[Respecting the opinion and approach of the other physician].
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Biomedical subjects
Publications and source records attributed to D Goldschmidt.
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A technique of coronary perfusion with diluted blood, giving homogenous myocardial cooling (10-12 degrees C) under lignocaine perfusion, with or without potassium (K) cardioplegia is presented. The first 75 operated cases were used to adjust the optimal lignocaine (5 mg/min) and K (2 meq/min in continuous coronary perfusion, 5 meq/min in discontinuous coronary perfusion) dosage in the myocardial protection circuit. Then, 123 operated patients (78 aortic valve replacement, 30 mitro-aortic double valve replacement, 15 other operations on the ascending aorta) were classified into four groups prospectively: 1. Continuous coronary perfusion 10 degrees C, 2. Continuous coronary perfusion 10 degrees C with associated K cardioplegia, 3. Discontinuous coronary perfusion 10 degrees C, 4. Discontinuous coronary perfusion 10 degrees C with K cardioplegia. The best return of cardiac activity was observed in Group 1 and this was statistically significant with a high percentage of spontaneous heart beating after declamping the aorta (average 10 minutes), immediate efficacity of left ventricular contraction, and absence of arrhythmias, especially the transient conduction defects observed with K cardioplegia. In Group 1, during mitro-aortic valve replacement, after over 60 minutes aortic clamping, no significant reduction of ATP or myocardial phosphocreatinine or changes of hexosemonophosphates were observed, contrary to the findings after 15 minutes aortic clamping at 28 degrees C in a control group of mitral valve replacements (n = 10). Myocardial changes on electron microscopy in the subendocardial region of the left ventricle were minimal or absent, especially with respect to the mitochondria. The early post-operative course was the same in all four groups: of the 123 patients operated, early mortality was 2.4 p. 100 (1.6 p. 100 from intercurrent causes), severe arrhythmias were observed in 1.6 p. 100, supraventricular arrhythmias in 4.9 p. 100, myocardial infarction in 0.8 p. 100, electrocardiographic ischaemia in 0.8 p. 100, and atrioventricular block in 0.8 p. 100. The average enzyme level (CPK, SGOT, LDH) in the early postoperative period were low, with no correlation with the duration of aortic clamping.
A study has been made of the simultaneous evolution of cardiac activity and metabolism in the dog heart in situ, during the perfusion of isoproterenol in a dose comparable to therapeutic doses (1 micrograms x kg-1 x min-1, 30 min). A total cardiopulmonary by-pass system allowed of taking the repeated myocardial tissue samples necessary for the determination of the main energetic substrate and high-energy phosphate content. Samples were taken from subendocardial and subepicardial layers separately. The acceleration of heart rate due to isoproterenol was quickly regressive but, in the well-irrigated heart, the drug elicited a rapid fall in glycogen content and a considerable rise in lactate content, a slower reduction in free fatty acid concentration restricted to the subendocardial layer, and no significant variation of creatine phosphate or ATP. In the ischemic heart, isoproterenol aggravated the glycolysis disturbances without completely losing its effects on lipolysis when the ischemia was not too marked.
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Restoration of blood flow after 15 or 45 min. of ischemia induced an immediate recovery of phosphocreatine level and adenylate energy charge whereas ATP and total adenine nucleotides remained significantly below their normal values. These results prove that oxidative phosphorylations are not impaired but that a pool of myocardial adenine nucleotides is lost during ischemia which cannot be restored shortly after reperfusion. The significance of energy charge as a regulatory parameter in the myocardium is discussed.
Theophylline-induced variations of cardiac metabolism have been investigated by determining concentrations of various energetic substrates and of high-energy phosphates in myocardial tissue, the repeated sampling of myocardium being made possible by an extracorporal circulation system. When administered in therapeutic, or even slightly higher doses, theophylline does not modify triglyceride, glycerol and free fatty acid content or phosphocreatine and ATP content in subepicardial and subendocardial layers, but it does lower glycogen and raise lactate concentration. Consequently, the changes in anaerobic glycolysis due to myocardial ischemia may be enhanced if, as is probably the case, theophylline fails to restore the supply of oxygen.
