How should we assess diastolic function in hypertension?

OBJECTIVE: the aim of our study was to assess the relative merits of three indices of diastolic LV function in a group of patients with hypertension and normal systolic function and a group of healthy controls. DESIGN: In this echocardiographic study, diastolic LV function was assessed by E/A ratio using pulsed Doppler recording and by atrial to total mitral annulus motion (AC) and maximal longitudinal LV relaxation velocity (RVm) by M-mode recordings from apical views. The study took place in the Department of Clinical Physiology in a secondary referral centre. Nineteen consecutive patients with uncomplicated hypertension referred to echocardiographic examination and 20 age- and sex-matched controls were included in the study. RESULTS: All three measures of diastolic function, E/A ratio, AC and RVm indicated impaired diastolic function in the hypertensive group, compared to the healthy controls. However, E/A ratio and AC showed a considerable overlap between the groups, whereas there was a highly significant difference in RVm between the hypertensive group and the controls, with much less of an overlap. CONCLUSION: The results indicate that of these three indices of diastolic function, RVm may be the most appropriate in patients with hypertension and normal systolic LV function.

Influence of body size and age on maximal systolic velocity of mitral annulus motion.

The maximal systolic velocity of the mitral annulus motion (or maximal systolic long-axis contraction velocity of the ventricle, MLACV) has been suggested as a means to assess left ventricular function. However, reference values for a wide range of age and body size are lacking. The maximal systolic velocity was studied with M-mode echocardiography using the apical four- and two-chamber views. Data are reported as the average of the measurements of four sites of the mitral annulus. Fifty-seven healthy subjects aged 6 months to 72 years were studied. In children and adolescents up to age 18, MLACV had a significant positive correlation with age, height, body surface area, weight and mitral annulus motion amplitude and a significant negative correlation with heart rate. In adults, there was a significant positive correlation between MLACV and height, mitral annulus motion amplitude and body surface area and a significant negative correlation with age and heart rate. Multiple stepwise analysis showed that the maximal systolic velocity is highly dependent on height and age in children and adolescents up to age 18, and on height in adults. The maximal long-axis contraction velocity (MLACV) can be described by the following equations: MLACV (mm s-1) = 24.0 + 0.34 x height (cm) (Standard Error of the Estimate (SEE)=10.5) in children and adolescents, and MLACV (mm s-1) = -50.5 + 0.75 x height (cm) (SEE=9.8) in adults over 18. There were significant differences between the four sites, with the highest velocity at the lateral site and the lowest velocity at the septal site. No significant difference was found between inspiratory and expiratory beats.

Echocardiographic assessment of ejection fraction in left ventricular hypertrophy.

OBJECTIVE: To investigate the value of Simpson's rule, Teichholz's formula, and recording of mitral ring motion in assessing left ventricular ejection fraction (EF) in patients with left ventricular hypertrophy. DESIGN: Left ventricular ejection fraction calculated by Simpson's rule and by Techholz's formula and estimated by mitral ring motion was compared with values obtained by radionuclide angiography. SETTING: Secondary referral centre. PATIENTS: 16 patients with left ventricular hypertrophy and a clinical diagnosis of hypertrophic cardiomyopathy or hypertension. RESULTS: Calculation by Teichholz's formula overestimated left ventricular ejection fraction by 10% (p = 0.002) and estimation based on mitral ring motion-that is, long axis measurements-underestimated ejection fraction by 19% (p = 0.002), without significant correlation between ring motion and ejection fraction. There was no significant difference between mean values of ejection fraction calculated by Simpson's rule and measured by the reference method, but a considerable scatter about the regression line with a standard error of the estimate of 9.3 EF%. CONCLUSIONS: In patients with left ventricular hypertrophy the ejection fraction, calculated by Teichholz's formula or Simpson's rule, is a poor measure of left ventricular function. When mitral ring motion is used for the assessment in these patients the function should be expressed in ways other than by the ejection fraction.

Left ventricular contraction pattern changes with age in normal adults.

Left ventricular ejection fraction is known to be unchanged or slightly increased with advancing age. This echocardiographic study, including 40 healthy subjects 18 to 70 years old, shows that this is a net effect of decreased contractions in the long axis and increased in the short axis. From age 18 to 70 years, the longitudinal shortening decreases by 20% (P < .001) and the short-axis diameter shortening increases by 18% (P=.012). Multiple regression analysis showed strong correlation to age for both short- and long-axis contractions and no significant additional explicatory power when the variables systolic blood pressure, left ventricular wall thickness, heart rate, or sex were included. There was no significant correlation between diameter changes during the isovolumic phases and age. The findings have practical implications when calculating ejection fraction from M-mode measurements. Teichholz's formula will overestimate ejection fraction in elderly subjects, and calculation of ejection fraction from mitral ring motion will overestimate it in young subjects.

