Isoflurane Alters the Recirculatory Pharmacokinetics of Physiologic Markers

2000 ◽  
Vol 92 (6) ◽  
pp. 1757-1768 ◽  
Author(s):  
Michael J. Avram ◽  
Tom C. Krejcie ◽  
Claus U. Niemann ◽  
Cheri Enders-Klein ◽  
Colin A. Shanks ◽  
...  

Background Earlier studies have demonstrated that physiologic marker blood concentrations in the first minutes after administration, when intravenous anesthetics exert their maximum effect, are determined by both cardiac output and its distribution. Given the reported vasodilating properties of isoflurane, we studied the effects of isoflurane anesthesia on marker disposition as another paradigm of altered cardiac output and regional blood flow distribution. Methods The dispositions of markers of intravascular space and blood flow (indocyanine green), extracellular space and free water diffusion (inulin), and total body water and tissue perfusion (antipyrine) were determined in four purpose-bred coonhounds. The dogs were studied while awake and while anesthetized with 1.7%, 2.6%, and 3.5% isoflurane (1.15, 1.7, and 2.3 minimum alveolar concentration, respectively) in a randomized order determined by a Latin square experimental design. Marker dispositions were described by recirculatory pharmacokinetic models based on very frequent early, and less frequent later, arterial blood samples. These models characterize the role of cardiac output and regional blood flow distribution on drug disposition. Results Isoflurane caused a significant and dose-dependent decrease in cardiac output. Antipyrine disposition was profoundly affected by isoflurane anesthesia, during which nondistributive blood flow was maintained despite decreases in cardiac output, and the balance between fast and slow tissue volumes and blood flows was altered. Conclusions The isoflurane-induced changes in marker disposition were different than those the authors reported previously for halothane anesthesia, volume loading, or hypovolemia. These data provide further evidence that not only cardiac output but also its peripheral distribution affect early drug concentration history after rapid intravenous administration.

1985 ◽  
Vol 248 (1) ◽  
pp. H98-H108
Author(s):  
D. G. van Wylen ◽  
L. G. D'Alecy

Regional blood flow distribution (microspheres) and cardiac output (CO, thermal dilution) were measured during the Cushing response in unblocked (UB), beta-receptor-blocked (BB, 2 mg/kg propranolol iv), or alpha-receptor blocked (AB, 0.5 mg/kg + 0.5 mg X kg-1 X min-1 phentolamine iv) chloralose-anesthetized dogs. Intracranial pressure was increased to 150 mmHg by infusion of temperature-controlled artificial cerebrospinal fluid into the cisterna magna. Similar increases in mean arterial pressure were seen in UB and BB, but in AB a Cushing response could not be sustained. In UB, cerebral blood flow (CBF) decreased 50%, coronary blood flow (CoBF) increased 120%, and peripheral tissue blood flow was reduced only in the kidneys (18%) and the intestines (small 22%, large 35%). Blood flow to the other viscera, skin, and skeletal muscle was unchanged. CO (16%) and heart rate (HR, 38%) decreased, and total peripheral resistance (TPR, 68%) and stroke volume (SV, 38%) increased. In BB, CBF decreased 50%, CoBF decreased 20%, and blood flow was reduced 40-80% in all peripheral tissues. CO (69%) and HR (62%) decreased, TPR increased 366%, and SV was unchanged. We conclude that the Cushing response in UB animals combines an alpha-receptor-mediated vasoconstriction with a beta-receptor cardiac stimulation. The beta-mechanism is neither necessary nor sufficient for the hypertension. However, the combination of alpha- and beta-adrenergic mechanisms maintains cardiac output and peripheral tissue blood flow relatively constant while producing a systemic hypertension.


1974 ◽  
Vol 2 (2) ◽  
pp. 149-163 ◽  
Author(s):  
Thomas G. Coleman ◽  
R. Davis Manning ◽  
Roger A. Norman ◽  
Arthur C. Guyton

1980 ◽  
Vol 238 (5) ◽  
pp. H736-H739 ◽  
Author(s):  
J. Bhattacharya ◽  
L. J. Beilin

When cannulation of the left ventricle and the left atrium were compared as methods for measuring for measuring renal blood flow distribution with radioactive microspheres in 9 conscious and 6 anesthetized rabbits, there were no differences between the two injection routes. Left ventricular cannulation per se did not affect cardiac output, nor the percentage of the cardiac output supplying the kidneys; but cardiac outputs estimated by thermodilution by injections via this route were up to 10% greater than those from left atrial injection. The advantages of left ventricular cannulation for experiments on regional blood flow distribution in conscious animals are discussed.


1981 ◽  
Author(s):  
B Lindblad ◽  
D Bergqviat

Dextran 70 and DHE are both effective in reducing the risk for postoperative thromboembolic complications. As they at least in part have different mechanisms of action it is important to analyse if their combination potentiates the prophylactic effect. Therefore it is necessary to study the effect on hemodynamics and tissue blood flow, a problem which is delt with in this report.MATERIAL AND METHODS: In 18 dogs the following parameters were followed: cardiac output, heart rate, arterial blood pressure, central venous pressure, pulmonary artery pressure, left atrium pressure and volume blood flow in the femoral vein. Blood flow distribution was determined by the radioactive microsphere technique.RESULTS: Dextran 70 gave an increase of cardiac output and femoral vein flow. Other hemodynamic parameters were mainly unaffected. Total peripheral resistance decreased. DHE increased arterial blood pressure, central venous pressure and pulmonary arterial pressure. Cardiac output and femoral vein flow were unchanged.Tissue blood flow increased in general slightly after infusion of dextran 70. No significant change in blood flow distribution was seen. DHE reduced pancreatic and thyroid blood flow and increased tissue blood flow to the central nervous system. The blood flow to other organs including the heart was unaffected. The combination of dextran 70 and DHE influenced hemodynamic parameters and flow distribution in an additative way.CONCLUSIONS: From this experimental study it is concluded that it is possible to combine dextran and DHE without inducing a circulatory overload. DHE increased tissue blood flow to the central nervous system.


