Br.J. Anaesth. (1979), 51, 1011
OXYGEN TRANSPORT DURING DOPAMINE INFUSION IN DOGS A. SCOTT, M. K. CHAKRABARTI AND G. M. HALL SUMMARY
Dopamine has been shown to be effective in improving cardiac output in a wide variety of shock conditions (Goldberg, McDonald and Zimmerman, 1963; Loeb et al., 1971; Thompson, 1977). In addition to its activity at specific dopamine receptors, dopamine has both alpha- and beta-adrenergic agonist activity (Goldberg, 1972). Catecholamines have profound effects on intermediary metabolism which result in an increased total body oxygen consumption (HimmsHagen, 1967) and may adversely affect pulmonary gas exchange (Finlay, Wightman and Sykes, 1970). Accordingly we have investigated the overall effects of dopamine on oxygen transport at two different doses. The results of metabolic studies will be reported separately (Hall, Young and Scott, 1979).
tube was inserted to the trachea and the lungs were ventilated with ambient air using a Cape Ventilator. The respiratory frequency was maintained at 15 b.p.m. Airway pressure was monitored throughout and whenever there was evidence of respiratory muscle activity (usually negative airway pressure during expiration or sometimes an increase in positive endinspiratory pressure) incremental doses of thiopentone 5 mg kg" 1 were given in order to maintain completely passive ventilation. Such increments of thiopentone were given at least 10 min before cardiorespiratory observations were made. During an experiment lasting 3.5-4 h, the average number of incremental doses administered was 3.9. Catheters for pressure measurement and blood sampling were placed in the aorta via the left femoral artery and in the main pulmonary artery via the METHODS Twelve cross-bred dogs (weight 11.7-34.2 kg) were right jugular vein. A Swan-Ganz catheter was studied. They were fed on a standard laboratory passed into a pulmonary artery from the left jugular diet and allowed water ad libitum for at least 3 days vein for measurement of pulmonary capillary wedge before each experiment. The animals were allocated pressure. Pressures were recorded continuously using randomly to either a small-dose (dopamine HC1 strain gauges, the amplified outputs displayed on a 10 (xg kg" 1 min"1) or a large-dose (dopamine HC1 six-channel hot-wire chart recorder (Devices Ml9). The strain gauges were calibrated against a column 30 jig kg" 1 min"1) treatment group. of saline. Mean pressures were derived electronically. The dogs were anaesthetized with thiopentone Cardiac output was determined by indocyanine 1 1 15-20 mg kg" and pentobarbitone 5-7 mg kg" . green dye dilution. Dye was injected into the right They were placed in the supine position, a cuffed atrium and sampled from the aorta. The output from the densitometer (Gilford 103) was recorded ANDREW SCOTT, M.B., B.S., F.F.A.R.C.S.; M. K. CHAKRABARTI, and the cardiac output calculated from the coB.SC, M.PHIL.; G. M. HALL, M.B., B.S., PH.D., F.F.A.R.C.S., Department of Anaesthetics, Royal Postgraduate Medical ordinates of the resulting curve by the method of School, DuCane Road, London W12 0HS. Simons and White (1976). The mean value of at 0007-O912/79/111011-O9 §01.00
© Macmillan Journals Ltd 1979
Downloaded from http://bja.oxfordjournals.org/ at University of Western Ontario on June 7, 2015
Catecholamines increase not only oxygen delivery to tissues but also oxygen consumption (Ko2). The effect of an infusion of dopamine hydrochloride has been studied at two doses, each in six dogs. Dopamine 10 ;xg kg" 1 min" 1 caused an increase in haemoglobin concentration and altered cardiac output, oxygen availability and total body oxygen consumption such that oxygen availability ratio increased and (CaOt — Cv0,) decreased although these changes were not statistically significant. Dopamine 30 (ig kg" 1 min" 1 increased (P 25 cm H2O). Between 5 and 10 min any final adjustment of the ventilation was made. After 15 min a venous blood sample for biochemical studies was drawn and the blood replaced with an equal volume of dextran 70. Between 25 and 30 min the cardiovascular and respiratory measurements were performed. At 30 min a second venous blood sample was taken (fig. 1) and the infusion changed immediately to dopamine HC1 (Intropin, Arnar Stone) either 10 fj.g kg" 1 min" 1 or 30 (ig kg" 1 min" 1 in sodium chloride 0.15 mol litre" 1 . This infusion was continued for 1 h during which the sequence of events described above was repeated twice. Finally, sodium chloride 0.15 mol litre" 1 was infused at the same rate for a further 1 h and two further sets of measurements were obtained (fig. 1).
