Hemodynamic effects of different H2-receptor antagonists

In a randomized, placebo-controlled, double-blind study, 10 healthy volunteers were treated orally once a day for 1 week each with placebo, 800 mg cimetidine, 300 mg ranitidine, and 40 mg famotidine. On the seventh treatment day, heart rate, blood pressure, systolic time intervals, and impedance cardiography were measured before the morning dose and at 2, 6, 12, and 24 hours after the morning dose. Heart rate and blood pressure were not markedly altered by any of the H2-receptor antagonists compared with the findings for placebo. Cimetidine and ranitidine did not markedly alter parameters of systolic time interval and impedance cardiography compared with placebo in contrast to famotidine, which significantly decreased stroke volume, cardiac output, and the Heather Index in impedance cardiography (p less than 0.05) and also significantly increased the ratio of the preejection period to the left ventricular ejection time in systolic time interval (p less than 0.05) 2 hours after the morning dose. Six hours after administration, most of these alterations could no longer be detected. The observed changes in hemodynamic parameters confirm that famotidine exerts negative effects on cardiac performance, whereas such influences could not be shown for cimetidine and ranitidine.     

Peripheral vascular effects and pharmacokinetics of the antimigraine compound, zolmitriptan, in combination with oral ergotamine in healthy volunteers

Members of the new class of antimigraine compounds, 5HT_1B/1D agonists, as well as ergotamine, may cause vasoconstriction through stimulation of 5HT receptors on peripheral vessels. The cardiovascular effects of 20 mg oral zolmitriptan (Zomig, formerly 311C90), 2 mg oral ergotamine and the combination were assessed in a randomized double-blind, placebo-corirolled crossover study in 12 healthy subjects. Pharmacodynamic measures included oscillometric blood pressure, systolic blood pressure at the toe and arm using a strain gauge technique, stroke volume and cardiac output using bioimpedance cardiography, high-resolution ultrasound to measure brachial arterial diameter and a novel Doppler method to measure blood flow velocity. Both drugs produced small degrees of peripheral vasoconstriction, including increases in diastolic blood pressure and blood flow velocity and decreases in arterial diameter and toe-arm systolic pressure gradient. These effects were generally additive with the combination but of no clinical importance. There were no significant changes in cardiac output, stroke volume heart rate or ECG. Zolmitriptan, at eight times the likely therapeutic dose, was generally well tolerated both alone and in combination with ergotamine. Ergotamine had no clinically important effects on zolmitriptan pharmacokinetics.     

Time course and nature of postprandial haemodynamic changes in normal man

Summary. The present study describes the nature and time course of the cardiovascular and neuro-endocrine changes that followed a standard 3100 kJ cold meal in 12 supine and fasting normal men who were studied in a balanced cross-over design. Heart rate, blood pressure, systolic time intervals and estimates of cardiac performance by impedance cardiography were measured every 10 min up to 4 h after eating. Eating caused a rapid and short-lasting increase in systolic blood pressure, estimated stroke volume and maximum velocity of impedance changes. Eating also caused a rapid and more protracted decrease in diastolic and mean blood pressure, PEP-i, QS₂-i and estimated systemic vascular resistance with an increase in heart rate and estimated cardiac output. In the later phase of the profiling a drop in LVET-i was also observed. The differences vs. fasting were statistically significant and judged to be biologically relevant. Venous plasma noradrenaline rose during eating as a consequence of the postural change, but eating itself did not alter venous plasma noradrenaline, and plasma adrenaline even tended to decrease. This reflects both the roughness of venous catecholamines in estimating adrenergic changes and the complexity of the underlying mechanisms and related reflexes.     

