A Comparison of Intermittent and Continuous Arrest for Prolonged Hypothermic Cardioplegia

A study was carried out to evaluate the best method of myocardial preservation in the pig-heart model. Two techniques for employing hypothermic potassium cardioplegia during prolonged ischemic arrest were compared. One entailed three one-hour periods of arrest interrupted with 30-minute intervals of reperfusion (intermittent arrest), and the other involved a single period of continuous hypothermic cardioplegic arrest (continuous arrest) of three hours' duration. In order to evaluate intermittent versus continuous cardioplegic arrest, prearrest and postarrest contractility, compliance, myocardial perfusion, and left ventricular adenosine triphosphate (ATP) and creatine phosphate (CP) levels were compared in 28 animals.The results show significant deterioration in myocardial contractility and compliance following three-hour cardioplegic arrest whether the arrest was intermittent or continuous. However, there were significant differences between the two groups studied. The animal having continuous arrest had less functional impairment than the animal having intermittent arrest. Myocardial perfusion 30 minutes following continuous arrest returned to prearrest levels whereas there was significant depression in perfusion in the group with intermittent arrest. This represented severe coronary vasoconstriction. The ATP level after completion of arrest is significantly higher in the group having continuous arrest and remains higher throughout the final reperfusion period.On the basis of these studies, it is thought that intermittent reperfusion may lead to a reperfusion injury, which is primarily reflected in decreased perfusion, contractility, and compliance. While hypothermic potassium cardioplegia does not optimally protect the myocardium during prolonged (three hour) ischemic arrest, the alternative of intermittent arrest provides poorer myocardial preservation.     

Effect of venting on myocardial protection by hypothermic cardioplegic arrest

Myocardial rewarming between cardioplegic (CP) infusions is in part attributable to blood circulating through the heart from collateral channels. This experiment was performed to determine if the type of left ventricular (LV) venting affects myocardial temperature (temp) or alters myocardial protection. Twelve dogs underwent cardiopulmonary bypass (CPB) at 37 degrees C and were subjected to 100 min of cardioplegic arrest by intermittent coronary infusion of 300 ml 0-4 degrees C CP solution. Arterial, central venous, left atrial, and LV pressures; cardiac output; systemic, septal (S), right ventricular (RV), and LV temp; myocardial ATP and glycogen were measured; LV pressure/volume curves and LV dp/dt were calculated. Group A (6 dogs) had an LV vent during CPB, and Group B (6 dogs) had the aorta vented via the CP line. CP infusion lowered LV temp to 8 degrees C in Group A vs 13 degrees C in Group B (P less than 0.000002); S temp was lowered to 7 degrees C in Group A vs 11 C in Group B (P less than 0.00007); and RV temp was lowered to 16 degrees C in Groups A and B. Ten minutes after CP, LV and S temp increased to 20-21 degrees C in Groups A and B, and RV temp to 24-25 degrees C in Groups A and B. Twenty minutes after CP all temperatures were the same. Hemodynamics and myocardial metabolic studies were similar in the two groups. CONCLUSIONS: Hearts vented via the LV cooled to a lower temperature vs those vented via the aorta. Venting did not affect myocardial rewarming, myocardial metabolites, or ventricular function.     

Anoxic hypothermic cardioplegia compared to intermittent anoxic fibrillatory cardiac arrest. Clinical and metabolic experience with 1080 patients.

Appropriately applied, hypothermic cardioplegia allows an excellent surgical setting that can significantly reduce the myocardial ischemic injury resulting from anoxia. One thousand eighty adult and pediatric patients underwent a variety of corrective cardial surgical procedures utilizing cold potassium cardioplegic solution injected into the coronary arteries via the aortic root. Myocardial septal temperature was maintained at 18--20 degrees during arrested time. This group of patients was compared to a group of 220 patients that underwent intermittent normothermic ischemic arrest to perform cardiac surgical procedures. Significant reduction in morbidity, mortality, perioperative myocardial infarction was noted in favor of the cardioplegic group. Metabolic coronary sinus blood analysis in the group undergoing surgery with cardioplegia revealed favorable changes in myocardial lactate and oxygen extraction.     