70 75 80 Time (min)
60 90 Time (min)
85
NaCI | 120
90
150
FIG. 1. Schematic representation of the experimental procedure. Top: Events occurring during each 30-min period of the experiment. Bottom: Time sequence of the control (sodium chloride 0.15 mol litre"1) and drug infusions. C.V.S. = cardiovascular system. Calculations
Correction factors were applied for temperature changes and blood-gas factors of the oxygen electrodes. The derived variables were computed using standard respiratory formulae. Venous admixture was calculated using the measured arteriovenous oxygen content difference (Ca02—CvOl) as described previously (Scott et al., 1978). Oxygen availability was calculated as the product of arterial oxygen content (CaOa) and cardiac output, oxygen availability ratio as the ratio of oxygen availability to oxygen consumption. Statistical comparisons were made as follows: (a) in each dose group the mean value of a variable at any time was compared with the mean value at each other time using two-way analysis of variance and Student's /test for paired data values; (b) between dose groups the mean value of a variable at any time was compared with the mean value of that variable at the same time but a different dose using Student's
Downloaded from http://bja.oxfordjournals.org/ at University of Western Ontario on June 7, 2015
least two satisfactory curves was used. Heart rate was measured by counting the aortic pressure pulses during a 15-s period recorded at a paper speed of 500 mm min" 1 . Expired gas was separated from the gas compressed in the ventilator tubing by a collect valve (Sykes, 1969). It was passed through a mixing chamber and the volume measured using a calibrated dry-gas meter. Mixed expired oxygen concentration was determined using a paramagnetic oxygen analyser (Servomex 101 A); end-tidal and mixed expired carbon dioxide concentration using an infra-red analyser (Hartmann-Braun URAS 4). During the gas sampling arterial and mixed venous blood samples were drawn into heparinized syringes and analysed immediately. Po 2 , Pco 2 and pH were measured in duplicate on separate electrode systems (ABL 1 and PHM-1, Radiometer, Copenhagen). The oxygen content of arterial and mixed venous blood (Ca0]!, Cv 0 ) was determined directly. Oxygen was displaced from haemoglobin by carbon monoxide and measured in an electrolytic cell (Lex-O2-Con, Lexington Instruments Corp.). Haemoglobin concentration was determined using the cyanmethaemoglobin method.
