Left Pulmonary Artery Blood Flow Research Articles

Inhaled nitric oxide improves gas exchange and lowers pulmonary vascular resistance in severe experimental hyaline membrane disease.

To determine the effects of inhaled nitric oxide (NO) on pulmonary hemodynamics and gas exchange in experimental hyaline membrane disease (HMD), we studied 16 premature lambs (0.78 term) in two separate protocols. All animals were treated with exogenous surfactant before mechanical ventilation. In protocol 1, we measured the acute response to brief treatment with inhaled NO (20 ppm, 20 min) after 2 h of mechanical ventilation with fraction of inspired oxygen of 1.00 (n = 5). After 2 h, brief NO treatment lowered pulmonary vascular resistance from 0.26 +/- 0.05 to 0.16 +/- 0.03 mm Hg.(mL/min)-1 (p < 0.01) and improved gas exchange (arterial PO2, 44 +/- 9 mm Hg baseline to 168 +/- 45 mm Hg NO, p < 0.01; arterial PCO2 45 +/- 5 mm Hg baseline to 35 +/- 4 mm Hg NO, p < 0.05). In protocol 2, to determine whether early and continuous treatment with inhaled NO could sustain improvement in gas exchange and pulmonary hemodynamics in severe HMD, we compared the physiologic effects of ventilation with high inspired oxygen concentrations for 3 h with NO (20 ppm, n = 6) and without NO (controls, n = 5). After 3 h, the NO treatment group had sustained reduction in pulmonary vascular resistance (0.10 +/- 0.01 mm Hg.(mL/min)-1 NO versus 0.25 +/- 0.04 mm Hg.(mL/min)-1 control, p < 0.05), increased left pulmonary artery blood flow (204 +/- 24 mL/min NO versus 109 +/- 15 mL/min control, p < 0.05), and increased arterial PO2 (114 +/- 27 mm Hg NO versus 36 +/- 11 mm Hg control, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Inhaled Nitric Oxide in the Management of a Premature Newborn With Severe Respiratory Distress and Pulmonary Hypertension

Persistent pulmonary hypertension of the newborn (PPHN) is a clinical syndrome, characterized by sustained elevation of pulmonary vascular resistance (PVR) with right-to-left shunting across the ductus arteriosus and/or foramen ovale, causing severe hypoxemia. Although generally associated with diseases of term or near-term newborns, including group B streptococcal sepsis, PPHN has been described in preterm neonates as well. Recent echocardiographic studies have demonstrated increased PVR in preterm neonates with hyaline membrane disease (HMD), which correlated with disease severity and mortality. Severe HMD was associated with lower aortopulmonary pressure gradients and left pulmonary artery blood flow velocities during the first 72 hours after birth, suggesting that high PVR contributes to the mortality of respiratory distress of premature neonates.

Effects of oxygen and exogenous L-arginine on EDRF activity in fetal pulmonary circulation.

To determine whether L-arginine, the precursor of endothelium-derived relaxing factor (EDRF), increases vasodilator activity in the fetal pulmonary circulation, we studied its effects on basal pulmonary vascular tone and on pulmonary vasodilation stimulated by oxygen and acetylcholine (ACh) in chronically prepared late-gestation fetal lambs. L-Arginine infusion (30-300 mg over 10 min) into the left pulmonary artery (LPA) increased blood flow (18-57%) without changing pulmonary artery pressure. To determine whether O2-induced vasodilation involves EDRF and is augmented by L-arginine treatment, we infused L-arginine or NG-nitro-L-arginine (L-NNA), an inhibitor of EDRF synthesis, while increasing fetal PO2 6 Torr by delivering 100% O2 to the ewe for 120 min. In controls, LPA blood flow progressively increased from 106 +/- 13 ml/min (baseline) to 257 +/- 34 ml/min (peak) at 40 min of increased PO2 (P < 0.05, baseline vs. peak) but steadily returned toward baseline during the next hour. Treatment with L-NNA markedly attenuated O2-induced pulmonary vasodilation (P < 0.05 vs. control). L-Arginine infusion did not augment or sustain the O2-induced vasodilator response. We also examined whether L-arginine could sustain pulmonary vasodilation to ACh, another EDRF-dependent stimulus, and found that the EDRF substrate neither potentiated nor sustained the ACh response. We conclude that: in the fetal lung 1) exogenous L-arginine is a fetal pulmonary vasodilator, 2) increased PO2 augments EDRF activity in the fetal lung, and 3) supplemental L-arginine does not sustain either O2- or ACh-induced vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of ATP-sensitive potassium channels in ovine fetal pulmonary vascular tone.

