Core-cooling, heart-perfusion, lung-immersion technique provides successful cardiopulmonary preservation for heart-lung transplantation

Mongrel dogs underwent heterotopic heart-orthotopic left lung transplantation. In Group I (N = 6), donor organs procured following core cooling to 15 degrees C on cardiopulmonary bypass (CPB) with cardioplegic arrest were immediately transplanted. In Group II (N = 6), following cardioplegic arrest without CPB core-cooling, the pulmonary artery was flushed with modified Collins' solution. Heart-lung blocks were immersed in extracellular solution for 6 hours and then transplanted. In Groups III and IV (N = 6 each), following CPB core-cooling to 15 degrees C and cardioplegic arrest, the organ blocks were immersed in extracellular solution (Group III) and the heart was perfused with oxygenated extracellular solution (Group IV). Evaluation of lung function using differences in arterial oxygen tension between the left and right atria demonstrated no differences between groups. However, extravascular lung water and pulmonary vascular resistance were significantly elevated in Group II. Cardiac function assessed by the ratio of end-systolic pressure to end-systolic dimension was significantly better in Group IV than in Groups II and III. Thus, adequate 6-hour hypothermic cardiopulmonary preservation with core cooling plus heart perfusion can be achieved for heart-lung transplantation.     

Collins' solution for cold storage of the heart for transplantation must be reversed with cardioplegic solution before reperfusion. A functional and metabolic study in the rat heart.

The following hypotheses were tested using an isolated perfused working rat heart model: (1) Collins' solution for cold storage of the heart is harmful for the heart during reperfusion; (2) a "reverse" of the intracellular-type Collins' solution with an extracellular-type cardioplegic solution before reperfusion is able to prevent this disadvantage of Collins' solution. The following two major groups (I and II) and five subgroups (-a to -e) in each group were prepared. In group I (reversed group); the hearts were initially stored in Collins' solution but were reversed by a 1-minute flush with cardioplegic solution followed by storage in cardioplegic solution for the last 1 to 180 minutes of the total 3-hour storage, that is, groups I-a (reversed for 1 minute), I-b (10 minutes), I-c (30 minutes), I-d (90 minutes), and I-e (180 minutes). In group II (nonreversed control group); the hearts were stored in Collins' solution throughout 3 hours and were also divided into five subgroups of groups II-a, II-b, II-c, II-d, and II-e in which only a 1-minute flush with Collins' solution was performed at the point corresponding to group I. The coronary flow in any of group II showed a marked decrease during the early reperfusion period. In group I, however, the coronary flow increased significantly in proportion to the duration of the reversing phase. The recovery of the aortic flow and the cardiac output in group I showed a bell-shaped pattern in relation to the duration of the reversing phase, reaching their peak values when reversed for 30 minutes (group I-c). The prolonged reverse (180 minutes) resulted in a deterioration of functional recovery associated with a poorer preservation of high-energy phosphates and a larger enzyme leakage. These results suggest that the beneficial effects of intracellular-type Collins' solution for cold storage of the heart were further improved by reversing Collins' solution with the extracellular-type cardioplegic solution for the last 30 minutes of the 3-hour cold storage because the disadvantageous vasoconstriction due to Collins' solution during reperfusion was successfully prevented by the replacement of intravascular and extravascular Collins' solution with cardioplegic solution before the reperfusion.     

Three solutions for preservation of the rabbit heart at 0 degree C. A comparison with phosphorus-31 nuclear magnetic resonance spectroscopy

Phosphorus-31 nuclear magnetic resonance has been used to measure changes in tissue adenosine triphosphate and pH that occur during hypothermic preservation of rabbit hearts. Three potential preservation solutions were studied: the St. Thomas' Hospital no. 1 cardioplegic solution, Bretschneider's HTP solution, and a solution originated in our laboratory, CP5, which we have previously studied in the rabbit heart with functional assessment by Langendorff perfusion. After being flushed with one of these solutions, each heart was stored at 0 degrees C for 12 hours, during which time it was subjected to repeated phosphorus-31 nuclear magnetic resonance scans. It was shown that adenosine triphosphate levels decayed more slowly with CP5 than with either of the other solutions or in the control experiments. Adenosine triphosphate decay was also slower with Bretschneider's HTP than with St. Thomas' Hospital solution, but pH was somewhat better maintained with Bretschneider's HTP than with either other solution or in the control hearts, although the pH did not decrease drastically in any group. CP5 was designed to prevent cell swelling and to reduce the uptake of calcium during storage, for which reasons it contains 30 mmol/L glucose and 0.1 mmol/L calcium. The potassium content is somewhat higher and the sodium and magnesium content somewhat lower than in St. Thomas' Hospital solution, with the objective of stabilizing intracellular concentrations of these ions during storage.     

