Bretschneider's Solution Research Articles

Extended cardiopulmonary preservation: University of Wisconsin solution versus Bretschneider's cardioplegic solution

Application of the University of Wisconsin cold storage solution has rapidly expanded to include medium-term to long-term preservation of virtually all intraabdominal organs. Its use in intrathoracic organ transplantation has also been suggested. We therefore examined the efficacy of the University of Wisconsin solution in a primate allotransplantation model for preservation of hearts, and as a simple single-solution system for static preservation of heart-lung blocks, for periods of ischemia ranging from 6 to 24 hours. For comparison, we employed the histidine-tryptophane-ketogluterate cardioplegic solution of Bretschneider. University of Wisconsin solution provided superior results with regard to clinical outcome and hemodynamic recovery of hearts after ischemic periods of up to 16 hours. This was in contrast to Bretschneider's solution, which allowed storage of hearts for periods of only up to 10 hours. Heart-lung blocks were equally well preserved with either University of Wisconsin or Bretschneider's solution after 6 to 12 hours, although the University of Wisconsin solution group exhibited a more notable increase in pulmonary water content. This was in accordance with histological data, which suggested that, although hemodynamic recovery of hearts stored for periods longer than 10 hours was poor, preservation of pulmonary ultrastructure was far superior using Bretschneider's solution as compared with University of Wisconsin solution after an ischemic period of up to 16 hours.

A comparison of intracellular solutions for donor heart preservation

Numerous solutions have been advocated for the preservation of donor hearts, and there has been much interest in universal and intracellular preservation solutions. This study compared the effects of Euro-Collins, University of Wisconsin, and Bretschneider's solutions with the use of an in vitro human right atrial muscle preparation to assess recovery of function after a 24-hour period of simulated cardiac arrest. There were no statistically significant differences among groups in length, weight, cross-sectional area, initial developed force, or resting force of muscles, including those muscles that were contracted in Krebs-Henseleit solution and served as a control. After the 24-hour arrest period at either 4 degrees or 12 degrees C, the solution was changed back to Krebs-henseleit at 34 degrees C and recovery was assessed over 30 minutes. At 30 minutes, developed forces for muscles that were cooled to 4 degree C were 58.9%, 76.6%, and 60.7% of the control for Euro-Collins, University of Wisconsin, and Bretschneider's solutions, respectively (p = not significant). For those cooled to 12 degrees C, developed forces were 9.5%, 30.5%, and 95.6% of the control for Euro-Collins, University of Wisconsin, and Bretschneider's solutions (p = 0.0001). Bretscheider's solution resulted in greatly improved recovery compared with both Euro-Collins and University of Wisconsin solutions (p = 0.005), and University of Wisconsin solution was better than Euro-Collins solution (p = 0.02). Recovery of developed force was affected by temperature for Euro-Collins and University of Wisconsin solutions (p = 0.005 and p = 0.001, respectively) but not for Bretschneider's solution. Resting force was elevated in muscles that were cooled in both Euro-Collins and University of Wisconsin solutions at 12 degrees C compared with almost normal values for Bretschneider's solution at either temperature (p = 0.07). Bretschneider's solution has a very high buffering capacity, which may be beneficial for long-term preservation. In conclusion, Bretschneider's solution resulted in the best recovery of human atrial myocardial function after a 24-hour preservation period compared with Euro-Collins and University of Wisconsin solutions and should be considered for use in donor heart transportation. The variability in quality of preservation at different temperatures with either Euro-Collins or University of Wisconsin solution make them less desirable as preservation solutions because uniform temperatures are seldom obtained during donor heart transplantation.

Lowered threshold for ventricular fibrillation in amiodarone-treated pigs undergoing cardiopulmonary bypass and cardioplegic arrest with St. Thomas' cardioplegic solution.

