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A model of stepwise isovolaemic blood exchange in anaesthetised, spontaneously breathing rats to evaluate the oxygen transport efficiency of artificial oxygen carriers

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ARTIFICIAL CELLS BLOOD SUBSTITUTES AND IMMOBILIZATION BIOTECHNOLOGY 2000年第2期28卷 113-127页

作者： Guth, S Dinkelmann, S Domack, U Pötzschke, H Barnikol, WKR Univ Mainz Klin Herz Thorax & Gefasschirurg D-55101 Mainz Germany Univ Tubingen Abt Transfus Med & Blutbank D-72076 Tubingen Germany Private Univ Witten Herdecke Bereich Klin Physiol D-58455 Witten Germany Sanguibiotech AG D-58455 Witten Germany

Our research pursues the production of hypo-oncotic artificial oxygen carriers, based on artificial covalently cross-linked hyperpolymeric mammalian haemoglobins. To evaluate their in vivo efficiency in oxygen delivery to the tissue we developed a small animal model of stepwise isovolaemic blood exchange in anaesthetised,, spontaneously breathing rats. With the aid of a two-way respiratory micro valve for small animals the overall oxygen uptake by the tissue of the animal can be determined. Measurements of oxygen contents in arterial and mixed venous blood and of some further blood parameters together with known oxygen-binding characteristics of artificial and native oxygen carriers, permits the determination of the way the two oxygen carriers contribute to the overall oxygen uptake. These so-called partial oxygen netto transport rates (i.e. partial oxygen uptakes), related to the corresponding intravascular mass flow of the transporters, are characteristic measures of the efficiency of the oxygen transporter, the so-called oxygen transport quality. Other biological indicators for an adequate oxygen supply are oxygen-dependent changes of ventilation, cardiac output, heart rate, and systemic vascular resistance. The performance of artificial oxygen carriers is elucidated by a comparison with experimental results from the analogous treatment of rats with non oxygen-transporting plasma expanders.

关键词：麻醉生物转运血液循环/药物作用血液代用品/药代动力学血量心排血量/药物作用评价研究血细胞比容血液稀释/方法血红蛋白类/药代动力学血红蛋白类/生理学氧/代谢氧耗量/药物作用氧耗量/生理学肺换气/药物作用肺通气/药物作用磷酸吡哆醛/类似物和衍生物磷酸吡哆醛/药代动力学磷酸吡哆醛/生理学大鼠 Sprague-Dawley 呼吸血管阻力/药物作用动物男(雄)性大鼠

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MATERNAL AND FETAL RESPONSES TO HALOTHANE IN PREGNANT MONKEYS

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ACTA ANAESTHESIOLOGICA SCANDINAVICA 1975年第2期19卷 154-158页

作者： ENG, M BONICA, JJ AKAMATSU, TJ BERGES, PU YUEN, DD UELAND, K UNIV WASHINGTON DEPT ANESTHESIOLSEATTLEWA 98195 UNIV WASHINGTON ANESTHESIA RES CTRDEPT OBSTET & GYNECOLSEATTLEWA 98195 UNIV WASHINGTON REG PRIMATE RES CTRSEATTLEWA 98195

Maternal cardiac output, blood pressure, heart rate, fetal blood pressure, heart rate and respiratory blood gases, and uterine blood flow were measured in six pregnant monkeys during halothane-nitrous oxide and oxygen anesthesia and compared to theses same parameters observed during nitrous oxide and oxygen anesthesia. Halothane 1.5% was associated with a decrease in maternal arterial pressure (54%), heart rate (10%), cardiac output (17%), total peripheral resistance (40%), and uterine blood flow (38%). Mean fetal heart rate decreased 18% and mean fetal blood pressure 22%. These changes in fetal hemodynamics were probably related to a direct depression of the fetal cardiovascular system and its usual compensatory mechanism as well as the fetal asphyxia secondary to the decrease in uterine blood flow.

