Reduction In Pulmonary Blood Flow Research Articles

Lung ultrasound score parallels trends in systemic haemodynamics after PDA ligation: a case series.

A sustained fall in LUS after PDA ligation was identified, which most likely reflects reduction in pulmonary blood flow and interstitial edema. Changes in LUS paralleled changes in LVO, suggesting physiologic linkage. These data suggest that LU may be a useful tool to guide monitoring the biologic nature of pulmonary disease after PDA ligation. • Sustained exposure to a high-volume left-to-right patent ductus arteriosus (PDA) shunt is associated with interstitial pulmonary oedema. • In the most immature patients, cardiorespiratory deterioration, named post-ligation cardiac syndrome, presents 6-12 h post-operatively. • An early and sustained fall in lung ultrasound score (LUS) after PDA ligation most likely reflects reduction in pulmonary blood flow and interstitial oedema. LUS changes parallel changes in left ventricular output, suggesting linkage. • LU is a promising adjunctive tool in the post-operative management of PDA ligation.

The effect of distal pulmonary obstruction or elevated atrial pressures on pulmonary flow and pulmonary vascular disease: a mathematical flow circuit analogy model-based analysis.

Late presentation of large left to right shunts is a major problem in developing countries and evaluating the operability is a challenge during preoperative evaluation. The factors that determine the development and progression of the pulmonary vascular disease are still largely unknown, though there is evidence to show that increased pulmonary flow is the main contributing factor. We have found cases of operability despite late presentation of ventricular septal defect (VSD). In some of these cases, the reason for operability may lie in associations. We herein attempt to provide a mathematical explanation for their operability. To assess the effect of different levels of obstruction and elevated ventricular end-diastolic pressure on pulmonary flow. Mathematical flow analogy models were constructed and analysed based on Ohm's law and the laws governing flow in series and parallel flow circuits. Any narrowing in the pulmonary circulation produces a reduction in pulmonary blood flow and the pulmonary to systemic blood flow ratio, irrespective of its position. This increases the systemic flow and blood pressure if the ventricular performance remains constant. A rise in ventricular end-diastolic pressure reduces the total cardiac output, pulmonary flow and systemic blood flow with a preserved pulmonary to systemic flow ratio. The absolute reduction in pulmonary flow will exceed the absolute reduction in systemic flow, with its ratio being in proportion to the ratio of systemic to pulmonary vascular resistance. However, a higher pressure will be transmitted distally in these settings. These mechanisms of flow reduction may prevent irreversible pulmonary vascular disease. Distal pulmonary obstruction or elevated ventricular end-diastolic pressure can reduce pulmonary blood flow and may prevent irreversible pulmonary vascular disease. Clinical studies in this direction are recommended for validation.

Neonatal cardiopulmonary transition in an ovine model of congenital diaphragmatic hernia

ObjectiveInfants with a congenital diaphragmatic hernia (CDH) are at high risk of developing pulmonary hypertension after birth, but little is known of their physiological transition at birth. We aimed to...

Functional Improvement and Regression of Medial Hypertrophy in the Remodeled Pulmonary Artery after Correction of Systemic Left-to-Right Shunt.

The presence of systemic left-to-right shunt and increased pulmonary blood flow can result in right heart failure and pulmonary arteriopathy. Correction of left-to-right shunt has been shown to improve cardiac function and physical performance. However, the cardiopulmonary remodeling processes following cessation of left-to-right shunt have yet to be reported. In this experimental study, excessive pulmonary flow was restored through ligation of the aortocaval fistula in rats with flow-induced pulmonary hypertension. The cardiopulmonary morphometric functions were assessed, and phenotypic switching of pulmonary vascular smooth muscle cells (VSMC) was determined. Ligation of aortocaval fistula significantly attenuated pulmonary blood flow and right ventricular mass, and potentiated the isometric contraction of pulmonary artery. Inflammatory cytokines IL-1β and IL-6 were reduced in the lung after ligation. Reduction of pulmonary blood flow restored the expressions of smooth muscle myosin heavy chain and α-smooth muscle actin in pulmonary artery, indicating the switching of VSMCs to the contractile phenotype. Our study demonstrated that normalization of pulmonary blood flow in flow-induced pulmonary hypertension reverses the remodeling in the right ventricle and pulmonary artery. The remodeling process of flow-induced pulmonary hypertension is functionally and morphometrically reversible by inducing transdifferentiation of pulmonary VSMC to contractile phenotypes and modulation of tissue inflammatory cytokines.

