Effects Of Vasoactive Drugs Research Articles

Systematic Errors in Estimating Mean Blood Pressure from Finger Blood Pressure Measurements

The mean blood pressure (BP) can be accurately estimated from indirect measurements of brachial artery pressure, i.e. mean BP = diastolic BP + 1/3 pulse pressure. Although this equation has been used as a surrogate of mean systemic pressure, it is unknown whether this approximation can be validly applied to distal vascular beds. Therefore we determined the accuracy of this method as an estimate of the mean pressure in distal arteries by measuring finger BP with the Finapres device in 16 normotensive and 12 hypertensive subjects. The "calculated" and measured values of mean BP were compared when subjects were resting and during manoeuvres which aimed to alter the shape of the pulse waveform. Although closely correlated with the measured value, the "calculated" resting mean BP was systematically greater (+2.7+/-0.7 mm Hg, p<0.001). Additionally, the rise in the mean pressure produced by infusion of phenylephrine, an alpha1-adrenoceptor stimulant (16.0+/-1.5 mm Hg) was underestimated by the calculation (13.1+/-1.5 mm Hg, p<0.05). Of even greater concern was that calculating the mean pressure during infusion of isoprenaline (a beta-adrenergic stimulant) suggested the mean pressure had increased by 5.8+/-1.6 mm Hg when it had actually fallen (-2.1+/-2.4 mm Hg, p<0.001 vs. the measured value). Thus, calculating the mean BP from Finapres measurements roughly approximates the measured value when subjects are at rest. However, this estimation becomes inaccurate when pulse wave dimensions are altered, and is probably unsuitable for assessing the acute effects of vasoactive drugs, in particular vasodilators, on BP.

Effect of vasoactive drugs on carotid diameter in humans.

We studied whether vasoactive drugs used to determine baroreflex sensitivity influence baroreceptor firing by affecting carotid sinus smooth muscle or simply by stretching the sinus wall through changes in pressure. In six young healthy subjects, the diameter of the carotid artery and its change with arterial pulse were measured with ultrasonography. Blood pressure was measured by Finapres. Phenylephrine and nitroglycerin doses were injected intravenously to raise and lower pressure by approximately 15-25 mmHg. Carotid dimensions increased in all subjects during the phenylephrine-induced rise and decreased during the nitroglycerin-induced fall in pressure. Diastolic diameter changed more than systolic diameter; changes were significantly different from the control value (assessed by single-factor analysis of variance and Scheffé's post hoc test). The systolic pressure-diameter relationship appeared to be nonlinear, with a steeper slope above than below baseline, and contributed significantly to the nonlinearity of the R-R interval-systolic pressure relationship. It is concluded that during drug-induced changes in blood pressure, baroreceptor activity in humans is influenced more by passive stretch than by local smooth muscle contraction.

An Integrated Noninvasive System for Monitoring the Microcirculatory Effects of Vasoactive Drugs: An Experimental Study

Background:No information is available on the effects of vasoactive drugs on the microcirculation and on the correlation between their effects on the capillary and the systemic circulation.Purpose:To characterize the effects of nitroglycerin (NTG), nitroprusside (NP), and metaraminol infusion on microcirculatory variables using a noninvasive monitoring system.Methods:Increasing doses of NTG (5–40 μg/kg/min) and NP (5–20 μg/kg/min) were intravenously infused to eight rabbits. The microcirculatory parameters were monitored by a combined noninvasive system which included laser Doppler flowmetry (LDF), photoplethysmograph (PPG), and transcutaneous oxygen tension (tc-PO2). Mean blood pressure (MBP) was measured simultaneously.Results:At maximal rate of NTG infusion, the values of LDF, PPG, tc-PO2, and MBP were 72.2 ± 23.9, 234.7 ± 165.6, 103.5 ± 37.4, and 82.7 ± 7.4% of baseline, respectively. Following NP infusion the LDF, PPG, tc-PO2, and MBP reached 70.8 ± 24.1, 190.5 ± 68.9, 70.0 ± 14.7, and 75.6 ± 14.6% of baseline, respectively. The tissue oxygenation was significantly reduced during NP infusion compared to NTG (P< 0.05). The values gradually returned to the baseline 10 min after termination of NP infusion, but not after NTG. After injection of 1 mg metaraminol there was a steep decline in LDF, PPG, and tc-PO2parallel to a significant increase in MBP. When metaraminol was administered after injection of 0.1 mg phenoxybenzamine, these changes were abolished.Conclusions:This noninvasive system effectively monitors microcirculatory hemodynamic changes induced by vasoactive drugs. NTG and NP cause similar changes in the systemic and microcirculatory bed, with the exception of peripheral oxygenation, which is reduced only during infusion of NP. The changes in the microcirculatory bed following metaraminol and phenoxybenzamine imply that their effects on the arterioles are mediated by adrenegic α-receptors.