To study the potential role of ATP-sensitive K+ (K+ATP) channels in fetal pulmonary vasoregulation, we studied the effect of a K+ATP channel agonist, lemakalim, and antagonist, glibenclamide, on the fetal pulmonary circulation in nine chronically instrumented late-gestation fetal lambs. Left pulmonary artery (LPA) blood flow was measured with an electromagnetic flow transducer. Brief (10 min) infusions of lemakalim at 3, 10, and 30 micrograms/min into the LPA produced dose-dependent increases in flow from 68 +/- 7 to 96 +/- 11, 160 +/- 15, and 204 +/- 34 ml/min, respectively. The duration of pulmonary vasodilation after the 10-min infusions of lemakalim at 3, 10, and 30 micrograms/min was 20 +/- 3, 47 +/- 10, and 55 +/- 15 min, respectively. Pulmonary blood pressure and flow did not change with intrapulmonary infusion of glibenclamide (10 mg), a K+ATP channel antagonist. Lemakalim-induced pulmonary vasodilation was not affected by nitro-L-arginine (10 mg), a competitive inhibitor of endothelium-dependent relaxing factor, but was blocked by glibenclamide. Prolonged (2 h) intrapulmonary infusions of lemakalim (2-6 micrograms/min) increased pulmonary blood flow by 137%. The increase in pulmonary blood flow was sustained throughout the infusion. Systemic and pulmonary arterial pressures decreased during prolonged infusion. We conclude that K+ATP channels are present in the fetal pulmonary circulation, but do not participate in the regulation of basal pulmonary vascular tone. K+ATP channel activation produces sustained vasodilation that is not mediated by endothelium-derived relaxing factor. We speculate that birth-related stimuli activate K+ATP channels to enhance the pulmonary vasodilation that occurs at birth.

Hemodynamic effects of exogenous nitric oxide in ovine transitional pulmonary circulation.

To determine the hemodynamic effects of exogenous nitric oxide (NO) on the immature pulmonary circulation, we studied the response to NO inhalation in 19 mechanically ventilated late-gestation ovine fetuses in three separate protocols. In protocol 1, we examined the relative effects of 1) mechanical ventilation while maintaining fetal arterial O2 tension (PaO2) constant [fractional inspired O2 concentration (FIO2) less than 0.10)], 2) NO inhalation [5-20 parts per million (ppm)] at fetal PaO2, and 3) high FIO2 (1.00) (n = 7). NO increased left pulmonary artery blood flow (Qlpa) in a dose-dependent fashion, from 254 +/- 62 (baseline) to 398 +/- 49 ml/min with 20 ppm NO (P less than 0.001). The response of Qlpa to a FIO2 equal to 1.00 was not different from NO alone. Systemic arterial pressure was not affected by NO. In protocol 2 we studied the effects of prolonged NO inhalation (2 h, 20 ppm) during mechanical ventilation with low FIO2 (n = 4). NO increased Qlpa from 267 +/- 92 to 468 +/- 75 ml/min at 10 min of NO inhalation (P less than 0.001). The increase in Qlpa was sustained during the entire 2-h study period. In protocol 3 we measured left ventricular output (LVO), systemic vascular resistance (SVR), and ductus arteriosus shunting using radiolabeled microspheres (n = 8) during baseline mechanical ventilation and 20 ppm NO inhalation. LVO and SVR were not significantly different in the two study periods; however, the percentage of LVO that reached the lungs (predominantly left-to-right shunting across the ductus arteriosus) increased from 18 +/- 5 to 43 +/- 4% during NO inhalation.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in PETCO2 and pulmonary blood flow after bronchial occlusion in dogs.

