinus occlusion on preservation of regionally ischemic myocardium after acute coronary artery occlusion and reperfusion

This study was conducted to assess the protective effects of antegrade infusion of cardioplegic solution with simultaneously controlled coronary sinus occlusion on regionally ischemic myocardium after acute coronary occlusion and reperfusion. Twelve sheep were subjected to 1 hour of occlusion of the distal left anterior descending coronary artery. Sheep in group I (n = 6) were subjected only to infusion of potassium crystalloid cardioplegic solution into the aortic root, whereas in group II (n = 6) a stitch was snared around the proximal coronary sinus for its subsequent occlusion during antegrade infusions of cardioplegic solution. All animals were placed on cardiopulmonary bypass. Five hundred milliliters of cardioplegic solution at 4 degrees to 8 degrees C was administered in three divided doses during the total cross-clamp period of 30 minutes. The occlusion of the left anterior descending artery was then released, and the animals were weaned from bypass and studied for an additional 4 hours. Coronary sinus pressure, myocardial temperature, regional function assessed by pairs of ultrasonic crystals, global function assessed by rate of rise of left ventricular pressure and cardiac output, and the area at risk and area of necrosis were determined. The heart was excised at the end of the experiment and stained. Animals treated by the technique of antegrade infusion combined with coronary sinus occlusion had more homogeneous myocardial cooling during cardioplegic infusions and better recovery of the first derivative of left ventricular pressure and regional segment shortening at 90 and 270 minutes of reperfusion than those treated with antegrade infusion alone (p less than 0.01 and p less than 0.05, respectively). The group treated by antegrade infusion of cardioplegic solution combined with coronary sinus occlusion had an area of necrosis/area at risk ratio of 40.5% +/- 1.2%; the antegrade infusion group, 58.3% +/- 4.1% (p less than 0.01). These data suggest that antegrade infusion combined with coronary sinus occlusion may be an improved method of global and regional myocardial protection in the presence of an occluded coronary artery.     

Distribution of cardioplegic solution infused antegradely and retrogradely in normal canine hearts

The adequacy of retrograde delivery of cardioplegic solution to the right ventricle and interventricular septum is controversial. To address this issue quantitatively, we infused blood cardioplegic solution labeled with radioactive microspheres (15 microns diameter) into the coronary sinus (n = 8 dogs) at a pressure of 51 +/- 1 mm Hg (mean +/- standard error of the mean) to be compared with the same quantity of labeled cardioplegic solution (20 ml/kg) delivered through the aorta (n = 6 dogs) at 97 +/- 7 mm Hg. Both methods of delivery produced cardiac arrest, but retrograde infusion required a significantly longer time to complete the infusion (6.2 +/- 0.8 minutes versus 1.5 +/- 0.1 minutes, p less than 0.01). Greater than 99% of the microspheres passing through the vasculature of the left ventricle were trapped in the left ventricular myocardium with antegrade infusion, and the distribution of the cardioplegic solution was uniform. Antegrade delivery (cardioplegic flow x infusion time) averaged approximately 3.0 to 4.0 ml/gm, except at the apex, where delivery averaged approximately 2.0 ml/gm. With retrograde infusion, 93% of the microspheres perfusing the left ventricle were trapped and delivery of the cardioplegic solution was not uniform. In the anterolateral free wall, delivery of cardioplegic solution averaged between 1.5 and 2.9 ml/gm (p less than 0.001 compared with antegrade) and only 0.6 to 0.8 ml/gm in the posteroseptal region of the basal left ventricle (p less than 0.001 compared with the antegrade group and anterolateral samples of the retrograde group). In the middle portion of the right ventricle, antegrade trapping of microspheres was 99% and delivery of cardioplegic solution averaged approximately 2.0 ml/gm. With retrograde delivery, only 16.5% (range 11.8% to 26.0%) of the microspheres passing through the right ventricular vasculature were trapped in the right ventricular myocardium, which indicates that substantial shunting had occurred. Corrected for the high shunt fraction, retrograde delivery of cardioplegic solution to the middle portion of the right ventricle averaged only 0.5 ml/gm (p less than 0.01). Retrograde delivery to the atrial septum and right atrium was also low. Because retrograde delivery of cardioplegic solution was markedly nonuniform, we conclude that inadequate cardioplegic delivery to the middle portion of the right ventricle and posteroseptal portion of the left ventricle could result with cardioplegic infusion through the coronary sinus.     

