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[New aspects in diagnosis and therapy of placental insufficiency. Placental perfusion measurements; placental perfusion test (PPT) and betamimetic long term treatment (clinical and experimental data (authors transl)].

The rate of utero-placental blood flow depends on functional components (perfusion pressure and flow resistance within the area of the vascular bed of the placenta), as well as on morphological factors (regressive changes in the placenta). Different primary maternal conditions and diseases may lower the rate of placental flow, leading to placental insufficiency; the highest percentage, by far, of placental dysfunction is found in patients suffering from gestosis. Hypocirculation initially present in cases of EPH gestosis and caused by arteriolar spasms triggers off a vicious circle involving placental infarction and severe reduction in the utero-placental perfusion rate. This in turn leads to fetal hypotrophy, a high rate of premature births and perinatal mortality. Verification of HPL, HCG, alpha-Fetoprotein or E3 in maternal serum and amniotic fluid or urine greatly improved the recording of partial placental functions. Along with ultrasonic biometry, cardiotocography and amnioscopy, these hormonal parameters allow only indirect assessment of the placental function. On the other hand, measurements of the utero-placental flow offers a direct approach. In order to evaluate the placental flow measurements it is imperative to obtain a curve indicating the course over the last third of the pregnancy-in addition to establishing a general normal range. In case of placental insufficiency, it is necessary to determine whether this is due to functional disorders alone, or to more extenisve morphological changes. A placental perfusion test (PPT) was developed in order to make this distinction. Beta2-mimetic treatment is indicated if functional factors predominate, whereby it appears essential to obtain the requisite experimental data for precise quantification of beta-mimetic action.

Adrenergic beta-Agonists↗

Brain tissue pH, oxygen tension, and carbon dioxide tension in profoundly hypothermic cardiopulmonary bypass. Pulsatile assistance for circulatory arrest, low-flow perfusion, and moderate-flow perfusion.

The brain tissue pH, oxygen tension, and carbon dioxide tension were experimentally examined during profoundly hypothermic cardiopulmonary bypass with core cooling and core rewarming. Sixty-minute circulatory arrests (n = 28, group I), 120-minute low-flow perfusions (25 ml/kg/min; n = 16, group II), and 120-minute moderate-flow perfusions (50 ml/kg/min; n = 16, group III) were accomplished with and without pulsatile flow. In group I, progressive brain tissue acidosis and hypercapnia were recovered with pulsatile assistance. In group II, brain tissue acidosis and hypercapnia were recovered completely with pulsatile assistance but incompletely without it. In group III mild acidosis was eliminated with pulsatile assistance where the pH was significantly higher than in groups I and II, and brain tissue carbon dioxide pressure was significantly lower than in groups I and II with and without pulsatile assistance. Brain tissue hypoxia was severe in group I, slight in group II, but not found in group III. We concluded that a perfusion flow rate will decide the safe period, and a pulsatile assistance will promote brain protection at any flow rate in profoundly hypothermic cardiopulmonary bypass.

Acidosis↗

[Pulsatile assistance for profoundly hypothermic circulatory arrest, low-flow perfusion, and moderate-flow perfusion: comparative study of brain tissue pH, PO2, and PCO2].

The pH, oxygen tension, and carbon dioxide tension of canine brain tissue were experimentally examined during profoundly hypothermic cardiopulmonary bypass with and without pulsatile assistance. After core cooling, a 60-minute of circulatory arrest was performed in group 1 (n = 16), a 120-minute of low-flow perfusion (25 ml/kg/min) in group 2 (n = 16), and 120 minute of moderate-flow perfusion (50 ml/kg/min) in group 3 (n = 16). The core rewarming was done to the temperature above 32 degrees C. Each group was divided into two subgroups with and without pulsatile assistance (subgroup-p; n = 8, subgroup-c; n = 8). In group 1, progressive brain tissue acidosis and hypercapnea were recovered by use of pulsatile assistance. In group 2, brain tissue acidosis and hypercapnea were recovered completely with pulsatile assistance, but incompletely without it. In group 3, mild acidosis and hypercapnea were eliminated with pulsatile assistance. Brain tissue hypoxia was severe in group 1, slight in group 2, but not found in group 3. We conclude that a pulsatile assistance provides brain protection at any flow-ratio, and that the less flow-ratio and the longer perfusion period will make the pulsatile assistance the more necessary.

Animals↗

Effect of glucagon on the perfused rat hind-quarter vessles and on perfused coronary arteries of rabbit.