关键词：麻醉全身血压/药物作用二氧化碳/血液心排血量/药物作用抑制化学性胎儿心脏/药物作用胎儿/药物作用氟烷/药理学心率/药物作用猕猴属母体胎儿间交换氧/血液局部血流子宫/血液供给血管阻力/药物作用动物女(雌)性妊娠

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HEMODYNAMIC OBSERVATIONS IN EARLY PERIOD AFTER HUMAN HEART-TRANSPLANTATION

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JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 1975年第2期69卷 264-270页

作者： STINSON, EB CAVES, PK GRIEPP, RB OYER, PE RIDER, AK SHUMWAY, NE STANFORD UNIV MED CTRDEPT CARDIOVASC SURGSTANFORDCA 94305

Serial hemodynamic measurements, including determination of cardiac output by the Fick technique, were obtained in 10 human cardiac recipients for intervals up to 38 days after transplantation. Immediately postoperatively, donor cardiac output was severely depressed because of limitation of stroke volume. Spontaneous recovery of cardiac output and stroke volume then occurred gradually over the first 4 postoperative days to normal or nearly normal levels. Rate augmentation by atrial and/or ventricular pacing early after transplantation had little effect on donor heart performance, but isoproterenol caused significant enhancement of graft function and is now used routinely in postoperative management. Serial hemodynamic monitoring proved to be of little use in the predicion or confirmation of acute graft rejection episodes.

关键词：血压/药物作用心排血量/药物作用导管插入术中心静脉压/药物作用移植物排斥心脏心率/药物作用心脏移植异丙肾上腺素/药理学心脏起搏器人工肺循环/药物作用移植同种人类

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CARDIAC RECEPTORS IN DUCKS - LINK BETWEEN VASOCONSTRICTION AND BRADYCARDIA DURING DIVING

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ACTA PHYSIOLOGICA SCANDINAVICA 1976年第1期97卷 13-19页

作者： BLIX, AS WENNERGREN, G FOLKOW, B UNIV GOTEBORG DEPT PHYSIOL Gothenburg SWEDEN

It was demonstrated that cardiac receptors, mostly likely of the left ventricular type, are present also in the duck''s heart. These receptors and their reflex responses (i.e. bradycardia and hypotension) could be blocked by intrapericardial administration of lidocaine. Initially, such receptor blockade did not affect efferent vagal control of heart rate, as revealed by undiminished bradycardia in response to a standardized vagal stimulation. After cardiac receptor blockade, however, the duck''s normal bradycardia response to head immersion was greatly reduced. The cardiovascular response to submersion was not characterized by a marked rise in arterial pressure, with superimposed bouts of intensified bradycardia and pressure reduction, evidently induced reflexly from the arterial baroreceptors. Meanwhile, the bradycardia response to standardized efferent vagal stimulation was still the same as before intrapericardial lidocaine injection. The marked rise in cardiac filling pressure following the intense chemoreceptor-induced constriction of both resistance and capacitance vessels, activates ventricular stretch receptors signalling in vagal afferents. Apparently, the activation of these receptors contributes crucially to the bradycardia and reduction of cardiac output, which balance off the greatly increased peripheral resistance in the diving duck.

关键词：血压/药物作用心排血量/药物作用潜水鸭/生理学电刺激心脏/生理学心率/药物作用心室/生理学利多卡因/药理学压力感受器/生理学迷走神经/生理学动物女(雌)性男(雄)性

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TREATMENT OF STATUS ASTHMATICUS AND RESPIRATORY-FAILURE

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PEDIATRIC CLINICS OF NORTH AMERICA 1975年第1期22卷 163-171页

作者： COTTON, EK PARRY, W UNIV COLORADO MED CTRCARDIOPULM DIV4200 E 9TH AVEDENVERCO 80220 FITZSIMONS ARMY MED CTR DEPT PEDIATPEDIAT PULM SECTDENVERCO

Mortality from status asthmaticus is very significant; however, over the past 6 years treatment has been developed which has lowered the number of deaths. This therapy consists of oxygen, fluids, bronchodilators, ster... 详细信息

