Increase In Left Ventricular Output Research Articles

Myocardial function in late preterm infants during the transitional period: comprehensive appraisal with deformation mechanics and non-invasive cardiac output monitoring.

There is a paucity of functional data on mid-to-late preterm infants between 30+0 and 34+6 weeks gestation. We aimed to characterise transitional cardiopulmonary and haemodynamic changes during the first 48 hours in asymptomatic mid-to-late preterm infants. Forty-five healthy preterm newborns (mean ± standard deviation) gestation of 32.7 ± 1.2 weeks) underwent echocardiography on Days 1 and 2. Ventricular mechanics were assessed by speckle tracking-derived deformation, rotational mechanics, tissue Doppler imaging, and right ventricle-focused measures (tricuspid annular plane systolic excursion, fractional area change). Continuous haemodynamics were assessed using the NICOM™ system to obtain left ventricular output, stroke volume, heart rate, and total peripheral resistance by non-invasive cardiac output monitoring. Right ventricular function increased (all measures p < 0.005) with mostly stable left ventricular performance between Day 1 and Day 2. NICOM-derived left ventricular output [mean 34%, 95% confidence interval 21-47%] and stroke volume [29%, 16-42%] increased with no change in heart rate [5%, -2 to 12%]. There was a rise in mean blood pressure [11%, 1-21%], but a decline in total peripheral resistance [-14%, -25 to -3%]. Left ventricular mechanics remained persevered in mid-to-late premature infants, but right ventricular function increased. Non-invasive cardiac output monitoring is feasible in preterm infants with an increase in left ventricular output driven by an improvement in stroke volume during the transitional period.

Maternal hyperoxygenation for the human fetus: should studies be curtailed?

Congenital hypoplasia of left heart structures in fetuses frequently progresses with gestational development. Interference with cerebral development is common in these fetuses. Chronic maternal hyperoxygenation (MHO) has been recommended to increase left ventricular size and to limit cerebral damage. The effects of MHO on cerebral blood flow and metabolism have been studied in normal fetuses and fetuses with left heart hypoplasia. Maternal hyperoxygenation increases fetal pulmonary blood flow. This is associated with reduction of foramen ovale flow, thus limiting the increase in left ventricular output. Modest increase in the size of left heart structures has been reported, but in another study, no significant improvement occurred. In sheep fetuses increased oxygenation results in marked reduction of cerebral blood flow, with no change in oxygen delivery or consumption by the brain, but significant reduction in cerebral glucose delivery and consumption. In one study of fetuses with left heart hypoplasia, chronic MHO was associated with decrease in head size. The effectiveness of MHO in improving left ventricular development is controversial. MHO is, however, associated with reduction of cerebral blood flow and possible interference with cerebral development. In view of this it is recommended that all studies of chronic maternal hyperoxygenation be curtailed.

2: Renal Haemodynamics and Acute Kidney Injury During Therapeutic Hypothermia and Re-Warming in Neonates with Hypoxic-Ischaemic Encephalopathy

Birth asphyxia is associated with acute kidney injury (AKI); severity may correspond with degree of hypoxia. Previous work by our group demonstrated lower cardiac output in neonates undergoing therapeutic hypothermia (TH). The relevance of these changes to AKI remains unknown. To describe longitudinal renal haemodynamic changes during TH and re-warming (RW) and evaluate their relationship with cardiac output in neonates with and without AKI. Prospective observational study of 18 term and near-term infants with hypoxic-ischaemic encephalopathy (HIE) who received TH. Doppler ultrasound was used to assess left ventricular output (LVO) and renal artery (RA) blood flow parameters – systolic and end-diastolic velocity (Vs and Vd), and resistive index (RI) during cooling [TH I (24 h) and II (72 h)] and post re-warming [RW I (12 h) and II (>24 h)]. AKI was defined as anuria/oliguria (100 mmol/L; or anuria/oliguria for >36 h; or any serum creatinine >125 mmol/L; or rising serum creatinine postnatally. There was no difference in baseline demographics or severity of HIE between neonates with (n=8) vs without (n=10) AKI. All 18 infants survived till discharge. Neonates who developed AKI had higher RA RI 24 h after TH was initiated [Table 1]. There was a temporal increase in LVO in both groups (P<0.01, two-way ANOVA), without intergroup difference. Neonates in the non-AKI group only showed an increase in RI (P=0.01) and a trend towards increase in RA Vs over time (P=0.05). Early changes in end-diastolic flow (EDF) were seen in both groups, which normalized over time. Elevated RA RI at 24 h after introduction of TH is associated with and predicts AKI. The fall in cardiac output and renal systolic flow after TH is not associated with AKI.

