Difference in the mechanical response to a cardioplegic solution observed between the neonatal and the adult guinea pig myocardium

We attempted in two types of preparations to delinate the difference in responses to St. Thomas' Hospital cardioplegic solution between the neonatal and the adult guinea pig myocardium. Isolated guinea pig hearts were perfused with Langendorff's method and the tension of the papillary muscle of the right ventricle was recorded. Continuous infusion of St. Thomas' Hospital cardioplegic solution (37 degrees C) for 30 minutes resulted in a significantly higher elevation of the resting tension (development of contracture) in the neonatal myocardium than in the adult. The recovery of normal contractile tension after the resumption of perfusion with normal Krebs-Ringer bicarbonate solution was smaller in the neonate with increases in the myocardial water and calcium contents. The membrane potential of the papillary muscle preparation was recorded by means of conventional glass microelectrodes. There was no significant difference in the control values of the resting membrane potential and in the degree of depolarization during exposure to St. Thomas' Hospital cardioplegic solution between the neonate and the adult. Thus the greater elevation of the resting tension produced in the neonatal myocardium by St. Thomas' Hospital cardioplegic solution was not due to a greater depolarization of the surface membrane.     

Interactions between pharmacological cardioplegia and hypothermia for intraoperative myocardial protection

Cold cardioplegia is currently the method of choice for providing myocardial protection during open-heart surgical procedures. Two components of protection, perfusion cooling and pharmacological cardiac arrest, were investigated in the guinea pig heart-lung model. The effects of two cardioplegic solutions, the University of Alabama Hospital solution and the St. Thomas' Hospital solution, and a control perfusate were compared. The results confirmed the efficacy of hypothermia as a protective agent and the additional protection afforded by pharmacological cardioplegia. Infusion temperature critically influenced the cardioprotective action of the Alabama solution: Striking protection was afforded only under hypothermic conditions, whereas myocardial damage was exacerbated by the infusion at 37 degrees C. The St. Thomas' Hospital solution provided substantial protection independent of infusion temperature. Thus, the safety margin of the Alabama solution was narrower than that of the St. Thomas' solution. It is suggested that the difference between the two cardioplegic solutions partially depends on their coronary vasoactivity, since the administration of the Alabama solution at 37 degrees C increased coronary perfusion pressure. It would seem worthwhile to use a temperature-independent cardioplegic solution devoid of coronary vasoconstricting action.     

Long-term preservation of explanted hearts perfused with L-aspartate-enriched cardioplegic solution. Improved function, metabolism, and ultrastructure.

The effects of supplementing oxygenated St. Thomas' Hospital cardioplegic solution No. 2 with L-aspartate and/or D-glucose for the long-term preservation of excised rat hearts were determined with isolated working heart preparations. Left ventricular function was assessed at 37 degrees C with a crystalloid perfusate, before cardioplegic arrest and after 20 hours of low-flow perfusion (1.5 ml/min) with continuing arrest at 4 degrees C, and after this period, again at 37 degrees C with a crystalloid perfusate. Four groups (n = 8/group) of hearts were studied with four cardioplegic solutions: St. Thomas' Hospital solution alone, St. Thomas' Hospital solution with aspartate 20 mmol/L, St. Thomas' Hospital solution with glucose 20 mmol/L, and St. Thomas' Hospital solution plus both aspartate and glucose (20 mmol/L each). The addition of glucose to St. Thomas' Hospital solution made no significant difference in the recovery of aortic flow rates (17.7% +/- 8.6% and 21.6% +/- 7.8% of prearrest values), but when aspartate or aspartate and glucose were present, hearts showed significant improvements (89.8% +/- 5.2% and 85.0% +/- 6.2%, respectively). These improvements were associated with a reduction in the decline of myocardial high-energy phosphates during reperfusion, a reduction in cellular uptake of Na+ and Ca++, and a reduction in ultrastructural damage. These results indicate that low-flow perfusion with St. Thomas' Hospital solution plus aspartate can considerably extend the duration of safe storage of explanted hearts.     

