Coronary endothelium and cardioplegic solutions

Using surface and transmission electron microscopy in eight isolated sheep hearts it was noted that cold crystalloid cardioplegic solution produced coronary endothelial damage which could be prevented if homologous blood or albumin was added into the preservation fluid. Similar endothelial damage was observed in the endothelium of aorto-coronary saphenous vein bypasses and in the endothelium of the proximal aorta after infusion with cold crystalloid cardioplegic fluid. No endothelial changes were seen after infusion of the grafts with cold blood. There was no correlation between the preservation of the high energy phosphates of the myocardium and the endothelial changes of the coronary arteries.     

A comparison of blood and crystalloid cardioplegia during heart transplantation after 5 hours of cold storage

Four methods of protecting the heart during implantation were compared. All hearts were arrested in situ by perfusing 4 degrees C cardioplegic solution into the aortic root and were stored by a nonperfused cold storage technique for 5 hours at 4 degrees C. The hearts were then transplanted orthotopically with the use of topical iced slush alone or with infusions of either blood cardioplegic solution or one of two crystalloid cardioplegic solutions after each atrial anastomosis. Five dog hearts were included in each group. Biopsy samples to test for adenylates were taken before the arrest, at the end of storage, before cross-clamp removal, and 3.5 hours after cross-clamp removal. The dogs were removed from cardiopulmonary bypass, and with the chest open, left ventricular function curves were measured at 1, 2, and 3 hours after cross-clamp removal. At 3.5 hours of reperfusion time, a full-width section was obtained from the left ventricle for measurement of tissue sodium and water content. No differences in tissue water, sodium, or potassium content were found among the groups. Left ventricular function was significantly better in the blood cardioplegia group than in any other groups. Adenosine triphosphate levels were significantly reduced 3.5 hours after reperfusion in the crystalloid cardioplegia groups but were not significantly depressed at any other measurement time. Excellent early graft function was observed after crystalloid cardioplegic arrest and blood cardioplegic reperfusion during graft implantation.     

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.)     

Effect of an oxygen-enriched solution and multiple dosing of antegrade crystalloid cardioplegic solution on myocardial metabolism during coronary artery bypass graft operations.

The metabolic effect of excessive oxygenation and frequency of administration of antegrade crystalloid cardioplegic solution was assessed in 33 patients undergoing routine coronary artery bypass graft operations. Four patient groups were designed in which the initial aortic root injection was 1000 ml and then 100 ml administered through the vein grafts after completion of each distal anastomosis. The groups were divided as follows: group 1, single dose, normally oxygenated cardioplegic solution infused via the aortic root; group 2, single dose, high oxygen content cardioplegic solution infused via the aortic root; group 3, normally oxygenated cardioplegic solution with additional 250 ml doses via the aortic root every 20 minutes; group 4, high oxygen content cardioplegic solution with additional 250 ml doses via the aortic root every 20 minutes. In all groups myocardial mean septal temperature showed an immediate fall to approximately 11 degrees C with the initial aortic root doses and then a gradual rewarming to approximately 20 degrees C during the crossclamp period (mean 58.6 minutes). Metabolic parameters measured or calculated from the coronary sinus effluent were myocardial oxygen extraction, lactate production, base deficit, inorganic phosphate, glucose, potassium, creatine kinase (total and myocardial band fraction), and catecholamine production. There was no statistically significant difference in any of these determinations between each patient group. Furthermore, myocardial recovery, myocardial performance, and postoperative recovery characteristics were not different. We conclude that single or multidose aortic root crystalloid cardioplegic solution (either oxygen enriched or normally oxygenated) is equally effective in routine coronary artery bypass graft operations when septal temperatures are maintained between 15 degrees and 21 degrees C for a total arrest time of 60 minutes or less. In this study, increasing the volume cardioplegic solution given in multiple doses appeared to offer no significant metabolic or functional advantage in patients without complications who had satisfactory left ventricular function.     

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.     

