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Biomedical subjects

H J Bretschneider

Publications and source records attributed to H J Bretschneider.

At least 55 records · Page 3Linked to original sources

31P-NMR spectroscopy of phosphate compartmentation during ischaemia in hearts protected by cardioplegic treatment.

Four tissue compartments, differing in proton and inorganic phosphate concentration, were resolved by 31P-NMR spectroscopy in samples from dog hearts after cardioplegic treatment with HTK solution. Inversion of the physiological cytoplasmic-mitochondrial pH gradient was observed. The considerable ensuing acidosis of the matrix is discussed with regard to a possible delocalization of ferrous ions.

Animals↗

Metabolic, energetic and structural changes in protected and unprotected kidneys at temperatures of 1 degree C and 25 degrees C.

In 110 canine kidneys, we examined the time course of energy rich phosphates, lactate, intrarenal ph and renal morphology with Euro-Collins- or with HTK-protection of Bretschneider and compared these findings with unprotected kidneys during complete ischemia at 1 degree C and at 25 degrees C. Both kidney protective solutions prolonged energy-rich phosphate-decline by a factor of 3-4 compared with that of unprotected kidneys. The lactate increase was greater in Euro-Collins-protected kidneys than in HTK-protected and in unprotected kidneys, leading to pH values of 6.5 in Euro-Collins and to 6.4 in unprotected kidneys after 24 hours, in contrast to a pH-value of 7.3 with HTK-protection. This may be the reason for structural deterioration seen in unprotected and in Euro-Collins-protected kidneys after 12, and 48 h of ischemia at 1 degree C, whereas in HTK-protected kidneys a sufficient preservation of structure can be seen. In one human kidney, protected with Euro-Collins-solution, we were able to show that at 1 degree C intrarenal pH and lactate accumulation is similar to the levels in canine kidneys. In Euro-Collins preserved kidneys lactate accumulation at 25 degrees C is even greater than at 1 degree C, leading to inhibition of energy metabolism and to structural deterioration, whereas HTK-solution, because of its high buffer concentration, is able to maintain ischemic metabolism leading to sufficient protection of intrarenal pH and of adenine nucleotides as well as structural protection at 1 degree C and at 25 degrees C.

Animals↗

[Ex situ operation on the liver. A new possibility in liver surgery].

A method for an ex situ operation of the liver is presented with the example of such an operation in a 40-year-old patient. With this operation bilateral liver metastases of a leiomyosarcoma--which were otherwise regarded as irresectable--were resected. Function of the liver after reimplantation was good. Liver protection was performed by perfusion with cardioplegic HTK-solution (Bretschneider). The techniques of liver ex- and implantation are based on the methods of liver transplantation. Extracorporal femoro-porto-axillary bypass for decompression of the inferior caval vein and portal vein was used throughout the anhepatic period of 6 h. It is supposed that the method described here--which according to the authors' knowledge has been performed for the first time in a patient--will open up new perspectives for the surgery of malignant and occasionally of benign tumors, if necessary also for other surgical liver diseases. As an additional possibility, in situ protection of the liver with consecutive operation of the bloodless liver in situ is discussed. This procedure will correspond for the most part to the ex situ technique described here.

Adult↗

Intracellular pH, Na+- and K+-activities at the onset of St. Thomas' cardioplegia: a study with ionselective microelectrodes.

