[PET--already a useful clinical tool].
Explore the source record for details and available documents.
Humans↗
Biomedical subjects
O A Smiseth
Publications and source records attributed to O A Smiseth.
High frame rate Doppler echocardiography in the rat: an evaluation of the method.
AIMS: In small animal models, two-dimensional (2D) and Doppler echocardiography should provide more information than M-mode, especially in animals with infarcted and distorted left ventricles, but has been limited by low frame rates and poor near field resolution. New, high frame rate echo-Doppler equipment with digital processing was tested for accuracy of measurements. METHODS AND RESULTS: Fourteen normal Wistar rats (232-328 g) were examined under halothane anaesthesia. Pulsed Doppler recordings from both left ventricular outflow tract(LVOT) and right ventricular outflow tract (RVOT) cor-responded well with simultaneous ultrasound transit time measurements of aortic flow (LVOT: v=0.99x+4.8, min R=0.93. Standard error of estimate (SEE)=8.3 ml x min(-1), and RVOT: v=0.97x -4.3. R=0.93. SEE =8.4 ml x min(-1). No systematic differences were observed over a flow range of 20-90 ml x min(-1). Left ventricular (LV) dimensions assessed by 2D parasternal long-axis and short-axis views were equal to M-mode measurements with LV diameter 6.6 + 0.44 mm, anterior wall 1.8 +/- 0.18 mm, and posterior wall 1.5 + 0.56 mm. Mean absolute difference 4.4-8.5%. Intra- and interobserver variability was 4.6 +/- 4.1% and 6.7 +/- 7.0% for Doppler measurements, and 4.3 +/- 3.8% and 3.8 +/- 4.6% for dimensions, respectively. CONCLUSION: High frame rate Doppler echocardiography provides accurate non-invasive measurements of cardiac structure and function in the rat.
Animals↗
Assessment of ventricular diastolic function.
A large number of patients suspected of having congestive heart failure have normal left ventricular systolic function and may, therefore, have primary diastolic heart failure. This diagnosis, however, should not be made unless there is also objective evidence of diastolic dysfunction, ie, signs of abnormal left ventricular relaxation and/or diastolic distensibility. The most useful noninvasive diagnostic approaches are the measurement of transmitral and pulmonary venous flow velocities by pulsed wave Doppler, and mitral annulus velocities by tissue Doppler echocardiography. In some patients, the assessment of intraventricular flow propagation by colour M-mode Doppler echocardiography provides additional information. Diastolic heart failure is most often due to coronary artery disease and/or hypertension; therefore, other noninvasive or invasive tests are needed to define the etiology of myocardial dysfunction. However, in the few patients who have constrictive pericarditis, the Doppler echocardiographic assessment of diastolic filling provides the most important clues to the etiology of the disease. Doppler echocardiographic assessment of left ventricular filling may also be used to obtain semiquantitative estimates of left ventricular diastolic pressure. Furthermore, left ventricular filling patterns, in particular, the deceleration time of early transmitral filling, are powerful predictors of patient prognosis. It is probably not cost effective to perform a comprehensive assessment of diastolic filling in every patient undergoing an echocardiographic examination. However, in selected patients, the assessment of diastolic filling provides information that is important for patient management.
Diastole↗
Myocardial strain by Doppler echocardiography. Validation of a new method to quantify regional myocardial function.