The antiarrhythmic agent amiodarone has been suspected of causing reduced cardiac performance after extracorporeal circulation and cardioplegic arrest in patients. This has recently been confirmed in an experimental model where pigs were exposed to cardiopulmonary bypass and cold cardioplegic arrest with Bretschneider's solution. Due to the high concentration of the cardio-depressant agent procain in Bretschneider's solution, it could be speculated whether it is the combination of amiodarone and this solution that may be potentially deleterious, rather than amiodarone alone. To investigate this, adult pigs (75 +/- 2 kg at surgery) were treated with amiodarone for 30 +/- 2 days (1400 mg/day: n = 8, untreated controls: n = 4, blind experiment), followed by exposure to cardiopulmonary bypass with universal cooling to 28 degrees C and topical cold cardioplegic arrest with St. Thomas' solution for 60 min. Apart from 1 g of calcium (Ca2+) at the end of bypass, no inotropic drugs were administered. Cardiac reserve was tested by right ventricular pacing (200 beats/min until death or up to 30 min). The two groups did not differ concerning preload or afterload, heart rate, cardiac output, left ventricular pressure, arterial pressure or rate of change in left ventricular relaxation (-dP/dt) before or after bypass was terminated, while the rate of change in left ventricular contraction (+dP/dt) was lower in the amiodarone-treated pigs. The time on bypass, before stable hemodynamics had recovered, was prolonged in amiodarone-treated animals, 46 +/- 4 min versus 31 +/- 3 min in the controls (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Phosphorus-31 nuclear magnetic resonance of isolated rat liver during hypothermic ischemia and subsequent normothermic perfusion

The effects of prolonged hypothermic ischemia and subsequent normothermic perfusion on the energetic metabolism and intracellular pH (pH in) of isolated rat livers were studied by phosphorus-31 nuclear magnetic resonance spectroscopy. Nucleoside triphosphate (NTP) depletion and intracellular pH were studied within an 18-h-storage phase, by using the following preservation media: Eurocollins (EC), UW Lactobionate (UW) and Bretschneider's solution (HTK). Values obtained after 8-h ischemia were chosen to estimate the performance of the various media: NTP levels were 37 ± 7%, 10 ± 5% and 0% of control levels, respectively, in livers stored in UW, HTK and EC solutions. pH in reached values of 7.15 ± 0.10 in UW and HTK, and 6.96 ± 0.10 in EC-stored livers. Ischemic damage was assessed by reperfusing the stored organ with Krebs medium: NTP recovery was around 70 ± 20% for the three solutions used. Recovery of pH in was near the control value (7.23 ± 0.08), except for EC solution (7.05 ± 0.20). The main results are that (i) the rates of NTP and pH in decrease are strongly dependent on the nature of the preservation solution, whereas (ii) NTP recovery is not significantly different during post-ischemic reperfusion. With regard to animal survival, UW solution is at present considered largely superior to EC medium for liver preservation. Thus, our data suggest that the rates of NTP depletion and pH in fall during cold preservation could be both considered as better indicators assessing liver injury than the post-ischemic NTP recovery.

Cytotoxicity of Various Crystalloid Solutions to the Endothelial Cells of Autologous Grafts

Harvesting and storage may influence the early failure of autologous grafts. We studied the endothelial layer of human saphenous veins (HSV) and bovine internal mammary arteries (BMA) after a two-hour storage period in comparison to vessel segments prepared immediately after harvesting. The storage solutions were 0.92% NaCl, 0.9% NaCL heparinized, Ringer's Lactate (RL), heparinized blood or Bretschneider's cardioplegic solution. To visualize the endothelial cell damage, specimens were stained with silver nitrate. The surface covered by morphologically intact endothelial cells was computed in percent. In a perfusion model using the carotid artery of rabbits, the increase of the permeability of the endothelium after two hours' perfusion was investigated (n = 5 each). In native HSV-segments 70.8 +/- 4.5% of the endothelium were found to be morphologically intact. The figures for stored grafts were: 14.7 +/- 4.4% (NaCl), 0.5 +/- 0.3% (hep. NaCl), 16.0 +/- 4.6% (RL), 37.2 +/- 5.3% (hep. blood) and 50.0 +/- 4.2% (Bretschneider). Comparable results were found with BMA specimens. BMA: 98.3 +/- 2.1% (native), 39.2 +/- 3.3% (NaCl), 8.4 +/- 3.5% (hep. NaCl), 11.2 +/- 4.8% (RL). 67.0 +/- 6.1% (hep. blood) and 78.1 +/- 4.7% (Bretschneider). In accordance with these results the increase of the permeability of the endothelial cell layer of the carotid artery of rabbits was significantly less after perfusion with Bretschneider's solution. The condition of the endothelial cells of autologous grafts at the time of implantation was found to be clearly dependent on the type of solutions used for perfusion and immersion. In comparison to all crystalloids studied in this series, Bretschneider's cardioplegic solution proved to be superior.

