Search

Background and Aims Acute-on-chronic liver failure ( ACLF) is a clinical entity where there is a potential for reversibility of hepatic dysfunction once the acute hepatic insult resolves. The portal and systemic hemodynamics in ACLF patients to study its relevance in determining the clinical outcomes was studied. Methods Clinical, laboratory, portal, and systemic hemodynamic assessments were done at admission and after 3 months. Standard medical care was given to all the patients. Results Fifty-seven patients with ACLF were enrolled, and they underwent baseline hepatic venous pressure gradient ( HVPG) measurement. Twenty-six (46%) patients died during the 3-month follow-up. Presence of high HVPG and hepatic encephalopathy were found to be independent baseline predictors of mortality. Of the 31 surviving patients, 24 consented for a repeat HVPG. The baseline HVPG reduced from 16 (range 12-30) to 13 (range 6-21) mm Hg; ( P < 0.05). The reduction in HVPG correlated with clinical and biochemical recovery, and reduction in Child- Turcotte- Pugh score score ( P < 0.05), while the aortic mean arterial pressure, cardiac index and systemic vascular resistance index improved significantly (< 0.05). Six (25%) patients developed upper gastrointestinal bleed; the median HVPG between bleeders and non-bleeders was not different possibly because of early onset of bleed (median 20 [15-45 days]). Conclusions Baseline HVPG is an independent predictor of mortality in ACLF patients. The portal and systemic circulatory anomalies regress substantially by 90 days and correlate with clinical recovery. However, in the initial phase, the raised portal pressure predisposes these patients to high risk of variceal bleeding. [ABSTRACT FROM AUTHOR]

Background & Aims: Platelet-derived growth factor (PDGF) is the most potent stimulus for proliferation and migration of stellate cells. PDGF receptor β (PDGFRβ) expression is an important phenotypic change in myofibroblastic cells that mediates proliferation and chemotaxis. Here we analyzed the relationship between PDGFRβ expression, hemodynamic deterioration, and fibrosis in CCl4-treated rats. Thereafter, we investigated the effects produced by an adenovirus encoding a dominant-negative soluble PDGFRβ (sPDGFRβ) on hemodynamic parameters, PDGFRβ signaling pathway, and fibrosis. Methods: Mean arterial pressure, portal pressure, PDGFRβ mRNA expression, and hepatic collagen were assessed in 6 controls and 21 rats induced to hepatic fibrosis/cirrhosis. Next, 30 fibrotic rats were randomized into three groups receiving iv saline and an adenovirus encoding for sPDGFRβ or β-galactosidase. After 7days, mean arterial pressure, portal pressure, serum sPDGFRβ, and hepatic collagen were measured. Results: CCl4-treated animals for 18weeks showed a significantly higher increase in PDGFRβ mRNA compared to those treated for 13weeks and control rats. In CCl4-treated rats, the fibrous tissue area ranged from moderate to severe fibrosis. A direct relationship between the degree of fibrosis, hemodynamic changes, and PDGFRβ expression was observed. Fibrotic rats transduced with the adenovirus encoding sPDGFRβ showed increased mean arterial pressure, decreased portal pressure, lower activation of the PDGFRβ signaling pathway, and reduced hepatic collagen than fibrotic rats receiving β-galactosidase or saline. Conclusions: PDGFRβ activation closely correlates with hemodynamic disorders and increased fibrosis in CCl4-treated rats. Adenoviral dominant negative soluble PDGFRβ improved fibrosis. As a result, the hemodynamic abnormalities were ameliorated. [Copyright &y& Elsevier]

Administering relaxin to conscious rats and humans elicits systemic and renal vasodilation. The molecular mechanisms vary according to the duration of relaxin exposure-so-called 'rapid' (within minutes) or 'sustained' (hours to days) vasodilatory responses-both being endothelium-dependent. Rapid responses are mediated by G protein coupling to phosphoinositol-3 kinase/Akt (protein kinase B)-dependent phosphorylation and activation of nitric oxide synthase. Sustained responses are mediated by vascular endothelial and placental growth factors, as well as increases in arterial gelatinase activity. Thus, after hours or days of relaxin treatment, respectively, arterial MMP-9 or MMP-2 hydrolyze 'big' endothelin (ET) at a gly-leu bond to form ET, which in turn activates the endothelial ET receptor/nitric oxide vasodilatory pathway. Administration of relaxin to conscious rats also increases global systemic arterial compliance and passive compliance of select isolated blood vessels such as small renal arteries (SRA). The increase in SRA passive compliance is mediated by both geometric remodeling (outward) and compositional remodeling (decreased collagen). Relaxin-induced geometric remodeling has also been observed in brain parenchymal arteries, and this remodeling appears to be via the activation of peroxisome proliferator-activated receptor-γ. Given the vasodilatory and arterial remodeling properties of relaxin, the hormone may have therapeutic potential in the settings of abnormal pregnancies, heart failure, and pathologies associated with stiffening of arteries. [ABSTRACT FROM AUTHOR]