Pulmonary vasospasm in systemic sclerosis: noninvasive techniques for detection.

In a subgroup of patients with systemic sclerosis (SSc), vasospasm affecting the pulmonary circulation may contribute to worsening respiratory symptoms, including dyspnea. Noninvasive assessment of pulmonary blood flow (PBF), utilizing inert-gas rebreathing (IGR) and dual-energy computed-tomography pulmonary angiography (DE-CTPA), may be useful for identifying pulmonary vasospasm. Thirty-one participants (22 SSc patients and 9 healthy volunteers) underwent PBF assessment with IGR and DE-CTPA at baseline and after provocation with a cold-air inhalation challenge (CACh). Before the study investigations, participants were assigned to subgroups: group A included SSc patients who reported increased breathlessness after exposure to cold air (n = 11), group B included SSc patients without cold-air sensitivity (n = 11), and group C patients included the healthy volunteers. Median change in PBF from baseline was compared between groups A, B, and C after CACh. Compared with groups B and C, in group A there was a significant decline in median PBF from baseline at 10 minutes (-10%; range: -52.2% to 4.0%; P < 0.01), 20 minutes (-17.4%; -27.9% to 0.0%; P < 0.01), and 30 minutes (-8.5%; -34.4% to 2.0%; P < 0.01) after CACh. There was no significant difference in median PBF change between groups B or C at any time point and no change in pulmonary perfusion on DE-CTPA. Reduction in pulmonary blood flow following CACh suggests that pulmonary vasospasm may be present in a subgroup of patients with SSc and may contribute to worsening dyspnea on exposure to cold.

Congenital Heart Defects: Early Surgical Correction and Heart Failure? Brief History

The first successful cardiac surgical procedure was performed by Robert Gross in 1938 in Boston. A 7 year-old patient underwent ligation of the ductus arteriosus [1]. In 1945, Crawford carried out the first correction for coarctation of the aorta in Sweden [2,3].Technological development that allowed for the introduction of extracorporeal circulation devices led to the beginning of open heart surgery. The first heart surgery using an extracorporeal circulation device was performed by Kirklin. Extracorporeal circulation devices had multiple negative effects on the physiology of the infant and the newborn, so that at the beginning of pediatric heart surgery, the delay of surgical correction was preferred. Initially, these devices required an extremely high priming volume that exposed the child to exanguinotransfusion. Inflammation mediators [4] caused excessive vascular permeability and tissue edema, all the more so as the age of the child was younger at the time of surgery.At first, anesthesia and intensive care for children were practically non-existent, and diagnosis was made using invasive techniques (cardiac catheterization), which most frequently generated complications. Surgical kits did not contain microsurgical instruments required for working on the fragile heart tissue of the newborn and infant. Thus, a number of palliative procedures were developed, in order to help the patient survive until the performance of surgical correction.The pathophysiology of congenital heart defects includes 3 main categories. There may be a volume load in which one or both ventricles must pump more blood than normal. This usually happens because of an increased pulmonary blood flow, as a result of a septal defect. There may be a pressure load of one or both ventricles. This can be the result of an obstruction at the outlet of the ventricle. The third possibility is cyanosis that can be secondary to a reduction in pulmonary blood flow or inadequate mixing between the two parallel circulations.Systemic pulmonary shunt reduces cyanosis by increasing pulmonary blood flow. Although from a conceptual point of view it is an easy procedure, systemic pulmonary shunt can be a challenge for the surgeon. Assessing the size of the shunt depending on the weight of the child is most important. The size of the shunt must take into consideration the subsequent development of the child, but it must not be too large in order to avoid postoperative ventricular volume overload. The Blalock-Taussig shunt was introduced by the surgeon Alfred Blalock and the cardiologist Helen Taussig [5]. The original BT shunt directly connected the sectioned subclavian artery to the right pulmonary artery and was of an adequate size to substitute for the pulmonary blood flow deficiency. In addition, this shunt had growth potential and thus, it could pathophysiologically support the patient for many years. The Waterston shunt is an anastomosis between the ascending aorta and the right pulmonary artery [6]. This shunt has the disadvantage to produce excessive pulmonary blood flow and a distortion of pulmonary arteries.The Potts shunt consists of the anastomosis of the descending aorta and the left pulmonary artery. This shunt has all the disadvantages of the Waterston shunt and in addition, it is extremely difficult to remove at the time of surgical correction.The modified BT shunt, which consists of the anastomosis of the arterial brachiocephalic trunk with the right pulmonary artery, by means of a vascular prosthesis, was introduced by deLeval [7]. This shunt was initially performed in the left subclavian artery and the left pulmonary artery through thoracotomy. It has the following advantages: it does not cause pulmonary artery distortion and pulmonary overload.High blood pressure and flow in pulmonary circulation, most frequently due to a septal defect, may lead in time to pulmonary hypertension and pulmonary vascular disease. In 1950, Muller and Dammann introduced pulmonary artery banding in order to reduce high blood pressure and flow in pulmonary circulation [8]. Like in the case of shunts, banding does not allow for an increase in diameter, so that in time, with the child’s growth, this becomes increasingly tight. It can also result in pulmonary artery distortion, so that correction and the removal of banding should be initiated as soon as possible after the regression of pulmonary hypertension.In 1950, Blalock and Hanlon introduced surgical atrial septectomy for children with transposition of the great vessels with insufficient mixing [9]. Nowadays, this septectomy is an interventional procedure performed through the rupture of the septum with a balloon catheter, according to the procedure described by Rashkind [10,11].