BACKGROUND: Myocardial strain is a measure of regional deformation, and by definition, negative strain means shortening and positive strain, elongation. This study investigates whether myocardial strain can be measured by Doppler echocardiography as the time integral of regional velocity gradients, using sonomicrometry as reference method. METHODS AND RESULTS: In 13 anesthetized dogs, myocardial longitudinal strain was measured on apical images as the time integral of regional Doppler velocity gradients. Ultrasonic segment-length crystals were placed near the left ventricular (LV) apex and near the base. Apical ischemia was induced by occluding the left anterior descending coronary artery (LAD), and preload was increased by saline. Percentage systolic strain by Doppler correlated well with strain by sonomicrometry (y=0.82x-1.79, r=0.92, P<0.01). During LAD occlusion, apical myocardium became dyskinetic, as indicated by positive strain values and negative Doppler velocities. At the LV base, myocardial strain by Doppler, strain by sonomicrometry, and velocity of shortening by sonomicrometry (dL/dt) were unchanged during apical ischemia. However, myocardial Doppler velocities at the base decreased from 4.2+/-0.7 (+/-SEM) to 2.7+/-0. 4 cm/s (P<0.05), probably reflecting loss of motion caused by tethering to apical segments. Volume loading increased myocardial Doppler velocities from 2.2+/-0.3 to 4.1+/-0.8 cm/s (P<0.05) and Doppler-derived strain from -12+/-1% to -22+/-2% (P<0.05), whereas peak LV elastance remained unchanged. CONCLUSIONS: Myocardial strain by Doppler echocardiography may represent a new, powerful method for quantifying regional myocardial function and is less influenced by tethering effects than Doppler tissue imaging. Like myocardial Doppler velocities, strain is markedly load-dependent.
Algorithms↗
Atrioventricular filling dynamics, diastolic function and dysfunction.
Left ventricular diastolic dysfunction is associated with slowing of LV relaxation and a decrease in LV chamber compliance. This impairment of function leads to changes in filling velocities as measured by pulsed wave Doppler echocardiography in the pulmonary veins and across the mitral valve, and in intraventricular flow propagation velocity as measured by color M-mode Doppler. This paper explores some of the physiology of LV filling in a clinical context.
Aortic Valve↗
Acute regional myocardial ischemia identified by 2-dimensional multiregion tissue Doppler imaging technique.
BACKGROUND AND OBJECTIVE: Tissue Doppler echocardiography (TDE) is a promising method for the assessment of regional myocardial function, but pulsed TDE does not provide quantitative data from multiple regions simultaneously. This feature is important for the objective assessment of regional differences in myocardial function. In the present study, we investigated a new off-line TDE method that provides quantitative pulsed velocity data from an unlimited number of regions selected within a 2-dimensional (2D) image. The goal of the study was to determine the ability of this new approach to quantify regional myocardial function during acute myocardial ischemia induced by balloon angioplasty. METHODS: Twenty-two patients undergoing angioplasty of the left anterior descending coronary artery (LAD) were studied. Left ventricular longitudinal wall motion was assessed by 2D TDE from the apical 4-chamber view before, during, and after angioplasty. Images were sampled at a rate of 69 +/- 15 frames/s, and the off-line analysis allowed simultaneous measurement of velocities in multiple myocardial segments. RESULTS: There were 3 major alterations in the systolic velocity pattern during LAD occlusion. Peak early systolic velocities along the apical septum were significantly reduced during LAD occlusion (2.8 +/- 1.2 cm/s to 0.6 +/- 1.7 cm/s, P <.001). Myocardial velocities in mid systole suggested paradoxical wall motion (1.0 +/- 1.2 cm/s to -0.8 +/- 0.9 cm/s, P <.001). When comparing the ischemic regions of the left ventricle with the nonischemic regions, each patient demonstrated lower myocardial systolic velocities in the ischemic region. Furthermore, during early diastole, the wall motion of the ischemic segments showed a postsystolic contraction pattern with velocities changing from -0.9 +/- 1.0 cm/s to 1.9 +/- 1.3 cm/s (P <.001). CONCLUSION: This new 2D TDE approach is able to quantify detailed myocardial velocity profiles from multiple regions simultaneously. Single-beat comparisons of ischemic and nonischemic regions might enhance the sensitivity for diagnosing ischemic heart disease. Reversed systolic wall motion during midsystole and marked positive velocity during early diastole might be new and important markers of myocardial wall ischemia.
Aged↗
Regulation of ET: pulmonary release of ET contributes to increased plasma ET levels and vasoconstriction in CHF.