Usefulness of coronary angiography for assessing left ventricular function.

The correlation of ejection fraction to left ventricular long-axis contractions, measured from left coronary ostium to apical arterial branches, on coronary angiograms was investigated.

Reduced left ventricular relaxation velocity after acute myocardial infarction.

Diastolic left ventricular function is usually described using Doppler recording of the early to atrial (E/A) ratio. However, because of pseudonormalization in patients with moderately impaired diastolic function, the E/A ratio does not allow a meaningful comparison between a group of patients with varying degrees of dysfunction, e.g. after acute myocardial infarction (AMI), and a group of healthy control subjects. In this study, diastolic function was assessed using the E/A ratio, deceleration time of early mitral inflow and maximal longitudinal relaxation velocity. The relaxation velocity was measured using echocardiographic M-mode recording of mitral annulus motion. Mitral annulus motion was recorded in four- and two-chamber views. Relaxation velocities were measured in the septal, lateral, anterior and posterior parts of the mitral annulus and the mean value (RVm) was calculated. Twenty-two consecutive patients were investigated 3-21 days after first transmural AMI. Twenty-two healthy subjects of similar age served as a control group. The group of patients with AMI had an RVm of 40.9 +/- 15.4 mm s-1 compared with 68.5 +/- 12.4 mm s-1 in the control group (P < 0.0001). In contrast, the E/A ratio, deceleration time and heart rate did not differ significantly between the two groups. The results suggest that maximal longitudinal relaxation velocity is a simple and appropriate measure of diastolic function in patients with transmural AMI.

Long and short axis dimensions of the left ventricle change in opposite ways during respiration.

Cardiac output and stroke volume are known to vary with respiration. While right ventricular stroke volume increases on inspiration, left ventricular stroke volume decreases. This is an echocardiographic study of the changes in left ventricular dimensions in 20 healthy subjects. Our results show that the decrease in left ventricular stroke volume on inspiration is a net effect of a decrease in short axis shortening due to a decrease in diastolic diameter by 4.8% (P < 0.001) and an increased motion in the long axis direction expressed as an increase in mitral ring motion by 5.5% (P < 0.001). The findings point to the importance of the interventricular septum for the regulation of stroke volume.

Influence of body size and age on mitral ring motion.

Left ventricular systolic and diastolic function can be assessed by studying mitral ring motion. Reference values for a wide range of age and body size are lacking however. The motion of the mitral ring was studied with M-mode echocardiography using the apical four- and two-chamber views. Data are reported as the average of measurements of four points on the mitral ring. Data were analysed using the stepwise multiple regression technique, with age, gender, height, weight, body surface area and heart rate as independent variables. A total of 70 healthy subjects were studied. In children and adolescents under age 18, there was strong correlation between mitral ring motion and body size, age and heart rate. The ring motion was best described as mitral ring motion (mm) = 2.2 + 0.078 x height (cm) (SEE = 1.0 mm). In adults, mitral ring motion was correlated with age, height and heart rate but not with weight or body surface area. Ring motion could be described from the following equations: mitral ring motion (mm) = 12.7 - 0.060 x age (years) + 0.031 x height (cm) (SEE = 1.2) or, if only age is taken into account, mitral ring motion = 18.4 - 0.065 x age (SEE = 1.2). In both children and adolescents up to age 18 and in adults, atrial contribution correlated significantly and positively to age and inversely to heart rate but not to height, weight, body surface area or gender. Atrial contribution was best described by the equation: atrial contribution = 0.15 + 0.0039 x age (SEE = 0.027). Thus, age and body size influences mitral ring motion and should be taken into account when interpreting patient data.

Small-bowel obstruction and the effects of lidocaine, atropine and hexamethonium on inflammation and fluid losses.

