Clinical validation of St. Thomas' Hospital cardioplegic solution No. 2 (Plegisol)

Recently, the St. Thomas' Hospital cardioplegic solution No. 2 (Plegisol) has become available commercially in the UK. In a series of patients (n = 28) undergoing open heart surgery for a variety of lesions, a clinical validation was performed. Preservation of myocardial contractility was assessed biophysically by quantitative birefringence measurements of myocardial biopsy samples (full thickness apical left ventricle and right ventricle) taken (1) prior to ischaemia, (2) at the end of ischaemia and (3) 10-15 min after reperfusion during cardiopulmonary bypass. In addition, serum CK-MB values were measured in samples taken throughout the operation and for 4 days postoperatively. Postoperative ECG traces (taken every 6 h for 48 h and then daily up to 7 days) were analysed to identify the occurrence of perioperative infarction. There were no hospital deaths. Chronotropic support was required in 5 of 28 patients (18%) for transient heart block. Low cardiac output did not occur postoperatively. Birefringence measurements in biopsy samples taken at the end of the ischaemic period (immediately prior to reperfusion) indicated an apparent left ventricular deterioration in myocardial contractility in 12 of 28 patients (43%) when compared to biopsies sampled prior to the ischaemic period. However, after 10-15 min of aerobic reperfusion, measurements indicated that myocardial contractility recovered to almost pre-ischaemic levels in the majority of patients. Thus, in 22 of 28 patients (79%), left ventricular deterioration did not occur in post-ischaemic biopsy samples when compared to the pre-ischaemic biopsies. Similarly, 21 of 28 patients (75%) had no deterioration of birefringence values in right ventricular biopsies.(ABSTRACT TRUNCATED AT 250 WORDS)     

The St. Thomas' Hospital cardioplegic solution. A comparison of the efficacy of two formulations

Two commercially available formulations of St. Thomas' Hospital cardioplegic solutions, known as No. 1 (MacCarthy) and No. 2 (Plegisol, Abbott Laboratories, North Chicago, Ill.), were compared in the isolated working rat heart subjected to a long period (3 hours) of hypothermic ischemic arrest with multidose infusion. Solution No. 2 was found to be superior in nearly all respects. Of the 10 hearts infused with solution No. 1, persistent ventricular fibrillation during postischemic reperfusion occurred in six. Two of the six hearts, still in fibrillation after 15 minutes of reperfusion, were returned to regular rhythm by electrical defibrillation but failed to maintain an output. In contrast, in the 10 hearts infused with solution No. 2, ventricular fibrillation was short lasting (p less than 0.01). In comparing mechanical function in all hearts returning to regular rhythm (either spontaneously or after electrical defibrillation), the mean postischemic recoveries for aortic flow and rate of rise of left ventricular pressure (expressed as a percentage of its preischemic control) were significantly greater with solution No. 2 than with solution No. 1 (74.3% +/- 6.9% compared with 18.7% +/- 8.9%, p less than 0.01, and 98.0% +/- 6.0% compared with 63.0% +/- 9.0%, p less than 0.005, respectively). Creatine kinase leakage tended to be lower in hearts infused with solution No. 2 (19.7 +/- 4.7 IU/15 min/gm dry weight as opposed to 27.5 +/- 4.7 IU/15 min/gm dry weight), although this difference did not achieve a level of statistical significance. Consideration is given to the differences in formulation between solutions, which might account for the improved performance with solution No. 2, and it is concluded that the lower calcium content of solution No. 2 (1.2 as opposed to 2.4 mmol/L) is likely to be the most important factor.     

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.     

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.     