The use of PETCO2 in detecting accidental bronchial intubation was investigated. The PETCO2 was measured in six mongrel dogs after occluding the left mainstem bronchus in three conditions; pentobarbital anaesthesia, 0.8% halothane insufflation together with pentobarbital anaesthesia, and simultaneous left pulmonary artery and bronchial airway occlusion with intravenous pentobarbital anaesthesia. An external flow probe measured left pulmonary artery blood flow. The PETCO2 decreased after bronchial occlusion during pentobarbital (35 +/- 3 vs 30 +/- 5 mmHg) and halothane-pentobarbital (30 +/- 6 vs 25 +/- 6 mmHg) conditions (P less than 0.05). However, within three minutes of bronchial occlusion, the values of PETCO2 had returned to their pre-occlusion values. After five minutes of bronchial occlusion pulmonary artery blood flow in the non-ventilated lung decreased (P less than 0.05) during pentobarbital (770 +/- 533 ml.min-1 vs 575 +/- 306 ml.min-1) and halothane-pentobarbital (495 +/- 127 ml.min-1 vs 387 +/- 178 ml.min-1) conditions. Simultaneous bronchial and pulmonary artery occlusion prevented any changes in PETCO2. It was concluded that accidental one-lung ventilation results in small and transient decreases in PETCO2. A redistribution of blood flow from the non-ventilated to ventilated lung occurs which restores PETCO2 to the original values observed with two-lung ventilation.

Hemodynamic effects of endothelin-1 on ovine fetal pulmonary circulation

To determine the hemodynamic effects of endothelin-1 (ET-1) in the fetal pulmonary circulation, we studied pulmonary vascular responses to brief and prolonged intrapulmonary infusions of the peptide in nine chronically prepared late-gestation fetal sheep. Left pulmonary artery (LPA) blood flow was measured with an electromagnetic flow transducer, and a catheter placed in the LPA allowed ET-1 infusion directly into the left lung. Brief (10-min) infusions of ET-1 (12.5-100 ng/min) increased flow up to 212% of baseline without changing pulmonary artery pressure. With prolonged (120-min) infusion of ET-1 (50 ng/min), flow increased from 69 +/- 8 to 164 +/- 23 ml/min at 10 min (P less than 0.05) but then declined and was not different from baseline at 120 min. The gradient between mean pulmonary artery and aortic pressures did not change, suggesting no constriction of the ductus arteriosus. Systemic (vena caval) infusion of ET-1 (100 ng/min for 30 min) caused systemic and pulmonary hypertension, as mean pulmonary artery pressure increased from 43 +/- 1 to 51 +/- 2 mmHg (P less than 0.05) and remained elevated for 30 min after cessation of the ET-1 infusion. We conclude that intrapulmonary ET-1 is a potent fetal pulmonary vasodilator, but its dilator effect is transient during prolonged infusion. In contrast, systemic infusion causes sustained hypertension, suggesting differential effects of ET-1 on the pulmonary and systemic circulations. These findings demonstrate marked vasoactivity of ET-1 in the fetus, suggesting a potential role in the normal or abnormal transitional circulation.

Time course of hypoxic pulmonary vasoconstriction after endotoxin infusion in unanesthetized sheep

Endotoxin [lipopolysaccharide (LPS)] has been reported to reduce hypoxic pulmonary vasoconstriction and thus increases venous admixture. The time course of this failure of pulmonary blood flow regulation was investigated in six chronically instrumented unanesthetized sheep after infusion of Escherichia coli LPS (1 microgram/kg). The change in left pulmonary arterial blood flow (LPBF, ultrasonic transit time) in response to unilateral lung hypoxia (10 min of N2 alternately to the left and right lungs) was compared before and at various time intervals after the administration of LPS. During baseline conditions, LPBF was 33% of total cardiac output and decreased to 15% when the left lung was ventilated with a hypoxic gas mixture. One hour after endotoxin infusion, LPBF remained at 33% of total cardiac output yet only decreased to 28% during the hypoxic challenge. The response to one-lung hypoxia was still significantly depressed 10 h post-LPS administration. It is concluded that hypoxic pulmonary vasoconstriction is almost completely abolished for a prolonged time period after a small dose of LPS.