In rat hind-quarter perfusion experiments, glucagon (1 microgram) produced a significant vasodilation. On the other hand, in experiments with isolated perfused rabbit heart, glucagon (1 microgram) caused coronary vasoconstriction irrespective of whether noradrenaline was added to perfusion fluid or not. Glucagon had no effect on rate or force of contraction of heart.

Animals↗

[Regional cerebral oxygen saturation as a monitor of cerebral oxygenation and perfusion during deep hypothermic circulatory arrest and selective cerebral perfusion].

In order to evaluate cerebral oxygenation and perfusion during deep hypothermic circulatory arrest (DHCA) and selective cerebral perfusion (SCP), continuous measurement of regional cerebral oxygen saturation (rSO2) by near-infrared spectroscopy (NIRS) was performed. Two patients undergoing aortic arch surgery performed under DHCA and SCP were studied. 1) Circulatory arrest produced a continuous decrease in rSO2. Introduction of SCP increased rSO2 to even above the pre-circulatory arrest level (reperfusion hyperoxia). 2) During SCP, changes in rSO2 correlated well with the naso-pharyngeal temperature, SCP flow rate, and level of carbon-dioxide insufflation to SCP. 3) These changes in rSO2 paralleled with those of jugular venous hemoglobin saturation (SjO2) measured simultaneously, although SjO2 frequently exhibited artifacts. We conclude that rSO2 measurement may be a non-invasive and continuous measure in the evaluation of cerebral oxygenation and perfusion during DHCA and SCP.

Adult↗

Twenty-four-hour intermittent perfusion storage of the isolated rat heart. II. Perfusion pressure and functional preservation.

This study investigated the effect of intermittent perfusion (IP) pressures on functional preservation of the cold-stored isolated rat heart. The heart was flushed with cardioplegic solution #11 with ethylene diamine-tetraacetic acid and 2, 3-butanedione monoxime (CP-11EB), and stored at 0 degree C for 24 hr. During storage, the heart was intermittently perfused for 3 min at 10 and 17 hr of storage with 25 degrees C oxygenated CP-11EB. The IP pressures studied were: 20, 30, 40, 50, 60, 70, 80, and 100 mm Hg. Poststorage recovery of function was assessed with 30 min of working reperfusion. Control function of the unstored heart was: aortic flow (AF), 51.3 +/- 2.2 ml/min; coronary flow (CF), 25.8 +/- 1.2 ml/min; cardiac output (CO), 77.7 +/- 2.3 ml/min; work, 92.0 +/- 4.9 g-m/min; and coronary vascular resistance (CVR), 2.64 +/- .21 mm Hg-min/ml. Functional return in the 30,40,50,60,70, and 80 mm Hg groups was similar. Recovery in a representative group (60 mm Hg) was: AF, 52 +/- 3%; CF, 41 +/- 2%; CO, 48 +/- 3%; work, 42 +/- 3%; and CVR, 225 +/- 10% of the control. The total IP volume in this group was 71.0 +/- 1.7 ml; total lactate dehydrogenase (LDH) release during IP was 8.62 +/- .37 units/g dry; and end-storage tissue lactate was 52.6 +/- 6.4 mumole/g dry. As IP pressure decreased to 20 mm Hg, cardiac functional recovery declined significantly to AF, 35 +/- 6%; CF, 33 +/- 2%; CO, 34 +/- 5%; and work, 27 = 4% of control (P < .05 vs. 60 mm Hg group). The total IP volume decreased to 10.1 +/- .9 ml, tissue lactate content rose to 87.1 +/- 10.9 (P < .05 vs. 60 mm Hg group), but LDH release fell to 5.59 +/- .46 (P < .05 vs. 60 and 100 mm Hg groups). When IP pressure increased to 100 mm Hg, cardiac function was depressed with AF recovered to 25 +/- 3%; CF, 30 +/- 3%; CO, 26 +/- 3%; work, 21 +/- 3%; and CVR, 294 +/- 26% of control (P < .05 vs. 60 mm Hg group). IP volume increased to 100.7 +/- 2.4 ml; total LDH release increased to 19.1 +/- 1.2 (P < .05 vs. 60 mm Hg group), although tissue lactate (58.9 +/- 3.9) was not different from the 60 mm Hg group. End-storage tissue wet/dry weight ratio and myocardial adenosine triphosphate content were not different among the 20, 60, and 100 mm Hg groups. In conclusion, IP has a broad pressure optimum ranging from 30 to 80 mm Hg for 24-hr hypothermic preservation of the rat cardiac explant.

