Immediate cardiopulmonary responses to consecutive pulmonary embolism: a randomized, controlled, experimental study.

BACKGROUND: Acute pulmonary embolism (PE) induces ventilation-perfusion mismatch and hypoxia and increases pulmonary pressure and right ventricular (RV) afterload, entailing potentially fatal RV failure within a short timeframe. Cardiopulmonary factors may respond differently to increased clot burden. We aimed to elucidate immediate cardiopulmonary responses during successive PE episodes in a porcine model. METHODS: This was a randomized, controlled, blinded study of repeated measurements. Twelve pigs were randomly assigned to receive sham procedures or consecutive PEs every 15 min until doubling of mean pulmonary pressure. Cardiopulmonary assessments were conducted at 1, 2, 5, and 13 min after each PE using pressure-volume loops, invasive pressures, and arterial and mixed venous blood gas analyses. ANOVA and mixed-model statistical analyses were applied. RESULTS: Pulmonary pressures increased after the initial PE administration (p < 0.0001), with a higher pulmonary pressure change compared to pressure change observed after the following PEs. Conversely, RV arterial elastance and pulmonary vascular resistance was not increased after the first PE, but after three PEs an increase was observed (p = 0.0103 and p = 0.0015, respectively). RV dilatation occurred following initial PEs, while RV ejection fraction declined after the third PE (p = 0.004). RV coupling exhibited a decreasing trend from the first PE (p = 0.095), despite increased mechanical work (p = 0.003). Ventilatory variables displayed more incremental changes with successive PEs. CONCLUSION: In an experimental model of consecutive PE, RV afterload elevation and dysfunction manifested after the third PE, in contrast to pulmonary pressure that increased after the first PE. Ventilatory variables exhibited a more direct association with clot burden.

Effect of systemic vascular resistance on the agreement between stroke volume by non-invasive pulse wave analysis and Doppler ultrasound in healthy volunteers.

BACKGROUND: Stroke volume can be estimated beat-to-beat and non-invasively by pulse wave analysis (PWA). However, its reliability has been questioned during marked alterations in systemic vascular resistance (SVR). We studied the effect of SVR on the agreement between stroke volume by PWA and Doppler ultrasound during reductions in stroke volume in healthy volunteers. METHODS: In a previous study we simultaneously measured stroke volume by PWA (SVPWA) and suprasternal Doppler ultrasound (SVUS). We exposed 16 healthy volunteers to lower body negative pressure (LBNP) to reduce stroke volume in combination with isometric hand grip to elevate SVR. LBNP was increased by 20 mmHg every 6 minutes from 0 to 80 mmHg, or until hemodynamic decompensation. The agreement between SVPWA and SVUS was examined using Bland-Altman analysis with mixed regression. Within-subject limits of agreement (LOA) was calculated from the residual standard deviation. SVRUS was calculated from SVUS. We allowed for a sloped bias line by introducing the mean of the methods and SVRUS as explanatory variables to examine whether the agreement was dependent on the magnitude of stroke volume and SVRUS. RESULTS: Bias ± limits of agreement (LOA) was 27.0 ± 30.1 mL. The within-subject LOA was ±11.1 mL. The within-subject percentage error was 14.6%. The difference between methods decreased with higher means of the methods (-0.15 mL/mL, confidence interval (CI): -0.19 to -0.11, P<0.001). The difference between methods increased with higher SVRUS (0.60 mL/mmHg × min × L-1, 95% CI: 0.48 to 0.72, P<0.001). CONCLUSION: PWA overestimated stroke volume compared to Doppler ultrasound during reductions in stroke volume and elevated SVR in healthy volunteers. The agreement between SVPWA and SVUS decreased during increases in SVR. This is relevant in settings where a high level of reliability is required.

Development and Validation of a Nomogram of Persistent Pulmonary Hypertension in Adult Pretricuspid Shunts After Correction.