Ameliorating Small Bowel Injury Using a Cavitary Two-Layer Preservation Method with Perfluorocarbon and a Nutrient-Rich Solution

The aim of this study was to improve small bowel (SB) quality during cold storage by combining two proven preservation strategies involving perfluorocarbon (PFC) and a novel luminal amino acid-rich solution. Rodent SB was flushed vascularly with UW solution and flushed luminally as follows: Group 1 (control)--no luminal flush, stored in UW; Group 2--luminal UW solution, stored in PFC; Group 3--luminal amino-acid (AA) solution, stored in PFC; and Group 4--luminal AA solution, stored in AA solution. Energetics, histology and mucosal function/electrophysiology were assessed over 24 h at 4 degrees C. ATP was consistently greater in Groups 2-4 than in the Control Group. Groups 3 and 4 exhibited significantly greater ATP, ATP/ADP ratios and energy charge levels after 12-h storage than in the other Groups. Histologic injury was generally lower in the AA-treated tissues (Groups 3 and 4); after 24 h, only minor epithelial clefting (Park's median grade 2) was present in Group 4; and consistent transmural infarction (grade 8) was evident in Groups 1 and 2. Combined treatment with luminal amino acid solution and oxygenated storage solution (PFC or AA solution) significantly improves energetics and mucosal function. This strategy may have implications for successful SB preservation in the clinic.     

Myocardial protection during transplantation procedure following cold storage in Collins' solution

The purpose of this study is to evaluate the myocardial protective effects of two types of solution during heart transplantation procedure following cold storage in Collins' solution. Based on the concept whether the ischemic time during the procedure is an extension of heart storage or is an usual aortic cross-clamped ischemic time, we compared the effects of our cardioplegic solution (Group I) and Collins' solution (Group II) using isolated working rat heart model. After 30 minutes of global ischemia at 25 degrees C following 2 hours of cold storage, the hearts in Group I exhibited better functional recovery than those in Group II (% recovery of cardiac output was 61.1 +/- 5.4% in Group I and 42.4 +/- 7.4% in Group II, p less than 0.01). In Group II, marked elevation of coronary vascular resistance occurred on reperfusion. CPK release during reperfusion period was greater in Group II (0.41 +/- 0.24 IU/15 min/heart in Group I, 1.92 +/- 1.25 IU/15 min/heart in Group II, p less than 0.01). Myocardial metabolites contents (ATP, TAN, creatine phosphate and lactate) and energy charge were not significantly different between two groups. We conclude that it is harmful to ischemic myocardium to use Collins' solution as myocardial protection during transplantation procedure even if following cold storage in Collins' solution.     

Long-term neonatal heart preservation

Donor availability is a major limiting factor in neonatal heart transplantation. Prolonging donor heart preservation would facilitate distant heart procurement. Forty-two neonatal (1 to 5 days) piglet hearts in seven groups were arrested with cold cardioplegic solutions, stored for 12 hours at 4 degrees C in storage solutions, and reperfused with blood from an adult support pig. The cardioplegic solutions used were a crystalloid solution with potassium chloride 30 mEq/L and bicarbonate (Stanford), the Stanford cardioplegic solution with the addition of calcium (1.2 mmol/L), or an intracellular solution (Sacks) with added glucose. Storage solutions were normal saline, Sacks II, or Sacks II with glucose 20 gm/L. Reperfusion was done with normal blood or modified blood for 20 minutes with superoxide dismutase, catalase, aspartate, glutamate, citrate-phosphate-dextrose, potassium, tromethamine, and 50% dextrose followed by normal blood. Evaluation of stroke work index after 60 minutes of recovery (as percent of control) was performed using the isolated, blood perfused, working heart preparation in all groups: Group I (Stanford cardioplegia, saline storage, normal blood reperfusion) had a recovery of 11%; group II (Stanford + calcium, saline, normal blood) 8%; group III (Stanford + calcium, saline, modified blood, superoxide dismutase 35,000 U/L, catalase 35,000 U/L) 37%; group IV (Stanford + calcium, Sacks II, modified blood, superoxide dismutase 35,000 U/L, catalase 35,000 U/L), 47%; group V (Stanford + calcium, Sacks + glucose, modified blood, superoxide dismutase 35,000 U/L, catalase 105,000 U/L) 89%; group VI (Stanford + calcium, Sacks + glucose, modified blood, superoxide dismutase 150,000 U/L, catalase 150,000 U/L) 107%; group VII (Sacks + glucose, Sacks + glucose, modified blood, superoxide dismutase 35,000 U/L, catalase 105,000 U/L) 115%. Conclusions: The neonatal heart stored hypothermically for 12 hours tolerates normal blood reperfusion poorly. Modified blood reperfusion markedly improves the recovery. Complete functional recovery was achieved by the intracellular Sacks plus glucose storage solution and modified blood reperfusion with oxygen-derived free radical scavengers (high catalase). Extended preservation of the neonatal heart is feasible.     

