Assessment of left atrial input impedance in normal subjects and in hypertensive patients

BACKGROUND: To assess left atrial (LA) input impedance in patients with signs and/or symptoms of heart failure and normal left ventricular ejection fraction, transesophageal Doppler pulmonary venous (PV) flow velocity and pulmonary capillary wedge pressure (PCWP) were studied in 20 patients and compared to 20 matched normal controls. METHODS: LA impedance was calculated as the ratio of harmonic terms of the PCWP (measured by right heart catheterization) to the corresponding harmonic terms of PV flow (measured by transesophageal Doppler echocardiography). Eight harmonics were analyzed. RESULTS: Left ventricular mass index (LVMI, p<0.001), heart rate (p<0.05), systolic and diastolic blood pressure (p<0.001), isovolumic relaxation time (IVRT, p<0.001), peak A transmitral flow velocity (p<0.001), peak reversal atrial PV flow velocity (p<0.001) and LA diameter (p<0.001) were increased in patients compared to controls. Spectra of impedance moduli were displaced upwards and to the right. The increase in the impedance moduli was observed at all frequencies of the first to seventh harmonic components (p<0.001). In multivariate tests LVMI (p=0.003), IVRT (p=0.001), and LA diameter (p=0.007) had a significant effect on all harmonic components of the impedance moduli (adjusted R2=0.970 to 0.999, p<0.001). CONCLUSIONS: LA input impedance derived from data obtained invasively and semi-invasively represents left ventricular diastolic function. Resistance to left ventricular filling is increased in hypertensive patients.     

Effects of ascorbic acid on the vasoactive intestinal peptide synthesis in the ileum submucous plexus of normal rats

BACKGROUND: The aging process is a deteriorating process that attacks the gastrointestinal tract, causing changes in the number and size of neurons from the enteric nervous system. The activity of free radicals on enteric neurons is helped by the significant reduction of antioxidants. AIM: Evaluate the effect of the ascorbic acid supplementation on the neurons that produce the vasoactive intestinal peptide (VIP) in the submucous plexus of the ileum of normal rats for a period of 120 days. METHODS: Fifteen rats were divided in three groups: untreated control with 90 days, untreated control with 210 days and ascorbic acid-treated rats with 210 days. Ascorbic acid was given for 16 weeks from the 90th day of age by adding it to drinking water (1 g/L prepared fresh each day). The ileums were processed according to the immunohistochemistry technique for whole-mount preparation in order to detect the presence of VIP immunoreactive in the cellular bodies and nervous fibers in the neurons of the submucous plexus. We have verified their immunoreactivity and measured the cellular profile of 80 cellular bodies of VIP-ergic neurons from each studied group. RESULTS: The ascorbic acid supplementation did not alter physiological parameters such as water intake and food consumption of the three studied groups. We observed a significant increase of the cellular profile of VIP-ergic neurons in untreated control with 210 days when compared to untreated control with 90 days. The cellular profile of VIP-ergic neurons in ascorbic acid-treated rats with 210 days was bigger than those observed in others groups. CONCLUSION: The ascorbic acid had a neurotrophic effect on VIP-ergic neurons on the ileum after period 120 days of supplementation.     

Effects of diet supplementation with olive oil and guar upon fructose-induced insulin resistance in normal rats

Exposure of normal rats to fructose-containing drinking water represents a current model of insulin resistance. The major aim of the present study was to assess the possible effect of diet supplementation with either olive oil or guar upon the metabolic consequences of exposure to exogenous fructose. For this purpose, the changes in body weight, plasma d-glucose and insulin concentrations, and d-glucose infusion rate during a hyperinsulinemic-euglycemic clamp were measured after 65 days exposure to exogenous fructose and either olive oil- or guar-enriched diet. The results were compared to those previously collected in control animals exposed for the same period to either tap water or the fructose-containing drinking water and a standard diet. Diet supplementation with olive oil or guar failed to affect the increase in the insulinogenic index and the decrease in insulin sensitivity and fasted/fed ratio for plasma insulin concentration caused by exogenous fructose. In the rats exposed to exogenous fructose, the olive oil-fed rats differed from other animals by the absence of a decrease in food intake and body weight gain, whilst the guar-fed rats differed from other animals in a lower plasma d-glucose concentration in fed state and an absence, at day 65, of a higher plasma d-glucose concentration than that at day 0 measured in after overnight fasting state. These findings argue in favour of guar, rather than olive oil, to oppose the effect of exogenous fructose on glucose homeostasis.     

