Effects of Isoproterenol, Diazoxide, Ethacrynic Acid, and Furosemide on Skeletal Muscle Vascular Resistance

1973 ◽  
Vol 51 (3) ◽  
pp. 183-189 ◽  
Author(s):  
P. Larochelle ◽  
E. Mikulic ◽  
R. I. Ogilvie
Keyword(s):  
Skeletal Muscle ◽  
Ethacrynic Acid ◽  
Perfusion Pressure ◽  
Gracilis Muscle ◽  
Maximal Effect ◽  
Vasodilator Response ◽  
Arterial Blood ◽  
Constant Rate ◽  
The Mean ◽  
The Right

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.

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
Keyword(s):  
Skeletal Muscle ◽  
Vascular Resistance ◽  
Ethacrynic Acid ◽  
Glucose Production ◽  
Gracilis Muscle ◽  
Oxygen Utilization ◽  
Blood Concentrations ◽  
Arterial Blood ◽  
Vasodilatory Effect ◽  
Electrolyte Flux

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.

Comparative Effects of Ethacrynic Acid, Furosemide, and Diazoxide in the Perfused Dog Hindlimb

1971 ◽  
Vol 49 (12) ◽  
pp. 1038-1043 ◽  
Author(s):  
R. I. Ogilvie ◽  
E. Schlieper
Keyword(s):  
Dose Response ◽  
Time Course ◽  
Ethacrynic Acid ◽  
Maximal Effect ◽  
Vasodilator Effect ◽  
Arterial Blood ◽  
The Mean ◽  
Mean Time ◽  
Higher Doses ◽  
Vasodilating Effect

The vasodilator effects of intravenous ethacrynic acid (EA), furosemide (F), and diazoxide (DZ) were compared in the hindlimb of anesthetized anephric dogs, perfused with a constant inflow of arterial blood. A dose-response relationship was demonstrated for all three agents. The curves for EA and F were parallel and relatively flat, with EA being 10 times more potent than F in producing vasodilatation of the perfused limb. The dose–response for DZ was steep and the maximal vasodilator response observed at the lowest dose of DZ (5 mg/kg) did not differ from that at the highest doses of EA (10 mg/kg) or F (100 mg/kg). The maximal vasodilator effect of DZ in the perfused hindlimb occurred within 2 min after intravenous administration. After the higher doses of F there was a transitory vasodilator effect within 2 min but the maximal and more persistent effect was not observed until much later. The mean time for maximal effect was 40 min for EA, 46 min for F, and 2 min for DZ. The time course of vasodilator effect and maximal observed effect for EA and F was not altered by intraarterial administration nor by sympathetic decentralization of the perfused hindlimb. We conclude that F, like EA, has a direct vasodilating effect on peripheral arterioles and both EA and F probably act by a different mechanism than DZ.

Plasma renin activity responses to graded decreases in renal perfusion pressure in fetal and newborn lambs

1992 ◽  
Vol 262 (3) ◽  
pp. R524-R529 ◽  
Author(s):  
N. D. Binder ◽  
D. F. Anderson
Keyword(s):  
Blood Pressure ◽  
Plasma Renin Activity ◽  
Perfusion Pressure ◽  
Plasma Renin ◽  
Renal Perfusion ◽  
Renin Activity ◽  
Renal Perfusion Pressure ◽  
Arterial Blood ◽  
The Right ◽  
The Relationship

We examined the relationship between acute reductions in renal perfusion pressure, as approximated by femoral arterial blood pressure, and plasma renin activity in the uninephrectomized fetal lamb. Renal perfusion pressure was reduced and maintained at a constant value by controlled partial occlusion of the aorta above the renal artery. After 15 min of reduced blood pressure, blood samples were taken for determination of plasma renin activity. This protocol was performed 22 times in 11 fetal lambs. Additionally, three of the fetuses were delivered by cesarean section and studied as newborns for the first week of life. In the fetus, there was a linear relationship between log plasma renin activity and femoral arterial blood pressure (P less than 0.01). After birth, the relationship still existed, although it was shifted to the right (P less than 0.0001). We conclude that there is a significant relationship between plasma renin activity and renal perfusion pressure in the fetal lamb, and as early as 1 day after birth, this relationship shifts to the right in the newborn lamb.