The systemic and peripheral hemodynamics was studied in male white rats under conditions of acute nitrite hypoxia (subcutaneous administration of sodium nitrite at doses of 1, 3, and 5 mg/100 g body mass). By the electrocardiographic, rheographic, and other methods there were recorded the heart rate (HR), minute circulation volume (MCV), cardiac output (CO), skeletal muscle circulation (SMC), brain circulation (BC), and systemic arterial pressure (AP). Nitrite was shown to produce a fast, dose-dependent AP fall accompanied by a decrease of MCV due to development of bradycardia and a fall of CO. At the phase of the steady hypotension, MCV increased due to a significant rise of CO on the background of the continuing bradycardia. The systemic circulatory effects of NaNO were found to be accompanied by a redistribution of peripheral circulation in the form of a dose-dependent increase of BC and a sharp fall of MCV. It was shown that 1-1.5 h after the nitrite injection the parameters of systemic and peripheral hemodynamics approached the initial levels. Possible triggering mechanisms of the initial stage of the rat cardiovascular adaptation to conditions of acute nitrite hypoxia are discussed. [ABSTRACT FROM AUTHOR]

Pregnancy is a unique physiological condition of profound maternal renal and systemic vasodilation. Our goal has been to unveil the reproductive hormones mediating this remarkable vasodilatory state and the underlying molecular mechanisms. In addition to advancing our knowledge of pregnancy physiology, reaching this goal may translate into therapeutics for pregnancy pathologies such as preeclampsia and for diseases associated with vasoconstriction and arterial stiffness in nonpregnant women and men. An emerging player is the 6 kDa corpus luteal hormone relaxin, which circulates during pregnancy. Relaxin administration to rats and humans induces systemic and renal vasodilation regardless of sex, thus mimicking the pregnant condition. Immunoneutralization or elimination of the source of circulating relaxin prevents renal and systemic vasodilation in midterm pregnant rats. Infertile women who become pregnant by donor eggs (IVF with embryo transfer) lack a corpus luteum and circulating relaxin, and they show a markedly subdued gestational increase in glomerular filtration rate. These data implicate relaxin as one of the vasodilatory reproductive hormones of pregnancy. There are different molecular mechanisms underlying the so-called rapid and sustained vasodilatory actions of relaxin. The former is mediated by Gαi/o protein coupling to phosphatidylinositol-3 kinase/Akt (protein kinase B)-dependent phosphorylation and activation of endothelial nitric oxide synthase, the latter by vascular endothelial and placental growth factors, and increases in arterial gelatinase(s) activity. The gelatinases, in turn, hydrolyze big endothelin (ET) at a gly-leu bond to form ET1-32, which activates the endothelial ETB receptor/nitric oxide vasodilatory pathway. [ABSTRACT FROM AUTHOR]

Background: Currently, albumin dialysis is the most widely used nonbiological liver support system. We hypothesized that direct peritoneal albumin exposure in the peritoneal cavity would stabilize blood flow and prevent liver and brain injury, in the same way that had previously been seen with extracorporeal albumin dialysis systems. Materials and Methods: Fourteen Landrace pigs (weight 25--30 kg) underwent 70%% right hepatectomy and were randomly assigned into a control (C, n == 7) and an intraperitoneal albumin treated group (A, n == 7). The systemic, cerebral, and pulmonary hemodynamic parameters of the animals were recorded at 0, 6, 9, and 12 hr following reperfusion of the liver remnant. Results: Mean arterial blood pressure, cardiac output, and stroke volume were significantly higher in group A at the end of the experiment. Significantly higher mean intracranial pressure (ICP) values were observed in group C compared to group A, both at 9 hr (21.3 ±± 5.2 versus 14.1 ±± 3.5 mmHg, p < .0005) and 12 hr (23 ±± 4.3 versus 11 ±± 3.5 mmHg, p < .0005). On the contrary, cerebral perfusion pressure (CPP) remained stable in albumin-treated groups after the sixth postreperfusion hour. Mean pulmonary artery pressure and pulmonary vascular resistance (PVR) were significantly lower in group A compared to group C at 12 hr, while pulmonary capillary wedge pressure (PCWP) stabilized in albumin-treated animals. Conclusions: This study provides the first evidence that intraperitoneal albumin may be able to attenuate systemic, pulmonary, and cerebral hemodynamic disturbances associated with acute liver failure. [ABSTRACT FROM AUTHOR]

Background & Aims: Increased activity of the vascular Akt/eNOS signaling pathway is involved in the hemodynamic and renal complications developed by patients and rats with cirrhosis and ascites. This occurs in the setting of impaired Akt/eNOS activity within the cirrhotic liver. Here we assessed the feasibility of selectively inhibiting vascular eNOS without further impairing the intrahepatic activity of this enzyme. Ultimately, we sought to determine whether endothelial transduction of a constitutively inactive mutant of Akt (AA-Akt) improves circulatory function and sodium excretion in cirrhotic rats with ascites. Methods: First, we administered recombinant adenoviruses that encode the β-galactosidase gene (β-gal) to 5 control rats and 5 cirrhotic rats with ascites and analyzed their tissue distribution by chemiluminescence. Next, urine samples were obtained from 18 cirrhotic rats with ascites and then the animal randomly received saline or adenoviruses containing the β-gal or the AA-Akt genes. Following a 24-h urine collection period, hemodynamic studies were performed and tissue samples were obtained to analyze Akt and eNOS expressions. Results: No β-gal activity was detected in the liver of cirrhotic rats compared to that of controls. This was paralleled by increased β-gal activity in other territories such as the thoracic aorta. AA-Akt transduction improved systemic hemodynamics, splanchnic perfusion pressure and renal excretory function in comparison with cirrhotic rats transduced with β-gal adenoviruses or receiving saline. Moreover, the AA-Akt transgene did not modify portal pressure. Conclusions: Inactivation of extrahepatic vascular Akt and the concomitant decrease in nitric oxide expression ameliorate systemic hemodynamics and renal excretory function in experimental cirrhosis. [ABSTRACT FROM AUTHOR]

