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Analysis of the pulmonary circulation using digital intravenous angiography.

We evaluated pulmonary transit time in dogs and humans using digital intravenous angiography. Digital data were acquired in both the control state and after isoproterenol was administered to alter the inotropic state. When compared with the control value, transit time was shortened with isoproterenol in both dogs and humans. The inter- and intraobserver variabilities were small (less than 4%), as were the variabilities in data obtained from two sequential injections (less than 5%). Digital analysis of the pulmonary circulation time is a simple technique that requires little image manipulation. This information may be obtained during standard digital cardiac studies, and it can assist in the analysis of cardiopulmonary dynamics.

Angiography↗

[Pulmonary circulation and right ventricular function in primary arterial hypertension].

Selected parameters of the pulmonary circulation and right ventricular performance were studied in 30 patients with primary arterial hypertension. Four patients belonged to the WHO class I, four to class I/II, 18 to class II and the remaining four to class III. Patients were eligible, if they were in sinus rhythm, without symptoms of left ventricular failure and diseases that night influence pulmonary pressures, and if drugs affecting cardiac performance could be withdrawn safely for 3 days. Ten healthy subjects served as control group. The mean pulmonary capillary wedge pressure and mean pulmonary artery pressure were similar in both groups. In contrast, the systolic pulmonary arterial pressure exceeded 30 mm Hg in 6 patients. Mean pulmonary vascular resistance was higher in examined patients than in the control group. Right ventricular end-diastolic pressure was above 5 mm Hg in as much as 50% of patients. Mean systolic ejection rate showed a tendency to decrease. The results indicate that part of patients with primary arterial hypertension exhibits disorders in the pulmonary circulation and right ventricular performance.

Adolescent↗

Effect of bradykinin on arteries and veins in systemic and pulmonary circulation.

Bradykinin is a potent vasodilating and natriuretic peptide, which is potentiated by angiotensin-converting enzyme (ACE) inhibitors. In our investigations we studied the effect of bradykinin on systemic and pulmonary circulation as well as on dorsal hand vein tone. The effects of bradykinin on systemic and pulmonary circulation were tested by injection of bradykinin into the right atrium. Parameters were determined for blood pressure, cardiac output, ECG and mean pressure in pulmonary artery. Heart rate, total peripheral resistance, pulmonary vascular resistance, and pulmonary arteriolar resistance were calculated by these measured parameters. The data raised in our investigations showed clearly that bradykinin reduced blood pressure by reducing total peripheral vascular resistance in a dose-dependent manner. In pulmonary circulation bradykinin develops a direct effect. All circulatory actions of bradykinin are not mediated by prostaglandins, since inhibition of prostaglandin synthesis by indomethacin (100-150 mg) was without any effect. ACE inhibition by ramipril (5 mg) or captopril (50 mg) potentiated all effects of bradykinin about 20- to 50-fold, whereas it decreased angiotensin I effects only about four- to fivefold. These results suggest, that endogenous kinins, if they will be similarly potentiated by ACE inhibition like the exogenous bradykinin in our experiments, might play an important role in the blood pressure lowering effect of ACE inhibitors. Dorsal hand vein tone was reduced by bradykinin too, indicating that kinins can lower cardiac preload by increasing venous blood pooling.

Adult↗

The effect of granulomatous pulmonary disease in dogs on the response of the pulmonary circulation to hypoxia.

We studied the effect of diffuse granulomatous pulmonary disease on the reponse of the pulmonary circulation to hypoxia in two series of experiments in intact dogs. First, in animals with unilateral disease, vasoconstriction in the diseased lung was compared to that in the contralateral control lung. Second, in animals with bilateral disease, the vasoconstriction of pulmonary shunt pathways was compared to that of the rest of the pulmonary vasculature. We assessed vasoconstriction in each study by measuring the distribution of pulmonary blood flow between the test and control set of vessels during 21 and 12% oxygen breathing. In the first set of experiments, we measured apportionment of the blood flow between the two lungs by bronchospirometry and the krypton bolus method. In normal dogs, hypoxia did not shift blood flow systematically from one lung to the other. In 10 dogs with unilateral disease, general hypoxia increased the proportion of blood flow to the diseased lung. The mean percent of blood flow to the left lung in eight dogs with disease in that lung rose from 29% during air breathing to 32% (P < 0.001). In the second set of experiments, we measured apportionment of the blood flow between shunt pathways and gas-exchanging pathways by a constant infusion of radio-active krypton and the standard shunt formula. In eight dogs with bilateral disease, hypoxia consistently increased the flow through shunt pathways, from a mean value of 10% of pulmonary blood flow to 14% (P < 0.005).Thus, diffuse granulomatous disease causes a decreased vasoconstrictive response to hypoxia both in diseased, gas-exchanging regions and in shunt pathways. In proliferative interstitial pulmonary disease, generalized hypoxia causes shifts in pulmonary blood flow which do not ameliorate but rather worsen the hypoxemia of systemic arterial blood.