Protection of the immature myocardium during global ischemia. A comparison of four clinical cardioplegic solutions in the rabbit heart

Controversy surrounds the reported beneficial effects of crystalloid cardioplegic solutions in the immature myocardium. In the present study we have investigated the efficacy of four clinical cardioplegic solutions in the immature myocardium to determine (1) whether cardioplegic protection could be demonstrated and, if so, (2) the relative efficacy of the four solutions. Isolated, working hearts (n = 6 per group) from neonatal rabbits (aged 5 to 8 days) were perfused aerobically (37 degrees C) for 20 minutes before a 2-minute infusion of one of four cardioplegic solutions: The St. Thomas' Hospital No. 2, Tyers, Bretschneider, and Roe solutions. Hearts were then rendered globally ischemic for 50 minutes at 37 degrees C before reperfusion for 15 minutes in the Langendorff mode and 20 minutes in the working mode. The postischemic recovery of cardiac function and leakage of creatine kinase were compared with results in noncardioplegic control hearts. Good protection was observed with the St. Thomas' Hospital and Tyers solutions: The postischemic recovery of cardiac output was increased from 21.2% +/- 12.7% in the cardioplegia-free group to 79.4% +/- 6.2% and 72.9% +/- 4.4%, respectively, in the St. Thomas' Hospital and Tyers groups (p less than 0.01). In contrast, no protection was observed with either the Bretschneider or Rose solutions: Cardiac output recovered to 31.7% +/- 10.3% and 5.1% +/- 3.2%, respectively, in these groups. Postischemic creatine kinase leakage was 72.4 +/- 12.3 and 92.1 +/- 18.6 IU/15 min/gm dry weight in the St. Thomas' Hospital and Tyers groups compared with 125.6 +/- 28.6 IU/15 min/gm dry weight in control hearts (p = no significant difference). In the Bretschneider group, creatine kinase leakage increased to 836.9 +/- 176.8 IU/15 min/gm dry weight (p less than 0.01 versus noncardioplegic control hearts), and with the Roe solution the value was 269.0 +/- 93.0 IU/15 min/gm dry weight (p = no significant difference). In conclusion, cardioplegic protection can be achieved in the immature rabbit myocardium with both St. Thomas' Hospital and Tyers solutions, but acalcemic solutions such as Bretschneider and Roe solutions (which may be effective in the adult heart) increased damage in this preparation. The reported lack of cardioplegic efficacy in the immature myocardium may therefore reflect the choice of cardioplegic solution rather than a greater vulnerability to injury in the neonatal heart.     

Mechanisms of myocardial protection by adenosine-supplemented cardioplegic solution: myofilament and metabolic responses

OBJECTIVE: Adenosine supplementation of cardioplegic solutions in cardiac operations improves postarrest myocardial recovery after cardioplegic arrest and reperfusion; however, the mechanism of the action of adenosine remains unknown. We tested the hypotheses that adenosine-supplemented cardioplegic solution improves myofibrillar protein cooperative interaction and increases myocardial anaerobic glycolysis. METHODS: The hearts of male Sprague-Dawley rats were randomized to undergo 120 minutes of cardioplegic arrest with 1 of 3 cardioplegic solutions: (1) St Thomas' Hospital No. 2 cardioplegic solution (St Thomas group), (2) St Thomas' Hospital No. 2 cardioplegic solution plus adenosine (100 micromol/L) (adenosine group), and (3) St Thomas' Hospital No. 2 cardioplegic solution plus adenosine (100 micromol/L) plus the nonspecific adenosine receptor antagonist 8-p -sulfophenyltheophylline (50 micromol/L) (sulfophenyltheophylline group). A fourth group of hearts underwent no cardioplegic arrest. RESULTS: Systolic and diastolic functional recovery was improved in the adenosine group compared with that in the other two groups, independent of coronary flow. Adenosine supplementation of cardioplegic solution prevented the decrease in myofibrillar protein cooperative interaction seen after cardioplegic arrest and reperfusion (St Thomas and sulfophenyltheophylline groups). Adenosine-supplemented cardioplegic solution also caused significantly increased anaerobic glycolysis during cardioplegic arrest. These responses were blocked in the sulfophenyltheophylline group. CONCLUSIONS: The changes in myocardial glycolytic activity and myofilament cooperativity coincided with functional recovery in the three cardioplegia groups and may represent mechanisms underlying protection with adenosine-supplemented cardioplegic solution.     