The effect of milrinone on right and left ventricular function when used as a rescue therapy for term infants with pulmonary hypertension.

Milrinone may be an appropriate adjuvant therapy for infants with persistent pulmonary hypertension of the newborn. We aimed to describe the effect of milrinone administration on right and left ventricular function in infants with persistent pulmonary hypertension not responding to inhaled nitric oxide after 4 hours of administration. This is a retrospective review of infants born after or at 34 weeks of gestation with persistent pulmonary hypertension who received milrinone treatment. The primary endpoint was the effect of milrinone on myocardial performance and haemodynamics, including right and left ventricular outputs, tissue Doppler velocities, right ventricle and septal strain, and strain rate. Secondary endpoints examined included duration of inhaled nitric oxide and oxygen support. A total of 17 infants with a mean (standard deviation) gestation and birth weight of 39.8 (2.0) weeks and 3.45 (0.39) kilograms, respectively, were included in the study. The first echocardiogram was performed 15 hours after the commencement of nitric oxide inhalation. Milrinone treatment was started at a median time of 1 hour after the echocardiogram and was associated with an increase in left ventricular output (p=0.04), right ventricular output (p=0.004), right ventricle strain (p=0.01) and strain rate (p=0.002), and left ventricle s` (p<0.001) and a` (p=0.02) waves. There was a reduction in nitric oxide dose and oxygen requirement over the subsequent 72 hours (all p<0.05). The use of milrinone as an adjunct to nitric oxide is worth further exploration, with preliminary evidence suggesting an improvement in both oxygenation and myocardial performance in this group of infants.

Clinical pharmacology of dobutamine and dopamine in preterm neonates

Dobutamine is a β1 selective stimulant. β Receptor agonists are used to stimulate the rate and the force of cardiac contraction. The chronotropic effect is useful for the treatment of arrhythmias whereas the inotropic effect is useful to augment the myocardial contractility. Dobutamine is about four times as potent as dopamine in stimulating myocardial contractility in low concentrations and increases left ventricular output in the hypotensive preterm infants. Dobutamine possesses a center of asymmetry. The (-)-isomer of dobutamine is a potent agonist of α1 receptors and is capable of causing marked pressor responses. In contrast, (+)-dobutamine is a potent α1 receptor antagonist which can block the effects of (-)-dobutamine. Dobutamine is relatively cardioselective at dosages used in clinical practice with its main action being on β1-adrenergic receptors. Dobutamine and dopamine undergo intense metabolism in neonates where they are conjugated with sulphate and O-methylated. The clearance and the half-life of dobutamine and dopamine range over one order of magnitude in neonates. Dopamine is widely used to increase blood pressure, cardiac output, urine output and peripheral perfusion in neonates with shock and cardiac failure. Dopamine is more effective than dobutamine in the short-term treatment of systemic hypotension in preterm infants. High doses of dopamine cause vasoconstriction, increase systemic vascular resistance, and, eventually, decrease renal blood flow. Treatment with dobutamine is associated with a significantly greater increase in left ventricular output in the single study reporting that outcome. Dobutamine is indicated for the short-term treatment of cardiac decompensation.

PH Effects on Cardiac Function and Systemic Vascular Resistance in Preterm Infants

