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[Effect of dihydroergotamine (DHE) on blood volume and circulation in the calf in peridural anesthesia in the human].

Dihydroergotamine (DHE) preferentially constricts capacitance vessels in the skin and striated musculature, thereby redistributing blood in favor of the pulmonary vascular bed in the presence of neurogenic vascular tone. The aim of this study was to see if DHE would act likewise when neurogenic vascular tone is absent. Filling and blood flow of the calves were measured plethysmographically in six healthy, supine male volunteers before and during peridural anesthesia (PDA) to the level of at least T5 and, in the denervated state, after the injection of DHE 7.5 micrograms/kg intravenously. Arterial blood pressure, central venous pressure (CVP), and heart rate were also determined. Both blood flow (+2.2 ml/min per 100 ml tissue) and volume (+1 ml/100 ml tissue) of the calves increased while CVP and systolic arterial pressure decreased during PDA (Table 1). DHE did not affect the PDA-included increase in blood flow, but strongly reduced calf volume (-1.7 ml/100 ml tissue). This was accompanied by an increase in CVP and systolic blood pressure (Fig. 1). In the absence much as in the presence of neurogenic vascular tone, DHE preferentially constricts capacitance but not resistance vessels. Thus, DHE counteracts the vascular effects of PDA, as it improves cardiac filling and consequently raises arterial blood pressure by redistributing blood from the dilated capacitance vessels without curtailing blood flow. It would appear, therefore, that DHE is a rational alternative to fluid therapy for the prophylaxis of arterial hypotension during major conduction anesthesia.

Adult↗

Effect of labetalol on limb haemodynamics in patients following coronary artery bypass graft surgery.

Labetalol is a competitive inhibitor of alpha- and beta-adrenergic receptors and has an antihypertensive action. To determine limb haemodynamic effects, we measured calf blood flow and venous capacitance by venous occlusion plethysmography before and after oral labetalol in 10 patients 3-7 days following coronary bypass surgery. Vascular resistance was calculated as the ratio of mean arterial pressure to arterial flow. The peak effect of labetalol was taken as the point of maximum blood pressure decline, and this interval was selected for evaluation of the limb haemodynamic response. Ninety to 120 min after administration of 100-200 mg of labetalol the mean blood pressure fell from 88 +/- 3 to 79 +/- 3 mm Hg; (P less than 0.005). The mean arterial blood flow registered 5.1 +/- 1.0 ml 100 ml-1 limb tissue min-1 which was not significantly different from the control value of 4.4 +/- 0.8 ml 100 ml-1 limb tissue min-1. The calculated index of limb vascular resistance was not affected by labetalol administration, averaging 37 +/- 12 mm Hg 100-1 ml limb tissue min-1 before labetalol and 30 +/- 11 mm Hg ml-1 100 ml limb tissue min-1 at the time of peak hypotensive effect. There was a slight but statistically significant increment in limb venous volume to 1.9 +/- 0.3 from 1.5 +/- 0.3 ml 100 ml-1 limb tissue (P less than 0.025). Placebo administration produced no consistent changes in blood pressure, arterial blood flow, vascular resistance or venous capacitance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

Clinical pharmacological aspects on nitrate tolerance.

There is strong evidence that nitrate tolerance develops rapidly during repeated administration in the systemic resistance vascular bed and that there exists cross tolerance between different nitrates. There are divergent opinions on how tolerance in the systemic capacitance and the pulmonary vascular bed develops. This may be explained by real differences in tolerance development in ischemic heart disease and congestive heart failure but also by the use of several different preparations of nitrates in the studies performed. Available data on the pharmacokinetics of nitrates present a complex picture with highly variable bioavailability, clearance and apparent volume of distribution both inter- and intraindividually. It is suggested that nitrate tolerance should be studied in very homogeneous groups of patients with well defined hemodynamics. The nitrate used should have a very short half-life allowing for simulation of various modes of administration by intravenous infusion.

Drug Tolerance↗

[Enflurane and extracorporeal circulation. Peripheral vascular effects and consequences of hypothermia on its biotransformation].