Enhancement of crystalloid cardioplegic protection against global normothermic ischemia by superoxide dismutase plus catalase but not diltiazem in the isolated, working rat heart

Oxygen-derived free radicals and intracellular calcium overload have been implicated as mediators of myocardial ischemia/reperfusion injury. We hypothesized that free radical scavengers or calcium channel blockers could enhance the protection afforded the isolated, working rat heart by crystalloid cardioplegia against this type of injury at 37 degrees C. Hearts from 42 male rats in seven groups (n = 6) were studied in an isolated, working heart preparation measuring aortic flow (ml/min/gm dry wt), peak systolic pressure (mm Hg), coronary artery flow (ml/min/gm dry wt), and calculated coronary vascular resistance (dyne.sec.cm-5/gm dry wt). Creatine kinase and lactate dehydrogenase release were measured before ischemia and at various times during the postischemic reperfusion period. Time-matched control hearts (group 1) were perfused for 2 hours. After finding that 30 minutes of ischemia and 10 minutes of reperfusion (group 2) produced significant (p less than 0.01) functional impairment that was completely protected (group 3) by a preischemic bolus of St. Thomas' Hospital cardioplegic solution, we again found significant (p less than 0.01) functional impairment after 40 minutes of ischemia and 10 minutes (group 4) or 20 minutes (group 5) of reperfusion despite a preischemic bolus of St. Thomas' Hospital cardioplegic solution. Diltiazem (10 mg/L) plus St. Thomas' Hospital cardioplegic solution (group 6) did not significantly (p less than 0.01) enhance functional recovery. Addition of superoxide dismutase plus catalase (200 microns/ml) (group 7) produced marked improvement in functional recovery that did not differ significantly (p less than 0.01) from control results (group 1). The creatine kinase and lactate dehydrogenase data strongly supported the preceding functional data. Coronary flow and vascular resistance were not significantly (p less than 0.01) changed from control values in any group. We conclude that the addition of superoxide dismutase and catalase but not diltiazem to St. Thomas' Hospital cardioplegic solution can significantly enhance myocardial protection against normothermic ischemia/reperfusion injury. This implicates oxygen-derived free radicals as mediators of this type of injury.     

St. Thomas' Hospital cardioplegic solution. Beneficial effect of glucose and multidose reinfusions of cardioplegic solution

The intention of this study was to determine whether glucose is beneficial in a cardioplegic solution when the end products of metabolism produced during the ischemic period are intermittently removed. The experimental model used was the isolated working rat heart, with a 3-hour hypothermic 10 degrees C cardioplegic arrest period. Cardioplegic solutions tested were the St. Thomas' Hospital No. 2 and a modified Krebs-Henseleit cardioplegic solution. Glucose (11 mmol/L) was beneficial when multidose cardioplegia was administered every 30 minutes. Including glucose in Krebs-Henseleit cardioplegic solution improved postischemic recovery of aortic output from 57.0% +/- 1.8% to 65.8% +/- 2.2%; p less than 0.025. The addition of glucose to St. Thomas' Hospital No. 2 cardioplegic solution improved aortic output from 74.6% +/- 1.9% to 87.4% +/- 1.9%; p less than 0.005. Furthermore, a dose-response curve showed that a glucose concentration of 20 mmol/L gave no better recovery than 0 mmol/L, and glucose in St. Thomas Hospital No. 2 cardioplegic solution was beneficial only in the range of 7 to 11 mmol/L. In addition, we showed that multidose cardioplegia was beneficial independent of glucose. Multidose St. Thomas' Hospital No. 2 cardioplegia, as opposed to single-dose cardioplegia, improved aortic output recovery from 57.4% +/- 5.2% to 74.6% +/- 1.9%; p less than 0.025, and with St. Thomas' Hospital No. 2 cardioplegic solution plus glucose (11 mmol/L) aortic output recovery improved from 65.9% +/- 2.9% to 87.4% +/- 1.9%; p less than 0.005. Hence, at least in this screening model, the St. Thomas' Hospital cardioplegic solution should contain glucose in the range of 7 mmol/L to 11 mmol/L, provided multidose cardioplegia is given. We cautiously suggest extrapolation to the human heart, on the basis of supporting clinical arguments that appear general enough to apply to both rat and human metabolisms.     