BACKGROUND: Pretricuspid shunts have been associated with poorer survival rates in patients with Eisenmenger syndrome compared with postricuspid shunts and complex lesions. However, the risk stratification for persistent pulmonary hypertension (PH) in this population remains uncertain. METHODS AND RESULTS: We retrospectively enrolled 103 patients with pretricuspid shunts with high total pulmonary resistance >4.5 Wood units (estimated pulmonary vascular resistance ≥3 Wood units). During a mean±SD follow-up of 20.95±24.84 months, 32 patients developed postoperative persistent PH after shunt correction. We identified 3 significant predictors of postoperative persistent PH, including mean pulmonary artery pressure after inhaled oxygen ≥40.5 mm Hg (odds ratio [OR], 7.78 [95% CI, 2.02-30.03]; P<0.01), total pulmonary resistance after inhaled oxygen ≥6.5 Wood units (estimated pulmonary vascular resistance ≥5 Wood units; OR, 12.23 [95% CI, 2.12-70.46]; P<0.01), and artery oxygen saturation at rest <95% (OR, 3.34 [95% CI, 1.07-10.44]; P=0.04). We established the prediction model with the C-statistics of 0.85 (95% CI, 0.77-0.93; P<0.01), and the C-statistic was 0.83 (95% CI, 0.80-0.86) after bootstrapping 10 000 times with a good performance of the nomogram calibration curve for predicting persistent PH. CONCLUSIONS: Our study presents a multivariable risk stratification model for persistent PH after shunt correction in adults with pretricuspid shunts. This model, based on 3 hemodynamic predictors after inhaled oxygen, may assist in identifying individuals at higher risk of persistent PH after shunt correction.

Impact of vessel volume on thermodilution measurements in patients with coronary microvascular dysfunction.

BACKGROUND: Two invasive methods are available to estimate microvascular resistance: bolus and continuous thermodilution. Comparative studies have revealed a lack of concordance between measurements of microvascular resistance obtained through these techniques. AIMS: This study aimed to examine the influence of vessel volume on bolus thermodilution measurements. METHODS: We prospectively included patients with angina with non-obstructive coronary arteries (ANOCA) undergoing bolus and continuous thermodilution assessments. All patients underwent coronary CT angiography to extract vessel volume. Coronary microvascular dysfunction was defined as coronary flow reserve (CFR) < 2.0. Measurements of absolute microvascular resistance (in Woods units) and index of microvascular resistance (IMR) were compared before and after volumetric adjustment. RESULTS: Overall, 94 patients with ANOCA were included in this study. The mean age was 64.7 ± 10.8 years, 48% were female, and 19% had diabetes. The prevalence of CMD was 16% based on bolus thermodilution, while continuous thermodilution yielded a prevalence of 27% (Cohen's Kappa 0.44, 95% CI 0.23-0.65). There was no correlation in microvascular resistance between techniques (r = 0.17, 95% CI -0.04 to 0.36, p = 0.104). The adjustment of IMR by vessel volume significantly increased the agreement with absolute microvascular resistance derived from continuous thermodilution (r = 0.48, 95% CI 0.31-0.63, p < 0.001). CONCLUSIONS: In patients with ANOCA, invasive methods based on coronary thermodilution yielded conflicting results for the assessment of CMD. Adjusting IMR with vessel volume improved the agreement with continuous thermodilution for the assessment of microvascular resistance. These findings strongly suggest the importance of considering vessel volume when interpreting bolus thermodilution assessment.

The Initial Experience of Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension in Latvia.

