Effect of prolonged selective intramesenteric arterial vasodilator therapy on intestinal viability after acute segmental mesenteric vascular occlusion.

OBJECTIVE: To evaluate the effect of selective intramesenteric artery vasodilator infusion on intestinal viability in a rat model of acute segmental mesenteric vascular occlusion. SUMMARY BACKGROUND DATA: Although intramesenteric arterial vasodilator infusion may be an effective treatment for nonocclusive mesenteric ischemia, it has also been advocated to increase collateral blood flow after mesenteric vascular occlusion. However, the authors have previously found that intraarterial vasodilators actually reduce collateral blood flow acutely, by preferentially dilating the vasculature of adjacent, nonischemic mesenteric vascular beds, a phenomenon well established in other organs. METHODS: A segment of rat ileum was acutely devascularized, with blood flow provided only by collateral arterial vessels from adjacent, nonischemic bowel. Papaverine (30 or 40 microg/kg/min), isoproterenol (0.06 microg/kg/min), norepinephrine (0.1 or 0.2 microg/kg/min), or vehicle saline was continuously infused into the cranial (superior) mesenteric artery for 48 hours. Viability was then assessed using previously established, objective gross and microscopic criteria. RESULTS: Although papaverine increased total mesenteric blood flow in normally vascularized rats, it not only failed to improve but actually significantly reduced the length of the devascularized segment maintained viable by collateral blood flow after 48 hours. Isoproterenol had a similar effect. Norepinephrine infusion decreased both normal mesenteric blood flow and viable segment length. CONCLUSIONS: These findings suggest that intraarterial vasodilator therapy fails to improve intestinal viability after segmental mesenteric vascular occlusion.

The fundamental hemodynamic mechanism underlying gastric "stress ulceration" in cardiogenic shock.

Acute hemorrhagic ulceration of the gastric mucosa is seen frequently in patients with hypovolemic or cardiogenic shock. Although such lesions clearly are related to regional gastric ischemia, little attention has been directed at the underlying mechanism(s) mediating the ischemia itself. To this end, anesthetized pigs were subjected to sustained cardiogenic shock (mild hemorrhage and pericardial tamponade) such that cardiac output was reduced to 38 +/- 1% of the baseline level for 4 hours, followed by release of the tamponade, reinfusion of the shed blood, and resuscitation for 2 hours. During the period of shock, there was profound regional gastric ischemia, resulting from severe and disproportionate gastric vasoconstriction. "Blinded" gross and microscopic evaluation of the stomachs removed after the experiment revealed severe mucosal ischemic necrosis, hemorrhage, and ulceration, whereas sham-operated pigs showed no lesions. The characteristics of this model therefore mimic the essential features of the gastric "stress ulceration" syndrome. Prior confirmed total alpha-adrenergic blockade with phenoxybenzamine failed to alter these features significantly. In contrast, prior ablation of the renin-angiotensin axis, whether by angiotensin-converting enzyme inhibition with teprotide or by bilateral nephrectomy, significantly and substantially ameliorated the ischemia, vasospasm, and mucosal injury. In this model of cardiogenic shock, acute gastric mucosal "stress ulceration" is caused by a disproportionately severe regional gastric ischemia resulting from selective splanchnic vasospasm that is unaffected by sympathetic blockade but abolished by prior ablation of the renin-angiotensin axis. Like nonocclusive small bowel ischemia, ischemic colitis, and the "shock liver" syndrome, gastric "stress ulceration" is yet another component of the multiple splanchnic organ failure syndrome that appears to be mediated primarily by the remarkable sensitivity of the splanchnic vascular bed to the renin-angiotensin axis.