Adenosine Triphosphate↗

Effects of perfusate flow rate on measured blood volume, disse space, intracellular water space, and drug extraction in the perfused rat liver preparation: characterization by the multiple indicator dilution technique.

The effect of hepatic blood flow on the elimination of several highly cleared substrates was studied in the once-through perfused rat liver preparation. A constant and low input concentration of ethanol (2.0 mM), [14C]-phenacetin and [3H]-acetaminophen (0.36 and 0.14 microM, respectively), or meperidine (8.1 microM) was delivered once-through the rat liver preparation in five flow periods (greater than 35 min each); control flow periods at 12 ml/min were interrupted by flow changes to 8 or 16 ml/min. The steady-state hepatic availabilities (F or outflow survivals) at 12 ml/min were ethanol, 0.075 +/- 0.038; [14C]-phenacetin, 0.15 +/- 0.059; [3H]-acetaminophen, 0.34 +/- 0.051; meperidine, 0.047 +/- 0.017. Flow-induced changes were different among the compounds: with reduced flow (8 ml/min), F was decreased for ethanol (0.061 +/- 0.032) and [3H]-acetaminophen (0.28 +/- 0.051), as expected, but was increased for [14C]-phenacetin (0.20 +/- 0.068) and meperidine (0.05 +/- 0.03); with an elevation of flow (to 16 ml/min), F was increased for all compounds, as expected of shorter sojourn times: ethanol, 0.13 +/- 0.065; [14C]-phenacetin, 0.22 +/- 0.062; [3H]-acetaminophen, 0.43 +/- 0.063; meperidine, 0.055 +/- 0.022. A marked increase in F for ethanol had occurred when flow changed from 12 to 16 ml/min due to nonlinear metabolism; the latter was confirmed by a reduction in the extraction ratios at increasing concentrations (1.8 to 11.4 mM); this condition was not present for the other compounds. In order to explain the observations, we used the multiple indicator dilution technique to investigate the flow-induced behaviors of tissue distribution spaces of vascular and intracellular references in the perfused rat liver preparation.

Acetaminophen↗

Residence time distributions of solutes in the perfused rat liver using a dispersion model of hepatic elimination: 2. Effect of pharmacological agents, retrograde perfusions, and enzyme inhibition on evans blue, sucrose, water, and taurocholate.

The effect of altered physiological conditions on the residence time distributions of sucrose, water, and taurocholate in the rat liver were studied using a bolus injection and quantifying fraction of total outflow per ml-time profiles. Retrograde perfusions increased the residence times of sucrose and water markedly and were associated with very low hepatic availabilities for taurocholate. Resistance by the inlet sinusoids sphincters, which become outlet sphincters during retrograde perfusions, is suggested as the explanation for the observation. Infusions of noradrenaline, propranolol, and lidocaine resulted in relatively small changes in the mean residence times for sucrose and water with no apparent relationship existing between the efficiency number of taurocholate and volumes of either water or sucrose. Taurochenodeoxycholate resulted in an increase in the availability and mean residence time for taurocholate relative to no infusion.

Animals↗

The platelet-perfused in-vitro heart: an alternative model for studying the role of endogenous prostacyclin and thromboxane in control of coronary perfusion.

A new experimental in-vitro model is described, which was used for studying prostacyclin (PGI2)-thromboxane A2 (TXA2)-interactions. Langendorff hearts of guinea pigs are perfused at constant volume with Krebs-Henseleit buffer and washed human platelets (4 x 10(8)/min). PGI2 and TXA2 release are measured by bioassay. The cardiac and coronary function and the myocardial oxygen consumption are continuously monitored. The platelet count in the cardiac effluent can be measured and the cAMP content has been estimated. This model might be a useful tool for studying the roles of PGI2 and TXA2 in platelet activation and coronary perfusion in terms of endogenously synthesized substances.

Animals↗

Perfusion preservation of cadaver rat pancreas: II. Culture after perfusion and successful transplantation.

We designed a new process for culturing pancreatic islets and applied this method to cultures of rat pancreatic islets which had degenerated during preservation by the perfusion-method for 6 hours under the condition of hypothermia and oxygenation. The objective was to determine the extent of the original function. Transplantation of these so-treated islets was also attempted. When pancreatic islets isolated from the pancreas after 6-hour-perfusion were cultured, morphological restoration was apparent within the first 3-4 days. Insulin contents of the culture media renewed every 3 days, ranged from 851 to 1,134 microU/ml/two islets during culture period of 21 days. In the glucose-loading test, insulin secretion of the islets was the same as that of islets in the control experiments. Transplantation of these islets into the portal vein of streptozotocin-induced diabetic rats resulted in a good recovery from the diabetic state.