Myocardial protection of neonatal heart by cardioplegic solution with recombinant human superoxide dismutase.

The effectiveness of high-potassium cardioplegic solution in the neonatal heart remains controversial. Our previous study indicated that the protection afforded by a cardioplegic solution was inadequate in the neonatal heart. On the hypothesis that oxyradicals were responsible for the ineffectiveness of cardioplegic solution in neonatal heart, the effects of a cardioplegic solution (a modified St. Thomas' Hospital cardioplegic solution) with recombinant human superoxide dismutase on the isolated perfused neonatal guinea pig hearts (within 2 days after delivery, body weight of 60 to 120 g) were studied in comparison with those on the adult hearts (6 to 8 weeks after delivery, body weight of 300 to 500 g). After arrest induced by modified St. Thomas' Hospital cardioplegic solution, hearts were subjected to 120 min of ischemia at 20 degrees C, during which time the cardioplegic solution was injected every 30 minutes. Then the heart was reperfused for 60 minutes at 37 degrees C. Under this condition, the left ventricular developed pressure recovered to 84.4% +/- 4.0% of the preischemic value in the adult heart, whereas the recovery was only 68.1% +/- 3.1% in the neonatal heart. Thiobarbituric acid-reactive substance level, a parameter of lipid peroxidation by oxyradicals, significantly increased during ischemic arrest both in the adult and neonatal heart. However, the increase was much greater in the neonatal heart than in the adult. Cardioplegia with recombinant human superoxide dismutase (300 and 1,000 U/mL) significantly inhibited this accumulation of thiobarbituric acid-reactive substance in the neonatal heart; at 1,000 U/mL, the myocardial function of the reperfused neonatal heart recovered to the level of the adult heart.(ABSTRACT TRUNCATED AT 250 WORDS)     

Absence of particle-induced coronary vasoconstriction during cardioplegic infusion: is it desirable to use a microfilter in the infusion line?

Many cardiac surgical units now use a microfilter in the infusion line for delivery of crystalloid cardioplegic solution to protect against the potential hazards of particulate contamination of cardioplegic solution. The aim of this group of studies was to determine the effects of particulate contamination of cardioplegic solutions, in order to establish whether a microfilter is needed in the infusion line. Total particle counts performed on two commercial cardioplegic solutions were low, but there were sufficient particles greater than 10 microns in diameter to cause coronary vasoconstriction. In isolated rat hearts a 20-minute infusion of St. Thomas' Hospital cardioplegic solution produced a progressive reduction in coronary flow, which was not prevented by the inclusion of a 0.8 micron filter in the infusion line. Two studies were performed on canine hearts to determine the effects of unfiltered cardioplegic solution on coronary vascular resistance. In the first, cardioplegic solution at 20 degrees C was infused for 20 minutes at a constant pressure of 50 mm Hg and flow rate was measured. In the second, the same solution at 4 degrees C was infused at a constant flow rate for 2 1/2 minutes and the infusion pressure was measured. In neither study did coronary vascular resistance rise. A final clinical study involving patients undergoing coronary bypass surgery compared the effects on coronary resistance of infusion at a constant flow of filtered versus unfiltered cardioplegic solution (n = 10 in each group). There was a similar rise in coronary perfusion pressure in both groups during the infusion. We conclude that there is insufficient evidence of particle-induced coronary vasoconstriction to justify the expense of a microfilter in the cardioplegic infusion line.     

Lowering the calcium concentration in St. Thomas' Hospital cardioplegic solution improves protection during hypothermic ischemia

