Hemodynamic responses to acute carboxyhemoglobinemia in the rat.

The effects of carbon monoxide on the hemodynamics of the adult rat were investigated. A number of parameters were measured using an open-chest, chloralose-urethan anesthetized preparation. Our experiments showed this anesthetic agent to have several advantages over pentobarbital sodium. One group inhaled 150 ppm CO for 0.5-2 h, carboxyhemoglobin (HbCO) reaching 16%. Heart rate, cardiac output, cardiac index, dF/dtmax (aortic), and stroke volume rose significantly; mean arterial pressure, total peripheral resistance, and left ventricular systolic pressure fell, whereas stroke work, left ventricular dP/dtmax, and stroke power changed little. These effects were evident at a HbCO saturation as low as 7.5% (0.5 h). A second group inhaled 500 ppm CO for 5-48 h, HbCO reaching 35-38%. The same parameters changed in the same direction as in the first group, with mean arterial pressure and peripheral resistance remaining depressed, while heart rate, cardiac output, cardiac index, and stroke volume remained elevated. Heart rate and arterial systolic pressure were also monitored in conscious rats; rats in one group inhaled 500 ppm CO for 24 h, and rats in a second group were injected with a bubble of pure CO ip. In both cases heart rate was sharply elevated and blood pressure depressed as HbCO saturation increased. Both parameters recovered on CO washout. There was no significant difference between the response to inhaled vs. injected CO.

Cardiac response of the fetal rat to carbon monoxide exposure.

Groups of pregnant rats were exposed to 200, 166, and 157 ppm CO for the last 17 out of 22 days of gestation. The number of fetuses per dam or live young per litter were unaffected. Neonatal red blood cell count was depressed, whereas mean corpuscular hemoglobin and volume were elevated. Birth weight was reduced; heart weight, heart weight-to-body weight ratio, placental weight, and placental weight-to-body weight ratio were elevated. Identical results were obtained in studies of fetuses examined daily during the final 4 days of gestation at 200 ppm. Cardiomegaly present at birth was not due to elevated myocardial water content, as dry heart weight and wet heart weight increased proportionately. Heart DNA content (microgram) was increased at both 157 and 200 ppm CO in neonates and fetuses, whereas DNA concentration (microgram/mg dry wt) was similar to the controls. Cardiac hydroxyproline concentration (microgram/mg dry wt) and content (microgram) were unaffected in neonates by fetal CO exposure at 157 and 200 ppm, although the hydroxyproline content was elevated in fetuses at 157 ppm CO. Cardiac lactate dehydrogenase (LDH) M subunit composition was elevated from 4 days before birth, until birth, at 200 ppm CO, whereas total LDH activity was unchanged. Although neonatal myocardial cytochrome c was unaltered by fetal CO exposure, myoglobin concentration (mg/g) and content (mg) were elevated. Prolonged maternal CO inhalation thus exerts significant effects on fetal body and placental weight, heart weight, enzyme constituents, and composition.

Postnatal carbon monoxide exposure: immediate and lasting effects in the rat.

Groups of newborn rats inhaled 500 ppm CO for 32 days, after which they continued development in ambient air. The ratio of heart weight to body weight increased sharply after birth, peaked at 14 days of age, and then fell progressively but remained above that of normal rats at 68 and 107 days of age. At 14 days of age, the weight of the left ventricle plus interventricular septum (LV + S) exceeded the controls by 80%, whereas the weight of the right ventricle (RV) was 100% greater. RV weight remained significantly greater than that of the controls at 68, 107, and 217 days of age. The ratio of RV weight to LV + S weight remained higher than that of the controls both during and after CO exposure. Myocardial deoxyribonucleic acid (DNA) concentration (microgram/mg dry wt) declined more rapidly in the CO-exposed groups during the first 2 wk. DNA content (microgram/LV + S + RV) was not significantly different. There were no differences in DNA concentration or content after CO exposure. Hydroxyproline, used as an index of collagen content, was unaffected by postnatal cardiomegaly. Hydroxyproline concentration was depressed only during the first 3 wk. Cardiac cytochrome c concentration was depressed and lactate dehydrogenase M subunit composition elevated only during CO exposure. Neither lactate dehydrogenase specific activity nor myoglobin concentration was altered during or after CO treatment. Neither the DNA nor hydroxyproline data provide an explanation for "persistent cardiomegaly."