Clinical evaluation of impedance cardiography

Summary. We tested the validity of thoracic impedance cardiography for measuring cardiac output in man by comparing absolute values obtained using the non-invasive impedance method with values obtained using the invasive thermodilution method. We also compared per cent changes in cardiac output using impedance cardiography and thermodilution in response to environmental manipulations including cardiac pacing and intravenous administration of ergonovine, dipyridamole, or isoproterenol. Among 19 patients, absolute values for cardiac output, using the impedance and the thermodilution techniques, agreed well (r=0·85, P<0·001). The per cent change in cardiac output by impedance cardiography was positively correlated with the per cent change by thermodilution for the several manipulations (overall r=0·87, P<0·001). Impedance cardiography does appear, in general, to measure cardiac output and stroke volume validly in man, even in situations where heart rate and stroke volume change in opposite directions.     

Evaluation of changes in cardiac output from the electrical impedance waveform in the forearm

We tested the validity of regional impedance cardiography (RIC) for measuring changes in both cardiac output and stroke volume by comparing the values with a 2D ultrasound technique in response to the breath-hold manipulation. Among 13 subjects, changes in the maximum amplitude of the regional impedance waveform from the forearm conformed to those in stroke volume (r = 0.86, p < 0.001) and cardiac output (r = 0.76, p < 0.003) measured with the ultrasound technique in baseline and immediately after a 30 s breath-hold maneuver. We also found that the per cent change in cardiac output (r = 0.73, p < 0.005) and the per cent change in stroke volume (r = 0.84, p < 0.0003) by the echocardiography were both positively correlated with the per cent change in the peak impedance amplitude. In addition, both the change and the per cent change in the mean area under the impedance curve were consistent with those in the stroke volume, respectively. Accordingly, the regional electrical impedance waveform from lower limbs may be helpful in providing a non-invasive and continuous assessment of left ventricular output, especially during cardiac procedures.     

Calcium blocker lacidipine and carotid arteriolar vasodilation in healthy volunteers

Systemic and carotid hemodynamics were studied in 10 healthy male volunteers before and after short-term administration of a 4 mg dose of the calcium entry-blocker lacidipine in a placebo-controlled, double-blind, crossover study. Hemodynamic parameters of the right common carotid artery were measured before and at 1 1/2 and 3 hours after dose administration by means of pulsed Doppler flowmetry. In addition, systemic hemodynamic parameters were calculated from cardiac impedance measurements at the same time. In comparison with placebo, lacidipine produced a significant decrease in blood pressure, together with systemic and carotid arteriolar dilatation. Heart rate increased sharply, whereas carotid arterial diameter and tangential tension did not change. The study provided evidence that the calcium entry-blocker lacidipine produces systemic and carotid arteriolar vasodilation and that the heart rate baroreflex response after administration of calcium inhibitor is not associated with a significant modification of the geometry of carotid arterial wall.     

40 MHz Doppler characterization of umbilical and dorsal aortic blood flow in the early mouse embryo

Physiological study of the developing mouse circulation has lagged behind advances in molecular cardiology. Using an innovative high-frequency Doppler system, we noninvasively characterized circulatory hemodynamics in early mouse embryos. We used image-guided 43 MHz pulsed-wave (PW) Doppler ultrasound to study the umbilical artery and vein, or dorsal aorta in 109 embryos. Studies were conducted on embryonic days (E) 9.5-14.5. Heart rate, peak blood flow velocities, and velocity time integrals in all vessels increased from E9.5-14.5, indicating increasing stroke volume and cardiac output. Heart rate, ranging from 192 bpm (E9.5) to 261 bpm (E14.5), was higher than previously reported. Placental impedance, assessed by the time delay between the peaks of the umbilical arterial and venous waveforms and by venous pulsatility, decreased with gestation. Acceleration time, a load-independent Doppler index of cardiac contractility, remained constant but seemed sensitive to heart rate. High-frequency PW Doppler is a powerful tool for the quantitative, noninvasive investigation of early mouse circulatory development.     

