Effects of Ethacrynic Acid on Vascular Resistance, Metabolism, and Electrolyte Flux in the Canine Gracilis Muscle

1972 ◽  
Vol 50 (10) ◽  
pp. 940-945
Author(s):  
R. J. Ogilvje ◽  
E. Mikulic

The effects of intra-arterial ethacrynic acid (EA) on vascular resistance, metabolism, and electrolyte flux was studied in the isolated denervated canine gracilis muscle perfused with a constant inflow of arterial blood. Skeletal muscle vascular resistance was markedly reduced from baseline by 25-min infusions of EA producing blood concentrations of 10−3 M but not at concentrations of 10−5 M. There were no consistent alterations in the uptake of glucose, production of lactate, or flux of potassium in the gracilis muscle during the drug infusions or 45 min postinfusion period. Venous osmolality did not change. However, the arterio venous difference for oxygen saturation across this skeletal muscle was significantly reduced by EA treatment suggesting that oxygen utilization had been inhibited. Thus, EA has a direct vasodilatory effect which is independent of measurable changes in gracilis muscle electrolyte flux or metabolism other than a possible reduction in oxygen uptake or utilization by this muscle.

1973 ◽  
Vol 51 (3) ◽  
pp. 183-189 ◽  
Author(s):  
P. Larochelle ◽  
E. Mikulic ◽  
R. I. Ogilvie

The vasodilator properties of isoproterenol, diazoxide, ethacrynic acid, and furosemide were compared in the isolated canine gracilis muscle perfused with arterial blood at a constant rate. Isoproterenol was the most potent agent with a steep vasodilator response to 10−8–10−6 M infusions and a maximal decrease in perfusion pressure of 45.5 ± 2.9% at the 10−6 M concentration. The dose – vasodilator responses for diazoxide and ethacrynic acid were parallel to that for isoproterenol but shifted three log doses to the right. The dose–response for furosemide was almost flat with a maximal vasodilator response of 15.5 ± 2.3% at the 10−2 M concentration. The maximal effect of isoproterenol was noted within 5 min of starting the infusion whereas for diazoxide and furosemide it was noted after 10 min and for ethacrynic acid after 20 min. The mean ratio of venous to arterial resistance was unaltered during isoproterenol infusions, decreased with 10−3 M diazoxide, and increased with 10−3 M ethacrynic acid; however, none of these changes were statistically significant. Capillary hydrostatic pressure was significantly decreased only with higher concentrations of isoproterenol and diazoxide, an average of 6 mm Hg with 10−7 M isoproterenol, 8 mm Hg with 10−6 M isoproterenol, and 9 mm Hg with 10−3 M diazoxide. No significant changes in capillary pressure were noted during infusion of ethacrynic acid or furosemide. The results clearly differentiate these agents on the basis of potency, onset, and characteristics of vasodilator effect on sequential segments of a skeletal muscle vascular bed.


1988 ◽  
Vol 66 (1) ◽  
pp. 101-105 ◽  
Author(s):  
P. Kubes ◽  
C. K. Chapler ◽  
S. M. Cain

Redistribution of blood flow away from resting skeletal muscle does not occur during anemic hypoxia even when whole body oxygen uptake is not maintained. In the present study, the effects of sympathetic nerve stimulation on both skeletal muscle and hindlimb blood flow were studied prior to and during anemia in anesthetized, paralyzed, and ventilated dogs. In one series (skeletal muscle group, n = 8) paw blood flow was excluded by placing a tourniquet around the ankle; in a second series (hindlimb group, n = 8) no tourniquet was placed at the ankle. The distal end of the transected left sciatic nerve was stimulated to produce a maximal vasoconstrictor response for 4-min intervals at normal hematocrit (Hct.) and at 30 min of anemia (Hct. = 14%). Arterial blood pressure and hindlimb or muscle blood flow were measured; resistance and vascular hindrance were calculated. Nerve stimulation decreased blood flow (p < 0.05) in the hindlimb and muscle groups at normal Hct. Blood flow rose (p < 0.05) during anemia and was decreased (p < 0.05) in both groups during nerve stimulation. However, the blood flow values in both groups during nerve stimulation in anemic animals were greater (p < 0.05) than those at normal Hct. Hindlimb and muscle vascular resistance fell significantly during anemia and nerve stimulation produced a greater increase in vascular resistance at normal Hct. Vascular hindrance in muscle, but not hindlimb, was less during nerve stimulation in anemia than at normal Hct. The data indicate that (i) maximal sympathetic stimulation produced a significant decrease in both skeletal muscle and hindlimb blood flow during anemia, (ii) the reduction in blood flow in these areas was less with sympathetic stimulation during anemia than at normal Hct., and (iii) the anemic stimulus (Hct. = 14%) does not activate maximal sympathetic vasoconstrictor tone in the skeletal muscle.