Cold blood as the vehicle for potassium cardioplegia

Cold blood with potassium, 34 mEq/L, was compared with cold blood and with a cardioplegic solution. Three groups of 6 dogs had 2 hours of aortic cross-clamp while on total bypass at 28 degrees C with the left ventricle vented. An initial 5-minute coronary perfusion was followed by 2 minutes of perfusion every 15 minutes for the cardioplegic solution (8 degrees C) and every 30 minutes for 3 minutes with cold blood or cold blood with potassium (8 degrees C). Hearts receiving cold blood or cold blood with potassium had topical cardiac hypothermia with crushed ice. Peak systolic pressure, rate of rise of left ventricular pressure, maximum velocity of the contractile element, pressure volume curves, coronary flow, coronary flow distribution, and myocardial uptake of oxygen, lactate, and pyruvate were measured prior to ischemia and 30 minutes after restoration of coronary flow. Myocardial creatine phosphate (CP), adenosine triphosphate (ATP), and adenosine diphosphate (ADP) were determined at the end of ischemia and after recovery. Changes in coronary flow, coronary flow distribution, and myocardial uptake of oxygen and pyruvate were not significant. Peak systolic pressure and lactate uptake declined significantly for hearts perfused with cold blood but not those with cold blood with potassium. ATP and ADP were lowest in hearts perfused with cardioplegic solution, and CP and ATP did not return to control in any group. Heart water increased with the use of cold blood and cardioplegic solution. Myocardial protection with cold blood with potassium and topical hypothermia has some advantages over cold blood and cardioplegic solution.     

The importance of hyperkalemia in a cold perfusion solution: a correlative study examining myocardial function, metabolism, tissue gases, and substrates.

Twenty-four pigs were studied to assess the effect of potassium in a cardioplegic solution on the ability of the swine myocardium to maintain functional and metabolic integrity following induced ischemia. The pigs were evaluated on total and right heart bypass with measurement at normothermia and after a one-hour intervention of stroke volume (SV), coronary blood flow (CBF), myocardial oxygen consumption (MVO2), and lactate extraction. Myocardial tissue gases (PmO2 and PmCO2) were continuously monitored and, at the conclusion of the procedure tissues were analyzed for adenosine triphosphate (ATP). There were five interventions: (1) hypothermic perfusion (28 degrees C) (Group 1); (2) hypothermic ischemia (28 degrees C) (Group 2); and hypothermic ischemia with a cardioplegic solution (nonlactated Ringer's solution, pH 7.4, 4 degrees C) using (3) normokalemia (4 mEq of potassium chloride/L, 300 mOsm/L (Group 3), (4) hyperkalemia (43 mEq of KCl/L, 390 mOsm/L) (Group 4), and (5) normokalemia with increased osmolarity (3.6 mEq of KCl/L, 400 mOsm/L) (Groups 5). A significant decrease in SV and elevation in peak PmCO2 were seen in all groups subjected to ischemia except those protected with hyperkalemic solution. We conclude that the presence of hyperkalemia in a cold root perfusion solution provides better myocardial protection than cold root perfusion alone. Furthermore, potassium arrest appears to be more protective than coronary perfusion at 28 degrees C.     