BACKGROUND: The profuse fluid losses and morbidity of patients suffering from obstructive ileus are closely related to inflammatory changes in the obstructed bowel wall. Previous experimental studies have shown that use of steroids and NSAIDs can reduce fluid losses in obstructive ileus. In the present study, we investigated the effects of lidocaine on fluid losses since local anesthetics have been shown to possess wide and potent anti-inflammatory properties. Hexamethonium and atropine were used to study the importance of the autonomic nervous system in bowel obstruction. METHOD: Experiments were performed in rats in vivo. After 18 h of total obstruction of the jejunum by thread ligation, a segment of the obstructed jejunum was placed in a chamber with intact nervous and vascular supply and net fluid transport was continuously registered by a gravimetric technique. Extravasation of Evans blue albumin as marker of inflammation was quantified by spectrophotometry. RESULTS: Hexamethonium (10 mg.kg-1 i.v.) significantly inhibited net fluid secretion (P < .05), while atropine (0.25 mg.kg-1 i.v.) had no significant effect. Net fluid secretion was reversed into absorption following an intravenous bolus dose of lidocaine (2 mg.kg-1) (P < 0.01) and topical administration of lidocaine (20 mg) on the serosa of the obstructed gut (P < 0.01). Single topical administration of lidocaine (20 mg) immediately before ligation significantly reduced net fluid secretion (P < 0.05) and inflammation (P < 0.05) in the obstructed bowel 20 h post-ligation compared to obstructed controls. CONCLUSION: Lidocaine significantly inhibited or prevented fluid losses when administered intravenously or topically to the obstructed gut. Mechanisms of action could be inhibition of nerve reflexes involved in fluid secretion and by inhibition of inflammation in the bowel wall. The inhibition of fluid losses by hexamethonium further supports the importance of the autonomic nervous system in the pathophysiology of bowel obstruction.

Influence of adrenoceptor agonists and antagonists on fluid secretion in small bowel obstruction.

OBJECTIVES: To investigate the importance of adrenoceptors on fluid losses in small bowel obstruction. DESIGN: Evaluation of the effects of adrenergic agonists and antagonists on in-vivo net fluid secretion in chronic small bowel obstruction in rats. METHODS: Net fluid transport in a jejunal segment was continuously registered in vivo after 18 h of mechanical obstruction of the small bowel in anaesthetized rats. The effect on net fluid transport of adrenoceptor agonists and antagonists and of isotonic saline was quantified. RESULTS: Clonidine, an alpha 2-agonist, had a significant (P < 0.05) anti-secretory effect, while yohimbine, an alpha 2-antagonist, significantly (P < 0.05) increased net fluid secretion. Phenylephrine, an alpha 1-agonist, and prazosin, an alpha 1-antagonist, lacked significant effects on net fluid transport. Similarly, prenalterol, a beta 1-agonist, and metoprolol, a beta 1-antagonist, had no significant effect on the net fluid transport. The beta 2-agonist salbutamol significantly (P < 0.001) decreased net fluid secretion, while the beta-antagonist propranolol significantly (P < 0.001) decreased net fluid secretion. CONCLUSION: Activation of alpha 2-adrenoceptors and blockade of beta 2-adrenoceptors significantly reduce net fluid secretion in small bowel obstruction. Results also demonstrate a continuous stimulatory effect on fluid secretion mediated by beta 2-receptors and a continuous inhibitory effect mediated by alpha 2-receptors.

Importance of vasoactive intestinal peptide and somatostatin for fluid losses in small-bowel obstruction.

BACKGROUND: Previous observations have shown vasoactive intestinal peptide (VIP) to be an important secretagogue in the gut, whereas somatostatin has been reported to inhibit VIP release and fluid secretion. METHODS: The possible role of VIP as mediator of the inflammation and fluid losses in obstructive ileus was investigated in vivo and in a chronic rat model with thread ligation of the jejunum. Extravasated Evans blue (Eb)-stained albumin was quantified by spectrophotometry. Net fluid secretion was measured by a gravimetric technique. VIP antiserum was used to inhibit the effects of endogenous VIP. A somatostatin analogue, octreotide, was used to inhibit the release of VIP. RESULTS: Results showed a pronounced plasma Eb-albumin extravasation in the wall of the obstructed gut, which was significantly inhibited by VIP antiserum (p < 0.05) or octreotide (p < 0.01). Obstruction of the jejunum resulted in net fluid secretion that was significantly reduced by administration of octreotide (p < 0.01) or VIP antiserum (p < 0.05). Net fluid secretion in control animals remained constant. CONCLUSIONS: These findings suggest that VIP is an important mediator of the pathophysiology in mechanical intestinal obstruction and that somatostatin may be involved in the endogenous control of fluid losses.

Non-invasive variant of Gorlin formula can be used to identify severe aortic stenosis.

In recent years the continuity equation has been established as a valuable non-invasive method for calculating aortic valve area. The continuity equation cannot be used if there is calcification or sub-valvular stenosis in the left ventricle-outflow tract, because the area of the outflow trace is not circular in those cases. The authors have tested the value of a non-invasive variant of the Gorlin formula, as an alternative method of identifying severe aortic stenosis. They examined 32 consecutive patients with aortic stenosis with both methods. Seventeen patients had severe stenosis (valve area < or = 0.7 cm2), calculated by the continuity equation. The other 15 patients had moderate stenosis (valve area 0.7-1.0 cm2). Using the non-invasive variant of the Gorlin formula, the authors were able to identify 16 of the 17 cases with severe stenosis, thus showing that the method is useful for identifying severe aortic stenosis. (P < 0.001 by chi 2-test).