Effect of oxygenation and consequent pH changes on the efficacy of St. Thomas' Hospital cardioplegic solution

The hypothesis tested is that shifts in pH, induced when a cardioplegic solution is oxygenated, can be detrimental. We added either 100% nitrogen, 95% nitrogen and 5% carbon dioxide, 100% oxygen, or 95% oxygen and 5% carbon dioxide to the cardioplegic solution (St. Thomas' Hospital No. 2 plus glucose 11 mmol/L), and determined postischemic recovery of isolated rat hearts after 3 hours of 10 degrees C cardioplegic protected ischemia. Hearts were arrested and reinfused every 30 minutes throughout the ischemic period with cardioplegic solution. When 5% carbon dioxide was added to nitrogen, the pH of the cardioplegic solution decreased from 9.1 (100% nitrogen) to 7.0 (95% nitrogen: 5% carbon dioxide), a change associated with improved postischemic functional recovery. Aortic output improved from 52.3% +/- 2.7% to 63.9% +/- 2.8%, p less than 0.05, and cardiac output from 60.8% +/- 3.6% to 75.4% +/- 3.3%, p less than 0.01. This improvement was associated with diminished efflux of lactate during ischemia but increased postischemic release of lactate dehydrogenase. When nitrogen was replaced with oxygen, the addition of 5% carbon dioxide resulted in a similar decrease of pH, which again was associated with improved postischemic functional recovery. Aortic output improved from 66.3% +/- 2.8% (100% oxygen) to 88.9% +/- 3.7% (95% oxygen: 5% carbon dioxide), p less than 0.005, and cardiac output from 75.3% +/- 4.1% to 88.9% +/- 2.4%, p less than 0.01. The efflux of lactate during ischemia and the postischemic release of lactate dehydrogenase were similar in both groups. Furthermore, provision of additional oxygen with perfluorocarbons in an electrolyte solution identical to the St. Thomas' Hospital plus glucose solution and oxygenated with 95% oxygen: 5% carbon dioxide conferred no extra protection. In conclusion, the St. Thomas' Hospital No. 2 plus glucose cardioplegic solution should be oxygenated but with 95% oxygen: 5% carbon dioxide and not 100% oxygen because of the additive effect of a relatively "acidotic" pH.     

31P-NMR study of cardiac preservation: St. Thomas' Hospital cardioplegic solution versus UW preservation solution

Ex vivo cardiac preservation was evaluated by measuring the catabolism of high-energy phosphate (ATP and creatine phosphate, CrP) using ³¹P-NMR spectroscopy. After cardioplegic arrest St. Thomas' Hospital cardioplegic solution (group A), and University of Wisconsin (UW) preservation solution (group B) were tested. The hearts were mounted in the 4.7 T horizontal bore magnet of the NMR spectrometer and were continuously perfused with the test solution under 25 cm H₂O pressure for 6 h at 10°C. Peak heights of the -phosphate of ATP and CrP were measured and expressed as percentages of the initial value. For both group A and group B, ATP declined less rapidly during preservation than CrP. In group A, ATP remained constant for 60 min while CrP decreased from the onset of preservation. After 6h of preservation 28.3% of ATP and 24.5% of CrP remained (group A). On the other hand, in group B, levels of both ATP and CrP remained much more stable: CrP did not decrease during the first 3 h of preservation, while ATP started to decrease after 5 h. At the end of preservation 76.1% of ATP and 71.5% of CrP were still present. We conclude that UW solution is superior to St. Thomas' Hospital solution for the preservation of high-energy phosphates during 6 h cardiac preservation with continuous hypothermic low-flow perfusion.     

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.     

Creatine phosphate (Neoton) as an additive to St. Thomas' Hospital cardioplegic solution (Plegisol). Results of a clinical study

Experimentally, creatine phosphate (CP) added to St. Thomas' Hospital cardioplegic solution (STH) improved post-ischaemic recovery of cardiac function in the rat heart. We investigated the effect of adding CP (10.0 mmol/l) to STH. Fifty open-heart surgery patients were randomized into control (STH) and treated (STH + CP) groups (25 per group). Patients underwent (a) monitoring for peri- and postoperative arrhythmias (48-h Holter monitoring). (b) quantitative birefringence assessment of intraoperative myocardial protection in left and right ventricular biopsies sampled at start of bypass (pre-isch.), end of bypass (end-isch.) and after 10 min reperfusion (post-isch.), and (c) measurement of serum creatine kinase-MB isozyme (CK-MB) values for up to 4 days postoperatively; results were assessed with respect to (d) haemodynamics and postoperative clinical outcome. Inotropic support (adrenaline) was required in three patients (12%) from each group; no patient died. All patients required defibrillation, and the number of direct current shocks required for sinus rhythm was the same in each group. The occurrence and incidence of reperfusion-induced arrhythmias were the same in both groups. Serum CK and CK-MB values were similar throughout the sampling period in both groups of patients; one patient in the control group had raised CK-MB levels postoperatively, but perioperative infarction was not indicated by the electrocardiogram.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of standard (non-oxygenated) vs. oxygenated St. Thomas' Hospital cardioplegic solution No. 2 (Plegisol)