Does pharmacotherapy influence the inflammatory responses during cardiopulmonary bypass in children?

Cardiopulmonary bypass (CPB) induces a systemic inflammatory response syndrome (SIRS) by factors such as contact of the blood with the foreign surface of the extracorporeal circuit, hypothermia, reduction of pulmonary blood flow during CPB and endotoxemia. SIRS is maintained in the postoperative phase, co-occurring with a counter anti-inflammatory response syndrome. Research on the effects of drugs administered before the surgery, especially in the induction phase of anesthesia, as well as drugs used during extracorporeal circulation, has revealed that they greatly influence these postoperative inflammatory responses. A better understanding of these processes may not only improve postoperative recovery but also enable tailor-made pharmacotherapy, with both health and economic benefits. In this review, we describe the pathophysiology of SIRS and counter anti-inflammatory response syndrome in the light of CPB in children and the influence of drugs used on these syndromes.

Acute COPD exacerbation: 3 T MRI evaluation of pulmonary regional perfusion – Preliminary experience

To compare pulmonary perfusion parameters by means of dynamic perfusion magnetic resonance in patients affected by chronic obstructive pulmonary disease (COPD), during and after acute exacerbation. Fifteen patients were successfully evaluated with perfusional MRI during an acute exacerbation of COPD and upon clinical stabilization. Inclusion criteria were a PaCO2 > 45 mmHg and respiratory acidosis (arterial blood pH < 7.35) at admittance. In the acute phase a reduction of pulmonary blood flow (PBF) and pulmonary blood volume (PBV), and a significant prolonging of the mean transit time (MTT) and time to peak (TTP) were observed in all patients. In the stabilization phase a significant increase of PBF and PBV and a significant reduction of MTT and TTP were observed in 6 patients; no significant variations were observed in the other 9 patients. 3D time-resolved contrast-enhanced MRI allows quantitative evaluation of pulmonary regional perfusion in patients affected by COPD, identifying patients in which perfusion defects are resolved in the clinical-stabilization phase. This technique might allow the identification of patients in whom vasospasm may be the main responsible of pulmonary hypoperfusion during acute COPD exacerbation, with potential advantages on the clinical management of these patients.

Automated measurement of blood flow velocity and direction and hemoglobin oxygen saturation in the rat lung using intravital microscopy.

Intravital microscopy of the pulmonary microcirculation in research animals is of great scientific interest for its utility in identifying regional changes in pulmonary microcirculatory blood flow. Although feasibility studies have been reported, the pulmonary window can be further refined into a practical tool for pharmaceutical research and drug development. We have established a method to visualize and quantify dynamic changes in three key features of lung function: microvascular red blood cell velocity, flow direction, and hemoglobin saturation. These physiological parameters were measured in an acute closed-chest pulmonary window, which allows real-time images to be captured by fluorescence and multispectral absorption microscopy; images were subsequently quantified using computerized analysis. We validated the model by quantifying changes in microcirculatory blood flow and hemoglobin saturation in two ways: 1) after changes in inspired oxygen content and 2) after pharmacological reduction of pulmonary blood flow via treatment with the β1 adrenergic receptor blocker metoprolol. This robust and relatively simple system facilitates pulmonary intravital microscopy in laboratory rats for pharmacological and physiological research.