IN VITRO INHIBITION OF PLATELET AGGREGATION BY THE LIVER WITH UW SOLUTION AS THE PRESERVATION FLUID

The influence of UW preservation fluid in comparison with that of Euro-Collins and Bretschneider solutions on collagen, adenosine diphosphate and ristocetin-induced platelet aggregation was investigated in vitro using platelet-rich plasma of 4 healthy volunteers. The concentrations of the solutions tested were comparable to those that may be used in the transplant situation. 2UW solution inhibited ADP and collagen-induced platelet aggregation--an effect that could be attributed mainly to adenosine and secondarily to penicillin in UW solution--whereas ristocetin-induced aggregation was not affected. Euro-Collins and Bretschneider solutions did not alter platelet aggregation. The inhibition of platelet aggregation by UW may, on the one hand, contribute to bleeding complications after reperfusion and, on the other hand, be responsible for the observed lower incidence of hepatic artery thrombosis.

THE USE OF MYOCYTES AS A MODEL FOR DEVELOPING SUCCESSFUL HEART PRESERVATION SOLUTIONS

The development of a successful method to preserve the heart for relatively long periods (24-48 hr) requires demonstrating successful orthotopic transplantation and long-term survival after preservation. There are, however, multiple variables that may affect the quality of heart preservation, and it is nearly impossible to systematically study all the variables in this complicated model. One model that may be useful to study how preservation parameters affect heart cell preservation is the isolated myocyte preparation. In this study myocytes were isolated from the rabbit heart and the effects of up to 24 hr cold storage on viability measured to determine if this would be a suitable preservation model. Myocytes were stored in various preservation solutions including; EuroCollins (EC), two cardioplegic solutions (Stanford [ST] and Bretschneider solution [HTK]) and the University of Wisconsin solution (UW) with or without the addition of polyethylene glycol. The viability of myocytes was judged by measuring the effects of preservation and rewarming after preservation on cellular morphology (percent rod-shaped cells), ATP concentration, and LDH release. Myocytes preserved in the cardioplegic solutions were least well preserved after 12 and 24 hr storage, as judged by the loss of rod-shaped morphology and lower ATP concentration. Preservation in EC resulted in a decrease in the percent rod-shaped cells after 12 hr and 24 hr storage that was greater than obtained in the UW solutions. The best preservation of myocyte morphology and highest content of ATP was obtained in myocytes stored in the UW solutions, especially those containing PEG. The myocyte model of heart preservation shows a loss of cell integrity that is related to the preservation solution (HTK greater than ST greater than EC greater than UW-PEG) and these results are similar to what has been shown in the past with other models of heart preservation. Thus the myocyte model appears to be a useful method to test how many preservation solutions and preservation variables affect heart cell metabolism. In the future, results from these types of studies may find use in developing improved heart preservation solutions for testing in the orthotopic transplant model.

Role of potassium concentration in cardioplegic solutions in mediating endothelial damage

We studied the effect of potassium concentration in cardioplegic solutions on endothelial function by examining its influence on 5-hydroxytryptamine- (5-HT) and nitroglycerin-induced vasodilation in the isolated rat heart. Forty-eight rat hearts were perfused on a modified Langendorff preparation. After a baseline record of increase in coronary flow induced by 10 −7 M 5-HT and 10 μg/mL nitroglycerin, the hearts were perfused for 30 or 60 minutes with either St. Thomas' solution or Bretschneider solution containing 20 mmol/L of potassium or for 30 minutes with either solution containing 30 mmol/L of potassium (n = 8 in each). Initially, 5-HT and nitroglycerin caused a 39.0% ± 3.3% and 39.7% ± 2.8% increase in coronary flow, respectively. After 30 or 60 minutes' perfusion with St. Thomas' solution containing 20 mmol/L of potassium, there was little change in the response to 5-HT or nitroglycerin (5-HT, 43.1% ± 4.1%; nitroglycerin, 38% ± 3.2%). Similarly, perfusion with Bretschneider solution (20 mmol/L K +) for 30 or 60 minutes did not alter the degree of vasodilation (5-HT, 39.2% ± 2.9%; nitroglycerin, 38.0% ± 3.3%). However, perfusion with St. Thomas' solution containing 30 mmol/L of potassium for 30 minutes abolished the endothelial-dependent 5-HT-induced vasodilation (5-HT, −1.6% ± 1.4%; nitroglycerin, 36.9% ± 2.2%). Perfusion with Bretschneider solution (30 mmol/L K +) gave similar results (5-HT, −2.1% ± 1.2%; nitroglycerin, 36.4% ± 1.7%). We conclude that the concentration of potassium in cardioplegic solutions plays a critical role in causing functional endothelial damage.