Background: Treatment options for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or persistent pulmonary hypertension after pulmonary endarterectomy (PEA) include targeted medical therapy and balloon pulmonary angioplasty (BPA). BPA is an emerging treatment modality that has been reported to improve functional capacity, pulmonary hemodynamics, and right ventricular function. Reports from expert centers are promising, but more data are needed to make the results more generalizable. Materials and Methods: We conducted a prospective analysis of nine consecutive CTEPH patients who underwent balloon pulmonary angioplasty (BPA) sessions at Pauls Stradins Clinical University Hospital in Riga, Latvia between 1 April 2022 and 1 July 2023. We assessed World Health Organization (WHO) functional class, 6 min walk distance (6MWD), blood oxygen saturation (SpO2), brain natriuretic peptide (BNP) level at baseline and 3 months after the first BPA session. For two patients on whom repeated BPA sessions were performed, we additionally assessed cardiac output (CO), pulmonary vascular resistance (PVR), and mean pulmonary artery pressure (mPAP). Results: A total of 12 BPA procedures for nine patients were performed; repeated BPA sessions were performed for two patients. Our results show a reduction in BNP levels and improvement in WHO functional class, 6MWD, and SpO2 after the first BPA session. Improvement in 6MWD was statistically significant. Additionally, an improvement in pulmonary hemodynamic parameters was observed. Conclusions: Our data show that BPA is an effective interventional treatment modality, improving both the pulmonary hemodynamics and functional status. Moreover, BPA is safe and excellently tolerated.

Angiographic Coronary Slow Flow Is Not a Valid Surrogate for Invasively Diagnosed Coronary Microvascular Dysfunction.

BACKGROUND: Ischemia with no obstructive coronary arteries is frequently caused by coronary microvascular dysfunction (CMD). Consensus diagnostic criteria for CMD include baseline angiographic slow flow by corrected TIMI (Thrombolysis In Myocardial Infarction) frame count (cTFC), but correlations between slow flow and CMD measured by invasive coronary function testing (CFT) are uncertain. OBJECTIVES: The aim of this study was to investigate relationships between cTFC and invasive CFT for CMD. METHODS: Adults with ischemia with no obstructive coronary arteries underwent invasive CFT with thermodilution-derived baseline coronary blood flow, coronary flow reserve (CFR), and index of microcirculatory resistance (IMR). CMD was defined as abnormal CFR (<2.5) and/or abnormal IMR (≥25). cTFC was measured from baseline angiography; slow flow was defined as cTFC >25. Correlations between cTFC and baseline coronary flow and between CFR and IMR and associations between slow flow and invasive measures of CMD were evaluated, adjusted for covariates. All patients provided consent. RESULTS: Among 508 adults, 49% had coronary slow flow. Patients with slow flow were more likely to have abnormal IMR (36% vs 26%; P = 0.019) but less likely to have abnormal CFR (28% vs 42%; P = 0.001), with no difference in CMD (46% vs 51%). cTFC was weakly correlated with baseline coronary blood flow (r = -0.35; 95% CI: -0.42 to -0.27), CFR (r = 0.20; 95% CI: 0.12 to 0.28), and IMR (r = 0.16; 95% CI: 0.07-0.24). In multivariable models, slow flow was associated with lower odds of abnormal CFR (adjusted OR: 0.53; 95% CI: 0.35 to 0.80). CONCLUSIONS: Coronary slow flow was weakly associated with results of invasive CFT and should not be used as a surrogate for the invasive diagnosis of CMD.

High output cardiac state: evaluating the incidence, plausible etiologies and outcomes.

INTRODUCTION: The high output cardiac state (HOCS) [cardiac index (CI) >4 L/min/m2 ], primarily driven by abnormally low systemic vascular resistance (SVR), is a relatively under-recognized condition. Although, majority of these patients meet criteria for heart failure (HF), their treatment should be aimed at the primary pathology, as the majority of guideline directed HF therapies can reduce SVR further. OBJECTIVES: To characterize patients with HOCS and provide valuable insight into the condition. METHODS: Patients investigated by right heart catheterization (RHC) at the St. Boniface Hospital, Winnipeg, Canada between January 2009 and November 2021 were reviewed. Two groups of patients were included: 1) HOCS [CI >4 L/min/m2], and 2) pre-HOCS [CI between 3.8-4.0 L/min/m2]. Their medical records were reviewed to identify plausible etiologies, relevant investigations, and outcomes. RESULTS: 177/2950 (6 %) patients met criteria for inclusion: 144/177 (81 %) with HOCS [mean age 51 years (range 19 - 82); 67/144 (47 %) female] and 33/177 (19 %) with pre-HOCS [mean age 55 years (range 30 - 83); 6/33 (18 %) female]. The most common plausible etiologies for the HOCS included anemia (36 %), obesity (34 %), cirrhosis (17 %), and lung disease (32 %). Trans-thoracic echocardiography and magnetic resonance imaging findings were non-specific and predominantly described preserved left ventricular ejection fraction, and pulmonary hypertension. The population experienced high rates of hospitalization, and significantly high mortality [36/144 (25 %) of HOCS at a median follow-up of 31.5 months, and 13/33 (39 %) of pre-HOCS at a median follow-up of 17 months]. CONCLUSIONS: HOCS is not an uncommon condition and is associated with high mortality. Current HF guideline should incorporate such evaluation into the diagnostic criteria.