1997 ◽  
Vol 155 (2) ◽  
pp. 351-358 ◽  
Author(s):  
CM Gillespie ◽  
AL Merkel ◽  
AA Martin

Two studies were conducted to investigate the haemodynamic effects of IGF-I and its analogue LR3IGF-I in normal anaesthetised rats. Infusion of IGF-I intravenously, at a dose of 125 micrograms/kg/h, for 20 min in the first study resulted in renal blood flow being significantly elevated by 35% above baseline. Mean arterial blood pressure (MABP) at this IGF-I dose fell by 18% of baseline, with LR3IGF-I also causing a significant decline in MABP (by 15%) at the dose of 125 micrograms/kg/h. In the second study the intravenous administration of IGF-I or LR3IGF-I, at a dose of 125 micrograms/kg/h, over a period of 60 min, resulted in MABP being significantly lowered by 25% of baseline values. Regional blood flow rates were determined using radioactive microspheres, 15 microns in diameter, injected systemically at the end of the peptide infusion period. The gastrocnemius, a representative skeletal muscle, was the only vascular region to show a significant increase in blood flow after IGF-I (by 58%) or LR3IGF-1 (by 308%) infusion. Vascular resistance in the brain was significantly reduced after infusion of IGF-I (by 60%) or LR3IGF-I (by 48%) as compared with vehicle. Skeletal muscle vascular resistance was also reduced by IGF-I (by 41%) and more particularly by LR3IGF-I (by 77%) in comparison to vehicle. These alterations to vascular tone produced by IGF infusion may be related to the central nervous system and systemic cardiovascular side-effects that have been reported during IGF-I administration in humans.


1989 ◽  
Vol 67 (5) ◽  
pp. 1791-1800 ◽  
Author(s):  
J. A. Taylor ◽  
M. J. Joyner ◽  
P. B. Chase ◽  
D. R. Seals

The purpose of this study was to determine whether blood flow (BF) and vascular resistance (VR) are controlled differently in the nonactive arm and leg during submaximal rhythmic exercise. In eight healthy men we simultaneously measured BF to the forearm and calf (venous occlusion plethysmography) and arterial blood pressure (sphygmomanometry) and calculated whole limb VR before (control) and during 3 min of cycling with the contralateral leg at 38, 56, and 75% of peak one-leg O2 uptake (VO2). During the initial phase of exercise (0-1.5 min) at all work loads, BF increased and VR decreased in the forearm (P less than 0.05), whereas calf BF and VR remained at control levels. Thereafter, BF decreased and VR increased in parallel and progressive fashion in both limbs. At end exercise, forearm BF and VR were not different from control values (P greater than 0.05); however, in the calf, BF tended to be lower (P less than 0.05 at 75% peak VO2 only) and VR was higher (23 +/- 9, 44 +/- 14, and 88 +/- 23% above control at 38, 56, and 75% of peak VO2, respectively, all P less than 0.05). In a second series of studies, forearm and calf skin blood flow (laser-Doppler velocimetry) and arterial pressure were measured during the same levels of exercise in six of the subjects. Compared with control, skin BF was unchanged and VR was increased (P less than 0.05) in the forearm by end exercise at all work loads, whereas calf skin BF increased (P less than 0.05) and VR decreased (P less than 0.05). The present findings indicate that skeletal muscle and skin VR are controlled differently in the nonactive forearm and calf during the initial phase of rhythmic exercise with the contralateral leg. Skeletal muscle vasodilation occurs in the forearm but not in the calf; forearm skin vasoconstricts, whereas calf skin vasodilates. Finally, during exercise a time-dependent vasoconstriction occurs in the skeletal muscle of both limbs.