Endothelin (ET) contributes to the increased systemic vascular resistance and elevated cardiac filling pressures seen in congestive heart failure (CHF). We investigated to what extent ET-mediated vasoconstriction in CHF occurs through an endocrine action of elevated plasma ET or by an autocrine/paracrine mechanism related to induction of vascular ET gene expression. Three weeks of pacing (225 beats/min) induced a marked release of ET-1 from the pulmonary circulation with a sixfold elevation of arterial plasma ET in CHF pigs compared with sham-operated pigs. Arterial plasma ET was the strongest and only independent predictor of systemic vascular resistance. In contrast, vascular preproET-1 and ET-receptor mRNA expression were unaltered or decreased in CHF pigs and did not correlate with indexes of vascular tone. However, myocardial preproET-1 mRNA expression increased twofold in CHF pigs. PreproET-2 and preproET-3 mRNAs were not detectable in cardiovascular tissues. In conclusion, plasma ET was markedly increased because of an augmented release from the pulmonary circulation during CHF, and arterial plasma ET correlated with systemic vascular resistance. The absence of ET induction in the peripheral vasculature suggests that ET increases vascular tone during CHF by an endocrine, not an autocrine/paracrine, mechanism.
Amino Acid Sequence↗
Methods for assessing hepatic distending pressure and changes in hepatic capacitance in pigs.
The equilibrium pressure obtained during simultaneous occlusion of hepatic vascular inflow and outflow was taken as the reference estimate of hepatic vascular distending pressure (P(hd)). P(hd) at baseline was 1.1 +/- 0.2 (mean +/- SE) mmHg higher than hepatic vein pressure (P(hv)) and 0.7 +/- 0.3 mmHg lower than portal vein pressure (P(pv)). Norepinephrine (NE) infusion increased P(hd) by 1. 5 +/- 0.5 mmHg and P(pv) by 3.7 +/- 0.6 mmHg but did not significantly increase P(hv). Hepatic lobar vein pressure (P(hlv)) measured by a micromanometer tipped 2-Fr catheter closely resembled P(hd) both at baseline and during NE-infusion. Dynamic pressure-volume (PV) curves were constructed from continuous measurements of P(hv) and hepatic blood volume increases (estimated by sonomicrometry) during brief occlusions of hepatic vascular outflow and compared with static PV curves constructed from P(hd) determinations at five different hepatic volumes. Estimates of hepatic vascular compliance and changes in unstressed blood volume from the two methods were in close agreement with hepatic compliance averaging 32 +/- 2 ml. mmHg(-1). kg liver(-1). NE infusion reduced unstressed blood volume by 110 +/- 38 ml/kg liver but did not alter compliance. In conclusion, P(hlv) reflects hepatic distending pressure, and the construction of dynamic PV curves is a fast and valid method for assessing hepatic compliance and changes in unstressed blood volume.
Animals↗
Mechanisms of retarded apical filling in acute ischemic left ventricular failure.
BACKGROUND: We examined the hypothesis that retardation of apical filling as measured by color M-mode Doppler echocardiography in the diseased left ventricle (LV) reflects a decrease in the intraventricular mitral-to-apical pressure gradient. METHODS AND RESULTS: In 9 open-chest anesthetized dogs, micromanometers were placed near the mitral tip and in the apical region. From the color M-mode Doppler images, the time delay (TD) between peak velocity at the mitral tip and the apical region was determined as an index of LV flow propagation. Acute ischemic LV failure was induced by coronary microembolization. Induction of ischemia caused a marked increase in LV end-diastolic pressure and a decrease in LV ejection fraction. The time constant of LV isovolumic apical pressure decay (tau) increased from 31+/-8 to 49+/-16 ms (P<0.001). The peak early diastolic mitral-to-apical pressure gradient (DeltaPLVmitral-apex) decreased from 1.9+/-0.9 to 0.7+/-0.5 mm Hg (P<0.01), and TD increased from 5+/-3 to 57+/-26 ms (P<0.001). The slowing of flow propagation was limited to the apical portion of the LV cavity. The TD correlated with DeltaPLVmitral-apex (r=-0.94, P<0.01) and with tau (r=0.92, P<0.01). Before ischemia, the mitral-to-apical flow propagation velocity far exceeded the velocity of the individual blood cells, whereas during ischemia, flow propagation velocity approximated the blood velocity. CONCLUSIONS: Retardation of apical filling in acute ischemic failure was attributed to a decrease in the mitral-to-apical driving pressure, reflecting slowing of LV relaxation. The slowing of flow propagation appeared to represent a shift in apical filling from a pattern of column motion to a pattern dominated by convection.
