Cardiac volume overload and pulmonary hypertension in long-term follow-up of patients with a transjugular intrahepatic portosystemic shunt.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPSS) cause haemodynamic changes in patients with cirrhosis, yet little is known about long-term cardiopulmonary outcomes. AIM: To evaluate the long-term cardiopulmonary outcome after TIPSS. METHODS: We evaluated cardiopulmonary parameters including echocardiography during long-term follow-up after TIPSS. Results at 1-5 years after TIPSS were compared to those of cirrhotic controls. Pulmonary hypertension (PH) diagnoses rates were included. Endothelin 1, thromboxane B2 and serotonin were measured. RESULTS: We found significant differences 1-5 years after TIPSS compared to pre-implantation values: median left atrial diameter (LAD) increased from 37 mm [interquartile range (IQR): 33-43] to 40 mm (IQR: 37-47, P = 0.001), left ventricular end-diastolic diameter (LV-EDD) increased from 45 mm (range: 41-49) to 48 mm (IQR: 45-52, P < 0.001), pulmonary artery systolic pressure (PASP) increased from 25 mmHg (IQR: 22-33) to 30 mmHg (IQR: 25-36, P = 0.038). Comparing results 1-5 years post-implantation to the comparison cohort revealed significantly higher (P < 0.05) LAD, LV-EDD and PASP values in TIPSS patients. PH prevalence was higher in the shunt group (4.43%) compared to controls (0.91%, P = 0.150). Thromboxane B2 levels correlated with PASP in the TIPSS cohort (P = 0.033). There was no transhepatic gradient observed for the vasoactive substances analysed. CONCLUSIONS: TIPSS placement is accompanied by long-term cardiovascular changes, including cardiac volume overload, and is associated with an increased rate of pulmonary hypertension. The need for regular cardiac follow-up after TIPSS requires further evaluation.

Positive inotropic and hemodynamic properties of flosequinan, a new vasodilator, and a sulfone metabolite.

Flosequinan, a new orally active vasodilator, and its sulfone metabolite were evaluated for inotropic activity in isolated ferret papillary muscles and pentobarbital anesthetized open-chest dogs. In vitro, flosequinan and its sulfone derivative increased tension development in a concentration-dependent manner (1-50 microM) in electrically stimulated papillary muscles pretreated with the beta-adrenergic blocking agent atenolol (2 microM). Peak increases in tension of 75 +/- 17%, and 111 +/- 46% with potencies (EC50) of 15 and 10 microM were observed for flosequinan and its metabolite, respectively. In vivo, flosequinan increased left ventricular dP/dtmax (74 +/- 12%) and right ventricular contractile force (CF) (104 +/- 10%) after administration of 1.875 mg/kg, i.v. Inotropic activity was dose-dependent and remained elevated for at least 60 min postinfusion. Flosequinan also increased heart rate (HR) (14 +/- 2%) and reduced mean arterial pressure (-9 +/- 3%). The i.v. potency of flosequinan (ED50 = 0.45 mg/kg) and its metabolite (ED50 = 0.38 mg/kg) were similar to that of the inotropic vasodilator amrinone (ED50 = 0.38 mg/kg). Inotropic activity was not significantly altered by pretreatment with propranolol (0.5 mg/kg) and atropine (1.0 mg/kg), further supporting the in vitro data indicating that flosequinan can directly stimulate myocardial contractility independent of beta-adrenergic receptor activation. Additional hemodynamic studies were conducted in an acute heart failure model produced by an overdose of propranolol. Flosequinan (2 mg/kg, i.v.) increased cardiac output (CO) (50 +/- 9%) and stroke volume (SV) (29 +/- 8%) while reducing total peripheral vascular resistance (TPR) (-36 +/- 4%), right atrial pressure (-62 +/- 5%), and left ventricular end-diastolic pressure (LVEDP) (-41 +/- 2%).(ABSTRACT TRUNCATED AT 250 WORDS)

Maintained aggressive behavior in gonadectomized male Siamese fighting fish (Betta splendens).

Adult male Betta splendens were gonadectomized and tested twice for aggressive behavior two weeks later. In a mutual viewing test environment, it was found that gonadectomized animals maintained their aggressive behavior on all six indices of aggression at a level equal to controls. Animals that showed some testis regeneration and sham operated fish were also equal to controls. The results are interpreted to mean that adult aggressive behavior in male B. splendens may not be under the control of gonadal hormones. Pituitary gonadotropins, interrenal gland, and critical period hypotheses are given as possible explanations of the maintained aggressiveness following castration.

Effects of intragastric water infusion and gastric distension on hypothalamic neuronal activity.

The effects of gastric water infusion and distension were examined in neurons from various parts of the rat brain. Neurons in the lateral preoptic-lateral hypothalamic-medial forebrain bundle (LPA-LH-MFB) neuropil were sensitive to gastric water infusion and distension. Cells randomly selected and examined in other brain areas were less sensitive to the same stimulation which indicated that the effects were relatively specific. The results, in terms of changes in neuronal discharge frequency from an established baseline, indicate that many cells in the lateral preoptic-lateral hypothalamic-medical forebrain bundle area are affected by intragastric water infusion and gastric distension within a time period during which changes in drinking would normally occur. These neurons were also affected differentially by acute water deprivation. LPA-LH-MFB neurons in 24 hr water deprived animals were significantly more sensitive to water infusions and less sensitive to stomach distension when compared to cells recorded in animals maintained on ad lib eating and drinking. Some of these same neurons were also sensitive to changes in the extracellular concentrations of sodium and glucose. The results are discussed in terms of the involvement of the lateral preoptic-lateral hypothalamic-medial forebrain bundle neuropil in ingestive behavior.