Effects of synthetic blood and crystalloid cardioplegic solutions on coronary endothelium: An experimental scanning electron microscope study

In an experimental study the effects of Fluosol DA (added with potassium chloride) on the vascular interface and endothelial cells were compared to those of crystalloid potassium cardioplegic solution using scanning electron microscope. Twenty rabbits (10 in each group) were sacrificed, the hearts with ascending aorta were immediately excised, and cold oxygenated solution was infused via a cannula inserted into the cross-clamped aorta. The hearts were left immersed in the perfusion medium for 2 hr. In the Fluosol DA group endothelial cover and endothelial cells were normal or minimal changes were seen in seven cases. Occasional breaking of intercellular attachments, small areas of denuded flow surface, and disappearance of microvilli were seen in three cases. In the crystalloid potassium cardioplegic group 7 of the 10 cases showed moderate or severe damage with large areas of denuded flow surface. The present experimental protocol represented an extreme situation where no collateral coronary blood was present. The coronary endothelial damage was obvious after the crystalloid potassium cardioplegic solution. Similar damage was not found following Fluosol DA infusion.     

Persistent atrial activity during cardioplegic arrest: a possible factor in the etiology of postoperative supraventricular tachyarrhythmias

We assessed the relationship between the duration of atrial activity during the cross-clamp period and the postoperative occurrence of supraventricular tachyarrhythmias in 50 patients undergoing elective coronary bypass operation. The atrial electrical activity was monitored continuously by means of a bipolar atrial electrogram from the onset of cardioplegic administration until removal of the aortic cross-clamp. While ventricular arrest was induced promptly and maintained in all patients, sustained atrial activity was observed in 44 out of 50 patients during the cross-clamp period. In the postoperative period, supraventricular tachyarrhythmias developed in 15 patients (Group 1). Thirty-five patients (Group 2) were free from such tachyarrhythmias. There was no significant difference between the two groups with respect to cross-clamp time, bypass time, amount of cardioplegic solution used, or number of grafts per patient. The mean duration of atrial activity during cardioplegic arrest, however, was significantly longer in Group 1 than in Group 2 (46 +/- 4.7 minutes versus 22.6 +/- 4.0 minutes, respectively, p less than 0.001). None of the 6 patients in whom atrial activity was completely abolished experienced supraventricular tachyarrhythmias. The strong correlation observed between the duration of atrial activity during cardioplegic arrest and the incidence of postoperative supraventricular tachyarrhythmias suggests the possibility that these arrhythmias may be a manifestation of inadequate atrial protection during global myocardial ischemia.     

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.     

Nitric oxide attenuates cardiomyocytic apoptosis via diminished mitochondrial complex I up-regulation from cardiac ischemia-reperfusion injury under cardiopulmonary bypass

OBJECTIVE: This study tested the hypothesis that cardioplegic solution supplemented with a nitric oxide donor agent attenuates postischemic cardiomyocytic apoptosis by reduction of mitochondrial complex I up-regulation during global cardiac arrest under cardiopulmonary bypass. METHODS: Twenty-four anesthetized dogs supported by total vented bypass were divided evenly into 4 groups (n = 6) and subjected to 60 minutes of hypothermic ischemia followed by 4 degrees C multidose crystalloid cardioplegic solution infusion. Hearts received either standard crystalloid cardioplegic solution (control), crystalloid cardioplegic solution supplemented with 2 mmol/L L-arginine (L-Arg group), crystalloid cardioplegic solution supplemented with 400 micromol/L N(G)-monomethyl-L-arginine (L-NMMA group), or crystalloid cardioplegic solution supplemented with 100 micromol/L of NO donor compound (3-morpholinosydnonimine; SIN-1 group). After 60 minutes of cardioplegic arrest, the heart was reperfused for a total of 240 minutes after discontinuation of bypass. The occurrence of cardiomyocytic apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling and Western blot analysis of caspase-3. RESULTS: The occurrence of cardiomyocytic apoptosis was significantly reduced in SIN-1 and L-Arg groups compared with the control group. Mitochondrial complex I mRNA was up-regulated in the control group, and its expression was significantly higher in the L-NMMA group but significantly reduced in the SIN-1 and L-Arg groups. Western blot analysis of Bcl-2 and cytochrome c, an index of mitochondrial damage in postischemic myocardium, revealed a similar pattern. CONCLUSION: Nitric oxide-supplemented crystalloid cardioplegic solution diminished postischemic cardiomyocytic apoptosis after global cardiac arrest under cardiopulmonary bypass, possibly via prevention of mitochondrial complex I up-regulation.     