Recent studies have suggested that oxygenation of crystalloid cardioplegic solutions improves myocardial preservation. To assess whether oxygenation of St. Thomas' Hospital cardioplegic solution No. 2 (Plegisol) improves its clinical efficacy, 50 patients were randomly assigned into 2 groups: (1) those receiving Plegisol and (2) those receiving O2-Plegisol (PO2 greater than 500 mmHg at 4 degrees C). Efficacy was assessed by (a) clinical and haemodynamic parameters, (b) quantitative birefringence changes in response to ATP and calcium as a measurement of myocardial preservation in left and right ventricular biopsies, (c) creatine kinase (MB isoenzyme) release for up to 4 days postoperatively, (d) electrocardiographic (ECG) monitoring for up to 7 days postoperatively. There were no differences in mean age, ejection fraction, aortic cross-clamp duration, or bypass duration between the 2 groups of patients. In the Plegisol group, 2 patients (8%) died and 4 patients (16%) required inotropic support, whereas in the O2-Plegisol group there were no deaths and only 2 patients (8%) required inotropic support. These differences, however, were not statistically significant. Birefringence assessment demonstrated an improved myocardial response to ATP and calcium (predominantly in the left ventricular epimyocardium and in the right ventricular biopsies) at the end of ischaemia and after reperfusion in patients given O2-Plegisol. Deterioration in cellular assessment of myocardial contractility (measured by a reduction in birefringence of greater than 0.4 nm) was reduced from 20% in Plegisol patients to 12.5% in O2-Plegisol patients. CK-MB values showed no difference at any sampling time between the 2 groups of patients; a mean peak CK-MB of 35 IU/l occurred 2 h postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical study on the use of retrograde cardioplegia with St. Thomas' Hospital solution

One hundred and three consecutive patients with aortic valve disease and twenty seven patients with ischemic heart disease of severe critical coronary stenosis or left main trunk stenosis underwent open heart operations with the use of retrograde cardioplegic technique for myocardial protection. Under complete cardiopulmonary bypass, a balloon catheter was inserted into the coronary sinus through small right atriotomy and secured in place. Retrograde cardioplegia was accomplished using cold St. Thomas' Hospital solution by drip method at height of 60 to 80 cm with topical saline slush. Cardiac resuscitation was very easy and acceptable hemodynamics were obtained in all patients. Even in 8 patients in which aortic crossclamping time was above 180 minutes cardiac recovery was excellent except one who needed IABP support. Eight patients in aortotomy group were died postoperatively from the reasons unrelated to myocardial protection. Postoperative hemodynamic data and enzymatic analyses of CK-MB revealed good myocardial protective effects. Retrograde cardioplegia with the use of cold St. Thomas' Hospital solution is thus an effective alternative of myocardial protection in aortic valve surgery or aortotomy surgery and in coronary revascularization for multiple coronary stenoses or left main trunk lesions.     