Living-related lobar lung transplantation in beagle puppies

Unilateral lung transplantation has provided effective short-term therapy in adults with end-stage lung disease. Rejection continues to be the most common cause of transplant failure. Living-related lung transplantation may decrease the recipient immune response. The purpose of this study is to test the technical and physiological feasibility of living-related lobar lung transplantation from adult beagles into beagle puppies in a chronic model. Twenty purebred adult beagle donors underwent left thoracotomy with harvest of the left lower lobe using cold perfusion of the pulmonary artery and cold immersion. Twenty recipient purebred beagle puppies from the same colony underwent left thoracotomy, left pneumonectomy, and implantation of the donor adult lobe. Anastomoses were performed in sequence: pulmonary vein to left atrium, bronchus, pulmonary artery. Postoperative immunosuppression was with Cyclosporine. Respiratory function of the implanted lobe was evaluated by pulmonary angiography and during balloon occlusion of the right pulmonary artery with arterial blood gases 1 month after transplantation. Ten recipient puppies died of rejection (4), infection (3), or bronchial dehiscence (3) prior to angiography. Seventeen pulmonary angiograms in 10 surviving animals showed normal left pulmonary arterial blood flow (2), diminished left pulmonary arterial flow (5), and occluded left pulmonary artery (3). In two recipients balloon occlusion of the right pulmonary artery was performed and respiratory function was maintained solely by the transplanted lobe for 2 days in one recipient and for 30 minutes at 1 month and 2 months postimplant in a second recipient. Living-related lung transplantation of adult beagle lobes into pneumonectomized beagle puppies is technically feasible. High mortality rates in a chronic model are related to infection and rejection. In survivors the transplanted lobe appears physiologically capable of providing full respiratory support.

Fetal pulmonary vasodilation after exogenous platelet-activating factor

To determine the fetal pulmonary vascular response to platelet-activating factor (PAF), we studied the hemodynamic effects of the infusion of PAF directly into the left pulmonary artery in 21 chronically catheterized fetal lambs. Left pulmonary arterial blood flow (Q) was measured with electromagnetic flow transducers. Ten-minute infusions of low-dose PAF (10-100 ng/min) produced increases in Q from a baseline of 71 +/- 5 to 207 +/- 20 ml/min (P less than 0.001) without changes in pulmonary arterial pressure. Pulmonary vasodilation with PAF was further confirmed through increases in Q with brief (15-s) infusions and increases in the slope of the pressure-flow relationship as assessed by rapid incremental compressions of the ductus arteriosus during PAF infusion. Infusion of Lyso-PAF had no effect on Q or pulmonary arterial pressure. Treatment with CV-3988, a selective PAF receptor antagonist, but not with meclofenamate, atropine, or diphenhydramine and cimetidine blocked the response to PAF infusion and did not affect baseline tone. Systemic infusion of high-dose PAF (300 ng/min) through the fetal inferior vena cava increased pulmonary arterial pressure (46.5 +/- 1.0 to 54.8 +/- 1.9 mmHg, P less than 0.01) and aorta pressure (44.3 +/- 1.0 to 52.7 +/- 2.2 mmHg, P less than 0.01) while also increasing Q. Neither PAF nor CV-3988 changed the gradient between pulmonary arterial and aorta pressures, suggesting that PAF does not affect ductal tone. We conclude that PAF is a potent fetal pulmonary vasodilator and that the effects are not mediated through cyclooxygenase products or by cholinergic or histaminergic effects.

Acute effects of partial compression of ductus arteriosus on fetal pulmonary circulation.