BRITISH JOURNAL OF ANAESTHESIA
DOPAMINE AND OXYGEN TRANSPORT
1013
two-sample t test. P Cvo,) sank, wenn auch diese Veranderungen statistisch gesehen nicht wesentlich waren. Eine Dosis von 30 ng kg" 1 min" 1 Dopamin (P < 0,05) erhohte das Herzminutenvolumen, die Hamoglobinkonzentration und Cao,, und senkte wesentlich das Schlagvolumen und KD/KT. Obwohl die Sauerstoffverfiigbarkeit stieg, waren die Anstiege des Sauerstoffverbrauches grosser, was zu statistisch unwesentlichen Abstiegen des Sauerstoffverfugbarkeitsverhaltnisses und zu einem Anstieg von (Cao, —CVQ,) fuhrte. Beendigung der Dopamin-Infusion fuhrte zu wesentlichen
(P
OXYGEN TRANSPORT DURING DOPAMINE INFUSION IN DOGS A. SCOTT, M. K. CHAKRABARTI AND G. M. HALL SUMMARY
Dopamine has been shown to be effective in improving cardiac output in a wide variety of shock conditions (Goldberg, McDonald and Zimmerman, 1963; Loeb et al., 1971; Thompson, 1977). In addition to its activity at specific dopamine receptors, dopamine has both alpha- and beta-adrenergic agonist activity (Goldberg, 1972). Catecholamines have profound effects on intermediary metabolism which result in an increased total body oxygen consumption (HimmsHagen, 1967) and may adversely affect pulmonary gas exchange (Finlay, Wightman and Sykes, 1970). Accordingly we have investigated the overall effects of dopamine on oxygen transport at two different doses. The results of metabolic studies will be reported separately (Hall, Young and Scott, 1979).
tube was inserted to the trachea and the lungs were ventilated with ambient air using a Cape Ventilator. The respiratory frequency was maintained at 15 b.p.m. Airway pressure was monitored throughout and whenever there was evidence of respiratory muscle activity (usually negative airway pressure during expiration or sometimes an increase in positive endinspiratory pressure) incremental doses of thiopentone 5 mg kg" 1 were given in order to maintain completely passive ventilation. Such increments of thiopentone were given at least 10 min before cardiorespiratory observations were made. During an experiment lasting 3.5-4 h, the average number of incremental doses administered was 3.9. Catheters for pressure measurement and blood sampling were placed in the aorta via the left femoral artery and in the main pulmonary artery via the METHODS Twelve cross-bred dogs (weight 11.7-34.2 kg) were right jugular vein. A Swan-Ganz catheter was studied. They were fed on a standard laboratory passed into a pulmonary artery from the left jugular diet and allowed water ad libitum for at least 3 days vein for measurement of pulmonary capillary wedge before each experiment. The animals were allocated pressure. Pressures were recorded continuously using randomly to either a small-dose (dopamine HC1 strain gauges, the amplified outputs displayed on a 10 (xg kg" 1 min"1) or a large-dose (dopamine HC1 six-channel hot-wire chart recorder (Devices Ml9). The strain gauges were calibrated against a column 30 jig kg" 1 min"1) treatment group. of saline. Mean pressures were derived electronically. The dogs were anaesthetized with thiopentone Cardiac output was determined by indocyanine 1 1 15-20 mg kg" and pentobarbitone 5-7 mg kg" . green dye dilution. Dye was injected into the right They were placed in the supine position, a cuffed atrium and sampled from the aorta. The output from the densitometer (Gilford 103) was recorded ANDREW SCOTT, M.B., B.S., F.F.A.R.C.S.; M. K. CHAKRABARTI, and the cardiac output calculated from the coB.SC, M.PHIL.; G. M. HALL, M.B., B.S., PH.D., F.F.A.R.C.S., Department of Anaesthetics, Royal Postgraduate Medical ordinates of the resulting curve by the method of School, DuCane Road, London W12 0HS. Simons and White (1976). The mean value of at 0007-O912/79/111011-O9 §01.00
© Macmillan Journals Ltd 1979
Downloaded from http://bja.oxfordjournals.org/ at University of Western Ontario on June 7, 2015
Catecholamines increase not only oxygen delivery to tissues but also oxygen consumption (Ko2). The effect of an infusion of dopamine hydrochloride has been studied at two doses, each in six dogs. Dopamine 10 ;xg kg" 1 min" 1 caused an increase in haemoglobin concentration and altered cardiac output, oxygen availability and total body oxygen consumption such that oxygen availability ratio increased and (CaOt — Cv0,) decreased although these changes were not statistically significant. Dopamine 30 (ig kg" 1 min" 1 increased (P 25 cm H2O). Between 5 and 10 min any final adjustment of the ventilation was made. After 15 min a venous blood sample for biochemical studies was drawn and the blood replaced with an equal volume of dextran 70. Between 25 and 30 min the cardiovascular and respiratory measurements were performed. At 30 min a second venous blood sample was taken (fig. 1) and the infusion changed immediately to dopamine HC1 (Intropin, Arnar Stone) either 10 fj.g kg" 1 min" 1 or 30 (ig kg" 1 min" 1 in sodium chloride 0.15 mol litre" 1 . This infusion was continued for 1 h during which the sequence of events described above was repeated twice. Finally, sodium chloride 0.15 mol litre" 1 was infused at the same rate for a further 1 h and two further sets of measurements were obtained (fig. 1).