Pulmonary vascular disease and optical coherence tomography imaging in patients with Fontan palliation.

INTRODUCTION: The Fontan procedure is the palliative procedure of choice for patients with single ventricle physiology. Pulmonary vascular disease (PVD) is an important contributor to Fontan circulatory failure. AREAS COVERED: We review the pathophysiology of PVD in patients with Fontan palliation and share our initial experience with optical coherence tomography (OCT) in supplementing standard hemodynamics in characterizing Fontan-associated PVD. In the absence of a sub-pulmonary ventricle, low pulmonary vascular resistance (PVR; ≤2 WU/m2) is required to sustain optimal pulmonary blood flow. PVD is associated with adverse pulmonary artery (PA) remodeling resulting from the non-pulsatile low-shear low-flow circulation. Predisposing factors to PVD include impaired PA growth, endothelial dysfunction, hypercoagulable state, and increased ventricular end-diastolic pressure. OCT parameters that show promise in characterizing Fontan-associated PVD include the PA intima-to-media ratio and wall area ratio (i.e. difference between the whole-vessel area and the luminal area divided by the whole-vessel area). EXPERT OPINION: OCT carries potential in characterizing PVD in patients with Fontan palliation. PA remodeling is marked by intimal hyperplasia, with medial regression. Further studies are required to determine the role of OCT in informing management decisions and assessing therapeutic responses.

Vitamin C deficiency can lead to pulmonary hypertension: a systematic review of case reports.

BACKGROUND: In the early literature, unintentional vitamin C deficiency in humans was associated with heart failure. Experimental vitamin C deficiency in guinea pigs caused enlargement of the heart. The purpose of this study was to collect and analyze case reports on vitamin C and pulmonary hypertension. METHODS: We searched Pubmed and Scopus for case studies in which vitamin C deficiency was considered to be the cause of pulmonary hypertension. We selected reports in which pulmonary hypertension was diagnosed by echocardiography or catheterization, for any age, sex, or dosage of vitamin C. We extracted quantitative data for our analysis. We used the mean pulmonary artery pressure (mPAP) as the outcome of primary interest. RESULTS: We identified 32 case reports, 21 of which were published in the last 5 years. Dyspnea was reported in 69%, edema in 53% and fatigue in 28% of the patients. Vitamin C plasma levels, measured in 27 cases, were undetectable in 24 and very low in 3 cases. Diet was poor in 30 cases and 17 cases had neuropsychiatric disorders. Right ventricular enlargement was reported in 24 cases. During periods of vitamin C deficiency, the median mPAP was 48 mmHg (range 29-77 mmHg; N = 28). After the start of vitamin C administration, the median mPAP was 20 mmHg (range 12-33 mmHg; N = 18). For the latter 18 cases, mPAP was 2.4-fold (median) higher during vitamin C deficiency. Pulmonary vascular resistance (PVR) during vitamin C deficiency was reported for 9 cases, ranging from 4.1 to 41 Wood units. PVR was 9-fold (median; N = 5) higher during vitamin C deficiency than during vitamin C administration. In 8 cases, there was direct evidence that the cases were pulmonary artery hypertension (PAH). Probably the majority of the remaining cases were also PAH. CONCLUSIONS: The cases analyzed in our study indicate that pulmonary hypertension can be one explanation for the reported heart failure of scurvy patients in the early literature. It would seem sensible to measure plasma vitamin C levels of patients with PH and examine the effects of vitamin C administration.