The effects of enflurane on systemic vascular resistance and venous capacitance, and its biotransformation during hypothermia, were studied in patients undergoing cardiovascular surgery with enflurane anaesthesia. When administered during cardiopulmonary bypass (CPB), cardiac regulatory mechanisms being therefore excluded, enflurane induced an arteriolar vasodilation related to the concentration inhaled. An inspired concentration of 2.5% in hypothermia (28 degrees C) produced a drop in systemic vascular resistance of 30% from control level. In the same conditions, venous capacitance was not altered. The rise in the blood gas solubility coefficient during hypothermia was only partly balanced by haemodilution. Therefore, inspired enflurane concentration should be higher during hypothermic CPB than during normothermic anaesthesia to obtain the same effects. For the same amount of enflurane inhaled, the fraction of enflurane metabolized was higher in hypothermia than in normothermia, but the inorganic fluoride plasma concentration at its highest never reached the level of 50 mumol X 1(-1) regarded as the nephrotoxic threshold.

Adult↗

Vascular determinants of univentricular support.

The dynamic coupling between cardiac pump performance and vascular arterial-venous capacitive and resistive properties was examined analytically and experimentally to determine the feasibility of maintaining systemic and pulmonary circulation, devoid of the right heart. Analysis of the cardiovascular system (excluding neurohumoral factors), used a mathematical representation of the major determinants involved in cardiac output and demonstrated that change in pump flow output has reciprocal effects on the venous and arterial pressures. Independent of the pump's performance characteristics, cardiac output reserve was restricted, reaching a critical plateau (50% of normal) because of the rapidly depleting pulmonary venous pressure, concurrent with the translocation of the venous stressed volume to the arterial side of the circulation. Animal experiments aided by computer modeling confirmed that near normal flow can be sustained by actively mobilizing or augmenting blood volume, or by reducing selectively the unstressed volume and venous pooling. A single blood pump, in a form of a mechanical substitute, or the biologic left heart acting alone, can support the entire circulation. The right heart is not essential for normal pulmonary circulation, but serves to maintain low systemic venous pressure and a relatively high left heart flow reserve state. Peripheral vascular parameters, i.e., stressed volume and venous capacitance, serve a vital role in preserving the mechanical self regulation of cardiac output.

Animals↗

Capacitance effects and blood reservoir function in the splanchnic vascular bed during non-hypotensive haemorrhage and blood volume expansion in anaesthetized cats.

1. These experiments were designed to measure how much blood is mobilized from or pooled in the liver, spleen and gastro-intestinal tract to compensate for a haemorrhage or infusion of blood.2. Hepatic volume, splenic weight and intestinal volume were recorded in cats anaesthetized with sodium pentobarbitone. Whole blood was removed or infused at rates of 0.5-0.6 ml. kg(-1).min(-1) until 10 ml./kg (19% blood volume) had been removed or 18 ml./kg (34% blood volume) had been infused. These blood volume changes produced only small changes in arterial and portal pressures except after removal of 8 ml./kg (15% blood volume) when arterial pressure began to decrease rapidly.3. With small haemorrhages of up to 4% blood volume, the liver contributed 16%, the gastro-intestinal tract 23% and the spleen a negligible proportion of the blood volume removed. With haemorrhages of 15% blood volume, the liver contributed 21%, the gastro-intestinal tract 22% and the spleen 19% of the volume removed; a total splanchnic contribution of 62%.4. During infusions of 5-18 ml./kg (10-34% blood volume), the liver pooled 20%, the gastro-intestinal tract 40% and the spleen 6% of the volume infused; a total splanchnic contribution of 66%.5. It is concluded that the splanchnic bed mobilizes or pools up to 65% of the volume of blood removed from or infused into the cats. The mechanisms responsible for this blood reservoir function are discussed. While several factors may be involved, it seems likely that a reflex regulation involving atrial receptors and the sympathetic innervation of the splanchnic capacitance vessels is of predominant importance.

Animals↗

Effects of hCGRP 8-37 and the NK1-receptor antagonist SR 140.333 on capsaicin-evoked vasodilation in the pig nasal mucosa in vivo.