Use of Venovenous Extracorporeal Membrane Oxygenation and an Atrial Septostomy for Pulmonary and Right Ventricular Failure

Right ventricular failure is a major contributor to morbidity and mortality on the lung transplant waiting list. This study was designed to evaluate the effectiveness of an atrial septostomy with venovenous extracorporeal membrane oxygenation (VV-ECMO) as a novel potential bridge to transplantation. Adult sheep (58±3 kg; n=12) underwent a clamshell thoracotomy and instrumentation to measure all relevant pressures and cardiac output (CO). Sheep with tricuspid insufficiency (TI [n=5]) and without tricuspid insufficiency (ØTI [n=7]) were examined. After creation of a 1-cm atrial septal defect and initiating VV-ECMO, the pulmonary artery (PA) was banded to allow progressive reduction of pulmonary blood flow, and data were collected. The CO in both groups remained unchanged from baseline at all pulmonary blood flow conditions. With TI, the CO was 5.1±1.2 L/min at baseline versus 5.1±1.2 L/min with a fully occluded PA (p=0.99). For ØTI, the CO was 4.5±1.4 L/min at baseline versus 4.5±1.2 L/min with no pulmonary blood flow (p=0.99). Furthermore, CO was not affected by the presence of TI (p=0.76). Mean right ventricular pressures were significantly lower in the TI group (TI=20.2±11 mm Hg versus ØTI=29.9±8.9 mm Hg; p<0.00001). Right and left atrial mean arterial pressures were not different between both groups (p>0.5). Lastly, VV-ECMO maintained normal blood gases, with mean O2 saturations of 99% ± 4.1% in both groups. Right to left atrial shunting of oxygenated blood with VV-ECMO is capable of maintaining normal systemic hemodynamics and normal arterial blood gases during high right ventricular afterload dysfunction.

Nitric oxide alterations following acute ductal constriction in the fetal lamb: a role for superoxide

Acute partial compression of the fetal ductus arteriosus (DA) results in an initial abrupt increase in pulmonary blood flow (PBF), which is followed by a significant reduction in PBF to baseline values over the ensuing 2-4 h. We have previously demonstrated that this potent vasoconstricting response is due, in part, to an endothelin-1 (ET-1)-mediated decrease in nitric oxide synthase (NOS) activity. In addition, in vitro data demonstrate that ET-1 increases superoxide levels in pulmonary arterial smooth muscle cells and that oxidative stress alters NOS activity. Therefore, the objectives of this study were to determine the potential role of superoxide in the alterations of hemodynamics and NOS activity following acute ductal constriction in the late-gestation fetal lamb. Eighteen anesthetized near-term fetal lambs were instrumented, and a lung biopsy was performed. After a 48-h recovery, acute constriction of the DA was performed by inflating a vascular occluder. Polyethylene glycol-superoxide dismutase (PEG-SOD; 1,000-1,500 units/kg, n = 7) or PEG-alone (vehicle control group, n = 5) was injected into the pulmonary artery before ductal constriction. Six animals had a sham operation. In PEG-alone-treated lambs, acute ductal constriction rapidly decreased pulmonary vascular resistance (PVR) by 88%. However, by 4 h, PVR returned to preconstriction baseline. This vasoconstriction was associated with an increase in lung superoxide levels (82%), a decrease in total NOS activity (50%), and an increase in P-eNOS-Thr495 (52%) (P < 0.05). PEG-SOD prevented the increase of superoxide after ductal constriction, attenuated the vasoconstriction, preserved NOS activity, and increased P-eNOS Ser1177 (307%, P < 0.05). Sham procedure induced no changes. These data suggest that an acute decrease in NOS activity that is mediated, in part, by increased superoxide levels, and alterations in the phosphorylation status of the endothelial NOS isoform, underlie the pulmonary vascular response to acute ductal constriction.