Ventilation-Perfusion Response After Fenoterol in Hypoxemic Patients With Stable COPD

The effects of vasoactive drugs, including bronchodilators, on vascular and pulmonary dynamics are interrelated, complex and difficult to measure, but important because of potential deleterious effects on gas exchange. To assess the effects of fenoterol at both high and low dose on pulmonary gas exchange in 24 hypoxemic patients with stable COPD: fenoterol, 5 mg; fenoterol, 1 mg and ipratropium bromide, 0.5 mg; ipratropium bromide, 0.5 mg; or matched placebo were nebulized in a double-blind, placebo-controlled fashion. Spirometry, ventilation, systemic hemodynamics, and respiratory and inert gases were measured before and 15, 60, and 120 min after each treatment. Compared with placebo, heart rate (p < 0.002) and cardiac output (p = 0.05) increased after high-dose fenoterol therapy to return to baseline values by 120 min. Following fenoterol at high dose, mean maximum PaO2 change from baseline decreased by 6.3 +/- 1.1 mm Hg (SD) and both alveolararterial oxygen pressure difference (P[A-a]O2), by 8.3 +/- 4.0 mm Hg, and ventilation-perfusion (VA/Q) mismatching increased, as evidenced by increments of the dispersion of pulmonary blood flow, without reaching significance; likewise, low-dose fenoterol therapy increased VA/Q inequalities while both PaO2 and P(A-a)O2 remained unchanged. In this population of COPD patients, high-dose fenoterol therapy [corrected] significantly increased heart rate and cardiac output resulting in minor adverse consequences on arterial oxygenation and VA/Q relationships.

The rabbit as an intracavernous injection study model.

We investigated the feasibility of using the rabbit as an animal model for intracavernous injection studies. The rabbit, having a penile structure rather similar to that of humans, offers the advantage of being a strain-specific, adequately sized, and easily controlled experimental animal. Using intracavernous injections of the two vasoactive drugs prostaglandin E1 (PGE1, 0.2-1.6 micrograms/kg) and papaverine (PAP, 0.25-1 mg/kg), which have been commonly used in the management of erectile dysfunction in man, increases intracavernous pressure (delta ICP) were induced. After intracavernous injection of PGE1, the maximal delta ICP ranged from 18 to 44 mmHg (mean 29.25 +/- 7.85 mmHg) with a duration of tumescence from 3.1 to 13.3 min (mean 8.61 +/- 3.71 min). Intracavernous injection of PAP also induced increases in ICP, with a maximal delta ICP ranging from 24 to 56 mmHg (mean 43.5 +/- 11.35 mmHg) and a duration of tumescence from 5.3 to 15 min (mean 10.25 +/- 3.39 min). The systemic blood pressures were unchanged after all intracavernous injections. In addition, administration of cAMP antagonist in combination with PGE1 inhibited the relaxing effects of PGE1 in a dose-dependent manner. Our results suggest that the effects of vasoactive drugs on the rabbit's corpus cavernosum are similar to those in humans; thus the rabbit model is a suitable alternative for further physiological and pharmacological studies of penile erection.

Assessment of variceal pressure by continuous non-invasive endoscopic registration: a placebo controlled evaluation of the effect of terlipressin and octreotide.