Animals↗

[New approaches to the evaluation of pulmonary circulation in surgical patients with tuberculosis].

Prior to and following surgery, 70 patients were examined for pulmonary tuberculosis who were divided into 2 groups: 1) 27 patients with limited processes (tuberculomas, infiltrating, cavernous tuberculosis in 1-2 segments) and 2) 43 patients with disseminated tuberculosis in 4 lobes or more. A comprehensive examination including studies of pulmonary circulation by radiotracer techniques (scanning, scintigraphy) and an original contactless study of pulmonary circulation (CSPC). There was a correlation between the results obtained by the two methods. The findings indicate a high validity of CSPC6 which makes it possible to recommend it as a screening technique for detection of pulmonary circulatory disorders.

Adult↗

Squamous and trophoblastic cells in the maternal pulmonary circulation identified by invasive hemodynamic monitoring during the peripartum period.

The antemortem diagnosis of amniotic fluid embolism has traditionally relied on the identification of amniotic fluid debris in the maternal circulation by central venous or pulmonary arterial catheterization. Pulmonary artery blood specimens from 14 term pregnant women with severe pregnancy-induced hypertension suggest that squamous or trophoblastic cells may be normally present in the maternal pulmonary circulation during the peripartum period and that their presence is not pathognomonic of clinically significant amniotic fluid embolism.

Amniotic Fluid↗

Mechanism of action of endothelin-1 in the canine pulmonary circulation.

Possible mechanisms of action by which endothelin (ET)-1 has an effect on pulmonary vascular resistance and compliance in the canine pulmonary circulation were investigated in the isolated blood-perfused dog lung by use of vascular occlusion techniques. In the present study, ET-1 (10(-8) M) increased pulmonary vascular resistance and pulmonary capillary pressure by postcapillary vasoconstriction. In addition, ET-1 decreased total vascular compliance and middle-compartment compliance. Pretreatment with the ETA receptor antagonist BQ-610 (10(-7) M) or the protein kinase C inhibitors staurosporine (10(-6) M) and calphostin C (10(-6) M) completely blocked the pressor effect of ET-1. Elimination of extracellular calcium mobilization through voltage-dependent calcium channels by verapamil (10(-5) M) or modulation of G protein signal transduction by pertussis toxin challenge (15 micrograms/kg) had no significant effect on the ET-1-induced pulmonary vascular response. The results of the present study indicate that ET-1 causes pulmonary vasoconstriction in the canine pulmonary circulation through ETA receptor mediation and protein kinase C activation, possibly leading to intracellular calcium release. In contrast, the ET-1-induced pulmonary vascular response does not appear to involve extracellular calcium entry through voltage-dependent calcium-channel activation or pertussis toxin-sensitive G protein-signaling mechanisms.

Animals↗

Optimal pulse pressure of pulmonary circulation under bi-ventricular assist after cardiogenic shock.

In order to evaluate an appropriate pulse pressure of pulmonary circulation during bi-ventricular assist, an experimental study was carried out in swine. The cardiogenic shock model was made by the left anterior descending (LAD) ligation method. When the hear fibrillated due to acute myocardial infarction, both left and right hearts were supported by ventricular assist devices (VADs) for two hours. The left heart assist was operated with a pneumatic pulsatile ventricular assist device (VAD) and the right was operated with a pneumatic VAD or centrifugal pump. According to the pulse pressure of the pulmonary artery these models were divided into three groups: Low-P group (n = 3), in which a low pulse pressure (less than 20 mmHg) was made by VAD, High-P group (n = 5), in which over 20 mmHg of pulse pressure was initiated. NP group (n = 10), in which nonpulsatile assist was done with a centrifugal pump. In pulmonary gas exchange, the Low-P group was superior to the other two groups. The average PaO2 was 214+/-57 mmHg in the Low-p group, and 117+/-41 mmHg and 148+/-81 mmHg in the NP group and High-P group respectively. In the pathological study, a remarkable extension of pulmonary lymphoducts was found in the High-P group. On the other hand, this change was not recognized in other groups. These results suggested that pulmonary microcirculation might deteriorate due to high pulse pressure of the pulmonary artery. We consider the most suitable pulmonary pulse pressure to be around 20 mmHg to maintain normal pulmonary circulation.