Effects of cardioplegic solutions on coronary artery and myocardium--comparison of the glucose-insulin-potassium solution and the St. Thomas' Hospital cardioplegic solution

Effects of two cardioplegic solutions on coronary artery and myocardium were experimentally investigated in three types of preparations. In the isolated perfused guinea pig heart, infusion of Glucose-Insulin-Potassium (GIK) solution (37 degrees C) caused contraction of coronary artery, whereas the St. Thomas' Hospital cardioplegic solution (37 degrees C) produced vasodilation. At the end of 30 minutes reperfusion after continuous infusion of cardioplegic solution, the St. Thomas' Hospital cardioplegic solution produced a greater recovery of cardiac function than GIK solution. In the isolated pig coronary artery, vasoconstriction caused by high potassium content was diminished by addition of magnesium in concentration dependent manner. In the electrophysiological examination, the membrane potential of the guinea pig papillary muscle was recorded by means of conventional glass microelectrodes. Though GIK solution produced greater depolarization of resting membrane potential than the St. Thomas' Hospital cardioplegic solution, effects of the two different cardioplegic solution was not so different after reperfusion of Tyrode solution. The St. Thomas' Hospital cardioplegic solution resulted in greater recovery of contracting activity after reperfusion than GIK solution. These data suggest that GIK solution causes coronary vasoconstriction and has deleterious effects on myocardium and that the St. Thomas' Hospital cardioplegic solution has a vasodilating action and produced a greater myocardial protection than GIK solution.     

Enhanced myocardial protection with high-energy phosphates in St. Thomas' Hospital cardioplegic solution. Synergism of adenosine triphosphate and creatine phosphate

The potential for improving myocardial protection with the high-energy phosphates adenosine triphosphate and creatine phosphate was evaluated by adding them to the St. Thomas' Hospital cardioplegic solution in the isolated, working rat heart model of cardiopulmonary bypass and ischemic arrest. Dose-response studies with an adenosine triphosphate range of 0.05 to 10.0 mmol/L showed 0.1 mmol/L to be the optimal concentration for recovery of aortic flow and cardiac output after 40 minutes of normothermic (37 degrees C) ischemic arrest (from 24.1% +/- 4.4% and 35.9% +/- 4.1% in the unmodified cardioplegia group to 62.6% +/- 4.7% and 71.0% +/- 3.0%, respectively, p less than 0.001). Adenosine triphosphate at its optimal concentration (0.1 mmol/L) also reduced creatine kinase leakage by 39% (p less than 0.001). Postischemic arrhythmias were also significantly reduced, which obviated the need for electrical defibrillation and reduced the time to return of regular rhythm from 7.9 +/- 2.0 minutes in the control group to 3.5 +/- 0.4 minutes in the adenosine triphosphate group. Under more clinically relevant conditions of hypothermic ischemia (20 degrees C, 270 minutes) with multidose (every 30 minutes) cardioplegia, adenosine triphosphate addition improved postischemic recovery of aortic flow and cardiac output from control values of 26.8% +/- 8.4% and 35.4% +/- 6.3% to 58.0% +/- 4.7% and 64.4% +/- 3.7% (p less than 0.01), respectively, and creatine kinase leakage was significantly reduced. Parallel hypothermic ischemia studies (270 minutes, 20 degrees C) using the previously demonstrated optimal creatinine phosphate concentration (10.0 mmol/L) gave nearly identical improvements in recovery and enzyme leakage. The combination of the optimal concentrations of adenosine triphosphate and creatine phosphate resulted in even greater myocardial protection; aortic flow and cardiac output improved from their control values of 26.8% +/- 8.4% and 35.4% +/- 6.3% to 79.7% +/- 1.1 and 80.7% +/- 1.0% (p less than 0.001), respectively. In conclusion, both extracellular adenosine triphosphate and creatine phosphate alone markedly improve the cardioprotective properties of the St. Thomas' Hospital cardioplegic solution during prolonged hypothermic ischemic arrest, but together they act additively to provide even greater protection.     