A novel pig in vivo model was used to study vascular effects of capsaicin, substance P and calcitonin gene-related peptide (CGRP) in the nasal mucosa and skin. An acoustic rhinometer was used to measure changes in nasal cavity volume, mainly representing changes in capacitance vessels in the vascular beds. The non-peptide NK1-receptor antagonist SR 140.333 and the CGRP-receptor antagonist hCGRP 8-37 were used to investigate the role of substance P and CGRP, respectively, in capsaicin-evoked vasodilation mediated through activation of sensory C-fibre afferents. In this study we show that SR 140.333 is a potent inhibitor of substance P-induced vasodilation in the nasal mucosa whereas it has no effect on the capsaicin-evoked responses. Substance P only elicited a minor and shortlasting increase in superficial skin blood flow; this response, however, was completely blocked after administration of SR 140.333. Capsaicin-evoked vasodilation in the skin was slightly reduced by SR 140.333. CGRP-induced vasodilation in the nasal mucosa and skin was of much longer duration than the substance P-induced response, and was thus similar to the vascular effects mediated by capsaicin. hCGRP 8-37 significantly reduced both the CGRP- and capsaicin-mediated vasodilation in the nasal mucosa and the decrease of nasal cavity volume. Although the peak vasodilation in the skin in response to capsaicin, was unaltered by blockade of CGRP-receptors, the integrated response was significantly reduced by hCGRP 8-37. The present results show that vasodilatory responses to activation of afferent nerves in the pig nasal mucosa and superficial skin are mainly dependent on CGRP, while NK1-receptor mechanisms seem to be of no or minor importance.

Animals↗

Effects of progestogens on haemostasis.

Epidemiological data suggested an involvement of the progestogen component in the pathomechanism of venous and arterial diseases during intake of oral contraceptives. The influence of progestogens on haemostasis parameters depend on type and dose of the progestogen, the presence of an estrogen, the route of application, and the duration of use. Treatment of women with progestogen-only preparations caused only minor effects on coagulation and fibrinolysis. Similarly, during hormone replacement therapy with natural estrogens, the additional application of progestogens induced no unfavourable changes on haemostasis. In contrast, the use of ovulation inhibitors resulted in an acceleration of coagulation and fibrinolysis. This is primarily induced by the marked action of ethinylestradiol on hepatic and vascular function. Progestogens with androgenic properties may counteract the estrogen-induced changes in the hepatic synthesis of platelet aggregation and readiness for coagulation. Estrogen and progesterone receptors are localized in endothelial and smooth muscle cells of the vessel wall, but there are differences in the response of veins and arteries to sex steroids. Estrogens and progestogens may influence collagen and elastin synthesis, and the release of vasoactive compounds and of factors controlling fibrinolysis from endothelium. In veins, progestogens may increase distensibility and capacitance resulting in a decreased blood flow. In predisposed women, this may lead to venous stasis and thrombosis. In arteries, progestogens may act as vasoconstrictors, and may enhance vasospasms at sites of injured endothelium which finally may lead to ischemic diseases.

Arteries↗

Importance of nitric oxide in hepatic arterial blood flow and total hepatic blood volume regulation in pigs.

The importance of nitric oxide in regulating basal arterial blood flow has been examined in several different vascular beds by intra-arterial infusion of inhibitors of nitric oxide synthesis, but not in the arterial vascular bed of the liver. In the present study, N(G)-nitro-L-arginine (L-NNA), in a dose of 0.5 and 1.0 mumol mL-1 of hepatic arterial blood flow, was infused for 5 min into the hepatic artery in seven pigs anaesthetized with pentobarbital sodium. The haemodynamic effects observed by the first infusion were not further enhanced by the second infusion. Hepatic arterial resistance increased by 143 +/- 38% and hepatic arterial blood flow declined by 38 +/- 10%. A systemic effect due to 'spillover' was observed, as evidenced by an increase in mean aortic blood pressure of 24 +/- 4 mmHg. However, no significant increase in arterial mesenteric resistance was observed and total liver blood flow remained unchanged. Hepatic arterial vasodilation in response to occlusion of the portal vein, the arterial buffer response, remained intact after inhibition of nitric oxide synthesis. Liver lobe thickness, measured by an ultrasonic technique, was not found to change with inhibition of arterial nitric oxide synthesis, excluding a significant direct effect of arterial nitric oxide on liver capacitance. In conclusion, nitric oxide is an important regulator of hepatic arterial resistance, but does not mediate the hepatic arterial buffer response and was not found to play any significant role in total hepatic capacitance regulation.