Studies of retrograde cardioplegia. II. Advantages of antegrade/retrograde cardioplegia to optimize distribution in jeopardized myocardium

This study tests the hypothesis that retrograde/antegrade cardioplegic delivery can overcome the limitations of poor cardioplegic distribution resulting from either technique alone and, potentially, may expand the safety of using internal mammary artery grafts in cardiac muscle in jeopardy of inadequate cardioplegic protection. Jeopardized myocardium was produced in 20 dogs by ligating the left anterior descending coronary artery for 15 minutes before starting cardiopulmonary bypass and by 1 hour of aortic clamping with multidose 6 degrees C cold blood cardioplegia. Five dogs received antegrade cardioplegia via the aortic root. Ten dogs received retrograde cardioplegia via the coronary sinus. Five additional dogs received retrograde/antegrade cardioplegia via both routes. The ligature on the left anterior descending coronary artery was removed after aortic unclamping, and regional myocardial temperature (thermistor probe), segmental shortening (ultrasonic crystals), and global left ventricular and right ventricular myocardial function were evaluated. Antegrade cardioplegia produced excellent right ventricular cooling (14 degrees C) and allowed complete right ventricular functional recovery. However, it failed to cool muscle supplied by the left anterior descending coronary artery (only 31 degrees versus 12 degrees C, p less than 0.05), postischemic global left ventricular function recovered only 38% (p less than 0.05), and segmental shortening in the region supplied by the left anterior descending coronary artery recovered only 22% (p less than 0.05). Retrograde cardioplegia produced homogeneous cooling (17 degrees C) and allowed near normal recovery of global and regional left ventricular function (99% and 86%), but right ventricular cooling was variable (19 degrees to 30 degrees C) and right ventricular function recovered inconstantly (range 64% to 100%, average 82%). The best myocardial protection occurred after retrograde/antegrade cardioplegia; myocardial cooling was homogeneous, left ventricular and right ventricular global function recovered completely (95% and 90%), and regional contractility in muscle supplied by the left anterior descending coronary artery returned to 84% of control. We conclude that retrograde/antegrade cardioplegia provides better myocardial protection than either technique alone, ensures good cardioplegic distribution to the left and right ventricles, and allows regional delivery of cardioplegic flow to segments supplied by occluded arteries.(ABSTRACT TRUNCATED AT 400 WORDS)     

The role of cardioplegia induction temperature and amino acid enrichment in neonatal myocardial protection