Myocardial oedema and ventricular function after cardioplegia with added mannitol

Myocardial oedema may contribute to the impaired myocardial performance which commonly follows open heart surgery with cardioplegia-induced cardiac arrest. The rate of oedema formation during crystalloid cardioplegia and the relation of this to changes in ventricular compliance and ventricular function following reperfusion were studied using an isolated rabbit heart preparation. Myocardial tissue water content increased during cardioplegic arrest and the water content prior to reperfusion demonstrated an inverse correlation with ventricular function after reperfusion. In further studies the effect of adding mannitol to a standard crystalloid cardioplegic solution was investigated. The preparations were divided into two groups: nine were administered a standard cardioplegic solution (Plegisol*) (control group) and a further eight were administered the same solution mixed with mannitol to adjust the osmotic pressure to 360 mOsmol.L-3 (mannitol group). The mannitol group demonstrated less increase in RV water content and superior LV dP/dtmax following reperfusion. It is concluded that mannitol enhances protection of the myocardium during cardioplegic cardiac arrest.     

Cellular and molecular therapeutic targets for treatment of contractile dysfunction after cardioplegic arrest

Transient left ventricular (LV) dysfunction can occur after hypothermic hyperkalemic cardioplegic arrest. This laboratory has developed an isolated LV myocyte system of simulated cardioplegic arrest and rewarming in order to examine cellular and molecular events that may contribute to the LV dysfunction after cardioplegic arrest. Contractile function was examined using high-speed video microscopy after reperfusion and rewarming. After cardioplegic arrest and reperfusion, indices of myocyte contractility were reduced by over 40% from normothermic control values. The capacity of the myocyte to respond to an inotropic stimulus was examined through beta-adrenergic receptor stimulation with isoproterenol. After cardioplegic arrest, the contractile response to isoproterenol was reduced by over 50% from normothermic values. The next series of studies focused upon preventing these changes in myocyte contractile processes after cardioplegic arrest. First, the cardioplegic solutions were augmented with adenosine or an ATP-sensitive potassium channel opener, aprikalim. Both adenosine and aprikalim augmentation significantly improved myocyte function compared with cardioplegia alone values. A potential intracellular mechanism for the protective effects of either adenosine or the ATP-sensitive potassium channel is the activation of protein kinase C (PKC). A brief period of PKC activation before cardioplegic arrest provided protective effects on myocyte contractility with subsequent reperfusion and rewarming. In another set of studies, the potential protective effects of the active form of thyroid hormone (T3) were examined. In myocytes pretreated with T3, myocyte contractile function and beta-adrenergic responsiveness were significantly improved after hypothermic cardioplegic arrest and rewarming. Thus, endogenous means of providing improved myocardial protection during prolonged cardioplegic arrest can be achieved through a brief period of PKC activation or pretreatment with T3. Future studies, which more carefully deduce the basis for these pretreatment effects, will likely yield novel methods by which to protect myocyte contractile processes during cardioplegic arrest.     

Myocardial protection with intermittent cold blood during aortic valve operation: antegrade versus retrograde delivery

BACKGROUND: Intermittent antegrade cold blood cardioplegia is superior to warm blood cardioplegia in patients who have aortic valve operation. This study compared the cardioprotective efficacy of intermittent antegrade and retrograde cold blood cardioplegia with emphasis on metabolic stress in the left and right ventricles. METHODS: Thirty-nine patients who had elective aortic valve replacement were prospectively randomly selected to receive intermittent antegrade or retrograde cold blood cardioplegia. Left and right ventricular biopsies were collected 5 minutes after institution of cardiopulmonary bypass and 20 minutes after cross-clamp removal and were used to determine metabolic changes. Metabolites (adenine nucleotides, amino acids, and lactate) were measured using high-powered liquid chromatography and enzymatic techniques. Serial measurement of troponin I release was also used as a marker of myocardial injury. RESULTS: Preoperative characteristics were similar between groups. There was no in-hospital mortality, and no differences were observed in postoperative complications. Preischemic concentration of taurine was significantly higher in left ventricular biopsies, whereas adenosine triphosphate tended to be lower in the left ventricle. At reperfusion adenosine triphosphate levels were significantly lower than preischemic levels in right but not left ventricles irrespective of the route of delivery. The alanine-glutamate ratio was significantly elevated in both ventricles. Myocardial injury as assessed by troponin I release was also significantly increased in both groups. CONCLUSIONS: Retrograde and antegrade intermittent cold blood cardioplegic techniques are associated with suboptimal myocardial protection. Metabolic stress was more pronounced in the right than the left ventricle irrespective of the cardioplegic route of delivery used.     