Lactate infusion elevates cardiac output through increased heart rate and decreased vascular resistance: a randomised, blinded, crossover trial in a healthy porcine model.

BACKGROUND: Lactate is traditionally recognized as a by-product of anaerobic metabolism. However, lactate is a preferred oxidative substrate for stressed myocardium. Exogenous lactate infusion increases cardiac output (CO). The exact mechanism underlying this mechanism has yet to be elucidated. The aim of this study was to investigate the cardiovascular mechanisms underlying the acute haemodynamic effects of exogenous lactate infusion in an experimental model of human-sized pigs. METHODS: In this randomised, blinded crossover study in eight 60-kg-pigs, the pigs received infusions with one molar sodium lactate and a control infusion of tonicity matched hypertonic saline in random order. We measured CO and pulmonary pressures using a pulmonary artery catheter. A pressure-volume admittance catheter in the left ventricle was used to measure contractility, afterload, preload and work-related parameters. RESULTS: Lactate infusion increased circulating lactate levels by 9.9 mmol/L (95% confidence interval (CI) 9.1 to 11.0) and CO by 2.0 L/min (95% CI 1.2 to 2.7). Afterload decreased as arterial elastance fell by  -1.0 mmHg/ml (95% CI  -2.0 to  -0.1) and systemic vascular resistance decreased by  -548 dynes/s/cm5 (95% CI  -261 to  -835). Mixed venous saturation increased by 11 percentage points (95% CI 6 to 16), whereas ejection fraction increased by 16.0 percentage points (95% CI 1.1 to 32.0) and heart rate by 21 bpm (95% CI 8 to 33). No significant changes in contractility nor preload were observed. CONCLUSION: Lactate infusion increased cardiac output by increasing heart rate and lowering afterload. No differences were observed in left ventricular contractility or preload. Lactate holds potential as a treatment in situations with lowered CO and should be investigated in future clinical studies.

Novel theory and potential applications of central diastolic pressure decay time constant.

Central aortic diastolic pressure decay time constant ( τ ) is according to the two-element Windkessel model equal to the product of total peripheral resistance ( R ) times total arterial compliance ( C ). As such, it is related to arterial stiffness, which has considerable pathophysiological relevance in the assessment of vascular health. This study aimed to investigate the relationship of the constant τ with the product T MBP cPP , given by heart period ( T ) times the ratio of mean blood pressure (MBP) to central pulse pressure ( cPP ). The relationship was derived by performing linear fitting on an in silico population of n1 = 3818 virtual subjects, and was subsequently evaluated on in vivo data (n2 = 2263) from the large Asklepios study. The resulted expression was found to be τ = k ' T MBP cPP , with k ' = 0.7 (R2 = 0.9). The evaluation of the equation on the in vivo human data reported high agreement between the estimated and reference τ values, with a correlation coefficient equal to 0.94 and a normalized RMSE equal to 5.5%. Moreover, the analysis provided evidence that the coefficient k ' is age- and gender-independent. The proposed formula provides novel theoretical insights in the relationship between τ and central blood pressure features. In addition, it may allow for the evaluation of τ without the need for acquiring the entire central blood pressure wave, especially when an approximation of the cPP is feasible. This study adds to the current literature by contributing to the accessibility of an additional biomarker, such as the central diastolic pressure decay time constant, for the improved assessment of vascular ageing.

Hypoxia in the pulmonary vein increases pulmonary vascular resistance independently of oxygen in the pulmonary artery.