The concentration of calcium (1.2 mmol/L) in clinical St. Thomas' Hospital cardioplegic solution was chosen several years ago after dose-response studies in the normothermic isolated heart. However, recent studies with creatine phosphate in St. Thomas' Hospital solution demonstrated that additional myocardial protection during hypothermia resulted principally from its calcium-lowering effect in the solution. The isolated working rat heart model was therefore used to establish the optimal calcium concentration in St. Thomas' Hospital solution during lengthy hypothermic ischemia (20 degrees C, 300 minutes). The calcium content of standard St. Thomas' Hospital solution was varied from 0.0 to 1.5 mmol/L in eight treatment groups (n = 6 for each group). During ischemia, hearts were exposed to multidose cardioplegia (3 minutes every 30 minutes). Postischemic recovery of function was expressed as a percentage of preischemic control values. Release of creatine kinase and the time to return of sinus rhythm during the reperfusion period were also measured. These dose-response studies during hypothermic ischemia revealed a broad range of acceptable calcium concentrations (0.3 to 0.9 mmol/L), which appear optimal in St. Thomas' Hospital solution at 0.6 mmol/L. This concentration improved the postischemic recovery of aortic flow from 22.0% +/- 5.9% with control St. Thomas' Hospital solution (calcium concentration 1.2 mmol/L) to 86.0% +/- 4.0% (p less than 0.001). Other indices of functional recovery showed similar dramatic results. Creatine kinase release was reduced 84% (p less than 0.01) in the optimal calcium group. Postischemic reperfusion arrhythmias were diminished with the loser calcium concentration, with a significant decrease in the time between initial reperfusion until the return of sinus rhythm. In contrast, acalcemic St. Thomas' Hospital solution precipitated the calcium paradox with massive enzyme release and no functional recovery. Unlike prior published calcium dose-response studies at normothermia, these results demonstrate that the optimal calcium concentration during clinically relevant hypothermic ischemia is considerably lower than that of normal serum ionized calcium (1.2 mmol/L) and appears ideal at 0.6 mmol/L to realize even greater cardioprotective and antiarrhythmic effects with St. Thomas' Hospital solution.     

Functional and metabolic protection of the neonatal myocardium from ischemia. Insufficient protection by cardioplegia

The effects of ischemia and cardiac arrest by cardioplegia on the mechanical function and energy metabolism of the ventricular myocardium of the neonatal guinea pig were investigated in the isolated perfused heart preparation and compared with these effects in the adult guinea pig. Whereas reperfusion after ischemia resulted in better recovery of mechanical function and a higher adenosine triphosphase content in the neonatal myocardium than in the adult, recovery from cardiac arrest induced by St. Thomas' Hospital cardioplegic solution was not as good in the neonatal myocardium as in the adult. Contracture developed in the neonatal myocardium on administration of the cardioplegic solution, but did not in the adult. This was considered to be the reason that the protective effect of the cardioplegic solution was inferior in the neonatal myocardium to that in the adult.     

Role played by oxygen in myocardial protection with crystalloid cardioplegic solution

To evaluate the importance of the oxygen dissolved in crystalloid cardioplegic solution, the protective effects of oxygenated glucose-insulin-potassium cardioplegic solution (O2-GIK) (oxygen tension greater than 600 mm Hg) on the isolated working guinea pig heart were compared with those of deoxygenated (N2-GIK) (oxygen tension less than 10 mm Hg) and aerated GIK solution (GIK) (oxygen tension = 140 to 160 mm Hg). Hearts were subjected to 180 minutes of ischemia with intermittent infusions (every 30 minutes) of cold cardioplegic solution, followed by 30 minutes of normothermic reperfusion. The O2-GIK solution tended to maintain high-energy phosphates at higher levels during ischemia, and resulted in the best recovery of cardiac function. Though not as effective as O2-GIK, GIK solution produced protective effects; N2-GIK solution failed to exert such effects. These results strongly suggest that the protective effects of crystalloid cardioplegic solution are due primarily to the oxygen dissolved in it; anaerobic metabolism or washout of the metabolites plays a minor part.     