Acute Disease↗
Mechanism of pulmonary venous pressure and flow waves.
The pulmonary venous systolic flow wave has been attributed both to left heart phenomena, such as left atrial relaxation and descent of the mitral annulus, and to propagation of the pulmonary artery pressure pulse through the pulmonary bed from the right ventricle. In this study we hypothesized that all waves in the pulmonary veins originate in the left heart, and that the gross wave features observed in measurements can be explained simply by wave propagation and reflection. A mathematical model of the pulmonary vein was developed; the pulmonary vein was modeled as a lossless transmission line and the pulmonary bed by a three-element lumped parameter model accounting for viscous losses, compliance, and inertia. We assumed that all pulsations originate in the left atrium (LA), the pressure in the pulmonary bed being constant. The model was validated using pulmonary vein pressure and flow recorded 1 cm proximal to the junction of the vein with the left atrium during aortocoronary bypass surgery. For a pressure drop of 6 mmHg across the pulmonary bed, we found a transit time from the left atrium to the pulmonary bed of tau approximately 150ms, a compliance of the pulmonary bed of C approximately 0.4 ml/mmHg, and an inertance of the pulmonary bed of 1.1 mmHgs2/ml. The pulse wave velocity of the pulmonary vein was estimated to be c approximately 1m/s. Waves, however, travel both towards the left atrium and towards the pulmonary bed. Waves traveling towards the left atrium are attributed to the reflections caused by the mismatch of impedance of line (pulmonary vein) and load (pulmonary bed). Wave intensity analysis was used to identify a period in systole of net wave propagation towards the left atrium for both measurements and model. The linear separation technique was used to split the pressure into one component traveling from the left atrium to the pulmonary bed and a reflected component propagating from the pulmonary bed to the left atrium. The peak of the reflected pressure wave corresponded well with the positive peak in wave intensity in systole. We conclude that the gross features of the pressure and flow waves in the pulmonary vein can be explained in the following manner: the waves originate in the LA and travel towards the pulmonary bed, where reflections give rise to waves traveling back to the LA. Although the gross features of the measured pressure were captured well by the model predicted pressure, there was still some discrepancy between the two. Thus, other factors initiating or influencing waves traveling towards the LA cannot be excluded.
Biomechanical Phenomena↗
The pulmonary venous systolic flow pulse--its origin and relationship to left atrial pressure.
OBJECTIVES: The purpose of this study was to determine the origin of the pulmonary venous systolic flow pulse using wave-intensity analysis to separate forward- and backward-going waves. BACKGROUND: The mechanism of the pulmonary venous systolic flow pulse is unclear and could be a "suction effect" due to a fall in atrial pressure (backward-going wave) or a "pushing effect" due to forward-propagation of right ventricular (RV) pressure (forward-going wave). METHODS: In eight patients during coronary surgery, pulmonary venous flow (flow probe), velocity (microsensor) and pressure (micromanometer) were recorded. We calculated wave intensity (dP x dU) as change in pulmonary venous pressure (dP) times change in velocity (dU) at 5 ms intervals. When dP x dU > 0 there is a net forward-going wave and when dP x dU < 0 there is a net backward-going wave. RESULTS: Systolic pulmonary venous flow was biphasic. When flow accelerated in early systole (S1), pulmonary venous pressure was falling, and, therefore, dP x dU was negative, -0.6 +/- 0.2 (x +/- SE) W/m2, indicating a net backward-going wave. When flow accelerated in late systole (S2), pressure was rising, and, therefore, dP x dU was positive, 0.3 +/- 0.1 W/m2, indicating a net forward-going wave. CONCLUSIONS: Pulmonary venous flow acceleration in S1 was attributed to a net backward-going wave secondary to a fall in atrial pressure. However, flow acceleration in S2 was attributed to a net forward-going wave, consistent with propagation of the RV systolic pressure pulse across the lungs. Pulmonary vein systolic flow pattern, therefore, appears to be determined by right- as well as left-sided cardiac events.