Improved myocardial protection by oxygenation of St. Thomas' Hospital cardioplegic solutions. Studies in the rat

The effect of oxygenation (100% oxygen) of the St. Thomas' Hospital cardioplegic solutions No. 1 (MacCarthy) and No.2 (Plegisol, Abbott Laboratories, North Chicago, Ill.) was examined in the isolated working rat heart subjected to long periods (3 hours for studies with solution No. 1 and 4 hours for studies with solution No. 2) of hypothermic (20 degrees C) ischemic arrest with multidose (every 30 minutes) cardioplegic infusion. At the aortic infusion point the oxygen tension of the oxygenated solutions (measured at 20 degrees C) was in the range of 320 to 560 mm Hg whereas that of the nonoxygenated solutions was less than 150 mm Hg. Twenty hearts (10 oxygenated and 10 nonoxygenated) were studied for each solution. The studies with solution No. 1 demonstrated that oxygenation led to a significant (p less than 0.05) reduction in the incidence of persistent ventricular fibrillation during postischemic reperfusion. Oxygenation of the cardioplegic solution also improved postischemic functional recovery so that the recovery of aortic flow was improved from 18.7% +/- 8.9% (of its preischemic control level) in the nonoxygenated group to 54.6% +/- 6.6% in the oxygenated group (p less than 0.025). Creatine kinase leakage was also significantly reduced from 27.5 +/- 4.8 to 9.9 +/- 0.6 IU/15 min/gm dry weight (p less than 0.005). Studies with solution No. 2 indicated that protection was better than with solution No. 1, even in the absence of oxygenation. A better degree of functional recovery was obtained after 4 hours of arrest with solution No. 2 than that obtained after only 3 hours of arrest with solution No. 1, and persistent ventricular ventricular fibrillation was never observed with solution No. 2. However, despite the superior performance with solution No. 2, further improvements could be obtained by oxygenation, with that time from the onset of reperfusion to the return of regular sinus rhythm being reduced from 55 +/- 8 to 35 +/- 2 seconds (p less than 0.01), postischemic recovery of aortic flow increasing from 59.8% +/- 7.4% to 85.7% +/- 2.5% (p less than 0.005), and creatine kinase leakage being reduced from 38.1 +/- 7.3 to 16.2 +/- 1.5 IU/15 min/gm dry weight (p less than 0.005). It is concluded that oxygenation of the St. Thomas' Hospital cardioplegic solutions improves their ability to protect the heart against long periods of ischemia and that this is manifested by improved postischemic electrical stability, functional recovery, and reduced creatine kinase leakage.     

31P-NMR study of cardiac preservation: St. Thomas' Hospital cardioplegic solution versus UW preservation solution

Abstract. Ex vivo cardiac preservation was evaluated by measuring the catabolism of high-energy phosphate (ATP and creatine phosphate, CrP) using ³¹P-NMR spectroscopy. After cardioplegic arrest St. Thomas' Hospital cardioplegic solution (group A), and University of Wisconsin (UW) preservation solution (group B) were tested. The hearts were mounted in the 4.7 T horizontal bore magnet of the NMR spectrometer and were continuously perfused with the test solution under 25 cm H₂O pressure for 6 h at 10°C. Peak heights of the β-phosphate of ATP and CrP were measured and expressed as percentages of the initial value. For both group A and group B, ATP declined less rapidly during preservation than CrP. In group A, ATP remained constant for 60 min while CrP decreased from the onset of preservation. After 6 h of preservation 28.3% of ATP and 24.5% of CrP remained (group A). On the other hand, in group B, levels of both ATP and CrP remained much more stable: CrP did not decrease during the first 3 h of preservation, while ATP started to decrease after 5 h. At the end of preservation 76.1% of ATP and 71.5% of CrP were still present. We conclude that UW solution is superior to St. Thomas' Hospital solution for the preservation of high-energy phosphates during 6 h cardiac preservation with continuous hypothermic low-flow perfusion.     

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.     

Oxygenation of St. Thomas' Hospital cardioplegic solutions--effects of myocardial temperature and carbon dioxide

