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Biomedical subjects

J Boldt

Publications and source records attributed to J Boldt.

At least 19 recordsLinked to original sources
PubMed1992

Recovery of penetration ability in protease-treated zona-free mouse eggs occurs coincident with recovery of a cell surface 94 kD protein.

Previous studies have demonstrated that protease treatment of zona-free mouse eggs impairs sperm-egg interaction (Boldt et al.: Biol Reprod 39:19-27, 1988) and causes modification of a 94 kD egg plasma membrane protein (Boldt et al., Gamete Res 23:91-101, 1989). In this report, the ability of eggs to recover penetration ability following protease treatment was examined. Zona-free mouse eggs were isolated and treated with either trypsin or chymotrypsin (1 mg/ml, 20 min), then cultured for 0, 3, or 6 hr before insemination. Eggs cultured for 3 or 6 hr displayed significantly higher penetration levels than eggs inseminated immediately after protease treatment, indicating a recovery of penetration ability during the 3 or 6 hr incubation period. The recovery of penetration ability was not blocked by inclusion of cyclohexamide (50 micrograms/ml) during the 3 or 6 hr culture period, indicating that protein synthesis was not required for recovery of fusion ability. Cell surface radiolabeling studies with 125I revealed that a 94 kD cell surface protein was lost immediately following trypsin or chymotrypsin treatment but was found on the egg surface after the 3 or 6 hr recovery period. Recovery of the 94 kD egg surface protein occurred in the presence of cyclohexamide, and metabolic radiolabeling studies with 35S-methionine confirmed that synthesis of a 94 kD protein was blocked by cyclohexamide. These results suggest that the recovery of penetration ability after protease treatment of zona-free eggs is due to recovery of the 94 kD cell surface protein, providing further evidence for the involvement of the 94 kD protein in sperm-egg interaction.

Animals↗
PubMed1992

Phosphodiesterase-inhibitors enoximone and piroximone in cardiac surgery: influence on platelet count and function.

OBJECTIVE: Some phosphodiesterase (PDE)-inhibitors are believed to alter platelet count and function due to changes in intracellular cAMP. Whether newly developed (specific) PDE-inhibitors negatively influence platelet function in cardiac surgery should be investigated in a randomized study. METHODS: Eighty patients undergoing aorto-coronary bypass grafting were divided into 4 groups and received either the new PDE-III-inhibitor piroximone (group 1), the PDE-III-inhibitor enoximone (group 2), epinephrine (group 3) or no inotropic support (control). PDE-III-inhibitors were given as a bolus followed by infusion until starting of cardiopulmonary bypass (CPB). In addition to platelet count and a thrombelastogram, platelet function was assessed by aggregometry (ADP, epinephrine, collagen). Measurements were done before, during and after CPB until the 1st postoperative day. RESULTS: Platelet count and postoperative blood loss did not differ between the groups within the entire investigation period. Maximum aggregation and maximum gradient of platelet aggregation to all stimuli were not changed by either PDE-inhibitor enoximone or piroximone. CPB resulted in a significant decrease of all aggregation variables which was without differences due to treatment. Platelet aggregation recovered in the post-bypass period and exceeded baseline values on the 1st postoperative day. CONCLUSION: It is concluded that enoximone and the new PDE-III-inhibitor piroximone do not affect platelet function and can be used before CPB without risking platelet-related bleeding in cardiosurgical patients in the perioperative period.

Adenosine Triphosphate↗
PubMed1992

Influence of 4 different membrane oxygenators on inflammation-like processes during extracorporeal circulation with pulsatile and non-pulsatile flow.

The influence of four different membrane oxygenators (HF 4000, BOS-CM 50, CML 2, Maxima) on leucocyte count, concentrations of PMN-elastase, clotting factor XII, AT-III, C1-INH, alpha 2-antiplasmin and C3a was registered before, during and after CPB with pulsatile and nonpulsatile flow in 80 male patients aged between 36 and 67 years. With all systems tested, there was a drop in the concentrations of clotting factor XII, AT-III, C1-INH and alpha 2-antiplasmin in the early extracorporeal circulation (ECC) phase, exceeding the average hematocrit reduction accounted for by dilution. This drop was the least distinct with CML 2 systems, both with pulsatile and nonpulsatile perfusion, indicating system-inherent influences. Leucocyte cound and PMN-elastase concentration rose significantly during ECC irrespective of oxygenator tested of flow type applied. The rise in leucocyte count even continued for about 4 h after ECC. During the first 40 min of ECC, these changes were paralleled by a significant rise in C3a concentration, suggesting complement activation as a main cause for PMN activation. However, there is reason to suppose involvement of further mechanisms operating in PMN activation, since the elevated C3a-concentrations began to fall off while leucocyte count and PMN-elastase concentrations were still increasing.