Comparison of alternative cardioplegic techniques

Cold potassium cardioplegia provides adequate protection for coronary bypass operations, but severe coronary stenoses limit cardioplegic delivery to ischemic regions. The traditional technique delivers cardioplegic solution into the aortic root during the performance of distal anastomoses. The proposed alternative technique constructs proximal as well as distal anastomoses during a prolonged cross-clamp period, but permits more uniform cooling. The two techniques were compared in a prospective concurrent trial of 45 patients undergoing elective coronary bypass grafting. The traditional technique was employed in 26 patients (Group A) and the alternative technique in 19 patients (Group B). In both groups, 700 to 1,000 ml of a crystalloid cardioplegic solution was infused into the aortic root after application of the aortic cross-clamp. In Group A (traditional technique), 500 ml was infused into the aortic root after each distal anastomosis. In Group B (alternative technique), cardioplegic solution was administered through the vein graft after each distal anastomosis, and a proximal anastomosis was constructed after distal anastomoses to the most ischemic regions to permit continued cardioplegic delivery to these regions. The cross-clamp period was shorter in Group A than in Group B (44 +/- 15 versus 60 +/- 18 minutes, p less than 0.01), but the mean temperature in the most ischemic region was warmer (Group A, 19 degrees +/- 3 degrees C; Group B, 15 degrees +/- 3 degrees C, p less than 0.05). The postoperative CK-MB was higher in Group A (Group A, 47 +/- 36; Group B, 21 +/- 9 IU/L, p less than 0.01). Cardiac lactate production persisted longer in Group A (Group A, 4 +/- 1; Group B, 1 +/- 1 hours postoperatively, p less than 0.05). Volume loading 4 hours postoperatively produced a similar increase in left atrial pressure and cardiac index in both groups. In response to volume loading, Group A patients produced lactate, but Group B patients extracted lactate (change in cardiac lactate extraction: Group A, -1.7 +/- 2.3; Group B, +2.5 +/- 5.1 mg/dl, p less than 0.05). The construction of proximal as well as distal anastomoses during a prolonged cross-clamp period permits more uniform cooling and immediate reperfusion. This alternative technique resulted in less injury (CK-MB release) and more rapid recovery of myocardial metabolism.     

Intraoperative coronary angioscopy. Technique and results in the initial 58 patients

Coronary angioscopy provides images of intravascular detail with greater than 0.2 mm spatial resolution and excellent contrast resolution. Using endoscopes of 1.25 to 1.8 mm outer diameter, we performed intraoperative angioscopy of the coronary arteries or saphenous vein grafts, or both, in 58 patients. Eighty-one native coronary arteries and 43 vein grafts were examined. A clear viewing field was created by infusion of crystalloid cardioplegic solution through the aortic root during cardiopulmonary bypass. Technical details crucial for obtaining high-quality images were as follows: sufficient coronary perfusion by cardioplegic solution to displace all blood; adequate intraluminal illumination; and high-quality fiberoptic and lens systems. Incomplete studies in approximately 14% of patients were related to failure to achieve these technical details and lack of scope steerability. In 30% of patients, previously unrecognized anatomic details were revealed by angioscopy. These included intimal flaps at the site of vein-to-artery anastomoses, atheromatous plaques with adherent thrombi, and hemorrhagic ulcerated plaques, not recognized on angiography. Although a coronary intimal flap developed proximal to the anastomosis during retrograde examination in two patients, no serious complications occurred as a result of the procedure. We conclude that intraoperative angioscopy is safe, provides novel information that may be clinically relevant, and has future potential for development of the techniques for coronary endarterectomy and intraoperative balloon and laser angioplasty.     

Cardiomyocyte apoptosis and duration of aortic clamping in pig model of open heart surgery.

