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Indomethacin-induced blood flow distribution in premature and full-term piglets
D L Dyess1, G L Peeples, J L Ardell
1Department of Surgery, University of South Alabama College of Medicine, Mobile.
Insights
Indomethacin (IND) can reduce intestinal blood flow, increasing the risk of gastrointestinal issues in infants. This effect is more pronounced in more developed animals, suggesting ischemic injury.
Area of Science:
- Neonatal physiology
- Gastrointestinal pharmacology
- Pediatric cardiology
Background:
- Indomethacin (IND) is used to close patent ductus arteriosus (PDA) in premature infants.
- IND has been linked to gastrointestinal (GI) complications like perforations and necrotizing enterocolitis (NEC).
- IND's vasoactive properties may reduce intestinal blood flow.
Purpose of the Study:
- To investigate the effects of IND on hemodynamic parameters and regional blood flow in preterm and term piglets.
- To determine if IND causes selective reduction in GI blood flow.
- To assess how animal development influences IND's impact on GI perfusion.
Main Methods:
- Intravenous infusion of IND (0.4 mg/kg) in three groups: preterm, 1-2 day old, and 7-14 day old piglets.
- Measurement of blood pressure (BP), heart rate (HR), cardiac output (CO), total peripheral resistance (TPR), and regional blood flows at baseline and 15, 60, 120 minutes post-infusion.
- Analysis of hemodynamic and regional blood flow data across different age groups.
Main Results:
- IND did not significantly alter hemodynamics or regional blood flow in preterm piglets.
- In 1-2 day old piglets, IND increased BP and TPR, decreasing GI blood flow in the esophagus, stomach, and rectosigmoid.
- In 7-14 day old piglets, IND decreased CO and increased TPR, causing significant GI blood flow reduction, particularly in the small intestine and colon, due to decreased mucosal blood flow.
Conclusions:
- Indomethacin can induce selective mucosal ischemia in the gastrointestinal tract.
- The ischemic effect of IND on the GI tract is more severe in more developed piglets.
- IND-induced GI disturbances may stem from ischemic injury to the mucosa, potentially exacerbated by prior ischemia-reperfusion injury.
Abstract:
Indomethacin (IND), widely used in premature infants to effect nonoperative closure of patent ductus arteriosus (PDA), has been implicated in gastrointestinal tract (GI) perforations and necrotizing enterocolitis (NEC). The vasoactive effects of IND could simultaneously affect regional blood flow distribution, specifically a decrease in intestinal blood flow. This study determined blood pressure (BP), heart rate (HR), cardiac output (CO), total peripheral resistance (TPR) and regional blood flows (mL/min/g) at baseline, 15, 60, and 120 minutes after intravenous infusion of IND (0.4 mg/kg) in three groups: preterm piglets delivered 7 to 10 days before term; 1- to 2-day-old piglets; and 7- to 14-day-old piglets. IND did not significantly affect hemodynamic parameters (BP, HR, CO, TPR) or regional blood flows to the heart, central nervous system, kidney or GI tract in the premature animals. In 1- to 2-day-old animals, a significant increase in BP and TPR occurred at 120 minutes, with significant decreases in blood flow to the GI tract in the esophagus, stomach, and rectosigmoid. In the 7- to 14-day group CO significantly decreased while TPR increased. Significant decreases in blood flow occurred throughout the GI tract, most pronounced in the small intestine and colon, essentially due to decreased mucosal blood flow. Our study indicates that indomethacin can cause selective GI tract mucosal ischemia, and that the effect is increased in the more developed animal. This effect on mucosal blood flow suggests the GI tract disturbances seen after IND administration are due to an ischemic injury to mucosa previously affected by ischemia-reperfusion injury from other stresses.