Aged↗
Diastolic flow pattern in the normal left ventricle.
OBJECTIVES: This study sought to clarify the diastolic flow pattern in the normal left ventricle. BACKGROUND: During left ventricular filling, basally directed (retrograde) velocities are seen in the outflow compartment. These velocities may represent blood returned from the apical region or a shortcut at a more basal level. METHODS: Left ventricular flow patterns were identified in 18 healthy individuals (age 47 +/- 12 years) with the use of high frame-rate two-dimensional color Doppler and color M-mode Doppler echocardiography techniques. Intraventricular velocities were measured with single pulsed Doppler at 3 levels in both inflow and outflow compartments (posterolateral and anteroseptal parts of the left ventricle). RESULTS: During early transmitral flow acceleration, all intraventricular velocities were directed towards the apex. However, after peak early and late inflow velocities and during diastasis, retrograde velocities were identified in the outflow compartment. These retrograde velocities occurred earlier, and were higher, at the level of the deflected anterior mitral leaflet tip compared with more apical levels (P <.001). A velocity pattern was established, consistent with early intraventricular vortex formation behind both mitral leaflets. The vortex adjacent to the anterior leaflet subsequently enlarged to include a major part of the left ventricle. CONCLUSION: Uniform diastolic flow patterns were identified in the normal left ventricles. The findings suggest that both early and late diastolic filling start with an initial motion of a fluid column, succeeded by vortex formation, which explains retrograde flow in the outflow compartment.
Adult↗
Early diastolic intraventricular filling pattern in acute myocardial infarction by color M-mode Doppler echocardiography.
The aim of the present study was to investigate whether slowing of mitral-to-apical filling is present in patients with acute myocardial infarction (AMI). Twenty-eight patients with their first AMI were examined by color M-mode Doppler echocardiography. Twenty-eight age- and sex-matched healthy individuals served as control subjects. From the color M-mode Doppler images, we measured the time difference (TD) between occurrence of peak flow velocity at the mitral tip and in the apical region by a blinded analysis. The TD was increased in the AMI group compared with the control subjects (70 +/- 60 versus 40 +/- 30 msec, p = 0.02) and correlated with peak SGOT (r = 0.46, p = 0.02) and age (r = 0.57, p < 0.01). In the 15 patients with anterior AMI, the correlation between TD and SGOT was better (r = 0.68, p < 0.01). This study demonstrated slowing of early diastolic mitral-to-apical flow propagation in patients with AMI. Infarction size and age appear to be of importance for the retardation of mitral-to-apical flow propagation.
Adult↗
Hepatic oxygen metabolism in porcine endotoxemia: the effect of nitric oxide synthase inhibition.