OBJECTIVE: Apoptotic cardiomyocyte death is induced during open heart surgery, but its determinants are poorly understood. Prolonged aortic clamping time is associated with adverse clinical outcomes. The purpose of this study was to determine whether occurrence of cardiomyocyte apoptosis is related to the duration of aortic clamping in experimental pig model of cardiac surgery with cardiopulmonary bypass. METHODS: The pigs (mean weight 29 +/- 1 kg) were randomly divided to undergo cardioplegic arrest for 60 (n = 4) or 90 (n = 4) min followed by reperfusion period of 120 min. Control group (n = 5) was connected to cardiopulmonary bypass for 120 min without cardioplegic arrest. Cardiomyocyte apoptosis was detected (TUNEL assay and immunohistochemical staining of active caspase-3) in left ventricular tissue samples obtained before ischemia and after the ischemia-reperfusion period. RESULTS: Apoptotic cardiomyocytes were found in all samples obtained after cardioplegic arrest and cardiopulmonary bypass alone with the TUNEL assay. The amount of apoptosis after the 120 min of cardiopulmonary bypass alone in the control group was 0.006 +/- 0.001%. Compared with this, cardiomyocyte apoptosis was increased after cardioplegic arrest. After 60 min of aortic cross-clamp the amount of apoptosis was 0.019 +/- 0.004% (p = 0.031). After 90 min of aortic cross-clamp the amount was 0.042 +/- 0.005% (p < 0.001) being significantly higher than after 60 min (p = 0.001). Aortic cross-clamp of 90 min also resulted in a detectable increase in caspase-3 activation when compared with controls. CONCLUSIONS: The occurrence of cardiomyocyte apoptosis increases with prolonged aortic clamping time during open heart surgery.     

Transesophageal echocardiographic evaluation of aortic valve integrity with antegrade crystalloid cardioplegic solution used as an imaging agent.

Forceful intravascular injection of crystalloid causes microbubble (cavitation) formation. The resulting ultrasound-opaque medium is widely used in echocardiography as a source of contrast. The following study was performed to determine the feasibility of using antegrade crystalloid cardioplegic solution as a transesophageal two-dimensional echocardiographic imaging agent to evaluate aortic valve integrity. In patients with preexisting aortic regurgitation (n = 12), cardioplegic solution administration (driving pressure 150 to 200 mm Hg) was associated with the appearance of intracardiac cavitations in 12 of 12 patients. Among patients without preexisting valve dysfunction (n = 22), intracardiac cavitations were manifested in 20 of 22, with extension of the cavitations to the left atrium in 17. Associated cardiac dimensions (left ventricular outflow tract area and left ventricular diameter) did not exceed preceding cardiopulmonary bypass values in these patients (2.0 +/- 1.6 cm2 versus 2.6 +/- 1.2 cm2 and 1.4 +/- 0.7 cm versus 1.5 +/- 0.8 cm, respectively). It was concluded that antegrade crystalloid cardioplegic solution can be used as an echocardiographic contrast agent in this context. The inability to establish a relationship between the extent of cardioplegic intracardiac penetration and left ventricular dimensional changes limits the technique, as presently employed, to qualitative analysis of valve dysfunction.     

Stimulation of neutrophil integrin expression during coronary artery bypass grafting: comparison of crystalloid and blood cardioplegic solutions

OBJECTIVES: This study was designed (1) to evaluate the influence of plasma obtained from patients undergoing coronary artery bypass grafting on L-selectin, CD11b, and CD18 expression on human neutrophils and (2) to determine the influence of the use of crystalloid or blood cardioplegia during bypass grafting on plasma-mediated expression of adhesion molecules on polymorphonuclear neutrophils.Patients and methods: Patients undergoing coronary artery bypass grafting were divided into 2 groups to receive crystalloid or blood cardioplegic solutions. Peripheral vein, radial artery, and coronary sinus blood samples were drawn at aortic crossclamping, aortic crossclamp release, and 30 minutes after reperfusion. Human neutrophils were incubated with patients' plasma, and the expression of CD11b, CD18, and L-selectin was determined with flow cytometry. RESULTS: In patients receiving crystalloid cardioplegic solutions, plasma samples collected from the coronary sinus at aortic clamp release and 30 minutes thereafter induced significantly higher expression of neutrophil CD11b and CD18 than plasma samples obtained from a peripheral vein or artery at the same time points. The expression of L-selectin on polymorphonuclear neutrophils was significantly reduced with plasma obtained 30 minutes after reperfusion as compared with samples collected at aortic crossclamp release. In the group receiving blood cardioplegia, no significant differences in CD11b, CD18, or L-selectin expression were found. CONCLUSIONS: (1) Ischemia/reperfusion after coronary artery bypass grafting is associated with the release of factors capable of neutrophil activation from myocardium into the circulating blood. (2) The release of soluble stimuli for neutrophils during bypass grafting may be modified by the cardioplegic solution.     