To investigate the effect of pH on cardiac function and systemic vascular resistance (SVR) in preterm infants. In this prospective observational study, we evaluated hemodynamically stable, ≤ 30 weeks' gestation preterm infants during the first 2 postnatal weeks. Cardiac function was assessed by echocardiography at the time of arterial blood draw for clinically indicated blood gas analysis. Data were separately analyzed for the transitional (days 1-3) and post-transitional (days 4-14) periods. We evaluated 147 pairs of arterial blood gases and echocardiograms in 29 preterm neonates (gestational age = 26.2 ± 1.5 weeks). Arterial pH ranged from 7.02-7.46. There was no linear relationship between pH and shortening fraction or stress-velocity index in transitional or post-transitional periods. We found a weak negative linear relationship between pH and left ventricular output and a positive linear relationship between pH and SVR only during the post-transitional period. These relationships were maintained after adjustment for the degree of base deficit. Arterial CO2 had effects similar to pH on myocardial function. Unlike adults, myocardial contractility remains relatively unaffected by acidosis even at pH values close to 7.00 in hemodynamically stable preterm neonates during the first 2 postnatal weeks. However, as in adults, worsening acidosis in preterm neonates after the immediate transitional period is associated with a decrease in SVR along with an increase in left ventricular output. Thus, although myocardial contractility remains unaffected in preterm neonates during the first 2 postnatal weeks, the vascular response to acidosis undergoes a relatively rapid postnatal maturational process.

The fetal circulation and essential organs—a new twist to an old tale

The fetal circulation and essential organs—a new twist to an old tale

Diagnosis and Treatment of Low Systemic Blood Flow in Preterm Infants

After completing this article, readers should be able to: 1. Delineate the short- and long-term adverse outcomes associated with low systemic blood flow. 2. Explain why it is not appropriate to use blood pressure and population criteria for hypotension to determine which infants who have low systemic blood flow need cardiovascular support. 3. Describe the various hemodynamic states in neonates and the assessment that is useful in allowing discrimination between these states. 4. Characterize the hemodynamic effects of dopamine and dobutamine in neonates. 5. Delineate the most common characteristics of infants who fail to maintain superior vena cava flows despite the use of inotropes. Low systemic blood flow (SBF) commonly occurs in preterm infants who have respiratory distress in the first postnatal day. Such low flows are strongly associated with neonatal morbidity, including peri/intraventricular hemorrhage (P/IVH), developmental impairments, and mortality. Diagnosing which infants have low SBF is problematic; use of blood pressure (BP) and signs of poor tissue perfusion, including capillary refill times (CRT), poor renal function, and acidosis, results in substantial delays in the initiation of cardiovascular support and a proportion of affected infants missing treatment. The traditional approach to cardiovascular support of the preterm infant has been to identify infants who have hypotension and to use agents, particularly dopamine, titrated to improve BP. However, this strategy may not be the best for improving SBF, and it is yet to be demonstrated that this approach improves neonatal outcomes. This review focuses on identifying which infants have low SBF or organ blood flow, discusses mechanisms for low flows, and examines potential therapies for treating or preventing low flow. Cardiovascular compromise occurs in a number of clinical scenarios in preterm infants, but it is most common on the first postnatal day. Not all infants who have low SBF will be suspected based on clinical signs, including …

Postnatal adaptation of cerebral blood flow using near infrared spectroscopy in extremely preterm infants undergoing high‐frequency oscillatory ventilation

To determine cerebral blood flow using near infrared spectroscopy in extremely preterm infants undergoing high-frequency oscillatory ventilation during the first three days of life. Low cerebral blood flow has been associated with both intra-ventricular haemorrhage and periventricular leucomalacia. It is well established that cerebral blood flow increases over the first three days of life in extremely preterm infants who are conventionally ventilated with intermittent positive pressure ventilation. However, there is no information about cerebral blood flow in preterm babies undergoing high-frequency oscillatory ventilation. In addition, there are concerns that high-frequency oscillatory ventilation may be associated with an increased incidence of intra-ventricular haemorrhage in premature infants. Thirteen appropriately grown, preterm infants of less than 28 wk gestation who were admitted to the neonatal unit at University College Hospital, London were studied using near infrared spectroscopy. Left ventricular output and right ventricular output were assessed echocardiographically. Extremely preterm infants undergoing high-frequency oscillatory ventilation have remarkably low cerebral blood flow in the first 12 h of life, median 6.7 (range 4.4-11) mls. 100 g(-1) min(-1) followed by an increase over the subsequent three days. Left ventricular output also increased over the first three days of life, whereas right ventricular output showed no clear relationship with time. Despite low cerebral blood flow only one infant had evidence of major cerebral injury. Cerebral blood flow is extremely low in this group of preterm babies. Despite this extremely low cerebral blood flow, the clinical outcome is good. There was an increase in cerebral blood flow and a corresponding increase in left ventricular output over the first few days of life.