Release of nitric oxide and prostaglandin H2 to acetylcholine in skeletal muscle venules

1997 ◽  
Vol 272 (6) ◽  
pp. H2541-H2546 ◽  
Author(s):  
G. Dornyei ◽  
G. Kaley ◽  
A. Koller
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Perfusion Pressure ◽  
Thromboxane A2 ◽  
No Synthase ◽  
Gracilis Muscle ◽  
Vasoactive Agents ◽  
Before And After ◽  
Higher Doses

The role of endothelium in regulating venular resistance is not well characterized. Thus we aimed to elucidate the endothelium-derived factors involved in the mediation of responses of rat gracilis muscle venules to acetylcholine (ACh) and other vasoactive agents. Changes in diameter of perfusion pressure (7.5 mmHg)- and norepinephrine (10(-6) M)-constricted venules (approximately 225 microns in diam) to cumulative doses of ACh (10(-9) to 10(-4) M) and sodium nitroprusside (SNP, 10(-9) to 10(-4) M), before and after endothelium removal or application of various inhibitors, were measured. Lower doses of ACh elicited dilations (up to 42.1 +/- 4.7%), whereas higher doses of ACh resulted in smaller dilations or even constrictions. Endothelium removal abolished both ACh-induced dilation and constriction. In the presence of indomethacin (2.8 x 10(-5) M), a cyclooxygenase blocker, or SQ-29548 (10(-6) M), a thromboxane A2-prostaglandin H2 (PGH2) receptor antagonist, higher doses of ACh caused further dilation (up to 72.7 +/- 7%) instead of constriction. Similarly, lower doses of arachidonic acid (10(-9) to 10(-6) M) elicited dilations that were diminished at higher doses. These reduced responses were, however, reversed to substantial dilation by SQ-29548. The nitric oxide (NO) synthase blocker, N omega-nitro-L-arginine (L-NNA, 10(-4) M), significantly reduced the dilation to ACh (from 30.6 +/- 5.5 to 5.4 +/- 1.4% at 10(-6) M ACh). In contrast, L-NNA did not affect dilation to SNP. Thus ACh elicits the release of both NO and PGH2 from the venular endothelium.

scholarly journals Effect of mean ocular perfusion pressure on primary open angle glaucoma

2018 ◽  
Vol 11 (4) ◽  
pp. 286-290
Author(s):  
Pallab Kumar Sen ◽  
Nazneen Khan ◽  
Md. Shafiqul Islam
Keyword(s):  
Odds Ratio ◽  
Primary Open Angle Glaucoma ◽  
Perfusion Pressure ◽  
Open Angle Glaucoma ◽  
Control Group ◽  
Open Angle ◽  
Ocular Perfusion Pressure ◽  
Ocular Perfusion ◽  
The Mean ◽  
The Right

Primary open angle glaucoma is the most common form of glaucoma and it remains asymptomatic until the late stage of the disease. The purpose of this study is to compare the mean ocular perfusion pressure with the primary open angle glaucoma. A total of 60 study subjects were divided into two following groups: a) newly diagnosed patients with primary open angle glaucoma (case) and b) age and sex-matched healthy volunteers (control). The intraocular pressure and blood pressure were measured 3 hourly from 8:00 am to 11:00 pm. The mean ocular perfusion pressure of the right eyes in untreated primary open angle glaucoma was 39.9 ± 7.5 mm Hg whereas it was 47.7 ± 7.7 mm Hg in the control. The odds ratio was 6.6 (95% CI, 2.1-20.5; p=0.002). The right eyes of untreated primary open angle glaucoma had 6.6 times more risk compared to the control group. The mean ocular perfusion pressure of left eyes in untreated primary open angle glaucoma was 39.9 ± 7.5 mm Hg and 48.6 ± 4.0 mm Hg in the control group. The odds ratio was 5.7 (95% CI, 1.8-17.5; p=0.004). The left eyes of untreated primary open angle glaucoma had 5.7 times more risk compared to control group. The findings revealed the evidence of vascular mechanism in glaucoma pathogenesis: Reduction of mean ocular perfusion pressure ≤48 mm Hg, may lead to daily repetitive ischemic insult to the optic nerve.

Relationship of perfusion pressure and size to risk of hemorrhage from arteriovenous malformations

1992 ◽  
Vol 76 (6) ◽  
pp. 918-923 ◽  
Author(s):  
Robert F. Spetzler ◽  
Ronald W. Hargraves ◽  
Patrick W. McCormick ◽  
Joseph M. Zabramski ◽  
Richard A. Flom ◽  
...  
Keyword(s):  
Perfusion Pressure ◽  
Feeding Artery ◽  
Content Type ◽  
Arterial Blood ◽  
The Mean ◽  
Feeding Pressure ◽  
Risk Of Hemorrhage ◽  
Relationship Of ◽  
The Relationship ◽  
Fine Print