Octreotide has been proposed for the treatment of variceal bleeding. The effects on portal pressure, however, have been variable in published studies. As bleeding is more directly related to pressure in the varices, this study investigated the effect on variceal pressure of octreotide and terlipressin, a vasoactive drug with a well established effect. Variceal pressure was measured during four to eight minutes by a continuous non-invasive endoscopic registration method. Thirty patients in whom a stable variceal pressure recording had been obtained during at least one minute, were randomised to receive either 2 mg terlipressin, 50 micrograms octreotide or an identical volume of saline, as a single intravenous injection given over 60 seconds. For the final analysis three patients had to be excluded because of lack of a satisfactory recording. There were no significant clinical differences between the three groups of patients. Placebo administration did not induce significant changes, but a mean decrease in variceal pressure of -27% was noted with terlipressin, starting from two minutes onwards. Variceal pressure changes after injection of octreotide were variable and the mean change in pressure did not reach statistical significance. Seven of 10 patients showed a temporary increase in variceal pressure. In conclusion, terlipressin induces a significant and progressive decrease in variceal pressure but inconsistent variations of variceal pressure changes were seen after octreotide administration. This is probably related to its effect on central venous pressure. This study also shows that continuous variceal pressure recording with the non-invasive endoscopic registration technique detects in an accurate way the effect of vasoactive drugs on variceal pressure, because placebo injection did not produce significant changes.

S2-6 - Effects of vasoactive drugs on tooth eruption in the rat incisor

S2-6 - Effects of vasoactive drugs on tooth eruption in the rat incisor

Effect of Vasoactive Drugs on Tumour Blood Flow as Determined by2H Nuclear Magnetic Resonance Spectroscopy

A selective reduction in tumour blood flow (TBF) could enhance the effects of hyperthermia treatment and of drugs toxic to hypoxic cells. Vasodilator-induced changes in TBF were monitored in transplanted rat fibrosarcomas by non-invasively measuring the uptake of D2O using 2H nuclear magnetic resonance spectroscopy. Hydralazine (1 or 5 mg kg-1) caused a large (45%) reduction in mean arterial blood pressure (MABP) and a 40-60% reduction in TBF. Low-dose hydralazine (0.1 mg kg-1) caused a 20% reduction in MABP but no significant change in TBF. The doses of prazosin (1 mg kg-1) and calcitonin-gene related peptide (CGRP, 1 nmol kg-1) which caused a 20% reduction in MABP led to a 50-60% reduction in TBF. These results demonstrate the advantage of prazosin and CGRP over hydralazine for the reduction of TBF despite a small hypotensive effect. CGRP may be the most suitable of these agents for clinical use because of its short physiological half-life.

Effects of vasoactive drugs on flows through left internal mammary artery and saphenous vein grafts in man : DiNardo JA, Bert A, Schwartz MJ, et al J Thorac Cardiovasc Surg 102:730–735, 1991

Effects of vasoactive drugs on flows through left internal mammary artery and saphenous vein grafts in man : DiNardo JA, Bert A, Schwartz MJ, et al J Thorac Cardiovasc Surg 102:730–735, 1991

Determination of lidocaine concentrations in skin after transdermal iontophoresis: effects of vasoactive drugs.

The purpose of this study was to investigate the effect of vasoactive drugs on transdermal lidocaine inotophoresis by measuring the concentrations of radiolabeled lidocaine which has penetrated the skin. Previous studies had demonstrated that coinotophoresis of vasoactive drugs could modulate the transcutaneous flux of lidocaine and suggested that a dermal depot of lidocaine was involved. To address this, lidocaine hydrochloride (14C) was iontophoresed in vivo in anesthetized weanling pigs either alone or with the vasodilator tolazoline or the vasoconstrictor norepinephrine. Tissue cores under the active electrode were then collected, quick-frozen, and sectioned on a cryostat, and then the radioactivity was determined in each 40-microns section. Coiontophoresis with norepinephrine resulted in increased concentrations of lidocaine in skin up to a depth of 3 mm. These concentrations decreased to lidocaine-alone levels after a 4-hr washout. Tolazoline decreased tissue concentrations of lidocaine. Concentrations were intermediate when lidocaine alone was administered. These studies support the hypothesis that coiontophoresis of vasoactive drugs modulates the transdermal delivery of lidocaine, in part by altering the cutaneous "depot."

