Intestinal Oxygen Research Articles

Dopamine effects on the intestinal circulation

The effects of intra-arterial infusion of dopamine on superior mesenteric artery blood flow, intestinal flow, intestinal oxygen consumption, and capillary density were studied in anesthetized dogs before and after blockade of dopamine receptors with haloperidol and after beta-adrenergic receptor blockade with propranolol. Mesenteric blood flow to a distal segment of the small intestine was measured with an electromagnetic blood flow-meter and intestinal oxygen consumption was calculated from the measured arteriovenous oxygen difference across the intestine and total blood flow. Intestinal capillary density was estimated from the clearance of 86Rb. In normal animals prior to dopaminergic or beta-adrenergic blockade, dopamine caused a dose-related decrease in mesenteric blood flow, intestinal oxygen consumption, and 86Rb clearance. Only the lowest dose of the drug, 1 mug/Kg.-min., did not significantly change the intestinal capillary density. In dogs pretreated with the dopamine receptor, antogonist, haloperidol, dopamine (20 mug/Kg.-min.) caused a significant increase in blood flow and oxygen consumption and did not significantly alter the number of perfused intestinal capillaries. These increases in haloperidol-blocked animals administered dopamine were reversed by propranolol. Our results indicate that dopamine caused smooth muscle contraction in mesenteric arterioles and precapillary sphincters, thereby producing intestinal ischemia and hypoxia. These findings with haloperidol and propranolol indicate that dopamine stimulates at least two different receptors in the canine mesenteric vascular bed: a constrictor receptor blocked by haloperidol and a dilator receptor blocked by propranolol.

Effects of vasoconstrictors on intestinal vascular resistance and oxygen extraction.

To delineate the mechanism through which vasoactive compounds alter intestinal oxygen consumption and to determine the pharmacological nature of the receptors involved, we quantitated the effects of vasoconstrictors on arteriovenous oxygen difference and on vascular resistance in isolated constant-flow perfused canine small bowel. Norepinephrine (NE) and sympathetic stimulation (SS) increased vascular resistance and depressed O2 extraction. These effects were not altered by beta-blockade, but were abolished by alpha-blockade. Since capillary filtration coefficients at constant-pressure perfusion and 86Rb extraction at constant flow are reported to diminish during NE and SS, it follows that these agents reduce O2 extraction by an alpha-adrenergic closure of precapillary sphincters. Vasopressin had similar effects which were not affected by adrenergic blocking agents. Epinephrine (Epi) in high doses or after propranolol produced the same effects as NE and SS. By contrast, Epi in low doses increased O2 and 86Rb extraction. This response to low doses of Epi was not affected by phentolamine, but was reversed by propranolol. We conclude that Epi in high doses or after propranolol depresses intestinal O2 extraction by the same mechanism as NE and SS, but the mechanism through which Epi increases intestinal O2 extraction is unclear.

Thyroid control of small intestinal oxygen consumption and the influence of sodium ions, oxyhen tension, glucose and anaesthesia.

1. Oxygen consumption of jejunum removed from either killed or anaesthetized euthytoid, hypothyroid and triiodothyronine (T3)-treated rats was measured polarographically in vitro. 2. Hypothyroidism induced by drinking 6-n-propyl-2-thiouracil depressed jejunal oxygen consumption. 3. Treatment of euthyroid rats with T3 stimulated jejunal oxygen consumption by 39% in the presence of 28 mM glucose and by 23% in its absence. 4. Sodium ions appear to play a major permissive role in the action of T3 on jejunal oxygen uptake. In the presence of sodium, T3 stimulated significantly the oxygen consumption by 23% while in the absence of sodium the stimulation was only 10% which was not significant. The sodium-sensitive oxygen uptake of the jejunum was expanded by 57% after T3 treatment.