Oxygenation of cardioplegic solutions. Potential for the calcium paradox

Oxygenation of crystalloid cardioplegic solutions is beneficial, yet bicarbonate-containing solutions equilibrated with 100% oxygen become highly alkaline as carbon dioxide is released. In the isolated perfused rat heart fitted with an intraventricular balloon, we recently observed a sustained contraction related to infusion of cardioplegic solution. In the same model, to record these contractions, we studied myocardial preservation by multidose bicarbonate-containing cardioplegic solutions in which first the calcium content and then the pH was varied. An acalcemic cardioplegic solution (Group 1) and the same solution with calcium provided by adding calcium chloride (Group 2) or blood (Group 3) were equilibrated with 100% oxygen. Ionized calcium concentrations were 0, 0.10 +/- 0.06, and 0.11 +/- 0.07 mmol/L and pH values were 8.74 +/- 0.07, 8.54 +/- 0.08, and 8.40 +/- 0.07, all highly alkaline. Hearts were arrested for 2 hours at 8 degrees +/- 2.5 degrees C and reperfused for 1 hour at 37 degrees C. At end-arrest, myocardial adenosine triphosphate was depleted in all three groups, significantly in Groups 2 and 3. In Group 1 the calcium paradox developed upon reperfusion, with contracture (left ventricular end-diastolic pressure = 60 +/- 7 mm Hg), creatine kinase release up to 620 +/- 134 U/L, a profound further decrease in adenosine triphosphate to 1.9 +/- 1.7 nmol/mg dry weight, and either greatly impaired or no functional recovery (17% +/- 10% of prearrest developed pressure). Three hearts in this group released creatine kinase during arrest and did not resume beating during reperfusion. In Groups 2 and 3, the calcium paradox did not occur; functional recovery was 61% +/- 4% and 71% +/- 9% at 5 minutes of reperfusion. In two additional groups (4 and 5), the pH of the acalcemic cardioplegic solution was decreased by equilibration with 2% and 5% carbon dioxide in oxygen to 7.53 +/- 0.03 and 7.11 +/- 0.02. Contractions during arrest were smaller than in Groups 1, 2, and 3; adenosine triphosphate was maintained during arrest; functional recovery was 101% +/- 3% and 96% +/- 4% at 5 minutes of reperfusion. We conclude that acalcemic solutions with carbon dioxide are superior to highly alkaline calcium-containing solutions. If oxygenation of cardioplegic solutions, of proved value, causes severe alkalinity, then calcium paradox may result even with hypothermia. This hazard is prevented by adding calcium or blood to the solution or carbon dioxide to the oxygen used for equilibration.     

冷浸泡法保存犬心3 h后原位心脏移植的实验研究

目的 探讨Ｓｔ Ｔｈｏｍａｓ仿细胞外液、Ｃｏｌｌｉｎｓ仿细胞内液及两种液体联合应用在冷浸泡法供心保存中的心肌保护效果。方法 １２只供犬随机平均分为３组;第１组：以Ｓｔ Ｔｈｏｍａｓ液作为停跳液、灌注冲洗液和保存液;第２组：以Ｃｏｌｌｉｎｓ液作为停跳液、灌注冲洗液和保存液;第３组：以ＳｔＴｈｏｍａｓ液作为停跳液、Ｃｏｌｌｉｎｓ液作为灌注冲洗和保存液。将离体共心放入４℃灌注冲洗液中保存３ｈ。观察指标：     

Effect of sodium aspartate on the recovery of the rat heart from long-term hypothermic storage.

