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.     

The advantages of normocalcemic continuous warm cardioplegia over low calcemic cardioplegia in myocardial protection

The effects of changing the calcium content of a continuous warm hyperkalemic crystalloid cardioplegia (CWCP) were investigated in an isolated rat heart preparation. The hearts were divided into eight groups of six each. A control group consisted of fresh nonarrested hearts and the remaining seven groups consisted of hearts perfused with continuous hyperkalemic (20 mM) modified Krebs-Henseleit bicarbonate buffer solution with calcium concentrations of 0.1, 0.3, 0.5, 1.0, 1.5, 2.0, or 2.5 mM, for either 180 or 240 min at 37°C. In the hearts arrested for 180 min, there were no significant differences in postarrest cardiac functions between the control group and any of the groups perfused with calcium concentrations of 0.5 mM or more. With a calcium concentration of 0.1 mM, the calcium paradox was provoked. The change in the calcium content of CWCP perfused for 240 min significantly affected myocardial protection. Maximum aortic flow recovery, of 74.5%±2.7%, and minimum CK release, of 15.7±2.4IU/15 min/g dry weight, were observed in hearts perfused with a calcium concentration of 1.5 mM. The calcium paradox occurred even at a calcium concentration of 0.3 mM; therefore, normal calcium concentrations should be maintained in cardiac surgery to prevent cardiac injury.     

Myocardial protection with oxygenated esmolol cardioplegia during prolonged normothermic ischemia in the rat

OBJECTIVE: We previously showed that arrest with multidose infusions of high-dose (1 mmol/L) esmolol (an ultra-short-acting beta-blocker) in oxygenated Krebs-Henseleit buffer (esmolol cardioplegia) provided complete myocardial protection after 40 minutes of normothermic (37 degrees C) global ischemia in isolated rat hearts. In this study we investigated the importance of oxygenation for protection with esmolol cardioplegia, compared it with that of St Thomas' Hospital cardioplegia, and determined the protective efficacy of multidose esmolol cardioplegia for extended ischemic durations. METHODS: Isolated rat hearts (n = 6/group) were perfused in the Langendorff mode at constant pressure (75 mm Hg) with oxygenated Krebs-Henseleit bicarbonate buffer at 37 degrees C. The first part of the first study had four groups: (i) multidose (every 15 minutes) oxygenated (95% oxygen/5% carbon dioxide) Krebs-Henseleit buffer during 60 minutes of global ischemia, (ii) multidose deoxygenated (95% nitrogen/5% carbon dioxide) Krebs-Henseleit buffer during 60 minutes of global ischemia, (iii) multidose oxygenated esmolol cardioplegia during 60 minutes of global ischemia, and (iv) multidose deoxygenated esmolol cardioplegia during 60 minutes of global ischemia. The second part of the first study had three groups: (v) multidose St Thomas' Hospital solution during 60 minutes of global ischemia, (vi) multidose oxygenated St Thomas' Hospital solution during 60 minutes of global ischemia, and (vii) multidose oxygenated esmolol cardioplegia during 60 minutes of global ischemia. In the second study, hearts were randomly assigned to 60, 75, 90, or 120 minutes of global ischemia and at each ischemic duration were subjected to multidose oxygenated constant flow or constant pressure infusion of (i) Krebs-Henseleit buffer (constant flow), (ii) Krebs-Henseleit buffer (constant pressure), (iii) esmolol cardioplegia (constant flow), or (iv) esmolol cardioplegia (constant pressure). All hearts were reperfused for 60 minutes, and recovery of function was measured. RESULTS: Multidose infusion of oxygenated esmolol cardioplegia completely protected the hearts (97% +/- 5%) after 60 minutes of 37 degrees C global ischemia. Deoxygenated esmolol cardioplegia was significantly less protective (45% +/- 8%). Oxygenation of St Thomas' Hospital solution did not alter its protective efficacy in this study (70% +/- 4% vs 69% +/- 7%). Infusion of esmolol cardioplegia at constant pressure provided complete protection for 60, 75, and 90 minutes (104% +/- 5%, 95% +/- 5%, and 95% +/- 3%, respectively), whereas protection with constant-flow esmolol cardioplegic infusion was significantly decreased at ischemic durations longer than 60 minutes. This decrease in efficacy of constant-flow esmolol cardioplegia was associated with increasing coronary perfusion pressure leading to myocardial injury. CONCLUSIONS: Oxygenation of esmolol cardioplegia (Krebs-Henseleit buffer plus 1.0 mmol/L esmolol) was essential for optimal myocardial protection. Multidose infusion of oxygenated esmolol cardioplegia provided good myocardial protection during extended periods of normothermic ischemia. Esmolol cardioplegia may provide an efficacious alternative to hyperkalemia.     