The role of endotoxin (lipopolysaccharide, LPS) and nitric oxide in hepatic oxygen metabolism was investigated in 36 pigs receiving 1) LPS (1.7 microgram. kg-1. h-1) for 7 h and NG-nitro-L-arginine methyl ester (L-NAME; 25 mg/kg) after 3 h, 2) LPS, 3) NaCl and L-NAME, and 4) NaCl. Infusion of LPS reduced hepatic oxygen delivery (DO2H) from 60 +/- 4 to 30 +/- 5 ml/min (P < 0.05) and increased the oxygen extraction ratio from 0.29 +/- 0.07 to 0.68 +/- 0.04 after 3 h (P < 0.05). Hepatic oxygen consumption (VO2H) was maintained (18 +/- 4 and 21 +/- 4 ml/min, change not significant), but acidosis developed. Administration of L-NAME during endotoxemia caused further reduction of DO2H from 30 +/- 3 to 13 +/- 2 ml/min (P < 0.05) and increased hepatic oxygen extraction ratio from 0.46 +/- 0.04 to 0.80 +/- 0.03 (P < 0.05). There was a decrease in VO2H from 13 +/- 2 to 9 +/- 2 ml/min that did not reach statistical significance, probably representing a type II error. Acidosis was aggravated. Administration of L-NAME in the absence of endotoxin also increased the hepatic oxygen extraction ratio, but no acidosis developed. In a different experiment, liver blood flow was mechanically reduced in the presence and absence of endotoxin, comparable to the flow reductions caused by L-NAME. The increase in hepatic oxygen extraction ratio (0.34) and maximum hepatic oxygen extraction ratio (approximately 0.90) was similar whether DO2H was reduced by occlusion or by L-NAME. We concluded that L-NAME has detrimental circulatory effects in this model. However, neither endotoxin nor L-NAME seemed to prevent the ability of the still circulated parts of the liver to increase hepatic oxygen extraction ratio to almost maximum when oxygen delivery was reduced. The effect of L-NAME on oxygen transport thus seems to be caused by a reduction in DO2H rather than by alterations in oxygen extraction capabilities.
Animals↗
Mechanics of intraventricular filling: study of LV early diastolic pressure gradients and flow velocities.
This study investigates mechanisms of left ventricular (LV) intracavitary flow during early, rapid filling. In eight coronary artery disease patients with normal LV ejection fraction we recorded simultaneous LV apical and outflow tract pressures and intraventricular flow velocities by color M-mode Doppler echocardiography. In five anesthetized dogs we also recorded left atrial pressure and LV volume by sonomicrometry. In patients, as the early diastolic mitral-to-apical filling wave arrived at the apex, we observed an apex-outflow tract pressure gradient of 3.5 +/- 0.3 mmHg (mean +/- SE). This pressure gradient correlated with peak early apex-to-outflow tract flow velocity (r = 0.75, P < 0.05). The gradient was reproduced in the dog model and decreased from 3.1 +/- 0.3 to 1.7 +/- 0.5 mmHg (P < 0.05) with caval constriction and increased to 4.2 +/- 0.5 mmHg (P < 0.001) with volume loading. The pressure gradient correlated with peak early transmitral flow (expressed as time derivative of LV volume; r = 0.95) and stroke volume (r = 0.97). In conclusion, arrival of the early LV filling wave at the apex was associated with a substantial pressure gradient between apex and outflow tract. The pressure gradient was sensitive to changes in preload and correlated strongly with peak early transmitral flow. The significance of this gradient for intraventricular flow propagation in the normal and the diseased heart remains to be determined.
Adult↗
ET-receptor antagonism, myocardial gene expression, and ventricular remodeling during CHF in rats.
Both myocardial and plasma endothelin-1 (ET-1) are elevated in congestive heart failure (CHF). However, the role played by endogenous ET-1 in the progression of CHF remains unknown. The aim of the present study was to investigate and correlate myocardial gene expression programs and left ventricular (LV) remodeling during chronic ET-receptor antagonism in CHF rats. After ligation of the left coronary artery, rats were randomized to oral treatment with a nonselective ET-receptor antagonist (bosentan, 100 mg . kg-1 . day-1, n = 11) or vehicle (saline, n = 13) for 15 days, starting 24 h after induction of myocardial infarction. Bosentan substantially attenuated LV dilatation during postinfarction failure as evaluated by echocardiography. Furthermore, bosentan decreased LV systolic and end-diastolic pressures and increased fractional shortening. Myocardial expression of preproET-1 mRNA and a fetal gene program characteristic of myocardial hypertrophy were increased in the CHF rats and were not affected by bosentan. Consistently, right ventricular-to-body weight ratios, diameters of cardiomyocytes, and echocardiographic analysis demonstrated a sustained hypertrophic response and a normalized relative wall thickness after intervention with bosentan. Thus the modest reduction of preload and afterload provided by bosentan substantially attenuates LV dilatation, causing improved pressure-volume relationships. However, the compensatory hypertrophic response was not altered by ET-receptor antagonism. Therefore, ET-1 does not appear to play a crucial role in the mechanisms of myocardial hypertrophy during the early phase of postinfarction failure.