1963 ◽  
Vol 204 (5) ◽  
pp. 925-932 ◽  
Author(s):  
Carl F. Rothe ◽  
Fred C. Schwendenmann ◽  
Ewald E. Selkurt

The neural control of the resistance vessels of a gracilis muscle, isolated except for its nerve, was monitored during the various phases of hemorrhagic shock in dogs. The circulation to the muscle was maintained at a constant pressure of 160 mm Hg with a pump, using blood from a donor dog to eliminate any blood-borne factors elaborated by the shock dog. The degree of neural vasoconstriction was evaluated by periodically blocking the nerve with cold and measuring the subsequent changes in blood flow. Vasoconstriction followed hemorrhage. In many of the experiments there was evidence of loss of neural control of vascular resistance after prolonged hypotension following hemorrhage or terminally following the progressive decline in blood pressure after transfusion. This reduction of neurogenic vasoconstriction may contribute to cardiovascular collapse during hypotension. Following transfusion, however, vasoconstriction greater than control was generally seen, suggesting a functioning homeostatic mechanism acting to maintain the declining arterial blood pressure. Thus, irreversibility following transfusion is not the result of a loss of neurogenic control of the vascular resistance of skeletal muscle under the conditions used.


1988 ◽  
Vol 254 (4) ◽  
pp. H702-H708 ◽  
Author(s):  
R. J. Korthuis ◽  
M. B. Grisham ◽  
B. J. Zimmerman ◽  
D. N. Granger ◽  
A. E. Taylor

The aim of this study was to determine whether ATP-MgCl2 or isoproterenol pretreatment would attenuate the increase in canine gracilis muscle vascular resistance and permeability associated with 4 h of occlusive ischemia followed by 1 h of reperfusion. To this end, the osmotic reflection coefficient for total plasma proteins (omega), isogravimetric capillary pressure (Pci), precapillary resistance (Ra), postcapillary resistance (Rv), and total vascular resistance (Rt) were determined for the following conditions: control, ischemia, and ischemia plus pretreatment with ATP-MgCl2 or isoproterenol. Reperfusion, after ischemia, significantly reduced omega from 0.94 +/- 0.02 to 0.64 +/- 0.02, whereas Pci was decreased by 50 +/- 4%, indicating a dramatic increase in vascular permeability. Ischemia-reperfusion was also associated with an increase in Rt of 230 +/- 22%. Similar results were obtained in muscles pretreated with isoproterenol. However, in muscles pretreated with ATP-MgCl2, omega averaged 0.98 +/- 0.09, Pci was reduced by only 15 +/- 8%, and Rt was increased by just 25 +/- 12%. The effect of ATP-MgCl2 on neutrophilic oxidative metabolism was evaluated by measuring superoxide production by activated neutrophils in the presence and absence of ATP-MgCl2. Superoxide production by activated neutrophils was significantly attenuated by ATP-MgCl2. The results of these studies indicate that pretreatment with ATP-MgCl2, but not isoproterenol, is remarkably effective in attenuating the increase in skeletal muscle vascular resistance and permeability induced by ischemia-reperfusion. The protective effect of ATP-MgCl2 may be related in part to its ability to inhibit neutrophilic superoxide production.


1990 ◽  
Vol 258 (3) ◽  
pp. G440-G446
Author(s):  
J. G. Wood ◽  
G. M. Wicina ◽  
L. Y. Cheung

The goal of this study was to compare the relative potency of histamine and its metabolite, 1,4-methylhistamine, as vasodilators of the gastric circulation. Changes in vascular resistance were measured during local intra-arterial infusion of graded doses of histamine and 1,4-methylhistamine to an ex vivo segment of dog stomach. Infusate concentrations were adjusted to deliver calculated arterial blood concentrations of 0, 3.7, 11, 33, 100, 300, and 900 ng/ml of each substance to the stomach segment. We found that histamine caused rapid dose-related decreases in gastric vascular resistance of up to -47.6 +/- 1.3% compared with control values. The effects of histamine were reversible when infusions ended. In contrast, there were no statistically significant changes in vascular resistance at any dose of 1,4-methylhistamine. In addition, modifications to previous methods using histamine antagonists resulted in greater attenuation of histamine-induced gastric vasodilation. Our results support a role for locally released histamine, but not for 1,4-methylhistamine, as a mediator of gastric vasodilation.


