Chronic hypoxia: a model for cyanotic congenital heart defects.
OBJECTIVE
The postoperative course of cyanotic children is generally more complicated than that of acyanotic children. A possible reason is reoxygenation injury at the beginning of cardiopulmonary bypass. In this study we tested the hypothesis that reoxygenation of chronically hypoxic hearts is worse than that of normoxic hearts.


METHODS
Two groups of rats (n = 9 each) were exposed to either room air (fraction of inspired oxygen, 0.21%) or chronic hypoxia (fraction of inspired oxygen, 0.10%) for 2 weeks. Hearts were then isolated and perfused for 30 minutes with hypoxic buffer (oxygen saturation, 10%), followed by 30 minutes of reoxygenation (oxygen saturation, 100%).


RESULTS
In hypoxic rats hematocrit values, hemoglobin concentrations, and red cells were higher (69% +/- 6% vs 40% +/- 6%, 219 +/- 14 vs 124 +/- 12 g/L, and 10.30 +/- 0.6 vs 6.32 +/- 0.5/microL/1000, respectively; P <.0001); the amount of ingested food was less (22.3 +/- 4.8 vs 30.7 +/- 3.9 g/d, P <.001), as was the amount of ingested water (21.0 +/- 3.1 vs 50.4 +/- 14.6 mL/d, P <.0001); and body weight was lower (182 +/- 14.2 vs 351 +/- 40.1 g, P <.0001), as was heart weight (1107 +/- 119 vs 1312 +/- 128 mg, P <.005). The heart weight/body weight ratio was higher (6.10 +/- 0.8 vs 3.74 +/- 0.1 mg/g, P <.0001). Systolic and diastolic functions, not different during the hypoxic baseline period, were more impaired in hypoxic than in normoxic hearts after the reoxygenation, whereas coronary resistance remained lower. During the hypoxic perfusion, the venous partial pressure of oxygen remained low in both groups, whereas during reoxygenation, partial pressure of oxygen was higher in hypoxic hearts, with a lower (P <.01) oxygen uptake. During hypoxic baseline adenosine triphosphate turnover, lactate production and lactate turnover were lower in hypoxic hearts (P <.005, P <.0001, and P <.0001, respectively).


CONCLUSIONS
Body and blood values are severely affected by chronic hypoxia, and the cardiac effects of uncontrolled reoxygenation after chronic hypoxia are more severe than after acute hypoxia.
Corno
Antonio F
AF
Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. Antonio.Corno@chuv.hospvd.ch
Milano
Giuseppina
G
Samaja
Michele
M
Tozzi
Piergiorgio
P
von Segesser
Ludwig K
LK
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002315:Cardiopulmonary Bypass; D002908:Chronic Disease; D003490:Cyanosis / Q000503:physiopathology; D004195:Disease Models, Animal; D006330:Heart Defects, Congenital / Q000601:surgery*; D006439:Hemodynamics / Q000502:physiology; D000860:Hypoxia / Q000503:physiopathology*; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D019344:Lactic Acid; D000255:Adenosine Triphosphate