Effects of varied cardioplegic perfusion pressure on myocardial preservation with critical coronary stenosis

Inadequate delivery of cardioplegic solution distal to coronary artery stenosis may result in increased injury during ischemic arrest. This study was performed to determine the effects of cardioplegic perfusion pressure on cardioplegia delivery and myocardial preservation in hearts with critical coronary artery stenosis. Twenty dogs underwent 90 minutes of cold potassium cardioplegic arrest with partial occlusion of the circumflex coronary artery. Group 1 received cardioplegia at 50 mm Hg pressure, Group 2 at 90 mm Hg pressure, and Group 3 at 130 mm Hg pressure. It was found that cooling rates were 5.4 degrees, 9.1 degrees, and 18.2 degrees C per minute in the nonischemic area (p = 0.004) and 2.0 degrees, 4.5 degrees, and 7.9 degrees C in the ischemic area (p = 0.008) in Groups 1, 2, and 3, respectively. Total of cardioplegic solution flows were 86, 188, and 262 ml per minute per 100 gm in Groups 1, 2, and 3, respectively (p = 0.001). However, flow did not differ significantly between groups in the ischemic area. Rate of rise of left ventricular (LV) pressure decreased significantly in Groups 1 and 2 but not in Group 3 (p = 0.002). Other measured variables did not differ significantly between groups, although LV function curves showed less deterioration in the high-pressure groups. It is concluded that higher cardioplegic perfusion pressure resulted in more rapid cooling in normal and ischemic areas and slightly better preservation of ventricular function as measured by some indexes. However, preservation was generally good for each of the pressures for up to 90 minutes of ischemia when the septum was consistently cooled to 10 degrees C.     

Myocardial protection in the neonatal heart. A comparison of topical hypothermia and crystalloid and blood cardioplegic solutions

Myocardial protection achieved during 2 hours of ischemic arrest was evaluated in 45 isolated, blood perfused, neonatal (1 to 5 days) piglet hearts. Comparisons were made among five methods of myocardial protection: Group I, topical cooling; Group II, hyperosmolar (450 mOsm) low-calcium (0.5 mmol/L) crystalloid cardioplegia; Group III, St. Thomas' Hospital cardioplegia; Group IV, cold blood cardioplegia with potassium (21 mmol/L), citrate-phosphate-dextrose (calcium level 0.6 mmol/L), and tromethamine; and Group V, cold blood cardioplegia with potassium alone (16 mmol/L) (calcium level 1.2 mmol/L). Hemodynamic recovery (percent of the preischemic stroke work) after 30 and 60 minutes of reperfusion was 82.9% and 86.7% in Group I, 35.7% (p less than 0.0001) and 43.7% (p less than 0.0001) in Group II, 76.1% and 77.7% in Group III, 67.4% (p less than 0.05) and 60.6% (p less than 0.05) in Group IV, and 110.7% and 100.6% in Group V. Conclusions: Topical cooling is an effective method of myocardial protection in the neonate. Cold blood cardioplegia with potassium alone and a normal calcium level provides optimal functional recovery. The improved protection obtained with both crystalloid and blood cardioplegia with normal calcium levels suggests an increased sensitivity of the neonatal heart to the calcium level of the cardioplegic solution.     