Acute-Phase Proteins↗
PubMed1992

The effects of preoperative aspirin therapy on platelet function in cardiac surgery.

Extracorporeal circulation is known to have profound effects upon platelets. Changes in platelet function were assessed in 20 patients undergoing elective coronary artery bypass grafting (CABG) who stopped taking aspirin (100 mg per day) 5-7 days before the operation compared with 20 patients undergoing aortic valve replacement (AVR) who had never taken anticoagulants or aspirin. Platelet aggregometry was carried out using the turbidimetric technique (inducing agents: adenosine diphosphate (ADP) 1.0 and 2.0 mumol/l; collagen 4 micrograms/ml; epinephrine 25 mumol/l), and maximum aggregation as well as the maximum gradient of aggregation were monitored before, during, and after cardiopulmonary bypass (CPB) until the 1st postoperative (p.o.) day. Until the 1st p.o. day blood loss was significantly higher in the CABG (890 +/- 160 ml) than in the AVR patients (420 +/- 120 ml). A total of 8 units of packed red cells (PRC) were given in the CABG group, whereas no homologous blood was necessary in the AVR patients (P < 0.05). The aggregation variables of the CABG patients were lower than in the AVR patients as early as after the induction of anesthesia (difference in maximum aggregation ranged from 13-29%). During CPB and immediately thereafter, all aggregation variables were significantly reduced in the CABG patients (reduction in maximum aggregation ranged from -32 to -49%) and were significantly different from the platelet aggregation in the AVR patients. Five hours after CPB and on the 1st p.o. day platelet aggregation in the CABG group almost returned to baseline values, however, without reaching the values of the AVR patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

The role of enoximone in cardiac surgery.

After cardiopulmonary bypass (CPB), some patients may require circulatory support. This study examined the role of the phosphodiesterase-III inhibitor, enoximone, in cardiac surgery. Eighty patients selected by chance were allocated randomly to two groups: 40 patients received enoximone 1.0 mg kg-1 approximately 10 min before weaning from CPB and 40 served as a control group. Additional pharmacological therapy (adrenaline, noradrenaline, nitroglycerin) was given, when necessary, by anaesthetists who were not involved in the study. In addition to standard monitoring, skin capillary blood flow was assessed using a laser Doppler technique before, during and after CPB until 2 h after the end of the operation. In the period after bypass, cardiac index was always significantly greater in the enoximone than in the control group. Systemic and pulmonary vascular resistance were less in the enoximone-treated patients, indicating a reduction in right and left ventricular wall stress. Oxygen consumption in the enoximone patients was significantly greater after CPB, whereas intrapulmonary shunting was comparable in the two groups. In comparison with baseline values, skin capillary blood flow in the enoximone patients was always greater than that in the control group. In comparison with the control patients, significantly fewer enoximone patients needed adrenaline, and in a smaller dose, even 2 h after operation, whereas more enoximone patients required noradrenaline therapy for a short period. We conclude that the use of enoximone before weaning from CPB improved overall cardiac function, reduced the need of catecholaminergic inotropic support, and provided increased organ perfusion up to 2 h after operation.

Adult↗
PubMed1992

Endothelin plasma levels in old and young patients during open heart surgery: correlations to cardiopulmonary and endocrinology parameters.