Effects of Ouabain on Intestinal Oxygen Consumption

Most patients with fatal hemorrhagic necrosis of the gut were being administered a cardiac glycoside at the onset of their illness. Previously, our laboratory found that the rapid-acting cardiac glycoside, ouabain, constricted intestinal arterioles and reduced mesenteric blood flow. Since tissue necrosis presumes hypoxia as well as ischemia, we determined the effect of ouabain on intestinal oxygen consumption. Two in situ canine preparations were used: (1) an isolated loop of gut was autoperfused at constant blood flow, and perfusion pressure was measured across the loop; and (2) a segment of gut with uninterrupted circulation was used, and its blood flow was measured with an electromagnetic blood flow meter. An oxygen difference analyzer continuously measured oxygen content in arterial and venous blood photometrically in both preparations. Ouabain decreased oxygen consumption and increased mesenteric vascular resistance in the constant-flow preparation, exhibiting a more marked effect on oxygen uptake. The glycoside also reduced oxygen consumption and blood flow in the free-flow preparation. Since a reduced oxygen consumption could result from either decreased capillary perfusion or decreased metabolism, we measured Rb86 clearance which is an index of capillary perfusion; Rb86 is not metabolized. The clearance of Rb86 was decreased by ouabain. Our findings indicate that ouabain not only decreases intestinal blood flow but also decreases intestinal oxygen consumption, probably by constricting precapillary sphincters.

Effects of norepinephrine and sympathetic stimulation on extraction of oxygen and 86Rb in perfused canine small bowel.

Previous studies have shown that sympathetic stimulation can cause a redistribution of intestinal capillary blood flow. Our computer model of the intestinal circulation predicted that the diffusion parameters (e.g., capillary surface area and mean capillaryto-cell diffusion distance) altered by precapillary sphincter closure would be sufficient to affect intestinal oxygen extraction. To test this prediction in an animal model, we made continuous measurements of arteriovenous oxygen difference (ΔO 2 ) and perfusion pressure during constant-flow perfusion of isolated loops of canine small bowel. Intraarterial infusion of norepinephrine or stimulation of sympathetic nerves for 7 minutes produced sustained increases in vascular resistance and sustained reductions in arteriovenous ΔO 2 . Maximal changes in resistance and arteriovenous ΔO 2 occurred by the second minute of norepinephrine or sympathetic nerve stimulation, and subsequently both parameters escaped somewhat. The maximal and steady-state values of these parameters were dose-dependent or frequency-dependent. In other experiments, sympathetic nerve stimulation caused synchronous decreases in arteriovenous ΔO 2 and 86 Rb extraction. These results support the hypothesis that the infusion of norepinephrine and the stimulation of sympathetic nerves cause sustained reductions in the density of the perfused capillary bed which are sufficient to reduce intestinal extraction of Rb and oxygen despite constant-flow perfusion.

Sympathetic nervous control of intestinal O2 extraction.

All three of the functionally defined series-coupled elements within the intestinal microcirculation respond to sympathetic nerve stimulation: the resistance vessels, the precapillary sphincters which govern the exchange vessels, and the capicitance vessels(1). In our computor model of the intestinal circulation (2,3), oxygen delivery to the intestinal tissues is regulated by arteriolar resistance to blood flow while the precapillary sphincters determine the number of open perfused capillaries; thus they control the diffusion parameters for oxygen (i.e., capillary surface area and mean capillary-to-cell diffusion distance). The model predicts that sympathetic-induced reductions in the density of the perfused capillary bed will depress intestinal oxygen extraction. Therefore, the purpose of this work has been to test that prediction in an animal model. Since oxygen delivery is the product of the arteriovenous oxygen difference (A–V ∆O2) and blood flow, we have studied the effects of norepinephrine infusion and sympathetic stimulation on intestinal oxygen extraction under constant-flow conditions in order to eliminate blood flow as a variable.

Continuous positive-pressure breathing in acute hemorrhagic pulmonary edema.

Continuous positive-pressure breathing in acute hemorrhagic pulmonary edema.