The treatment of patent ductus arteriosus in preterm infants. A review and overview of randomized trials

Patent ductus arteriosus (PDA) is a common problem in very preterm infants. It results in a significant left-to-right shunt and an increase in left ventricular output. Pulmonary compliance can be reduced. Systemic effects result from the diastolic steal and retrograde diastolic blood flow. Randomized controlled trials of PDA closure fall into three groups: (i) prophylactic treatment in the first 24h, (ii) pre-symptomatic treatment on ultrasound evidence of a PDA or the first clinical signs and (iii) treatment when it becomes haemodynamically significant. Prophylactic treatment with indomethacin reduces the incidence of intraventricular haemorrhage. All the trials have a decreased need to treat a subsequent PDA in the treatment group. There are no other improvements in outcome, without any change in mortality, bronchopulmonary dysplasia, necrotizing enterocolitis or retinopathy of prematurity. Clinical decisions on the treatment of the ductus should be individualized and based on the gestation of the baby, the respiratory condition and the size of the ductal shunt.

Relationship between heart rate, left ventricular output, and stroke volume in preterm infants during fluctuations in heart rate.

The relationship between changes in heart rate, left ventricular output, and left ventricular stroke volume was studied in 18 preterm infants, with mean gestational age 29 wk (range 26-33 wk) and mean postnatal age 10 d (range 1-21 d). To yield left ventricular output, the blood flow velocity in the ascending aorta was measured by range-gated Doppler technique and multiplied by the aortic cross-sectional area measured by cross-sectional and M-mode echocardiography. Stroke volume was calculated by dividing left ventricular output by heart rate. The individual mean left ventricular output correlated poorly with heart rate (r2 = 0.17), and, accordingly, there was a closer relationship between stroke volume and left ventricular output. In only four of the 18 infants was a significant correlation between heart rate changes and left ventricular output found. Substantial changes in stroke volume were seen in most infants, and in 13 of the 18 infants the changes exceeded 25%. These variations in stroke volume were closely related to left ventricular output. In 15 of the 18 infants, the maximum heart rate change was associated with a stroke volume change in the opposite direction. The group average of the maximum heart rate increase in each individual, 24 bpm (18%), corresponded to a decrease in stroke volume of 0.15 mL.kg-1 (9%) (p less than 0.05) and an increase in left ventricular output of 22.7 mL.min-1.kg-1 (9%) (p less than 0.05). A reciprocal relationship was seen between afterload and left ventricular output.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute fetal ductal occlusion in lambs

To assess fetal right ventricular and hemodynamic responses to acute occlusion of the ductus arteriosus, the pulmonary pressure, right and left ventricular output, and right ventricular dimensions of five fetal lambs were measured with simultaneous echocardiographic monitoring. Ductal occlusion resulted in a rise in pulmonary arterial pressure, a decrease in right ventricular output of 68%, an increase in left ventricular output of 18%, and a fall in combined cardiac output of 34%. The right ventricular systolic dimension increased, and the shortening fraction decreased from 0.41 to 0.14. Tricuspid regurgitation started within two heartbeats after ductal occlusion and resolved as soon as the occlusion was released. Acute fetal ductal occlusion imposes a marked increase in the right ventricular afterload, resulting in reversible triscuspid regurgitation.

