cyclic-gmp and Cyanosis

Whether chronic hypoxia attenuates myocardial ischemia-reperfusion injury remains controversial because conflicting data have been reported probably due to the existence of many factors influencing the functional recovery of hearts. These factors include the differences of species, the time at which hypoxia begins, the degree of hypoxia, and so on. Regarding chronic hypoxia from birth, so far the only available data are based on findings in rabbit hearts. The purpose of this study was to describe the effect of chronic hypoxia from birth on myocardial reperfusion injury in the rat heart.. Normoxic hearts were obtained from rats housed in ambient air for 6 weeks (normoxic group); hypoxic hearts were obtained from rats housed in a hypoxic chamber (13%-14% oxygen) from birth for 6 weeks (hypoxic group). Isolated, crystalloid perfused working hearts were subjected to 30 min of global normothermic ischemia followed by 15 min of reperfusion; functional recovery was then measured in the two groups. The excretion of cyclic guanosine monophosphate (cGMP) in the coronary drainage was measured at the end of the preischemia and reperfusion periods.. The percent recovery of the left ventricular developed pressure and the first derivative of left ventricular pressure were significantly better in the hypoxic group than in the normoxic group. cGMP excretion in the coronary drainage was significantly increased during both the preischemia and reperfusion periods.. Chronic hypoxia from birth increased myocardial tolerance to ischemia-reperfusion injury with increased cGMP synthesis in the isolated heart model in rats.

Topics: Animals; Chronic Disease; Cyanosis; Cyclic GMP; Disease Models, Animal; Heart; Hypoxia; KATP Channels; Male; Myocardial Contraction; Myocardial Reperfusion Injury; Myocardium; Rats; Rats, Sprague-Dawley; Recovery of Function; Up-Regulation; Ventricular Function, Left; Ventricular Pressure

Lung function is often impaired after cardiac surgery and cardiopulmonary bypass (CPB), particularly in chronically cyanotic patients. This study aimed to evaluate lung function in a surgically created chronic cyanotic neonatal lamb model after CPB and deep hypothermic circulatory arrest (DHCA) and to assess the role of nitric oxide (NO) in the pathogenesis of increased pulmonary vascular resistance.. A chronic cyanosis model was surgically created in 7 lambs (4.7+/-0.8 days old) by anastomosing the pulmonary artery (PA) to the left atrium (LA). Another 7 lambs underwent a sham operation (control). One week later, the animals underwent shunt takedown and CPB with 90 minutes of DHCA at 18 degrees C. Cardiac index (CI), pulmonary vascular resistance index (PVRI), lung dynamic compliance (Cdyn), alveolar-arterial oxygen difference (AaDO2), left atrial plasma nitrate/nitrite (NO metabolites) levels, and pulmonary cGMP production (concentration difference between LA and PA) were measured before CPB and at 1 and 2 hours after reperfusion.. The cyanosis model consistently produced significantly lower arterial oxygen tension (34.8+/-2.3 vs 93.1+/-8.8 torr in control, p < 0.001) and Qp/Qs (0.6+/-0.1 vs 1.0+/-0.0 in control, p < 0.001) than controls. Postoperative PVRI was significantly lower in the cyanosis group than in controls, although CPB with DHCA significantly elevated PVR in both cyanotic and control animals. There were no significant differences in AaDO2 and Cdyn after CPB between groups. The level of NO metabolites did not change before or after CPB in either cyanotic or acyanotic animals. NO metabolite levels tended to be higher in the cyanotic animals (p = 0.08). There was no significant difference in pulmonary cGMP production between both groups.. These findings suggest that CPB with DHCA, per se, does not affect NO production in cyanotic or acyanotic neonatal lambs but causes increased PVR in both groups. Chronic cyanosis does not result in reduced pulmonary function after CPB with DHCA, and is associated with lower PVR. The mechanism may involve an increased NO production in cyanotic animals.

Topics: Animals; Animals, Newborn; Cardiac Output; Cardiopulmonary Bypass; Chronic Disease; Cyanosis; Cyclic GMP; Disease Models, Animal; Endothelium, Vascular; Heart Arrest, Induced; Lung; Lung Compliance; Nitrates; Nitric Oxide; Nitrites; Pulmonary Diffusing Capacity; Sheep; Vascular Resistance