We compared endothelin (ET) plasma levels during and after aortocoronary bypass (CPB) grafting in old and young patients. Correlations to cardiopulmonary parameters and catecholamines were tested. The study included 22 patients (11 aged greater than 70 years and 11 aged less than 55 years). Measurements were performed after induction of anesthesia (baseline), before bypass, during bypass, after patients were weaned off bypass, at the end of operation, and after 4-h intensive care (IC) treatment. ET [radioimmunoassay (RIA) technique] and catecholamines [high pressure liquid chromatography (HPLC) technique] plasma levels were determined from arterial blood samples; hemodynamics (pulmonary artery catheter), oxygen data, and laser Doppler flow were also monitored. Baseline ET plasma levels were within normal range (young, 3.1 +/- 0.9 pg/ml, old, 4.5 +/- 1.4 pg/ml). Old patients had higher values during the entire investigation period. During CPB ET plasma levels increased to a maximum immediately after patients were weaned off bypass. A significant increase (twofold to baseline) was noted during IC therapy. ET plasma levels did not correlate to catecholamine plasma levels or to hemodynamic or laser Doppler flow parameters. A significant correlation existed between ET plasma levels and oxygen consumption. Monitoring ET plasma levels appears to be of minor value in predicting circulatory changes and assessing surgical stress. Further investigations must elucidate the increase in oxygen consumption and its correlation to ET plasma level.

Aged↗
PubMed1992

Influence of five different priming solutions on platelet function in patients undergoing cardiac surgery.

The ideal choice of a priming solution of the cardiopulmonary bypass (CPB) and its influence on the hemostatic system are not clear. Addition of albumin was reported to inhibit platelet damaging by blood-surface interactions ("coating"). To explore this possibility in 60 consecutive male patients undergoing elective aortocoronary bypass grafting, five different priming solutions were randomly used: (1) 1000 mL of 5% dextrose + 1000 mL of Ringer's solution (RS) + 250 mL of 5% human albumin (HA); (2) 1850 mL of RS + 400 mL of 20% HA; (3) 1750 mL of RS + 500 mL of 10% low molecular weight hydroxyethyl starch (molecular weight average: 200,000; molar substitution ratio: 0.5); (4) 1750 mL of RS + 500 mL of 3.5% gelatin; (5) 2250 mL of RS. Platelet function was studied by aggregometry (= turbidometric technique; 1.0 and 2.0 mumol/L of adenosine diphosphate (ADP), 4 microL/mL of collagen, 25 mumol/L of epinephrine) before, during, and after CPB until the first postoperative day. Blood loss and need for homologous blood was not different between the groups. During CPB, maximum platelet aggregation induced by ADP was least compromised in group 1 and group 4. At the end of the operation ADP-induced aggregation increased in group 1 (+27%), whereas aggregation was decreased in the other priming solution groups. A significant increase in maximum aggregation was found in group 1 even on the first postoperative day (+132% +/- 16%). Collagen-induced aggregation was also least compromised in group 1. Epinephrine-induced platelet aggregation did not change and was similar for all groups. Maximum gradient of aggregation was influenced in an identical way as maximum aggregation.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Platelets↗
PubMed1992

[Cardiorespiratory and microcirculatory effects following volume replacement using a new hydroxyethyl starch preparation].