Dynamic responses to intravenous urapidil and dihydralazine in normal subjects

Hemodynamic responses after urapidil were compared with those after dihydralazine in placebo-controlled, double-blind studies after cumulative intravenous doses. We recorded heart rate, blood pressure, systolic time intervals corrected for heart rate (electromechanical systole and preejection period), electrical impedance cardiography [(dZ/dt)/RZ index and mean electrical thorax impedance], and M-mode echocardiogram (end-systolic and -diastolic diameters, end-systolic wall stress, fractional shortening, and cardiac output). Both drugs induced dose-dependent reductions in total peripheral resistance, which resulted in reduction in left ventricular end-systolic wall stress and increases in heart rate (limited at +10 bpm with urapidil), fractional shortening, cardiac output, and the (dZ/dt)/RZ index. With each drug, diastolic blood pressure fell by 5 mm Hg, the corrected preejection period shortened (dihydralazine greater than urapidil), the corrected electromechanical systole did not change, and mean electrical thorax impedance rose with urapidil. The spectrum of effects indicates that both drugs reduce left ventricular afterload, thereby increasing left ventricular pump performance. Urapidil also exerts some preload reduction.     

Impedance Cardiography for Cardiac Output Estimation in Pacemaker Patients: Review of the Literature

Impedance curdiogrciphy permits noninvasive beat-to-beat determination of cardiac output, the product of the amplitude of the first derivative of thonicic impedance signal (dZ/dt), the venfricular ejection time, and heart rate corrected by the distance between the measuring electrodes. Its use is based on: (1) the dZ/dt signal that originates from the upper thorax; (2) the ventricular ejection period measured by the dZ/dt curve that occurs between the opening and closing of the aortic vnlve: (3) the dZ/dt curve is similar in morphology and timing to the aortic flow curve measured by an electromagnetic flowmefer with a significant linear correlation (r = 0.9) between dZ/dt and peak aortic flow; (4) similarity of the linear correlation between stroke volume, determined by the flowmeter and the impedance signal; and (5) significant reduction of the dZ/dt signal by 90% follows simultaneous occlusion of the aorta and the pulmonary artery. The rapid systolic portion of the impedance signal occurs only when blood is ejected into the aorta and is independent of right ventricular ejection. Most studies comparing impedance cardiography results with standard cardiac output determination have shown a correlation of 0.7–0.9. While the accuracy of impedance cardiography remains controversial and can be affected by the inherent limitations of the technique and by low cardiac output, intracardiac shunts. and valvular regurgitation. the high reproducibility of the method is established and may be comparable or superior to other commonly used techniques. When accurate determination of cardiac output is crucial, impedance cardiography may be used in conjunction with a standard technique to establish a baseline reference, thereby permitting further analysis. If only the trend need be followed, the high reproducibility of impedance cardiography measurements allows small changes in cardiac output to be detected on a frequent and ongoing basis. The ease and precision of this technique warrants its more widespread use in the assessment of pacemaker patients. Further use of this promising technique will allow a better definition of its role in the assessment of a wide range of cardiac patients.     

Relative sensitivity of four noninvasive methods in assessing systolic cardiovascular effects of isoproterenol in healthy volunteers.

STUDY OBJECTIVE: The study was performed to evaluate the relative sensitivity of various noninvasive methods to detect and describe the systolic cardiovascular effects of stepwise increasing doses of isoproterenol: two-dimensional left ventricular echocardiography (main variable, ejection fraction), ACVF (attenuation compensated volume flow)--dual-beam Doppler echoaortography (time-averaged mean velocity), electrical impedance cardiography [(dZ/dtmax)/RZ index], and systolic time intervals from mechanocardiography (PEP and QS2c). METHODS: Isoproterenol was administered by constant rate intravenous infusion in consecutive steps of 0.1, 0.2, 0.4, 0.75, and 1.5 micrograms/min (each for 15 minutes). Saline control infusions were given in analog fashion. The treatments (isoproterenol and saline solution) were administered in a period-balanced two-way crossover design with randomly allocated sequences. The subjects, observers, and analysts were blinded to the treatment protocol. Study subjects were 10 healthy male volunteers (age range, 23 to 31 years; mean age, 26.6 years). RESULTS: Compared with saline solution, isoproterenol caused a dose-related increase in ejection fraction, (dz/dt)/RZ index, and time-averaged mean velocity and a dose-related shortening of PEP and QS2c. The responses are congruent with an enhancement of cardiac systolic performance caused by a positive inotropic stimulation and an afterload reduction ("inodilatory" response). The effects on systolic time intervals reached statistical significance (alpha = 0.05) at the first isoproterenol dose step, the effects on the impedance cardiography and the Doppler echoaortography variables reached statistical significance at the second dose step, and the effects on the two-dimensional echocardiography reached statistical significance at the third dose step. CONCLUSIONS: All methods allowed to detect isoproterenol-related changes. Systolic time intervals were the most sensitive, followed by impedance cardiography, ACVF--dual-beam Doppler echoaortography, and two-dimensional echocardiography. The practical convenience and high sensitivity of the systolic time intervals makes them suitable to evaluate investigational systolic inodilatory changes in humans.     