INTRODUCTION: Hypoxic pulmonary vasoconstriction (HPV) can be a challenging clinical problem. It is not fully elucidated where in the circulation the regulation of resistance takes place. It is often referred to as if it is in the arteries, but we hypothesized that it is in the venous side of the pulmonary circulation. METHODS: In an open thorax model, pigs were treated with a veno-venous extra corporeal membrane oxygenator to either oxygenate or deoxygenate blood passing through the pulmonary vessels. At the same time the lungs were ventilated with extreme variations of inspired air from 5% to 100% oxygen, making it possible to make combinations of high and low oxygen content through the pulmonary circulation. A flow probe was inserted around the main pulmonary artery and catheters in the pulmonary artery and in the left atrium were used for pressure monitoring and blood tests. Under different combinations of oxygenation, pulmonary vascular resistance (PVR) was calculated. RESULTS: With unchanged level of oxygen in the pulmonary artery and reduced inspired oxygen fraction lowering oxygen tension from 29 to 6.7 kPa in the pulmonary vein, PVR was doubled. With more extreme hypoxia PVR suddenly decreased. Combinations with low oxygenation in the pulmonary artery did not systematic influence PVR if there was enough oxygen in the inspired air and in the pulmonary veins. DISCUSSION: The impact of hypoxia occurs from the alveolar level and forward with the blood flow. The experiments indicated that the regulation of PVR is mediated from the venous side.

Renal vascular control during normothermia and passive heat stress does not differ between healthy younger men and women.

Men are likely at greater risk for heat-induced acute kidney injury compared with women, possibly due to differences in vascular control. We tested the hypothesis that the renal vasoconstrictor and vasodilator responses will be greater in younger women compared with men during passive heat stress. Twenty-five healthy adults [12 women (early follicular phase) and 13 men] completed two experimental visits, heat stress or normothermic time-control, assigned in a block-randomized crossover design. During heat stress, participants wore a water-perfused suit perfused with 50°C water. Core temperature was increased by ∼0.8°C in the first hour before commencing a 2-min cold pressor test (CPT). Core temperature remained clamped and at 1-h post-CPT, subjects ingested a whey protein shake (1.2 g of protein/kg body wt), and measurements were taken pre-, 75 min, and 150 min post-protein. Beat-to-beat blood pressure (Penaz method) was measured and segmental artery vascular resistance (VR, Doppler ultrasound) was calculated as segmental artery blood velocity ÷ mean arterial pressure. CPT-induced increases in segmental artery VR did not differ between trials (trial effect: P = 0.142) nor between men (heat stress: 1.5 ± 1.0 mmHg/cm/s, normothermia: 1.4 ± 1.0 mmHg/cm/s) and women (heat stress: 1.4 ± 1.2 mmHg/cm/s, normothermia: 2.1 ± 1.1 mmHg/cm/s) (group effect: P = 0.429). Reductions in segmental artery VR following oral protein loading did not differ between trials (trial effect: P = 0.080) nor between men (heat stress: -0.6 ± 0.8 mmHg/cm/s, normothermia: -0.6 ± 0.6 mmHg/cm/s) and women (heat stress: -0.5 ± 0.5 mmHg/cm/s, normothermia: -1.1 ± 0.6 mmHg/cm/s) (group effect: P = 0.204). Renal vasoconstrictor responses to the cold pressor test and vasodilator responses following an oral protein load during heat stress or normothermia do not differ between younger men and younger women in the early follicular phase of the menstrual cycle.NEW & NOTEWORTHY The mechanisms underlying greater heat-induced acute kidney injury risk in men versus women remain unknown. This study examined renal vascular control, including both vasodilatory (oral protein load) and vasoconstrictor (cold presser test) responses, during normothermia and heat stress and compared these responses between men and women. The results indicated that in both conditions neither renal vasodilatory nor vasoconstrictor responses differ between younger men and younger women.

Hemodynamic evaluation in preterm infants using ultrasonic cardiac output monitor (USCOM).

