Effect of interferon gamma on intrahepatic haemodynamics of the cirrhotic rat liver.

Sublethal injury of the liver with carbon tetrachloride (CCl4) induces the modulation of hepatic stellate cells to their myofibroblast (MFB) phenotype. Pretreatment or concomitant treatment with interferon gamma (IFNgamma) has been shown to inhibit this phenomenon. The aim of this study was to investigate the influence of IFNgamma treatment (50000 IU s.c. each day for 5 days) in rats with an established cirrhosis. Cirrhosis was induced with nine doses of CCl4. Comparison of biopsies before and after treatment with IFNgamma showed that the number of MFB present, identified by their alpha-smooth muscle actin immunoreactivity, was markedly reduced. Pressure-flow curves were constructed in isolated perfused liver preparations from IFNgamma-treated and saline-treated cirrhotic rats and analysed to obtain the extrapolated zero-flow intercept (Po, an index of hepatic vascular distensibility) and the vasodilator-induced change in resistance at a flow rate of 1 mL/min per g (deltaR1, an indication of the level of intrinsic vascular tone). In IFNgamma-treated rats, portal venous pressure measured in vivo was significantly reduced compared with controls (11.9+/-1.2 vs 16.0+/-0.5 mmHg, P< 0.05), Po was lower (2.03+/-0.18 vs 2.87+/-0.32 mmHg, P<0.05) and deltaR1 was decreased (0.39+/-0.15 vs 1.02+/-0.19 mmHg/mL per min per g, P< 0.05). The findings indicate that treatment with IFNgamma is effective in reducing MFB density in established CCl4-cirrhosis in the rat and results in a marked improvement in intrahepatic haemodynamics.

The effect of hepatocyte enlargement on the hemodynamic characteristics of the isolated perfused rat liver preparation.

The influence of hepatocyte enlargement on intrahepatic hemodynamics was assessed in the isolated perfused rat liver preparation (IPRL) using two experimental models: hypotonic liver cell swelling and phenobarbitone-induced hepatocyte hypertrophy. The analysis of pressure-flow data obtained from the portal vascular bed over a flow range of 0 to 70 mL/min in the presence of a maximally-effective concentration of the vasodilator agent papaverine hydrochloride (6 x 10(-4) mol/L) enabled the calculation of P0, an estimate of the pressure required to passively distend the intrahepatic vasculature, and Gmax, the maximal portal vascular conductance. By comparison with an isotonic perfusion medium (Krebs-Henseleit buffer [KH] containing 2.5% bovine serum albumin [BSA]), perfusion with a hypotonic medium induced a significant increase in mean hepatocyte cross-sectional area (H(A)) (590 +/- 21 vs. 324 +/- 23 microm(-2), p < .05), a fall in Gmax (0.39 +/- 0.08 vs. 2.02 +/- 0.18 mL/min/g/mm hg, P < .001), and an increase in P0 (2.96 +/- 0.38 vs. 1.58 +/- 0.07 mm hg, P < .001). Phenobarbitone administered in drinking water (0.5 g/L) over a period of 60 days also induced a significant degree of hepatocyte enlargement (HA, 510 +/- 29 microm2, P < .05). On day 7, portal pressure measured in vivo in this group was significantly elevated compared with untreated controls (10.5 +/- 0.3 vs. 8.4 +/- 0.2 mm hg, P < .001), while in the IPRL Gmax was reduced (0.48 +/- 0.01 mL/min/g/mm hg, P < .001), and P0 was increased (2.23 +/- 0.17 mm hg, P < .05). However, with continued phenobarbitone treatment portal pressure, Gmax and P0 returned toward control values. The results confirm that hepatocyte enlargement is associated with a significant disturbance of intrahepatic hemodynamics but also that some adaptation occurs if hepatocyte enlargement is sustained over a prolonged period of time.

Endothelin-induced vasoconstriction in isolated perfused liver preparations from normal and cirrhotic rats.