Effects of food on the central and peripheral haemodynamic response to upright exercise in normal volunteers.

The central and peripheral haemodynamic effects of a modest meal were investigated in healthy volunteers at rest and in response to submaximal exercise. The meal increased heart rate, cardiac output, oxygen consumption, carbon dioxide production, and minute ventilation at rest and during exercise. The effects of food were additive to those induced by the exercise. Food had no effect on limb blood flow and lowered total systemic vascular resistance suggesting that there were no compensatory changes in regional blood flow to help redirect blood to the gut. An increase in cardiac output, and therefore myocardial work, is the predominant cardiovascular response to eating and this may help explain the postprandial deterioration in symptoms of some patients with cardiovascular disorders.     

Response of normal and diseased epicardial coronary arteries to vasoactive drugs: quantitative arteriographic studies

Coronary vasodilators known to be effective in effort and vasospastic angina were studied in 93 patients undergoing catheterization for evaluation of chest pain. The ischemia-provoking stresses were isometric handgrip (25% of maximum for 4 to 5 minutes) or ergonovine maleate (0.2 mg intravenously). Hemodynamic changes and changes in angiographic diameter of epicardial coronary arteries were measured during these stresses, with and without drug administration. Drugs included intravenous diltiazem (0.25 mg/kg load + 0.003 mg/kg/min), intravenous verapamil (0.14 mg/kg load + 0.0075 mg/kg/min) and intracoronary (0.012 mg/min X 4 minutes) and sublingual (0.4 mg) nitroglycerin. From these studies, the following statistically valid conclusions were reached. First, nitroglycerin is a potent dilator of epicardial coronary arteries, increasing normal luminal area an average of 28% and luminal area in significantly stenotic segments by 29%. Second, verapamil and diltiazem are nonsignificant epicardial coronary dilators (9% and 4% luminal area increase, respectively). Similarly, diltiazem does not dilate significant coronary stenoses. Third, sustained isometric handgrip increases systemic blood pressure and heart rate by reflex activation of the sympathetic nervous system. By this means, handgrip also constricts luminal area in normal and diseased coronary segments by 20% and 22%, respectively. One result of these changes is a handgrip-induced, ischemic 56% rise in pulmonary wedge pressure in patients with significant stenosis. Fourth, intracoronary nitroglycerin, in very small doses, does not block the systemic hemodynamic response to handgrip, but prevents handgrip-induced coronary constriction and the associated ischemic left ventricular dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Aortic input impedance in heart failure: comparison with normal subjects and its changes during vasodilator therapy

This study was aimed at the evaluation of aortic impedance inpatients with congestive heart failure. Aortic impedance (simultaneousmeasurements of aortic pressure and blood flow), mean (W_m) andpulsatile (W_p) powers were compared in 11 normal subjects andin 12 patients with heart failure. Pulse wave velocity (C: modifiedMoens-Korteweg equation, simultaneous measurements of aorticpressure and radius) was determined under control conditionsin all normal subjects and in 7 patients with heart failure.Impedance curves in patients with heart failure were characterizedby increased values of the impedance modulus at 0 Hz (peripheralresistance) and at low frequencies. The characteristic impedance,C, and phase were not different from normal subjects. In sixpatients with heart failure, impedance curves were studied duringnitroprusside infusion. During the infusion of the vasodilator,the impedance modulus at 0 Hz and at low frequencies decreased.The characteristic impedance was unchanged. The zero interceptof the phase was shifted towards lower frequencies. These resultsshow that the changes in impedance curves in patients with heartfailure are due to greater peripheral resistance and wave reflection.During nitroprusside infusion the stroke volume increased andthe aortic blood flow became more pulsatile (greater valuesof low frequency components). This modification accounts forthe increased values ofW_m and W_p, and is related to decreasedperipheral resistance and wave reflection.     

