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[Effect of prostaglandin E1 treatment on peripheral circulation during extracorporeal circulation--with special reference to its influence on body temperature recovery].

In patients undergoing open heart surgery, we assessed the effect of prostaglandin E1 (PGE1) treatment, 0.1 micrograms/min/kg dosage, during extracorporeal circulation. This treatment resulted in a marked perfusion pressure reduction. As a result, PGE1-treated group showed less urine volume than untreated control group. However, the degree of urine volume reduction relative to the decrease in blood pressure was less in PGE1-treated group than in untreated control group, suggesting a diuretic action of PGE1. We infer from these results that renal blood flow was maintained even after PGE1-induced intense perfusion pressure reduction, allowing for avoidance of renal impairment during extracorporeal circulation. In PGE1-treated adults, recovery of rectal temperature after hypothermic extracorporeal circulation was poorer but that of muscle temperature was better than in untreated adults. This phenomenon can be interpreted as representing improvement of blood-mediated heat transfer from deep regions of trunk to muscles and superficial skin due to PGE1-induced improvement of peripheral circulation. The ameliorative effect of PGE1 on peripheral circulation during extracorporeal circulation was further confirmed by the fact that the amount of NaHCO3 required for correction of metabolic acidosis was significantly lower in PGE1-treated group than in untreated control group. These results indicate that PGE1 treatment during extracorporeal circulation makes body temperature control easier, favorably affects postoperative body temperature recovery and improves peripheral tissue metabolism.

Alprostadil

Degradation of circulating DNA by extracorporeal circulation over nuclease immobilized on nylon microcapsules.

Studies were undertaken to determine whether deoxyribonuclease I, (DNase I) once immobilized on activated nylon microspheres, would be capable of degrading circulating DNA in vitro and in vivo in an extracorporeal circulation system in dogs. Nylon microspheres were prepared and after gentle hydrolysis and glutaraldehyde treatment, demonstrated a retention of up to 4.73 mg of Dnase I. In vitro studies showed that DNase I immobilized on microspheres degreded a significant percentage of 125I-native DNA (nDNA) within 15 min. Mongrel dogs were injected with 125I-nDNA and a variation in initial t 1/2 in individual animals was observed. Therefore, for experimental studies, 125I-nDNA was injected and decay was recorded during a control period in which untreated microcapsules were utilized in the extracorporeal system. DNase I microspheres were then introduced into the extracorporeal circuit which resulted in an acceleration of degradation of acid precipitable 125I-nDNA. When 200 mug of unlabeled DNA with 125I-nDNA was injected, a similar augmentation of DNA degradation was noted after extracorporeal circulation over DNase I microcapsules. This effect could not be attributed to release of DNase I from the microspheres since no 131I-DNase was detected in the serum or organs of the dogs at the conclusion of the experiments. 125I-nDNA:anti-DNA complexes were passively injected into dogs and after a similar control period of circulation over untreated microcapsules. DNase I microspheres were introduced. Results showed a rapid acceleration in the degradation rate of 125I-nDNA:anti-DNA complexes precipitable with (NH4)2SO4. Extracorporeal circulation over nylon microspheres resulted in no significant alteration of the host's hematocrit or platelet count, and little residual cellular debris on the microcapsules. These data suggest that DNAase immobilized on nylon microspheres may have a potential role in the specific therapy of systemic lupus erythematosus, when it is desirable to hydrolyze DNA circulating free or in combination with antibody.

Animals

[Influence of thiopental administration on peripheral circulation during cardiac surgery with extracorporeal circulation].

The influence of thiopental administration on peripheral circulation during cardiac surgery with extracorporeal circulation was examined. The subjects were 28 patients who were divided into one group of 14 patients receiving thiopental and the other group of 14 patients receiving no thiopental. The time lag of changes in peripheral temperature (sole) from that in central temperature (forehead) according to the deep body temperature determination, and base excess were used as indices of the quality of the peripheral circulation. A single shot of thiopental at a dose of 4 mg.kg-1 was initially given i.v. at the start of extracorporeal circulation and subsequently thiopental at a dose of 2 mg.kg-1.hr-1 was continuously infused i.v. up to the time of the aortic declamping. The results indicate a significantly smaller lag in the group receiving thiopental than in the group receiving no thiopental. Base excess was maintained within normal limits in the former group compared with negative base excess in the latter group as well as a significantly smaller requirement of postoperative catecholamine in the former group. The above findings suggest that thiopental administration during cardiac surgery with extracorporeal circulation is not only useful for maintaining peripheral circulation, but also beneficial for post-operative cardiac function.

Aged

[Renal functions and extracorporeal circulation].