Cellular edema and cardiac arrhythmias are often closely related to intracellular ionic alterations and, moreover, are an actual problem of clinical cardioplegia and ischemia of the heart. In order to investigate whether the clinically widely used cardioplegic solution of the St. Thomas' Hospital may predispose for these complications, membrane potential (EM), intracellular pH (pHi), and intracellular sodium and potassium activity (aiNa- and aiK) in sheep heart Purkinje fibres were directly measured by means of neutral-carrier ion-selective microelectrodes during equilibration of the fibres' extracellular space with the cardioplegic solution. The experimental temperature was 35 degrees C throughout. During control conditions under superfusion of a HEPES-buffered Tyrode solution EM was -74.4 +/- 5.1 mV (n = 39), pHi was 7.18 +/- 0.05 (n = 16), and aiNa and aiK were 7.6 +/- 1.4 mmol/l (n = 15) and 118.9 +/- 4.6 mmol/l (n = 15) respectively. Superfusing the Purkinje strand for 10 minutes with the cardioplegic St. Thomas' solution led to a depolarization to -57.3 +/- 4.7 mV (n = 21), a slight aiNa decrease to 6.7 +/- 1.6 mmol/l (n = 15; p less than 0.01; cardioplegic solution without procaine) and an increase of aiK to 127.1 +/- 4.4 mmol/l (n = 6; p less than 0.01). pHi needed 15 minutes to reach a steady state value of 7.25 +/- 0.05 (n = 9). The alterations on post-cardioplegic reperfusion with Tyrode solution were reversible within 15 minutes. Simulation of the clinical situation of ice-cold application of the solution by inhibiting the cellular Na/K pump via 0.1 mmol/l dihydroouabaine added to the St. Thomas' solution resulted in a marked increase of aiNa to 10.7 +/- 1.5 mmol/l (n = 6; p less than 0.01; no procaine) during cardioplegic superfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗

Comparison of the effects of right atrial, right ventricular apex and atrioventricular sequential pacing on myocardial oxygen consumption and cardiac efficiency: a laboratory investigation.

As the impact of cardiac pacing on myocardial energetics has not yet been established, this laboratory investigation was undertaken to evaluate the effects of right atrial (AP), right ventricular apex (VP) and atrioventricular sequential pacing (AVP) on cardiac energetics in a closed-chest model. Ninety-two pacing interventions were performed in ten anesthetized mongrel dogs with normal loading conditions and contractile states. The energetic effects of pacing were assessed in terms of myocardial oxygen consumption (MVO2), its hemodynamic determinants and cardiac efficiency. Efficiency was calculated as the ratio of O2-equivalent of external cardiac work to MVO2, using standard definitions. In the first series of experiments 36 intra-individual comparisons were made between AP and VP at identical rates (95-210 beats/min). In the second series AVP was compared to VP in 10 intra-individual comparisons at identical rates (109-190 beats/min). MVO2 was lower (p less than 0.001) during AP (8.30 +/- 2.14 ml O2/min.100 g) compared to VP (10.16 +/- 3.15 ml O2/min.100 g) at the same rate (158 +/- 32 beats/min). Efficiency (p less than 0.001) was considerably higher during AP (21.6 +/- 5.7%) compared to VP (12.8 +/- 5.9%). During AVP, MVO2 (10.85 +/- 1.76 ml O2/min.100 g) was not significantly different from VP (10.57 +/- 1.34 ml O2/min.100 g) at the same rate (146 +/- 25 beats/min). Hemodynamics were superior with AVP compared to VP. Efficiency was significantly higher (p less than 0.01) with sequential (15.4 +/- 3.9%) as compared to ventricular pacing (12.0 +/- 3.2%). In conclusion, this study indicated that VP exerts disadvantageous effects on MVO2 and cardiac efficiency. AP has beneficial effects on cardiac energetics because it improves the relationship between mechanical performance of the heart and its energy requirements. AVP results in a higher efficiency than VP due to superior hemodynamics, despite MVO2 levels comparable to those of VP. The mechanism of energy waste with right ventricular apex pacing is probably related to an asynchronous contraction in the ventricular myocardium due to a nonphysiological spread of excitation.

Animals↗

[Clinical use of the Bretschneider HTK cardioplegic solution for in situ protection of the kidney].

The first clinical use of Bretschneider's HTK-solution for in-situ-protection of the kidney in mild hypothermia is reported. By means of this protective method renal surgery can be performed in a bloodless field without permanent loss of renal function. After initial protective perfusion of the kidney no repeated perfusions or additional surface cooling must be done. There are no systemic side effects when the HTK-solution is applied appropriately.

Cardioplegic Solutions↗

Short-term perfusion and "equilibration" of canine kidneys with protective solutions.

