Regurgitant volume in aortic regurgitation from a parameter estimation procedure.

The regurgitant volume and regurgitant orifice area as well as total peripheral resistance and arterial compliance were estimated in a cardiovascular hydromechanical simulator and in 10 patients with aortic regurgitation. A parameter estimation procedure based on a simple model of the cardiovascular system, Doppler measurements of the regurgitant jet, aortic systolic flow, and systolic and diastolic blood pressures was used. In the cardiovascular simulator the estimated regurgitant orifice area was compared with the size of a hole in the disk of a mechanical aortic valve. In the patients the regurgitant fraction was compared with semiquantitative grading from echocardiography routinely performed in our laboratory. In the hydromechanical simulator, the estimated regurgitant orifice area of 26.5 +/- 3.5 (SD) mm2 (n = 9) was not different from the true value of 24 mm2. In the patients there was a fair relationship between the estimated regurgitant fraction and the semiquantitative grading. The estimated regurgitant orifice areas varied between 1.6 and 31.2 mm2. The estimated mean values of total peripheral resistance and arterial compliance were 1.67 +/- 0.55 mmHg.s.ml-1 and 1.30 +/- 0.42 ml/mmHg, respectively.

Regioselective metabolism of phenanthrene in Atlantic cod (Gadus morhua): studies on the effects of monooxygenase inducers and role of cytochromes P-450.

The polycyclic aromatic hydrocarbon phenanthrene was converted mainly (greater than 90%) to the 1,2-dihydrodiol when metabolized in vivo by the marine teleost cod. This is also found in other bony fishes, but contrary to what is known from cartilaginous fish, crustaceans and mammals, where the K-region 9,10-dihydrodiol is the main metabolite. When liver microsomal preparations from differently pretreated cod were incubated with phenanthrene in vitro, the metabolic profile was dramatically different from the in vivo pattern, as shown by gas chromatography-mass spectrometry. The microsomes from untreated, phenanthrene, phenobarbital and pregnenolone-16 alpha-carbonitrile-treated cod converted phenanthrene mainly, but to a varying extent, to the 9,10-dihydrodiol. Treatment with beta-naphthoflavone (BNF), however, resulted in a large increase in the oxidation at the 1,2-position, along with a four- to seven-fold increase in specific activity. The major cytochrome P-450 isozyme purified from BNF-treated cod liver (P-450c) showed highest activity with phenanthrene (a turnover of 0.18 nmol/min per nmol P-450), but with about equal selectivity for the 1,2- and 9,10-region of the substrate in a reconstituted system with phospholipid and NADPH-cytochrome P-450 reductase. The low regioselectivity was also observed as a lack of regioselective inhibition of microsomal phenanthrene metabolism with antiserum to cod P-450c. Two of the minor isozymes, cod cytochromes P-450b and d, showed a similar turnover to P-450c, but with a stronger selectivity for the 1,2-position (55-60%). The results indicate that other control systems, in addition to the content of individual P-450-forms in the regulatory systems, in addition to the content of individual P-450-forms in the endoplasmic reticulum, are involved in the in vivo transformation of phenanthrene by cod to the 1,2-dihydrodiol metabolite.

Estimation of regurgitant volume and orifice in aortic regurgitation combining CW Doppler and parameter estimation in a Windkessel-like model.

A method for noninvasive estimation of regurgitant orifice and volume in aortic regurgitation is proposed and tested in anesthetized open chested pigs. The method can be used with noninvasive measurement of regurgitant jet velocity with continuous wave ultrasound Doppler measurements together with cuff measurements of systolic and diastolic systemic pressure in the arm. These measurements are then used for parameter estimation in a Windkessel-like model which include the regurgitant orifice as a parameter. The aortic volume compliance and the peripheral resistance are also included as parameters measurements in the open chest pigs are used. Electromagnetic flow measurements in the ascending aorta and pulmonary artery are used for control, and a correlation between regurgitant volume obtained from parameter estimation and electromagnetic flow measurements of 0.95 over a range from 2.1 to 17.8 mL is obtained.

Estimation of arterial compliance in aortic regurgitation: three methods evaluated in pigs.

Three methods for measuring arterial compliance when aortic regurgitation is present are examined. The first two methods are based on a Windkessel model composed of two elements, compliance C and resistance R. Arterial compliance was estimated from diastolic pressure waveforms and diastolic regurgitant flow for one method, and from systolic aortic pressure waveforms and systolic flow for the other method. The third method was based on a three-element Windkessel model, composed of characteristic resistance r, compliance C and resistance R. In this method arterial compliance was calculated by adjusting the model to the modulus and phase of the first harmonic term of the aortic input impedance. The three methods were compared and validated in six anaesthetised pigs over a broad range of aortic pressures. The three methods were found to give quantitatively similar estimates of arterial compliance at mean aortic pressures above 60 mm Hg. Below 60 mm Hg, estimates of arterial compliance varied widely, probably because of poor validity of the Windkessel models in the low pressure range.