✓ The relationship between the size of an arteriovenous malformation (AVM) and its propensity to hemorrhage is unclear. Although nidus volume increases geometrically with respect to AVM diameter, hemorrhages are at least as common, in small AVM's compared to large AVM's. The authors prospectively evaluated 92 AVM's for nidus size, hematoma size, and arterial feeding pressure to determine if these variables influence the tendency to hemorrhage. Small AVM's (diameter ≤ 3 cm) presented with hemorrhage significantly more often (p < 0.001) than large AVM's (diameter > 6 cm), the incidence being 82% versus 21%. Intraoperative arterial pressures were recorded from the main feeding vessel(s) in 24 of the 92 patients in this series: 10 presented with hemorrhage and 14 presented with other neurological symptoms. In the AVM's that had hemorrhaged, the mean difference between mean arterial blood pressure and the feeding artery pressure was 6.5 mm Hg (range 2 to 15 mm Hg). In the AVM's that did not rupture, this difference was 40 mm Hg (range 17 to 63 mm Hg). Smaller AVM's had significantly higher feeding artery pressures (p < 0.05) than did larger AVM's, and they were associated with large hemorrhages. It is suggested that differences in arterial feeding pressure may be responsible for the observed relationship between the size of AVM's and the frequency and severity of hemorrhage.

Hydrogen ion concentration and oxygen uptake in an isolated canine hindlimb

1976 ◽  
Vol 40 (1) ◽  
pp. 1-5 ◽  
Author(s):  
A. H. Harken
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Oxygen Consumption ◽  
Lactate Production ◽  
Hydrogen Ion ◽  
Arterial Oxygen ◽  
Hydrogen Ion Concentration ◽  
Membrane Lung ◽  
Arterial Blood ◽  
The Mean

Oxygen utilization (VO2) and lactate production by an isolated perfused canine hindlimb was evaluated at various hydrogen ion concentrations. A membrane lung perfusion system was established such that blood flow and temperature could be fixed at normal levels. Oxygen, nitrogen, and carbon dioxide (CO2) gas flows to the membrane lung were independently regulated to provide a fixed arterial oxygen content (CaO2). By changing CO2 flow, the pH of the arterial blood was varied between 6.9 and 7.6 at 10-min intervals. The mean O2 delivery (CaO2 X blood flow) was between 16.3 ML O2/min and 20.5 ml O2/min. Standard error of the mean in each dog, however, was less than 0.4 ml O2/min. VO2 was linearly related to the pH of the perfusing blood: VO2% = 100.1 pH - 643 (r = 0.866). Oxygen consumption was inversely related to PCO2: VO2% = -0.62 PCO2 + 124, but the correlation was less good (r = 0.729). Lactate production was linearly related to the pH of the perfusing blood (above a pH of 7.4): lactate produced = 22.5 pH - 162.5 (r = 0.75). At a pH below 7.4, lactate was not produced. Oxygen consumption of skeletal muscle appears critically dependent on extracellular fluid pH. A change in pH of 0.1 alters VO2 almost exactly 10%. Alkalosis is a potent stimulus to lactic acid production by skeletal muscle.

Effect of 71 ATA He-O2 on organ blood flow in the rat

1985 ◽  
Vol 59 (5) ◽  
pp. 1369-1375 ◽  
Author(s):  
L. Aanderud ◽  
J. Onarheim ◽  
I. Tyssebotn
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Cardiac Output ◽  
Organ Blood Flow ◽  
Arterial Blood Sampling ◽  
Arterial Blood ◽  
Constant Rate ◽  
The Mean ◽  
Leg Muscle ◽  
Increased Blood Flow

Cardiac output and organ blood flow to major organs were investigated in awake rats at 1 atmosphere absolute (ATA) air and at 71 ATA He-O2. Radioactively labeled microspheres [15 +/- 1 (SD) micron] were injected into the left ventricle during constant-rate arterial blood sampling at 1 ATA air and subsequently at 71 ATA He-O2. Intra-arterial blood pressure was continuously recorded. The partial pressure of O2 was kept between 0.4 and 0.6 ATA. The results indicate that the mean blood pressure, heart rate, cardiac output, and organ blood flow are essentially unaltered in the rat at 71 ATA except for increased blood flow to the liver (122%, P less than 0.05), whereas the blood flow to the adrenals, the diaphragm, and the leg muscle fell (P less than 0.05).