BACKGROUND: Warm cardioplegic induction improves the ischemically "stressed" adult heart. However, it is rarely used in infants, despite the fact that many newborn hearts are stressed by other factors such as hypoxia. The need for amino acids as well as their mechanism of action has also not been studied. METHODS: We first assessed the role of cardioplegic induction temperature in 10 nonhypoxic neonatal piglets undergoing 70 minutes of multidose blood cardioplegic arrest. Five piglets (group 1) received a cold (4 degrees C) induction, and 5 (group 2) a warm (37 degrees C) induction. Twenty-six other piglets underwent ventilator hypoxia (fraction of inspired oxygen, 8% to 10%) for 60 minutes before cardiopulmonary bypass (stress). Six piglets (group 3) then underwent 70 minutes of cardiopulmonary bypass without ischemia (hypoxia controls), and 20 underwent 70 minutes of cardioplegic arrest. Five of these (group 4) received cold cardioplegic induction, and 15 received warm induction; in 5 of these (group 5), the warm cardioplegic solution contained amino acids, in 5 others (group 6), it was unsupplemented, and in the remaining 5 (group 7), nitroglycerin was added to determine the role of vasodilation. Myocardial function was assessed by pressure-volume loops (expressed as a percent of control), and coronary vascular resistance was measured with cardioplegic infusions. RESULTS: In nonhypoxic (normal) piglets, cold (group 1) and warm (group 2) induction completely preserved systolic function (end-systolic elastance, 100% versus 104%) and preload recruitable stroke work (100% versus 102%), with minimal increase in diastolic compliance (162% versus 156%). Hypoxia-reoxygenation alone (group 3) depressed systolic function (end-systolic elastance, 51%+/-2%) and preload recruitable stroke work (54%+/-3%), and raised diastolic stiffness (260%+/-15%). The detrimental effects of reoxygenation persisted (unchanged from reoxygenation alone) with cold induction (group 4) or warm induction without amino acids (groups 6 and 7). In contrast, warm induction with amino acids (group 5) restored systolic function (end-systolic elastance, 105%+/-3%; p < 0.001 versus groups 3, 4, 6, and 7) and preload recruitable stroke work (103%+/-2%; p < 0.001 versus groups 3, 4, 6, and 7), and decreased diastolic stiffness (154%+/-7%; p < 0.001 versus groups 3, 4, 6, and 7). However, there was no difference in myocardial oxygen consumption in hypoxic hearts receiving a warm induction (6.9 versus 6.5 versus 7.3 mL/g per 5 minutes) (groups 5, 6, 7), and coronary vascular resistance was lowest with nitroglycerin (group 7). CONCLUSIONS: Cardioplegic induction can be given either warm or cold in nonhypoxic neonatal hearts. In contrast, only warm induction with amino acids repairs the hypoxic injury, but the primary mechanism of action is not related to increased metabolic activity or vasodilation.     

Studies of retrograde cardioplegia. I. Capillary blood flow distribution to myocardium supplied by open and occluded arteries

This study defines the nutritive (i.e., capillary) distribution of blood cardioplegic solutions delivered via retrograde and antegrade techniques to muscle supplied by open and occluded coronary arteries where myocardial segments are in jeopardy of inadequate cardioplegic protection. Open-chest anesthetized dogs were studied by mixing radioactive microspheres (15 +/- 5 microns) with a blood cardioplegic solution and administering cardioplegia either into the coronary sinus or into the proximal aorta with the left anterior descending coronary artery open or occluded (30% +/- 2% area at risk). Nutritive flow (i.e., percentage of delivered 15 microns microspheres trapped in myocardial capillaries) during retrograde infusions averaged 65% versus 87% with antegrade cardioplegia (p less than 0.05). Retrograde and antegrade cardioplegic nutritive flow to all left ventricular regions was comparable with the left anterior descending coronary artery open (65 versus 82 ml/100 gm/min, p greater than 0.05), and both methods provided preferential hyperperfusion of subendocardial muscle (endocardial/epicardial ratios 1.6 and 1.5, respectively). Nutritive flow to muscle supplied by the occluded left anterior descending coronary artery was preserved better by retrograde than antegrade cardioplegia (35 versus 5 ml/100 gm/min, p less than 0.05). Preferential subendocardial hyperperfusion was maintained during retrograde cardioplegia (52 ml/100 gm/min, endocardial/epicardial ratio 1.6), but flow was redistributed away from subendocardial muscle with antegrade cardioplegia (less than 2 ml/100 gm/min, endocardial/epicardial, 0.29, p less than 0.05). Left ventricular flow was reduced markedly during retrograde infusion with the left anterior descending coronary artery open or occluded (23 and 12 ml/100 gm/min), but septal cooling was superior to antegrade cardioplegia (15 degrees +/- 1 degree C versus 20% +/- 3%, p less than 0.05) despite near-normal antegrade septal flow (the left anterior descending coronary artery was ligated beyond the first septal branch). Right ventricular nutritive flow was only 7 ml/100 gm/min during retrograde coronary sinus perfusion and was maintained normally with antegrade cardioplegia.(ABSTRACT TRUNCATED AT 400 WORDS)     

Right ventricular myocardial protection through intracavitary cooling in cardiac operations