Surgery for critical congenital aortic stenosis during the first three months of life

Open commissurotomy for critical aortic stenosis has been performed in a consecutive series of 28 neonates and infants below 3 months of age (average age 1 month) including 5 patients with severe organic mitral valve disease in need of concomitant correction. In the majority of cases, aortic stenosis was due not only to fused commissures but also to excessive immature valve tissue protruding into the valve area. Therefore a technique of extended commissurotomy has been adopted resecting such nodules responsible for a secondary level stenosis. All operations were done under deep hypothermia (17 degrees C), circulatory arrest (33 +/- 11 min) and cardioplegia using the Bretschneider solution (35-50 ml/kg). Hospital mortality was 18% (5) including 1 infant dying at 2 months of thrombosed mitral prosthesis inserted at a secondary operation. Severe organic mitral valve disease proved to be the only significant risk factor for early mortality. During the follow-up period of up to 10 years (average 5 years), 1 child with a hypoplastic left heart died and 2 children had to undergo reoperation for residual and recurrent stenosis, respectively. Actuarial survival for the present series is 78% at 10 years while reoperation free survival for the aortic valve is 64%. It is concluded that careful and if necessary extended open commissurotomy still represents the method of choice in this age group. Alternative methods such as transventricular or percutaneous dilatation did not show a lower risk until now and long-term results are not convincing as yet.

Intraoperative Protektion freier mikrochirurgischer Transferlappen: „Cold Storage” in HTK-Lösung*

There is a rule of thumb that an ischaemia time of 6 hours should not be exceeded when preserving a free flap. Microsurgical reconstructions sometimes require a long operation time and a long tolerance of ischaemia of the free flap. Using Bretschneider's HTK solution for the intraoperative cold storage of free flaps with a temperature of 5-7 degrees C, an ischaemia time of 12 hours should not affect the free flap, and hence the time limit of the ischaemic tolerance looses its importance. Based on Bretschneider's research results of cardioplegia and of the ischaemic tolerance of the kidney and the liver, we chose the HTK solution for the intraoperative protection of free microsurgical flaps.

Effectiveness of modified University of Wisconsin solution for heart preservation as assessed in heterotopic rat heart transplant model

A solution developed at the University of Wisconsin is an excellent preservation solution for the kidney, pancreas, and liver. We studied the effectiveness of a modified University of Wisconsin solution, which was made by reversing the sodium and potassium concentrations, in heart preservation. We first examined the relationship between total ischemic time and 1-week graft survival rates using a saline solution as a control preservation solution by transplanting a heart to the neck of test animals. To determine preserved heart viability, we palpated the heart 1 week postoperatively. The 1-week graft survival rates for the various total ischemic times were as follows: less than 1 hour, six of six; 4 hours, five of six; 8 hours, two of six, 12 hours, one of six; and 16 hours, one of six. These results demonstrate a correlation between total ischemic time and survival rate. Then we compared three preservation solutions--glucose-insulin-potassium, Bretschneider's solution, and the modified University of Wisconsin solution--for 16 hours of simple preservation. The 1-week graft survival rates were one of six for glucose-insulin-potassium, two of six for Bretschneider's solution, and five of six for the modified University of Wisconsin solution. The high survival rate for the modified University of Wisconsin solution under adverse conditions indicates its effectiveness in heart preservation.

European Versus North American Cardioplegia: Comparison ofBretschneider's and Roe'sCardioplegic Solutions in a Canine Model of Cardiopulmonary Bypass

Roe's and Bretschneider's crystalloid cardioplegic solutions were compared in a canine model of total cardiopulmonary bypass with 4.5 hours of hypothermic (27 degrees C) ischemic arrest and 60 minutes of reperfusion. Bretschneider's solution (Group I, six dogs) preserved tissue adenosine triphosphate (ATP) near control levels and maintained coronary effluent pH near 7.0 throughout the ischemic interval, while Roe's solution (Group II, six dogs) allowed progressive acidosis and depletion of ATP (P less than 0.005 versus control). Group I had supranormal left ventricular function during reperfusion (greater than 100% of pre-arrest function) but Group II regained only 40-75% of pre-arrest function. Group I had 2.82% +/- 3.61% necrosis of heart mass and Group II 9.33% +/- 8.26 (P less than 0.10). We conclude that Bretschneider's solution provided better myocardial protection than Roe's solution. The development of acidosis in the Roe group suggests that the more effective buffering of Bretschneider's solution with histidine is the probable basis for its superiority.