Comparison of myocardial protective effects between GIK solution and St. Thomas solution by use of canine isolated heart-lung preparations

The myocardial protection afforded by GIK solution, widely used as cardioplegic solution in this country, was compared with that provided by St. Thomas solution or oxygenated St. Thomas solution. Eighteen isolated heart-lung preparations of dogs were made and their hearts were subjected to 3 hours cold (4 degrees C) cardioplegic arrest. GIK group hearts (n = 6) received 20 ml/kg of GIK solution at the time of aortic cross-clamp perfused through the aortic root and were subsequently given 10 ml/kg of GIK solution every 30 minutes. St. Thomas group hearts (n = 6) and oxygenated St. Thomas group hearts (n = 6) were treated identically except that cardioplegic solution were St. Thomas solution or fully oxygenated one. Four hearts of GIK group showed ventricular fibrillation immediately after reperfusion that required DC countershock. Temporary A-V block was recognized in two hearts. In the other two groups, however, neither ventricular fibrillation nor A-V block was found. Heart rate, coronary flow, aortic flow and LVSW were measured before arrest and after 60 minutes of reperfusion (mean aortic pressure 70 mmHg, left atrial pressure 4 mmHg). Post reperfusion % recovery rates (post-reperfusion/before arrest) of heart rate, coronary flow, aortic flow and LVSW (mean value +/- standard deviation) were 93.4 +/- 10.32%, 104.6 +/- 24.91%, 18.8 +/- 8.54%, 32.6 +/- 6.12% respectively for GIK group, 81.4 +/- 6.50%, 125.9 +/- 15.23%, 35.4 +/- 9.91%, 56.3 +/- 12.90% for St. Thomas group and 83.1 +/- 8.40%, 121.6 +/- 16.92%, 47.0 +/- 7.89%, 69.1 +/- 9.71% for oxygenated St. Thomas group. St. Thomas and oxygenated St. Thomas groups revealed significantly (p less than 0.05, p less than 0.01 respectively) more excellent functional preservation than GIK group. Intramyocardial pH was also measured by use of glass needle pH electrode punctured into the anterior interventricular septum. Preischemic intramyocardial pH (at 37 degrees C) was 7.49 +/- 0.106 in GIK group, 7.48 +/- 0.113 in St. Thomas group and 7.43 +/- 0.114 in oxygenated St. Thomas group. During 3 hours of cardioplegic arrest, intramyocardial pH (at 4 degrees C) decreased to 6.84 +/- 0.101 in GIK group, 7.03 +/- 0.088 in St. Thomas group and 7.23 +/- 0.239 in oxygenated St. Thomas group, which was significantly higher than GIK group (p less than 0.01). Therefore oxygenated St. Thomas solution was found to maintain more favorable energy supply to ischemic myocardium. These results clearly evidenced that St. Thomas and oxygenated St. Thomas solutions would provide more effective myocardial protection during ischemic arrest than GIK solution.     

Age-related effects of St Thomas' Hospital cardioplegic solution on isolated cardiomyocyte cell volume.

OBJECTIVES: We tested the hypothesis that neonatal cells are more sensitive to cardioplegia-induced cell swelling than more mature cells and spontaneous swelling in the absence of ischemia can be prevented by cardioplegia with a physiologic KCl product. METHODS: Cell volumes of isolated ventricular myocytes from neonatal (3-5 days), intermediate (10-13 days), and adult (>6 weeks) rabbits were measured by digital video microscopy. After equilibration in 37 degrees C physiologic solution, cells were suprafused with 37 degrees C or 9 degrees C St Thomas' Hospital solution (standard or low Cl(-)) or 9 degrees C physiologic solution followed by reperfusion with 37 degrees C physiologic solution. RESULTS: Neonatal cells swelled 16.2% +/- 1.8% (P <.01) in 37 degrees C St Thomas' Hospital solution and recovered during reperfusion, whereas more mature cells maintained constant volume. In contrast, 9 degrees C St Thomas' Hospital solution caused significant age-dependent swelling (neonatal, 16.8% +/- 1.5%; intermediate, 8.6% +/- 2.1%; adult, 5.6% +/- 1.1%). In contrast to more mature cells, neonatal cells remained significantly edematous throughout reperfusion (8.1% +/- 1.5%). Swelling was not due to hypothermia because 9 degrees C physiologic solution did not affect volume. Lowering the KCl product of St Thomas' Hospital solution by partially replacing Cl(-) with an impermeant anion prevented cellular edema in all groups. CONCLUSION: In the absence of ischemia, neonatal cells were more sensitive to cardioplegia-induced cellular edema than more mature cells, and edema observed in all groups was avoided by decreasing the KCl product of St Thomas' Hospital solution to the physiologic range. Differences in cell volume regulation may explain the sensitivity of neonatal hearts to hyperkalemic cardioplegic arrest and suggest novel approaches to improving myocardial protection.     