Comparison of intermittent warm and cold blood perfusion during hypothermic myocardial preservation on functional and metabolic recovery

Numerous techniques are used to maintain intraoperative heart viability. The studies presented here evaluated heart function and metabolism after various periods of preservation up to 4 hours with intermittent warm and cold blood perfusion. Using a heterotopic heart model cooled to 10 degrees C and maintained for 1, 2, 3, and 4 hours, various preservation techniques were compared. Changes in myocardial metabolism were determined from substrate uptakes and biopsy samples of the left ventricular muscle for high-energy phosphates. Preservation techniques included: (1) sustained hypothermia, (2) 1 or 2 hours of sustained warm blood perfusion with fibrillation, (3) intermittent cold blood perfusion during 2, 3, and 4 hours of preservation, (4) intermittent warm blood perfusion during 2, 3, and 4 hours of preservation and (5) a control group (no preservation). Normothermic fibrillation had no effect on postpreservation functional or metabolic parameters. Sustained hypothermia reduced functional recovery proportional to the length of ischemia. The cold intermittent procedures maintained function and metabolism better than sustained hypothermia, while warm intermittent preservation maintained function and metabolism at control levels throughout the recovery period for all preservation techniques. Changes in ATP mirrored the functional changes. Creatine phosphate (CP) was markedly reduced during heart isolation and preservation and exceeded the control by 100% during reperfusion. For operative procedures of 2 hours or less, functional and metabolic recovery was not affected by the various preservation methods applied. Warm intermittent perfusion during hypothermic preservation offered the best protection for the myocardium. The warming cycles during hypothermia may provide some degree of preconditioning and protect the myocardium during reperfusion.     

Myocardial protection during prolonged aortic cross-clamping. Comparison of blood and crystalloid cardioplegia

We compared the ability of blood and crystalloid cardioplegia to protect the myocardium during prolonged arrest. Twelve dogs underwent 180 minutes of continuous arrest. Group I (six dogs) received 750 ml of blood cardioplegic solution (potassium chloride 30 mEq/L) initially and every 30 minutes. Group II (six dogs) received an identical amount of crystalloid cardioplegic solution (potassium chloride 30 mEq, methylprednisolone 1 gm, and 50% dextrose in water 16 ml/L of electrolyte solution). Temperature was 10 degrees C and pH 8.0 in both groups. Studies of myocardial biochemistry, physiology, and ultrastructure were completed before arrest and 30 minutes after normothermic reperfusion. Biopsy specimens for determination of adenosine triphosphate were obtained before, during, and after the arrest interval. Regional myocardial blood flow, total coronary blood flow, and myocardial oxygen consumption were statistically unchanged in Group I (p greater than 0.05). Total coronary blood flow rose 196% +/- 49% in Group II (p less than 0.005), and left ventricular endocardial/epicardial flow ratio fell significantly in this group from 1.51 +/- 0.18 to 0.8 +/- 0.09, p less than 0.01 (mean +/- standard error of the mean. The rise in myocardial oxygen consumption was not significant in this group (34% +/- 36%, p greater than 0.05). Ventricular function and compliance were statistically unchanged in both groups. In Group II, adenosine triphosphate fell 18% +/- 3.4% (p less than 0.005) after 30 minutes of reperfusion; it was unchanged in Group I. Ultrastructural appearance in both groups correlated with these changes. We conclude that blood cardioplegia offers several distinct advantages over crystalloid cardioplegia during prolonged arrest.     

Experimental study on myocardial preservation with perfluorochemical

The effect of perfluorochemical as cardioplegic solution was studied with isolated canine hearts. They were divided into two groups as follows each consisting of ten, and cardioplegia was made every 30 minutes during 3 hours of ischemia. Group I: The solution was oxygenated to PaO2 of 542 +/- 67 mmHg (mean +/- SD). Group II: The solution was deoxygenated to PaO2 of 55 +/- 12 mmHg. Both temperature were 20 degrees C. After 3 hours cardiac arrest, the hearts were fixed to the perfusion unit filled up with the diluted blood. Then hemodynamic and biochemical variables were measured every 30 minutes. There were some significant differences between the groups. Hemodynamic indices especially negative LV max dp/dt were recovered excellently in Group I but not so much in Group II. Negative LV max dp/dt, which was the distinction of the diastole, showed significant difference more than positive LV max dp/dt, which was the distinction of the systole. It was considered that under the same condition, negative LV max dp/dt reflected not only compliance but also preparatory ability of the left ventricle, and it could be one of the important indices evaluating cardiac function. As regarding metabolism, delivery of oxygen with cardioplegic solution was good for the aerobic metabolism also after reperfusion, and in these circumstances, catecholamine was available effectively to the hearts. The conclusion is as follows. It is important for myocardial preservation to suppress the anaerobic metabolism and to keep the circumstances in which catecholamine was available effectively. And oxygenated PFC is good to preserve myocardium and useful as cardioplegic solution.     