In an attempt to protect the right ventricle, we designed and tested a closed cooling system that circulates cold saline through a double-lumen, balloon-tipped catheter positioned in the right ventricular cavity. Fourteen sheep were randomly assigned to two groups. In group A (n = 7), the right ventricular cooling catheter system was used in addition to coronary cardioplegic perfusion and systemic hypothermia for myocardial protection. Group B (n = 7) served as a control group. In group A, the right ventricular temperatures were significantly lower than those of the control group (16.1 degrees +/- 0.3 degrees C versus 23.9 degrees +/- 0.4 degrees C; p less than 0.0001, Student's t test). The most common temperature range was 12 degrees to 18 degrees C (67.1%, frequency distribution analysis), and 63.2% of temperatures were below 16 degrees C. The catheter system also maintained the temperatures of the interventricular septum at a lower level than those recorded in the control group and prevented septal rewarming, which was significant in group B (from 16.5 degrees +/- 1.5 degrees C to 25.0 degrees +/- 0.9 degrees C; p less than 0.04, Mann-Whitney U test). Left ventricular temperatures were not changed by the catheter system. By better cooling the right ventricle and the septum, the right ventricular cooling catheter system should decrease the prevalence of right ventricular failure and allow more time to safely complete multiple coronary anastomoses in coronary artery bypass graft operations.     

Right ventricular function in retrograde cardioplegia for myocardial protection--an experimental study

Anterior cardiac veins which are the main drainage vessels of the right ventricle drain directly into the right atrium. Therefore, the right ventricular wall may not be perfused effectively during open heart surgery by the use of retrograde cardioplegic method resulting in postoperative right ventricular dysfunction. Seventeen mongrel dogs were subjected to this study and were placed on cardiopulmonary bypass using a conventional heart-lung machine. Total aortic cross-clamping time was 60 minutes in all dogs. In Group I (n = 6), 4 degrees C St. Thomas' Hospital solution (15 ml/kg body weight) was injected into the aortic root by the use of a syringe. Cardioplegic solution was replenished every 20 minutes with a half of the initial dose (7.5 ml/kg body weight). Group II (n = 6) were the dogs with the retrograde cardioplegia in which 4 degrees C St. Thomas' Hospital solution (15 ml/kg body weight) was given retrogradely from the coronary sinus by the drip method at the height of 60 cm, and the replenishing dose and interval of cardioplegia were the same as Group I. Group III (n = 5) was the dogs treated with retrograde cardioplegia identical to Group II and the combined use of topical cooling with ice-slush. The hearts were resuscitated after 60 minutes of aortic cross-clamping. Right ventricular functions such as cardiac output, right atrial pressure, right ventricular end-diastolic pressure, right ventricular max dp/dt, and shortening fraction of the right ventricle were measured 15, 30, 45, and 60 minutes after cardiac resuscitation respectively. In Group II, right atrial pressure was significantly elevated from the control value 15 and 30 minutes after cardiac resuscitation. On the other hand, all indices of right ventricular functions in Group III showed insignificant changes. The present experimental study demonstrated the retrograde cardioplegic method could produce right ventricular perfusion resulting in right ventricular dysfunction early after cardiac resuscitation. This deleterious effect however could be prevented by the combined use of topical cooling of the right ventricle with ice-slush.     

A new technique of internal cardiac cooling improves atrial protection

We developed a technique for selectively cooling the right heart during cardioplegic arrest by intracavitary right atrial (RA) perfusion with cold blood. In dogs during hypothermic cardioplegic arrest, we compared the effects on myocardial temperature of RA perfusion and two snared caval cannulas with three methods of venous cannulation without perfusion: a two-stage atriocaval cannula, two caval cannulas and two snared caval cannulas. The mean atrioventricular (AV) node temperature with RA perfusion (16.5 degrees +/- 0.4 degrees C) was significantly lower than with the atriocaval cannula (25.1 degrees +/- 0.2 degrees C), two caval cannulas (25.2 degrees +/- 0.3 degrees C) or two snared caval cannulas (21.6 degrees +/- 0.2 degrees C) (p less than 0.01, RA perfusion versus other groups). The results for RA wall temperature showed a similar pattern. RA perfusion produced similar results in 6 patients undergoing coronary artery bypass grafting. We conclude that hypothermic protection of the right atrium and AV node is inadequate with conventional techniques of cannulation and cooling, and may be improved by the use of internal RA cooling.     