Effect of cardiopulmonary bypass and aortic clamping on functional residual capacity and ventilation distribution in children

To characterize factors that contribute to lung function impairment after cardiopulmonary bypass, we assessed functional residual capacity and ventilation homogeneity during the perioperative period in children with congenital heart disease who are to undergo surgical repair. Functional residual capacity and lung clearance index were measured by using a sulfur hexafluoride washout technique in 24 children (aged 0-10 years). Measurements of functional residual capacity and ventilation distribution were performed after induction of anesthesia, at different stages of the surgical procedure, and up to 90 minutes after skin closure. Anesthesia was standardized, and ventilator settings, including the fraction of inspired oxygen, were kept constant throughout the study period. Sternotomy and retractor insertion led to a significant increase in functional residual capacity (mean [SD], 24% [14%]), followed by a similar percentage decrease in the resting volume after a significant reduction in pulmonary blood flow during cardiopulmonary bypass with aortic clamping. Although reestablishing pulmonary blood flow increased functional residual capacity (10% [6%]), chest closure led to a decrease in functional residual capacity of 36% (14%) that only slightly improved during the first 90 minutes after surgical intervention. Changes in lung clearance index were affected conversely compared with changes in functional residual capacity at all assessment times. These results confirmed that chest wall condition and pulmonary circulation affect lung volumes and ventilation homogeneity. Although opening of the chest wall improved alveolar recruitment and ventilation homogeneity, blood flow appeared essential for alveolar stability, presumably by exerting a tethering force caused by the filled capillaries on the alveolar walls and therefore contributing to an increase in resting lung volume.

Preoperative pulmonary hemodynamics determines changes in airway and tissue mechanics following surgical repair of congenital heart diseases

To characterize the effect of changes in pulmonary hemodynamics on airway and tissue mechanics, forced oscillatory input impedance of the respiratory system (Zrs) was measured between 0.4-12 Hz in two groups of children undergoing surgical repair of congenital heart disease (CHD) immediately before sternotomy and after chest closure during short apneic intervals. Children with lesions associated with high pulmonary blood flow and/or pressure (septal defects; HP group, n = 12) and children with hypoperfused lungs (tetralogy of Fallot; LP group, n = 12) were included in the study. Airway resistance (Raw), and coefficients of respiratory tissue damping (G) and elastance (H), were estimated from Zrs by model-fitting. A postoperative reduction in pulmonary blood flow and/or pressure in the HP group resulted in an immediate decrease in Raw of 29 +/- 9 (SE)% (P < 0.05), whereas children in the LP group had increases in Raw (24 +/- 17%, no significance) after surgery. No significant change was observed in G in either the HP (6.4 +/- 13%) or LP (27 +/- 23%) group, while H increased in children of both the HP (23 +/- 8%, P < 0.05) and LP (36 +/- 7%, P < 0.01) groups. These results suggest that the preoperative pulmonary hemodynamic condition determines changes in airway mechanics: surgical repair of CHD leads to an improvement in airway function only in children with congested lungs. The adverse effects of surgery, mechanical ventilation, and/or cardiopulmonary bypass may be responsible for the increased stiffness of the respiratory system observed in both groups of children.

Ventilatory Markers During Exercise for Congestive Heart Failure

The exaggerated ventilatory response in patients with heart failure is clearly multifactorial and complex beyond a mere reduction in pulmonary blood flow. Pulmonary dysfunction, including ventilation-perfusion mismatching, decreased lung compliance, restriction, airway obstruction, decreased diffusion capacity, and decreases in respiratory muscle strength and endurance, contributes to an inefficient breathing pattern and increased work of breathing. This is further compounded by the limited ability of the failing heart to meet the metabolic demands of the respiratory muscles, leading to underperfusion and ischemia.Although VO2max has important implications with regard to functional capacity, exercise test personnel must be knowledgeable concerning the clinical physiology of ventilation during exercise in the patient with heart failure. Ventilatory markers, as Arena and coworkers have demonstrated, are most indicative of disease severity and enhance the prognostic value of the test results.

Delayed Desaturation at the Periphery during a Reduction in Pulmonary Blood Flow Is Associated with Systemic Hypotension in Children with Cyanotic Heart Disease

Delayed Desaturation at the Periphery during a Reduction in Pulmonary Blood Flow Is Associated with Systemic Hypotension in Children with Cyanotic Heart Disease

Effects of chronic hypoxia and altered hemodynamics on endothelial nitric oxide synthase expression in the adult rat lung.