Induction of cardioplegia with blood and crystalloid potassium solutions during prolonged aortic cross-clamping

Recent controversy concerns the proper vehicle for delivery of potassium cardioplegia. In the present study, adult dogs supported by cardiopulmonary bypass were subjected to 2 hours of multidose, hypothermic potassium cardioplegic arrest with 30 minutes of reperfusion with either autologous blood or crystalloid solution as the cardioplegic vehicle. Preservation of myocardial high-energy nucleotide stores was assessed by serial left ventricular biopsies assayed for adenosine triphosphate (ATP) and creatine phosphate. Preischemic and postischemic ventricular function was assessed by the use of an isovolumic intraventricular balloon. ATP stores were equally maintained at preischemic levels after ischemia and reperfusion by both autologous blood and crystalloid solution. Although creatine phosphate stores significantly declined (P less than 0.01, both groups) after 2 hours of arrest, reperfusion allowed equal restoration of preischemic levels. Maximum first derivative of left ventricular pressure and measured velocity were not depressed by either mode of protection. Similarly, myocardial compliance, as assessed by length-tension curves, showed no change following either autologous blood or crystalloid solution. The data show equal and significant myocardial protection by multidose, hypothermic potassium cardioplegia when both delivery vehicles were used.     

Cold Blood–Diltiazem Cardioplegia

The calcium channel blocker, diltiazem, has been studied in the same model used for evaluation of cold blood–potassium cardioplegia. Six dogs (Group 1) had one hour of myocardial ischemia with topical ice (myocardial temperature, 7° ± 2°C) after coronary perfusion with 200 ml of cold blood (5° ± 1°C) containing diltiazem, 400 μg per kilogram of body weight. Seven dogs (Group 2) had two hours of ischemia after perfusion with 200 ml of cold blood containing 200 μg/kg and reperfusion every 30 minutes with 100 ml of cold blood and diltiazem, 100 μg/kg. Baseline studies were repeated after rewarming and 40 minutes of reperfusion. No inotropic agents or calcium were used.Heart rate, peak systolic pressure, velocity of the contractile element, peak + rate of rise of left ventricular pressure (dP/dt), peak ? dP/dt, dP/dt over common peak isovolumic pressure, left ventricular compliance and stiffness, and heart water were unchanged in Group 1. In Group 2, heart rate slowed (p < 0.025) and compliance decreased (p < 0.02). In both groups, coronary vascular resistance declined (p < 0.001) and recovery of adenosine triphosphate (p < 0.001), adenosine diphosphate (p < 0.025), and the adenosine pool (p < 0.001) was impaired. Ultrastructure was well preserved, but myofibrillar lesions were noted in Group 2.Diltiazem cardioplegia was associated with good functional recovery, but there was impairment of high-energy phosphate metabolism.     

