ET-1 infusion increases systemic vascular resistance and depresses cardiac output in patients with chronic hypoxaemia and pulmonary hypertension.
The pulmonary vascular effects of the endothelium-derived peptide endothelin (ET) vary depending on the existing vascular tone, modes of administration and species studied; ET can cause both pulmonary vasodilatation and vasoconstriction. Increased plasma levels of ET have been reported in hypoxic pulmonary hypertension, although it is unclear whether ET is a mediator or a marker of hypoxia-induced increase in pulmonary vascular resistance (PVR). In our study, the plasma levels of ET-1 and the functional effects of ET-1 infusion in patients (n = 4) with chronic hypoxaemia and elevated PVR were evaluated. At rest, the arterial and venous ET-1-levels (13 +/- 2 and 12 +/- 1 fmol/ml, respectively) were significantly higher than those detected in venous plasma of an age-matched healthy control group (7 +/- 1 fmol/ml). Consecutive 10 min infusions of ET-1 at 1, 5, 10 and 15 ng/kg/min into the pulmonary artery decreased cardiac output (by 32%) and stroke volume (by 33%) and increased the systemic vascular resistance (by 62%) and arteriovenous oxygen difference (by 83%) at the highest dose. No deleterious effect was observed in the pulmonary circulation. The present study therefore suggests that intra-pulmonarily administered ET does not attenuate the increased PVR associated with chronic hypoxaemia.
Franco-Cereceda
A
A
Department of Thoracic Surgery, Karolinska Hospital, Stockholm, Sweden. andfra@mbox.ki.se
Holm
P
P
Brodin
L A
LA
Liska
J
J
Larsen
F F
FF
D015746:Abdominal Pain / Q000139:chemically induced; D000368:Aged; D002245:Carbon Dioxide / Q000097:blood; D002302:Cardiac Output / Q000187:drug effects*; D016022:Case-Control Studies; D019332:Endothelin-1 / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000503:physiopathology*; D000860:Hypoxia / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D014655:Vascular Resistance / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects
D019332:Endothelin-1; D002245:Carbon Dioxide; D010100:Oxygen