Effects of potassium cardioplegia on high-energy phosphate kinetics during circulatory arrest with deep hypothermia in the newborn piglet heart

The protective effects of hypothermia and potassium-solution cardioplegia on high-energy phosphate levels and intracellular pH were evaluated in the newborn piglet heart by means of in vivo phosphorus nuclear magnetic resonance spectroscopy. All animals underwent cardiopulmonary bypass, cooling to 20 degrees C, 120 minutes of circulatory arrest, rewarming with cardiopulmonary bypass, and 1 hour off extracorporeal support with continuous hemodynamic and nuclear magnetic resonance spectroscopic evaluation. Group I (n = 5) was cooled to 20 degrees C; group II (n = 4) was given a single dose of 20 degrees C cardioplegic solution; group III (n = 7) was given a single dose of 4 degrees C cardioplegic solution; and group IV (n = 4) received 4 degrees C cardioplegic solution every 30 minutes. At end ischemia, adenosine triphosphate, expressed as a percent of control value, was lowest in group I 54% +/- 6.5% but only slightly greater in group II 66% +/- 7.0%. Use of 4 degrees C cardioplegic solution in groups III and IV resulted in a significant decrease in myocardial temperature, 9.9 degrees C versus 17 degrees to 20 degrees C, and significantly higher levels of adenosine triphosphate at end ischemia; with group III levels at 72% +/- 6.0% and group IV levels at 73% +/- 6.0%. Recovery of adenosine triphosphate with reperfusion was not related to the level of adenosine triphosphate at end ischemia and was best in groups I and II, with a recovery level of 95% +/- 4.0%. In group IV, no recovery of adenosine triphosphate occurred with reperfusion, resulting in a significantly lower level of adenosine triphosphate, 74% +/- 6.0%, than in groups I and II. Recovery of ventricular function was good for all groups but was best in hearts receiving a single dose of 4 degrees C cardioplegic solution. In this model, multiple doses of cardioplegic solution were not associated with either improved adenosine triphosphate retention during arrest or improved ventricular function after reperfusion, and in fact resulted in a significantly lower level of adenosine triphosphate with reperfusion. The complete recovery of adenosine triphosphate in groups I and II, despite a nearly 50% adenosine triphosphate loss during ischemia, may result from a decrease in the catabolism of the metabolites of adenosine triphosphate consumption in the newborn heart.     

Improved myocardial preservation during global ischemia by continuous retrograde coronary sinus perfusion

To investigate whether retrograde continuous low-pressure perfusion of the coronary sinus could deliver cardioplegic solutions with oxygen and substrate beyond stenoses and result in improved myocardial preservation, we subjected 41 canine hearts to 90 minutes of ischemia with an occlusion on the circumflex coronary artery. There were four groups: Group I, antegrade (aortic root) crystalloid cardioplegia every 30 minutes during ischemia; Group II, antegrade plus topical cooling; Group III, continuous retrograde perfusion; Group IV, same as Group III, with an oxygenated perfluorocarbon. All solutions had a PO2 of 400 to 500 mm Hg. Intramyocardial oxygen and carbon dioxide tensions (PO2 and PCO2) and mean myocardial temperatures were monitored during ischemia, and left ventricular (LV) function was assessed before ischemia and after reperfusion. After global ischemia, the circumflex occlusion was released and the hearts reperfused. Following 60 minutes of reperfusion, isovolumic developed pressure returned to 36% +/- 4% and 41% +/- 5% of preischemic levels, respectively, in Groups I and II. By contrast, Groups III and IV (retrograde perfusion) had a significantly greater percent of recovery (78% +/- 5% and 73% +/- 5%). Circumflex area intramyocardial PO2 fell 20 and 25 mm Hg below preischemic levels in Groups I and II during ischemia, whereas in Group III, intramyocardial PO2 in the circumflex region remained near preischemic levels, and in Group IV, it rose 19 mm Hg. Mean myocardial temperature during ischemia in the circumflex area was significantly higher in Group I than in Groups II, III, and IV. Peak intramyocardial PCO2 in the circumflex region was significantly less in the retrogradely perfused hearts. Retrograde coronary sinus perfusion resulted in significant improvement in recovery of LV function, uniform myocardial cooling, normal intramyocardial PO2, and less intramyocardial PCO2 accumulation, despite the presence of a total circumflex coronary artery occlusion.     