Kidneys were perfused either with Euro-Collins-solution or with HTK-solution of Bretschneider. The perfusion pressure as well as the perfusion flow were measured during a six-minute perfusion. The perfusion resistance was higher in Euro-Collins-kidneys than during HTK-perfusion. The venous outflow of the kidney as well as the ureteral outflow was measured during each minute of the perfusion and has analysed for osmolality, and for sodium and potassium concentrations. In Euro-Collins-kidneys a complete "equilibration" of the extracellular space was not achieved, while during HTK-perfusion concentrations in the venous as in the tubular outflow, similar to those in the HTK-solution itself, could be reached. At the end of the different perfusions, tissue was analysed for biochemical parameters such as ATP, ADP, AMP and lactate as well as for morphological features. Lactate had increased and ATP had decreased during perfusion with Euro-Collins-solution, while ATP had not changed and lactate had decreased during perfusion with HTK-solution. Normal glomerular, tubular and dilated vascular structures can be seen after HTK-perfusion, while a glomerular and vascular contraction takes place during Euro-Collins-perfusion.

Adenine Nucleotides↗

Effects of glucose in protected ischemic kidneys.

Energy reserves (TAN) and anaerobic substrates (glucose, glycogen) are lower in renal than in myocardial tissue. Euro-Collins-solution contains nearly 200 mmol/l glucose, while the HTK-solution of Bretschneider contains none. Therefore the influence of glucose on kidney lactate production, on energy reserves (TAN), intrarenal pH and on morphology during the protection of ischemic kidneys was analysed using either Euro-Collins-solution, or modified "Euro-Collins-solution", containing mannitol instead of glucose, or HTK-solution with and without the addition of 5, 10 and 20 mmol/l glucose. Glucose content changed during kidney perfusion with Euro-Collins-solution from about 60 to 800 mumol/gdw. While intrarenal pH decreased from 7.1 to 5.1 in Euro-Collins-kidneys during 420 min of ischemia at 25 degrees C, pH decreased to 6.7 with the modified, mannitol containing "Euro-Collins-solution". In HTK-protected kidneys intrarenal pH decreased with increasing glucose addition to the solution. Although Total Adenine Nucleotides are highest at the end of ischemia with Euro-Collins-solution, structural protection after the same ischemic stress was best in HTK-protected kidneys without glucose addition. We conclude that glucose stimulated lactate production, reduced interstitial pH in the kidney even in combination with a highly buffered solution and that it might cause greater membrane permeability leading to a structural deterioration. Mannitol seemed more appropriate than glucose in this respect, although other substances, which provide energy substrate and prevent structural damage, may exist.

Acidosis↗

Impedance spectroscopy: a method for surveillance of ischemia tolerance of the heart.

UNLABELLED: During myocardial ischemia the phase angle phi of the complex electric impedance of myocardial tissue at 5 kHz AC exhibits a characteristic behaviour, the progress of which depends on the cardioplegic method applied. By extending the frequency range to 200 Hz and 10 MHz and by analyzing in addition to phase and magnitude also real and imaginary part of the impedance it was possible to elucidate which ischemic changes in the myocardium are responsible for the course of phi (5 kHz). This method we call impedance spectroscopy. Canine hearts were cardioplegically perfused with either the standard solution HTK[4] or the solution HTK[4] + 50 mumol/l Ca++. During the following ischemia at 25 degrees C energy-rich phosphate level, the ultrastructure, the real part, imaginary part and phase angle of the impedance between 200 Hz and 10 MHz were analyzed. RESULTS: phi (5 kHz) displays very similar characteristics during the ischemic period to those of the real part of the impedance at 200 Hz, Re (200 Hz). Re (200 Hz) increases, when--according to electron microscopic findings--an intracellular myocardial edema begins to develop. The changes of Re(200 Hz) are always smaller, however, than those of phi (5 kHz). This indicates that phi (5 kHz) increases in the course of ischemia not only as a consequence of confinement of the extracellular space by myocardial cellular edema but also because of changes of passive electrical characteristics of the myocardial cell membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Myocardial protection: left ventricular ultrastructure after different forms of cardiac arrest.