Experimental study on myocardial protection with verapamil and salvia miltiorrhiza Bunge cardioplegia

Myocardial 45Ca sequestration was studied in dogs during 60 minutes of global ischemia and 30 minutes of reperfusion using cardiopulmonary bypass (CPB) and myocardial function was studied before and after CPB. Group A (n = 5), as a control, received cold hyperkalemic cardioplegic solution, Group B (n = 5) received the same solution plus verapamil (150 micrograms/kg/L) and Group C plus specific activity (TSA = DPM x 10(4)/g) and plasma specific activity (PSA = DPM x 10(4)/ml) were determined by biopsy before and after release of the cross-clamp The results showed that myocardial function in Group B and C were better than that in Group A (P less than 0.01). It is suggested that verapamil and Salvia miltiorrhiza Bunge effectively control myocardial calcium sequestration during early reperfusion and reduce myocardial reperfusion injury As to myocardial protection, cardioplegia with verapamil and Salvia miltiorrhiza Bunge were superior to hyperkalemic alone. Verapamil cardioplegia was still better than Salvia miltiorrhiza Bunge.     

Differential electrical activity of the atria during cardioplegic arrest in pigs

To elucidate the electrical interrelationship of the atria during cardioplegic arrest, simultaneous bipolar right atrial (RA) and left atrial (LA) electrograms and myocardial temperatures of all four chambers of the heart were recorded in 10 pigs during an hour of aortic clamping. Five pigs (Group 1) underwent single venous cannulation; in 5 others (Group 2), snared double caval cannulation, RA venting, and intracavitary RA irrigation with cold saline solution were employed. Myocardial protection was provided by systemic hypothermia (28 degrees C) and intermittent intraaortic administration of cold (4 degrees C) hyperkalemic (20 mEq/L) crystalloid cardioplegic solution. Single RA cannulation was associated with sustained RA activity during cardioplegic arrest and with the warmest mean myocardial temperatures. Electrical activity was infrequent in the left atrium, which was often silent while RA impulses continued to be observed. Four Group 1 pigs exhibited high-grade RA-LA block, whereas in 2 animals completely asynchronous RA-LA electrical activity occurred. Isolated LA activity was not encountered. The combined methods used in Group 2 pigs significantly reduced mean myocardial temperatures. Both RA and LA impulses were practically abolished, and their mean durations decreased 96% and 85%, respectively. It is concluded that the pattern of electrical activity differs in the two atria during cardioplegic arrest when a single venous cannula is employed. Intracavitary RA irrigation with cold saline solution in the presence of snared caval cannulas provides improved myocardial hypothermia and effectively eliminates both RA and LA activity in the course of cold crystalloid cardioplegia.     

The effect of short-term coronary perfusion using oxygenated diluted blood following cold storage for long-term heart preservation

BACKGROUND: The aim of this study was to compare the results obtained from the use of both University of Wisconsin (UW) solution and diluted blood in short-term coronary perfusion following 12-hour cold storage. METHODS: Following coronary vascular washout of adult mongrel dogs with the UW solution, the heart was excised and immersed in a cold (4 degrees C) UW solution for 12 hours followed by 1-hour of coronary perfusion. Two different solutions were used for the coronary perfusion; a 4 degrees C oxygenated UW solution (Group U, n=7) and 15 degrees C oxygenated diluted blood (Group B, n=7). Myocardial high energy phosphate (HEP) levels, tissue water content (TWC), interstitial tissue space (ITS) rates and histological findings were evaluated at 0- and 12-hour cold storage and also following coronary perfusion. The preserved graft was then evaluated through orthotopic transplantation. The control group in this experiment consisted of seven hearts transplanted after 12-hour cold storage without coronary perfusion. RESULTS: Myocardial HEP levels significantly decreased after 12-hour cold storage. The recovery rate of myocardial HEP levels after coronary perfusion was significantly (p<0.05) higher in Group B than in Group U. The increase of myocardial TWC during coronary perfusion was significantly (p<0.01) higher in Group B than in Group U. After 1-hour coronary perfusion, the subendocardial ITS rate was significantly (p<0.01) higher compared with the value at 0-hour cold storage in Group U, whereas it demonstrated no significant change in Group B. PAS stain revealed the glycogen content of the subendocardial tissues was higher in Group B than in Group U. The recovery rate of hemodynamic parameters 2 hours after heart transplantation was higher in Group U and significantly (p<0.05) higher in Group B than in the control. CONCLUSIONS: Myocardial HEP levels recovered significantly after additional coronary perfusion. Though the UW solution prevented myocardial cellular edema, subendocardial perfusion was incomplete and the recovery rate of myocardial HEP levels was lower, suggesting that diluted blood may become the solution of choice as a perfusate.     