Effects of tactile and electrical stimuli upon release of vasoactive intestinal polypeptide in the mammalian penis

Plasma levels of vasoactive intestinal polypeptide (VIP) in the corpora cavernosa penis and dorsal penile veins greatly exceeded those measured in the limb or caudal veins during anaesthesia in various mammals (Bennett's wallaby, Barbary sheep, cheetah, puma, sooty mangabey, pigtail macaque and chimpanzee). Tactile stimulation of the penis immediately before or during collection of blood samples resulted in an increase. In the wallaby, VIP levels (mean +/- S.E.M.) in blood samples collected from the flaccid penis in the absence of tactile stimulation were very low (0.6 +/- 0.5 pmol/l). A 36-fold increase in VIP occurred after manual extension of the flaccid penis (24.8 +/- 3.2 pmol/l) or during manually stimulated erections (25.1 +/- 1.7 pmol/l). Electrical stimulation of erection produced no significant increase in VIP levels (2.3 +/- 0.9 pmol/l) unless accompanied by tactile stimulation (17.5 +/- 1.4 pmol/l). These studies provide the first demonstration that sensory feedback from the penis plays an important role in regulating vasoactive intestinal polypeptidergic activity. Since VIP is a potent vasodilator its release due to tactile stimuli during copulation may play a role in the maintenance of penile erection.     

人参二醇组皂苷对内毒素休克大鼠体内血管活性物质的调节作用

目的 探讨人参二醇组皂苷(PDS)对内毒素休克大鼠体内血管活性物质的调节作用.方法 大鼠舌下静脉注射PDS进行预治疗,10 min后注射细菌内毒素(LPS,5 mg/kg)复制感染性休克模型.实验动物随机分为对照组(C组),内毒素休克组(L组),地塞米松预治疗组(LD组),PDS预治疗组(LP组).各组大鼠于休克2、4 h腹主动脉取血,硝酸还原酶法测定血清中一氧化氮合酶(NOS) 活性和NO-2/NO-3的变化,间接反映NO的水平.于休克后4 h处死动物,称取肝组织20 mg匀浆后测血栓素B2(TXB2)及6-酮-前列腺素F1α(6-Keto-PGF1α)的含量.结果 肝组织中TXB2、6-keto-PGF1α及6-Keto-PGF1α/TXB2在LP组均显著低于L组.注射内毒素2 h后L组的血清NOS和NO-2/NO-3明显升高,LD组和LP组NOS活性、NO-2/NO-3显著低于L组.结论 PDS能够降低内毒素休克大鼠TXA2、PGI2和NO的水平,改善微循环状态,起到抗休克的作用.     

Effects of nicorandil on aortic input impedance: a comparative study with nitroglycerin

A study of aortic input impedance was performed to evaluate the effects of nicorandil on the systemic circulation, and the effects were compared with those of nitroglycerin. Sixteen patients with coronary artery disease were divided into 2 age-matched groups. Aortic input impedance was obtained from Fourier analysis of aortic pressure and flow signals at baseline conditions, after intravenous administration of either 4 mg (Group 1) or 8 mg (Group 2) nicorandil, and 20 min after 0.3 mg sublingual nitroglycerin. In Group 1, the first harmonic impedance modulus (Z1, 304+/-140 dyne x s x cm(-5)) and the average of the first to third harmonics (Z1-3, 207+/-99 dyne x s x cm(-5)), indices of wave reflection, significantly decreased (24.4% (p<0.05) and 24.7% (p<0.01), respectively) after nicorandil, and 41.3% (p<0.01) and 33.9% (p<0.01) after nitroglycerin. The effects between the 2 vasodilators were not significantly different. In Group 2, Z1 and Z1-3 (275+/-138 and 196+/-93 dyne x s x cm(-5), respectively) also decreased after administration of nicorandil (28.4% (p<0.01) and 35.9% (p<0.01), respectively), and after administration of nitroglycerin (23.9% (p<0.01) and 28.7% (p<0.01), respectively), without any significant difference between the 2 drugs. Characteristic impedance and total peripheral resistance (R) in both groups remained unchanged except for R after 8 mg nicorandil (from 1830+/-415 to 1433+/-428 dyne x s x cm(-5); p<0.01). Like nitroglycerin, both doses of nicorandil reduced wave reflection. The reduction in R after 8 mg nicorandil is related to decreased tone in the resistance arteries, probably due to potassium channel opener effects.     