Quantification of aortic regurgitation by Doppler echocardiography: a new method evaluated in pigs.

We have developed a method to quantify aortic regurgitant orifice and volume, based on measurements of the velocity of the regurgitant jet, aortic systolic flow, the systolic and diastolic arterial pressures, a Windkessel arterial model, and a parameter estimation technique. In six pigs we produced aortic regurgitant flows between 2.1 and 17.8 ml per beat, i.e. regurgitant fractions from 0.06 to 0.58. Pulmonary and aortic flows were measured with electromagnetic flow probes, aortic pressure was measured invasively, and the regurgitant jet velocity was obtained with continuous-wave Doppler. The parameter estimation procedure was based on the Kalman filter principle, resulting primarily in an estimate of the regurgitant orifice area. The area was multiplied by the velocity integral of the regurgitant jet to estimate regurgitant volume. A strong correlation was found between the regurgitant volumes obtained by parameter estimation and the electromagnetic flow measurement. These results from our study in pigs suggest that it may be possible to quantify regurgitant orifice and volume in patients completely noninvasively from Doppler and blood pressure measurements.

Distribution and elimination of [14C]-hexachlorobenzene after single oral exposure in cod (Gadus morhua) and flounder (Platichthys flesus).

Distribution and elimination of hexachlorobenzene (HCB) after administration to COD (Gadus morhua) of a single oral dose of 5 microCi [14C]HCB/100 g body weight were studied by whole-body autoradiography and liquid scintillation counting. To obtain some information on the physicochemical properties of the radiolabeled compounds, whole-body autoradiography was performed exposing parallel sagittal sections, treated at -20 degrees C, evaporated at 50 degrees C, and extracted separately with polar and nonpolar solvents. The highest concentration of radioactivity was found in the liver, the bile, and the central nervous system (CNS). Radioactivity in the liver and CNS, which was completely evaporable, was considered to represent the highly volatile HCB itself, and/or metabolites with high vapor pressure. No part of radioactivity in bile was evaporable, but it was completely extractable with water. Radioactivity in the intestinal content, the skin, and the uveal tract of the eye was partly evaporable. No radioactivity remained in any tissue after extraction with polar and nonpolar solvents. The rate of elimination was slow, and substantial amounts remained in the body 60 d after administration. In addition to bile excretion of nonevaporable, water-soluble radioactivity, a possible excretion through the intestinal mucosa was suggested. Whole-body autoradiography of female flounders (Platichthys flesus) revealed a high content of radioactivity in the developing eggs.

Distribution and elimination of [14C]octachlorostyrene in cod (Gadus morhua), rainbow trout (Salmo gairdneri, and blue mussel (Mytilus edulis).

Cod (Gadus morhua) and rainbow trout (Salmo gairdneri) were given a single oral dose of 100 microCi/kg b.w. of [14C]octachlorostyrene [( 14C]OCS) in peanut oil. Blue mussel (Mytilus edulis) was exposed to [14C]OCS in water. The distribution and elimination of the compound was studied by liquid scintillation counting and whole-body autoradiography. The highest degree of radioactivity in the cod and rainbow trout was measured in the liver and the visceral fat, respectively. The degree of radioactivity in the brain of cod exceeded that of the rainbow trout by a factor between 2 and 4 at all survival times. In addition to bile excretion of [14C]OCS-derived radioactivity, a possible excretion over the intestinal mucosa was suggested. The rate of elimination was slow in both species, and substantial amounts of radioactivity remained in the tissues 90 d after administration. In the blue mussel, the highest degree of radioactivity was found in the hepatopancreas. Substantial amounts of radioactivity were present in the mussel tissues 60 d after administration.

Urinary and biliary metabolites of phenanthrene in the coalfish (Pollachius virens).

Metabolites present in the urine and bile of coalfish (Pollachius virens) 48 hrs after the intragastric administration of phenanthrene (75 mg/kg) were studied. Using gas chromatographic-mass spectrometric methods small amounts of unchanged compound, all five of the possible monohydroxy derivatives and the 1,2- and 9,10-dihydrodiols of phenanthrene were identified inthese samples. The major metabolite detected was phenanthrene-1,2-dihydrodiol which was excreted mainly as glucuronide and/or sulfate conjugates.