Glucose Content and Efficiency of Glycolysis in Protected Ischemic Kidneys of Different Species

In ischemic canine kidneys protected by Bretschneider's HTK solution the glycolytic lactate production is limited by a low renal substrate content. However, for anaerobic energy supply ischemic organs depend on glycolysis. To evaluate the role of glycolysis in renal protection, the relationship between lactate production and anaerobic energy supply was examined in protected kidneys of dogs, sheep, and swine. Additionally, in canine kidneys an attempt was made to improve anaerobic energy provision by adding glucose to the protective solution. The results were as follows: (1) According to increasing lactate production from swine to dog to sheep, intraischemic ATP decay was delayed least in swine and most in sheep. (2) Glucose addition (10 mM) to the HTK solution roughly doubled the time for ATP to fall to 1 mumol/g dry wt (tATP) in dogs. (3) The greater the lactate production in all three species, the lower the decrease in SAN (ATP + ADP + AMP) from 5 to 120 min of ischemia. (4) A glucose additive in the protective solution led to a significant (p less than .005) increase of SAN in dogs at 120 min of ischemia. A sufficient substrate supply seems to be an essential component of a reliable renal protection.

Recovery after Cold Cardioplegic Arrest of Isolated Blood-Perfused Hearts Excised from Non-Anesthetized Pigs

An isolated blood-perfused pig heart model has been established in order to evaluate the recovery of hearts obtained from slaughterhouse domestic pigs avoiding anesthesia and direct experiments on animals. Eleven hearts subjected to 9 min of normothermic ischemia were infused with cold modified Bretschneider solution. After 180 min of cardioplegic-induced global ischemia (including 9 min of normothermic ischemia) 8 hearts were reperfused for 120 min. Left ventricular function (measured isovolumetrically by means of a balloon, and expressed as developed left ventricular pressure, positive and negative dP/dt) was stable during the whole reperfusion period. Lactate production was abolished after 25 min of reperfusion, while there was a small glucose extraction during the whole reperfusion period. Slight deterioration of the mitochondria was found during the induced cardiac arrest, however, reversing during the reperfusion. Thus, due to the stability of left ventricular function, improved metabolism and ultrastructure during the reperfusion period, the model with no use of laboratory animals, and without any influence of anesthesia, seems to be suitable for testing the pure effect on the performance of the left ventricle of drugs and substrates added to the reperfusate during the reperfusion period.

Ultrastructural study comparing the myocardial protective effects of four different infusates (Bretschneider's, St Thomas's, standard Ringer's and blood potassium solutions) in the human heart

Comparative mitochondrial ultrastructural changes during myocardial ischaemic periods have been assessed when using four different solutions: Bretschneider's solution (BS) (K+ = 10 mEq/l) at 4°C; St Thomas's hospital solution (STS) (K+ = 20 mEq/l) at 4°C; standard Ringer's solution (SRS) (K+ = 2.7 mEq/l) at 4°C; blood potassium cardioplegic solution (BPS) (K+ = 21 mEq/l) at 15°C. BS (n = 8), STS (n = 10), SRS (n = 8) and BPS (n = 8) were infused in 34 patients undergoing aortic valve replacement (n = 17) or aortocoronary bypass grafting (n = 17), after aortic crossclamping, either in the aorta or in both coronary ostia, until the septal myocardial temperature reached 10-13°C for crystalloid solutions or 15°C for blood cardioplegia. Myocardial biopsies were taken from the left ventricular apex, on a beating heart, at the beginning and end of bypass. To assess the degree of ischaemic injury, an ultrastructural evaluation of the mitochondria was done and four histological classes have been defined: class I- dense matrix and cristae; class II — occasional mitochondrial swelling; class III — decrease in matrix density with extensive swelling; class IV — severe swelling and/or rupture of matrix. This study showed that: (1) only the St Thomas's and Bretschneider's solutions provide a rapid electromechanical asystole; (2) isolated hypothermic crystalloid solution with low potassium concentration (standard Ringer) is not sufficient either to induce cardiac arrest or to prevent detrimental mitochondrial changes; (3) Bretschneider's solution appears to provide the best ultrastructural mitochondrial preservation during myocardial ischaemia.