Animals↗

Perfusible and non-perfusible supports with monoclonal antibodies for bioaffinity chromatography of Escherichia coli penicillin amidase within its pH stability range.

Several monoclonal antibodies (mABs) have been prepared and immobilized for the biospecific isolation of penicillin amidase (PA) from Escherichia coli (EC 3.5.1.11), an enzyme without S-S bridges and a pH stability range of 4-9. During the immobilization the fluorescence emission maxima of the mABs were found to change from 336 nm to ca. 350 nm. Only one of these mABs was found to be suitable for preparative bioaffinity chromatography of PA within the pH stability range. This mAB was immobilized on different spherical supports (Eupergit C 250 L and Sepharose) and one perfusible support (Knauer Quick Disc) and used for analytical and preparative bioaffinity chromatography. Under isocratic conditions the plate height for the perfusible biospecific adsorbent was found to be an order of magnitude lower than for the other supports. The different forms of this proteolytically processed bacterial enzyme could not be separated, however, by the biospecific adsorbents. At the mAB density used in the adsorbents (10-30 microM), less than 30% of the theoretical binding capacity of the immobilized mABs could be used to adsorb the enzyme.

Animals↗

Corticosteroids inhibit prostaglandin release from perfused mesenteric blood vessels of rabbit and from perfused lungs of sensitized guinea pig.

Infusion of norephinephrine (NE) (1 - 3 mug/ml/min) into the isolated mesenteric vascular preparation of rabbit resulted in a rise in perfusion pressure, which was associated with the release of prostaglandin E-like substance (PGE) at a concentration of 2.81 +/- 0.65 ng/ml in terms of PGE2. Indomethacin (3 mug/ml) abolished the NE-induced release of PGE. Arachidonic acid (0.2 mug/ml) in the presence of indomethacin did not restore the NE-induced release of PGE. Hydrocortisone (10 - 30 mug/ml) and dexamethasone (2 - 5 mug/ml) also inhibited the NE-induced release of PGE. The inhibitory action of both corticosteroids was abolished by arachidonic acid (0.2 mug/ml). Antigen-induced release of a prostaglandin-like substance (PGs) (43.1 +/- 3.8 ng/ml in terms of PGE2 and a rabbit aorta contracting substance (RCS) from perfused lungs of sensitized guinea pigs was completely abolished by indomethacin (5 mug/ml) or by hydrocortisone (100 mug/ml). Indomethacin, however, increased histamine release up to 280% of the control level, which was 470 +/- 54 ng/ml, while hydrocortisone diminished histamine release down to 30% of the control level. A superimposed infusion of arachidonic acid (1 mug/ml) into the pulmonary artery reversed the hydrocortisone-induced blockade of the release of RCS and PGs. It may be concluded that corticosteroids neither inhibit prostaglandin synthetase nor influence prostaglandin transport through the membranes but they do impair the availability of the substrate for the enzyme.

Animals↗

In vitro cell perfusion. I. System for continuous observation of cells and analysis of perfusion fluid suitable for isolated mast cell and macrophage studies.

A system is described in which cells are perfused continuously with appropriate medium while simultaneously recording any change in cell morphology together with assay of released products (enzymes and mediators) following immunologic or non-immunologic perturbation. The released products in the perfusate are monitored continuously by automated fluorimetric assay procedures. The system is particularly applicable to investigate or toxicological studies of isolated mast cells or cultured macrophages.

Animals↗

Vasoconstrictor-mediated release of purines and pyrimidines from perfused rat hindlimb, perfused mesenteric arcade and incubated de-endothelialized aorta.

1. Reperfusion of hindlimbs that had previously been exposed to either 10 or 60 min global ischaemia resulted in transient washouts of uracil and uric acid in approximate proportion to the interval of ischaemia. However, changing the interval of sequential angiotensin II infusions from 10 to 60 min did not affect the magnitude of sustained uracil and uric acid release. 2. Perfused rat mesenteric artery arcade released uracil and uric acid and each was further increased approximately 2-fold by exposure to the vasoconstrictor, serotonin (6.7 microM). 3. Incubated de-endothelialized rat aorta also released purines and pyrimidines and this was increased further when subjected to increased work loads. 4. The increased rates of release of purines and pyrimidines from hindlimb, and the simpler vascular preparations of mesenteric arcade and aorta, were in proportion to the relative rates of increase in oxygen consumption under maximum vascular load. 5. It is concluded that the release of purine and pyrimidine nucleosides and their catabolites from perfused rat hindlimb occurring as a consequence of vasoconstriction is not the result of release from previously ischaemic tissue. In addition, release of purines and pyrimidines appears to be a general feature of vascular smooth muscle subjected to high workloads.