Isolated, perfused rat liver preparations (IPRL), obtained from rats with carbon tetrachloride-induced cirrhosis and normal controls, were used to investigate responses to the vasoactive peptide endothelin-1 (ET-1). The mean perfusion resistance (R) of cirrhotic IPRL was significantly greater than that of controls (2.63 +/- 0.24 vs 1.54 +/- 0.14 mmHg/mL per min per g; P < 0.01). Both control and cirrhotic IPRL demonstrated a concentration-related increase in resistance (delta R) in response to ET-1, with a minimum effective concentration of approximately 3 x 10(-11) mol/L. The EC50 (-log of the 50% effective concentration) was not significantly different between cirrhotic and control IPRL (8.48 +/- 0.19 and 8.79 +/- 0.11, respectively); however, the maximum response to ET-1 was significantly greater in cirrhotic preparations (R: 10.4 +/- 2.2 vs 4.4 +/- 0.5 mmHg/mL per min per g, P < 0.01; DR, 7.8 +/- 2.1 vs 2.8 +/- 0.4 mmHg/mL per min per g, P < 0.01). Following maximal stimulation by ET-1, the mean portal-hepatic venous pressure gradient at a physiological flow rate of 1 mL/min per g was approximately 90% greater across cirrhotic IPRL than that across normal IPRL (11.2 +/- 2.0 vs 5.9 +/- 0.9 mmHg, respectively; P < 0.05). These results support the hypothesis that endogenously released ET-1 has a significant influence on the portal vascular resistance of cirrhotic liver in vivo and has an important role in the pathogenesis of portal hypertension.

Defying circadian rhythm: the emergency nurse and the night shift.

The human body cannot change its preprogramming to meet the demands of working the night shift for a period of years. The effects are devastating to women and have been proven to shorten their life expectancy. Although the human body cannot change to meet society's demands of nighttime employment, society can change its expectations to better accommodate women who work the night shift. Nurses play a vital role in the resolution of this situation in a variety of settings. For my own health and welfare, I have already begun to follow the recommendations learned through the literature review and research of this article. My sleep time has always been guarded carefully, although I am more committed to that now. I am no longer bashful when scheduling appointments and meetings with those who function on a daytime schedule. I have modified my diet to be better balanced and have initiated a regular pattern of exercise. The statistics cited have alarmed my family, who are now more protective than ever of my night schedule and subsequent needs. I am able to advocate for the nurses that I work with, by sharing information with them. Many have worked nights for extended periods of time and are very interested in the facts from the literature. My colleagues who work in management positions are curious as to what I have found in the literature search and have obtained copies of the articles I reviewed to assist in the maintenance and scheduling within their own departments. They, too, are challenged to discover a healthier way to cover the needs of each department and maintain a healthy atmosphere for their staff.

Effect of changes in vascular tone on the haemodynamic characteristics of the portal vascular bed of the isolated perfused rat liver.

The effect of altered vascular tone on the haemodynamic characteristics of the intrahepatic portal vascular bed was studied in the isolated perfused rat liver preparation. The relationship between portal venous inflow (Q) and portal perfusion pressure (P) was determined in the presence of a maximally effective concentration of a vasoconstrictor agent (noradrenaline, NAmax, 3 x 10(-5)mol/L), an intermediate concentration (NAmed, 1 x 10(-6)mol/L) or a vasodilator agent (papaverine, PAP, 6 x 10(-4)mol/L). At flow rates greater than 20 mL/min, the pressure-flow relationship could be regarded as linear (P < 0.001), with mean values for the extrapolated intercept with the pressure axis (Po) of 6.8 +/- 0.9 mmHg for NAmax, 4.5 +/- 0.5 mmHg for NAmed, and 1.65 +/- 0.05 mmHg for PAP-treated preparations. Over the full flow range (0-70 mL/min), in both NA- and PAP-treated preparations, portal vascular conductance (G = Q/P) was related directly to perfusion pressure. Thus, G = C.P, where C is a constant (mean values for NAmax, NAmed, and PAP-treated preparations were 0.0090 +/- 0.0020, 0.023 +/- 0.005, and 0.26 +/- 0.02 mL/min per g per mmHg2, respectively). It is concluded that both C and Po may be useful indices of tone in the isolated perfused rat liver, and that analysis of hepatic portal haemodynamics in this manner may have considerable practical value in studies of the action of vasoactive agents.