Therapy of unresectable hepatic metastases may include tumor necrosis factor (TNF)-α treatment. Because of its serious systemic side effects, TNF-α is only used in isolated hepatic perfusion. This, however, is a technically demanding procedure with a substantial mortality rate. The infusion of TNF-α via the hepatic artery without hepatic isolation would be less invasive. Systemic side effects, however, have not been studied yet. Therefore, we evaluated in pigs the effects of TNF-α hepatic artery infusion (HAI) on systemic hemodynamics, inflammation, and organ injury. Animals were randomized in three groups. In group 1, HAI was performed with 0.9% NaCl ( n = 6). In group 2, 20 µg/kg TNF-α ( n = 6), and in group 3, 40 µg/kg TNF-α ( n = 6) were added. HAI was performed over 15 min, followed by 120 min of observation. Finally, 250 ml hydroxyethylstarch (HAES; 6%) was administered for resuscitation and hemodynamics were analyzed for another 30 min. Hepatic artery TNF-α infusion did not cause complications such as bleeding, cardiac depression, pulmonary dysfunction, or SIRS. TNF-α induced a 30% decrease of MAP and systemic vascular resistance, as well as a rise in heart rate and endexspiratory pCO2. TNF-α also moderately (10–20%) lowered the cardiac preload and induced a metabolic acidosis, which, however, could easily be controlled. TNF-α HAI did not induce liver toxicity, and all hemodynamic changes normalized either spontaneously within the 120-min observation period, or, at least, after HAES resuscitation. TNF-α-based HAI, which may represent a minimally invasive alternative to isolated hepatic perfusion, can be performed without early systemic hemodynamic complications. [ABSTRACT FROM AUTHOR]

Objective: The progression of liver cirrhosis eventually increases cardiac output, while blood pressure and systemic vascular resistance are reduced. A complex behavior of portal hemodynamic to hepatic artery and system circulation has not yet been presented. There is a lack in knowledge about the correlation of local and systemic circulation parameters to the degree of liver failure, with respect to presence of ascites and esophageal varices.Patients and Methods: The study sample was 76 patients hospitalized for established alcoholic liver cirrhosis. Patients were divided into groups according to Child-Pugh clinical score; grade A (n = 24), B (n = 18) and C (n = 18). Ascites was found in 28 patients and esophageal varices in 46. Portal vein flow velocity (PVFV), hepatic artery resistance index (HARI), heart and great vessels within mediastinal cavity were assessed with ultrasound devices equipped with spectral Doppler.Results: Significant differences in mean blood pressure, systemic vascular resistance index (SVRI) minute volume, cardiac index and PVFV were found in the group of patients with the most severe stage (C). In regard to presence of ascites statistically significant difference was observed in elevated mean blood pressure and SVRI. Correlation was found between conjugated HARI to blood pressure and to SVRI.Conclusions: In patients with liver cirrhosis there is an inversely reciprocal relationship of conjugated HARI with PVFV, correlating to disease grade. PVFV in cirrhosis decreases and HARI values were over 0.7. Study demonstrated that combining echocardiography with abdominal Doppler ultrasound served as valuable non-invasive diagnostic insight in liver and systemic circulation among different grade of cirrhosis. [ABSTRACT FROM AUTHOR]

Background/Aims: Muscle wasting likely influences blood flow to muscle districts in advanced cirrhosis. Thus, we assessed systemic hemodynamics and femoral artery blood flow corrected by muscle mass of the lower limb in 13 patients (Child-Pugh classes B and C) and 11 healthy controls. Methods: Systemic hemodynamics were assessed by transthoracic electrical bioimpedance, femoral artery blood flow by duplex-Doppler and muscle mass by magnetic resonance imaging. Results: As expected, patients exhibited increased cardiac index and reduced peripheral vascular resistance. Femoral artery blood flow did not differ between patients and controls. However, when this parameter was indicized by the muscle mass of the lower limb, which was reduced in patients (median: 3391; range: [2546–4793] vs 5118 [3562–7077]cm3, p =0.0006), it proved almost doubled in patients (91.1 [59.9–119.4] vs 50.5 [38.6–69.8]μl/mincm3; p =0.0001). Patient femoral blood flow indicized by muscle mass correlated inversely with peripheral vascular resistance (r =−0.65; p =0.017) and directly with cardiac index (r =0.57; p =0.042). Conclusions: Vasodilation of muscle districts contributes to the reduced peripheral vascular resistance in advanced cirrhosis. Our findings provide a stronger rationale for the use of non-selective vasoconstrictors to treat hemodynamic-dependent complications of cirrhosis, such as hepatorenal syndrome. [Copyright &y& Elsevier]