Changes in left ventricular output from fetal to early neonatal life

Using pulsed Doppler and two-dimensionally directed M-mode echocardiographic techniques, we measured left ventricular (LV) output, stroke volume, heart rate, LV end-diastolic dimension (LVEDD), LV end-systolic dimension, and LV percent fractional shortening (%FS) in 34 normal term infants 12 to 24 hours before parturition and thereafter serially 1, 24, and 96 hours after birth. Stroke volume was calculated as the product of the aortic flow velocity integral and aortic valve area. There was a twofold increase in LV output 1 hour after birth (fetal 170 +/- 46 ml/min/kg vs 1 hour 327 +/- 66 ml/min/kg; p less than 0.01) which was associated with significant increases in stroke volume, %FS, and LVEDD (stroke volume 1.21 +/- 0.33 ml/kg vs 2.25 +/- 0.37 ml/kg; %FS 34.3% +/- 5.8% vs 37.7% +/- 5.4%; LVEDD 15.4 +/- 1.1 mm vs 17.7 +/- 1.4 mm). Heart rate did not change 1 hour after birth. During the subsequent hours after birth, LV output decreased significantly to a value of 245 +/- 56 ml/min/kg (p less than 0.01) at 24 hours, which did not change 96 hours after birth. There were significant declines in stroke volume, LVEDD, and heart rate 24 hours after birth (stroke volume 2.02 +/- 0.42 ml/kg; LVEDD 17.0 +/- 1.1 mm; heart rate 121 +/- 11 beats/min). The %FS remained unchanged within the first 96 hours of age. These results indicate that the major regulator of LV output immediately after birth is stroke volume and not heart rate. The increase in stroke volume is related to an increase in LV size and LV myocardial contractility. Our data provide a useful basis for the interpretation of abnormal LV function in the early neonatal period.

Cardiovascular Effects of Caffeine Therapy in Preterm Infants

Theophylline therapy increases left ventricular output in preterm infants by a combination of positive inotropic and chronotropic effects. The cardiovascular effects of caffeine were evaluated in 20 clinically stable preterm infants. Ten infants received intravenous caffeine citrate with a loading dose of 20 mg/kg and a maintenance dose of 5 mg/kg every 24 hours, and 10 infants were control subjects. Left ventricular output, stroke volume, and heart rate were measured by using a combination of two-dimensional and pulsed Doppler echocardiography and mean arterial blood pressure by oscillometry (Dinamap, Critikon, Division of McNeil Laboratories, Irvine, Calif) before the start and on days 1, 2, 3, and 7 of caffeine therapy and 7 days after discontinuation of therapy. Compared with controls, left ventricular output and stroke volume were significantly increased on days 1 to 7 of caffeine therapy. Caffeine led to an increase in the mean arterial blood pressure on the first 3 days of therapy, but the heart rate did not change. These data indicated that caffeine administration leads to a significant increase in left ventricular output in preterm infants and that this inotropic effect is accompanied by a pressor effect.

Hemodynamic Changes in a Term Newborn Piglet Model of Patent Ductus Arteriosus

Patent ductus arteriosus (PDA) is a common form of congenital heart disease in full-term infants. To investigate the morbidities associated with a left to right PDA shunt, we produced a PDA in six full-term newborn piglets (less than 36 hours old) by bathing the ductus arteriosus with prostaglandin E (PGE) and infiltrating it with formalin. In five age-matched piglets, the ductus arteriosus was ligated to serve as controls. Microsphere determinations of left ventricular output (LVO) and regional blood flow (Q) were made on three consecutive days. We produced left to right shunts of 36 to 47% (mean) in the experimental piglets. The experimental piglets had a 22 to 36% increase in LVO with a one- to twofold reduction in percentage of LVO to the kidneys and carcass (p less than 0.05). Although percentage of LVO to the gastrointestinal tract was reduced (p less than 0.05), no reduction of absolute Q to the gastrointestinal tract was observed. Brain and heart Q were similar in both groups. We conclude that significant hemodynamic changes result from left to right shunting in the full-term newborn piglet with PDA. These hemodynamic changes, such as reduction in renal blood flow, are relevant information that will help explain the morbidities observed in infants with a hemodynamically significant PDA with a left to right shunt.

Pulsed Doppler measurement of left ventricular output as early predictor of symptomatic patent ductus arteriosus in very preterm infants.

High left ventricular output (LVO) values are associated with symptomatic left-to-right ductal shunting in preterm infants. However, LVO data prior to the occurrence of symptomatic patent ductus arteriosus (SPDA) are lacking. To determine whether serial measurements could predict a SPDA, we measured LVO from day 1 until day 10 with pulsed Doppler echocardiography in 25 preterm infants with birth weights of less than 1,250 g and hematocrits of more than 0.40. Eleven infants never developed patent ductus arteriosus symptoms and had LVO values within the normal range (190-310 ml/min/kg) with only minimal daily variations. The remaining 14 infants developed SPDA which required treatment with indomethacin, ductal ligation, or fluid restriction on days 2-5. From day 1 until day 5 their mean LVO values were significantly higher compared to the group without left-to-right ductal shunt and this increase was secondary to higher stroke volume values. An increase in LVO of more than 60 ml/min/kg consistently preceded SPDA by at least 24 h. Serial measurements of LVO using a single-pulsed Doppler approach can be used for early prediction of SPDA.