Animals↗

Subtype specific regulation of human vascular alpha(1)-adrenergic receptors by vessel bed and age.

BACKGROUND: alpha(1)-adrenergic receptors (alpha(1)ARs) regulate blood pressure, regional vascular resistance, and venous capacitance; the exact subtype (alpha(1a), alpha(1b), alpha(1 d)) mediating these effects is unknown and varies with species studied. In order to understand mechanisms underlying cardiovascular responses to acute stress and chronic catecholamine exposure (as seen with aging), we tested two hypotheses: (1) human alpha(1)AR subtype expression differs with vascular bed, and (2) age influences human vascular alpha(1)AR subtype expression. METHODS AND RESULTS: Five hundred vessels from 384 patients were examined for alpha(1)AR subtype distribution at mRNA and protein levels (RNase protection assays, ligand binding, contraction assays). Overall vessel alpha(1)AR density is 16+/-2.3fmol/mg total protein. alpha(1a)AR predominates in arteries at mRNA (P<0.001) and protein (P<0.05) levels; all 3 subtypes are present in veins. Furthermore, alpha(1)AR mRNA subtype expression varies with vessel bed (alpha(1a) higher in splanchnic versus central arteries, P<0.05); competition analysis (selected vessels) and functional assays demonstrate alpha(1a) and alpha(1b)-mediated mammary artery contraction. Overall alpha(1)AR expression doubles with age (<55 versus > or = 65 years) in mammary artery (no change in saphenous vein), accompanied by increased alpha(1b)>alpha(1a) expression (P< = 0.001). CONCLUSIONS: Human vascular alpha(1)AR subtype distribution differs from animal models, varies with vessel bed, correlates with contraction in mammary artery, and is modulated by aging. These findings provide potential novel targets for therapeutic intervention in many clinical settings.

Adrenergic alpha-Agonists↗

Sympathetic vascular control of the pig nasal mucosa: (I). Increased resistance and capacitance vessel responses upon stimulation with irregular bursts compared to continuous impulses.

An in vivo model is described in which pentobarbital anaesthetized pigs were used to study the sympathetic nervous control of the nasal mucosal vascular bed. Changes in blood flow in the sphenopalatine artery (representing nasal blood flow) and in the volume of the nasal cavity (mainly reflecting blood content in venous sinusoids), upon electrical stimulation of the cervical sympathetic trunk, were recorded simultaneously. Single impulses (15V, 5 ms) reduced both the arterial flow and the volume of the nasal mucosa. The effects of nerve stimulation with a continuous train of impulses at 0.59, 2 and 6.9 Hz were compared with those caused by stimulation with the irregular bursting pattern, triggered by recorded human sympathetic vasoconstrictor nerve activity, with the same average frequencies. Both types of stimulation reduced nasal blood flow and volume, but the responses were significantly larger with burst stimulation at 0.59 Hz. The volume reduction was already maximal at 0.59 Hz while the blood flow response increased further higher frequencies. Local intra-arterial pretreatment with the alpha-adrenoceptor antagonist phenoxybenzamine significantly attenuated the flow and volume responses to single impulses, while clear-cut reductions in blood flow (by 40%) and volume (by 80%) remained, upon stimulation, at 6.9 Hz. Noradrenaline given intra-arterially caused a dose-dependent reduction in nasal blood flow and volume. The noradrenaline effects were blocked by phenoxybenzamine treatment. The results show that the pig nasal mucosa represents a model where both blood flow and volume changes can be studied in parallel in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Haemodynamic effects of furosemide and ethacrynic acid (author's transl)].