To determine the acute effects of increased pulmonary artery pressure and flow on the fetal pulmonary circulation, we studied the response of pulmonary blood flow and vascular reactivity to partial compression of the ductus arteriosus in 22 chronically prepared late-gestation fetal lambs. An inflatable occluder was placed loosely around the ductus arteriosus for compression. Partial compression of the ductus rapidly increased mean pulmonary artery pressure from 45 +/- 1 to 60 +/- 1 mmHg (mean +/- SE) and left pulmonary artery blood flow from 65 +/- 6 to 151 +/- 11 ml/min at 30 min (P less than 0.001; 12 animals). Despite keeping pulmonary artery pressure constant, pulmonary blood flow steadily declined and by 2 h was not different from base-line values. Pulmonary vascular resistance initially fell during the first 30 min of partial compression but then steadily increased and remained elevated above base-line values for at least 30 min after the release of the occluder (P less than 0.001). The decline of pulmonary vascular resistance during the first 30 min of compression was blunted after treatment with the cyclooxygenase inhibitor, meclofenamate (P less than 0.001; 6 animals). Rapid incremental ductus compressions demonstrated a decrease in the slope of the pressure-flow relationship from 3.30 +/- 0.27 (control) to 1.59 +/- 0.21 ml.min-1.mmHg-1 during the postcompression period (P less than 0.001; 12 animals). The vasodilation response to small increases of fetal PO2 was markedly blunted during the postcompression period (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Failure of postnatal adaptation of the pulmonary circulation after chronic intrauterine pulmonary hypertension in fetal lambs.

To determine the effects of chronic intrauterine pulmonary hypertension on the perinatal pulmonary circulation, we induced chronic elevations of pulmonary artery pressure in 24 late-gestation fetal lambs by maintaining partial compression of the ductus arteriosus with an inflatable vascular occluder. Pulmonary artery pressure was increased from 44 +/- 1 to 62 +/- 3 mmHg for 3-14 d. Although left pulmonary artery blood flow initially increased during acute partial ductus compression, the increase in flow was not sustained during chronic ductus compression despite persistent elevations of pulmonary artery pressure (P less than 0.01). Chronic hypertension decreased the slope of the pressure-flow relationship from 3.4 +/- 0.3 (initial) to 0.9 +/- 0.1 ml/min per mmHg, and blunted the fetal pulmonary vascular response to small increases in PO2 (P less than 0.0001). Pulmonary hypertension for greater than 8 d increased the wall thickness of small pulmonary arteries (P less than 0.001). Compared with controls, hypertensive animals had higher pulmonary artery pressure, lower pulmonary blood flow, and predominant right-to-left ductus shunting after cesarean-section delivery (P less than 0.0001). We conclude that chronic pulmonary hypertension in utero, in the absence of hypoxemia or sustained increases in blood flow, causes abnormal fetal pulmonary vasoreactivity, structural remodeling, and the failure to achieve the normal decline in pulmonary resistance at birth.

Haemodynamic effects of atropine during halothane or isoflurane anaesthesia in infants and small children.

In this study, two-dimensional and pulsed Doppler echocardiography were used to measure cardiovascular changes before and after IV atropine in 31 infants and small children during halothane (n = 15) or isoflurane (n = 16) anaesthesia. Prior to induction of anaesthesia heart rate (HR), mean blood pressure (MBP), and two-dimensional echocardiographic dimensions of the left ventricle and pulmonary artery blood flow velocity were measured by pulsed Doppler echocardiography. Cardiovascular measurements were repeated while anaesthesia was maintained at 1.5 MAC halothane (n = 15) or isoflurane (n = 16). Atropine 0.02 mg.kg-1 IV was then administered and two minutes later, a third set of cardiovascular data was obtained. Heart rate decreased during halothane anaesthesia but did not change significantly during isoflurane anaesthesia. Mean blood pressure, cardiac output (CO) and stroke volume (SV) decreased similarly during 1.5 MAC halothane or isoflurane anaesthesia. Ejection fraction (EF) decreased and left ventricular end-diastolic volume (LVEDV) increased significantly in both groups, but decreases in EF (32 +/- 5 per cent vs 18 +/- 5 per cent) and increases in LVEDV (18 +/- 7 per cent vs 7 +/- 5 per cent) were significantly greater during halothane than during isoflurane anaesthesia. Following atropine, HR increased more in the patients maintained with halothane (31 +/- 6 per cent), than during isoflurane anaesthesia (18 +/- 5 per cent). Atropine increased CO in both groups of patients, but SV and EF remained unchanged. When compared with awake values, HR increased similarly and significantly (18 +/- 4 per cent) following atropine in both groups, and CO returned to control levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Persistent fetal pulmonary hypoperfusion after acute hypoxia