Clinically applied methods of cardioplegia show very different effects on the rapidity of decay of energy-rich phosphates as well as on kind and progression of ultrastructural alterations of the ischemic myocardium. Comparing the methods of cardioplegia according to Kirklin, St. Thomas's Hospital and Bretschneider (solution HTK) with pure ischemia at 25 degrees C (model A) and Kirklin's or St. Thomas's cardioplegia and subsequent 210 min or HTK cardioplegia and 300 min ischemia at 22 degrees C plus 20 min subsequent reperfusion (model B) leads to the following results: Model A: Compared with pure ischemia cardioplegia according to Kirklin and the St. Thomas's Hospital slows down the decay of the left ventricular ATP-concentration by a mean factor of 3 and the progression of structural alterations of the left ventricular subendocardium by a factor of 2. HTK retards the ATP-decay by a factor of 6, the alterations of ultrastructure by a factor of 6.5. St. Thomas's solution, in contrast to all other methods of cardioplegia, at the onset of ischemia already causes a cellular edema of myocytes; the edema increases during ischemia, and at the ATP-concentration of 4 mumol per gram myocardium is more pronounced than with pure ischemia, Kirklin or HTK. After application of Kirklin's solution, in contrast, a cellular edema of capillary endothelia develops during ischemia, which at 4 mumol ATP is more pronounced than with each of the other methods. Model B: After global ischemia until the ATP-concentration of left ventricular myocardium is 4 mumol/g and a subsequent 20 minutes post-ischemic recovery the ultrastructural alterations in principle resemble those occurring during ischemia (model A).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

[Kidney function parameters following ischemia stress using the Euro-Collins solution or the Bretschneider cardioplegic HTK solution].

Protection-methods, for an improvement of ischemic tolerance of the kidney, can be investigated by intraischemic analysis of metabolism and structure. A definite proof for the effectiveness of a protection method is only postischemic function in combination with postischemic structure-regeneration. For this reason postischemic function was chosen for examination of the protective ability of the Euro-Collins-solution and the HTK-solution during a two-hour reperfusion period. We perfused 57 dog kidneys either with the Euro-Collins- or with the HTK-solution prior to ischemia. Ischemia was 7, 60, 90 and 120 min after Euro-Collins-perfusion and 7, 120, 150 and 180 min after HTK-protection. The protected and ischemic kidneys were left in-situ; the mean ischemic temperature was therefore 20-25 degrees C for the shorter ischemic times and 30-34 degrees C for the longer ischemic times. We compared the protected and ischemic kidneys with 14 untreated kidneys (control). Postischemic renal blood flow (RBF) was measured by an electromagnetic flow probe; renal oxygen consumption (V02/min) was calculated by arterio-venous oxygen content difference and the renal blood flow. If urine could be collected, the glomerular filtration rate (GFR) was measured by an endogenous creatinine clearance. In Euro-Collins-protected kidneys after 60-120 min ischemia the RBF was after 15 min of reperfusion between 20 and 100 ml/min/100 g. After 30 min we got values of 100-200 ml/min/100 g. The V02/min, which was in the control kidneys between 5-6 ml/min/100 g, was about 2 ml/min/100 g.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Post-ischemic renal function after kidney protection with the HTK-solution of Bretschneider.

The cardioplegic solution HTK of Bretschneider was used for canine kidney protection. The kidneys were perfused with this solution for 6-10 min prior to the induction of ischemia. The kidneys were left in-situ for 60, 90, 120 and 135 min ischemia time at a temperature of 25-34 degrees C (n = 13). As a control group we used unilateral nephrectomized dogs (n = 9). After unilateral nephrectomy an elevated plasma creatinine in comparison to preoperative values was observed. After 60 and 90 min under HTK-protection the postoperative plasma creatinine was not elevated compared to the control group. After 120 min of ischemia creatinine level was slightly increased to an average of 2.1 mg% on the first and second postoperative day. These experiments indicate the protective effect of the cardioplegic solution for canine kidney preservation in situ.

Animals↗

Construction and experimental application of a catheter for selective arterial kidney perfusion in situ.

