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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.

Phosphorylation rates of canine heart mitochondria isolated after various periods of myocardial ischemia after cardioplegic arrest were correlated with the myocardial ATP-, lactate- and undissociated lactic acid content as well as with interstitial H+-concentration. The following correlation coefficients were found: ATP: 0.87, lactate: 0.93, interstitial H+: 0.73. The calculated undissociated lactic acid content and the mitochondrial phosphorylation rate during ischemia showed a correlation coefficient of r = 0.95. Swelling measurements of mitochondria, isolated immediately after cardioplegic arrest, demonstrated that an undissociated lactic acid- and an ATP-concentration of 70 microM and 28 microM respectively are necessary for a half maximal swelling reaction under anaerobic conditions. The results suggest that the accumulation of undissociated lactic acid during myocardial ischemia could play an important role for mitochondrial damage in vivo.

In 10 to 66% blunt chest traumata lead to cardiac traumata. As it is shown in our special collective (n = 12) injuries of the pericardial sac of the myocardium, of the myocardial septum, of the coronary arteries and of the cardiac valves have occurred. Therefore clinical symptoms are various and the diagnosis remains difficult with regard to the causative polytrauma. Bleedings and/or pericardial tamponade caused by rupture of the atrial or ventricular wall, injury of main coronary vessels or cardiac dislocation after pericardial rupture urgently require a surgical intervention. Aneurysms caused by blunt trauma, ventricular septal defects, valve insufficiencies may be mostly treated in the interval.

The influence of pre-ischemic treatment with propranolol (0.8 mg/kg bw) or with verapamil (0.1 mg/kg bw) on myocardial O2 consumption and on coronary resistance after cardioplegic arrest (300 minutes at 22 degrees - 24 degrees C) was investigated, using a Langendorff technique in open chest experiments (canine hearts). For myocardial protection histidine buffered Bretschneider solution was used, while for standardization all hearts were postischemically reperfused with a modified Tyrode solution at 35 degrees C. Both drugs were given intravenously in two fractions, 60 and 30 minutes before the onset of cardioplegic perfusion; a third group was not pretreated. Although the verapamil group had the lowest O2 consumption post-ischemically, the most impressive results were found in coronary resistance. Propranolol significantly diminished coronary resistance (p less than 0.05), while verapamil distinctly enhanced it compared to the non treated group. The "membrane labilizing" effect of verapamil combined with calcium-free cardioplegic solution was confirmed by a massive postischemic myocardial sodium uptake.

The functional behaviour of membrane systems of the cardiac cell during oxygen deficiency was analyzed and the alterations were related to the metabolic state of the tissue as an index of injury. 1. The retention function of the cell membrane for proteins. With increasing energy deficiency the cardiac sarcolemma loses its ability to retain macromolecules (myoglobin, enzymes) within the cell. Close correlations exist between protein release and oxygen supply as well as ATP content of the tissue. 2. Function of isolated mitochondria after ischemia. In parallel with a strong impairment of oxidative phosphorylation (decrease of QO2, RCI values, phosphorylation rates) the Ca++-transporting activity of mitochondria is continuously depressed with decreasing myocardial ATP. 3. Function of isolated sarcoplasmic reticulum after ischemia. With breakdown of high energy phosphates during ischemia rate and extent of Ca++ binding with decrease markedly.

In canine hearts the myocardial equilibration processes (temperature, pO2, pCO2, Na+, K+) and the myocardial energy turnover were analyzed at the beginning of a cardioplegically induced cardiac arrest during a coronary perfusion of 10 minutes. The investigated hearts (n = 10) were perfused with the Bretschneider histidine-buffered cardioplegic solution according to the recommendations worked out for clinical use. The results show that during the cardioplegic coronary perfusion of 10 minutes the cooling and temperature equilibration of the myocardium occur considerably faster than the establishment of a new energy steady-state at a very low level. The minimalization of the coronary resistance and of the myocardial O2 consumption are only reached after an extended perfusion period of 7 to 9 minutes. In consequence of the results, the following recommendations can be given for the clinical use of the Bretschneider cardioplegic solution: a) the solution should be used at a temperature of between 5 degrees and 10 degrees C, b) the cardioplegic coronary flow should be between 60 and 80 ml/min . 100 gww, c) the human heart should be perfused for 8 to 10 minutes and, d) the perfusion pressure should be maintained at 40 to 50 mmHg after cardiac arrest has set in. So far the action of equilibration procedures when using the Bretschneider cardioplegic method has not been compared with that of other cardioplegic methods.

Preischaemic doubling of the myocardial buffer capacity optimizes the energy supply of the ischaemic heart by anaerobic glycolysis. For osmotic reasons this method of improving ischaemia tolerance can only be realized in combination with cardioplegia by extracellular Na+ and Ca2+ reduction. The cardioplegic solution 'HTK' which has been developed according to these considerations. (1) delays the decay velocity of myocardial ATP by a factor of 7-8 in comparison with pure ischaemia; (2) leads to a good myocardial recovery with regard to metabolic, morphological, and functional criteria after an ischaemic stress of 300 min at 23 +/- 1 degrees C--especially after the addition of quinine; (3) is considerably reduced in its protective efficacy by adding 50 mumol l-1 Ca2+; (4) causes a calcium paradox if it is infused for 30 min at 35 degrees C; this does not happen if it is infused for 60 min at 25 degrees C or for 120 min at 15 degrees C; on adding 50 mumol l-1 Ca2+ to the solution the risk of a calcium paradox is significantly reduced, even after infusion for 35 min at 35 degrees C; (5) effects an evident delay of recovery, if a continuous ischaemic stress of 300 min at 23 degrees +/- 1 degree C is reduced to 3 X 100 min of ischaemia at 17 +/- 1 degrees C by intermittent cardioplegic reperfusion; (6) considerably improves the myocardial recovery even after intermittent cardioplegia if 50 mumol l-1 Ca2+ are added or Mg2+ is reduced from 9 to 4 mmol l-12. The metabolic, morphological, and functional results are equivalent to those after 300 min of continuous ischaemia. Further investigations must show to what extent the 'membrane stabilizing effect' of [Ca2+]o can be achieved by taking advantage of mutual ionic interaction on the level of plasmalemma (e.g. H+-Mg2+-Ca2+) or by adding membrane effective substances (quinine).