Effects of vasoactive drugs on flows through left internal mammary artery and saphenous vein grafts in man

Vasoactive agents are commonly used in the postcardiopulmonary bypass period to elevate the mean arterial pressure of myocardial revascularization patients. Concern exists that administration of vasoactive agents in this setting may affect flow through saphenous vein and internal mammary artery grafts. Twenty-eight patients were randomly assigned to receive one of the six two-drug combinations of phenylephrine, norepinephrine, and epinephrine. After termination of cardiopulmonary bypass baseline, hemodynamic measurements and electromagnetic flow probe measurements of saphenous vein and internal mammary artery graft flow were made. The first agent was then infused to elevate mean arterial pressure 20 mm Hg. After 5 minutes of stability, hemodynamic and graft flow measurements were repeated. The infusion was terminated, 5 minutes of stability were obtained, and baseline measurements were repeated. The second agent was then infused, and measurements were repeated after a 5-minute stabilization period. Phenylephrine induced a nonsignificant increase in saphenous vein graft flow (68 +/- 31 versus 81 +/- 49 ml/min) and a significant decrease in internal mammary artery graft flow (40 +/- 16 versus 32 +/- 12 ml/min). Norepinephrine induced a significant increase in saphenous vein graft flow (80 +/- 39 versus 97 +/- 39 ml/min) and no significant change in internal mammary artery graft flow (44 +/- 20 versus 45 +/- 20 ml/min). Epinephrine induced a significant increase in both saphenous vein (82 +/- 38 versus 96 +/- 40 ml/min) and internal mammary artery (38 +/- 12 versus 55 +/- 24 ml/min) graft flows. We conclude that administration of vasoactive agents in the postcardiopulmonary bypass period may significantly affect saphenous vein and internal mammary artery graft flows.

Responsiveness of peripheral veins to vasodilators and the effect of nifedipine on alpha-adrenergic responsiveness in hypertension.

Vasodilators have varying hemodynamic properties that may be important in determining their efficacy for different disorders. We used the dorsal hand vein technique to measure the effects of several vasodilators infused locally and to measure the action of systemically administered nifedipine. The venodilatory effects of hydralazine, verapamil, diazoxide, and nitroglycerin were determined in peripheral veins of healthy subjects. The potency (ED50, the dose producing half-maximal response) was as follows: nitroglycerin (0.0007 micrograms/min) greater than verapamil (6.5 micrograms/min) greater than diazoxide (75 micrograms/min) greater than hydralazine (660 micrograms/min). The effect of oral nifedipine on alpha-adrenergic responsiveness of hand veins was determined. Nifedipine given in therapeutic doses for the treatment of hypertension was associated with a threefold increase in the ED50 for phenylephrine (92 to 277 ng/min; p less than 0.05) and norepinephrine (2.9 to 11.5 ng/min; p less than 0.05). Therapeutic doses of nifedipine are associated with measurable shifts in the dose-response curves to these two alpha-adrenergic agonists in the hand vein. The hand vein technique can be used not only to compare the potency of locally infused drugs but also to measure venous effects of vasoactive drugs at therapeutic concentrations achieved after systemic administration.

Effects of Vasoactive Drugs on Transdermal Lidocaine Iontophoresis

The effect of co-administration of vasoactive drugs on the transdermal iontophoretic delivery of lidocaine · HCI was studied in in vitro cells, in the isolated perfused porcine skin flap (IPPSF), and in vivo in pigs. Iontophoresis of lidocaine in vitro across human and porcine skin were similar, supporting the use of porcine skin as an appropriate animal model. Co-iontophoresis of the vasodilator tolazoline marginally decreased lidocaine flux in vitro, but significantly increased it in the IPPSF and in vivo. In contrast, norepinephrine decreased lidocaine flux in the IPPSF. Vasomodulation also changed the shape of the venous efflux profile in the IPPSF as evidenced by changes in fractional absorption index, as well as the AUC. These studies demonstrate that co-iontophoresis of vasoactive compounds may significantly alter the transdermal delivery of lidocaine and that use of in vitro animal model systems which possess a functional microcirculation are essential to study this process if reliable extrapolation to the in vivo setting is desired.