1976 ◽  
Vol 231 (5) ◽  
pp. 1579-1587 ◽  
Author(s):  
GR Heyndrickx ◽  
DH Boettcher ◽  
SF Vatner

A comparison was made of the effects of vasopressin (ADH), methoxamine (MX), and angiotensin II (AN) on coronary and left ventricular dynamics, cardiac output, and regional blood flow distribution in intact, consci9us dogs. At an equal percent pressure elevation, ADH reduced cardiac output and cardiac rate the most, while AN had the least effect. After denervation of arterial baroreceptors, ADH still reduced heart rate, while AN increased it, suggesting nonbaroreceptor negative and positive chronotropic effects, respectively. A differential pattern on peak dP/dt was also observed, with ACH causing a greater reduction than MX while AN did not decrease dP/dt. With heart rate held constant, AN did not reduce dP/dt, suggesting a direct positive inotropic effect since dP/dt should have fallen slightly due to reflex mechanisms, as was observed with MX and ADH. ADH induced the greatest increase in coronary resistance (140%), while the least (46%) was observed with AN, which could be explained, in part, by the differential effects observed on cardiac rate and contractility. The greatest increase in resistance in the iliac bed occurred with ADH (30%), and the least with AN (34%). Conversely, the greatest constriction in the renal bed occurred with AN (95%), and lesser amounts were observed with ADH (36%) and MX (35%). Thus ADH, MX, and AN exert potent yet differential vasoconstricting actions on peripheral beds. In addition, while all three agents elicited coronary vasoconstriction, the differential effects on coronary vascular resistance appeared to be due predominantly to a difference in chronotropic and inotropic actions.


1958 ◽  
Vol 193 (1) ◽  
pp. 161-168 ◽  
Author(s):  
Leo A. Sapirstein

K42 Cl, Rb86Cl and iodoantipyrine (I131) were given in single intravenous injections to rats. The isotope content of the organs and the arterial blood concentrations were studied as a function of time. K42Cl and Rb86Cl reached a stable level in all organs other than the brain in 6–9 seconds and maintained this level until 64 seconds. The arterial concentration curves for the isotopes showed that the injected dose was almost completely transferred into the arterial system at about 6–8 seconds. The isotopes showed subsequent recirculation amounting to about 40% of the original dose between the first recirculation and 64 seconds. The organs which displayed stability during the period of recirculation must have had extraction ratios from zero time less than 1.00 but equal to that of the whole body. The fractional uptake of indicator by such organs must therefore have been equal to their blood flow fraction of the cardiac output. The brain reached its maximum content of Rb86 and K42 in 5–6 seconds; both isotopes then disappeared rapidly. The brain was thus shown to have a lower extraction ratio toward these isotopes than the body as a whole; its flow fraction could not therefore be measured by their use. Most organs failed to show stability of their iodoantipyrine content between 9 and 64 seconds; this indicator is not suitable for the measurement of the flow fraction of such organs. By combining values for the cardiac output and the fractional uptake of K42 in dog organs, regional blood flow values were obtained. For those other organs where flow values by other methods are available, the agreement was good. The following blood flow values were obtained in the major organs of the dog: Heart (coronary flow), 1.0 ml/gm/min.; kidney, 3.0 ml/gm/min.; liver, 1.2 ml/gm/min. (0.4 ml/gm/min. hepatic artery, 0.8 ml/gm/min. portal vein); skin, 0.07 ml/gm/min.


1993 ◽  
Vol 183 (1) ◽  
pp. 301-321 ◽  
Author(s):  
A. S. Kolok ◽  
M. R. Spooner ◽  
A. P. Farrell

Cardiac output (Q.) and blood flow distribution were measured in adult largescale suckers at rest and while swimming. Cardiac output was directly measured using an ultrasonic flowprobe in fish during the summer (16°C), fall (10°C) and winter (5°C). Largescale suckers were adept at holding station against a current without swimming and, when engaged in this behavior, they did not significantly increase Q. relative to that found in fish in still water. When fish began to swim, Q. increased significantly. From 16 to 10°C, the critical swimming speed (Ucrit), maximum Q. and scope for Q. of the suckers did not change. However, from 10 to 5°C all three traits were significantly reduced. Thus, these fish respond to variation in water temperature in two different ways. From 16 to 10°C, the fish compensate perfectly for the change in temperature with respect to cardiac and swimming performance. From 10 to 5°C, however, largescale suckers experience a dramatic decline in cardiac and swimming performance that may be associated with a quiescent overwintering strategy. Blood flow distribution in the fish at rest and while swimming was measured at 16°C using injection of colored microspheres. In the resting fish, over 10 % of the microspheres were recovered from the kidney and over 43 % were recovered from white muscle. When the fish were swimming, there was a 60-fold increase in blood flow to the red muscle while blood flow to all other tissues remained consistent with that at rest.


Sign in / Sign up

Export Citation Format

Share Document