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Hypoxia and the pulmonary circulation: a brief review.

Hypoxia constricts small pulmonary arteries. Local hypoxia regulates blood flow/ventilation ratios, while general hypoxia elevates pulmonary artery pressure (Ppa). There is a continuum of responses from flow reduction to Ppa elevation dependent on the proportion of lung involved. Stimulus-response curves to hypoxia show the effect is maximal within the physiological range and resemble that for the carotid body. In widespread lung disease so much of the lung becomes hypoxic, that blood flow/ventilation matching fails, hypoxaemia and pulmonary hypertension follow. In chronic hypoxia structural changes take place which maintain a high pressure even when hypoxia is removed; small arterioles become muscularized and there is right ventricular hypertrophy and polycythaemia. Animal models of hypoxic pulmonary hypertension have brought some understanding of the growth processes involved and shown that several drugs will prevent these changes. The reactivity of the restructured pulmonary vessels in chronic hypoxia is altered.

Animals↗

A novel model for post-transplant obliterative airway disease reveals angiogenesis from the pulmonary circulation.

We present a novel animal model for post-transplant obliterative airway disease in which the donor trachea is implanted into the recipient's lung parenchyma. Although this procedure is technically more challenging than the heterotopic model of implantation into a subcutaneous pouch, it has several important advantages some of which are the appropriate local environment and the possibility of local immunosuppressive therapy after transtracheal gene, cell or drug delivery. This model has revealed new insights into angiogenic potential of the pulmonary circulation.

Animals↗

[Hemodynamic indicators, phase structure of the systole of the left and right heart ventricles and the state of pulmonary circulation and microcirculation in patients with hypertension treated with adelphane-esindex].

A total of 58 patients were treated with adelphane-esidrex for hypertension, Stage II. Their general condition improved considerably and arterial blood pressure obviously decreased. The hypotensive effect of the treatment was associated with a considerable fall of high systemic peripheral resistance in most patients, and with reduced systolic and minute blood volume in others. An improvement was noted in the phasic pattern of left and right ventricular systole, pulmonary circulation, external respiratory function and also microcirculation.

Adult↗

Effect of pulmonary circulation on vector impedance cardiogram.

Vector impedance cardiograms in horizontal lead configuration [VICG(H)] were recorded in 34 normal subjects, 18 patients with mitral stenosis, 9 patients with mitral regurgitation, 14 patients with aortic regurgitation and 13 patients with non- cyanotic septal disorders. Data in normal subjects revealed that most of the phase reversal points in VICG(H) waveform did not coincide with those of conventional impedance cardiogram. The shape of VICG(H) waveform and values of VICG indices were observed to be markedly affected in patients having significant alteration in the pulmonary circulation and the changes observed were specific of the type of the disorder. The results of the study suggested that right side of the heart had dominant contribution in generation of VICG(H) waveform.

Adolescent↗

Extracorporeal circulation does not induce intra-alveolar release of Endothelin 1, but only a modest overproduction in pulmonary circulation.

OBJECTIVE: To investigate whether ECC may produce regional liberation of inflammatory mediators capable of inducing vascular effects and organ damage. EXPERIMENTAL DESIGN: Comparative study [corrected]. SETTING: Cardiac surgery department in a University hospital. PATIENTS: Fifteen patients undergoing coronary artery bypass grafting (CABG, group A) and ten patients operated for infrarenal abdominal aortic aneurysm (controls, group B) have been studied. MEASURES: Levels of Interleukin 1beta (IL1), Tumor Necrosis Factor alpha (TNF), Interleukin 6 (IL6), and Endothelin 1 (ET1) were measured in pulmonary capillary, arterial, and venous blood and in bronchoalveolar lavages (BAL) before, during and after extracorporeal circulation (ECC) or surgical intervention. RESULTS: TNF-alpha (never >35 pg/ml) and IL1beta (range 20-300 pg/ml) values did not change over time for both groups. IL6 concentrations in all samples of group A increased between five and twenty fold, during and after ECC (from 3-5 pg/ml up to 240 pg/ml, p<0.001). This trend was similar in controls after surgical stress. Endothelin 1 was always undetectable in the BAL fluid, with a modest, but significant increase in pulmonary capillary blood of group A, after ECC, (from 11+/-4 pg/ml to 18+/-5 pg/ml, p<0.001). This increment correlated well with the PVR increase, but was transient and after 24 hours, ET1 values returned to baseline levels. Mean values of ET1 increased also in controls, but not significantly. CONCLUSIONS: ECC may induce ET1 liberation in pulmonary circulation with transient pulmonary vasoconstriction, but wihout intra-alveolar release, or lung damage. Augmented concentrations of IL6 probably express a response to surgical procedure rather than an effect exclusively related to ECC.

Adult↗

Type I nitric oxide synthase is decreased in the fetal pulmonary circulation of hypertensive lambs.

The nitric oxide (NO)/guanosine 3',5'-cyclic monophosphate (cGMP) pathway plays an essential role in mediating pulmonary vasodilatation during transition of the pulmonary circulation at birth. We used immunoblot analysis (Western) and semiquantitative immunohistochemistry to study the presence, distribution, and relative amounts of type I nitric oxide synthase (NOS-I). Immunoblots were performed on normal fetal sheep lungs, whereas immunohistochemistry for NOS-I was compared between lungs from normal fetal lambs vs. fetal lambs with persistent pulmonary hypertension of the newborn (PPHN) induced by ligation of the ductus arteriosus. Western blot analysis using a polyclonal antibody detected NOS-I protein in homogenates of normal fetal sheep lungs. Abundant NOS-I immunoreactivity was observed exclusively in the precapillary resistance vessels, i.e., terminal bronchiole-associated arteries (TA) and respiratory bronchiole-associated arteries (RA) in normal fetal lung. In marked contrast, immunoreactivity for NOS-I was significantly reduced in the TA and RA of hypertensive lungs. We conclude that there is a heterogeneous distribution of NOS-I in the normal fetal sheep lung, but that NOS-I staining is significantly reduced in lambs with PPHN.

Animals↗

Behavior of the human pulmonary circulation during head-up tilt.

Pulmonary blood volume (PBV), flow, and pressures were measured in 15 cardiopulmonary normal subjects, while supine and at 60 degrees head-up passive tilt. PBV, cardiac index (CI), right ventricular diastolic volume (VDVR), and mean pulmonary arterial (Ppa), venous (Pv), and mean right atrial (Pra) pressures all decreased during the first 4 min of tilting, with little subsequent change thereafter, to 30 min. Relative changes of CI, PBV, and VDVR were of similar magnitude (25--30%; mean Ppa and Pv fell 3.2 and 2.3 Torr, respectively. From measurements of thoracic dimensions and changes in intravascular pressures, we calculate that 11% of the pulmonary vascular bed falls into zone I condition, 34% goes from zone III to zone II, and 55% remains in zone III condition during tilt. A highly significant correlation exists between PBV and CI (P less than 0.001), with no significant change in pulmonary mean transit time during tilt. Significant correlations also exist between PBV and Pra (P less than 0.001), Pv (P less than 0.01), and Ppa (P less than 0.05). We conclude that outflow pressure plays a significant role in determining PBV during head-up tilt, but the major determinant is venous return to the right heart.

Adult↗