关键词：肾上腺皮质激素类/治疗应用哮喘/并发症哮喘/药物疗法哮喘/治疗碳酸氢盐类/治疗应用支气管扩张药/治疗应用心排血量/药物作用插管法气管内/副作用异丙肾上腺素/药理学肺/药物作用氧吸入疗法物理治疗技术呼吸人工/副作用呼吸功能不全/病因学呼吸功能不全/病理生理学呼吸功能不全/治疗水电解质平衡人类

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Complement-mediated acute effects of liposome-encapsulated hemoglobin

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ARTIFICIAL CELLS BLOOD SUBSTITUTES AND IMMOBILIZATION BIOTECHNOLOGY 1999年第1期27卷 23-41页

作者： Szebeni, J Alving, CR Walter Reed Army Inst Res Dept Membrane Biochem Washington DC 20307 USA

Recent studies an liposome-encapsulated hemoglobin (LEH) have indicated that this potential blood substitute can activate the complement (C) system of rats, pigs and man. The reaction can involve both the classical and the alternative pathways, and is mediated, in part, by the binding of natural anti-lipid antibodies to the lipid membrane of liposomes. The significance of these discoveries lies in the fact that C activation appears to be the primary cause of the acute physiological, hematological and laboratory changes that have been observed previously in rats and pigs following the administration of LEH or liposomes, which changes include pulmonary vasoconstriction with decreased cardiac output. In light of the proposed use of LEH as an emergency blood substitute, the latter impairment of cardiopulmonary function may warrant particular circumspection as it could aggravate the clinical state of trauma patients who are prone to develop respiratory distress partly as a consequence of C activation by the injury. Our studies on rats and pigs suggest that the above acute side effects of LEH, including the cardiopulmonary distress, can be efficiently inhibited with soluble complement receptor type I, a specific inhibitor of C activation.

关键词：血液代用品/药理学心排血量/药物作用补体激活/药物作用药物载体血红蛋白类/药理学脂质体/药理学受体补体/代谢血管收缩/药物作用动物人类大鼠

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SENSITIVITY AND AFTERLOAD INDEPENDENCE OF ZERO-LOAD AORTIC FLOW

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ANNALS OF BIOMEDICAL ENGINEERING 1976年第4期4卷 330-342页

作者： MIN, BG FICH, S KOSTIS, JB DOBLAR, D KUO, PT RUTGERS STATE UNIV COLL ENGN DEPT ELECT ENGN NEW BRUNSWICK NJ 08903 USA

The computed zero-load flow is the expected aortic flow when the aortic pressure is zero, thus eliminating the effect of afterload on ventricular ejection. Zero-load flow was computed in 15 anesthetized dogs (sodium pentobarbital 25 mg/kg, i.v.) by studying the response of left-ventricular pressure or aortic pressure, and aortic flow to the change in aortic input impedance induced by partial snare occlusion of the aorta. The waveform and peak value of zero-load flow were computed from a theoretical model of the left ventricle and verified by measurements of aortic flow in the first beat after transection of the aorta. To study the sensitivity, changes of zero-load flow were computed under the enhanced inotropic state produced by isoproterenol (0.1 .mu.g/kg per min), and under the depressed contractile state induced by propranolol (0.15 mg/kg). Administration of isoproterenol resulted in an increase in the peak zero-load by 143.9% (P < 0.001), compared with a 50.6% increase (P < 0.05) in peak dp/dt [change in pressure with time]. The difference of the variations was statistically significant in a paired t test. After injection of propranolol, peak zero-load flow decreased by 32.0% (P < 0.005). Afterload independence of zero-load flow was studied by computing zero-load flow before and after increasing arterial pressure by partial aortic occlusion or injection of 5 mg methoxamine. After injection of methoxamine in denervated dogs, the peak zero-load flow increased by 11.2% (N.S. [not significant]), while input resistance increased by 153% (P < 0.025). The peak zero-load flow decreased by 8% (N.S.) after partial aortic occlusion, while cardiac output decreased by 26.7% (P < 0.001). The computed peak zero-load flow may be an afterload independent index of the pumping capability of the left ventricle in the intact heart.