Intraischemic metabolic effects of different disaccharides on protected canine kidneys

The addition of the disaccharides maltose (10, 20, 30 mM) and sucrose (30, 60 mM) to Bretschneider's organ protective HTK solution was evaluated to improve renal protection by an enhanced glycolytic energy supply. Canine kidneys were perfused for 8 min with either HTK solution or HTK solution containing additional disaccharides. After nephrectomy the kidneys were incubated at 25 degrees C and metabolic parameters were determined at regular intervals. Maltose and sucrose are slowly cleaved during renal ischemia but maltose distinctly faster than sucrose. Maltose increases intraischemic ATP supply. However, 30 mM maltose was no better than 10 mM. 60 mM sucrose was about as effective for glycolysis as 10 mM maltose. However, possibly due to fructose release there was an accelerated decrease of adenine nucleotides with sucrose. Although fructose enters glycolysis it seems to have negative side-effects. Hence, probably neither sucrose nor fructose are appropriate for renal substrate supply during ischemia.

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

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

Cerebral Blood Flow during Early Cardiopulmonary Bypass in Man. Effect of Procaine in Cardioplegic Solutions

Cerebral blood flow (CBF), plasma procaine concentrations, and somatosensory evoked potentials (SSEP) were recorded in 2 groups of patients in whom either a high-procaine cardioplegic solution (Bretschneider's n = 29), or a low-procaine cardioplegic solution (St. Thomas', n = 13) was used. In the Bretschneider's group, marked changes in CBF occurred (p less than 0.001). Mean CBF was 27 (range 18 to 51) ml/(100 g X min) between sternotomy and the onset of extracorporeal circulation (ECC). A mean of 6 minutes after the onset of ECC, and before the administration of Bretschneider's cardioplegic solution, CBF increased to 39 ml/(100 g X min). After administration of the cardioplegic solution, CBF decreased significantly within the first 15 minutes, and then gradually increased to a mean of 68 (range 43 to 108) ml/(100 g X min). Cerebral blood flow was 45 ml/(100 g X min) just after ECC was stopped. Marked plasma procaine concentrations, up to 100 mg/l, were reached just after the infusion of Bretschneider's solution. The flow was significantly reduced (p less than 0.015) in patients with plasma procaine greater than or equal to 10 mg/l, when compared to patients with plasma procaine values less than 10 mg/l. In the St. Thomas' cardioplegic solution group the same reduction in CBF did not occur (p less than 0.02). Despite the depressant effect of procaine on CBF in the Bretschneider group, a consistent brain hyperperfusion was observed in all patients during hypothermic ECC if their blood pressure was sufficient to produce hyperemia. In rats (n = 6), during normothermia without extracorporeal circulation, the effect of procaine was much more pronounced. The CBF fell from a mean resting level of 108 ml/(100 g X min) to 68 and 54 ml/(100 g X min) after 15 and 35 minutes, respectively, of continuous infusion of Bretschneider's solution. The flow returned to the resting level about 40 minutes after termination of the infusion.

Protection of the Hypertrophied Human Heart by Adjusting Regional Myocardial Temperature to a Safe Level

Uneven distribution of temperature and the persistence of electro-mechanical activity after aortic cross-clamping are 2 factors limiting the myocardial protection during cardioplegic arrest, especially in hypertrophied hearts which are known to be extremely vulnerable to ischemia. In the present study regional myocardial temperature (T) was continuously controlled, and the time until arrest occurred (delta t) was determined in 61 patients undergoing aortic valve replacement. In addition, the myocardial contents of high energy phosphates and lactate were assessed. Three different cardioplegic solutions were employed: In the first group we used Bretschneider solution (Br), in the second group St. Thomas' solution (St), and in the third group the so-called "Hamburg cardioplegia" (H). During cardiac arrest the regional myocardial temperature was adjusted to temperatures not exceeding 15 degrees C by intermittent infusions of cold cardioplegic solution. We found a positive correlation between left ventricular muscle mass (LVMM) and delta t. A negative correlation existed between LVMM and adenosine triphosphate (ATP) contents at the end of the ischemic period. The cooling characteristics and delta t were significantly longer and the cooling to 15 degrees C was less rapid when H was used. Adenosine-triphosphate contents were well preserved during ischemia in all 3 groups. We conclude that all 3 cardioplegic solutions tested protect the hypertrophied myocardium adequately if the regional myocardial temperature does not increase above 15 degrees C during cardiac arrest. Hearts with a higher LVMM showed a decreased myocardial ATP content at the end of the ischemic period. Therefore, the LVMM may limit myocardial protection.

A-II-3 A Comparative Study on the Effect of Myocardial Protection of Multiple and Single Dose Coronary Perfusion with Bretschneider's Solution during Open Heart Surgery

A-II-3 A Comparative Study on the Effect of Myocardial Protection of Multiple and Single Dose Coronary Perfusion with Bretschneider's Solution during Open Heart Surgery