不同剂量谷胱甘肽对体外循环下心内直视手术患儿心肌损伤的影响

目的 评价不同剂量谷胱甘肽(GSH)对体外循环(CPB)下心内直视手术患儿心肌损伤的影响.方法 择期CPB下行室间隔缺损修补术患儿48例,年龄2～5岁,ASA分级Ⅱ或Ⅲ级,采用随机数字表法,将患儿随机分为4组(n＝12):对照组(C组)和不同剂量GSH组(G1-3组).G1～3组分别于含血停搏液中加入GSH 50、75、100 mg/kg,C组单用含血停搏液.分别于切皮前即刻(T0)、主动脉开放后30 min(T1)、停CPB后6、12、24 h(T2-4)时取颈内静脉血样,测定血浆心肌肌钙蛋白Ⅰ(cTnI)浓度.于主动脉阻断前即刻及主动脉开放后15 min取心肌组织,观察心肌超微结构,对心肌细胞行线粒体量化评分.结果 与C组比较,G1,2组T3,4时、G3组T1～4时血浆cTnI浓度降低(P<0.05);与G1组和G2组比较,G3组T1～4时血浆cTnI浓度降低(P<0.05);与C组和G1,2组比较,G3组主动脉开放后15 min时心肌细胞线粒体量化评分降低(P<0.05).G3组心肌损伤程度较C组明显减轻.结论 GSH可呈剂量依赖性地减轻CPB下心内直视手术患儿心肌损伤,剂量100 mg/kg时效果较好.     

Use of Cold Cardioplegic Solution for Vein Graft Distention and Preservation: A Light and Scanning Electron Microscopic Study

To evaluate the effect of a cardioplegic solution on the endothelium of the saphenous vein, portions of this vein were harvested from each of 5 patients undergoing coronary artery bypass operation. Each sample was divided into five segments. One segment was distended with heparinized saline solution, one with heparinized blood, and one with heparinized cardioplegic solution (25 mEq of potassium per liter). All of the distending solutions were kept at 10°C, and pressure was carefully limited to 200 mm Hg. The fourth segment of vein was distended with heparinized saline solution but no effort was made to limit distending pressure, and the fifth segment was not distended. All samples were then examined with light and scanning electron microscopy.There were no great morphological differences in the endothelium of veins distended to 200 mm Hg with saline solution, blood, or cardioplegic solution. The morphology of these samples compared favorably with the control vein endothelium although scattered areas of endothelial disruption were present in every sample. Veins distended without pressure control showed massive endothelial disruption. The particular solution used to distend the saphenous veins is not as important as limiting the distending pressure.     

Methods of cardiac preservation alter the function of the endothelium in porcine coronary arteries

This study was undertaken to determine whether clinical methods for preservation and storage of hearts explanted for transplantation affect the responsiveness of coronary arteries to vasoactive agents. Porcine hearts were perfused with crystalloid or blood cardioplegic solution. Rings of coronary arteries were suspended in organ chambers for measurement of isometric force (1) immediately after perfusion and (2) after 5 hours' storage of the hearts at 4 degrees C in the same cardioplegic solution (n = 6 in each group). The maximal contraction of the smooth muscle to potassium chloride, 40 mmol/L, was reduced significantly after perfusion with crystalloid cardioplegic solution (10.8 +/- 1.2 gm) compared with blood cardioplegic solution (17.3 +/- 0.8 gm) and nonperfused coronary arteries (control group 16.9 +/- 1.8 gm). The sensitivity of the arteries with endothelium to the contractile effects of prostaglandin F2 alpha increased after perfusion with crystalloid cardioplegic solution (ED50, [-log mol/L] 5.8 +/- 0.04) compared with blood cardioplegic solution (5.3 +/- 0.02) and the control group (5.7 +/- 0.03). In addition, relaxations to the calcium ionophore A23187, bradykinin, and the alpha 2-agonist BHT-920, which depend on the presence of endothelial cells, were significantly reduced after perfusion with crystalloid compared with blood cardioplegic solution or the control group. The responsiveness of the endothelium and smooth muscle after 5 hours' cold storage was unaltered in the blood cardioplegia group, whereas storage resulted in functional recovery in the crystalloid cardioplegia group, with the result that all groups were comparable. These data suggest an immediate and reversible change in vascular function with crystalloid cardioplegia, which was not apparent with blood cardioplegia.     