Internal cardiac cooling improves atrial preservation: electrophysiological and biochemical assessment

This study was designed to determine if the improved hypothermia that can be achieved with cold perfusion of the right atrium is associated with improved atrial preservation. During 120 minutes of cardioplegic arrest, 7 dogs with occlusive caval cannulation underwent right atrial (RA) perfusion with cold blood and 7 dogs with a single atriocaval cannula served as controls. RA perfusion produced a lower atrial septal temperature than atriocaval cannulation, 96% less electrical activity during arrest, and a lesser prolongation of the A-H interval after reperfusion (40% versus 123%; p less than 0.01). At the end of arrest, compared with atriocaval cannulation, RA perfusion was associated with improved preservation of creatine phosphate (71 +/- 10% versus 40 +/- 7% of control; p less than 0.05) and a lower level of lactate in the RA wall (8 +/- 1 mumol/gm versus 15 +/- 2 mumol/gm; p less than 0.01). We conclude that improved hypothermia reduces electrical activity and anaerobic metabolism in the atrial myocardium during cardioplegic arrest and improves atrioventricular conduction following arrest.     

The effects of cardioplegic arrest on right atrial function

Atrial electrical and mechanical activity persists during cardioplegic arrest. It has been postulated that atrial ischemia may occur and cause deterioration in atrial function. This study was designed to assess the effect of cardioplegic arrest on right atrial function. Twenty-one pigs were placed on cardiopulmonary bypass (CPB), and the right atrium was isolated from the circulation by snaring both venae cavae and incising the coronary sinus. The tricuspid valve was closed through a small right ventriculotomy, and baseline atrial function was assessed using a compliant balloon in the atrium. Fourteen pigs underwent one hour of cardioplegic arrest (7 with cardioplegia alone [CCA group] and 7 with the addition of topical hypothermia [CCA + TH group]) followed by one hour of normothermic reperfusion. Seven other pigs were placed on CPB for the same period of time (CPB group). Atrial electrical and mechanical activity persisted at 45 beats per minute in the CCA group but was virtually abolished in the CCA + TH group. Cardioplegic arrest caused considerable deterioration in right atrial function (developed pressure, 18.9 +/- 0.8 [baseline] versus 14.1 +/- 0.7 mm Hg; p less than 0.05; first derivative of atrial pressure [dP/dt], 187 +/- 19 versus 134 +/- 25 mm Hg per second; p less than 0.05; 60 minutes of reperfusion and balloon volume of 20 ml). It was not affected by topical cooling. Right atrial developed pressure was maintained, but dP/dt was significantly reduced in the CPB group. This study suggests that cardioplegic arrest does not protect the atrium.     

Retrograde coronary sinus perfusion of cardioplegic solution in Jatene operation in neonates and infants