Application of impedance cardiography in critical care medicine

In spite of good correlations between cardiac output measurements by impedance and established invasive procedures (dye- and thermo-dilution) reported by numerous authors it is doubtful uptil now whether calculations of stroke volume according to the formula of Kubicek et al. (1974) can provide absolutely reliable results. The origin of the dz/dt curve and influencing factors of impedance wave have to be cleared up prior to the total acception of impedance cardiography as a reliable method for determining non-invasive stroke volume. This is true in spite of the agreement of all authors we know, that the reproducibility of the impedance cardiography values is as good as in dye or thermo-dilution measurements. However, for patient monitoring it is sometimes more important to assess the relative changes in stroke volume than to measure its absolute value. For long-term non-invasive monitoring of myocardial contractility in critically ill patients or after pharmacological interventions impedance cardiography may be recommended. Besides systolic time intervals, such as pre-ejection time and ventricular ejection time, three more reliable parameters can be derived from the first derivate of impedance wave. Impedance plethysmography has been shown as a reliable method to diagnose deep vein thrombosis and good correlations between impedance and strain-gauge plethysmography and phlebographic findings are reported. In addition fluid volume changes in the leg, venous capacity, venous outflow and arterial inflow may be determined by impedance plethysmography in a simple way. There is no doubt that alterations in the fluid content of biological tissue may measured by impedance technique. However, correlations between changes in the transthoracic impedance and fluid content of the thorax can be quantified only in a single subject which serves as its own control. Overall standardization is not possible. The reason for interindividual differences in the thoracic impedance at a given reduction of body water are due to anatomical differences, intrapulmonary air volume and pressure, location of the electrodes, electrical conductivity of the tissue and, above all, due to the position of the body. Therefore if transthoracic impedance is determined sequentially measurements must be performed with special attention to the position of the body to get reproducible results. Rapid infusion of colloids or blood transfusion may decrease transthoracic impedance due to intravascular volume expansion even at a net fluid lost during forced furosemide-induced diuresis or extracorporal hemodialysis.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of a histamine H2-receptor antagonist, famotidine, on gastric secretion in healthy subjects

The effects of 20 mg of famotidine or placebo on secretion of gastric juice and gastric acid were studied in ten healthy subjects in a randomized, crossover study. Gastric juice was aspirated and collected at hourly intervals for 24 hours after oral administration, and acid output was calculated based on gastric juice output and acid concentration. Secretion of gastric juice and acid output were lower after famotidine was administered than after placebo; over the 12-hour post-administration period, the hourly acid concentrations were significantly lower after famotidine than after placebo. During the 12 hours after famotidine or placebo, gastric juice output was 180.7 +/- 32.1 ml (mean +/- SE) in the placebo group and 64.7 +/- 9.1 ml in the famotidine group (P less than 0.01); acid concentrations were 49.3 +/- 3.8 mmol/L in the placebo group and 9.6 +/- 3.1 mmol/L in the famotidine group (P less than 0.01); acid output was 8.89 +/- 1.59 mmol in the placebo group and 0.55 +/- 0.17 mmol in the famotidine group (P less than 0.01). These results support the effectiveness of a 12 hour or possibly a 24-hour dosing interval for famotidine.     