Non-depolarizing cardioplegia activates Ca-ATPase in sarcoplasmic reticulum after reperfusion

Objectives: Depolarizing cardioplegia is the most common method for myocardial preservation in cardiac operations. However, depolarizing cardioplegia causes depolarization of the membrane potential by extracellular hyperkalemia, resulting in depletion of energy stores and calcium overload. This study examined the hypothesis that non-depolarizing cardioplegia would provide superior protection compared with depolarizing cardioplegia. Methods: In an isolated rat heart Langendorff model, hearts were perfused for 10 min with St. Thomas' Hospital cardioplegic solution (Group I: n=20), St. Thomas' Hospital cardioplegic solution+Lidocaine 1 mM (Group II: n=20) or non-depolarizing cardioplegia (Group III: n=20). The hearts then were subjected to 60 min of normothermic global ischemia, after which they were perfused with Krebs–Henseleit buffer at 37 °C for 30 min. The percent recovery of functional data, myocardial cyclic AMP contents, and myocardial cyclic GMP contents were recorded at each time point (base, after the administration of cardioplegia, after global ischemia, and after 30 min of reperfusion). Ca²⁺-ATPase in sarcoplasmic reticulum was measured at pre-ischemia and 30 min of reperfusion. Results: The percent recovery of developed pressure and ±dp/dt were significantly higher in Group III than in other groups. Myocardial cyclic AMP and GMP contents were elevated after reperfusion in all groups. However, in Group III, myocardial cyclic AMP contents after 30 min of reperfusion were significantly higher than in other groups (Group III: 14.7±1.6 vs. Group I: 8.7±1.0, Group II: 8.3±0.2 pmol/mg dry weight, P=0.05) but not cGMP. The sarcoplasmic reticulum Ca²⁺-ATPase activities at 30 min of reperfusion significantly increased in Group III compared with Groups II and I (Group III: 70.3±3.6 vs. Group I: 46.8±3.4, Group II: 53.9±6.1 μmol Pi/mg per h, P=0.025 and P=0.030). Conclusions: Non-depolarizing cardioplegia induced the activity of Ca²⁺-ATPase in sarcoplasmic reticulum after reperfusion. The activity would be increased by the cyclic AMP pathway. These findings suggested that non-depolarizing cardioplegia prevented calcium overload after reperfusion, especially decreased cytosolic calcium during the diastolic phase.     

Free hemoglobin impairs cardiac function in neonatal rabbit hearts

BACKGROUND: Hemolysis caused by cardiopulmonary bypass causes renal dysfunction and other organ failure presumably by superoxide production catalyzed by iron derived from free hemoglobin (f-Hb). It might also impair cardiac function by the same mechanism, especially in the ischemia-reperfusion period and in neonates where serum antioxidant activity is lower than adults. METHODS: We evaluated effects of f-Hb on cardiac function with or without ischemia and reperfusion using a newborn (7 days old) rabbit crystalloid-perfused Langendorff model. After baseline measurements, the hearts were divided into the following four groups (8 hearts per group): (1) those perfused with regular Krebs-Henseleit bicarbonate buffer, (2) those perfused 30 minutes with KH buffer containing 1 mg/mL of f-Hb obtained from osmotic hemolysis, (3) those subjected to 180 minutes of cold global ischemia with infusion of crystalloid cardioplegia and reperfused with Krebs-Henseleit buffer, and (4) those subjected to the same ischemia and reperfused with Krebs-Henseleit buffer containing 1 mg/mL of f-Hb. The left ventricular function (using conductance catheter and isovolumic balloon) and coronary flow were measured. RESULTS: Free hemoglobin significantly impaired not only left ventricular function but also coronary flow even without ischemia (p < 0.05). When ischemia and reperfusion were involved, the group reperfused with f-Hb showed the worst left ventricular function and coronary flow among the groups. CONCLUSIONS: This study shows that f-Hb directly impaired cardiac function and coronary flow in neonatal hearts especially in ischemia and reperfusion.     