We have investigated the reported ability of aspartate to enhance greatly the cardioprotective properties of the St. Thomas' Hospital cardioplegic solution after prolonged hypothermic storage. Rat hearts (n = 8 per group) were excised and subjected to immediate arrest with St. Thomas' Hospital cardioplegic solution (2 minutes at 4 degrees C) with or without addition of monosodium aspartate (20 mmol/L). The hearts were then immersed in the same solution for 8 hours (4 degrees C) before heterotopic transplantation into the abdomen of homozygous rats and reperfusion in vivo for 24 hours. The hearts were then excised and perfused in the Langendorff mode (20 minutes). Addition of aspartate to St. Thomas' Hospital cardioplegic solution gave a small but significant improvement in left ventricular developed pressure, which recovered to 82 +/- 3 mm Hg compared with 70 +/- 2 mm Hg in control hearts (p less than 0.05). However, coronary flow and high-energy phosphate content were similar in both groups. In subsequent experiments hearts (n = 8 per group) were excised, arrested (2 minutes at 4 degrees C) with St. Thomas' Hospital cardioplegic solution containing a 0, 5, 10, 20, 30, 40, or 50 mmol/L concentration of aspartate, stored for 8 hours at 4 degrees C, and then reperfused for 35 minutes. A bell-shaped dose-response curve was obtained, with maximum recovery in the 20 mmol/L aspartate group (cardiac output, 48 +/- 5 ml/min versus 32 +/- 5 ml/min in the aspartate-free control group; p less than 0.05). However, additional experiments showed that a comparable improvement could be achieved simply by increasing the sodium concentration of St. Thomas' Hospital cardioplegic solution by 20 mmol/L. Similarly, if sodium aspartate (20 mmol/L) was added and the sodium content of the St. Thomas' Hospital cardioplegic solution reduced by 20 mmol/L, no significant protection was observed when recovery was compared with that of unmodified St. Thomas' Hospital cardioplegic solution alone. In still further studies, hearts (n = 8 per group) were perfused in the working mode at either high (greater than 80 ml/min) or low (less than 50 ml/min) left atrial filling rates. Under these conditions, if functional recovery was expressed as a percentage of preischemic function, artifactually high recoveries could be obtained in the low-filling-rate group. In conclusion, assessment of the protective properties of organic additives to cardioplegic solutions requires careful consideration of (1) the consequences of coincident changes in ionic composition and (2) the characteristics of the model used for assessment.     

Improved myocardial preservation during cold storage using substrate enhancement

This study was undertaken to determine whether substrate enhancement with L-glutamate during periods of cold storage would improve ventricular function in transplanted hearts. Thirty-one rabbit hearts were rapidly excised and perfused with Krebs-Henseleit buffer (37 degrees C) on a Langendorff apparatus. They were arrested with hypothermic (4 degrees C), crystalloid, potassium (25 mEq/L) cardioplegia and stored at 3 degrees C for three hours, followed by reperfusion with Krebs-Henseleit buffer for one hour. Hearts were treated in one of several ways: Group 1 (n = 8) did not receive any L-glutamate and serve as controls; group 2 (n = 8) had L-glutamate (4 mmol/L) added to both the cardioplegic and reperfusate solutions; group 3 (n = 5) received L-glutamate only before ischemia; group 4 (n = 5) received L-glutamate only in the cardioplegic solution; and group 5 (n = 5) received L-glutamate only in the reperfusate. Hearts receiving L-glutamate in the reperfusate with or without its addition to the cardioplegic solution (groups 2 and 5) had the best recovery of the first derivative of positive and negative change in left ventricular peak systolic pressure and no significant changes in left ventricular compliance. Pretreatment with L-glutamate alone (group 3) resulted in no better recovery than in group 1 hearts. We conclude that addition of L-glutamate to reperfusate solutions after periods of cold storage for transplantation enhances the recovery of ventricular function.     

Ischemic preconditioning with opening of mitochondrial adenosine triphosphate-sensitive potassium channels or Na/H exchange inhibition: which is the best protective strategy for heart transplants?

