No abstract

The synthetic amino terminal fragment of parathyroid hormone, PTH-(1-34), is a potent coronary artery vasodilator in the dog. In the present study, using instrumented open-chest dogs, we have performed the initial characterization of this effect and showed other dose-related cardiovascular effects of the hormone. A near-maximal flow response was obtained after intracoronary injection of 0.024 nmol X kg-1 PTH-(1-34) with minor, if any, concomitant changes in mean blood pressure, contractile force, or heart rate. At higher doses, mean blood pressure decreased while contractile force and heart rate increased in dose-dependent fashion. Infusion of PTH-(1-34) for 20 min showed that the vasodilatory effect could be sustained without a concomitant decrease in mean arterial pressure. Pharmacological characterization showed for the first time that the coronary response to PTH-(1-34) was unaltered in the presence of beta- or alpha-adrenergic, muscarinic, or histaminergic blockades. We conclude that PTH-(1-34), an endogenous circulating calcemic peptide, produces a large increase in coronary blood flow at doses sufficiently low to preclude complicating effects on blood pressure, contractile force, and heart rate. Furthermore, the results suggest that the vasodilatory effects may be specific.

ABSTRACT. Ultrastructural changes in cardiac sarcoplasmic reticulum (SR) have been reported during postnatal development of the mammalian heart, but the functional significance of these observations has not been well characterized. Calcium release from SR in intact myocardial preparations was determined by the contractile characteristics of postrest contractions. Isometric tension and the maximum rate of tension development of the first contraction following intervals of electromechanical quiescence (rest) were related to steady-state tension and maximum rate of tension development during contraction at constant frequency (1.0 Hz) in isolated left atrial strips from newborn (1-7 days), immature (14-21 days), and adult (more than 6 months) rabbits. The first postrest contraction was increased as a function of the rest interval rate of tension development, defined as postrest potentiation, in all three age groups and reached a maximum value at rest intervals of more than 20 s. Tension developed by the first contraction following a 60-s rest interval was potentiated less in newborn and immature atria than in adult atria at an extracellular calcium concentration ([Ca],) of 2.5 mM, an age-related difference most marked in the immature. Ryanodine (5.0 x M), a putative blocker of calcium release from cardiac SR, abolished postrest potentiation providing evidence that calcium release from SR is the predominant determinant of the postrest contraction. Postrest tension in atria from the immature rabbit heart was significantly increased both in absolute terms and relative to steady-state tension following stabilization under conditions which increase intracellular [Ca] ([Cali), i.e. increasing [Ca],, increasing tonicity, or decreasing extracellular sodium concentration ([Na],). In contrast, postrest tension in atria from the adult rabbit heart decreased relative to steady-state tension under conditions that increase [Cali. Rest potentiated contraction to a similar extent in both age groups (approximately 300% of steady-state) but this maximum was obtained under markedly different ionic conditions. Maximum postrest potentiation occurred at 2.5 mM [Ca], and 153.0 mM [Na], in the adult atria whereas maximum potentiation occurred at 5.0 mM [Ca], and 87.0 mM [Na], in immature atria. Results from experiments in which [Ca], was increased during a 60-s rest interval suggest that the predominant effects of [Ca], on postrest potentiation are attributable to [Ca],-dependent changes in [Cali as opposed to rest-dependent changes in

A ratio of mean aortic systolic and diastolic velocitiesdetermi ned by continuous wave dopp 1 er (Cl•/) has been shown to correlate with ductal {PDA) % left-to-right shunt (LRS). A new simpler ratio, velocity index (VI), of peak systolic to diastolic velocities can be determ ined from peripheral arteries without planimetry. Shown to correlate with clinical estimates of POA-LRS in 22 infants, VI has not been va lidated by measured LRS. We examined 8 pigs (mean weight 6.1 kg, mean age 23.6 days). PDAwas created by balloon cat heter dilation. 4 stud ies were before PDA (no angiographic shunt) , 4 acute PDA, and 7 chronic (mean 15. 8 days) PDA.