Volume therapy is often necessary in cardiac surgery to maintain stable haemodynamics. Various different hydroxyethyl starch (HAES) solutions with different concentrations, mean molecular weights, and degrees of substitution are available for this purpose. In determining the ideal type of volume therapy, not only changes in macrohaemodynamics, but also the influence on microcirculatory blood flow have to be taken into account. The efficacy of a new 10% HAES 130/0.5 solution was studied in cardiac surgery patients in comparison to a standard 10% HAES 200/0.5 preparation. METHODS. In patients scheduled for elective aortocoronary bypass grafting who had a pulmonary capillary wedge pressure (PCWP) of less than 4 mm Hg after induction of anaesthesia, either a new 10% HAES 130/0.5 (n = 15) or a standard 10% HAES 200/0.5 solution (n = 15) was infused to double the reduced PCWP; 15 patients without volume therapy served as controls (n = 15). A two-channel laser Doppler skin blood-flux monitor was used to evaluate microcirculatory alterations. Measurements of laser Doppler flux (LDF) was simultaneously performed at the patient's forehead and forearm before and after volume infusion as well as during and after cardiopulmonary bypass (CPB). In addition, changes in gross haemodynamics were documented using a pulmonary artery catheter. Plasma viscosity and various laboratory parameters, including calculation of intrapulmonary right-to-left shunting (Qs/Qt), were also measured. RESULTS. Cardiac index (CI) increased in both volume groups (HAES 130: max. +38%; HAES 200: +55%). The increases in PCWP and CI were maintained at 40 min after volume infusion only in the HAES 200 patients. Systemic vascular resistance (SVR) decreased most markedly after infusion of HAES 200 (-34%; HAES 130: -18%). No further differences in gross haemodynamics could be seen after CPB. Plasma viscosity and colloid osmotic pressure increased in both HAES groups without significant differences. During the entire investigation period, pulmonary gas exchange (paO2) and Qs/Qt did not differ between the groups. Infusion of both HAES solutions resulted in an increase in LDF that was most pronounced after infusion of HAES 200 (forehead LDF: +81%; HAES 130: +18%) and was evident in the post-bypass period only in these patients (LDF: HAES 200: +82%; HAES 130: -20%; control: -43%). No correlation between LDF values and the other haemodynamic and laboratory parameters could be demonstrated. CONCLUSION. The improvement in macrohaemodynamics was of shorter duration after infusion of the new HAES 130 solution than after standard HAES 200. Volume replacement with HAES 200 resulted in an increase in microcirculatory blood flow that was more pronounced and of longer duration than in the HAES 130 patients. Thus, HAES 130 seems to be less effective than HAES 200 for volume replacement; HAES 200 should be preferred in patients undergoing cardiac surgery.

Cardiac Surgical Procedures↗
PubMed1992

Heparin management during cardiac surgery with respect to various blood-conservation techniques.

BACKGROUND: Various methods to reduce blood consumption are used in cardiac surgery. This study was designed to investigate the influence of various blood-conservation techniques on heparin plasma levels and coagulation variables in the perioperative period. METHODS: Anticoagulation was achieved by application of 300 units/kg bovine heparin before cardiopulmonary bypass (CPB). Ninety patients undergoing coronary bypass surgery were randomly divided into six groups according to different blood-conservation methods: group 1, blood during and after CPB was concentrated by a cell saver (CS); group 2, blood was concentrated by means of a hemofiltration device (HF); group 3, acute normovolemic hemodilution (ANH) was performed in combination with the CS technique (ANH-CS); group 4, ANH was carried out in combination with an HF during CPB (ANH-HF); group 5, acute plasmapheresis (APP) was performed and a CS was used during CPB (APP-CS); and group 6, APP was used in combination with an HF device (APP-HF). RESULTS: Heparin plasma concentration during CPB did not differ significantly among the six groups, ranging from 1.60 to 2.03 units/ml. Antagonization with protamine sulfate after termination of bypass in a 1:1 ratio decreased heparin concentration almost to baseline values. Fibrinogen concentration and antithrombin-III level were lowest in the CS group but were not decreased critically during the entire investigation period. Activated clotting time differed widely among the patients (range 383 to 807 seconds) and showed no significant correlation to heparin plasma levels. Partial thromboplastin time was higher than 300 seconds during the entire period of CPB, also indicating sufficient anticoagulation. Blood loss until day 1 after surgery was significantly most pronounced in the CS group and least in the APP-HF group. CONCLUSIONS: The blood conservation techniques used in this study were safe with regard to sufficient anticoagulation during CPB. No insufficient antagonization with protamine could be observed in the postbypass period.

Antithrombin III↗
PubMed1991

Replication of acetylaminofluorene-adducted plasmids in human cells: spectrum of base substitutions and evidence of excision repair.

In rats fed the liver carcinogen 2-acetylaminofluorene (AAF), the two most abundant types of DNA adduct are N-(deoxyguanosin-8-yl)-2-acetylaminofluorene and its deacetylated derivative. When plasmids carrying AAF adducts replicate in bacteria, the predominant mutations are frameshifts, whereas with deacetylated (AF) adducts, they are mainly base substitutions, just as we found when plasmids carrying AF adducts replicated in human cells. We have investigated the frequency and spectrum of mutations induced when a shuttle vector carrying AAF adducts (85% bound to the C8 position of guanine, 15% to the N2 position) replicated in human cells. The frequency induced per initial AAF adduct was higher than with AF adducts, but the kinds of mutations were similar--i.e., 85% base substitutions, principally G.C----T.A transversions. There was good correlation between the "hot spots" for mutations and hot spots for AAF adduct formation, suggesting that mutational hot spots reflect preferential binding of the carcinogen to DNA. 32P-postlabeling analysis of the adducts before and after the DNA was transfected into the human cells showed that there was no deacetylation of AAF adducts and that 85% of both types of adducts were removed within 3.5 hr, most probably by excision repair.