Adrenergic, cholinergic and VIP-ergic influence on gastric phasic motility in the rat.

We investigated the effects of adrenergic, cholinergic and vasoactive intestinal polypeptide (VIP)-ergic agonists and antagonists on the amplitude of gastric phasic contractions in the anaesthetized rat using a volumetric model. The amplitude of the phasic contractions was reduced significantly by atropine, hexamethonium or bilateral cervical vagotomy indicating that cholinergic neural activity involving both muscarinic and nicotinic receptors and intact vagal nerve function are integral parts of the control of basal gastric phasic motility. In contrast, neither selective alpha 1-, alpha 2- or non-selective beta-blockers had any significant influence on the amplitude of the gastric contractions suggesting that adrenergic neurones are not tonically active in the maintenance of basal phasic motility in the stomach. The amplitude of the gastric phasic contractions was, however, significantly reduced by the alpha 1-agonist L-phenylephrine, the alpha 2-agonist clonidine and a close intraarterial injection of VIP (3 micrograms kg-1) but not be the selective beta 1-agonist, prenalterol, or the beta 2-agonist, salbutamol. These data suggest the presence of superimposed inhibitory control of phasic activity by VIP-ergic stimulation and by adrenergic neurones via alpha-receptor stimulation.

Involvement of vasoactive intestinal polypeptide in gastric reflex relaxation.

We have previously presented evidence for a non-adrenergic, vagally mediated colono-gastric inhibitory reflex induced by distension of the colon. We also found that pain stimulation by putting pressure on a testicle induced a pronounced gastric relaxation mediated by both adrenergic and vagal non-adrenergic fibres in anesthetized rats. Previous in vitro studies by other workers have strongly indicated that vasoactive intestinal polypeptide (VIP) is a neural mediator of gastric relaxation. The aim of the present in vivo study was to investigate, in anesthetized rats, whether VIP is involved in the gastric reflex relaxation induced by colonic distension and pain stimulation. A volumetric method was used to monitor changes in gastric volume. Gastric reflex relaxation following colonic distension was significantly and markedly inhibited by VIP antiserum as compared to the control relaxation before administration of the antiserum. Non-immunized control serum did not significantly influence gastric relaxation caused by colonic distension. Pain-induced gastric relaxation was moderately but significantly reduced after the administration of VIP antiserum but not after control serum. The selective beta 2-adrenoceptor agonist, salbutamol, induced a pronounced gastric relaxation of the same magnitude before and after the administration of VIP antiserum. VIP antiserum changed the pattern of gastric motility by inducing a specific type of gastric contraction appearing spontaneously or in response to colonic distension. A close intra-arterial injection of VIP induced gastric relaxation and inhibition of phasic gastric contractions. The present results in the rat suggest that VIP or a VIP-like peptide is involved in gastric reflex relaxation induced by colonic distension and pain stimulation.

Pain-induced inhibition of gastric motility is mediated by adrenergic and vagal non-adrenergic reflexes in the rat.

Painful stimuli have been shown to inhibit gastric motility in animal experiments and delay gastric emptying in humans. The aim of the present study was to investigate in detail mechanisms involved in pain-induced gastric inhibition. Pain stimulation by exerting pressure on a testicle induced a prompt gastric relaxation which lasted throughout the period of stimulation. Pain-induced gastric relaxation was significantly reduced by the selective alpha-1 blocker, prazosin, and by the non-selective beta-blocker, propranolol. Similarly pain-induced inhibition of gastric tone was significantly reduced by bilateral cervical vagotomy. In contrast, gastric relaxation following pain stimulation was significantly potentiated by the selective adrenergic alpha-2 blocker, yohimbine. Combined administration of prazosin and propranolol followed by bilateral cervical vagotomy abolished gastric relaxation in response to pain stimulation. In conclusion, gastric relaxation in response to painful stimulation was found to be reflex-mediated via sympathetic neurons acting on alpha-1 and beta receptors and possibly also via vagal non-adrenergic fibres. Pain-induced inhibition of gastric tone was significantly increased by yohimbine. It is suggested that yohimbine by blocking presynaptic inhibitory receptors on adrenergic neurons facilitates the release of noradrenaline in response to pain stimulation.