Hemodynamic characteristics of the intrahepatic portal vascular bed over an extended flow range: a study in the isolated perfused rat liver.

The relationship between the perfusion pressure (P) and resistance (R) of the intrahepatic portal vascular bed was determined in isolated rat liver preparations perfused with fresh, heparinized rat blood (hematocrit 30%), with rat blood containing a vasodilator agent (sodium nitroprusside, 1 X 10(-3) mol/L), or with 2.5% bovine serum albumin in Krebs-Henseleit buffer (BSA-KH). Pressure-flow curves were constructed over an extended range of portal venous inflow (0 to 70 mL.min-1, corresponding to a flow rate per gram liver wet weight, Q, of approximately 0 to 7 mL.min-1.g-1). Subsequent analysis showed that two mathematical expressions adequately described the data over the full range of flow. Thus, the pressure-flow curve could be represented by (a) the sum of a linear plus a hyperbolic function, i.e., P = Q.R' + Pmax.Q/(Q + Km), where R', Pmax, and Km are constants, or (b) by the simple equation G = C.P, where G is the conductance (Q/P), and C is a conductivity constant. The values of R', Pmax, Km, and C were significantly different under each of the circumstances investigated, but the form of the curve was not altered. Hence, it is proposed that these parameters can be used to describe the fundamental hemodynamic properties of the portal vascular bed of the isolated rat liver. The results are discussed in terms of the microvascular recruitment and distensible resistance vessel models of the hepatic microcirculation.

Enhanced vasoconstrictor response of the isolated perfused cirrhotic rat liver to humoral vasoconstrictor substances found in portal venous blood.

Humoral vasoconstrictor factors in portal venous blood have an important influence on hepatic vascular tone. The aim of this study was to determine whether there is altered reactivity of the intrahepatic portal vascular bed of cirrhotic livers to such factors. Isolated perfused rat liver preparations (IPRLP) obtained from rats with carbon tetrachloride-induced cirrhosis and from normal controls were treated with small aliquots of fresh, heparinized venous blood (4% vol/vol) added to a synthetic perfusate composed of 2.5% bovine serum albumin in Krebs-Henseleit buffer. Compared with blood from the inferior vena cava, portal venous blood produced a greater increase in perfusion resistance of normal IPRLP (2.8 +/- 0.7 vs 15 +/- 3%, P less than 0.05). There was no significant difference in the response of normal IPRLP to portal venous blood obtained from cirrhotic animals compared with portal blood from normal controls (10 +/- 4 vs 15 +/- 3%). However, cirrhotic IPRLP were significantly (P less than 0.05) more responsive to portal venous blood than were control livers, regardless of whether the blood was obtained from control (28 +/- 6%) or cirrhotic (24 +/- 6%) rats. The response of both control and cirrhotic IPRLP to portal blood could be partially inhibited by the alpha-adrenoceptor antagonist phentolamine (5 x 10(-6) mol/L) and cirrhotic IPRLP were more responsive than controls to exogenous noradrenaline (518 +/- 27 vs 363 +/- 21%, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

[The effect of hydrogenated ergot alkaloids on immune functions. II. The primary antibody response and proliferative activity in mouse spleen cells in vitro]. / Vliv hydrogenovaných námelových alkaloidu na imunitní funkce. II. Primární protilátková odpoved' a proliferacní aktivita mysích slezinných bunek in vitro.