Objective: To determine whether alterations in extracellular volume expansion observed during normal and hypertensive pregnancy run in parallel to changes in the mRNA expression of renal transporters. Methods: Wistar rats were divided into four groups: control (C, n = 5); pregnancy (P, n = 5); Nω-nitro-l-arginine methyl ester (L-NAME; 50 mg/kg/d)-treated control (H, n = 6); and pregnant rats (HP, n = 6). Hemodynamic studies were performed on day 14 of pregnancy, at which time we also analyzed of the sodium transporters (NHE3, Na/K/2Cl and Na/Cl), potassium channel (ROMK2) and water channel (AQP2). Results: As expected, P rats presented high cardiac output (CO) and normal blood pressure (BP), whereas H rats presented lower CO and elevated BP. A significant (threefold) increase in total vascular resistance and a decrease in stroke volume were observed in the HP group. Hypertension resulting from nitric oxide (NO) synthesis inhibition blunted systemic hemodynamic adaptations during pregnancy. Compared with C rats, mRNA expression of ROMK2 in P rats was lower, whereas that of AQP2 was higher. Expression of AQP2 was significantly higher in H than in C or HP groups. Expression of BSC and NHE3 was lower in the HP than in the P group. The NO inhibition also provoked renal transporter alterations in HP. Conclusions: Our results suggest that tubule transporter variants may mediate the hemodynamic adaptations seen during pregnancy, although we cannot rule out the hypothesis that other factors are also mediating hemodynamic changes. [ABSTRACT FROM AUTHOR]

Presents several studies about the relationship between kidney and hypertension. "Long-Term Comparative Antiproteinuric Effect of Single Versus Combination Therapy Based on Olmesartan in Non-Diabetic Nephropathies," by Pedro Aranda et al; "History of Hypertension and Blood Pressure Are Independently Associated With Impaired Renal Function During Myocardial Infarction," by Giuseppe Berton et al; "Inflammatory Polymorphisms and Stress Induced Pressure Natriuresis," by Yanbin Dong et al.

Objective: To investigate whether neuromuscular block can affect bispectral index (BIS) or cerebral hemodynamics under moderate or deep sedation produced by propofol.Design and Setting: Prospective, controlled study in a university hospital affiliated intensive care unit.Patients: Seventeen surgical patients undergoing elective esophagectomy.Interventions: After stabilization with either light or deep sedation we investigated whether the BIS, electromyographic activity (EMG), or cerebral and systemic hemodynamic parameters were affected by administration of muscle relaxant.Measurements and Main Results: Neuromuscular block reduced the BIS during moderate sedation but not during deep sedation although the EMG at both levels of sedation was significantly reduced. No positive effects of neuromuscular block on cerebral hemodynamics were obtained with monitoring of regional cerebral oxygen saturation and middle cerebral artery blood velocity; however, significant effects on systemic hemodynamic parameters were observed only at moderate propofol sedation. The values of BIS and systemic hemodynamic variables with moderate sedation were also very similar to those with deep sedation and neuromuscular block although these values differed without neuromuscular block.Conclusions: Neuromuscular block altered the BIS score in moderately sedated patients but not in deeply sedated patients although cerebral hemodynamics was not affected by neuromuscular block during either moderate or deep sedation. Muscular relaxant also enhanced cardiovascular stability with moderate sedation. These results suggest that level of consciousness may be decreased by neuromuscular block during moderate sedation but not affected during deep sedation. [ABSTRACT FROM AUTHOR]

Abstract: The aim of our study was to evaluate the effects of thromboxane A2 (TXA2) agonist, U-46619, on systemic circulatory parameters in the pigs before and after administration of a novel TXA2 receptor antagonist and synthase inhibitor (BM-573). Twelve anesthetized pigs were randomly assigned in two groups: in Ago group (n =6), the animals received six consecutive injections of U-46619 at 30min interval, while in Anta group (n =6) they received an increasing dosage regimen of BM-573 10min before each U-46619 injection. The effects of each dose of BM-573 on ex vivo platelet aggregation induced by arachidonic acid, collagen or ADP were also evaluated. Vascular properties such as characteristic impedance, peripheral resistance, compliance, arterial elastance were estimated using a windkessel model. Intravenous injections of 0.500mg/ml of BM-573 and higher doses resulted in a complete inhibition of platelet aggregation induced by arachidonic acid. In the same conditions, BM-573 completely blocked the increase of arterial elastance, and stabilized both mean aortic blood pressure and mean systemic blood flow. In conclusion, BM-573 could therefore be a promising therapeutic approach in pathophysiological states where TXA2 plays a main role in the increase of vascular resistance like in pathologies such as systemic hypertension. [Copyright &y& Elsevier]

Renal hemodynamic effects of somatostatin are not related to inhibition of endogenous insulin release. Background. Somatostatin inhibits endocrine and exocrine secretions and exerts renal vasoconstriction. The mechanism underlying somatostatin's vascular effects is unknown. Since insulin can cause vasodilation, we hypothesized that removal of basal insulin release by somatostatin may contribute to somatostatin-induced renal vasoconstriction. Methods. The study was conducted in different protocols comprising forty-six healthy male volunteers. Randomized studies were performed to compare the effects of somatostatin alone (0.1 μg/kg/min) to the effects of somatostatin + low dose insulin (0.1 mU/kg/min), the effects of somatostatin + low dose insulin to the effects of somatostatin + high dose insulin (1.5 mU/kg/min), and the effects of insulin (1.5 mU/kg/min) + somatostatin. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured with the para -aminohippurate (PAH) and the inulin clearance technique, respectively. Blood pressure and pulse rate were measured non-invasively. Results. Somatostatin alone decreased GFR (-14 ± 6%, P < 0.001) and RPF (-16 ± 7%, P < 0.001) whereas systemic hemodynamics were unchanged. Preceding or concomitant infusion of insulin at high doses (insulin plasma concentration of 127 ± 25 or 144 ± 17 μU/mL) but not co-infusion with low dose insulin (insulin plasma concentration of 11 ± 3 μU/mL) mitigated or reversed the vasoconstrictive actions of somatostatin on GFR and RPF. Conclusions. Somatostatin induces marked renal vasoconstriction and exogenous restoration of fasting insulin concentrations does not influence the renal vascular effects. Therefore, it is unlikely that somatostatin-induced vasoconstriction is due to removal of basal insulin. Plasma insulin concentrations in the high postprandial range can reverse somatostatin-induced renal vasoconstriction, suggesting functional... [ABSTRACT FROM AUTHOR]