Functional and metabolic effects of nicardipine on ischemic rat hearts with multidose potassium cardioplegia

This study was undertaken to assess the effect of a calcium antagonist, nicardipine (N), added in a cardioplegic solution on the ischemic myocardium. Isolated rat hearts were perfused with oxygenated Krebs Ringer Bicarbonate (KRB) solution by Langendorff's perfusion method and were subjected to 2 hours of ischemic arrest at 30 degrees C with multidose cardioplegia (every 30 min, for 5 min) and a subsequent 60 min of reperfusion. HR, LVP, coronary flow and oxygen tension of coronary effluent were monitored. Oxygen saturation of intracellular myoglobin and redox state of mitochondrial cytochrome aa3 in the myocardial cell were continuously measured throughout studies by a spectrophotometer. Oxygenated crystalloid cardioplegic solution (KRB) containing 25 mM of potassium was used. 40 rats were divided into 4 groups (10 rats each) according to the concentration of N (none, 0.5, 1 and 2 mg/L) in fully oxygenated potassium cardioplegic solution (PO2: 601 +/- 31 mmHg). The percent recovery of pressure-rate product after reperfusion was compared in each group and the optimal concentration of N was found to be 1 mg per liter of cardioplegic solution. No significant difference was found between Group Ia (N = 0 mg/L) and Group Ib (N = 1 mg/L) in metabolic or hemodynamic recovery after reperfusion. In other experiments, 40 rats in Group IIa (N = 0 mg/L, n = 20) and Group IIb (N = 1 mg/L, n = 20) received 10 ml of poorly oxygenated cardioplegic solution (PO2: 215 +/- 10 mmHg) on each reinfusion followed by a 25 min interval of ischemic arrest. The index of oxygen utilization, MVO2/pressure-rate product after reperfusion was significantly lower in Group IIb than in Group IIa (p less than 0.05). The results show that the addition of N (1 mg/L) to the cardioplegic solution preserved a more aerobic state (higher intracellular oxygen level) in the myocardium by further suppressing myocardial oxygen demand during the ischemic period which resulted in better myocardial protection. Therefore, it is concluded that the addition of N to the cardioplegic solution enhances myocardial preservation during myocardial ischemia.     

Effects of coenzyme Q10 added to a potassium cardioplegic solution for myocardial protection during ischemic cardiac arrest

To evaluate effects of coenzyme Q10 added to a potassium cardioplegic solution for myocardial protection, 17 mongrel dogs underwent 60 minutes of ischemic cardiac arrest under cardiopulmonary bypass. Cardiac arrest was induced by infusing the cardioplegic solution into the aortic root every 20 minutes. Experimental animals were divided into three groups according to the cardioplegic solution used. In Group 1, we used our clinical potassium cardioplegic solution (K+, 22.31 mEq/L); in Group 2, potassium cardioplegic solution with coenzyme Q10 added (coenzyme Q10, 30 mg/500 ml of solution); and in Group 3, cardioplegic solution with coenzyme Q10 solvent. Exogenous coenzyme Q10 in the cardioplegic solution provided significantly high myocardial stores of adenosine triphosphate and creatine phosphate and a low level of lactate during induced ischemia and reperfusion. Furthermore, percent recovery of the aortic flow in Group 2 was significantly higher than that in the other two groups. Ultrastructures of the ischemic myocardium in Group 2 were better preserved than those in Group 1. Addition of coenzyme Q10 to potassium cardioplegia resulted in improved myocardial oxygen utilization and accelerated recovery of myocardial energy metabolism after reestablishment of circulation.