Mechanisms that regulate endothelial nitric oxide synthase (eNOS) expression in normal and hypoxic pulmonary circulation are poorly understood. Lung eNOS expression is increased after chronic hypoxic pulmonary hypertension in rats, but whether this increase is due to altered hemodynamics or to hypoxia is unknown. Therefore, to determine the effect of blood flow changes on eNOS expression in the normal pulmonary circulation, and to determine whether the increase in eNOS expression after chronic hypoxia is caused by hemodynamic changes or low oxygen tension, we compared eNOS expression in the left and right lungs of normoxic and chronically hypoxic rats with surgical stenosis of the left pulmonary artery (LPA). LPA stenosis in normoxic rats reduced blood flow to the left lung from 9.8+/-0.9 to 0.8+/-0.4 ml/100 mg/min (sham surgery controls vs. LPA stenosis, P < 0.05), but there was not a significant increase in right lung blood flow. When compared with the right lung, eNOS protein and mRNA content in the left lung was decreased by 32+/-7 and 54+/-13%, respectively (P < 0.05), and right lung eNOS protein content was unchanged. After 3 wk of hypoxia, LPA stenosis reduced blood flow to the left lung from 5.8+/-0.6 to 1.5+/-0.4 ml/100 mg/min, and increased blood flow to the right lung from 5.8+/-0.5 to 10.0+/-1.4 ml/ 100 mg/min (sham surgery controls vs. LPA stenosis, P < 0.05). Despite reduced flow and pressure to the left lung and increased flow and pressure to the right lung, left and right lung eNOS protein and mRNA contents were not different. There were also no differences in lung eNOS protein levels when compared with chronically hypoxic sham surgery controls (P > 0.05). We conclude that reduction of pulmonary blood flow decreases eNOS mRNA and protein expression in normoxic adult rat lungs, and that hypoxia increases eNOS expression independently of changes in hemodynamics. These findings demonstrate that hemodynamic forces maintain eNOS content in the normoxic pulmonary circulation of the adult rat, and suggest that chronic hypoxia increases eNOS expression independently of changes in hemodynamics.

Hemodynamic and Humoral Conditions in Stepwise Reduction of Pulmonary Blood Flow During Venoarterial Bypass in Awake Goats

The effects of reduced pulmonary arterial blood flow (PAF) during venoarterial bypass (VAB) on hemodynamic and humoral conditions were investigated in a series of experiments in a chronic animal model. A biventricular bypass system was installed in five adult goats weighing 49.8 +/- 1.1 kg. Two weeks later, the extracorporeal circuitry was changed to VAB without anesthesia. The PAF was reduced stepwise from 100% to 50, 25, 10, and 0% of total systemic flow. The mean aortic pressure and systemic vascular resistance decreased from 110 +/- 14 to 66 +/- 3 mmHg and from 1,288 +/- 77 to 740 +/- 73 dyne.sec/cm5, respectively, in proportion to the decrease in PAF from 100 to 0%. The prostaglandin E2 concentration increased from 1.5 +/- 0.6 to 8.8 +/- 0.6 pg/ml following the decrease in PAF from 100 to 0%. The renin-angiotensin system increased in proportion to the decrease in PAF. In contrast, the epinephrine and norepinephrine concentrations (60 +/- 10 and 227 +/- 80 pg/ml, respectively, at 100% PAF) did not change appreciably even at 10% PAF, but were markedly elevated to 335 +/- 117 and 2,088 +/- 1,503 pg/ml at 0% PAF. The antidiuretic hormone level similarly changed. In conclusion, decrease in PAF during VAB exerts significant effects on hemodynamics in a proportional manner and on vasoactive humoral factors in a diverse manner.