Background: In patients with cirrhosis, glucose may induce splanchnic and renal vasodilation. Since the antidiabetic sulfonylurea glibenclamide is known to induce splanchnic and renal vasoconstriction in portal hypertensive animals, this drug may inhibit glucose-induced hemodynamic responses in patients with cirrhosis. The aim of the present study was to investigate, in patients with cirrhosis, the short-term effects of glibenclamide on hemodynamic and humoral responses to glucose. Methods: Patients were randomly assigned to receive either glibenclamide (5-mg tablet) or a placebo. All patients received an infusion of 10% glucose (62.5 ml/h for 12 h) that was started at the same time as glibenclamide or placebo administration. Studies were performed prior to and 90 min after glibenclamide or placebo. Results: Glibenclamide (i.e. glibenclamide plus glucose) significantly increased plasma insulin concentrations and glycemia while placebo (i.e. glucose alone) significantly increased glycemia but did not change plasma insulin levels. Glibenclamide did not significantly change the hepatic venous pressure gradient while this value was significantly increased following glucose alone. Glibenclamide did not significantly change renal blood flow and glomerular filtration rate while glucose alone significantly increased renal blood flow without affecting the glomerular filtration rate. Glibenclamide significantly decreased cardiac index while glucose alone did not change this value. Conclusions: In patients with cirrhosis receiving glucose, glibenclamide blunted glucose-induced splanchnic and renal vasodilation. In addition, glibenclamide per se induced a decrease in cardiac index. These findings should be taken into account when glibenclamide is administered to patients with cirrhosis and type 2 diabetes. [ABSTRACT FROM AUTHOR]

Octreotide is effective during 48 h in the treatment of acute variceal bleeding, probably by reducing variceal blood flow and pressure. Its basal and postprandial effects on splanchnic and systemic hemodynamics, and hormonal changes over this time interval have not yet been studied. Twenty-four patients with cirrhosis and portal hypertension were randomized to receive a liquid meal and either octreotide (Oct, 100 μg bolus intravenous, followed after 2 h by a continuous infusion of 25 μg/hr for 20 hr) or placebo (Plac) given at three consecutive days. Splanchnic (Doppler ultrasound) and systemic hemodynamics (noninvasive cardiac monitoring) were assessed on four consecutive days (one control day and three treatment days) during 2 hr. The postprandial increase in mean blood velocity of the superior mesenteric artery (SMA- Vmean, +44%), portal blood velocity (PV- Vmean, +44%) and total hepatic blood flow (HBF, +40%) observed in the placebo group during the control day was abolished during the first day of treatment (SMA-Vmean, +3%, P < 0.01; PV-Vmean, +6%, P < 0.05; HBF, −25%, P < 0.01) and still reduced after 48 hr in the octreotide group (SMA-Vmean, +28%, P < 0.05; PV-Vmean, +22%, P > 0.05; HBF, −8%, P < 0.05). The postprandial increase in cardiac index (CI, +10%) and decrease in systemic vascular resistance index (SVRI, −6%) were blunted after the initial injection of octreotide only (CI, −8%, P < 0.05; SVRI, +18%, P < 0.01). Endothelin-1-levels, which were increased at baseline (Plac 25 ± 17, Oct 16 ± 13 ng/liter, P > 0.05) decreased significantly after 48 hr of treatment with octreotide (Plac 27 ± 20, Oct 8 ± 4 ng/liter, P < 0.05). Octreotide is effective during 48 hr in the prevention of postprandial hyperemia in cirrhotics, even if its efficacy is decreasing over time. Moreover it may have positive effects on systemic vasodilation in cirrhotics. These findings suggest a potential role of this drug in the chronic treatment of portal hypertension. [ABSTRACT FROM AUTHOR]

Correlation between blood pressure and parameters of systemic hemodynamics was studied on cats using electrical stimulation of the ventral medulla oblongata. Changes in blood pressure induced by presoor activation were related to venous hemodynamics in the anterior rather than posterior vena cava. Venous blood flow is assumed to be involved in hemodynamic changes caused by stimulation of pressor centers but not depressor centers in the ventral medulla oblongata. [ABSTRACT FROM AUTHOR]

The first dose of angiotensin-converting enzyme (ACE) inhibitors may trigger a considerable fall of blood pressure in chronic heart failure. The response may be dose-related. To determine hemodynamic and systemic oxygenation effects of low-dose enalaprilat, we administered intravenous enalaprilat (0.004 mg/kg) as bolus (group B) or continuous 1-hour infusion (group C) in 20 patients with congestive heart failure due to ischemic heart disease with acute decompensation refractory to inotropic, vasodilator and diuretic therapy. Hemodynamic and systemic oxygenation variables were recorded at baseline (+0 min), +30, +60, +120, +180, and +360 min after the start of intervention. Mean arterial pressure (MAP) (p < 0.001), mean pulmonary artery pressure (MPAP) (p < 0.001), pulmonary artery occlusion pressure (PAOP) (p < 0.001), oxygen extraction ratio (ER) (p < 0.026) decreased regardless of enalaprilat application. Compared to group B, there was in group C prolonged decrease of MAP, MPAP, PAOP, ER and increase of pulmonary artery oxyhemoglobin saturation in regard to baseline values. Cardiac index, heart rate, central venous pressure and oxygen consumption index did not change. A low dose of intravenous enalaprilat (0.004 mg/kg) can be used to safely improve hemodynamics and systemic oxygenation in congestive heart failure due to ischemic heart disease with acute refractory decompensation. [ABSTRACT FROM AUTHOR]