关键词：主动脉/生理学血液循环/药物作用血压心排血量/药物作用去神经支配心率/药物作用心室/生理学异丙肾上腺素/药理学甲氧明/药理学模型生物学血管阻力/药物作用动物狗

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Responses to constant work rate bicycle ergometry exercise in primary pulmonary hypertension:: The effect of inhaled nitric oxide

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2000年第2期36卷 547-556页

作者： Riley, MS Pórszász, J Engelen, MPKJ Shapiro, SM Brundage, BH Wasserman, K Univ Calif Los Angeles Harbor Med Ctr Div Resp & Crit Care Physiol & Med Torrance CA 90509 USA Univ Calif Los Angeles Harbor Med Ctr St Johns Cardiovasc Res Ctr Div Cardiol Torrance CA 90509 USA

OBJECTIVES The purpose of this study was to investigate the responses oipatients with primary pulmonary hypertension (PPH) to constant work rate exercise and to examine the effect of nitric oxide (NO) inhalation. BACKGROUND Maximal exercise tolerance is reduced in PPH, but gas exchange responses to constant work rate exercise have not been defined. We hypothesized that increased pulmonary vascular resistance in PPH would reduce the rate of rise of minute oxygen consumption in response to a given work rate. Because NO may lower pulmonary Vascular pressures in PPH, we also postulated that inhaled NO might ameliorate gas exchange abnormalities. METHODS Nine PPH patients and nine matched normal subjects performed 6-min duration constant work rate cycle ergometry exercise (33.9 +/- 13.4 W). Patients performed two experiments: breathing air and breathing air with NO (20 ppm). Preexercise right ventricular systolic pressure was assessed by Doppler echocardiography. Normal subjects performed the air experiment only. Gas exchange and heart rate responses were characterized by fitting monoexponential curves. RESULTS In PPH patients, resting right ventricular systolic pressure fell after NO inhalation (from 83.8 +/- 16.9 to 73.9 +/- 21.6 mm Hg, p < 0.01, analysis of variance with Tukey correction), but not after breathing air alone (from 88.0 +/- 20.8 to 86.7 +/- 20.6 mm Hg, p = NS). Nitric oxide did not affect any of the gas exchange responses. Minute oxygen consumption was similar by the end of exercise in patients and normals, but increased more slowly in patients (mean response time [MRT]: air, 63.17 +/- 14.99 s;NO, 61.60 +/- 15.45 s) than normals (MRT, 32.73 +/- 14.79, p < 0.01, analysis of variance, Tukey test). Minute oxygen consumption kinetics during recovery were slower in patients (MRT air: 82.50 +/- 29.94 s;NO, 73.36 +/- 15.87 s) than in normals (MRT, 34.59 +/- 7.11 s, p < 0.01). Heart rate kinetics during exercise and recovery were significantly slower in patients

关键词：心排血量/药物作用运动(Exercise)/生理学运动试验血流动力学/药物作用高血压肺性/药物疗法高血压肺性/病理生理学一氧化氮/药理学一氧化氮/治疗应用氧耗量肺换气/药物作用血管舒张药/药理学血管舒张药/治疗应用成年人女(雌)性人类中年人

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EFFECTS OF EPINEPHRINE ON DISTRIBUTION OF BLOOD-FLOW IN PREGNANT EWE

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AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY 1976年第2期124卷 156-163页

作者： ROSENFELD, CR BARTON, MD MESCHIA, G UNIV COLORADO MED CTRDEPT PEDIATDIV PERINATAL MEDBOULDERCO UNIV COLORADO MED CTRDEPT PHYSIOLBOULDERCO UNIV COLORADO MED CTRDEPT ANESTHESIOLBOULDERCO