2-Acetylaminofluorene↗
PubMed1991

Potassium dependence for sperm-egg fusion in mice.

In this study, we examined the potassium requirements for sperm-egg fusion in mouse. Zona-free mouse eggs prepared by the method described by Boldt and Wolf were inseminated with capacitated sperm in culture media containing 0-6 mM extracellular K+, and scored for penetration. Penetration of zona-free eggs was dependent on extracellular K+, with no penetration observed under K(+)-free conditions. Media transfer experiments indicated that the lack of penetration observed was due to effects on fusion, and not on postpenetration events such as sperm head decondensation. To analyze whether the K+ effect was attributable to an effect on the sperm (i.e., occurrence of acrosome reactions), sperm were treated with the Ca2+ ionophore A23187 before insemination. Less than 5% of zona-free eggs were penetrated with ionophore-treated sperm under K(+)-free conditions, suggesting that K+ is required for fusion per se. Addition of ionophore to insemination cultures similarly did not overcome the block to fusion observed under K(+)-free conditions. The potassium channel blockers 4-aminopyridine (0.1-5 mM) and tetraethyl ammonium chloride (5-50 mM) had no inhibitory effect on fusion. These data indicate that extracellular K+ is required for sperm-egg fusion and that this requirement may not involve membrane K+ channels.

Analysis of Variance↗
PubMed1991

RETRACTED: Six different hemofiltration devices for blood conservation in cardiac surgery.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor. Reason: By comparing the results of this article with results reported by Berend Fedderson (Hämofiltration als blutsparendes Verfahren in der Herzchirurgie: sechs verschiedene Hämofilter im Vergleich; Niebüll, Germany; http://d-nb.info/930239350), it has been determined that experimental outcomes have been altered. Thus, the research published in this article was misrepresented to The Annals of Thoracic Surgery and the article should be retracted from the scientific record.

Aged↗
PubMed1991

Cardiorespiratory responses to hypertonic saline solution in cardiac operations.

Infusion of small volumes of hypertonic saline solution (HS) seems to be of benefit in patients with impaired perfusion. The cardiorespiratory response to a 7.2% NaCl solution prepared in hydroxyethylstarch (HES) solution was investigated prospectively in patients undergoing prolonged cardiopulmonary bypass (CPB) (HS-HES group; n = 15); 6% HES 200/0.5 solution was infused in a control group (HES group; n = 15). Volume was given preoperatively to double low pulmonary artery occlusion pressure (less than 4 mm Hg) within 20 minutes. Hemodynamics, oxygen transport variables, and pulmonary gas exchange were studied before and after infusion as well as before and after CPB. Significantly less HS-HES solution (3.06 +/- 0.2 mL/kg) than 6% HES 200/0.5 solution (10.3 +/- 0.9 mL/kg) was necessary to double baseline pulmonary artery occlusion pressure. Fluid balance during CPB was negative in the HS-HES patients (-0.05 mL/kg.min CPB) and was lowest in this group even 5 hours after CPB. Mean arterial pressure, pulmonary arterial pressure, and heart rate were without differences between the groups. Changes in cardiac index (+40%) and total systemic resistance (-25%) were significantly most pronounced in the HS-HES patients, continuing even until the end of operation. Pulmonary gas exchange (arterial oxygen tension, intrapulmonary right-to-left shunting) was least compromised in these patients, particularly after bypass. Oxygen consumption was without difference between the groups; oxygen delivery increased significantly more in the HS-HES patients due to the larger increase in cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiopulmonary Bypass↗
PubMed1991

Pediatric heart transplantation for congenital heart disease and cardiomyopathy.