Analysis of Variance↗

Prospective comparative study of brain protection in total aortic arch replacement: deep hypothermic circulatory arrest with retrograde cerebral perfusion or selective antegrade cerebral perfusion.

BACKGROUND: The purpose of this study was to compare the results of total aortic arch replacement using two different methods of brain protection, particularly with respect to neurologic outcome. METHODS: From June 1997, 60 consecutive patients who underwent total arch replacement through a midsternotomy were alternately allocated to one of two methods of brain protection: deep hypothermic circulatory arrest with retrograde cerebral perfusion (RCP: 30 patients) or with selective antegrade cerebral perfusion (SCP: 30 patients). Preoperative and postoperative (3 weeks) brain CT scan, neurological examination, and cognitive function tests were performed. Serum 100b protein was assayed before and after the cardiopulmonary bypass, as well as 24 hours and 48 hours after the operation. RESULTS: Hospital mortality occurred in 2 patients in the RCP group (6.6%) and 2 in the SCP group (6.6%). New strokes occurred in 1 (3.3%) of the RCP group and in 2 (6.6%) of the SCP group (p = 0.6). The incidence of transient brain dysfunction was significantly higher in the RCP group than in the SCP group (10, 33.3% vs 4, 13.3%, p = 0.05). Except in patients with strokes, S-100b values showed no significant differences in the two groups (RCP: SCP, prebypass 0.01+/-0.04: 0.05+/-0.16, postbypass 2.17+/-0.94: 1.97+/-1.00, 24 hours 0.61+/-0.36: 0.60+/-0.37, 48 hours 0.36+/-0.45: 0.46+/-0.40 microg/L, p = 0.7). There were no intergroup differences in the scores of memory decline (RCP 0.74+/-0.99; SCP 0.55+/-1.19, p = 0.6), orientation (RCP 1.11+/-1.29; SCP 0.50+/-0.76, p = 0.08), or intellectual function (RCP 1.21+/-1.27; SCP 1.05+/-1.15, p = 0.7). CONCLUSIONS: Both methods of brain protection for patients undergoing total arch replacement resulted in acceptable levels of mortality and morbidity. However, the prevalence of transient brain dysfunction was significantly higher in patients with the RCP.

Adult↗

Comparative clinical study between retrograde cerebral perfusion and selective cerebral perfusion in surgery for acute type A aortic dissection.

OBJECTIVE: Selection of a brain protection method is a primary concern for aortic arch surgery. We performed a retrospective study to compare the respective advantages and disadvantages of retrograde cerebral perfusion (RCP) and selective cerebral perfusion (SCP) in patients who underwent surgery for acute type A aortic dissection. METHODS: The study reviewed 166 patients who underwent surgery at Nagoya University or its eight branch hospitals between January 1990 and August 1996. There were 91 patients who received SCP and 75 patients who underwent RCP. Results for these two groups were compared. RESULTS: There were no significant differences in age, gender, Marfan syndrome rate, DeBakey classification, or emergency operation rate. Rates of various preoperative complications were similar except for aortic valve regurgitation. Arch replacement was performed more often in SCP than in RCP patients (49% vs. 27%, P = 0.0028). There were no significant differences between groups in cardiac ischemic time or visceral organ ischemic time. However, RCP group showed shorter cardio-pulmonary bypass time (297+/-99 vs. 269+/-112 min, P = 0.013) and lower the lowest core temperature (21.6+/-3.1 degrees C vs. 18.7+/-2.1 degrees C, P = 0.0001). SCP duration was longer than RCP duration (103+/-56 vs. 54+/-24 min, P < 0.0001). Despite these differences, RCP patients were not significantly different from SCP patients with regard to any postoperative complication, neurological dysfunction (16 vs. 19%), or operative mortality (all deaths within the hospitalization; 24 vs. 21%). Regarding neurologic dysfunction, there were six cases of coma, six of motor paralysis, two of paraplegia and one of visual loss among SCP patients, and eight cases of coma, three of motor paralysis, and three of convulsion in the RCP group. The incidence of motor paralysis was higher in the SCP group, while the incidence of coma was higher in the RCP group. CONCLUSIONS: RCP can be performed without clamping or cannulation of the cervical arteries, which is an advantage in reducing the chances of arterial injury or cerebral embolization. RCP is comparable to SCP in terms of clinical outcome.

Acute Disease↗