Non-invasive assessment of cardiac output in children.

BACKGROUND: Stroke distance, the systolic velocity integral of aortic blood flow, is a linear analogue of stroke volume; its product with heart rate is minute distance, analogous to cardiac output. OBJECTIVE: To investigate the feasibility of assessing cardiac output in children with a simple non-invasive Doppler ultrasound technique, and to determine the normal range of values. METHODS: Peak aortic blood velocity, stroke distance, and minute distance were measured through the suprasternal window in 166 children (mean age 9.6 years, range 2-14) using a portable non-imaging Doppler ultrasound instrument. RESULTS: The technique was well tolerated by all the children participating. Mean peak aortic blood velocity was 138 cm/s and was independent of age. Mean stroke distance was 31.8 cm and showed a small but significant increase with age; mean minute distance was 2490 cm and fell with age, as did heart rate. CONCLUSIONS: Suprasternal Doppler ultrasound measurement of stroke distance is a convenient, well tolerated, non-invasive technique for the assessment of cardiac output in children. The normal range of values during childhood has been established. The technique has great potential for assessing hypovolaemia in children.     

Haemodynamic effects of depot zinc protamine glucagon in heart failure (author's transl)]

In contrast to intravenously-administered crystallene glucagon, which acts for 20 minutes only, the depot form, zinc protamine glucagon, shows a prolonged haemodynamic action. Fourteen patients with pre-existing heart failure received a single dose of 20 mg Zn protamine glucagon intramuscularly. The stroke volume and cardiac output were increased, whereas the mean and end-diastolic pulmonary pressure were decreased, indicating a positive inotropic action of the administered drug. Heart rate and mean arterial pressure remained almost unchanged. The haemodynamic changes started 60 minutes after intramuscular administration of the drug, reached a maximum effect at 3 hours and started to decrease after the fourth hour. Zn protamine glucagon can, therefore, be considered a beneficial drug in the treatment of digitalis-resistant heart failure on the basis of its long duration of action and easy route of administration.     

The effect of steady-state increases in systemic arterial pressure on the duration of left ventricular ejection time

The effect of steady-state increases in systemic arterial pressure on the duration of left ventricular ejection time was studied in 11 normal male subjects. Methoxamine, a pressor amine of predominantly vasoconstrictor activity but lacking significant inotropic effect, was administered intravenously resulting in an average increase in mean arterial pressure of 27 mm Hg. Heart rate was held constant by high right atrial pacing, and there was no significant change in cardiac output. During methoxamine infusion, when stroke volume, heart rate, and inotropic state were held constant, left ventricular ejection time increased as mean arterial pressure increased. There was a highly significant correlation between the increase in mean systolic blood pressure and the prolongation of left ventricular ejection time (r = 0.870). In one subject, an increase in mean systolic pressure of 75 mm Hg prolonged left ventricular ejection time 55 msec, producing paradoxical splitting of the second heart sound. The prolongation of left ventricular ejection time during infusion was not blocked by the prior intravenous administration of atropine sulfate or propranolol hydrochloride, thus ruling out both vagal inhibition of the left ventricle and reflex withdrawal of sympathetic tone as its cause. In three subjects, left ventricular end diastolic pressure was measured and found to be significantly increased. This finding suggests that the normal left ventricle maintains a constant stroke volume in the presence of an increased pressure load by the Frank Starling mechanism. This study concludes that arterial pressure must be included as a prime determinant of left ventricular ejection time along with stroke volume, heart rate, and inotropic state in intact man.     

Assessment of beat to beat changes in cardiac output during the Valsalva manoeuvre using electrical bioimpedance cardiography

Beat to beat changes in cardiac output during standardized Valsalva's manoeuvres were recorded using electrical bioimpedance cardiography in 13 normal subjects. Cardiac output increased by 12 +/- 5% after 1 s of straining solely because of an increase in heart rate. Subsequently, cardiac stroke volume and cardiac output fell during the strain to lows of -40 +/- 6% and -21 +/- 3% respectively at 15 s. There was a sustained increased in cardiac output (maximum +17 +/- 4%) in the late post strain period. The mean coefficient of variation in impedance measurements of cardiac output was 6.8% during all parts of Valsalva's manoeuvre, with no single value exceeding 10%.     