Cardioplegia-induced damage to ischemic immature myocardium is independent of oxygen availability

The known benefits of hypothermic pharmacological cardioplegia in protecting the ischemic adult heart may not extend to children. Protection of the ischemic immature rabbit heart with hypothermic Krebs-Henseleit bicarbonate buffer is better than with hypothermic St. Thomas' II cardioplegic solution. We investigated whether the availability of oxygen in the preischemic perfusate is responsible for the increased tolerance to ischemia of immature (7- to 10-day-old) hearts perfused with Krebs buffer in comparison with St. Thomas' II solution immediately before ischemia. After obtaining preischemic control data in the "working" mode, we perfused hearts (n = 8 per group) for 3 minutes with hypothermic (14 degrees C) Krebs buffer or hypothermic St. Thomas' II solution saturated with 0%, 25%, or 95% oxygen. This was followed by 2 hours of global ischemia at 14 degrees C. Hearts were reperfused for 15 minutes in the Langendorff mode and 35 minutes in the working mode, and recovery of function was measured. For preischemic oxygen concentrations of 0%, 25%, and 95%, recovery of aortic flow in hearts protected by hypothermia alone during ischemia was 74% +/- 9%, 82% +/- 4%, and 99% +/- 2% of preischemic values, respectively. In hearts protected by hypothermia plus cardioplegia, the values were 69% +/- 6%, 72% +/- 3%, and 86% +/- 5%, respectively. Thus, at equal oxygen concentrations, recovery of postischemic function was better in hearts protected by hypothermia alone compared with hypothermia plus cardioplegia. We conclude that factors other than oxygen availability are responsible for the damaging effect of St. Thomas' II solution on the ischemic immature rabbit heart.     

Terminal Warm Blood Cardioplegia Improves Cardiac Function Through Microtubule Repolymerization

Background. To elucidate the mechanisms responsible for the beneficial effects of terminal warm blood cardioplegia, we studied dynamic change in microtubules induced by cold cardioplegia followed by rewarming. Further, we investigated the relationship between cardiac function and morphologic changes in microtubules caused by hyperkalemic, hypocalcemic warm cardioplegia during initial reperfusion.

Methods. In protocol 1 isolated rat hearts were perfused at 37°C with Krebs-Henseleit buffer (KHB). After 3 hours of hypothermic cardiac arrest at 10°C, hearts were reperfused at 37°C with one of two buffers: group C, 60-minute reperfusion with KHB (K⁺, 5.9 mmol/L; Ca²⁺, 2.5 mmol/L); and group TC, 10-minute initial reperfusion with modified KHB (K⁺, 15 mmol/L; Ca²⁺, 0.25 mmol/L), followed by 50 minutes of reperfusion with KHB. Cardiac function after reperfusion was determined as a percentage of the prearrest value. In protocol 2 hearts were perfused at 37°C with KHB containing colchicine (10⁻⁵ mol/L) for 60 minutes.

Results. There was spontaneous contractile recovery after 10 minutes of initial reperfusion in hearts from group TC as well as improved cardiac function after 15, 30, and 60 minutes of reperfusion compared with that in group C. Immunohistochemical staining and immunoblot analysis demonstrated microtubule depolymerization during hypothermic cardiac arrest and complete repolymerization after 10 minutes of reperfusion with warm buffers in both groups. Colchicine-induced microtubule depolymerization is associated with deterioration of cardiac function.