Comparative intracellular distribution of Ca2+, Mg2+ and adenine nucleotides has been studied in pig heart by differential centrifugation or fractional extraction and has shown that Mg2+ and ATP are associated mainly with soluble fractions whereas Ca2+ and ADP are more tightly bound to subcellular structures. Ca2+ accumulation and Ca2+ stimulated respiration were studied in pig heart mitochondria under different energetic conditions in the absence or presence of phosphate. Ca2+ concentrations of about 1200 nmoles/mg protein inhibit Ca2+ accumulation, site I substrate oxidation and induce an efflux of mitochondrial Mg2+. These deleterious effects of Ca2+ on respiration occur even in the absence of phosphate or oxidizable substrate; they are completely prevented by ruthenium red only, and partially prevented by the addition of M2+ to the medium. The kinetics of Ca2+ uptake become of the sigmoidal type when Mg2+ is present. This cation strongly inhibits the rate of Ca2+ uptake in the presence of added phosphate and decreases the affinity of Ca2+ for its transport system. In the absence of phosphate, Mg2+ has no effect on Ca2+ uptake. The possible physiological implications of these findings are discussed
In open-chest dogs transient occlusion of the left anterior descending coronary artery induced an immediate decline in the creatine phosphate content of the ischaemic area, a lesser decline of the ATP and total adenine nucleotide contents and a rise in S-T segments. Reperfusion after 15 min restored creatine phosphate level and intramyocardial electrograms to normal whereas ATP and total adenine nucleotide levels stayed down. None of these parameters were modified in the nonischaemic area during the experiments. This study shows that there is no close relationship between electrical and biochemical events during either ischaemia or reflow.
Comparison between the effects on various rat liver mitochondrial functions of ethacrynate, a thiol reagent inhibitor of oxidative phosphorylations [3, 4] and those of dihydroethacrynate its saturated derivative which is not a thiol reagent, has been performed. Both, ethacrynate and dihydroethacrynate increase oxygen consumption by mitochondria in state 4 (succinate as substrate) in a concentration dependent way (from 1 to 5 X 10(-4) M EA or DHEA). This activation is followed, only with ethacrynate, by an inhibition appearing sooner with higher concentrations. After preincubation or mitochondria with ethacrynate (1 to 5 X 10(-4) M), the stimulation of respiration by (ADP + Pi) is completely inhibited whereas it is only weakly affected by dihydroethacrynate at the same concentrations. Ethacrynate and dihydroethacrynate provoke variations of intramitochondrial Mg2+ and K+ levels which need energy from the respiratory chain. These are affected by Pi or (Pi + ADP) in a different way with ethacrynate and with dihydroethacrynate. After preincubation with mitochondria, ethacrynate and to a smaller extent dihydroethacrynate, inhibit partially ADP translocation; ADP increases the inhibitory effect of EA on translocation and not that of dihydroethacrynate. Ethacrynate increases the oligomycin sensitive ATPase activity and dihydroethacrynate still more. After a ten minutes preincubation with mitochondria, ethacrynate and dihydroethacrynate hardly affect the 2.4 DNP stimulated ATPase activity. Preincubation with succinate or ADP strongly increases the ethacrynate inhibition whereas it decreases dihydroethacrynate inhibition. Ethacrynate and dihydroethacrynate do not affect the efflux of Pi produced by ATP hydrolysis but ethacrynate enforces the inhibitory effect of mersalyl (Mg2+ containing medium). After ten minutes of preincubation with mitochondria, ethacrynate binds 25 nmoles of -SH/mg protein (DTNB titration) and dihydroethacrynate has no effect. These results show an effect of ethacrynate on two types of thiols linked with energy conservation mechanisms and ADP translocation. These thiols could be unmasked or made accessible by conformational modifications of the inner membrane upon energization or addition of ADP.
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We have compared in open-chest dogs the evolution of adenine nucleotides and creatine phosphate to that of regional mechanical function during ischemia and reperfusion. Reperfusion restored normal value of creatine phosphate whereas adenine nucleotide level remained depressed. The percentage of systolic shortening, which after occlusion has a zero or negative value, increased to about 20% of control, after reperfusion similarly the pressure-length loop areas decreased to 14.9% of control during ischemia and increased to 39.3% of control during the early phase of the reperfusion period. No individual correlation was found between the ATP content and segmental function during ischemia or reperfusion, suggesting that a low level of ATP did not prevent some restoration of mechanical function. However, the ATP content measured at the end of the ischemic period was correlated with mechanical function measured 75 min after reperfusion, and thus ATP depletion could appear as an indicator of the severity of ischemic damage.
Lipomas are the most frequent benign tumours. Usually they are removed for cosmetic reasons only. For the treatment of giant lipomas, liposuction was proposed to reduce the size of the skin incision. The reliability of this technique was compared to surgical resection in a series of 30 patients presenting with a giant lipoma. One year follow-up of these patients showed a high percentage of recurrences after liposuction but only one after excision.
This article describes the microsurgical approach of the head and neck team of the Bordet Institute. During a period of 2 1/2 years 35 free flaps, 71 Pectoralis Major and 9 local flaps were performed for oropharyngeal reconstruction. Different types of free flaps were used and analyzed: 15 latissimus dorsi myocutaneous, 8 radial forearm, 1 gastric, 3 jejunum, 2 crista iliaca osteocutaneous, 1 scapular osteomyocutaneous, 3 scapular osteo-muscular of a new type (discovered in our department), 1 serratus anterior muscular and 1 flap composed of 3 others (a latissimus myocutaneous, a serratus anterior and a scapular osteo-muscular flap). 60% of the microvascular anastomoses were performed in a previously heavily irradiated area and none failed. The indications of some of these flaps are discussed and summarized.
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