Biomedical subjects

Dane A Crossley

Publications and source records attributed to Dane A Crossley.

5 recordsLinked to original sources

PubMed2003

Maturation of cardiovascular control mechanisms in the embryonic emu (Dromiceius novaehollandiae).

Our understanding of avian embryonic cardiovascular regulation has been based on studies in chickens. The present study was undertaken to determine if the patterns established in chickens are generally applicable to the emu, a ratite bird species. We studied cardiovascular physiology over the interval from 60% to 90% of the emu's 50-day incubation period. During this period, embryonic emus exhibit a slight fall in resting heart rate (from 171 beats min(-1) to 154 beats min(-1)) and a doubling of mean arterial pressure (from 1.2 kPa to 2.6 kPa). Exposures to 15% or 10% O(2) initially decreased heart rate during the first period of emu incubation studied [60% of incubation (60%I)] but increased heart rate in the 90%I group. Arterial pressure responded to hypoxia with an initial depression (-1.6 kPa) at 60%I and 70%I but showed no response during the later periods of incubation (80%I and 90%I). In addition, tonic stimulation of both cholinergic and adrenergic (alpha and beta) receptors was present on heart rate at 70%I, with the cholinergic and beta-adrenergic tone increasing in strength by 90%I. Arterial pressure was dependent on a constant beta-adrenergic and constant alpha-adrenergic tone from 60%I to 90%I. A comparison with embryonic white leghorn chickens over a similar window of incubation revealed that emus and white leghorn chickens both possess an adrenergic tone on heart rate and pressure but that only emus possess a cholinergic tone on heart rate. Collectively, these data indicate that the maturation of cardiovascular control systems differs between white leghorn chickens and emus, inviting investigation of additional avian species to determine other patterns.

Animals↗

PubMed2003

Ontogeny of baroreflex control in the American alligator Alligator mississippiensis.

Baroreflex regulation appears in different species at different points in embryonic development. This study was designed to understand the development of the baroreflex in embryos of the American alligator at four different points of embryonic development (60%, 70%, 80% and 90% of a total incubation period of 72 days) and in 1-week-old hatchlings. Data from a separate study on 1-year-old alligators were included for comparison. The gain of the cardiac limb of the baroreflex was calculated from heart rate changes triggered by pharmacological manipulation of arterial pressure with sodium nitroprusside and phenylephrine. The results demonstrated that a vagally mediated hypertensive baroreflex was present during the final 30% of alligator development. A hypotensive baroreflex was not present in embryos but appeared in hatchlings, mediated by a combined effect of vagal and sympathetic efferents. Absolute baroreflex gain was maximal at 80% of incubation (41.22 beats kPa(-1) min(-1)) and dropped thereafter, reaching a minimum in 1-year-old alligators (9.69 beats kPa(-1) min(-1)). When the baroreflex gain was normalized to resting arterial pressure and heart rate, the maximum gain was observed in 1-year-old alligators (normalized index of 2.12 versus 0.75 in hatchlings and 0.69 as the highest gain in embryos). In conclusion, baroreflex regulation appeared during embryonic development with a substantial gain. These findings indicate that embryonic development is a period of preparation for cardiovascular regulatory mechanisms that will be necessary in adult life and that the baroreflex control mechanism is required for cardiovascular control during ontogeny.

Alligators and Crocodiles↗

PubMed2002

Cardiovascular regulation during hypoxia in embryos of the domestic chicken Gallus gallus.

