Enhancement of hypoxic pulmonary vasoconstriction by metabolic acidosis in dogs.
The effects of HCl infusion on multipoint mean pulmonary arterial pressure (PAP)/cardiac index (CI) plots in pentobarbital-anesthetized dogs whose lungs were ventilated alternately in hyperoxia (fraction of inspired O2 [FIO2], 0.4) and hypoxia (FIO2, 0.1) were investigated. Over the range of CI studied (1 to 5 l.min-1.m-2), hypoxia increased PAP in 22 dogs (responders) and did not affect PAP in 16 other dogs (nonresponders). In eight nonresponders, two repetitions of alternated 0.4 and 0.1 FIO2 exposures did not restore hypoxic pulmonary vasoconstriction (HPV), defined as a hypoxia-induced increase in PAP at a given flow. Intravenous infusion of 2 M HCl (2 mmol.kg-1.h-1) decreased arterial pH from normal to around 7.20 in eight responders and eight nonresponders. This metabolic acidosis increased PAP at all levels of CI in hyperoxia and in hypoxia in all the dogs, enhanced HPV in the responders, and restored HPV in the nonresponders. In eight responders, 2 M HCl infusion (2 mmol.kg-1.h-1) together with a 7% sodium bicarbonate infusion (adjusted to maintain arterial pH unchanged) did not affect hyperoxic or hypoxic PAP/CI plots. Pretreatment with 1 g acetylsalicylic acid iv (6 dogs) did not affect the pulmonary vasoreactivity to HCl-induced (2 M HCl, 2 mmol.kg-1.h-1) metabolic acidosis. It was concluded that in intact dogs: 1) metabolic acidosis enhances HPV; 2) at the given dose, HCl does not produce pulmonary vascular effects unrelated to the circulating blood pH; and 3) it is unlikely that the pulmonary vasoreactivity to metabolic acidosis is mediated by products of the cyclooxygenase pathway.
Lejeune
P
P
Laboratory of Cardiovascular and Respiratory Physiology, Erasme University Hospital, Brussels, Belgium.
Brimioulle
S
S
Leeman
M
M
Hallemans
R
R
Melot
C
C
Naeije
R
R
D000138:Acidosis / Q000503:physiopathology*; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001639:Bicarbonates / Q000008:administration & dosage; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002245:Carbon Dioxide / Q000097:blood; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D006851:Hydrochloric Acid / Q000008:administration & dosage / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply*; D010100:Oxygen / Q000097:blood; D011651:Pulmonary Artery; D011652:Pulmonary Circulation / Q000502:physiology; D011669:Pulmonary Wedge Pressure / Q000187:drug effects / Q000502:physiology; D012964:Sodium / Q000008:administration & dosage; D017693:Sodium Bicarbonate; D014661:Vasoconstriction / Q000502:physiology*
D001639:Bicarbonates; D002245:Carbon Dioxide; D017693:Sodium Bicarbonate; D012964:Sodium; D006851:Hydrochloric Acid; D001241:Aspirin; D010100:Oxygen