Metabolic and haemodynamic responses to adrenaline in normal dogs

Summary The metabolic and haemodynamic effects of adrenaline were investigated in 6 intact anaesthetized dogs, which were subjected to an infusion of adrenaline. The dose given was similar to the endogenous production rate of adrenaline in experimental myocardial infarction. Adrenaline infusion (0.8, 1.17 or 1.05g · kg^–1. min^–1) over two hours led to a variable rise in blood level of this amine, regardless of the rate of infusion. Dogs with high blood adrenaline (over 3.5 ng·ml^–1) exhibited haemodynamic deterioration, i.e a rise in peripheral vascular resistance together with a fall in cardiac output and external cardiac work. Dogs with low blood adrenaline showed little change in peripheral vascular resistance, a rise in cardiac output and external cardiac work. The myocardial consumption of each of the substrates lactate, pyruvate, glucose and FFA was measured, and its equivalent oxygen consumption expressed as a percentage of the total myocardial oxygen consumption. No relationship was found between myocardial utilisation of individual substrates and the type of haemodynamic response. Thus in intact dogs exposed to adrenaline excess, similar to that found in acute myocardial infarction, the different types of haemodynamic response cannot be attributed to the type of substrate utilization by the myocardium, but to different rates of clearance of adrenaline. Low clearance rates lead to high blood adrenaline levels and an unfavourable response of the cardiovascular system.

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Zusammenfassung An 6 narkotisierten Hunden wurden die metabolischen und hämodynamischen Auswirkungen einer Adrenalin-Infusion untersucht. Die Dosierung stimmte weitgehend mit der endogenen Produktionsrate von Adrenalin bei experimentellem Herzinfarkt überein. Eine Adrenalin-Infusion (0,8; 1,17 oder 1,05 g/kg) über 2 Stunden führte zu einem variablen Anstieg des Blutspiegels von Adrenalin. Hunde mit einem hohen Blutspiegel (über 3,5 g · kg^–1 · min^–1) zeigten hämodynamische Störungen, d. h. einen Anstieg des peripheren Widerstandes, verbunden mit einem Abfall des Herzminutenvolumens und der äußeren Herzarbeit. Hunde mit niedrigem Blutspiegel zeigten nur geringe Änderungen des peripheren Widerstandes sowie einen Anstieg des Herzminutenvolumens und der äußeren Herzarbeit. Der myokardiale Verbrauch der Substrate Laktat, Pyruvat, Glucose und freie Fettsäuren wurde gemessen und der äquivalente Sauerstoffverbrauch als Prozentsatz des gesamten myokardialen Sauerstoffverbrauchs ausgedrückt. Es wurde keine Beziehung zwischen myokardialer Utilisation der einzelnen Substrate und der Art der hämodynamischen Reaktion gefunden. Ähnlich wie beim akuten Myokardinfarkt können auch bei Hunden unter starkem Adrenalineinfluß die verschiedenen hämodynamischen Reaktionstypen nicht auf die Art der Substratutilisation im Myokard bezogen werden, sondern auf unterschiedliche Geschwindigkeiten der Adrenalin-Elimination. Niedrige Eliminationsgeschwindigkeit führt zu hohen Adrenalinblutspiegeln und ungünstigen Reaktionen des kardiovaskulären Systems.