To determine the effects of duration of hypoxia on fetal pulmonary blood flow and vasoreactivity, we studied the response of the fetal pulmonary vascular bed before, during, and after prolonged (2-h) and more brief (30-min) exposures to acute hypoxia in 19 chronically instrumented unanesthetized fetal lambs. Left pulmonary arterial blood flow was measured by an electromagnetic flow transducer. Fetal PO2 was lowered by delivering 10-12% O2 to the ewe. During 2-h periods of hypoxia left pulmonary arterial blood flow decreased, and main pulmonary arterial and pulmonary vascular resistance increased. The increase in pulmonary vascular resistance was sustained throughout the 2-h period of hypoxia. After the return of the ewe to room air breathing, pulmonary vascular resistance remained elevated for at least 1 h despite the rapid correction of hypoxemia and in the absence of acidemia. In contrast, after 30 min of hypoxia, left pulmonary arterial blood flow, pulmonary arterial pressure, and pulmonary vascular resistance returned to base-line values rapidly with the termination of hypoxia. The persistent pulmonary hypoperfusion after 2 h of hypoxia was attenuated by alpha-adrenergic blockade and was characterized by a blunted vasodilatory response to increases in fetal PO2. When fetal PO2 was elevated during the posthypoxia period in the presence of alpha-blockade, pulmonary blood flow still remained unresponsive to increases in fetal PO2. We conclude that 2-h periods of acute hypoxia can decrease fetal pulmonary vasoreactivity, and we speculate that related mechanisms may contribute to the failure of the normal adaptation of the pulmonary circulation at birth.

Time-dependent response of fetal pulmonary blood flow to an increase in fetal oxygen tension

We describe the temporal characteristics of the response of the fetal pulmonary circulation to the vasodilatory stimulus of a sustained increase in fetalP O 2 (5.1 ± 0.7 Torr) in 13 chronically prepared fetal sheep. Left pulmonary arter blood flow was measured by electromagnetic flow transducer. Fetal P O 2 was increased by delivery of 100% oxygen to the ewe and did not significantly change during the 2 h period of oxygen administration. Fetal left pulmonary artery blood flow slowly increased to a peak approximately 2.7 times the control value 40–50 min after the onset of increased P O 2 . It then steadily declined toward baseline over the next hour of increased P O 2 . Maximal pulmonary blood flow in response to the increase in P O 2 increased with gestational age. Pulmonary arterial, aortic, and left atrial blood pressures did not change significantly in the animals in which measurements were made. We conclude that the changes in fetal pulmonary blood flow increased fetal P O 2 depend upon the time after the P O 2 is increased. The adaptation seen during the second hour suggests the existence of mechanisms that tend to keep the fetal pulmonary circulation chronically constricted at any P O 2 likely to be encountered in fetal life.

Perfusion and ventilation radioisotope lung scans in stenosis of the pulmonary arteries and their branches

In ten patients with stenosis of the pulmonary arteries, the relative distribution of right and left pulmonary blood flow was related to the localization of the coarctation by angiography and the degree of stenosis. To evaluate the distribution of pulmonary blood flow, the scintillation lung scan after injection of 131I macroaggregated albumin (MAA) was utilized. Scintillation scanning of the lungs after inhalation of xenon-133 gas was also performed to assess the distribution of ventilation. The relative right to left pulmonary arterial blood flow distribution showed a good correlation with the catheterization pressure gradients and the angiographic findings. The distribution of ventilation was relatively unaffected. In a patient with a precordial murmur that exhibits disproportionate radiation to the axilla and back, an altered distribution of right to left perfusion helps to substantiate the diagnosis of stenosis of the pulmonary arteries. However, if the obstruction is bilateral and of equal degree, the distribution of blood flow may be normal. In patients with isolated acyanotic left to right shunts, the right to left distribution of pulmonary blood flow is apparently unaltered so that a lateral shift from the normal pattern raises the question of stenosis of the pulmonary arteries as an additional lesion. The finding of patchy areas of decreased radioactivity in both perfusion and ventilation lung scans in four of ten patients suggest that there may be a high incidence of emphysema or other lung disease in these patients.