70 75 80 Time (min)
60 90 Time (min)
85
NaCI | 120
90
150
FIG. 1. Schematic representation of the experimental procedure. Top: Events occurring during each 30-min period of the experiment. Bottom: Time sequence of the control (sodium chloride 0.15 mol litre"1) and drug infusions. C.V.S. = cardiovascular system. Calculations
Correction factors were applied for temperature changes and blood-gas factors of the oxygen electrodes. The derived variables were computed using standard respiratory formulae. Venous admixture was calculated using the measured arteriovenous oxygen content difference (Ca02—CvOl) as described previously (Scott et al., 1978). Oxygen availability was calculated as the product of arterial oxygen content (CaOa) and cardiac output, oxygen availability ratio as the ratio of oxygen availability to oxygen consumption. Statistical comparisons were made as follows: (a) in each dose group the mean value of a variable at any time was compared with the mean value at each other time using two-way analysis of variance and Student's /test for paired data values; (b) between dose groups the mean value of a variable at any time was compared with the mean value of that variable at the same time but a different dose using Student's
Downloaded from http://bja.oxfordjournals.org/ at University of Western Ontario on June 7, 2015
least two satisfactory curves was used. Heart rate was measured by counting the aortic pressure pulses during a 15-s period recorded at a paper speed of 500 mm min" 1 . Expired gas was separated from the gas compressed in the ventilator tubing by a collect valve (Sykes, 1969). It was passed through a mixing chamber and the volume measured using a calibrated dry-gas meter. Mixed expired oxygen concentration was determined using a paramagnetic oxygen analyser (Servomex 101 A); end-tidal and mixed expired carbon dioxide concentration using an infra-red analyser (Hartmann-Braun URAS 4). During the gas sampling arterial and mixed venous blood samples were drawn into heparinized syringes and analysed immediately. Po 2 , Pco 2 and pH were measured in duplicate on separate electrode systems (ABL 1 and PHM-1, Radiometer, Copenhagen). The oxygen content of arterial and mixed venous blood (Ca0]!, Cv 0 ) was determined directly. Oxygen was displaced from haemoglobin by carbon monoxide and measured in an electrolytic cell (Lex-O2-Con, Lexington Instruments Corp.). Haemoglobin concentration was determined using the cyanmethaemoglobin method.
BRITISH JOURNAL OF ANAESTHESIA
DOPAMINE AND OXYGEN TRANSPORT
1013
two-sample t test. P Cvo,) sank, wenn auch diese Veranderungen statistisch gesehen nicht wesentlich waren. Eine Dosis von 30 ng kg" 1 min" 1 Dopamin (P < 0,05) erhohte das Herzminutenvolumen, die Hamoglobinkonzentration und Cao,, und senkte wesentlich das Schlagvolumen und KD/KT. Obwohl die Sauerstoffverfiigbarkeit stieg, waren die Anstiege des Sauerstoffverbrauches grosser, was zu statistisch unwesentlichen Abstiegen des Sauerstoffverfugbarkeitsverhaltnisses und zu einem Anstieg von (Cao, —CVQ,) fuhrte. Beendigung der Dopamin-Infusion fuhrte zu wesentlichen
(P