Harvesting hearts for long-term preservation. Detrimental effects of initial hypothermic infusion of cardioplegic solutions

Current procedure for harvesting human donor hearts for long-term storage before transplantation involves direct infusion of a hypothermic (4 degrees C) crystalloid cardioplegic solution into the normothermic (37 degrees C) heart in situ. We used the isolated perfused working rat heart preparation to investigate whether infusing cold crystalloid solutions into normothermic blood-containing hearts was consistent with maximal myocardial protection. Hearts (n = 6 per group) were excised and subjected to a primary (1 minute) infusion with either the St. Thomas' Hospital cardioplegic solution or a bicarbonate buffer solution, at 7.5 degrees C, 22 degrees C, or 37 degrees C. This was followed by a secondary infusion (2 minutes) with cold (7.5 degrees C) cardioplegic solution, after which all hearts were stored at 7.5 degrees C for 6 hours and then reperfused at 37 degrees C for 60 minutes, during which time creatine kinase leakage and cardiac function were measured. Primary infusion with warm solutions resulted in (1) decreased coronary vascular resistance during cardioplegic infusion and (2) greater postischemic cardiac function. This suggests that their use, before the standard cold infusion, might be beneficial to the long-term preservation of transplant donor hearts.     

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

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

Comparison of three cardioplegic solutions during hypothermic ischemic arrest in neonatal blood-perfused rabbit hearts

Inadequate myocardial preservation continues to be an important cause of postoperative morbidity and mortality after pediatric cardiac operations. To investigate methods of improving preservation in neonatal myocardium, we compared three cardioplegic solutions with topical hypothermia during 120 minutes of ischemic arrest in isolated, blood-perfused, neonatal rabbit hearts. Topical hypothermia (15 degrees C) without cardioplegia resulted in 71% +/- 5% recovery of preischemic contractile function. A high potassium (30 mEq/L) cardioplegic solution resulted in a 76% +/- 6% recovery of function, not significantly different from that obtained with hypothermia alone. In contrast, the St. Thomas' Hospital and H?pital Lariboisiere cardioplegic solutions resulted in recoveries of 89% +/- 6% and 88% +/- 7%, respectively, both of which were significantly greater (p less than 0.001) than recoveries obtained with the high potassium solution or hypothermia alone. Thus the cardioplegic solutions used at St. Thomas' Hospital and H?pital Lariboisiere provided excellent protection during 2 hours of hypothermic ischemic arrest in neonatal rabbit hearts and resulted in functional recovery superior to that achieved with hypothermia alone or with the high potassium cardioplegic solution.     

L-aspartate improves the functional recovery of explanted hearts stored in St. Thomas' Hospital cardioplegic solution at 4 degrees C

Explanted rat hearts were subjected to cardioplegic arrest by 3 minutes' perfusion with oxygenated St. Thomas' Hospital solution no. 2 and then were stored by immersion in the same solution at 4 degrees C. Prearrest and postischemic left ventricular functions were compared by means of an isolated working heart apparatus. Hearts (n = 8 per group) arrested and stored for up to 8 hours all resumed the spontaneous rhythm of contraction during reperfusion for 30 minutes at 37 degrees C. There was good recovery of aortic flow rate (105% +/- 3%) against a pressure of 100 cm H2O, of heart rate (102% +/- 2%), and of aortic pressure (86% +/- 5% of prearrest values). Hearts stored for 10 and 20 hours showed poor or no postischemic recovery of cardiac pump function (aortic flow, 16% +/- 11% and 0%, respectively). Enrichment of St. Thomas' Hospital solution with L-glutamate (20 mmol/L) also failed to improve functional recovery of hearts subjected to 10 hours of storage, but hearts treated with St. Thomas' Hospital solution containing L-aspartate (20 mmol/L) or L-aspartate plus L-glutamate (20 mmol/L each) reestablished aortic flow rates of 99% +/- 5% and 93% +/- 4%, respectively. These results indicate that the addition of L-aspartate to St. Thomas' Hospital solution improves the functional recovery and extends the safe preservation of explanted hearts stored at 4 degrees C.     

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.     

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.