OBJECTIVE: This study was designed to compare ischemic preconditioning with opening of mitochondrial adenosine triphosphate-sensitive potassium channels and Na(+)/H(+) exchange inhibition in an isolated heart model of cold storage, simulating the situation of cardiac allografts. METHODS: Sixty-seven isolated isovolumic buffer-perfused rat hearts were arrested with and stored in Celsior solution (Imtix-Sangstat) at 4 degrees C for 4 hours before a 2-hour reperfusion. Group I hearts served as controls and were arrested with and stored in Celsior solution. In group II, hearts were preconditioned by two 5-minute episodes of global ischemia, each separated by 5 minutes of reperfusion before arrest with Celsior solution. Group III hearts were arrested with and stored in Celsior solution supplemented with 100 micromol/L of the mitochondrial adenosine triphosphate-sensitive potassium channel opener diazoxide. In group IV, hearts received an infusion of diazoxide (30 micromol/L) during the first 15 minutes of reperfusion. Group V hearts underwent a protocol combining both interventions used in groups III and IV. In group VI, hearts were arrested with and stored in Celsior solution supplemented with 1 micromol/L of the Na(+)/H(+) exchange inhibitor cariporide. Group VII hearts received an infusion of cariporide (1 micromol/L) during the first 15 minutes of reperfusion. In group VIII, hearts underwent a protocol combining both interventions used in groups VI and VII. Group IX hearts were ischemically preconditioned as in group II, and sustained Na(+)/H(+) exchange inhibition during both storage and early reperfusion was used as in group VIII. RESULTS: On the basis of comparisons of postischemic left ventricular contractility and diastolic function, coronary flow, total creatine kinase leakage, and myocardial water content, values indicative of improved protection were obtained by combining ischemic preconditioning with Na(+)/H(+) exchange inhibition by cariporide given during storage and initial reperfusion. The endothelium-dependent vasodilatory postischemic responses to 5-hydroxytryptamine or acetylcholine and endothelium-independent responses to papaverine were not affected by these interventions. CONCLUSIONS: These data suggest that cardioprotection conferred by the Na(+)/H(+) exchange inhibitor cariporide is additive to that of ischemic preconditioning and might effectively contribute to improve donor heart preservation during cardiac transplantation.     

1，6—二磷酸果糖和巯甲丙脯酸对心脏术后心肌缺血—再灌注损伤的保护

目的：探讨1，6－二磷酸果糖（FDP）和巯甲丙腈酸（CAP）增强心脏停搏液对缺血心肌保护的临床效果，方法：将60例患者随机分成三组，I组：作为对照组，应用我院体外循环下心肌保护方法，即首剂应用冷钾晶体心脏停搏液，从第二剂量开始改用15度稀释氧合血灌注，Ⅱ组：在冷钾晶体心脏停搏液中加入FDP（5mmol/L)；Ⅲ组：在冷钾晶体心脏停搏液中加FDP（5mmol/L)和CAP（12．5mg/L)。观察血浆丙二醛（MDA），肌酸磷酸激酶同工酶（CPK－MB），血栓素B2（TXB2），6－酮－前列腺素F1（6－酮－PGF1a)及电子显微镜检查结果：结果：与I组比较，Ⅱ组和Ⅲ组MDA，CPK－MB明显降低，且Ⅲ组较好地维持了TXB2和6－酮－PGF1a二者的比例平衡，Ⅱ组和Ⅲ组对线粒体也有较好地保护及提高毛细血管通畅率的作用。结论：FDP和CAP能明显增加心脏停搏液对缺血心肌保护的效果。     

Effect of multidose cardioplegia and cardioplegic solution buffering on myocardial tissue acidosis

Multidose administration of cardioplegic solution during cardiac operation is intended to maintain both electromechanical arrest of the heart and myocardial hypothermia as well as to remove accumulated metabolites of anaerobic glycolysis. This study was conducted to assess the effect of multidose infusion of three different types of cardioplegic solution on tissue acidosis during global myocardial ischemia. Three groups of five dogs each were placed on cardiopulmonary bypass and the aorta was cross-clamped for 3 hours. The hearts were maintained at a constant temperature (20 degrees C) and cardioplegic solution was infused at an initial dose of 500 ml and five supplementary doses of 250 ml administered every 30 minutes. Group 1 received a crystalloid solution weakly buffered with sodium bicarbonate, Group 2 received a blood-based solution, and Group 3 received a crystalloid solution strongly buffered with histidine (Bretschneider's solution). The buffering capacities of the solutions used in Groups 2 and 3 were 40 and 60 times, respectively, that of the solution used in Group 1. The average myocardial tissue pH at the end of 3 hours of ischemia was 6.54 +/- 0.07 in Group 1, 7.23 +/- 0.05 in Group 2, and 7.19 +/- 0.06 in Group 3 (Group 1 significantly lower than Groups 2 and 3). Multidose infusion of a cardioplegic solution with low buffering capacity was unable to prevent the progressive development of tissue acidosis during 3 hours of ischemia. However, the multidose infusion of either blood-based or crystalloid solutions with high buffering capacity completely prevented any further reduction of tissue pH after the first 30 minutes of ischemia.     