Effects of Vasoactive Drugs on Thromboxane A2 Mimetic-Induced Pulmonary Hypertension in Newborn Lambs

Isoproterenol, dobutamine, dopamine, and nitroprusside are four vasoactive drugs used to decrease pulmonary arterial pressure and increase cardiac output in newborns, infants, and children with sepsis. Thromboxane A2 likely produces some of the hemodynamic changes in sepsis, and U46619, a thromboxane A2 mimetic, produces similar changes in lambs. We studied the hemodynamic effects of these four vasoactive drugs in 10 spontaneously breathing newborn lambs during an infusion of U46619. After baseline hemodynamic measurements, U46619 (1-2 micrograms/kg/min) was infused to increase pulmonary arterial pressure and to decrease cardiac output. Then, either isoproterenol (0.05-1.0 micrograms/kg/min), dobutamine (5-20 micrograms/kg/min), dopamine (3-30 micrograms/kg/min), or nitroprusside (0.5-10.0 micrograms/kg/min) was infused. Every 10 min, measurements were repeated and the dose increased. U46619 significantly increased pulmonary arterial pressure by 182% and decreased cardiac output by 25% (p less than 0.05). Isoproterenol decreased pulmonary arterial pressure by 30% (p less than 0.05) and increased cardiac output by 25% (p less than 0.05) at low doses, and increased cardiac output by 115% at the maximum dose (p less than 0.05). Dobutamine decreased pulmonary arterial pressure by 11% (p less than 0.05) at low doses, and increased cardiac output by 28% (p less than 0.05) at low doses, and increased cardiac output by 71% at the maximum dose (p less than 0.05). Dopamine did not decrease pulmonary arterial pressure or increase cardiac output. Nitroprusside decreased pulmonary arterial pressure by 11% at the maximum dose (p less than 0.05). Isoproterenol and dobutamine may be more useful than dopamine and nitroprusside in the management of pulmonary hypertension and decreased cardiac output during sepsis.

Relationship between oxygen transport and oxygen uptake in patients with cirrhosis: Effects of vasoactive drugs

To elucidate the relationship between oxygen transport and uptake in cirrhosis, we studied the effects of three vasoactive drugs that change O2 transport. Systemic hemodynamics, blood gases and lactate concentration were measured in patients with alcoholic cirrhosis before and after intravenous dobutamine, propranolol and nitroglycerin. Nine patients received successively dobutamine and then propranolol. Ten patients received nitroglycerin. Three other patients without cirrhosis (controls) received dobutamine. In patients with cirrhosis, dobutamine infusion was accompanied by a significant increase in cardiac output (+21%), systemic O2 transport (+21%) and O2 uptake (+12%), whereas O2 extraction ratio and arterial lactate concentration did not change significantly. Propranolol administration was followed by a significant decrease in cardiac output (-24%) and systemic O2 transport (-25%) and a significant increase in O2 extraction ratio (+19%), whereas O2 uptake and arterial lactate concentration did not change. Nitroglycerin infusion was accompanied by a significant decrease in cardiac output (-21%), systemic O2 transport (-26%) and O2 uptake (-10%), whereas O2 extraction ratio (+18%) and arterial lactate concentration (+31%) significantly increased. In control patients, dobutamine infusion was accompanied by an increase in cardiac output and in systemic O2 transport and by a decrease in O2 extraction ratio, whereas O2 uptake was not modified. These results suggest that O2 uptake may be abnormally dependent on O2 transport in patients with cirrhosis.

Pathophysiology and evaluation of severity of congestive heart failure on the basis of venous characteristics.