     

Effects of food on the central and peripheral haemodynamic response to upright exercise in normal volunteers

The central and peripheral haemodynamic effects of a modest meal were investigated in healthy volunteers at rest and in response to submaximal exercise. The meal increased heart rate, cardiac output, oxygen consumption, carbon dioxide production, and minute ventilation at rest and during exercise. The effects of food were additive to those induced by the exercise. Food had no effect on limb blood flow and lowered total systemic vascular resistance suggesting that there were no compensatory changes in regional blood flow to help redirect blood to the gut. An increase in cardiac output, and therefore myocardial work, is the predominant cardiovascular response to eating and this may help explain the postprandial deterioration in symptoms of some patients with cardiovascular disorders.     

Effects of pacing tachycardia and balloon valvuloplasty on pulmonary artery impedance and hydraulic power in mitral stenosis.

BACKGROUND. Mitral stenosis is characterized by progressive pulmonary hypertension and eventual right ventricular failure. However, the correlation between right ventricular failure and the level of pulmonary hypertension is poor, suggesting that factors other than those recognized from nonpulsatile hemodynamic parameters may contribute to impaired right ventricular performance in this condition. METHODS AND RESULTS. We studied 16 patients with severe mitral stenosis (mean valve area, 1.0 +/- 0.2 cm2) at supine rest and during pacing tachycardia using high-fidelity catheter recordings of pulmonary artery (PA) pressure and flow velocity. Pulmonary impedance spectra, wave reflection properties, and hydraulic power data were derived from Fourier analysis of signal-averaged data. Pacing tachycardia (baseline heart rate, 81 +/- 11 beats per minute; pacing, 132 +/- 11 beats per minute) significantly raised pulmonary wedge and mean PA pressures. There was no change in pulmonary vascular resistance (209 +/- 144 to 232 +/- 164 dyne-sec/cm5) or PA characteristic impedance (62 +/- 25 to 55 +/- 28 dyne-sec/cm5). However, first harmonic impedance (Z1) significantly decreased (134 +/- 71 to 100 +/- 68 dyne-sec/cm5; p < 0.001). Accordingly, oscillatory and total dissipated hydraulic power per unit forward flow (WT/CO) fell during tachycardia (2.6 +/- 1.6 to 2.3 +/- 1.4 mW/ml.sec-1; p = 0.06) despite acute pulmonary hypertension. Reflected pressure waves returned earlier to the proximal PA, suggesting increased vessel stiffness. Immediately after percutaneous balloon mitral valvuloplasty (PBV) in eight of the patients, baseline and pacing data were again recorded. Compared with the pre-PBV baseline state, post-PBV resting data demonstrated no change in resistance or characteristic impedance, but there was a significant fall in Z1 (166 +/- 75 to 103 +/- 45 dyne-sec/cm5; p < 0.05) and in the magnitude of pulmonary wave reflections. WT/CO tended to decrease after PBV, and pacing after PBV produced a further decrease in WT/CO, again in association with lower Z1. CONCLUSIONS. These data demonstrate that 1) increased pulmonary characteristic impedance, although a feature of mitral stenosis, is not exacerbated by the acute effects of increased distending pressure; 2) pacing tachycardia in mitral stenosis causes little change in the pulmonary impedance spectrum except at low frequencies, where decreased impedance lowers power requirements per unit flow; and 3) relief of mitral stenosis produces immediate improvement in low-frequency impedance and in hydraulic power requirements. These findings suggest that although characteristic impedance may be a measure of the long-term effects of pulmonary hypertension on the pulmonary circulation, acute increases and decreases in PA pressure produce effects on right ventricular load that are best described in terms of the low-frequency properties of the PA system. Improvement in low-frequency impedance diminishes hydraulic power requirements and thus reflects improved ventricular-vascular coupling, irrespective of distending PA pressure. Efforts to treat or prevent right heart failure in the presence of pulmonary hypertension should take account of the potential benefit of changes in low-frequency impedance characteristics of the pulmonary vascular bed.     

Noninvasive determination of aortic input impedance and external left ventricular power output: a validation and repeatability study of a new technique.