In order to improve dog kidney perfusion in situ with a protective solution, a perfusion catheter was constructed which allowed continuous pressure measurement in the center of the catheter tip during perfusion. Using this catheter, the equilibration of the extracellular space with a protective solution (HTK solution) was found to be pressure dependent. Continuous pressure and resistance control is therefore a prerequisite for reliable organ protection.

Animals↗

Effects of preservation conditions and temperature on tissue acidification in canine kidneys.

The influence of temperature (5, 15, 25, and 35 degrees C) on the degree of tissue acidification was examined using 74 canine kidneys with simple ischemia or after protection of the kidneys with Euro-Collins solution or with the HTK-solution of Bretschneider. At an incubation temperature of 5 degrees C, the intrarenal pH value in HTK-protected kidneys is continuously higher than 7.3 during 36 hr of ischemia. In Euro-Collins kidneys the pH value decreases to a pH of 6.4 during this time. In simple ischemic kidneys pH is 6.3 after 36 hr. At 15 degrees C the pH value falls to a lower level in Euro-Collins kidneys than in purely ischemic kidneys, but the pH in HTK-protected kidneys is higher than 6.9 for 24 hr. At 25 degrees C, and especially at 35 degrees C the intrarenal acidosis in Euro-Collins kidneys is much stronger than in unprotected kidneys, and the pH in HTK-protected kidneys does not decrease below 6.7. The lactate production in simple ischemic kidneys and in HTK-protected kidneys is nearly the same (80-100 mumol/gdw), although Euro-Collins kidneys have a steeper increase and reach higher lactate levels (330 mumol/gdw). The HTK solution guarantees satisfactory protection against damaging acidosis over the whole temperature range (5-35 degrees C), but the Euro-Collins solution leads to a stronger and more dangerous acidosis the higher the temperature.

Acidosis↗

Different effects of cardioplegic solution HTK during single or intermittent administration.

Since intermittent cardioplegic reperfusion during an ischemic period may reduce the ischemic stress of the heart at least by lowering myocardial temperature, we compared the post-ischemic recovery of the dog heart following cardioplegia and subsequent continuous ischemia of 1 X 300 minutes at 22 +/- 1 degree C (model 1) and following cardioplegia and subsequent 3 X 100 minutes of ischemia at 17 +/- 1 degree C with intermittent 4-minute cardioplegic reperfusion every 100 minutes (model 2). The parameters of post-ischemic recovery were the cardiac O2 consumption per beat at work (MVO2-E0): HR), the stability of cardiac rhythm, the left ventricular content of high-energy phosphates, and ultrastructure. Solution HTK with a magnesium concentration of 9 mM/L, in clinical use up to the beginning of 1984, resulted in a significantly better post-ischemic recovery in model 1, despite about 40% lesser ischemic stress in model 2. A reduction of Mg concentration from 9 to 4 mM/l, as in the HTK solution clinically tested since February 1984, did facilitate the post-ischemic recovery in model 1 as indicated by the stability of cardiac rhythm but led to a significant improvement of all parameters of recovery in model 2. Moreover, recovery in model 2 after reduced Mg was also clearly better than in model 1 corresponding to the lesser ischemic stress. The parameters myocardial O2 consumption (MVO2) and potassium loss during HTK perfusion containing 9 and 4 mM/l, respectively, gave indications of specific membrane labilizing effects of Mg in the cardioplegic solution HTK.

Adenine Nucleotides↗

A new model for testing therapeutic interventions during myocardial ischemia.

An open-chest dog heart model is presented which shows highly reproducible hemodynamic, electrophysiologic, and metabolic changes during and after short-term coronary occlusions. We repeatedly performed 3-min coronary ligations of the proximal ramus interventricularis anterior followed by reperfusion periods of 45 min. Thus, hemodynamic, metabolic, and electrophysiologic parameters of myocardial damage were fully reversible. The experimental model presented seems well suited to evaluate interventions which aim at influencing the extent and damage of myocardial ischemia without needing a large number of separate experiments.

Animals↗