To elucidate the possibility of grading the severity of congestive heart failure by using venous characteristics, we constructed venous pressure-volume curves (PVR) and calculated venous stiffness constants (K). In addition, effects of vasoactive drugs on venous distensibility were studied. A venous pressure-volume curve could be fit well by an exponential curve (r = 0.98 +/- 0.01). The PVR was shifted to the left with an increase in the clinical severity of congestive heart failure. The exponent of these curves, K, increased as the PVR was shifted to the left. K correlated with heart rate (r = 0.52, p less than 0.01), right atrial pressure (r = 0.54, p less than 0.02) and mean pulmonary arterial pressure (r = 0.47, p less than 0.04). Nitroglycerin and amrinone dilated veins and decreased K by 19.6 +/- 6.9% (p less than 0.03) and 14.0 +/- 4.3% (p less than 0.02), respectively. Changes in K (delta K) during the nitroglycerin and amrinone infusions correlated closely with the baseline K (delta K = -0.41 K + 0.22, r = 0.92, p less than 0.01). Therefore, the venodilating effects of these drugs were greater in patients with more severe congestive heart failure. The venous stiffness constant could be useful to grade the severity of congestive heart failure.

Vascular permeability and interstitial diffusion of macromolecules in the hamster cheek pouch: Effects of vasoactive drugs

A simple one-dimensional mathematical model which relates the number of “leaky” sites in postcapillary venules to the extravasation of macromolecules in terms of an effective microvascular permeability, P, and an effective interstitial diffusion coefficient, D, is developed. The model is used to analyze the data of E. Svensjö and K. Roempke [ in “Progress in Microvascular Research II” (F. C. Courtice, D. C. Garlick, and M. A. Perry, Eds.), pp. 449–463, 1984] and C. G. A. Persson and E. Svensjö [ in “Handbook of Inflammation” (J. L. Bonta, M. A. Bray, and M. J. Parnham, Eds.), pp. 61–82, 1985] for the transport of 70,000 molecular weight dextran in a hamster cheek pouch prior to and following topical application of two vasoactive agents: histamine and bradykinin. D ranged from 2.2 to 4.0 × 10 −9 cm 2/sec, and P was found to be 4.1 × 10 −8 cm/sec. The increased number of leaky sites resulted in a sixfold increase in P due to histamine, at a dose of 2.5 × 10 −6 M, and a fourfold increase in P due to bradykinin, at a dose of 4.0 × 10 −7 M.

Effects of Vasoactive Drugs on Blood Flow in Rabbits - Photoplethysmographic Assessment -

Effects of Vasoactive Drugs on Blood Flow in Rabbits - Photoplethysmographic Assessment -

Effects of vasoactive drugs on O 2 utilization in patients with cirrhosis: Evidence for a subclinical tissue hypoxia

Effects of vasoactive drugs on O 2 utilization in patients with cirrhosis: Evidence for a subclinical tissue hypoxia

Mechanical effects of vasoactive drugs on carotid sinus.

Carotid sinus diameter (CSD) is influenced by changes in sympathetic tone and vasoactive agents. This study was designed to determine which mechanical properties of the carotid sinus region were influenced by infusing vasoconstrictors (epinephrine, 4.56 X 10(-6) M, and phenylephrine, 9.85 X 10(-5) M) and a vasodilator (nitroprusside, 1.68 X 10(-4) M). CSD, carotid sinus length (CSL), pressure (CSP), and compliance (CSC), and arterial pressure were all recorded simultaneously from the isolated constant-flow-perfused carotid sinus region of 11 anesthetized dogs (35 mg/kg pentobarbital sodium) before and after drug perfusion. CSC was measured by a method previously described in which 13 microliters of perfusate is injected into the segment in a step-like manner and the resultant step change in pressure recorded. The compliance of the vessel segment is read on-line after a calibration procedure. CSD and CSL were measured using sonomicrometer length gauges positioned across and along the length of the carotid sinus segment. At a CSP of 99.9 +/- 0.6 (SE) mmHg, CSD, CSL, and CSC were 8.50 +/- 0.44 mm, 9.44 +/- 0.84 mm, and 0.46 +/- 0.05 microliter/mmHg, respectively. Decreasing CSP to 50 mmHg significantly reduced CSD and CSL and increased CSC. Increasing CSP to 150 mmHg produced opposite results. Vasoconstrictor drug infusion significantly decreased and vasodilator drug infusion significantly increased both CSD and CSL, producing parallel shifts in the CSP-CSD and -CSL curves toward and away from the pressure axis. The shift to new pressure-volume curves resulted in no change in CSC in response to the vasoactive agents.