Conclusions. One mechanism responsible for improved cardiac function mediated by terminal warm blood cardioplegia is the restart of contraction after complete microtubule repolymerization.     

Effects of calcium in continuous cardioplegia on myocardial protection

The effects of calcium (Ca) on a hyperkalemic cardioplegic solution for continuous cardioplegia were examined in an isolated perfused working rat heart model. The coronary arteries were perfused with a modified Krebs-Henseleit bicarbonate buffer (K-H) solution, containing various concentrations of Ca(0.1, 0.6, 1.2, and 2.5 mmol/l) and a high concentration of potassium (20 mmol/l), for 180 min, after which cardiac arrest was induced at 37°C for 180 min. Cardiac function and creatine kinase (CK) were measured. In the control group, K-H solution was infused in place of the cardioplegic solution, and cardiac arrest was not induced. No significant differences were observed between the groups infused with the K-H solution containing Ca concentrations of 0.6, 1.2, and 2.5 mmol/l in the percent recovery of aortic flow (82.1±2.9%, 80.6±2.0%, and 71.5±3.7% (mean±SEM) respectively) or in the recovery of other indices of cardiac function, or in CK leakage. There were also no significant differences in the recovery of cardiac function and CK leakage between these groups and the control group. In the Ca 0.1 mmol/l group, however, the characteristic Ca paradox was observed. These findings suggest that if the Ca concentration in a cardioplegic solution is higher than 0.6 mmol/l during continuous cardioplegia, excellent cardioprotective effects will be achieved.     

Preventive effect of post-ischemic reperfusion injury by terminal Nicorandil-Mg cardioplegia

In this study, we evaluated the preventive effect of post-ischemic reperfusion injury by Nicorandil-Mg cardioplegia (Nic: 8 mg/l, Mg: 20 mEq/l) given just prior to reperfusion as "terminal cardioplegia". Nineteen dogs were placed on cardiopulmonary bypass and the aorta was cross-clamped for 90 min under hypothermic (17-19 degrees C) cardioplegic arrest. The hearts of ten dogs were reperfused without terminal cardioplegia (Group A). In the other nine dogs, terminal cardioplegia was given for 2 min prior to reperfusion (Group B). During and after a period of ischemia, myocardial tissue calcium ion (t-Ca) and PCO2 (t-PCO2) were continuously monitored by ISFET (ion sensitive filed effective transistor) sensor. Myocardial tissue blood flow, oxygen consumption and lactate flux were calculated at 5, 10, 20, 40 min of reperfusion. And myocardial function was evaluated at 45 min of reperfusion. In the initial reperfusion period, Group B showed an improved myocardial tissue blood flow compared to group A (at 5 min of reperfusion in group A: 29.4% of control, in group B: 42.7% of control, p less than 0.025). T-Ca and T-PCO2 in Group B were rapidly and significantly decreased at 5 min of reperfusion (t-Ca in group A: 2.8 +/- 0.5 mM----1.7 +/- 0.5 mM, in group B: 3.1 +/- 0.6----1.2 +/- 0.4, p less than 0.05; t-PCO2 in group A: 117.5 +/- 23.0 mmHg----82.5 +/- 17.4 mmHg, in group B: 127.5 +/- 22.5----42.5 +/- 9.7, p less than 0.001), and group B had better metablic recovery evaluated by myocardial oxygen consumption and lactate flux.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adding bupivacaine to high-potassium cardioplegia improves function and reduces cellular damage of rat isolated hearts after prolonged, cold storage