Effect of systemic hypotension on cerebral energy metabolism during chronic cerebral vasospasm in primates

1993 ◽  
Vol 78 (1) ◽  
pp. 112-119 ◽  
Author(s):  
Yuji Handa ◽  
Tetsuya Kubota ◽  
Akira Tsuchida ◽  
Masanori Kaneko ◽  
Hakan Caner ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Cerebral Vasospasm ◽  
Mr Spectroscopy ◽  
High Energy ◽  
Cerebral Energy Metabolism ◽  
Systemic Hypotension ◽  
Arterial Blood ◽  
The Mean ◽  
The Right ◽  
Chronic Cerebral Vasospasm

✓ The influence of systemic hypotension on cerebral blood flow (CBF) and energy metabolism during chronic cerebral vasospasm after subarachnoid hemorrhage was studied in 15 monkeys. Changes in the phosphorus spectrum, as demonstrated by in vivo phosphorus-31 (31P) magnetic resonance (MR) spectroscopy, or in regional CBF were measured in the parietal cortex during graded hypotension. Sequential changes in the phosphorus spectrum were observed during moderate hypotension in the animals 7 days after the introduction of an autologous blood clot around the right middle cerebral artery (MCA). Angiograms revealed a reduction in vessel caliber by approximately 50% in the right MCA. The mean CBF in the spasm side decreased in parallel with a decrease in the mean arterial blood pressure (MABP) from 120 to 40 mm Hg, indicating the abolition of autoregulation. There were no significant differences in the mean percentage totals of inorganic phosphate (Pi), phosphocreatine (PCr), adenosine triphosphate (ATP), and pH between the hemispheres at baseline MABP before hypotension. The values of PCr, ATP, and pH decreased significantly (p < 0.05) and Pi increased significantly (p < 0.05) at an MABP of less than 60 mm Hg in the involved hemisphere. The ratio of PCr:Pi decreased in parallel with a decrease in MABP. The ATP showed a stepwise decrease during moderate hypotension (MABP 60 mm Hg) and was reduced significantly 20 minutes after the beginning of hypotension (p < 0.05). The results indicate that, during chronic vasospasm, changes in cerebral energy metabolism are coupled with changes in CBF in the state of impaired autoregulation. There exists a critical level for ischemia below which high-energy phosphorus metabolites become markedly depleted. It is suggested that 31P MR spectroscopy may be useful to evaluate the ischemic vulnerability of brain tissue in order to prevent delayed neurological deficit during cerebral vasospasm.

Cerebral autoregulation following head injury

2001 ◽  
Vol 95 (5) ◽  
pp. 756-763 ◽  
Author(s):  
Marek Czosnyka ◽  
Piotr Smielewski ◽  
Stefan Piechnik ◽  
Luzius A. Steiner ◽  
John D. Pickard
Keyword(s):  
Head Injury ◽  
Cerebral Autoregulation ◽  
Perfusion Pressure ◽  
Content Type ◽  
Arterial Blood ◽  
Head Injured ◽  
The Mean ◽  
Injured Patients ◽  
The Relationship ◽  
Fine Print

Object. The goal of this study was to examine the relationship between cerebral autoregulation, intracranial pressure (ICP), arterial blood pressure (ABP), and cerebral perfusion pressure (CPP) after head injury by using transcranial Doppler (TCD) ultrasonography. Methods. Using ICP monitoring and TCD ultrasonography, the authors previously investigated whether the response of flow velocity (FV) in the middle cerebral artery to spontaneous variations in ABP or CPP provides reliable information about cerebral autoregulatory reserve. In the present study, this method was validated in 187 head-injured patients who were sedated and receiving mechanical ventilation. Waveforms of ICP, ABP, and FV were recorded over intervals lasting 20 to 120 minutes. Time-averaged mean FV and CPP were determined. The correlation coefficient index between FV and CPP (the mean index of autoregulation [Mx]) was calculated over 4-minute epochs and averaged for each investigation. The distribution of averaged mean FV values converged with the shape of the autoregulatory curve, indicating lower (CPP < 55 mm Hg) and upper (CPP > 105 mm Hg) thresholds of autoregulation. The relationship between the Mx and either the CPP or ABP was depicted as a U-shaped curve. Autoregulation was disturbed in the presence of intracranial hypertension (ICP ≥ 25 mm Hg) and when mean ABP was too low (ABP < 75 mm Hg) or too high (ABP > 125 mm Hg). Disturbed autoregulation (p < 0.005) and higher ICP (p < 0.005) occurred more often in patients with unfavorable outcomes than in those with favorable outcomes. Conclusions. Autoregulation not only is impaired when associated with a high ICP or low ABP, but it can also be disturbed by too high a CPP. The Mx can be used to guide intensive care therapy when CPP-oriented protocols are used.

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