Orthotopic heart transplantation has become an accepted therapy for adult patients with end-stage heart disease. In newborns and infants, this procedure is still controversial because of the unknown long-term results and the lack of donor organs. Since March 1988, we have performed orthotopic heart transplantation in 11 infants and children with hypoplastic left heart syndrome (n = 6), cardiomyopathy (n = 4), or congenital endocardial fibroelastosis (n = 1). The smallest infant was 3 days old and weighed 2,650 g. Four of 15 potential donors had to be refused for various medical reasons, and 4 were transferred to our hospital for organ retrieval. Seven hearts were procured remotely. We accepted weight mismatches up to 105% between donor and recipient. There were three perioperative deaths, two in patients 5 and 17 days old with hypoplastic left heart syndrome and 1 in a 2-year-old patient with a dilated cardiomyopathy. All 3 patients had drug-resistant right heart failure. A 2-year-old girl with a dilated cardiomyopathy died 2 months after transplantation owing to severe pulmonary embolism originating from the superior vena cava. The remaining 7 patients are alive and well between 1 month and 31 months after transplantation. Angiographic follow-up has not revealed signs of graft atherosclerosis at 2 years.

Cardiomyopathy, Dilated↗
PubMed1991

Does the technique of cardiopulmonary bypass affect lung water content?

Several efforts have been made to improve the technique of cardiopulmonary bypass (CPB), including the use of pulsatile flow and the modification of cannulation technique. The present study focused upon extravascular lung water (EVLW) in 60 aortocoronary bypass patients subjected to four different perfusion techniques during CPB: group 1 (n = 15): non-pulsatile flow and standard cannulation; group 2 (n = 15); pulsatile flow and standard cannulation; group 3 (n = 15): nonpulsatile flow and monoatrial cannulation (i.e., always "partial" bypass during CPB); group 4 (n = 15): pulsatile flow and monoatrial cannulation. EVLW content was measured using the double-indicator dilution technique with indocyanine green; in addition, various hemodynamic and laboratory variables were measured. Lung water content rose above normal values (mean: 5.79 +/- 0.33 ml/kg) only in the groups submitted to the standard cannulation technique, irrespective of whether the perfusion flow was pulsatile or not (group 1: + 27.4%; group 2: + 25.5%). Pulmonary gas exchange, too, was compromised only in these patients (PaO2 in group 1 -19% and in group 2 -17%; Qs/Qt in group 1 + 36 rel. % and in group 2 + 29 rel. %), whereas all patients with monoatrial cannulation and partial bypass throughout the CPB period showed no rise in EVLW content or Qs/Qt and no drop in PaO2. From the results of this study we conclude that pulsatile perfusion during open heart surgical procedure has no advantages in regard to lung water content. Monoatrial cannulation with partial bypass at all times during CPB, however, seems to be beneficial, probably owing to the maintenance of pulmonary circulation during the bypass period.

Aged↗
PubMed1991

RETRACTED: Does the preparation of heparin influence anticoagulation during cardiopulmonary bypass?

Various preparations of heparin from different manufacturers are commercially available. The influence of bovine lung heparin (BLH) and porcine mucosal heparin (PMH) on anticoagulation and heparin plasma concentration was investigated in four groups of 10 patients undergoing elective aortocoronary bypass grafting either after single dose or repetitive dose (after 60 minutes) of one of these heparin preparations. Heparin plasma concentration increased significantly after injection of heparin (BLH: minimum, 1.67 U/mL; maximum, 2.10 U/mL; PMH: minimum, 1.69 U/mL; maximum, 2.15 U/mL). Sixty minutes after the initial dose, heparin plasma levels were higher in the patients who received PMH. Supplemental heparin doses 60 minutes after the loading dose increased plasma heparin concentration only with porcine mucosal heparin. Elimination of heparin in the urine was not different among the groups. Fibrinogen and antithrombin III concentrations, as well as activated clotting time (ACT; always greater than 400 seconds) and partial thromboplastin time (PTT; always greater than 300 seconds), did not differ among the groups, indicating effective anticoagulation during the bypass period with both types of heparin. It can be concluded that sufficient anticoagulation can be achieved with either kind of heparin. PMH seems to be longer acting and a repeat dose in these patients seems to be necessary only if cardiopulmonary bypass lasts longer than 90 minutes.

Aged↗