During 76 extracorporeal circulations (CEC) carried out for open heart operations using an identical protocol, the authors carried out renal function tests from the time of administration of the anesthetic to the post-operative period. Various periods may be distinguished: pre-operative, anesthesia induction (CEC 1, CEC 2) post induction (CEC 1, post CEC 2) finally, the post-operative period (post-operative 1 to 4). As far as renal hemodynamics are concerned, the authors made the following observations: constant reduction in thiosulphate clearance and endogenous creatinine clearance, which reflect glomerular filtration. Reduction in PAH clearance, which reflects renal perfusion. Taking into consideration changes in the hematocrit, one may consider that there is a reduction in renal blood flow at all stages of anesthesia. Taking into consideration concomitant variations in blood pressure, one may calculate that intrarenal resistances are increased. The diuresis/minute increases in very great proportions during induction of anesthesia. Plasma osmolality also increases, urinary osmolality becomes reduced and osmolar clearance rises. The ratio between osmolar clearance and creatinine clearance rises. The clearance of free water rises from negative values. The serum sodium becomes slightly reduced, and sodium diuresis increases. Serum potassium becomes slightly reduced and urinary potassium rises. The interpretation of these phenomena is difficult and should take into consideration the experimental conditions. Comparison with published results shows that there are definite differences depending on whether pure or diluted blood is used. It is however, possible to seek the role of the anesthetic, the thoracotomy or the extracorporeal circulation itself and its load, quite independent of prior changes due to decompensation or not of the congenital heart disease, whether or not it has been treated. The study of these changes in renal function permits one to understand better the precariousness of renal perfusion during extracorporeal circulation, imperfectly corrected by osmotic diuresis and responsible for transient and reversible renal hypofunction, liable to lead however, in cases of complications and prolonged low blood flow, to organic renal failure.

Adolescent

Coronary circulation and myocardial oxygen consumption after extracorporeal circulation and after cardioplegic arrest.

The influence of haemodilution or of blood perfusion on the coronary circulation, myocardial oxygen consumption and on haemodynamic parameters was examined in two comparable groups of patients with slight congenital acyanotic cardiac malformation without indications of myocardial damage. In a third group of patients similar data were collected before and after artificial cardiac arrest by cardioplegic solutions. No findings concerning this question could be found in the literature. Coronary circulation was measured by the argon-gas-technique of Bretschneider et al. A fall in haemoglobin of 4.8% caused by haemodilution resulted in the first group in an increase in the cardiac index of about 8% and an increase in the coronary circulation of about 100% over the initial value with a simultaneous decrease in the coronary resistance due to coronary dilatation and reduction in blood viscosity. The myocardial O2 consumption was raised in spite of an increase in the coronary-venous O2 saturation and a clear reduction in the AVD O2. In contrast, the patients in the blood perfusion group showed no change in the coronary circulation and coronary resistance although a decrease of the myocardial O2 consumption was observed. The cardiac index fell to about 16% in these patients. After cardioplegic cardiac arrest there was no significant reduction in myocardial blood flow except for a decrease of myocardial oxygen consumption of about 20% The results are discussed and cantra-indications of haemodilution perfusion and cardioplegic cardiac arrest mentioned.

Cardiac Output

Estimation of total body fluid shifts between plasma and interstitium in man during extracorporeal circulation.

Fluid transport between plasma and interstitium during extracorporeal circulation was studied in seven patients undergoing aortocoronary bypass grafting. The absolute shifts in plasma volume during hypothermia were determined as the difference between input and loss of fluid and the changes in blood volume. The change in haemoglobin concentration due to acute haemodilution when starting extracorporeal circulation was used to calculate the absolute blood and plasma volume. The Starling equation for exchange across the capillary wall was used to describe fluid shifts. The total fluid filtered during the 60- to 90-min period of extracorporeal circulation averaged 34.1 +/- 11.1 (s.d.) ml/min. The total body filtration coefficient from the Starling relationship averaged 0.046 +/- 0.012 ml/kg.mmHg.min (0.354 +/- 0.092 ml/kg.kPa.min). Haemodilution, reducing colloid osmotic pressure in plasma (COPP) by approximately 10 mmHg (1.3 kPa) will result in a loss of plasma fluid of around 2 1 per hour. When corrected for lower fluid viscosity due to hypothermia during extracorporeal circulation, CFC would be about 40% higher, and a filtered volume of nearly 3 1 in a normothermic 70-kg person would be expected. Crystalloid haemodilution for shorter periods of time does not produce excessive oedema and thus may be well tolerated.

Aged

Prophylactic administration of tranexamic acid preserves platelet numbers during extracorporeal circulation in rabbits.

Neonatal extracorporeal life support is associated with platelet consumption and hemostatic disorders. This study in rabbits was undertaken to evaluate the effect of heparin coating and of the plasminogen and plasmin inhibitor, tranexamic acid on platelet consumption during extracorporeal circulation. Fibrinogen consumption was prevented by heparin coating, but platelet consumption was only prevented after the prophylactic administration of tranexamic acid. The authors concluded that inhibition of the fibrinolytic system had a specific effect on preserving platelet numbers, rather than improving the thromboresistance of the artificial surface. The main advantage of a heparin coating is the anticoagulant activity of the surface. Thus systemic heparinization can be reduced or omitted.

Animals

Predictive criteria for the need of extracorporeal circulation in single-lung transplantation.

