The heart is the first organ to function in the vertebrate embryo (Burggren and Keller, 1997; Gilbert, 1990). Concomitant with heart development is the formation of blood elements and hemoglobin (Hb). The early convection of these newly formed elements has led to speculation on their importance to gas exchange (Adolph, 1979; Boell et al. 1963; Burggren and Just, 1992; Burggren and Pinder, 1991; Burggren and Territo, 1995). The assumption that blood convection is critical to gas exchange has gained circumstantial support from morphological observations that gill differentiation, and blood flow in both the gills and the caudal arteries, occurs immediately after the heart begins to beat (Ballard, 1968; Medvedev, 1937; Nieuwkoop and Faber, 1967; Taylor and Kollros, 1946). Furthermore, it has been suggested that these changes in circulation may contribute to the sharp initial rise in M . O ∑ during early development (Romanoff, 1960). The synchronous appearance of blood convection and the need for convection to supplant diffusive O 2 delivery between the environment and the tissues has been termed ‘synchronotropy’ (Burggren and Territo, 1995). Although the link between Hb convection and early embryonic/larval O 2 consumption has become dogma, there exist no data that have explicitly tested the hypothesis of synchronotropy. However, we have put forward an opposing hypothesis that specifically questions these assumptions of synchronotropy (Burggren and Territo, 1995). This alternative hypothesis, termed ‘prosynchronotropy’, argues that the cardiovascular system begins to generate convective blood flow well before there is an absolute need for internal convection of oxygenated blood. Early results have begun to clarify our understanding of when convective O 2 transport becomes necessary in embryos and larvae (Mellish et al. 1998; Pelster and Burggren, 1996), but these studies do not include complete metabolic and cardiovascular profiles throughout development and the interplay that occurs between these two systems. The purpose of this study was to evaluate the validity of ‘prosynchronotropy’ utilizing embryos of the clawed frog Xenopus laevis. This particular species is well suited to test this hypothesis because it has a well-studied developmental sequence, lays large numbers of eggs in a laboratory setting, has embryos that are free-living and transparent and because considerable descriptive physiological and morphological 1461 The Journal of Experimental Biology 201, 1461–1472 (1998) Printed in Great Britain © The Company of Biologists Limited 1998 JEB1232 The present study investigates the ontogeny of cardio- respiratory physiology in Xenopus laevis where O 2 transport is obstructed. Animals were raised from eggs (NF stage 1) to metamorphic climax (NF stage 63), while maintained either in air or in chronic 2 kPa CO, which functionally ablates O 2 transport by hemoglobin (Hb). Whole-animal rate of oxygen consumption (M . O ∑), whole- body lactate concentration, individual mass, heart rate (fH) and stroke volume (VS) were measured. Additionally, cardiac output (Q . ) and the ratio of the rate of oxygen consumption to the total rate at which oxygen is transported in the blood (M . O ∑/Q . O ∑) were calculated to determine limitations imparted when O 2 transport is impaired. Our data on early development suggest that the onset of convective blood flow occurs prior to the absolute need for convection to supplement diffusive transport. Values for M . O ∑, whole-body lactate concentration, mass and fH did not differ significantly between controls and CO-exposed animals. However, CO-exposed animals showed a significant (P<0.05) increase in VS, M . O ∑/Q . O ∑ and Q . compared with controls. These results indicate that limiting blood O 2 transport is not deleterious to metabolism and development as a whole and that convective oxygen transport via Hb is not essential for normal cardiovascular or respiratory function during larval development. Key words: ontogeny, development, Xenopus laevis, carbon monoxide, oxygen consumption, lactate, heart rate, stroke volume, cardiac output, O2 consumption/transport quotient. Summary Introduction CARDIO-RESPIRATORY ONTOGENY DURING CHRONIC CARBON MONOXIDE EXPOSURE IN THE CLAWED FROG XENOPUS LAEVIS PAUL R. TERRITO* AND WARREN W. BURGGREN Department of Biological Sciences, University of Nevada at Las Vegas, 4505 Maryland Parkway, Las Vegas, NV 89154-4004, USA *Present address: National Institutes of Health, National Heart, Lung, and Blood Institute, Laboratory of Cardiac Energetics, NHLBI, Building 1, Room B3-07, 9000 Rockville Pike, Bethesda, MD 20892, USA (e-mail: territop@zeus.nhlbi.nih.gov) Accepted 23 February; published on WWW 20 April 1998