ACUTE HAEMODYNAMIC EFFECT OF SODIUM BICARBONATE IN CANINE RESPIRATORY OR METABOLIC ACIDOSIS

This study has examined the acute haemodynamic effects of 7% sodium bicarbonate solution 1 mmol kg-1 (1.2 ml kg-1) administered into the right atrium over 5 s in 25 anaesthetized dogs allocated randomly to respiratory (arterial pH (pHa) 7.18, PaCO2 10.1 kPa (n = 8)) or metabolic acidosis (pHa 7.27, base deficit -9.0 mmol litre-1 (n = 7)) or metabolic neutrality (pHa 7.39 (n = 10)). The pHa and PaCO2 in the respiratory acidosis group differed from those in the two other groups (P < 0.01). One dog with respiratory acidosis developed progressive circulatory depression and cardiac arrest 6 min after injection of sodium bicarbonate. In the remaining seven dogs with respiratory acidosis, administration of sodium bicarbonate 1 mmol kg-1 produced transient decreases in mean arterial pressure, right ventricular dP/dt, and pulmonary blood flow, with increased right atrial pressure, followed by a gradual return of these variables to the baseline. The magnitude of reduction in pulmonary blood flow after sodium bicarbonate was greater in dogs with respiratory acidosis (P < 0.05) compared with the changes in the two other groups. The haemodynamic depression after bicarbonate was pronounced during respiratory acidosis and this may be attributed to a smaller pHa in the respiratory acidosis group, further reduction of intracellular pH, or both. It is suggested that when metabolic acidosis is corrected, bicarbonate should be administered with caution in the presence of respiratory acidosis.

Factors affecting movement of excitatory substances from pulmonary capillaries to type J receptors of anaesthetized cats.

1. Using phenyl diguanide (PDG) as an excitatory substance, the role of certain factors that could influence the movement of such substances across the pulmonary capillaries to the J receptors was studied in cats anaesthetized with sodium pentobarbitone. This was aided by using a new method for estimating continuously in vivo the concentration (C) of PDG in the blood of the pulmonary artery. 2. Reduction of pulmonary blood flow by partial occlusion of the inferior vena cava enhanced the responses of the J receptors to PDG significantly in twelve out of thirteen trials. These effects, which occurred at a time when pulmonary capillary pressure (PCP) had fallen, could be related to the increase in the estimated mean C of PDG over the first 3 s or to the C t (concentration x time) area to 50% of peak C. The responses bore no relation to peak C or rate of rise of C. 3. The responses of the receptors to PDG increased significantly after three out of eight injections of PDG while the PCP was raised by partial occlusion of the mitral orifice; reduced responses were recorded after two injections. These results, showing relatively much weaker stimulation by PDG in spite of the enhanced level of J receptor excitability produced by the raised PCP itself, suggest that movement of PDG out of the capillaries to the J receptors must be influenced primarily by forces governing diffusion, not filtration. 4. In addition to C of PDG there appear to be other factors that influence the responses of the receptors to PDG.

Partial lung bypass reduces pulmonary edema induced by kerosene aspiration in dogs

Kerosene aspiration causes severe pulmonary capillary leak in dogs that is reduced by lowering pulmonary vascular pressures with plasmapheresis. In this study, we tested the possibility that partial lung bypass (PLB) with a veno-arterial extracorporeal circuit previously used for membrane oxygenation (ECMO) would decrease kerosene-induced pulmonary edema. Twelve dogs having a stable pulmonary capillary wedge pressure (Ppw) of 10 tort received 0.25 mL/kg of kerosene into each mainstem bronchus. After 1 hour, the dogs were separated into two equal groups: a control group (C) in which Ppw was maintained at 10 torr until 5 hours after injury, and a PLB group in which PLB reduced Ppw to 5 torr, associated with a 25% reduction in pulmonary blood flow. The blood was pumped back into the distal aorta with blood gas tensions matched by ECMO to the values exiting the lungs as sampled in the left ventricle. In the C group, extravascular thermal volume (ETV) increased from 8.7 ± 4.7 mL/kg to 32.9 ± 26.2 mL/kg between 1 and 5 hours postinjury ( P < .05). In the PLB group, ETV increased less between 1 hour (11.7 ± 3.3 mL/kg) and 5 hours (16.5 ± 6.8 mL/kg). Therefore, the values at 5 hours were different between the groups ( P < .05). The wet lung weight to body weight ratios of lungs excised at 5 hours were also much less ( P < .05) in PLB (20 ± 5 mL/kg) than in group C (40 ± 18 mL/kg). We conclude that PLB reduces edema formation during a pulmonary capillary leak state by reducing pulmonary vascular pressures and/or flows. This supports a therapeutic approach to kerosene pneumonitis that seeks the lowest Ppw compatible with adequate cardiac output and oxygen transport, and suggests an additional benefit of the ECMO circuit in pulmonary vascular leak over and above supporting inadequate lung oxygen exchange at reduced FIO 2 and oxygen toxicity.