Seven pregnant ewes ranging from 85 to 140 days of gestation were infused with systemic doses of epinephrine and uterine arterial flow dose-response curves were determined. With a constant systemic infusion of epinephrine at a mean rate of 0.29 ± 0.03 μg/Kg. min., and the radionuclide labeled microsphere method to measure arterial blood flow, a 38.5 per cent decrease in total uterine arterial blood flow was demonstrated while systemic pressure was unaltered. At this dose the reduction in endometrial blood flow was significantly greater (−58.7 per cent) than that in either the myometrium (−36.9 per cent) or placental cotyledons (−34.5 per cent) (p < 0.025 and < 0.005, respectively). There also occured a decrease in blood flow to the mammary gland and the pancreas, whereas increases in blood flow to the skektal muscle, adipose tissue, and spleen were documented. It is evident from this study that during the period of ovine pregnancy investigated, the vascular beds of all tissues comprising the pregnant uterus, including the placental cotyledons, are sensitive to the vasoconstrictive effects of epinephrine.

关键词：血液循环/药物作用血压/药物作用心排血量/药物作用肾上腺素/药理学妊娠动物绵羊/生理学子宫/血液供给血管阻力/药物作用血管舒缩系统/药物作用动物女(雌)性妊娠

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HEMODYNAMIC AND METABOLIC EFFECTS OF ISOSORBIDE DINITRATE IN CHRONIC CONGESTIVE HEART-FAILURE

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AMERICAN HEART JOURNAL 1975年第3期90卷 346-352页

作者： GRAY, R CHATTERJEE, K VYDEN, JK GANZ, W FORRESTER, JS SWAN, HJC UNIV CALIF DEPT MED LOS ANGELES CA USA CEDARS SINAI MED CTR DEPT CARDIOL 4833 FOUNTAIN AVE LOS ANGELES CA 90029 USA

To assess the potential beneficial effects of a nonparenteral vasodilator, sublingual isosorbide dinitrate (5 to 15 mg.) was administered in 12 patients with chronic congestive heart failure refractory to conventional therapy. Hemodynamic measurements were performed before and at 15 minute intervals after drug administration for 90 minutes. Venous capacitance was measured at 5 minute intervals. Myocardial metabolism was also studied in five patients before and after drug administration. Hemodynamic effects were characterized by a modest decrease in mean arterial pressure (85 ± 3 to 78 ± 2 [S.E.M.] mm. Hg) and substantial decrease in right atrial (10 ± 1 to 6 ± 1), pulmonary arterial (39 ± 4 to 30 ± 4) and pulmonary capillary wedge pressures (28 ± 2 to 21 ± 2). These changes were accompanied by an increase in venous capacitance (2.46 ± 0.16 to 3.99 ± 0.24 c.c./100 c.c. of tissue). Along with a decrease in left ventricular filling pressure, cardiac index increased (1.99 ± 0.13 to 2.37 ± 0.15 L./min./M.2 ). No significant effect on heart rate was seen. ΔP Δt , an index related to left ventricular dp dt , increased in all but one patient (253 ± 31 to 298 ± 39 mm. Hg/sec.) (p < 0.02 for all changes) in the face of decreased preload and afterload and unchanged heart rate, suggesting improved contractile state. A decrease in coronary blood flow (165 ± 13 to 131 ± 15 c.c./min.) and myocardial oxygen consumption (18.1 ± 1.6 to 14.5 ± 1.6 c.c./min.) was noted (p < 0.02). No change in arterial-coronary sinus oxygen difference or lactate extraction was observed. These data demonstrate that the objectives of therapy in congestive heart failure, namely improved forward output and decreased ventricular filling pressures, can be achieved without metabolic deterioration by using sublingual isosorbide. The mechanisms responsible are related to diminished impedance to ventricular ejection and peripheral pooling of blood. Since the duration of action does not usually exceed 90 minutes,

关键词：投药口服血压/药物作用心排血量/药物作用冠状动脉循环/药物作用药物评价心率/药物作用异山梨酯硝酸/投药和剂量异山梨酯硝酸/治疗应用乳酸盐类/代谢心肌/代谢氧耗量/药物作用肺循环/药物作用片剂血管阻力/药物作用静脉压/药物作用成年人老年人女(雌)性人类男(雄)性中年人

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