1991 ◽  
Vol 80 (6) ◽  
pp. 595-598 ◽  
Author(s):  
Bo Grønlund ◽  
Arne Astrup ◽  
Peter Bie ◽  
Niels Juel Christensen

1. In adipose tissue and in skeletal muscle the extracellular noradrenaline levels were studied by microdialysis in the conscious dog and compared with the noradrenaline concentration in arterial plasma. 2. The experiments were performed with and without tyramine added to the perfusion medium, and noradrenaline was measured by a sensitive radioenzymic assay. 3. In the absence of tyramine, the interstitial noradrenaline levels in adipose tissue and skeletal muscles were similar to arterial blood concentrations, provided that the former were corrected for recovery. The recovery estimated from experiments in vitro averaged 16% at room temperature. 4. With tyramine added to the perfusates, noradrenaline levels increased 10-fold. Arterial noradrenaline concentrations did not change, indicating that noradrenaline was released only locally in the tissue. 5. Our results indicate that the microdialysis technique combined with a sensitive assay for measuring noradrenaline may be applicable to the assessment of local noradrenaline release in adipose tissue and in skeletal muscle. This may be of interest, especially in adipose tissue during physiological stimulation in which sympathetic activity is difficult to evaluate by other techniques.


2021 ◽  
Vol 49 (1) ◽  
pp. 030006052098326
Author(s):  
Myoung Hwa Kim ◽  
Young Chul Yoo ◽  
Sun Joon Bai ◽  
Kang-Young Lee ◽  
Nayeon Kim ◽  
...  

Objective We aimed to determine the physiological and hemodynamic changes in patients who were undergoing hyperthermic intraperitoneal chemotherapy (HIPEC) cytoreductive surgeries. Methods This prospective, observational study enrolled 21 patients who were undergoing elective cytoreductive surgery with HIPEC at our hospital over 2 years. We collected vital signs, hemodynamic parameters including global end-diastolic volume index (GEVI) and extravascular lung water index (ELWI) using the VolumeView™ system, and arterial blood gas analysis from all patients. Data were recorded before skin incision (T1); 30 minutes before HIPEC initiation (T2); 30 (T3), 60 (T4), and 90 (T5) minutes after HIPEC initiation; 30 minutes after HIPEC completion (T6); and 10 minutes before surgery completion (T7). Results Patients showed an increase in body temperature and cardiac index and a decrease in the systemic vascular resistance index. GEDI was 715.4 (T1) to 809.7 (T6), and ELWI was 6.9 (T1) to 7.3 (T5). Conclusions HIPEC increased patients’ body temperature and cardiac output and decreased systemic vascular resistance. Although parameters that were extracted from the VolumeView™ system were within their normal ranges, transpulmonary thermodilution approach is helpful in intraoperative hemodynamic management during open abdominal cytoreductive surgery with HIPEC. Trial registry name: ClinicalTrials.gov Trial registration number: NCT02325648 URL: https://clinicaltrials.gov/ct2/results?cond=NCT02325648&term


1997 ◽  
Vol 273 (3) ◽  
pp. R1126-R1131 ◽  
Author(s):  
Y. X. Wang ◽  
J. T. Crofton ◽  
S. L. Bealer ◽  
L. Share

The greater pressor response to vasopressin in male than in nonestrous female rats results from a greater increase in total peripheral resistance in males. The present study was performed to identify the vascular beds that contribute to this difference. Mean arterial blood pressure (MABP) and changes in blood flow in the mesenteric and renal arteries and terminal aorta were measured in conscious male and nonestrous female rats 3 h after surgery. Graded intravenous infusions of vasopressin induced greater increases in MABP and mesenteric vascular resistance and a greater decrease in mesenteric blood flow in males. Vasopressin also increased renal vascular resistance to a greater extent in males. Because renal blood flow remained unchanged, this difference may be due to autoregulation. The vasopressin-induced reduction in blood flow and increased resistance in the hindquarters were moderate and did not differ between sexes. Thus the greater vasoconstrictor response to vasopressin in the mesenteric vascular bed of male than nonestrous females contributed importantly to the sexually dimorphic pressor response to vasopressin in these experiments.


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