BACKGROUND: Bupivacaine retards myocardial acidosis during ischemia. The authors measured function of rat isolated hearts after prolonged storage to determine whether bupivacaine improves cardiac protection compared with standard cardioplegia alone. METHODS: After measuring cardiac function on a Langendorff apparatus, hearts were perfused with cardioplegia alone (controls), cardioplegia containing 500 microm bupivacaine, or cardioplegia containing 2 mm lidocaine; were stored at 4 degrees C for 12 h; and were then reperfused. Heart rate and left ventricular developed pressures were measured for 60 min. Maximum positive rate of change in ventricular pressure, oxygen consumption, and lactate dehydrogenase release were also measured. RESULTS: All bupivacaine-treated, four of five lidocaine-treated, and no control hearts beat throughout the 60-min recovery period. Mean values of heart rate, left ventricular developed pressure, maximum positive rate of change in ventricular pressure, rate-pressure product, and efficiency in bupivacaine-treated hearts exceeded those of the control group (P < 0.001 at 60 min for all). Mean values of the lidocaine group were intermediate. Oxygen consumption of the control group exceeded the other groups early in recovery, but not at later times. Lactate dehydrogenase release from the bupivacaine group was less than that from the control group (P < 0.001) but did not differ from baseline. CONCLUSIONS: Adding bupivacaine to a depolarizing cardioplegia solution reduces cell damage and improves cardiac function after prolonged storage. Metabolic inhibition may contribute to this phenomenon, which is not entirely explained by sodium channel blockade.     

Developmental changes in reperfusion injury. Comparison of intracellular ion accumulation in ischemic and cardioplegic arrest

Developmental differences in ischemic and potassium cardioplegic arrest were evaluated in newborn (birth to 7 day old) and adult (6 to 12 month old) New Zealand white rabbit hearts isolated and perfused by Langendorff's method. An extracellular space washout technique was used to measure intracellular sodium and calcium in the two age groups after ischemia alone, after normothermic and hypothermic cardioplegia, and after cardioplegia with reperfusion. Although the intracellular ionic contents of nonreperfused adult hearts after 30 and 40 minutes of ischemia were identical, there was a twofold elevation in intracellular sodium level after 40 minutes of ischemia in the newborn hearts. Adult hearts arrested by normothermic potassium cardioplegia demonstrated no alteration in the intracellular ionic content, whereas in the newborn hearts, potassium cardioplegia produced excess intracellular calcium loading before reperfusion, which was greater than that occurring with ischemia alone. When hypothermia (12 degrees C) was combined with cardioplegic arrest, a prereperfusion influx of sodium and calcium was not observed in the newborn hearts, and ionic reperfusion injury was blunted in both newborn and adult hearts. These studies demonstrate that the newborn heart is more susceptible than the adult to both ischemia and cardioplegia. This may be due to age-dependent differences in transmembrane passive diffusion, sodium/calcium exchange, or calcium slow channel properties and suggests alternative myocardial protective strategies for the newborn infant.     

Adding Bupivacaine to High-potassium Cardioplegia Improves Function and Reduces Cellular Damage of Rat Isolated Hearts after Prolonged, Cold Storage

Background: Bupivacaine retards myocardial acidosis during ischemia. The authors measured function of rat isolated hearts after prolonged storage to determine whether bupivacaine improves cardiac protection compared with standard cardioplegia alone.

Methods: After measuring cardiac function on a Langendorff apparatus, hearts were perfused with cardioplegia alone (controls), cardioplegia containing 500 [mu]m bupivacaine, or cardioplegia containing 2 mm lidocaine; were stored at 4[degrees]C for 12 h; and were then reperfused. Heart rate and left ventricular developed pressures were measured for 60 min. Maximum positive rate of change in ventricular pressure, oxygen consumption, and lactate dehydrogenase release were also measured.

Results: All bupivacaine-treated, four of five lidocaine-treated, and no control hearts beat throughout the 60-min recovery period. Mean values of heart rate, left ventricular developed pressure, maximum positive rate of change in ventricular pressure, rate-pressure product, and efficiency in bupivacaine-treated hearts exceeded those of the control group (P < 0.001 at 60 min for all). Mean values of the lidocaine group were intermediate. Oxygen consumption of the control group exceeded the other groups early in recovery, but not at later times. Lactate dehydrogenase release from the bupivacaine group was less than that from the control group (P < 0.001) but did not differ from baseline.     

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.     