The effect of oxygenation of St. Thomas' Hospital cardioplegic solutions (ST solutions) was examined in isolated working rat hearts. They were subjected to hypothermic arrest (12 degrees C, 22 degrees C) for 3 hours with infusions of cardioplegic solutions repeated for 5 minutes every 30 minutes. Based on myocardial temperature and mode of oxygenation, the hearts were divided into six groups. Group I: 12 degrees C and non-oxygenated; Group II: 12 degrees C and 100%-oxygenated; Group III: 12 degrees C and 95% O2 + 5% CO2-oxygenated; Group IV: 22 degrees C and non-oxygenated; Group V: 22 degrees C and 100%-oxygenated; Group IV: 22 degrees C and 95% O2 + 5% CO2-oxygenated. The pH of ST solutions varied with the mode of oxygenation as follows: 7.9-8.2 in Groups I and IV; 8.7-8.9 in Groups II and V; 7.1-7.4 in Groups III and VI. In the two Groups (II and V) with 100%-oxygenated ST solutions, the functional recovery of the hemodynamic parameters was significantly inferior to that of Group I and III, VI with 95% O2 + 5% CO2-oxygenated ST solutions. It was concluded that 95% O2 + 5% CO2-oxygenated ST solutions were superior to 100%-oxygenated ones and the functional recovery at 22 degrees C of 95% O2 + 5% CO2-oxygenated ST solutions were comparable to that of non-oxygenated ones at 12 degrees C.     

Potassium-channel opener cardioplegia is superior to St. Thomas' solution in the intact animal.

BACKGROUND: In isolated hearts, the potassium-channel opener pinacidil is an effective cardioplegic agent. This study tested the hypothesis that pinacidil is superior to St. Thomas' solution in the more clinically relevant intact animal. METHODS: Sixteen pigs were placed on full cardiopulmonary bypass. Hearts underwent 2 hours of global ischemia (10 degrees to 15 degrees C). Either St. Thomas' or 100 micromol/L pinacidil was administered every 20 minutes (10 mL/kg). Preischemic and postreperfusion slopes of the preload-recruitable stroke work relationship were determined. Changes in myocardial adenine nucleotide levels and cellular ultrastructure were analyzed. RESULTS: Pinacidil cardioplegia resulted in an insignificant change in the slope of the preload-recruitable stroke work relationship (40.6+/-2.1 mm Hg/mm before ischemia and 36.5+/-3.7 mm Hg/mm after ischemia; p = 0.466). In contrast, St. Thomas' solution resulted in a significant decrease in the slope after reperfusion (34.3+/-5.5 mm Hg/mm and 13.5+/-2.3 mm Hg/mm; p = 0.003). Adenine nucleotide levels, myocardial tissue water, and ultrastructural changes were similar between groups. CONCLUSIONS: Pinacidil ameliorated myocardial stunning associated with traditional hyperkalemic cardioplegia without causing significant differences in cellular metabolism.     

Evaluation of myocardial protection by combination of lidoflazine pretreatment and St. Thomas' Hospital cardioplegia in aorto-coronary bypass grafting.

The concept of pretreatment of the myocardium with a pharmacological agent protecting the cell against ischemic and reperfusion injury is very attractive. Lidoflazine, a calcium overload blocker, predominantly membrane stabilizing, is able to prevent cell damage during ischemic arrest and reperfusion. The purpose of this study was to determine whether the combination of lidoflazine pretreatment and St. Thomas' Hospital cardioplegia can provide, in clinical practice, better myocardial protection in aorto-coronary bypass grafting than St. Thomas' Hospital cardioplegia alone. As indices for myocardial protection, recovery of cardiac function, enzyme release, and clinical outcome were registered. Ninety-three patients undergoing aorto-coronary bypass surgery were studied. These patients were randomized into two groups in a double blind fashion. Patients in group A (n = 48) received lidoflazine 1 mg/kg intravenously over a period of 20 min before initiation of cardiopulmonary bypass. Group B (n = 45) receiving placebo, acted as a control group. Myocardial protection consisted of intermittent infusion of cold 4 degrees C St. Thomas' Hospital cardioplegia, topical slush ice, and systemic hypothermia (28 degrees C rectal). No significant differences between the two groups were noted in terms of recovery of cardiac function, enzyme release, incidence of myocardial infarction, low cardiac output, rhythm, and conduction disturbances. In conclusion, our data suggest that the combination of intravenous pretreatment with lidoflazine and St. Thomas' Hospital cardioplegia did not provide significant additional myocardial protection in the clinical situation.     

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.