The clinical benefits of retrograde coronary sinus perfusion of a cardioplegic solution were investigated in 7 neonates and 23 infants undergoing Jatene operation. After an initial infusion of albumin-containing crystalloid cardioplegic solution via the aortic root, 21 patients received additional solution delivered by retrograde coronary sinus perfusion (retrograde group) and 9 patients received by selective antegrade coronary perfusion (antegrade group) every 20 to 30 minutes. There were no differences in age, weight, and left ventricular preoperative pressure and morphology between the two groups. Aortic cross-clamping time was 130 +/- 18 minutes in retrograde group and 147 +/- 20 minutes in antegrade group. Postoperative assays of CPK-MB, GOT and LDH, and hemodynamic measurements immediately after cessation of cardiopulmonary bypass (CPB) were carried out in all patients. Although there was no significant difference between the two groups in terms of enzyme indexes, retrograde group showed a greater variation of sigma CPK-MB from patient to patient than antegrade group. However, hemodynamic parameters of CVP, left atrial pressure and rate-pressure product at 20-30 minutes after CPB were similar in the two groups. Six neonates in retrograde group also demonstrated the similar enzyme indexes and hemodynamic state immediately after CPB to other older patients. We concluded, therefore, that retroperfusion of cardioplegic solution in neonates and infants provides satisfactory myocardial protection as well as antegrade perfusion, and it was a useful means of cardioplegic delivery in Jatene operation, because of its simplicity.     

Electrophysiological evaluation of retrograde cardioplegia--experimental study of efficacy for the right ventricle

Recently, coronary artery bypass grafting operations for patients with total proximal multi-vessel coronary obstructions are increased. In these cases, antegrade cardioplegia through the aortic root has been applied as usual. But it seems to be difficult to deliver cardioplegic solution to myocardium uniformly beyond coronary stenosis. Retrograde coronary sinus cardioplegia in the presence of proximal coronary artery obstruction could maintain improved cardioplegic delivery and satisfactory myocardial protection. Because of the limitation of antegrade cardioplegia, retrograde cardioplegic technique has, once again, been cited as a reasonable alternative to antegrade cardioplegia. But on the other hand, retrograde cardioplegia includes the potential for relatively inadequate preservation of right ventricle based on the venous drainage communication to the coronary sinus. The object of the present work is mainly to evaluate the efficacy of retrograde coronary sinus cardioplegic technique for right ventricle by electrophysiological method. Thirty-six adult mongrel dogs divided three groups. Sixteen animals (Group I) received GIK cardioplegia through the coronary sinus, thirteen animals (Group II) received GIK added diltiazem cardioplegia through the same way, and seven animals (Group III) received GIK cardioplegia through aortic root. No large temperature gradients of myocardium between right and left ventricle in each group and also temperature gradients of right ventricle between three groups have been observed. The time duration from starting of injection of cardioplegia to disappear the electrical activity in right and left ventricle were 11.4 +/- 8.2, 3.4 +/- 1.2 minutes in group I, 2.9 +/- 1.5, 2.2 +/- 1.4 minutes in group II, and 0.9 +/- 0.4, 0.9 +/- 0.2 minutes in group III. The time duration from starting of injection of cardioplegia to reappear the electrical activity in right and left ventricle were 6.4 +/- 8.7, 13.4 +/- 7.9 minutes in group I, 20.0 +/- 3.5, 21.3 +/- 1.6 minutes in group II and 18.0 +/- 5.5, 18.7 +/- 4.5 minutes in group III. Unipolar peak-to-peak amplitude (UPPA) analysis reveals the condition of myocardial preservation during ischemic arrest and we compared preischemic UPPA with post-ischemic UPPA. In group I, UPPA declined of 44.1 +/- 29.3% in right ventricle and 72.7 +/- 27.6% in left ventricle, in group II, 78.7 +/- 28.7%, 81.9 +/- 23.6%, in group III, 71.4 +/- 18.7%, 76.7 +/- 9.89%. Analysis of ultrastructural changes in the myocardium are shown that injury was most manifest in the right ventricle of group I, but in group II, ultrastructure of right ventricle maintained nearly normal condition.(ABSTRACT TRUNCATED AT 400 WORDS)     

Studies of myocardial protection in the immature heart. V. Safety of prolonged aortic clamping with hypocalcemic glutamate/aspartate blood cardioplegia

