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Biomedical subjects

A H From

Publications and source records attributed to A H From.

79 records · Page 5Linked to original sources
PubMed1970

Complement in endotoxin shock: effect of complement depletion on the early hypotensive phase.

The complement (C) inhibition caused by bacterial endotoxin is well known, but the relationship of this reaction to endotoxin shock is unclear. Anesthetized dogs were therefore given Escherichia coli endotoxin intravenously with or without prior C depletion by a purified cobra venom factor (CVF). Mean aortic blood pressures (MAP) and C levels were measured. Intravenous CVF usually caused an early transient drop of MAP and a profound, long-lasting drop in C. Bacterial lipopolysaccharide (LPS) alone always caused a sudden (within 2 min) drop in MAP which was followed by partial recovery and then more long-lasting depression. Moderate drops in C usually occurred. In animals pretreated with CVF so that C levels were markedly depressed (<25% of control), LPS did not elicit the immediate MAP drops; however, a later (after 5 to 20 min) MAP drop always occurred. CVF pretreatment did not modify LPS-induced mortality. CVF effects were not caused by LPS contamination. These data show that the early hemodynamic responses of the dog to LPS may be mediated through the complement system.

Journal Article↗
PubMedDate not supplied

In vivo interaction of AR-L 115BS (Vardax) with the adrenergic nervous system.

In vitro studies have demonstrated that AR-L 115BS (AR-L), a new orally active nonglycosidic inotropic agent with vasodilator properties, does not act via adrenergic receptors. However, because AR-L is a phosphodiesterase inhibitor and interaction with the adrenergic nervous system may exist in vivo, we compared the actions of intravenous AR-L, isoproterenol, and propranolol, alone and in combination, in normal dogs. In seven awake morphine-sedated dogs, AR-L (4 mg/kg i.v.) did not alter circulating catecholamines despite increasing maximum rate of change of left ventricular pressure (dP/dt) by 76%. In anesthetized dogs, peak inotropic effect of AR-L occurred at 6 mg/kg (dP/dt from 5,450 +/- 1,280 to 12,000 +/- 3,050 mm Hg/s). Propranolol (1 mg/kg) depressed dP/dt from 5,725 +/- 2,032 to 2,530 +/- 631 mm Hg/s, and this was completely reversed by increasing doses of AR-L (2-30 mg/kg) but the maximum dP/dt attained in these dogs (6,050 +/- 221 mm Hg/s) remained below the level achieved by AR-L in the absence of propranolol. To determine if that difference was due to an interaction of AR-L with the adrenergic nervous system, the effect of AR-L on isoproterenol activity was studied in groups of beta-blocked and unblocked animals. In either group, the dose-response curve of dP/dt to isoproterenol was shifted upward by AR-L, but the actions of the two drugs were additive without real synergism (e.g., after propranolol:isoproterenol 10 micrograms/min 73%; AR-L 6 mg/kg 81%; both 160%. In unblocked dogs, the results were: isoproterenol 2 micrograms/min 96%; AR-L 1 mg/min 39%; both 138%). Similarly, isoproterenol and AR-L were only additive in their effects on heart rate and systemic vascular resistance. Thus, although AR-L is a phosphodiesterase inhibitor, its predominant mechanism of action appears to be independent of the adrenergic nervous system.

Animals↗