Pretreatment with nicardipine preserves ventricular function after hypothermic ischemic arrest

Calcium antagonists have a protective effect on postischemic myocardial function when included in normothermic cardioplegia solutions. This effect varies with the calcium antagonist, but is generally lost under hypothermic conditions. The hypothesis tested was that a calcium antagonist would increase postischemic myocardial performance if given before the onset of hypothermic arrest. Isolated working rat hearts were used with an oxygenated modified Krebs-Henseleit buffer solution as a perfusion media. Rats were pretreated with 1 of 9 doses of a nicardipine solution (0 to 100 micrograms/kg, intraperitoneally) 20 minutes before excision of the heart. Nicardipine is a light-stable, water-soluble calcium antagonist with minimal myocardial depressant effects. The hearts were arrested for 25 minutes at 37 degrees C or 93 minutes at 24 degrees C with 20 mL of cardioplegia solution containing 0.05 mmol/L CaCl2. Postischemic performance and adenosine triphosphate content were used as determinants of efficacy. Eighty-three percent of 101 treated hearts recovered in contrast to a mortality of 50% in the 24 nontreated hearts. Pretreatment with 25 micrograms/kg significantly increased (p less than 0.05) the percent recovery (compared with the nontreated group) of the following variables of cardiac function: systolic pressure, 74% to 96% (37 degrees C), 76% to 90% (24 degrees C); cardiac output, 61% to 90% (37 degrees C), 62% to 84% (24 degrees C); stroke work, 49% to 95% (37 degrees C), 50% to 92% (24 degrees C); and adenosine triphosphate, 76% to 87% (37 degrees C), 58% to 68% (24 degrees C). Progressive increases in postischemic function at 37 degrees and 24 degrees C were seen as the dose of nicardipine was increased from 0 to 25 micrograms/kg and decreased function was seen with a pretreatment dose greater than 25 micrograms/kg of nicardipine. Pretreatment with nicardipine significantly improved postischemic myocardial performance under hypothermic conditions and should be administered or at least not discontinued before cardiac operations.     

Fetal myocardial protection is markedly improved by reduced cardioplegic calcium content

BACKGROUND: Fetal cardiac surgery holds a clear therapeutic benefit in the treatment of lesions that increase in complexity due to pathologic blood flow patterns during development. Fetal and neonatal myocardial physiology differ substantially, particularly in the regulation of myocardial calcium concentration. To examine issues of calcium homeostasis and fetal myocardial protection, a novel isolated biventricular working fetal heart preparation was developed. METHODS: Hearts from 20 fetal lambs, 115 to 125 days gestation, were harvested and perfused with standard Krebs-Henseleit (K-H) solution. The descending aorta was ligated distal to the ductal insertion and the branch pulmonary arteries were ligated to mimic fetal cardiovascular physiology. Hearts were arrested for 30 minutes with normocalcemic (n = 8), hypocalcemic (n = 6), or hypercalcemic (n = 6) cold crystalloid cardioplegia before reperfusion with K-H solution. RESULTS: Compared with normocalcemic cardioplegia, hypocalcemic cardioplegia improved preservation of left ventricular (LV) systolic function (88% +/- 2.2% vs 64% +/- 15% recovery of end-systolic elastance, p = 0.02), diastolic function (12% +/- 21% vs 38% +/- 11% increase in end-diastolic stiffness, p = 0.04), and myocardial contractility (97% +/- 9.6% vs 75.2% +/- 13% recovery of preload recruitable stroke work [PRSW], p = 0.04). In contrast, the fetal myocardium was sensitive to hypercalcemic arrest with poor preservation of LV systolic function (37.5% +/- 8.4% recovery of elastance), diastolic function (86% +/- 21% increased stiffness), and overall contractility (32% +/- 13% recovery of PRSW). Myocardial water content was reduced in hearts arrested with hypocalcemic cardioplegia (79% +/- 1.8% vs 83.7% +/- 0.9%, p = 0.0006). CONCLUSIONS: This study demonstrates the sensitivity of the fetal myocardium to cardioplegic calcium concentration. Hypocalcemic cardioplegia provides superior preservation of systolic, diastolic, and contractile function of the fetal myocardium.     