This study tests the hypothesis that multidose, hypocalcemic aspartate/glutamate-enriched blood cardioplegia provides safe and effective protection during prolonged aortic clamping of immature hearts. Of 17 puppies (6 to 8 weeks of age, 3 to 5 kg) placed on vented cardiopulmonary bypass, five were subjected to 60 minutes of 37 degrees C global ischemia without cardioplegic protection and seven underwent 120 minutes of aortic clamping with 4 degrees C multidose aspartate/glutamate-enriched blood cardioplegia ([Ca++] = 0.2 mmol/L), preceded and followed by 37 degrees C blood cardioplegic induction and reperfusion. Five puppies underwent blood cardioplegic perfusion for 10 minutes without intervening ischemia to assess the effect of the cardioplegic solution and the delivery techniques. Left ventricular performance was assessed 30 minutes after bypass was discontinued (Starling function curves). Hearts were studied for high-energy phosphates and tissue amino acids. One hour of normothermic ischemia resulted in profound functional depression, with peak stroke work index only 43% of control (0.7 +/- 0.1 versus 1.7 +/- 0.2 gm x m/kg, p less than 0.05). There was 70% depletion of adenosine triphosphate (7.6 +/- 1 versus control 20.3 +/- 1 mumol/gm dry weight, p less than 0.05) and 75% glutamate loss (6.6 +/- 1 versus control 26.4 +/- 3 mumol/gm, p less than 0.05). In contrast, after 2 hours of aortic clamping with multidose blood cardioplegia preceded and followed by 37 degrees C blood cardioplegia, there was complete recovery of left ventricular function (peak stroke work index 1.6 +/- 0.2 gm x m/kg) and maintenance of adenosine triphosphates, glutamate, and aspartate levels at or above control levels adenosine triphosphate 18 +/- 2 mumol/gm, aspartate 21 +/- 1 versus control 2 mumol/gm, and glutamate 25.4 +/- 2 mumol/gm). Puppy hearts receiving blood cardioplegic perfusion without ischemia had complete recovery of control stroke work index. We conclude that methods of myocardial protection used in adults, with amino acid-enriched, reduced-calcium blood cardioplegia, can be applied safely to the neonatal heart and allow for complete functional and metabolic recovery after prolonged aortic clamping.     

Myocardial perfusion during warm antegrade and retrograde cardioplegia: a contrast echo study.

BACKGROUND: We evaluated distribution of warm antegrade and retrograde cardioplegia in patients undergoing coronary artery bypass grafting (CABG). METHODS: Myocardial perfusion was evaluated pre- and post-CABG using transesophageal echocardiography with injection of sonicated albumin microbubbles (Albunex) during warm antegrade and retrograde cardioplegia. The left ventricle (LV) was evaluated in five segments and the right ventricle (RV) was evaluated in two segments. Segmental contrast enhancement was graded as absent (score = 0), suboptimal or weak (score = 1), optimal or excellent (score = 2), or excessive (score = 3). RESULTS: Pre-CABG cardioplegic perfusion correlated weakly with severity of coronary artery stenoses (r = -0.331 and 0.276 for antegrade and retrograde cardioplegia, respectively). Antegrade cardioplegia administration resulted in 98% and 96% perfusion to the left ventricle pre- and post-CABG, respectively. Retrograde cardioplegic administration resulted in reduced LV perfusion, with 86% (p = 0.032 from antegrade) and 59% (p<0.001 from antegrade) pre- and post-CABG, respectively. The average LV perfusion score (mean +/- SEM) was greater with antegrade than retrograde cardioplegia both pre-CABG (1.93+/-0.04 vs. 1.53+/-0.11, p<0.001) and post-CABG (1.63+/-0.07 vs. 1.19+/-0.13, p = 0.004). RV perfusion was poor with both techniques pre-CABG, but improved significantly with antegrade cardioplegia post-CABG. CONCLUSIONS: We conclude that warm antegrade cardioplegia results in better left ventricular perfusion than warm retrograde cardioplegia. Right ventricular cardioplegic perfusion was suboptimal, but the best delivery was achieved with antegrade cardioplegia after coronary bypass. We therefore recommend construction of the saphenous vein graft to the right coronary artery early in the operative procedure.