Animals↗

[Life achievements of Dr. Dusan Kentera (1925-1999). Aspects of pulmonary circulation].

Dusan Kentera was born on April 2nd 1925 in Stip. He finished high school in Belgrade in 1944, graduated from Medical school, University of Belgrade in 1951, and completed his internal medicine residency in 1957. In 1960 he fulfilled the requirements for the teaching position at the University with a thesis "The use of dilution methods in the study of circulation" and defended his PhD thesis "Hemodynamic characteristics of pulmonary hypertension with increased precapillary resistance" in 1964 at the School of Medicine, University of Belgrade. Dusan Kentera was awarded Swedish government's scholarship in 1958 and spent a year in the laboratory of Gustav Nylin in Stockholm. As a fellow of the National Institutes of Health, he spent 15 months at the Institute of Physiology at The Medical College of Georgia in Augusta, USA, in the Laboratory of William F. Hamilton in 1962 and 1963. As a "visiting scientist" he spent three months in Memorial Research Center, University of Tennessee, in Knoxville, USA, in 1972. In 1980 and again in 1988 Dusan Kentera gave a series of lectures at leading medical research institutions in USA, including Medical School, University of Colorado in Denver, Tulane University Medical School in New Orleans, University of Tennessee Medical School in Memphis, and Texas Research and Rehabilitation Institute in Houston. He spent his career in research at the Institute for Medical Research in Belgrade, where he was appointed Research Fellow in 1952 and became Professor of Research in 1976. Simultaneously, he held teaching position at the Institute of Physiology, School of Dentistry, University of Belgrade, where he was appointed first Instructor in 1952 and full Professor in 1977. In 1964, Dusan Kentera founded the Laboratory for Hemodynamics at the Institute for Medical Research, which he headed until retirement in 1991. He was Assistant Director of the Institute for Medical Research from 1974 until 1978 and Director from 1978 until 1991. He was very much involved in postgraduate teaching at the Medical School, University of Belgrade, where he lectured at the courses in Pulmonary Diseases and Cardiology until death. Numerous Master and PhD theses were completed under his mentorship and in his Laboratory. Many of his students hold at present leading positions in academic institutions worldwide. As a researcher, Dusan Kentera has an outstanding record. He published 120 papers in peer-reviewed journals and authored chapters in several books. Main research interest of Dusan Kentera was related to cardiovascular pathophysiology, particularly in the fields of regulation of pulmonary circulation and pathogenesis of hypoxic pulmonary hypertension, control mechanisms in systemic circulation and pathogenesis of arterial hypertension, contractility of skeletal muscles and myocardium, and control mechanisms in regional circulation. Most impressive, by significance and extent, is his work on the regulation of pulmonary circulation and particularly on the pathogenesis of hypoxic pulmonary hypertension. Most of the research on hypoxic pulmonary hypertension was done on experimental model that he established. As opposed to all other models, which employed hypobaric hypoxia with consequent hypocapnia, in his model experimental animals were exposed to normobaric hypoxia and controlled level of carbon dioxide, thus most closely simulating hypoxic pulmonary hypertension in humans. Using this model, he examined the role of numerous factors in the pathogenesis of acute and chronic hypoxic pulmonary hypertension. His pioneering work in this field is well incorporated into today's understanding of the pathophysiologic mechanisms underlying hypoxic pulmonary hypertension as well as in therapeutic approaches to this disorder Dusan Kentera was always recognized as an outstanding figure in scientific community, yet awards and formal acknowledgments somehow by-passed him. He did share though the October Award of the City of Belgrade for research with his long time friend Dr. Vladislav Varagić in 1976. Dusan Kentera died on his birthday, April 2nd 1999. As an inspired teacher, outstanding scientist, authoritative leader and, above all, as wonderful human being, he set high standards for coming generations. It is on his disciples to carry on.

History, 20th Century↗

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.