Use of extracorporeal circulation is mandatory in heart-lung and en bloc double-lung transplantation. However, no criteria exist to predict the necessity of its application during single-lung transplantation for parenchymal lung diseases. We therefore reviewed our experience in 23 patients undergoing single-lung transplantation for idiopathic pulmonary fibrosis. All patients were evaluated by preoperative right heart catheterization. For intraoperative monitoring, a pulmonary artery thermodilution catheter was placed in the contralateral lung to repeatedly assess pulmonary artery pressure, cardiac output, and pulmonary vascular resistance. Extracorporeal circulation was necessary during graft implantation in 4 patients, whereas 19 patients underwent operation without it. Preoperative demographic patient data, time of ischemia, and hemodynamic values obtained preoperatively and before the clamping of the pulmonary artery showed no significant differences between groups. In contrast, after the clamping of the pulmonary artery, a significant drop in cardiac index of about 1.5 L.min-1.m-2 (p less than 0.01) and a concomitant rise in pulmonary vascular resistance (p less than 0.01) was observed in the group requiring extracorporeal circulation, whereas these variables showed no significant changes in the other 19 patients. Pulmonary artery pressure rose significantly in both groups (p less than 0.05), without significant differences between them. It is concluded that intraoperative assessment of cardiac index and pulmonary vascular resistance is essential for estimation of cardiac performance during single-lung transplantation. A decrease in cardiac index of more than 1.5 L.min-1.m-2 after the clamping of the pulmonary artery rather than the degree of pulmonary hypertension is indicative of the need of extracorporeal circulation.

Adult

Autacoids affecting vascular tone in the human fetal extracorporeal circulation.

1. The human fetal extracorporeal circulation is normally a vasodilated, low pressure system. 2. As this vasculature lacks innervation, autacoids have been postulated as being of great importance in controlling its tone. 3. This has now been confirmed by pharmacological in vitro techniques, particularly utilizing perfusion of the isolated umbilical cord and placental lobule. 4. The fetal umbilical-placental vessels are sensitive to a wide range of vasoconstrictor autacoids, some of which can cause intense vasospasm. 5. Thromboxane A2 receptors have been identified in both umbilical vein and placental villous vessels. 6. Prostacyclin and endothelial cell-derived relaxing factor (or nitric oxide) may be largely responsible for the low vascular resistance normally found in the fetal extracorporeal circulation. 7. Immediately after birth it is likely that stimuli such as cooling, stretching and handling of the umbilical cord cause release of eicosanoids and other autacoids from the vessels, leading to their complete closure.

Autacoids

Inhibition of kinin formation by a kallikrein inhibitor during extracorporeal circulation in open-heart surgery.

Involvement of the kinin system was studied in 58 patients during extracorporeal circulation in open heart surgery. At the onset of extracorporeal circulation, there was no increase of free kinin in blood and no reduction of plasma kininogen, when the latter was expressed as mug bradykinin/mg plasma protein. With the lapse of time, kinin in the blood increased significantly, and decrease of kininogen was also significant. The longer the circulation time, the greater the consumption of kininogen. The site of the kinin formation was presumed to be the heart-lung machine since the level of kinin increased slightly and kininogen decreased gradually in the blood leaving the machine, compared with those levels entering the machine. The difference in kininogen was significantly different from zero at termination of extracorporeal circulation. Administration of a kallikrein-trypsin inhibitor, trasylol (A. G. Bayer), infused into the heart-lung machine, prevented the decrease of kininogen. Reduction of the total peripheral resistance during this circulation was also prevented. The hemoconcentration, presumably the result of vascular permeability increase caused by increased kinin, was prevented by trasylol in cases in which extracorporeal circulation lasted over 60 minutes. Trasylol applied thus appears to be an effective counteragent for circulatory disturbances which occur during extracorporeal circulation.

Adolescent

[Clinical and experimental study of the production of renal hemodynamic effects of IABP-assisted pulsatile flow extracorporeal circulation].

Renal hemodynamics during IABP-assisted pulsatile flow extracorporeal circulation was assessed in terms of measurement values for intraoperative renal blood flow obtained by the local thermodilution method in human clinical patients. In addition, the effect of IABP on renal hemodynamics was investigated in an animal model of renal denervation in a study undertaken to elucidate the action mechanism of IABP. Eighteen patients with acquired heart disease were involved in the study and measured for the renal blood flow (RBF), cardiac output (CO), renal-systemic partition coefficient for blood flow (RBF/CO), renal vascular resistance (RVR) and perfusion pressure. In the pulsatile flow group, the RBF/CO increased as the number of pump runs increased, whole the RVR was conversely reduced with increasing pump runs. The experimental study without extracorporeal circulation was conducted on 19 mongrel dogs. During IABP runs RBF/CO increased, while the RVR decreased. After renal denervation, no noticeable influence of IABP upon renal hemodynamics was observed. Following a loading dose of noradrenaline (Norad), the RVR increased in a Norad concentration-dependent fashion, independently of IABP and renal denervation. These results indicate that IABP reduces the RVR and thereby exerts a favorable action on renal hemodynamics during pump times. The study thus warrants us to surmise that a mechanism involving the renal sympathetic nerves might play an important role in the production of favorable renal hemodynamic effects of IABP-assisted pulsatile flow extracorporeal circulation.

Animals