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Biomedical subjects

E D Hawkins

Publications and source records attributed to E D Hawkins.

5 recordsLinked to original sources
PubMed1995

Cardiovascular and antilipolytic effects of the adenosine agonist GR79236.

Adenosine is known to produce cardiovascular effects such as bradycardia and hypotension via activation of myocardial (A1) and vascular (A2) receptors and antilipolytic effects through activation of adipocyte (A1) receptors. We established the cardiovascular and antilipolytic profile of the adenosine A1 agonist GR79236 (N6-[(1S,trans)-2-hydroxycyclopentyl]-adenosine) and compared it with CPA (N6-cyclopentyl-adenosine). GR79236 was approximately 3-fold less potent than CPA in inhibiting in vitro lipolysis. In conscious rats, both agents were shown to have antilipolytic and glucose-lowering properties. In rats instrumented with telemetry transmitters, orally administered CPA was one log unit more potent than GR79236 as a hypotensive and bradycardiac agent. In summary, GR79236 is an A1-selective adenosine agonist which reduces heart rate and mean arterial pressure and produces decreased plasma lipids and glucose levels.

Adenosine↗
PubMed1990

Two equally valid interpretations of the linear multicompartment mammillary pharmacokinetic model.

In pharmacokinetic modeling it is common to use compartmental structures to describe the disposition of a drug in the blood or plasma. Typically, a linear multicompartment mammillary model is equated with the multiexponential equation derived from observing the decay of the plasma drug concentration following an intravascular injection. Classically, the mammillary models are constructed so that the concentrations in each of the compartments are equal at steady state, the apparent volume of distribution at steady state is equal to the sum of the individual compartment volumes, and the apparent volume of each peripheral compartment is equal to the ratio of its intercompartmental rate constants times the central compartment volume. On the basis of what can be measured in the plasma, however, it is equally valid to assume that the sizes of the peripheral compartment volumes are equal to the central compartment volume and that the steady-state concentration in each peripheral compartment is equal to the ratio of its intercompartmental rate constants times the concentration in the central compartment. In fact, these are but two of an infinite number of interpretations of the peripheral compartment volumes.

Infusions, Intravenous↗
PubMed1988

alpha 1-Adrenergic responsiveness during coronary artery bypass surgery: effect of preoperative ejection fraction.

Elevated catecholamines and beta-adrenergic receptor hyporesponsiveness (or desensitization) have been demonstrated in failing human myocardium, but the role of the alpha-adrenergic receptor remains unclear. The authors tested the hypothesis that alpha 1-adrenergic responsiveness decreases in patients with impaired ventricular function undergoing coronary artery revascularization. Impaired ventricular function was defined prospectively by left ventricular ejection fraction less than or equal to 40% (group I, n = 12), and normal ventricular function by ejection fraction greater than 40% (group II, n = 22). Phenylephrine (Phe) pressor dose-response curves were established prior to anesthesia, during fentanyl anesthesia, and during fentanyl anesthesia plus hypothermic cardiopulmonary bypass at the time of aortic cross-clamp (anes + CPB/AXC). Polynomial regression of the Phe dose response curve estimated the Phe dose required to increase mean arterial blood pressure 20%, designated PD20. Although pre-anesthesia PD20 and anes + CPB/AXC PD20 values were not affected by ejection fraction, significant differences in PD20 (P less than 0.05) between groups occurred during fentanyl anesthesia (group I = 2.28 +/- 1.60 micrograms.kg-1, group II 1.57 +/- 0.98 micrograms.kg-1; mean +/- SD). Anes + CPB/AXC was associated with a significant reduction in PD20 in both groups compared with pre-anesthesia (P less than 0.01). Our results suggest impairment of alpha 1-adrenergic responsiveness occurs during fentanyl anesthesia in patients with ejection fractions less than or equal to 40% (evidenced by greater PD20 values). Although this impairment may be due to altered Phe pharmacokinetics, these results also support the possible existance of alpha 1-adrenergic receptor desensitization in this group. Reduction in PD20 during anes + CPB/AXC in all patients points to more powerful effects than fentanyl anesthesia alone; such influencing effects may include hemodilution, hypothermia, elevated plasma catecholamines, exclusion of the pulmonary circulation, or altered Phe pharmacokinetics.

Anesthesia, Intravenous↗
PubMed1980

The immotile cilia syndrome--one cause of persistent upper respiratory tract infection.

Four patients with persistent recurrent upper respiratory tract infections are presented. Electron microscopic studies of respiratory mucosal biopsies from these patients reveal ultrastructural abnormalities of cilia consisting of partial to complete loss of dynein arms, radial spoke disruption, and compound cilia. The concept of immotile cilia as an important cause of recurrent infections is receiving more attention. This study stresses the need for simple, rapid screening tests for cilial activity followed by electron microscopic evaluation in selected cases.

Biopsy↗