The present paper investigated the proliferative response of murine splenic cells in the tissue culture after stimulation with the polyclonal activators PHA, ConA and PWM. Proliferation of cells and DNA synthesis were measured by means of radioactively labelled thymidine. Furthermore, the primary antibody response of murine splenic cells in the tissue culture after activation with sheep red blood cells was examined. The response was measured by determining the number of plaque forming cells (PFC). The number of PFC's was determined by the plaque method of local haemolysis, in modification by the drop method. In these tests the ergot alkaloids dihydroergocornine, dihydroergocristine, dihydro-alpha-ergocryptine and dihydro-beta-ergocryptine were evaluated in two doses, 600 and 1200 micrograms/kg/day p. o. for the period of 14 days. Dihydroergocornine in these tests increased the primary antibody response in a statistically significant manner; on the other hand, after its administration in the higher dose decreased proliferation after PHA was found. The finding after dihydroergocristine administration was of interest. This ergot alkaloid slightly increased proliferation of cells after PHA and PWM as well as the primary antibody response of murine cells. After the administration of dihydro-alpha-ergocryptine increased proliferation after stimulation with PWM and increased primary antibody response, and after the administration of dihydro-beta-ergocryptine increased proliferation of cells after stimulation with PHA were found.

99mTc-aminohexylidendiphosphonate and 99mTc-pyrophosphate in the scintigraphic diagnosis of experimental myocardial infarction in dogs.

99mTc-aminohexylidendiphosphonate (99mTc-AHDP) is a new Czechoslovak pharmaceutical of the phosphonate line which contains the amino group NH2 in its molecule. This substance was tested in 5 dogs with experimentally provoked 48-h old myocardial infarction. The in-vivo scan and the radioactivity of tissue samples demonstrated that 99mTc-AHDP is as suitable for imaging acute myocardial infarction as is the commonly used 99mTc-pyrophosphate.

99mTc-aminohexylidendiphosphonate and 99mTc-pyrophosphate in the scintigraphic diagnosis of experimental cardiomyopathy in dogs.

Experimental cardiomyopathy was provoked in 24 dogs with high intravenous doses of adrenaline and theophylline. These lesions were studied by means of the new agent 99mTc-AHDP and 99mTc-PYP in comparison. Cardiomyopathy could be imaged as early as 4 h after the onset of involvement but not later than 7 days. A maximum accumulation occurred in lesions 24 h old. 99mTc uptake in the myocardium was graded scintigraphically. 99mTc-AHDP was accumulated in the altered myocardium to a greater extent than 99mTc-PYP. Scintigraphic findings were in good agreement with plasma levels of creatine-kinase. A comparison with histology demonstrated that the maximum accumulation of radiopharmaceuticals occurred at the time when the development of myocardium involvement reached the stage of myocytolysis.

Method for resection and prosthetic replacement of aneurysm of aortic arch.

We shall describe a case of aneurysm of the transverse aortic arch. The patient was operated upon successuflly. Severe respiratory distress owing to tracheal compression was the indication for emergency surgical therapy. A method is described comprising total cardiopulmonary bypass, hypothermia (28 C.) and local deep myocardial hypothermia. Catheters to cerebral vessels are brought off the main arterial line beyond the pump. Cerebral vascular resistance regulates local blood flow. Coronary perfusion is omitted.

Ascending aorta-right pulmonary artery anastomosis in children with complex cardiac malformations. Long-term results in 30 cases.

In this report, we shall analyze the results obtained with palliative treatment in 30 patients with congenital heart disease who were operated upon at the University Hospital of Caracas during the period 1968 to 1972. In all cases, an ascending aorta-right pulmonary artery anastomosis was performed. Although we believe that the Blalock-Taussig and Potts shunt are satisfactory operations in some cases, at the present time we prefer the aorta-right pulmonary branch anastomosis in Fallots tetralogy and other congenital heart diseases such as single ventricle. In Fallot's tetralogy, particularly, this procedure provides better results, because the anastomosis can be closed through the aorta when these patients are later subjected to total correction with extracorporeal circulation.