Animals↗

Effects of elevated-hematocrit levels on pulmonary circulation in conscious sheep.

We investigated the effects of stepwise hematocrit (Ht) increase on pulmonary circulation in conscious sheep (n = 7). The Ht was increased by an isovolumic exchange transfusion of blood with centrifuged red cells. By increasing the Ht-values, both systemic (PSA) and pulmonary artery pressures (PPA) were increased, with the degree of PPA increment greater than that of PSA. Cardiac output (CO) was slightly decreased by increasing the Ht. Also, A-V difference values of blood oxygen tension were reduced with elevation of the Ht values. The ratio of the right ventricular work rate (RVW) to the left one (LVW), RVW/LVW, was shown to increase remarkably with increased Ht. This increase was considered to be supporting evidence for the right ventricular hypertrophy in high altitude acclimatization. A strong positive correlation was observed between Ht and blood viscosity. It was thus confirmed that Ht effect was greater in pulmonary circulation than in systemic circulation.

Altitude↗

Assessment of an airway-to-pulmonary circulation reflex in cats.

In anesthetized, mechanically ventilated cats we studied the effects on pulmonary circulation of sustained distension or increased air flow stream in an isolated, innervated upper airway segment constituted by the cervical trachea, the larynx and the pharynx. Direct and averaged pulmonary artery pressures and blood flows were measured. In intact cats, sustained distension as well as increased air flow stream in the upper airway segment induced significant, marked increase in pulmonary artery pressure with concomitant decrease in blood flow. No change in heart rate occurred. Section of the superior laryngeal nerves (SLNs), which denervated the tracheolaryngeal segment but not the epipharynx, markedly reduced and delayed the pulmonary vascular response to mechanical stimulation of the upper airways. The response was not found after cervical bivagotomy. The present observations demonstrate the existence of an airway-to-pulmonary circulation reflex, largely mediated through SLNs afferent pathways, the vagus nerve constituting the efferent arm of the reflex.

Air Pressure↗

Developmental effects of endothelin-1 on the pulmonary circulation in sheep.

Endothelin-1 (ET-1) is a polypeptide that has potent hemodynamic effects on the pulmonary circulation. To determine whether there are changes in these effects with increasing postnatal age, we investigated the effects of ET-1 (250 ng/kg) at rest and during pulmonary hypertension in eight lambs (< 1 wk old) and 11 juvenile sheep (6-12 mo old). At rest, ET-1 did not change pulmonary arterial pressure in lambs, but increased pulmonary arterial pressure by 64.0 +/- 37.5% (p < 0.05) in sheep. During pulmonary hypertension, ET-1 produced greater decreases in pulmonary arterial pressure in lambs than in sheep (26.6 +/- 3.4% versus 18.7 +/- 8.3%, p < 0.05). In juvenile sheep, the increase in resting pulmonary arterial pressure produced by ET-1 was inhibited by meclofenamic acid, an inhibitor of prostaglandin synthesis (40.3 +/- 9.9% versus 2.3 +/- 4.7%, p < 0.05); during pulmonary hypertension, the decrease in pulmonary arterial pressure produced by ET-1 was inhibited by N omega-nitro-L-arginine, an inhibitor of endothelium-derived nitric oxide synthesis (21.4 +/- 10.7% versus 8.0 +/- 3.6%, p < 0.05) and by glybenclamide, an ATP-dependent potassium-channel blocker (18.8 +/- 8.4% versus 4.0 +/- 4.4%, p < 0.05). The hemodynamic effects of ET-1 on the pulmonary circulation are dependent on postnatal age. Pulmonary vasoconstriction is mediated by prostaglandin production, and pulmonary vasodilation is mediated, in part, by release of endothelium-derived nitric oxide and activation of ATP-dependent potassium channels.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Pulmonary circulation and thyroid hormone levels in pacemaker patients with and without atrial fibrillation.

The pulmonary haemodynamics and thyroid hormone level were investigated in 21 patients with EKS-222 (VVI) pacemaker, implanted after successful transvenous electrical endocardial His-bundle fulguration (TEF). Triiodthyronine (T3) and thyroxine (T4) were determined by radioimmunoassay, pulmonary circulation parameters were estimated by means of radiocardiography and radionuclide ventriculography using an Omega 500 gamma-camera and a "Scintron MX" computer system. Patients with atrial fibrillation (AF) during VVI pacing had higher level of T3 and T4 and better pulmonary circulation parameters than those with persistent sinus node activity during paced rhythm.