The relationship between the method of cardioplegia and vascular endothelial cell derived soluble adhesion molecules in myocardial ischemia-reperfusion injury

The relative role of different adhesion molecules in the ischemia-reperfusion injury after cardioplegic arrest in the clinical setting is unknown, because of protective effects of cardioplegia and hypothermia. The aim of this study is to determine the relationship between the method of the cardioplegia and endothelial derived soluble adhesion molecules; soluble vascular adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) in myocardial ischemia- reperfusion injury. Fourteen male patients who underwent aortocoronary bypass surgery with cardiopulmonary bypass were included in this study. They were randomised to be given blood or crystalloid cardioplegia for myocardial protection. Group I (n=7) received blood cardioplegia and group II (n=7) received crystalloid cardioplegia. The cross-clamp times were not significantly different between the two groups, 49.4+/-4.6 min for group I and 54.8+/-2.5 min for group II. Mean age of patients was 58+/-2.1 years for group I and 54+/-2.6 years for group II. Blood samples were taken from both the aorta and coronary sinuses of all patients before cross-clamp, after cross-clamping and at 30th min of reperfusion. Plasma were obtained from blood samples and then stored at -70 degrees C. sVCAM-1 and sICAM-1 levels were measured by ELISA in the samples. There were no significant differences in the levels of sICAM-1 and sVCAM-1 at the beginning of reperfusion and at 30th min of reperfusion in coronary sinus of group I patients. But, increased sICAM-1 and sVCAM-1 levels were observed at 30th min of reperfusion in blood taken from coronary sinuses of group II patients compared with beginning of reperfusion (respectively p=0.01, p=0.03). In conclusion, these results have shown that ischemia-reperfusion injury is more likely to occur in patients protected by crystalloid cardioplegia, and suggest that blood cardioplegia may be preferred especially in borderline myocardial functioned patients.     

Hyperkalemia in cardioplegic solutions causing increased cholesterol accumulation in vein grafts

Hyperkalemic cardioplegic solutions are frequently infused through vein grafts during aorta-coronary bypass operations. Although some reports have suggested the potential for physical damage to grafts by such exposure, the effects of these solutions on graft atherogenesis have not been studied. We evaluated the influence of potassium and colloid content of cardioplegic solutions on graft cholesterol accumulation in our established animal model of graft atherogenesis. Fourteen cephalic vein grafts were interposed bilaterally in the femoral arteries of seven normolipemic stump-tailed macaque monkeys. Before grafting, each vein was distended at 350 torr for 1 minute with autologous blood. Half of each vein was then filled for 30 minutes with either balanced crystalloid solution or with balanced crystalloid plus albumin (5 mg/ml). The other half of the vein was filled with the same solution plus potassium chloride (27 mEq/L). Grafts were harvested at 12 weeks. Cholesterol content was significantly greater (p less than 0.01) in graft segments exposed to hyperkalemia than in their control counterparts. Onconicity had no effect on cholesterol content. In this animal model, prolonged exposure of vein grafts to hyperkalemic cardioplegic solutions caused increased lipid uptake. This finding may presage accelerated atheromatous degeneration.     

Myocardial protection by retrograde cardioplegia in arterial switch operation

Retrograde coronary sinus perfusion of cold cardioplegic solution was evaluated in infants undergoing an arterial switch operation for transposition of the great arteries. To assess myocardial injury during ischemia, hemodynamic measurements were conducted at weaning from cardiopulmonary bypass and a postoperative assay of creatine kinase isoenzyme MB was performed. In 22 infants with retrograde coronary sinus perfusion, the initial cardioplegic infusion was performed through the aortic root and additional infusion was repeated every 30 minutes by retrograde coronary sinus perfusion. The other 11 infants received additional solution by antegrade selective coronary artery perfusion. The aortic cross-clamp time in the retrograde coronary sinus perfusion group was significantly shorter than that in the antegrade selective coronary perfusion group (128 +/- 19 versus 143 +/- 21 minutes, p less than 0.05). There were no significant differences between the two groups in terms of postoperative hemodynamic variables and enzyme indexes. Eight neonates in the retrograde coronary sinus perfusion group also exhibited enzymatic and hemodynamic indexes similar to those of older infants. These results suggested that retroperfusion of cardioplegic solution was a safe and useful means of myocardial protection in infants and neonates because of the simplification of the operative procedure and the avoidance of traumatic injury to the coronary ostia.