Inclusion of lidocaine in cardioplegic solutions provides additional myocardial protection

AIM: Lidocaine inhibits depolarization by blocking sodium and calcium influx and potassium release, abolishing the action potentials of cells in the Hiss-Purkinje system and myocit cells. As it can directly influence cardiac electric and mechanical activities, this study evaluated the efficacy of lidocaine in providing myocardial protection during normothermic blood cardioplegia. METHODS: Twenty-six dogs were randomly assigned to groups based on the cardioplegic induction solution they were to receive. Group I dogs (n=10) received a solution consisting of lidocaine (5 mg/kg), KCL (41.6 mEq/L) and 180 ml of normothermic blood. Group II dogs (n=10) received the same solution, except for the lidocaine and group III dogs (n=6) received only normothermic blood. In addition, 120 ml of normothermic blood was reinfused every 20 min. All dogs underwent cardiopulmonary bypass, 2 hours of global myocardial ischemia and 3 hours of reperfusion. Statistical differences were determined with the chi squared test, the two-way analysis of variance and Bonferroni's test. RESULTS: There were no deaths in group I. The survival rate in group II was 60%, and no dogs in group III survived (p=0.025). No difference in lactate liberation or left ventricular function (i.e., cardiac outflow and ejection fraction) was observed between groups. However, animals in group I demonstrated less enzymatic releases (troponin I, p=0.049 and CK, p=0.026) and less mitochondrial ultrastructural changes (p=0.022). CONCLUSIONS: Lidocaine offers myocardium additional protection against ischemia during cardiopulmonary bypass.     

Adenosine cardioplegia. Adenosine versus potassium cardioplegia: effects on cardiac arrest and postischemic recovery in the isolated rat heart

Adenosine is a potential cardioplegic agent by virtue of its specific inhibitory properties on nodal tissue. We tested the hypothesis that adenosine could be more effective than potassium in inducing rapid cardiac arrest and enhancing postischemic hemodynamic recovery. Isolated rat hearts were perfused with Krebs-Henseleit buffer or cardioplegic solutions to determine the time to cardiac arrest and the high-energy phosphate levels at the end of cardioplegia. Cardioplegic solutions contained adenosine 10 mmol/L, potassium 20 mmol/L, or adenosine 10 mmol/L + potassium 20 mmol/L and were infused at a rate of 2 ml/min for 3 minutes at 10 degrees C. Both time taken and total number of beats to cardiac arrest during 3 minutes of cardioplegia were reduced by adenosine 10 mmol/L and adenosine 10 mmol/L + potassium 20 mmol/L when compared with potassium 20 mmol/L alone (p less than 0.001). Tissue phosphocreatine was conserved by adenosine 10 mmol/L when compared with potassium 20 mmol/L, being 7.1 +/- 0.2 (mumol/gm wet weight (n = 7) and 6.0 +/- 0.3 mumol/gm wet weight (n = 5), respectively (p less than 0.05). Postischemic hemodynamic recovery was tested in isolated working rat hearts. After initial cardiac arrest, the cardioplegic solution was removed with Krebs-Henseleit buffer at a rate of 2 ml/min for 3 minutes at 10 degrees C, and thereafter total ischemia was maintained for 30 or 90 minutes at 10 degrees C before reperfusion. Adenosine 10 mmol/L enhanced recovery of aortic output when compared with potassium 20 mmol/L or adenosine 10 mmol/L + potassium 20 mmol/L, the percentage recovery after 30 minutes of ischemia being 103.0% +/- 4.4% (n = 6), 89.0% +/- 5.8% (n = 6), and 86.6% +/- 4.3% (n = 6), respectively (p less than 0.05 for comparison between adenosine 10 mmol/L and potassium 20 mmol/L). Thus adenosine cardioplegia caused rapid cardiac arrest and improved postischemic recovery when compared with potassium cardioplegia and with a combination of these two agents.     