Objective: Lipopolysaccharide (LPS) induces early (within 1 h) and delayed (after several hours) impairment of vascular reactivity to catecholamines whose mechanisms are different, although they probably both involve nitric oxide (NO). Temporal and quantitative relationships between hyporeactivity to noradrenaline and NO production were investigated in a rat model of endotoxaemia allowing to clearly distinguish the two phases of hyporeactivity. Methods: Anaesthetised rats were infused with LPS (14 mg kg−1 h−1) for 1 h. Pressure responses to noradrenaline (NA) and circulating NO derivatives (nitrosyl haemoglobin, NO2−, NO3−) were monitored for 5 h after the onset of infusion. Reactivity to NA and tissue cyclic GMP level were also assessed ex vivo, in aortic rings taken at different experimental times. Results: LPS-induced early hyporeactivity to NA was associated with a moderate but significant increase in plasma NO3− level, without any significant change in concentration of the other circulating NO derivatives. Neither reactivity ex vivo nor cyclic GMP content were modified in aortae taken after 1 h of LPS infusion. By contrast, delayed hyporeactivity (5 h after the onset of LPS infusion) was associated with a large increase in all circulating NO derivatives (up to 2.5 fold), enhanced aortic cyclic GMP level and aortic hyporeactivity ex vivo. Pre-treatment of rats with NG-nitro-L-arginine methyl ester (1 mg kg−1 i.v.) entirely prevented early hyporeactivity and rise in NO3− concentration. In addition it attenuated in comparable proportion both delayed hyporeactivity to NA in vivo and circulating levels of NO derivatives. Conclusion: The results confirm the involvement of NO in the two phases of hyporeactivity to NA induced by LPS. They strongly support the view that a circulating factor is involved in triggering endothelial NO release during the early phase, whereas the delayed phase is associated with a high production of NO in vascular smooth muscle resulting from the induction of NO synthase. [ABSTRACT FROM PUBLISHER]

Objectives: The purpose of this study was to investigate the changes in β-adrenoceptor density (Bmax) and distribution in a model of chronic myocardial infarction in rats, and to relate possible changes to hemodynamic and neurohumoral abnormalities. In addition, we examined the effects of 8 weeks treatment with ibopamine and captopril. Methods: There were 3 experiments: (1) Bmax and plasma catecholamines were examined (n = 46), (2) Bmax was compared in infarcted and non-infarcted tissue (n = 13), and (3) contractile function was evaluated by isolated heart perfusion (n = 40). Of rats in Expts. (1) and (3), 50% had myocardial infarction induced by coronary ligation and 50% were controls. Each group was divided between ibopamine, ibopamine and captopril, or standard (no drug) treatment. Results:Bmax was not decreased in rats with myocardial infarction (10.8 ± 0.8 fmol/mg protein), compared to normal rats (11.4 ± 0.6 fmol/mg protein), and the ratio β1/β2 was also unaffected. In infarcted tissue, Bmax was significantly (P = 0.03) lower than in non-infarcted tissue. Baseline left ventricular pressure, systolic and diastolic dP/dT were all impaired (P < 0.001), and plasma norepinephrine levels were elevated in rats with myocardial infarction (16.03 ± 230 vs. 1287 ± 83 pg/ml; P < 0.05), compared to normals. Both ibopamine alone and in combination with captopril reduced the elevated plasma norepinephrine levels in infarcted rats (P < 0.001), but only the combination of the 2 drugs significantly increased Bmax in infarcted rats (14.7 ± 0.8 fmol/mg protein; P = 0.03 vs. untreated myocardial infarction), while ibopamine alone had no significant effect (13.1 ±1.1 fmol/mg protein; p = ns). Also, active drug treatment had no significant effect on the hemodynamic changes. Conclusions: In this coronary artery ligation model of myocardial infarction in rats, no β-adrenoceptor down-regulation is observed, despite marked abnormalities in baseline left ventricular function and plasma norepinephrine levels. The combination of ibopamine and captopril significantly increases Bmax in infarcted rats, which is accompanied by a reduction in plasma norepinephrine levels, but not by an improvement in hemodynamic parameters. [ABSTRACT FROM PUBLISHER]