The haemodynamic effects of intravenous injections of furosemide and ethacrynic acid were studied in 12 patients during rest and exercise. Cardiac output, heart rate and arterial blood pressure showed no significant changes after injection of furosemide or ethacrynic acid. Few minutes after injection of furosemide there were significant falls of pulmonary artery diastolic pressure and right atrial pressure, whereas no changes were seen after injection of ethacrynic acid. This initial effect of furosemide apparently is of primarily vascular origin, causing an increased peripheral venous capacitance. Ethacrynic acid failed to exhibit any direct vascular effect.

Acute Disease↗

[Nitroglycerin, furosemide and ethacrynic acid effect on hemodynamics in rest and during ergometric load in coronary disease patients].

The haemodynamic effects of intravenous injections of furosemide and ethacrynic acid as well as those of peroral administration of nitroglycerin were studied in 32 patients (4-12 weeks after acute myocardial infarction) during rest and exercise. Cardiac output, heart rate and arterial blood pressure showed no significant changes after administration of nitroglycerin, furosemide and ethacrynic acid (fig 3). A few minutes after application of nitroglycerin or furosemide there were significant falls of pulmonary arteria diastolic pressure and right atrial pressure (fig. 1 and 2), whereas no changes were seen after injection of ehtacrynic acid. This initial effect of furosemide as well as the effect of nitroglycerin is primarily of vascular origin, causing an increased peripheral venous capacitance. Ethacrinic acid failed to exhibit any direct vascular effect. Therefore during pulmonary oedema nitroglycerin together with furosemide should be given.

Blood Pressure↗

Nitric oxide inhibits capacitative Ca2+ entry and enhances endoplasmic reticulum Ca2+ uptake in bovine vascular endothelial cells.

In vascular endothelial cells, elevation of cytosolic free calcium concentration ([Ca2+]i) causes activation of nitric oxide synthase (NOS) and release of nitric oxide (NO). The goal of the study was to characterize the interplay between [Ca2+]i and NO production in this cell type. Simultaneous measurements of [Ca2+]i and intracellular NO concentration ([NO]i) in cultured bovine vascular endothelial cells (CPAE cell line) with the fluorescent indicators fura-2 and DAF-2, respectively, revealed that Ca2+ influx following agonist-induced intracellular Ca2+ store depletion (capacitative Ca2+ entry, CCE) represents the preferential Ca2+ source for the activation of the Ca2+-calmodulin-dependent endothelial NOS (eNOS). Exposure to the NO donor sodium nitroprusside (SNP) showed that high NO levels suppressed CCE and had an inhibitory effect on Ca2+ extrusion by the plasmalemmal Ca2+-ATPase. This inhibitory effect on CCE was mimicked by the membrane-permeant cGMP analogue 8-bromo-cGMP, but was reversed by the NO scavenger haemoglobin and prevented by the inhibitor of the NO-sensitive guanylate cyclase ODQ. Brief exposure to SNP reduced the peak of ATP-induced Ca2+ release from the endoplasmic reticulum (ER) and accelerated Ca2+ reuptake into the ER. Prolonged incubation with SNP resulted in enhanced Ca2+ loading of the ER, as revealed by direct measurements of store content with the ER-entrapped low-affinity Ca2+ indicator mag-fura-2. The results suggest that in vascular endothelial cells, NO synthesis is under autoregulatory control that involves NO-dependent [Ca2+]i regulation. Via cGMP-dependent inhibition of CCE and acceleration of Ca2+ sequestration into the ER, NO can lower [Ca2+]i and therefore exert an autoregulatory negative feedback on its own Ca2+-dependent synthesis.

Adenosine Triphosphate↗

Sarcoplasmic reticulum-sarcolemma interactions and vascular smooth muscle tone.