三维彩色多普勒超声心动图评价心脏收缩功能的实验研究—无创测量心脏每搏动能的准确性

评价三维彩色多普勒超声心动图测量心脏每搏动能的可行性。方法实验动物选用犬10只,体重10.5～20.5kg。左前胸进行彩色多普勒超声心动图探查,并利用TomTec三维彩色多普勒成像工作站进行三维图像获取和重建,利用三维彩色多普勒重建图像测量收缩期通过主动脉瓣瓣口的血流速度(V)和血流量(Q);根据V和Q计算出心脏每搏动能EK＝1/2     

No effect of famotidine on cardiac performance by noninvasive hemodynamic measurements

In a randomized, double-blind, placebo-controlled, two-way crossover study, 12 healthy volunteers were treated once daily for 1 week each with 40 mg famotidine or placebo. Stroke index, cardiac index, preejection period, left ventricular ejection time, and carotid and femoral blood flow were measured noninvasively with Doppler ultrasonography. No significant changes in these hemodynamic parameters were observed when differences between baseline and each time point after administration of famotidine were compared with corresponding differences after placebo. The findings of this study are in accord with those of other studies that have failed to demonstrate a negative inotropic effect after administration of H2-antagonists.     

A Selective, Non-lschemic, Non-Pharmacological Left Ventricular Failure Animal Model

Selective left ventricular failure was induced in 13 acute anesthetized, closed chest dogs ranging in weight from 18–26 kg. Failure was induced by passing a single, high intensity pulse of current from a defibrillator connected to a left ventricular catheter electrode and a left chest electrode. The intensity of the myocardial damaging shock was related to the predicted current required for transventricular defibrillation, based on heart weight. Thermodilution cardiac output, left ventricular pressure, impedance stroke volume, the cardiac electrogram, and lead IIECG were recorded, along with the pressure impedance (volume) loop, which is a measure of stroke work. It was found that the cardiac output decreased with increasing current intensity. Immediately following the high current shock, cardiac output, and stroke work decreased. In some animals, with a moderate intensity shock, there was a transient increase in cardiac output, followed by a decrease. In the five animals that were monitored continuously for 4 hours, the average percent reduction in cardiac output at this time was 42.5% for an average current overdose ratio of 5.39. The energy setting on the defibrillator to obtain this range of reduction in cardiac output was 175–350 joules. The method described herein is easily applied to the closed chest animal and will allow evaluation af the pumping capabilities of cardiac augmentation techniques, such as dynamic cardiomyoplasty and the skeletal muscle ventricle.     

Cardiac output determined by ultrasound-Doppler: clinical applications

Summary. A non-invasive method for cardiac output determination (COD) based on ultrasound-Doppler technique was evaluated in patients with cardiac disease at rest and during exercise, including patients with heart transplants. The aortic blood flow velocity was measured with pulsed Doppler technique from the jugulum, placing the sample volume just above the aortic valve, and the area from a parasternal 2-D echocardiographic measurement of the aortic annulus diameter assuming a circular area. Cardiac output was calculated as the product of the systolic velocity integral, the aortic annulus area and the heart rate. A high correlation was found between this method and a simultaneously performed invasive cardiac output (COF) and stroke volume (SVF) determination by the direct Fick method (COD = 0.3+0.9 x COF, r= 0.96, SD_res= 0.5 1 min^-1 and SVD = 3.9+0.92 × SVF, r= 0.94, SD_res= 6.9 ml). However, looking just at the systolic velocity integral compared to stroke index determined with the Fick method we found a low correlation, especially in patients with heart transplants. We conclude that cardiac output can reliably be measured non-invasively with this method—also in patients with heart transplants. The systolic velocity integral alone can be used for assessing changes in stroke volume but for absolute values of stroke volume and stroke index flow area should also be determined.