Objective: Effects of OPC-18790, a novel positive inotropic agent, on cardiohaemodynamics and cardiac energetics were assessed simultaneously in dogs with cardiac ischaemia using phosphorus-31 magnetic resonance spectroscopy (31P-MRS) and compared with those of amrinone, a pure cGMP-inhibited PDE inhibitor. Methods: Cardiac ischaemia was produced by partial stenosis of the coronary artery. Dogs with cardiac ischaemia were instrumented for the determination of regional coronary blood flow (non-radioactive coloured microsphere method), regional contractile function (sonomicrometry), and haemodynamics. Myocardial phosphate compounds were measured simultaneously by 31P-MRS. Results: Coronary stenosis produced regional dyskinesis, a slight decrease in cardiac output (CO), intracellular acidosis, an increase in the inorganic phosphate (Pi)/creatine phosphate (PCr) ratio concomitantly with a decrease in regional coronary blood flow (CBF) in the ischaemic region. OPC-18790 dose-dependently produced an increase in contractility (measured by peak LVdP/dt) and CO, with only slight changes in heart rate (HR) and mean blood pressure (mBP). OPC-18790 did not change regional dyskinesis, but improved the Pi/PCr ratio at the high dose compared with ischaemic values (before drug administration). Amrinone produced an increase in CO comparable to that of OPC-18790; however, the increase in peak LVdP/dt was smaller while the increase in HR and decrease in mBP were larger than those seen with OPC-18790. Amrinone worsened the Pi/PCr ratio and intracellular acidosis only at the high dose. Conclusion: These observed differences in energy metabolism between OPC-18790 and amrinone at the high dose may be due to the ability of OPC-18790 to increase CBF in the ischaemic region and which may attributed to its differing effect on overall haemodynamics. Thus, OPC-18790 may be useful in the management of ischaemic heart failure. [ABSTRACT FROM PUBLISHER]

By its regulating effects on blood vessel tone, nitric oxide (NO) may play an important role in the coupling of oxygen delivery (DO2) to metabolic rate. We reasoned that if endogenous NO synthesis is an important modulator of oxygen extraction ratio (O2ER), then administration of a NO donor will alter oxygen extraction capabilities during a fall in blood flow. We studied the effects of the NO donor, nitroprusside, on the relationship between DO2 and oxygen uptake (VO2) during an acute reduction in DO2 induced by cardiac tamponade. Twenty-one healthy, anaesthetised, mechanically ventilated dogs were randomly divided into 3 groups. Group 1 (n = 7) served as control; Groups 2 and 3 were given sodium nitroprusside at 1.0 μg/kg · min (n = 7), and 2.5 μg/kg · min intravenously (n = 7), respectively. All animals were given normal saline i.v. at a rate of 20 ml/kg · h throughout the study. Cardiac tamponade was induced by bolus injections of normal saline into the pericardial space. In the control animals the critical DO2 (DO2crit) was found at 10.1 ± 1.5 ml/kg · min and critical O2ER (O2ERcrit) at 63.3 ± 10.9%. Nitroprusside at the lower dose decreased systemic vascular resistance but did not significantly influence arterial pressure, cardiac output, DO2 or VO2; neither DO2crit nor O2ERcrit was altered (9.3 ± 2.9 ml/kg · min and 70.4 ± 20.9%). Nitroprusside at the higher dose induced significant decreases in mean arterial pressure and systemic vascular resistance, but had no significant effect on cardiac output. DO2crit (9.2 ± 2.0 ml/kg · min) and O2ERcrit (59.8 ± 13.2%) were similar to the control group. We concluded that the NO donor, sodium nitroprusside, does not significantly influence tissue oxygen extraction capabilities during a fall in cardiac output. [ABSTRACT FROM PUBLISHER]

Calcitonin gene-related peptide (CGRP) produces vasodilation, hypotension, and tachycardia. We compared the hemodynamic effects of CGRP-induced hypotension with the effects of prostaglandin E (PGE), which is currently used as a hypotensive agent during anesthesia. Eighteen mongrel dogs were anesthetized with pentobarbital (25 mg·kg), and 0.87% halothane in oxygen (1MAC). Measurements of hemodynamic variables were made before, during, and after induced hypotension. The mean arterial pressure (MAP) was lowered to 60 mmHg by the infusion of either CGRP ( n=10) or PGE ( n=8). This decrease in MAP was appoximately 50% of the baseline value. The CGRP- and PGE-induced hypotension resulted in 61% and 51% maximum reductions ( P<0.01, respectively) in systemic vascular resistance associated with a significant increase in stroke volume index; the two treatments, however produced inconsistent changes in cardiac index (CI). With CGRP, a maximum increase of 144% ( P< 0.01) in CI was observed during induced hypotension. In contrast, PGE-induced hypotension caused no significant changes in CI throughout the observation period. Left ventricular maximum dP/dt decreased ( P<0.01) during the hypotensive period with PGE, whereas it remained un-changes during CGRP-induced hypotension. The different results for changes in CI and cardiac contractility during the CGRP- and PGE-induced hypotension were probably due to differences in ventricular filling pressure. Hypotension induced by PGE was associated with a significant decrease in heart rate (HR), whereas CGRP did not affect HR. This study shows that both CGRP and PGE are effective in decreasing afterload and in inducing hypotension; the results suggest that CGRP is a useful vasodilator for inducing hypotension during halothane anesthesia. [ABSTRACT FROM AUTHOR]

Calcitonin gene-related peptide (CGRP) is known to produce vasodilation, hypotension, and tachycardia. To investigate the interaction between CGRP and anesthetics, the hemodynamic response to infusions of CGRP was studied in dogs anesthetized with halothane or pentobarbital. In halothane-anesthetized dogs given 0.4 μg·kg of CGRP, mean arterial pressure (MAP) did not change significantly. However, there was a significant reduction in systemic vascular resistance (SVR) associated with significant increases in cardiac index (CI) and stroke volume index (SVI). Higher doses (4 and 40 μg·kg) of CGRP produced dose-dependent decreases in MAP accompanied by a reduction in SVR. Further, both CI and SVI significantly increased at 4 μg·kg CGRP but remained unchanged at the 40 μg·kg infusion rate. Heart rate (HR) was not increased at all doses but was decreased at 40 μg·kg. In pentobarbital-anesthetized dogs, CGRP at doses of 4 μg·kg produced a qualitatively similar cardiovascular responses as that observed in halothane-anesthetized dogs, but with one exception: HR was significantly increased. The results show that the hemodynamic profiles induced by CGRP during halothane or pentobarbital anesthesia are a decrease in MAP accompanied by a reduction in SVR and no consistent alterations in CI. However, CGRP effects on HR showed in a different way. The results also show that HR response differs depending on the anesthetics used: HR increases during pentobarbital anesthesia, while it does not increase during halothane anesthesia. [ABSTRACT FROM AUTHOR]