Calcium content of St. Thomas' II cardioplegic solution damages ischemic immature myocardium

Clinical application of hypothermic pharmacologic cardioplegia in pediatric cardiac surgery is less than satisfactory, despite its well known benefits in adults. Protection of the ischemic immature rabbit heart with hypothermia alone is better than with hypothermic St. Thomas' II cardioplegic solution. Control of cellular calcium is a critical component of cardioplegic protection. We determined whether the existing calcium content of St. Thomas' II solution (1.2 mmol/L) is responsible for suboptimal protection of the ischemic immature rabbit heart. Modified hypothermic St. Thomas' II solutions (calcium content, 0 to 2.4 mmol/L) were compared with hypothermic Krebs bicarbonate buffer in protecting ischemic immature (7- to 10-day-old) hearts. Hearts (n = 6 per group) underwent aerobic "working" perfusion with Krebs buffer, and cardiac function was measured. The hearts were then arrested with a 3-minute infusion of either cold (14 degrees C) Krebs buffer (1.8 mmol calcium/L) as hypothermia alone or cold St. Thomas' II solution before 6 hours of hypothermic (14 degrees C) global ischemia. Hearts were reperfused, and postischemic enzyme leakage and recovery of function were measured. A bell-shaped dose-response profile for calcium was observed for recovery of aortic flow but not for creatine kinase leakage, with improved protection at lower calcium concentrations. Optimal myocardial protection occurred at a calcium content of 0.3 mmol/L, which was better than with hypothermia alone and standard St. Thomas' II solution. We conclude that the existing calcium content of St. Thomas' II solution is responsible, in part, for its damaging effect on the ischemic immature rabbit heart.     

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.     

Potassium-verapamil cardioplegia for myocardial protection: an experimental evaluation through preservation and transplantation

The efficacy of potassium-verapamil cardioplegia for myocardial protection was studied using the canine heart preservation and transplantation system. Coronary vascular washout of the grafts was performed via the aortic root both in Group I (n=8) with 4 degrees C high potassium cardioplegic solution and in Group II (n=8) with 4 degrees C high potassium and 1 mg/L verapamil solution. The heart were immersed into the same solution as used for washout and stored at 4 degrees C for 6 hours, without oxygenation and perfusion. The grafts were transplanted orthotopically under conditions of cardiopulmonary (CP) bypass. Adequate hemodynamics without the support of CP bypass was obtained in all the grafts of Group II during a 2-hour observation period. In contrast, only five out of eight grafts in Group I were able to support the recipient circulation. Contraction bands were more prominently and frequently observed in the histology in Group I. Thus, the combination of coronary vascular washout with cold potassium-verapamil cardioplegia and storage at 4 degrees C with the same solution seems to be effective for myocardial protection of the canine heart in cases of orthotopic transplantation.     

Adenosine and lidocaine: a new concept in nondepolarizing surgical myocardial arrest, protection, and preservation

