Decreased blood oxygen diffusion in hypercholesterolemia.
BACKGROUND
Improvement of angina pectoris symptoms after cholesterol lowering has raised questions as to the underlying mechanisms.


METHODS
Rabbit experiment: We compared arterial blood samples from New Zealand White cholesterol-supplemented rabbits (n = 6) with nonsupplemented rabbit samples (n = 4) in a closed-loop circulation diffusion system. The pH and partial pressures of oxygen (pO2) and carbon dioxide (pCO2) were measured continuously. The samples were first oxygen (O2) saturated (pO2, 160 mm Hg; pCO2, 4 mm Hg) and then desaturated in 100% nitrogen. Cholesterol levels were determined in whole blood, plasma (P Chol), red blood cells (RBCs), and RBC membranes. Human experiment: We exposed quadruple desaturated venous blood samples (n = 4) with P Chol levels of 87 to 400 mg/dL in a gas exchanger to capillary gas conditions (pO2, 23 mm Hg; pCO2, 46 mm Hg). After 15 minutes we performed blood gas analyses and compared our results to baseline values.


RESULTS
In the rabbit experiment the cholesterol-supplemented group as compared to the control group showed higher plasma pO2 levels during the saturation phase and lower plasma pO2 levels during the desaturation phase. It also had a markedly increased RBC membrane cholesterol content: 121 +/- 3 (standard error of the mean [SEM]) mg/dL versus 22 +/- 1.7 mg/dL in the control group (P < .05). This barrier to RBC membrane O2 diffusion caused delayed O2 entry into the RBCs during saturation, with a higher plasma pO2, and delayed O2 release from the RBCs during desaturation, with a lower plasma pO2. In the human experiment the P Chol level was inversely correlated with the percentage change of O2 content in milliliters of O2 per deciliter of blood (P < .05).


CONCLUSIONS
Increased RBC membrane cholesterol in hypercholesterolemia appears to decrease the transmembrane O2 diffusion rate.
Menchaca
H J
HJ
Department of Surgery, University of Minnesota, Minneapolis, USA.
Michalek
V N
VN
Rohde
T D
TD
O'Dea
T J
TJ
Buchwald
H
H
D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D004058:Diffusion; D004910:Erythrocyte Membrane / Q000737:chemistry; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood*; D066298:In Vitro Techniques; D008297:Male; D010100:Oxygen / Q000097:blood*; D010313:Partial Pressure; D011817:Rabbits
D002245:Carbon Dioxide; D010100:Oxygen