A characteristic of vascular smooth muscle cell morphology is a close apposition of its peripheral sarcoplasmic reticulum (SR) with the sarcolomma; this arrangement gives rise to important functional interactions whereby the peripheral SR regulates Ca2+ influx and vascular tone. We review here the key evidence supporting the following aspects of SR-sarcolemma interactions while establishing a conceptual framework encompassing (i) the SR ultrastructure and functions, (ii) the integration of the sarcolemmal Na+-Ca2+ exchanger and the peripheral SR in the mediation of a bidirectional Ca2+ exchange between the peripheral SR and the extracellular space, (iii) the existence of a higher myoplasmic free Ca2+ concentration [Ca2+]myo in the subsarcolemmal space formed between the sarcolemma and the peripheral SR relative to the [Ca2+]myo of the inner myoplasm in the resting smooth muscle cell, (iv) the division of the subsarcolemmal space into functional microdomains, (v) the existence of spontaneous localized bursts of Ca2+ release from the peripheral SR (Ca2+ sparks) towards the sarcolemma, (vi) the physiological triggering of nonlocalized Ca2+ release from the peripheral SR by Ca2+ influx (Ca2+-induced Ca2+ release), and (vii) capacitative Ca2+ entry in vascular smooth muscle. We present an overview of the physiological and pathological implications of these interactions.

Animals↗

Vasodilator effects of the sodium acetate in pooled protein fraction.

Paradoxical hypotension during rapid infusion of plasma protein fraction (PPF) has been attributed to vasodilation by bradykinin in PPF. This study employed a canine, controlled right heart bypass preparation to assess changes in systemic vascular resistance and venous capacitance during infusion of PPF and other possibly vasoactive mediators. Plasma protein fraction caused consistent vasodilation, whereas purified human albumin did not. This vasodilation could be ascribed entirely to acetate, present in PPF as a buffer. Bradykinin in PPF had no effect during venous infusion. Acetate is used widely as a buffer in intravenous and dialysate solutions. Its vasoactive properties must be recognized when such solutions are administered to patients with limited capacity to compensate for sudden vasodilation.

Acetates↗

Lack of effect of cyclandelate in peripheral arterial disease.

While cyclandelate is widely used in the therapy of peripheral arterial disease, objective evidence of its efficacy remains controversial. For this reason, 12 patients with intermittent claudication (average age of 66.8 years) received both cyclandelate 400 mg qid and placebo in a double-blind crossover trial lasting two months. During the cyclandelate and placebo periods, the following peripheral hemodynamic measurements were obtained using a plethysmograph and treadmill claudication testing: mean calf blood flow, vascular resistance and venous capacitance; finger and toe blood flow, pulsation amplitude and temperature before and after vasodilating maneuvers; arm and leg arterial pulsation amplitudes, one and ten minute calf reactive hyperemia reaction; 30 pound/30 second calf active hyperemia reactions and times of onset of claudication as measured on a treadmill. No major significant difference could be demonstrated between placebo and cyclandelate on any subjective symptom or any objective measurement. It is concluded that cyclandelate 400 mg qid for 4 weeks was of little objective value in treating this group of 12 patients with peripheral arterial disease and suffering from intermittent claudication.

Aged↗

Prevalence and determinants of cardiac and vascular hypertrophy in hypertension.

Hypertrophy of the capacitance arteries has recently been documented in hypertensive patients by noninvasive ultrasound techniques. To better define the prevalence and determinants of vascular hypertrophy and its potential association with ventricular hypertrophy in hypertension, we compared carotid and cardiac ultrasound findings in 172 normotensive and 172 unmedicated hypertensive subjects matched for age and sex. Despite similar body size, hypertension was associated with increased left ventricular wall thicknesses, mass, and mass index (89 versus 80 g/m2, P < .0001 for all comparisons) and increased carotid wall thickness (0.82 versus 0.77 mm) and cross-section area (17.1 versus 15.3 mm2, P < .005 for both comparisons). Among the 172 normotensive subjects, left ventricular hypertrophy was noted in 9 (5.2%) and arterial hypertrophy was found in 9 (5.2%), whereas ventricular hypertrophy was found in 21 (12.2%) and arterial hypertrophy in 19 (11%) hypertensive subjects. Arterial hypertrophy was found in 9% of hypertensive subjects with normal ventricular mass and in 24% with left ventricular hypertrophy (P < .05). Among hypertensive subjects carotid wall thickness and cross-sectional area were most strongly related to age and systolic pressure (P < .0001 for all comparisons), with little contribution form body size. Carotid relative wall thickness was only related to increasing age (P < .01). In contrast, left ventricular wall thickness and mass were strongly related to body size and systolic pressure (P < .0001 for comparisons) but not to age (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