Angiotensinogen↗
Regulation of hepatic vascular volume: contributions from active and passive mechanisms during catecholamine and sodium nitroprusside infusion.
BACKGROUND: It is unclear how the liver contributes to regulation of cardiac filling. The aims of this study were to establish an animal model to quantify hepatic vascular capacitance and to determine the mechanisms whereby catecholamines and sodium nitroprusside modify hepatic blood volume. METHODS AND RESULTS: In 8 anesthetized pigs we measured hepatic and systemic pressures and flows. Liver vascular volume was measured by sonomicrometry calibrated against integrated hepatic inflow during outflow occlusion. Pressure-volume (P-V) curves were constructed during outflow occlusion. Sonomicrometry accurately reflected hepatic blood volume (r=.99+/-.001), and hepatic P-V curves were highly reproducible. Norepinephrine (0.3 and 0.7 microg x kg body weight (bwt)(-1) min(-1) intraportally) significantly reduced hepatic blood volume by 3.3+/-1 and 4.3+/-1 mL x kg bwt(-1), respectively. Nitroprusside (8 and 18 microg x kg bwt(-1) x min(-1) intraportally) increased hepatic blood volume by 1.1+/-0.2 and 1.9+/-0.3 mL x kg bwt(-1), respectively. Norepinephrine and nitroprusside parallel shifted the hepatic P-V curves, indicating reduced and increased unstressed blood volume, respectively. These curve shifts accounted for more than 90% of the respective blood volume changes. Compliance was unchanged. Phenylephrine but not isoprenaline yielded similar results as norepinephrine. CONCLUSIONS: The pig model used in this study, accurately quantified hepatic capacitance. Alpha-adrenergic stimulation decreased and nitroprusside increased capacitance by changing unstressed blood volume. These changes in capacitance correspond to expulsion of 300 mL and pooling of 130 mL of blood, respectively, in a 70-kg individual, reflecting that the liver is not only a passive blood reservoir but can respond actively and vigorously to pharmacological interventions.
Animals↗
Increased cardiac expression of endothelin-1 mRNA in ischemic heart failure in rats.
OBJECTIVES: Plasma endothelin (ET) concentrations are increased in heart failure. The aims of the present study were to investigate to what extent cardiac ET mRNA expression is induced in ischemic heart failure and whether there may be compensatory downregulation of myocardial mRNA levels for the ETA and ETB receptor subtypes. METHODS: In rats with ischemic heart failure (left ventricular end-diastolic pressure > 15 mmHg) due to left coronary artery ligation. Northern blot analyses were performed on mRNA isolated from cardiac tissues. RESULTS: A substantial upregulation was revealed in all chambers of the failing hearts. Up to 27-fold upregulation (mean 10.6 +/- 4.0, P = 0.002) of left ventricular ET-1 mRNA levels was measured 1 week after myocardial infarction, whereas only a modest upregulation was detected after 6 weeks (mean 2.7 +/- 0.5, P < 0.05). Ribonuclease protection assay revealed 2.8 +/- 0.4-fold higher levels of ET-1 mRNA in the left ventricular area subjected to myocardial infarction compared to the non-infarcted tissue after 1 week. Left ventricular ET-1 mRNA correlated significantly with left ventricular end-diastolic pressure after 1 week (r2 = 0.86, P = 0.007). The ETA and ETB receptor mRNA levels tended to increase 1 week after myocardial infarction although these changes were not statistically significant. CONCLUSIONS: Cardiac ET-1 mRNA levels are increased in ischemic heart failure and correlate significantly with left ventricular end-diastolic pressure 1 week after myocardial infarction. The increase in cardiac ET-1 mRNA is not accompanied by a decrease in ET receptor mRNA.
Animals↗