Risk of low calcium and high magnesium in continuous warm hyperkalemic cardioplegia.

BACKGROUND: The recent introduction of operations on a warm heart has prompted clinical reports on the usefulness of continuous blood cardioplegia, but no in-depth basic evaluation of continuous cardioplegia has been done. The cardioprotective effects of magnesium (Mg) and calcium (Ca) in continuous warm hyperkalemic crystalloid cardioplegic solutions were investigated in an isolated rat heart model. METHODS: Isolated rat hearts were arrested for 180 minutes at 37 degrees C with a continuous warm hyperkalemic (20 mmol/L) modified Krebs-Henseleit bicarbonate buffer solution containing 1.2, 8.0, or 16.0 mmol/L of Mg and 0.1 to 2.5 mmol/L of Ca in different concentrations. Recovery of cardiac function and tissue damage were estimated. RESULTS: For each Mg concentration, the percentage recovery of aortic flow generated dose-response curves depending on Ca concentration. However, as Mg concentration increased, the recovery of aortic flow decreased in the groups with 0.5 mmol/L of Ca or less. CONCLUSIONS: In continuous warm cardioplegia the combination of low Ca and high Mg concentration caused severe cardiac injury, and normal Ca concentration avoids cardiac injury regardless of Mg concentrations.     

Effect of oxygenated crystalloid cardioplegia on the functional and metabolic recovery of the isolated perfused rat heart

The use of an oxygenated crystalloid cardioplegic solution to improve myocardial preservation during elective cardiac arrest was evaluated with the isolated perfused rat heart used as a model. Experiments were conducted at 4 degrees C and 20 degrees C. The oxygen tension of the nonoxygenated and oxygenated cardioplegic solutions averaged 117 and 440 mm Hg, respectively. At 4 degrees C, the adenosine triphosphate content of hearts subjected to 120 minutes of oxygenated cardioplegia was significantly higher than that of the nonoxygenated cardioplegia group. However, functional recovery during reperfusion was similar for both groups. At 20 degrees C, the myocardial adenosine triphosphate concentration decreased at a significantly faster rate during ischemia in the group receiving nonoxygenated cardioplegia compared with the oxygenated cardioplegia group. Hearts subjected to 180 minutes of ischemia with oxygenated cardioplegia had a normal ultrastructural appearance whereas hearts subjected to 120 minutes of nonoxygenated cardioplegia showed severe ischemic damage. Myocardial functional recovery in the group receiving oxygenated cardioplegia exceeded that of the group receiving nonoxygenated cardioplegia. The use of myocardial adenosine triphosphate concentration at the end of the ischemic period to predict subsequent cardiac output, peak systolic pressure, and total myocardial work showed significant positive correlations.     

Cardiac function and myocardial performance of 24-hour-preserved asphyxiated canine hearts.

A method of 24-hour storage of asphyxiated canine hearts for orthotopic cardiac transplantation was studied to expand the geographical size of the donor pool. Left ventricular function of asphyxiated hearts preserved for 24 hours (group 1, n = 8) was compared with that of hearts donated on-site (group 2, n = 5). Group 1 donors were pretreated with verapamil hydrochloride, propranolol hydrochloride, and prostacyclin. The donor hearts were perfused with warm blood cardioplegia in situ after 10 minutes of asphyxiation and then perfused with cold crystalloid cardioplegia for 2 hours. The hearts were excised and stored in ice-cold University of Wisconsin solution for 22 hours. At orthotopic transplantation, coronary perfusion with warm blood cardioplegia was performed before the graft aorta was unclamped. Conventional cardiac variables (eg, cardiac output and maximum rate of rise of left ventricular pressure), myocardial performance, and diastolic compliance of grafted hearts were assessed 1 hour after weaning from bypass. All recipients in both groups were easily weaned from cardiopulmonary bypass without inotropic agents, and there were no significant differences in cardiac variables between the two groups. These results strongly suggest that cadaver hearts can be preserved for 24 hours with satisfactory cardiac function.