OBJECTIVE: Depolarizing potassium cardioplegia has been increasingly linked to left ventricular dysfunction, arrhythmia, and microvascular damage. We tested a new polarizing normokalemic cardioplegic solution employing adenosine and lidocaine as the arresting, protecting, and preserving cardioprotective combination. Adenosine hyperpolarizes the myocyte by A1 receptor activation, and lidocaine blocks the sodium fast channels. METHODS: Isolated perfused rat hearts were switched from the working mode to the Langendorff (nonworking) mode and arrested for 30 minutes, 2 hours, or 4 hours with 200 micromol/L adenosine and 500 micromol/L lidocaine in Krebs-Henseleit buffer (10 mmol/L glucose, pH 7.7, at 37 degrees C) or modified St Thomas' Hospital solution no. 2, both delivered at 70 mm Hg and 37 degrees C (arrest temperature 22 degrees C to 35 degrees C). RESULTS: Adenosine and lidocaine hearts achieved faster mechanical arrest in (25 +/- 2 seconds, n = 23) compared with St Thomas' Hospital solution hearts (70 +/- 5 seconds, n = 24; P=.001). After 30 minutes of arrest, both groups developed comparable aortic flow at approximately 5 minutes of reperfusion. After 2 and 4 hours of arrest (cardioplegic solution delivered every 20 minutes for 2 minutes at 37 degrees C), only 50% (4 of 8) and 14% (1 of 7) of St Thomas' Hospital solution hearts recovered aortic flow, respectively. All adenosine and lidocaine hearts arrested for 2 hours (n = 7) and 4 hours (n = 9) recovered 70% to 80% of their prearrest aortic flows. Similarly, heart rate, systolic pressures, and rate-pressure products recovered to 85% to 100% and coronary flows recovered to 70% to 80% of prearrest values. Coronary vascular resistance during delivery of cardioplegic solution was significantly lower (P <.05) after 2 and 4 hours in hearts arrested with adenosine and lidocaine cardioplegic solution compared with hearts arrested with St Thomas' Hospital solution. CONCLUSIONS: We conclude that adenosine and lidocaine polarizing cardioplegic solution confers superior cardiac protection during arrest and recovery compared with hyperkalemic depolarizing St Thomas' Hospital cardioplegic solution.     

Arresting donor hearts with extracellular-type cardioplegia prevents vasoconstriction induced by UW solution.

The effects of arresting donor hearts with University of Wisconsin solution was investigated. Donor dogs were divided into two groups according to the technique used for arresting the heart. In group I (n = 6) the heart was arrested with University of Wisconsin solution, whereas in group II (n = 6) extracellular-type cardioplegia (K+ = 20 mmol/liter) was used to induce cardioplegic arrest. Aortic root pressure was measured during the infusion of solution at constant flow. In both groups, the hearts were then flushed and stored in cold University of Wisconsin solution for 6 h. The hearts were transplanted orthotopically and disconnected from cardiopulmonary bypass. Left ventricular function was evaluated by pressure-volume relations using a conductance catheter. Peak aortic root pressure during the infusion was significantly higher in group I than in group II, although post-transplant left ventricular function was similar in both groups. Although there was no difference in cardiac function after implantation, donor hearts should be arrested by extracellular-type cardioplegia to prevent coronary vasoconstriction associated with preservation in University of Wisconsin solution.     

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.     

Optimal temperature of continuous lidocaine perfusion for the heart preservation

Objective: During cardiovascular surgery, lidocaine is administered to the cardioplegic system to stabilize cell membrenes and prevent arrhythmia. Lidocaine is also commonly used in hypothermia Both lidocaine and hypothermia are myocardially protective. Under normothermia, lidocaine displays its full pharmacological effects, which are apt, however, to be suppressed under hypothermia. We conducted experiments to determine the optimal temperature for myocardial protection in continuous lidocaine cardioplegia. Methods: In Langendorff mode, rat hearts were continuously perfused with 1 mMol/l of lidocaine solution at 36±0.5°C (Group A), 24±0.5°C (Group B), or 7±0.5°C (Group C) during preservation. Cardiac function and intracellular calcium concentration were measured during both preservation and reperfusion. Heat shock protein 70 (HSP70) was subsequently analyzed by Western blotting. Results: Rapid cardiac arrest was obtained in Groups A and C. Heart rate recovery was good and ultimately the best in Group B, but worst in Group A. During lidocaine perfusion, the volume of coronary perfusion flow decreased gradually in all groups. After reperfusion, Group A showed only a slight increase in coronary perfusion, While Groups B and C showed a marked increase. Left ventricular contractility showed good recovery in all groups. The calcium concentration increased slightly in Group A, but decreased in Groups B and C. No calcium overload was evident in Group A. The same HSP70 level was detected in all groups. Conclusion: Lidocaine used in normothermia does not decrease cardiac metabolism or oxygen consumption, and displays full, pharmacological effectiveness in preventing ischemic injury. We found 36°C to be the optimal temperature for heart preservation by coronary perfusion with lidocaine cardioplegia.