Renewed interest in the use of the embryonic chicken as a model of perinatal cardiovascular regulation has inspired new questions about the control mechanisms that respond to acute perturbations, such as hypoxia. The objectives of this study were to determine the cardiovascular responses, the regulatory mechanisms involved in those cardiovascular responses, and whether those mechanisms involved the central nervous system (CNS) of embryonic chickens. Heart rate (f(H)) and blood pressure were measured in chicken embryos of different incubation ages during exposure to different levels of hypoxia (15, 10, and 5% O(2)). At all levels of hypoxia and at all developmental ages, a depression of f(H) and arterial pressure was observed, with the exception of day 20 embryos in 15 and 10% O(2). The intensity of the embryonic f(H) and blood pressure responses were directly related to the level of hypoxia used. Muscarinic and alpha-adrenergic receptor stimulation limited the hypoxic hypotension on days 15-19 and 15-21, respectively, as indicated after blockade with atropine and phentolamine. During the final 3 days of incubation, the intensity of the hypoxic hypotension was magnified due to alpha-vasodilation caused by beta-adrenergic and muscarinic receptor stimulation. In 19- to 21-day-old embryos, the f(H) response to hypoxia was limited by alpha-adrenergic receptor stimulation as indicated by the accentuated bradycardia after blockade with phentolamine. Furthermore, on day 21, atropine limited the hypoxic bradycardia, indicating that muscarinic receptors also play a role in the f(H) response at this age. In addition, the muscarinic actions on the heart and the adrenergic effects on the vasculature appeared to occur through a hypoxic-induced direct release from chromaffin tissue and autonomic nerve terminals. Thus, in embryonic chickens, the only cardiovascular response to hypoxia that involves the CNS was the cholinergic regulation of arterial pressure after day 15 of incubation. Therefore, although embryonic chickens and fetal sheep, the standard models of perinatal cardiovascular physiology, respond to hypoxia with a similar redistribution of cardiac output, the underlying mechanisms differ between these species.

Adrenergic Antagonists↗

PubMed2002

Cardiomyopathy in zebrafish due to mutation in an alternatively spliced exon of titin.

The zebrafish embryo is transparent and can tolerate absence of blood flow because its oxygen is delivered by diffusion rather than by the cardiovascular system. It is therefore possible to attribute cardiac failure directly to particular genes by ruling out the possibility that it is due to a secondary effect of hypoxia. We focus here on pickwickm171 (pikm171), a recessive lethal mutation discovered in a large-scale genetic screen. There are three other alleles in the pik complementation group with this phenotype (pikm242, pikm740, pikm186; ref. 3) and one allele (pikmVO62H) with additional skeletal paralysis. The pik heart develops normally but is poorly contractile from the first beat. Aside from the edema that inevitably accompanies cardiac dysfunction, development is normal during the first three days. We show by positional cloning that the 'causative' mutation is in an alternatively-spliced exon of the gene (ttn) encoding Titin. Titin is the biggest known protein and spans the half-sarcomere from Z-disc to M-line in heart and skeletal muscle. It has been proposed to provide a scaffold for the assembly of thick and thin filaments and to provide elastic recoil engendered by stretch during diastole. We found that nascent myofibrils form in pik mutants, but normal sarcomeres are absent. Mutant cells transplanted to wildtype hearts remain thin and bulge outwards as individual cell aneurysms without affecting nearby wildtype cardiomyocytes, indicating that the contractile deficiency is cell-autonomous. Absence of Titin function thus results in blockage of sarcomere assembly and causes a functional disorder resembling human dilated cardiomyopathies, one form of which is described in another paper in this issue.

Alternative Splicing↗

PubMed2002

Comparative cardiovascular development: improving the conceptual framework.

Immature vertebrates-either as an embryo in an egg, as free-living larva, or as an in utero fetus, are clearly not just small versions of adults. Their cardiovascular physiology (and doubtlessly other aspects of physiology) differs from that of adults both qualitatively and quantitatively. Yet, comparative cardiovascular physiologists have been relatively conservative in constructing a new (or at least modified) conceptual framework for the understanding of developmental cardiovascular physiology. We recommend that this framework rely less on the established cardiovascular truisms for adult cardiovascular physiology that are proving to be less useful and in instances even inaccurate for interpreting development of the heart and vasculature. We have suggested that three methodologies in particular be incorporated to a greater extent in studies of comparative cardiovascular development: (a) emphasis on multivariate approaches; (b) differentiation between absolute (extrinsic) and relative (intrinsic) time for development, and; (c) employment of time lines for both intra- and interspecific comparisons of the ontogeny of cardiovascular processes. While certainly none of these approaches are novel and others have previously dwelt at length on their importance in other contexts, we feel that the emerging framework for investigating cardiovascular physiological development would benefit from incorporating these and other approaches into experimental design as well as data analysis. Failing to do so results in a heavy dependence on analytical approaches typically used for adults, and thus under-appreciates the novelty and complexity of the developing vertebrate cardiovascular system.

Animals↗