We aimed to establish reference ranges for USCOM parameters in preterm infants, determine factors that affect cardiac output, and evaluate the measurement repeatability. This retro-prospective study was performed at Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy. We included infants below 32 weeks of gestational age (GA) and/or 1500 g of birth weight (BW). We excluded infants with congenital heart diseases or hemodynamic instability. Measurements were performed at 3 ± 1, 7 ± 2, and 14 ± 2 postnatal days. We analyzed 204 measurements from 92 patients (median GA = 30.57 weeks, BW = 1360 g). The mean (SD) cardiac output (CO) was 278 (55) ml/min/kg, cardiac index (CI) was 3.1 (0.5) L/min/m2, and systemic vascular resistance (SVRI) was 1292 (294) d*s*cm-5/m2. CO presented a negative correlation with postmenstrual age (PMA), while SVRI presented a positive correlation with PMA. The repeatability coefficient was 31 ml/kg/min (12%).  Conclusion: This is the first study describing reference values for USCOM parameters in hemodynamically stable preterm infants and factors affecting their variability. Further studies to investigate the usefulness of USCOM for the longitudinal assessment of patients at risk for cardiovascular instability or monitoring the response to therapies are warranted. What is Known: • The ultrasonic cardiac output monitoring (USCOM) has been widely used on adult and pediatric patients and reference ranges for cardiac output (CO) by USCOM have been established in term infants. What is New: • We established reference values for USCOM parameters in very preterm and very-low-birth-weight infants; the reference ranges for CO by USCOM in the study population were 198-405 ml/kg/min. • CO normalized by body weight presented a significant negative correlation with postmenstrual age (PMA); systemic vascular resistance index presented a significant positive correlation with PMA.

Pulmonary Vascular Regulation in the Fetal and Transitional Lung.

Fetal lungs have fewer and smaller arteries with higher pulmonary vascular resistance (PVR) than a newborn. As gestation advances, the pulmonary circulation becomes more sensitive to changes in pulmonary arterial oxygen tension, which prepares them for the dramatic drop in PVR and increase in pulmonary blood flow (PBF) that occur when the baby takes its first few breaths of air, thus driving the transition from fetal to postnatal circulation. Dynamic and intricate regulatory mechanisms control PBF throughout development and are essential in supporting gas exchange after birth. Understanding these concepts is crucial given the role the pulmonary vasculature plays in the development of complications with transition, such as in the setting of persistent pulmonary hypertension of the newborn and congenital heart disease. An improved understanding of pulmonary vascular regulation may reveal opportunities for better clinical management.

Pathogenesis and Physiologic Mechanisms of Neonatal Pulmonary Hypertension: Preclinical Studies.

Neonatal pulmonary hypertension (PH) is a devastating disorder of the pulmonary vasculature characterized by elevated pulmonary vascular resistance and mean pulmonary arterial pressure. Occurring predominantly because of maldevelopment or maladaptation of the pulmonary vasculature, PH in neonates is associated with suboptimal short-term and long-term outcomes because its pathobiology is unclear in most circumstances, and it responds poorly to conventional pulmonary vasodilators. Understanding the pathogenesis and pathophysiology of neonatal PH can lead to novel strategies and precise therapies. The review is designed to achieve this goal by summarizing pulmonary vascular development and the pathogenesis and pathophysiology of PH associated with maladaptation, bronchopulmonary dysplasia, and congenital diaphragmatic hernia based on evidence predominantly from preclinical studies. We also discuss the pros and cons of and provide future directions for preclinical studies in neonatal PH.

Targeted Neonatal Echocardiography in the Management of Neonatal Pulmonary Hypertension.

Pulmonary hypertension (PH) in neonates, originating from a range of disease states with heterogeneous underlying pathophysiology, is associated with significant morbidity and mortality. Although the final common pathway is a state of high right ventricular afterload leading to compromised cardiac output, multiple hemodynamic phenotypes exist in acute and chronic PH, for which cardiorespiratory treatment strategies differ. Comprehensive appraisal of pulmonary pressure, pulmonary vascular resistance, cardiac function, pulmonary and systemic blood flow, and extrapulmonary shunts facilitates delivery of individualized cardiovascular therapies in affected newborns.