92 CARDIOPULMONARY EFFECTS OF A PATENT DUCTUS ARTERIOSUS

The premature newborn's response to increasing degrees of Lt→Rt PDA shunt is unknown. In 14 fetal lambs at 128d gestation (term 147d), we infiltrated the ductus with formalin and placed a mechanical occluder about it so that its patency could be regulated. 3d later the lamb was delivered, given sheep surfactant, paralyzed and mechanically ventilated. Microsphere measurements of left ventricular output (LVO) and its distribution were made prior to and 1.25 h after a change in ductus patency. Twenty four changes from open→closed or closed→open were assigned randomly from 3 to 7 h after delivery. Lambs with ductus shunts < 50% LVO (38%) had a significant increase in LVO (167 vs. 268 ml/kg/min:closed vs. open) with no change in effective systemic blood flow or BP. There was a significant increase in coronary flow but no change in flow to the kidneys, GI tract, brain, or carcass (ml/100 gm/min). Although lambs with shunts > 50% LVO (65%) had a significant increase in LVO (164 vs. 300 ml/kg/min), there was a significant decrease in effective systemic blood flow and BP. There were significant decreases in flow to the kidneys, GI tract, brain and carcass. Coronary flow was unchanged but there was a decrease in subendocardial flow. There was no change in HR or pulmonary compliance at either degree of shunt. Preterm lambs are capable of compensating for moderate degrees of PDA shunt by increasing preload and increasing stroke volume; highe degrees of shunt significantly decrease organ blood flow.

The effects of changes in inspired oxygen concentration on the experimental production of pulmonary edema in the dog with chronic left ventricular overload.

A twofold increase in left ventricular output was achieved by suturing a Telfon graft between the aorta and left atrium in dogs. Three weeks after surgery the animals were anesthetized and found to have left ventricular end-diastolic pressures averaging 36 mmHg with markedly elevated right ventricular systolic pressures (RVSP). Oxygen breathing resulted in a decrease in left ventricular pressures, RVSP, and arterial pressure in those animals which survived hypoxia. Fifty percent of the shunted dogs subsequently developed fatal pulmonary edema when allowed to breathe 10% oxygen in nitrogen. These animals showed no change in left ventricular function or pulmonary artery pressure (RVSP) in response to pure oxygen administration. It is suggested that there is a gradation of hemodynamic response to pure oxygen depending on the severity of left ventricular overload. In the severest case the 'fixing' of pulmonary hypertension may be due to neurohumoral mechanisms. The subsequent development of pulmonary edema in these animals with hypoxia either involves a change in permeability or a redistribution of hydrostatic pressure within the pulmonary vasculature.

HYPOTENSIVE AND VASODILATOR ACTIONS OF SK&amp;F 24260, A NEW DIHYDROPYRIDINE DERIVATIVE

1 The blood pressure of conscious normotensive, Goldblatt-hypertensive and genetic-hypertensive rats and normotensive dogs was lowered by SK&F 24260 (1,4-dihydro-2,6-dimethyl-4-(2-trifluormethylphenyl)-3,5-pyridinedicarboxylic acid diethyl ester).2 Tachycardia always accompanied the hypotension. In rats propranolol abolished the tachycardia but in dogs there was only a small reduction in the heart rate response.3 In conscious dogs there was an increase in left ventricular output and a marked fall in total peripheral resistance.4 SK&F 24260 dilated resistance vessels in rat hindquarters. Dilatation was caused by doses of SK&F 24260 some 50 times smaller than those of hydrallazine.5 In preparations of cat skeletal muscle and intestinal vascular beds SK&F 24260 selectively dilated resistance vessels in preference to capacitance vessels and resembled hydrallazine rather than papaverine which has no such selectivity.6 Pre-capillary sphincter vessels were also dilated by SK&F 24260. Changes in fluid equilibrium caused by SK&F 24260 were consistent with selective dilatation of resistance vessels.