Cardiac morphology and function following long-term exposure to carbon monoxide at high altitude in rats

Although chronic exposure to high altitude or carbon monoxide (CO) induces several cardiovascular adaptations in mammals, very little information is available on the cardiovascular effects due to exposure to these concomitant stresses. In particular, cardiac functional responses to chronic CO inhalation at high altitude has never been investigated. Thirty-two male Dark Agouti rats were exposed for 10 wk in steel chambers to (1) normoxic conditions (N rats), (2) 4000 m simulated high altitude (chronic hypobaric hypoxia, CH rats), (3) 50 ppm CO (CO rats), or (4) 50 ppm CO at 4000 m simulated high altitude (CH + CO rats). Left ventricular (LV) morphology and function were evaluated in normoxic conditions (1) using transthoracic Doppler echocardiography, just before as well as after exposure to environments, and (2) using transparietal intraventricular catheterisms following a short ventilatory-controlled thoracotomy (10 ml/kg volume inflow, pO2 ~159 torr) after exposure. Right ventricular (RV) function was evaluated using the same catheterism process after exposure. Body weight increased in all groups during exposure, but to a lesser extent in CH and CH + CO than in N and CO rats. At the end of exposure, hematocrit ratio was higher in CH than in CO rats, and in CH + CO than in CH rats. Carboxyhemoglobin levels were higher in CH + CO than in CO, CH, or N rats. Although neither a simulated high altitude nor CO alone had an effect on LV morphology and function, combined environments increased LV + septum weight, interventricular and posterior wall thicknesses, relative wall thickness, and LV systolic function. LV diastolic function was not altered by environmental conditions in the four groups. CO intensified the altitude-induced RV hypertrophy as well as the altitude-induced decrease in RV diastolic function. RV systolic function increased in CH rats, but adding CO did not amplify this adaptation process. Moreover, significant polynomial relationships were obtained between hematocrit ratio and LV + septum weight or left ventricular systolic pressure. Our results indicate that CO at high altitude induced severe hematological responses that could be involved in morphological and functional cardiac adaptations of both ventricles. Data indicate that CO at high altitude may be more detrimental to cardiac function than CO inhaled at sea level.