The cardiovascular responses to an infusion of KRN2391, a potassium channel opener, was studied in halothane-anesthetized dogs. Intravenous administration of KRN2391 at 1.0 and 5.0 μg·kg·min for 60 min produced dose-dependent decreases in mean arterial pressure (MAP) and systemic vascular resistance (SVR) associated with dose-dependent increases in the cardiac index (CI) and stroke volume index (SVI) but was not accompanied by an increase in heart rate (HR). The maximum decrease in MAP during the infusion of KRN2391 at 1.0 and 5.0 μg·kg·min was −13±7% (P<0.01) and −37±10% (P<0.01), respectively. The maximum reduction in SVR after 1.0 and 5.0 μg·kg·min was −20±11% (P<0.01) and −60±16% ( P<0.01), respectively. A KRN2391 infusion of 1.0 and 5.0 μg·kg·min increased Cl a maximum of 11±13% ( P<0.05) and 65±33% (P<0.01), respectively. KRN2391 1.0 μg·kg·min showed a tendency to increase SVI but this change was not significant, KRN2391 5.0 μg·kg·min, however, produced a significant increase in SVI. The present results demonstrate that the decrease in MAP and the increases in CI and SVI caused by KRN2391 are due to a reduction in the afterload. Therefore, we conclude that these cardiovascular profiles of KRN2391 may be benificial in perioperative uses including the control of systemic blood pressure and the treatment of hypertension during halothane anesthesia in clinical practice. [ABSTRACT FROM AUTHOR]

The effects of five sclerosants used for treating esophageal varices on blood coagulation and fibrinolysis, systemic hemodynamics, and vascular endothelial cells were studied in mongrel dogs. With each sclerosant, hemolysis and a decrease in the platelet count were observed. Changes in the blood coagulation system occurred immediately after sclerosant administration. Prolongation of the PT and APTT and decreases in fibrinogen and ga-PI were seen in the thrombin (TH), sodium tetradecyl sulfate (STS), and ethanolamine oleate (EO) groups. Polidocanol (PO) and absolute ethanol (ET) had less pronounced effects on these systems. A transient decrease in the cardiac index (CI), pulmonary artery pressure (PAP) and pulmonary artery resistance (PAR) was observed with the administration of the sclerosants, especially in the TH and STS groups. Excessive vascular endothelial damage was observed in the ET group, marked damage was seen in the EO and STS groups and slight damage was recorded in the PO and TH groups. [ABSTRACT FROM AUTHOR]

Portal pressure and systemic hemodynamics were evaluated for 30 minutes after intravenous injection of 400 mg of cimetidine in patients with and without liver cirrhosis when they were operated upon for varying surgical diseases. A transient fall of arterial pressure was seen in both groups of patients, but the change was statistically significant only in those with cirrhosis. Cimetidine did not substantially alter pulse rate, CVP, and portal pressure in both groups. The present results seem to indicate that rapid administration of cimetidine does not induce a fall of portal venous pressure in both cirrhotic and non-cirrhotic patients. [ABSTRACT FROM AUTHOR]

The features of systemic hemodynamics were analyzed in 19 non-cirrhotic patients with prominent esophageal varices. The patients were divided into two groups; Group I comprised 8 patients with an occluded extra-hepatic portal vein and Group II comprised 11 patients with a patent extra-hepatic portal vein whose histopathological diagnosis was idiopathic portal hypertension or hepatic fibrosis. An increase in the cardiac index and a decrease in the total peripheral resistance were significant in both groups when compared with 12 control patients (p<0.01). There was a significant correlation between the cardiac index and plasma volume in the 14 non-cirrhotic patients with portal hypertension (r=0.537, p<0.05), but no significant relationships were identified between the cardiac index and liver functional values. These results reveal that the systemic hemodynamics in non-cirrhotic portal hypertension are significantly hyperdynamic, as in cirrhotic portal hypertension. They also suggest that the expanded plasma volume secondary to the enlargement of the portal bed might be closely related to the mechanism of hyperdynamic systemic circulation in non-cirrhotic portal hypertension. [ABSTRACT FROM AUTHOR]

The randomized single-blind study was designed to compare the effects of captopril (Cap) and nadolol (Nad) on renal hemodynamics in 60 patients with essential hypertension. They were divided into two groups at random. Cap was given in dosage of 37. 5-75 mg/d per os and Nad 40-80 mg/d. The results show that both drugs increase the blood volume distributed to the kidneys from cardiac output (renal blood flow/cardiac output), Cap increasing 10% ( P<0. 05) and Nad 8% ( P<0. 05). Renal vascular resistance (RVR) is lowered by the two drugs, 13% ( P<0. 05) by Cap and 11% ( P<0. 05) by Nad. These suggest that both drugs facilitate the maintenance of renal blood circulation in patients with essential hypertension, being beneficial for longterm treatment of hypertension. [ABSTRACT FROM AUTHOR]