OBJECTIVE. The study was designed to test whether aortic input impedance and left ventricular power output can be accurately assessed noninvasively. BACKGROUND. Aortic input impedance describes both the pulsatile and nonpulsatile artery load encountered by the left ventricle. Until now, this measure of afterload has only been determined by invasive techniques. METHODS. The aortic pressure wave was estimated by recording the calibrated carotid artery pressure wave noninvasively with use of a micromanometer-tipped probe by the technique of applanation tonometry. Flow was determined with pulsed wave Doppler measurement of ascending aortic velocity profile and aortic diameter. In 18 subjects undergoing cardiac catheterization, invasive measurements were taken to assess the accuracy of noninvasive data. In 17 other subjects noninvasive measurements were taken on different days to assess the reproducibility of results. RESULTS. Noninvasive pressure measurements correlated well with invasive data: systolic pressure (mm Hg), noninvasive 126 +/- 28 versus invasive 127 +/- 28, r = 0.96, p less than 0.001; diastolic pressure (mm Hg), noninvasive 71 +/- 10 versus invasive 66 +/- 7, r = 0.60, p less than 0.02; augmentation index (%), noninvasive 23.9 +/- 9.3 versus invasive 30.7 +/- 11.9, r = 0.87, p less than 0.001. Doppler-measured cardiac output was closely correlated with invasively measured flow (liters/min): Doppler, 5.3 +/- 1.2 versus invasive, 5.5 +/- 1.3, r = 0.98, p less than 0.001. Impedance and left ventricular power variables calculated from noninvasive and invasive techniques were also closely related: systemic vascular resistance (dynes.s.cm-5), noninvasive 1,479 +/- 488 versus invasive 1,502 +/- 498, r = 0.91, p less than 0.001; characteristic impedance (dynes.s.cm-5), noninvasive 137 +/- 52 versus invasive 136 +/- 79, r = 0.92, p less than 0.001; pulsatile power (mW), noninvasive 249 +/- 94 versus invasive 291 +/- 103, r = 0.91, p less than 0.001; mean power (mW), noninvasive 1,107 +/- 319 versus invasive 1,144 +/- 266, r = 0.93, p less than 0.001. Repeated measures of impedance variables and power output showed coefficients of variation of less than 9%. CONCLUSIONS. Measurement of noninvasive impedance by this technique provides an accurate and repeatable assessment of mean and pulsatile cardiac load.     

Aortic and pulmonary input impedance in patients with cor pulmonale

The hydraulic load of the right and left ventricles and the clinical effects of nifedipine were evaluated in 8 normal subjects (mean age: 55 years) and 8 patients with cor pulmonale secondary to chronic obstructive lung disease (mean age: 57 years). It was found that there were differences in the right ventricular resistance (174.62 +/- 25.96 vs 468.57 +/- 178.81 dyne/sec/cm-5), first zero crossing frequency (3.62 +/- 0.34 vs 6.07 +/- 3.56 Hz), steady power (218.95 +/- 32.25 vs 359.44 +/- 37.46 mW) and total power of right ventricle (275.81 +/- 36.18 vs 440.46 +/- 85.16 mW) between the normal and cor pulmonale patients, respectively. However, no significant changes in characteristic impedance, pulsatile power or aortic impedance were observed in the right pulmonary artery. After administration of nifedipine to patients with cor pulmonale, there were significant changes in resistance (468.57 +/- 178.81 vs 256.36 +/- 178.56 dyne/sec/cm-5), steady power (359.44 +/- 37.46 vs 225.51 +/- 114.64) and total power (440.46 +/- 85.16 vs. 289.27 +/- 50.85) of the pulmonary artery, respectively. Otherwise there were no significant changes in aortic input impedance or characteristic impedance of right pulmonary artery and pulsatile power. In conclusion, we found that: 1) the hydraulic vascular load in the right ventricle was higher in patients with cor pulmonale, 2) characteristic impedance that was not increased in cor pulmonale patients may be due to a dilated pulmonary artery, 3) there was no impedance mismatch between left ventricle and systemic arterial system in patients with cor pulmonale, and 4) by reducing the pulmonary vascular resistance through nifedipine administration, the total external right ventricular power might be reduced, without affecting the proximal pulmonary arterial compliance.