Adolescent↗

Left ventricular overload caused by collateral pulmonary circulation in chronic pneumopathies-myth or reality?

The collateral pulmonary blood flow was measured by the dye dilution method in four patients with chronic obstructive pulmonary disease, in 16 patients with diffuse pulmonary fibrosis, in 15 patients with pulmonary embolism, and in three patients with primary pulmonary hypertension. The authors found that collateral pulmonary circulation was small in the first two groups (0.3 % and 1.7% of the pulmonary blood flow, respectively), absent in primary pulmonary hypertension, and high (14.0% of pulmonary flow) in pulmonary embolism. The magnitude of the bronchopulmonary collateral circulation did not correlate with degree of precapillary pulmonary hypertension, left atrial pressure and left ventricular enddiastolic pressure. It seems that the bronchopulmonary collateral flow does not produce diastolic left ventricular overload in chronic pneumopathies.

Chronic Disease↗

Hypoxia, leukocytes, and the pulmonary circulation.

Data are rapidly accumulating in support of the idea that circulating monocytes and/or mononuclear fibrocytes are recruited to the pulmonary circulation of chronically hypoxic animals and that these cells play an important role in the pulmonary hypertensive process. Hypoxic induction of monocyte chemoattractant protein-1, stromal cell-derived factor-1, vascular endothelial growth factor-A, endothelin-1, and tumor growth factor-beta(1) in pulmonary vessel wall cells, either directly or indirectly via signals from hypoxic lung epithelial cells, may be a critical first step in the recruitment of circulating leukocytes to the pulmonary circulation. In addition, hypoxic stress appears to induce release of increased numbers of monocytic progenitor cells from the bone marrow, and these cells may have upregulated expression of receptors for the chemokines produced by the lung circulation, which thus facilitates their specific recruitment to the pulmonary site. Once present, macrophages/fibrocytes may exert paracrine effects on resident pulmonary vessel wall cells stimulating proliferation, phenotypic modulation, and migration of resident fibroblasts and smooth muscle cells. They may also contribute directly to the remodeling process through increased production of collagen and/or differentiation into myofibroblasts. In addition, they could play a critical role in initiating and/or supporting neovascularization of the pulmonary artery vasa vasorum. The expanded vasa network may then act as a conduit for further delivery of circulating mononuclear cells to the pulmonary arterial wall, creating a feedforward loop of pathological remodeling. Future studies will need to determine the mechanisms that selectively induce leukocyte/fibrocyte recruitment to the lung circulation under hypoxic conditions, their direct role in the remodeling process via production of extracellular matrix and/or differentiation into myofibroblasts, their impact on the phenotype of resident smooth muscle cells and adventitial fibroblasts, and their role in the neovascularization observed in hypoxic pulmonary hypertension.

Animals↗

Ductus arteriosus-dependent pulmonary circulation secondary to cardiac malformations in fetal life.

The objective of this study was to describe the characteristic prenatal findings of a ductus arteriosus-dependent pulmonary circulation secondary to cardiac malformations. B-mode, color and pulsed wave Doppler echocardiography were performed in seven fetuses with severe pulmonary stenosis or atresia. All findings were confirmed postnatally by echocardiography and cardiac catheterization or autopsy. Severe fetal pulmonary stenosis or atresia was characterized by decreased pulmonary valve diameters, frequently with reduced pulmonary artery diameters, increased flow velocities or absent flow across the stenotic pulmonary valve, increased ascending aorta diameters, slightly increased aortic velocities and normal umbilical and middle cerebral artery Doppler wave forms. In all cases, prenatal assessment of neonatal ductus dependence was possible by demonstrating reverse flow across the fetal ductus with peak systolic velocities ranging from 0.9-2.0 m/s and absent diastolic flow. Ductal diameters were slightly decreased, ranging from 2-4 mm. Prenatal detection of a ductus-dependent pulmonary circulation is a strong indication of the presence of severe pulmonary stenosis or atresia. Its diagnosis allows avoidance of maternal administration of drugs with constrictive effects upon the ductus, interdisciplinary planning of perinatal management, early postnatal confirmation of the diagnosis, and early postnatal intervention, in particular administration of prostaglandins to prevent life-threatening ductal closure.

Blood Flow Velocity↗