Oxidized-raffinose cross-linked hemoglobin, Hemolink, at doses < or =0.6 g/kg were well tolerated in healthy volunteers with no evidence of organ dysfunction. Further investigation of its potential use in surgical and trauma settings appears warranted.

No abstract

Ethanol has been shown to increase markedly portal blood flow, primarily by increasing intestinal blood flow. This effect of ethanol is reproduced by acetate, infused at rates equivalent to those leading to endogenous acetate production following ethanol administration. The physiological mediator, adenosine, is also known to increase markedly intestinal and portal tributary blood flow. We have shown that adenosine receptor blockade with 8-phenyltheophylline completely abolishes the effects of ethanol, acetate, and adenosine on intestinal and portal blood flow, suggesting that increases in adenosine tone may constitute a common mechanism mediating the actions of both ethanol and acetate on the splanchnic vasculature. Studies are also presented that show that acetate administration has marked effects on central nervous system function. On two tests, motor coordination and anesthetic potency, both ethanol and acetate showed similar effects. The effects of acetate were fully abolished by 8-phenyltheophylline. The effects of ethanol were partially blocked by 8-phenyltheophylline, with a greater effect of this blocker being seen at low doses of alcohol. Whereas ethanol at low doses increased locomotor activity in mice, acetate markedly reduced it. The effect of acetate on locomotion was fully reversed by the adenosine receptor blocker 8-phenyltheophylline, whereas the activating effect of ethanol on locomotion was markedly enhanced by this blocker. These data suggest that the actions of ethanol on locomotor activity normally result from the combination of a direct stimulatory effect of ethanol per se and an inhibitory effect of acetate, produced endogenously from ethanol. When the latter effect of acetate is abolished by adenosine receptor blockade, the activating effect of ethanol is fully expressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Recent studies have shown neuroprotective effects of acetylsalicylic acid (ASA) in cell cultures and hippocampal slices. The present study demonstrates similar effects in a whole-animal modal of focal ischemic stroke. Focal cortical ischemia was produced in Wistar rats by ligation of the common carotid and middle cerebral arteries. Subjects were sacrificed 8 days after ligation, and infarct volume was assessed via automated densitometry. Significant reductions in infarct volume were seen with i.p. ASA doses of 15 mg/kg and above. Reductions occurred when ASA was injected 2 h or 30 min before ligation, but not when it was injected 8 or 24 h before, or 30 min after ligation.

In this study we report the effect on splanchnic hemodynamics of acute oral ethanol at doses ranging from 0.25 to 4.0 g/kg body wt. Flows were determined by use of a radioactive microsphere technique. Ethanol was found to increase portal blood flow by 23-57%. In awake rats this increase reached a plateau at the 0.5 g/kg dose. In ketamine-anesthetized rats, the increase was observed only at doses of 3.0 g/kg or more, with the response at doses of 0.5, 1.0, and 2.0 g/kg being suppressed by ketamine. Inhibition of alcohol dehydrogenase by intra-arterial administration of 4-methylpyrazole resulted in suppression of the liver blood flow increase after ethanol was administered to awake animals. Ethanol in the range of doses studied did not result in changes in blood glucagon levels. Rats fed ethanol-containing diets for 4 wk and withdrawn for 18 h had the same response to acute oral ethanol as did naive rats. It is suggested that ethanol metabolism mediates the effects of ethanol on splanchnic blood flow. An increase in splanchnic blood flow when concurrent with an increase in liver O2 consumption induced by ethanol might protect the liver from hypoxic damage.

This study compared systemic hemodynamic and organ blood flow responses to equipotent concentrations of halothane and sevoflurane during spontaneous ventilation in the rat. The MAC values for halothane and sevoflurane were determined. Cardiac output and organ blood flows were measured using radiolabeled microspheres. Measurements were obtained in awake rats (control values) and at 1.0 MAC halothane or sevoflurane. The MAC values (mean +/- SEM) for halothane and sevoflurane were 1.10% +/- 0.05% and 2.40% +/- 0.05%, respectively. The PaCO2 increased to a similar extent in both groups compared with control values. During halothane anesthesia, heart rate decreased by 12% (P < 0.01), cardiac index by 26% (P < 0.01), and mean arterial blood pressure by 18% (P < 0.01) compared with control values. Stroke volume index and systemic vascular resistance did not change. During sevoflurane anesthesia, hemodynamic variables remained unchanged compared with control values. Coronary blood flow decreased by 21% (P < 0.01) and renal blood flow by 18% (P < 0.01) at 1.0 MAC halothane, whereas both remained unchanged at 1.0 MAC sevoflurane. Cerebral blood flow increased to a greater extent with halothane (63%; P < 0.01) than with sevoflurane (35%; P < 0.05). During halothane anesthesia, hepatic arterial blood flow increased by 48% (P < 0.01), whereas portal tributary blood flow decreased by 28% (P < 0.01). During sevoflurane anesthesia, hepatic arterial blood flow increased by 70% (P < 0.01) without a concomitant reduction in portal tributary blood flow. Total liver blood flow decreased only with halothane (16%; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The increase in portal blood flow induced by ethanol appears to be adenosine mediated. Acetate, which is released by the liver during ethanol metabolism, is known to increase adenosine levels in tissues and in blood. The effects of acetate on portal blood flow were investigated in rats using the microsphere technique. The intravenous infusion of acetate (7-250 mumol.kg-1.min-1) resulted in vasodilation of the preportal vasculature and in a dose-dependent increase in portal blood flow [control, 39.1 +/- 2.6 ml.kg-1.min-1; acetate (250 mumol.kg-1. min-1), 68.7 +/- 4.0 ml.kg-1.min-1]. This acetate-induced increase in portal blood flow was suppressed by the adenosine receptor blocker, 8-phenyltheophylline. Using the A1-adenosine receptor agonist N-6-cyclohexyl adenosine and the A2-agonist 5'-N-ethylcarboxamido adenosine, we demonstrate that the effect of adenosine on the preportal vasculature is mediated by the A2-subtype of adenosine receptors. In conclusion, these data support the hypothesis that the increase in portal blood flow after ethanol administration results from a preportal vasodilatory effect of adenosine formed from acetate metabolism in extrahepatic tissues.

The relationship between portal tributary blood flow (PBF) and hepatic arterial blood flow (HAF) was studied in awake, unrestrained rats with the radiolabeled microsphere technique. Six distinct patterns of response emerged. In group A (PBF+, HAF 0), ethanol, acetate, glucagon, prostacyclin, and a mixed diet increased PBF without a change in HAF; in group B (PBF+, HAF+), adenosine and histamine increased both PBF and HAF; in group C (PBF 0, HAF+), isoflurane and triiodothyronine did not change PBF but increased HAF; and in group D (PBF-, HAF+), halothane and vasopressin decreased PBF and increased HAF. Acute partial portal vein ligation decreased PBF (56%) and increased HAF (436%). Hypoxia (7.5% O2) decreased PBF (28%) and increased HAF (110%). In group E (PBF+, HAF-), acute hepatic artery ligation increased PBF (35%) and reduced HAF (74%), while in group F (PBF-, HAF-), thyroidectomy reduced PBF and HAF (36 and 47%, respectively). All blood flow responses were accompanied by the expected changes in both portal tributary and hepatic arterial vascular resistances. The data suggest that the portal and hepatic arterial vascular territories have regulatory mechanisms that allow for independent changes.