The antigen specific rosette test was used for the evaluation of a specific sensibilization of a tumour bearer to TAA. The frequency of the rosettes formed by peripheral blood leucocytes of breast carcinoma patients with antigen-coupled particles is significantly higher than that produced by leucocytes of normal donors. Following operation normally the number of TAA specific rosettes decrease, in 4 cases with recidives we found high numbers of TAA binding cells. In another 11/98 patients following ablatio mammae later than half a year we found positive test results and also in 17/60 patients with mastopathy. The clinical relevance of these results must be proofed in further investigations.

The influence of different cardioplegic methods (Bretschneider, Cardiac Surgery in Hamburg, Kirklin, St. Thomas' Hospital in London) on the progressive myocardial acidosis during global ischemia of up to 24 hours' duration was investigated in arrested, nonperfused canine hearts (n = 36). The increasing acidosis of the ischemic heart muscle was continuously measured and registered with the aid of interstitial pH measurement (pHi) using glass implant electrodes. With various buffered and unbuffered cardioplegic solutions there were relatively wide fluctuations of the pHi courses in the myocardial extracellular space. The "critical" interstitial pH values ("pHcrit") relative to a defined myocardial ATP concentration (4 mumol/g ww) vary between 6.10 (Bretschneider) and 5.6 (Kirklin) (p less than 0.001). These striking results cannot be attributed solely to different total myocardial lactate concentrations, but variations in a "cellular" and an "extracellular factor" must also be taken into account. Measurement of interstitial pH for intraoperative monitoring of myocardial ischemic stress can therefore be used only within limits and with knowledge of the specific protective procedure applied. The method continues an important tool in basic investigations of partial or global ischemia of organs, particularly as regards the spectrum of metabolic, morphological and functional parameters.

The ORION SPACE-STAT (SS-30) and the TECHNICON STAT/ION were used to investigate quality control of Na+- and K+-determinations in test sera (n=8) and in the plasma of 100 patients. The flame photometer IL 543 was used as a reference apparatus. The ion-selective electrode instruments, SS-30 and STAT/ION, gave results very similar to those of flame photometry. The values from the SS-30 were higher by an average of 3% to 5% compared with the values from the other instruments. An explanation for this bias may be the fact that the SS-30 (unlike the STAT/ION and the IL 543) measures electrolyte activities or concentrations in undiluted plasma water. On the basis of these results the routine use of ion-selective electrodes for Na+- and K+-determination can be recommended for clinical laboratories.

Heart muscle mitochondria with satisfactory functional parameters of oxidative phosphorylation and with morphologically intact structure were isolated from canine myocardium employing a modified KEA-medium (0.18 M KCl, 10 mM EDTA, 0.5% bovine serum albumin, pH 7.1) according to Sordahl and Schwartz (1). The functional behaviour of mitochondria was investigated after different durations of in situ ischemia (cardioplegia, 15 degrees C) and correlated with metabolic findings. During ischemia the following changes were seen: 1. Successive reduction of electron flow. 2. Relatively small impairment of phosphorylation efficiency. 3. Less damage of FAD- than NAD-catalyzed oxidative phosphorylation. 4. A marked increase of electron flow and thus recovery of phosphorylation rate even after longer ischemic periods by addition of cytochrome c. As important factors of accelerating mitochondrial impairment during ischemia the myocardial ATP decrease, the lactate and H+-activity increase are discussed.

Human adult hearts with aortic valve disease (n = 20) and hypertrophic obstructive cardiomyopathy (n = 1) were perfused intraoperatively with cold histidine buffered Bretschneider solution. During a seven minute cardioplegic perfusion the temperature level, the electrolyte level, the resistance of the left (LCA) and right coronary artery (RCA), and myocardial O2 consumption were analysed. Equilibration of K+ was terminated shortly after the start of the perfusion while Na+ equilibration lasted for about 5 minutes. Resistance of RCA did not change significantly, but that of the LCA was diminished significantly (p less than 0.025) within the perfusion period indicating a delayed washout of calcium from the extracellular space. Myocardial O2 consumption was reduced from 2.71 ml/min (1. minute) to 1.51 ml/min (4. minute) to 0.93 ml/min (7. minute) although the temperature had reached a low level after 3 minutes. The difference between 4. to 7. minutes is significant (p less than 0.001). By our results it is concluded that in adult hearts high-volume cardioplegic perfusion at a flow rate of 1 ml/min X gm at a perfusion pressure of 40 to 50 mmHg should be performed for at least 6 to 7 minutes to achieve a sufficient intra-ischemic myocardial protection.