title: Effects of radiographic contrast media on pulmonary vascular resistance of normoxic and chronically hypoxic pulmonary hypertensive rats.
abstract: Intravascular radiographic contrast media (RCM) can be associated with significant morbidity in patients with pulmonary hypertension (PH). This study investigated the direct effect of the four main classes of RCM (high osmolar ionic monomer "diatrizoate"; low osmolar ionic dimer "ioxaglate"; low osmolar non-ionic monomer "iopromide"; and iso-osmolar non-ionic dimer "iotrolan") in ex vivo isolated rat lungs perfused with blood at 20 ml min(-1) under basal conditions (air + 5% CO2 ventilation, pulmonary artery pressure (Ppa) 16-20 mmHg) and when Ppa was raised by hypoxic vasoconstriction in normal rats (2-3% O2+5% CO2 ventilation, Ppa increased by 4-14 mmHg). The effects of low osmolar RCM (ioxaglate, iopromide and iotrolan) were also studied in rats with PH induced by chronic hypoxia (3 weeks 10% O2, Ppa 26-36 mmHg). Increasing volumes (0.05 ml, 0.1 ml, 0.3 ml, and 0.5 ml) of RCM, mannitol (osmolar and pH control) or normal saline (volume control) were added to the 10 ml blood reservoir (n=4-9 per group). In normal rats, RCM caused a dose-dependent slow rise in Ppa. The maximum rise in mean+/-SEM Ppa at the cumulative dose of 0.95 ml was ioxaglate 13.8+/-1.6 mmHg>iotrolan 7.3+/-1.7 mmHg=diatrizoate 9.8+/-2.2 mmHg>iopromide 3.0+/-0.8 mmHg (p<0.05). The rise in Ppa induced by ioxaglate and iotrolan was significantly greater than in the mannitol and saline controls (p<0.05). Pre-treatment with endothelin receptor A/B blockade (SB209670) did not abolish the rise in Ppa induced by diatrizoate (0.95 ml) in the normal rat (3.8+/-1.3 mmHg diatrizoate alone and 3.4+/-1.1 mmHg in the presence of 40 microM SB209670, n=5 per group). When Ppa was raised by acute hypoxia, ioxaglate and diatrizoate (0.5 ml) caused a fall in Ppa (percentage fall -53+/-23 and -118+/-10, respectively, p<0.001) while iotrolan and iopromide caused a small further rise in Ppa, which was significant with iotrolan at a dose of 0.3 ml (percentage rise in pressure 14.2+/-2.3, p<0.05). In chronic pulmonary hypertensive rats, RCM (0.95 ml) caused an overall slow progressive rise in Ppa (iopromide 6.8+/-1.7 mmHg< ioxaglate 11.6+/-2.5 mmHg=iotrolan 12.7+/-1.1 mmHg). However, ioxaglate initially induced an acute fall of Ppa (maximum fall 4.22+/-0.9 mmHg, p<0.05) for almost 20 min. In summary, iopromide induced the least change in Ppa of normal and pulmonary hypertensive rats. The pathophysiology of the effects of RCM on the pulmonary circulation remains uncertain.
authors.affiliation: Respiratory Medicine, Sheffield University Medical School, Sheffield S10 2JF, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: Emery
authors.forename: L
authors.initials: L
authors.lastname: Fang
authors.forename: E A
authors.initials: EA
authors.lastname: Laude
authors.forename: S K
authors.initials: SK
authors.lastname: Morcos
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003287:Contrast Media / Q000009:adverse effects*; D003973:Diatrizoate / Q000009:adverse effects; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications / Q000503:physiopathology*; D007472:Iohexol / Q000009:adverse effects / Q000031:analogs & derivatives*; D007485:Ioxaglic Acid / Q000009:adverse effects; D008297:Male; D023421:Models, Animal; D009994:Osmolar Concentration; D011651:Pulmonary Artery / Q000187:drug effects* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D014283:Triiodobenzoic Acids / Q000009:adverse effects; D014655:Vascular Resistance / Q000187:drug effects*
chemical_list: D003287:Contrast Media; D014283:Triiodobenzoic Acids; D003973:Diatrizoate; C033300:iotrolan; D007472:Iohexol; C038192:iopromide; D007485:Ioxaglic Acid