Original ArticleProinflammatory Events in Right Ventricular Damage During Pulmonary Embolism: Effects of Treatment With Ketorolac in RatsWatts, John A PhD; Gellar, Michael A BS; Stuart, Lori K BS; Obraztsova, Maria MS; Kline, Jeffrey A MDAuthor Information From the Emergency Medicine Research, Carolinas Medical Center, Charlotte, NC. Received for publication April 17, 2009; accepted June 10, 2009. The authors report no conflicts of interest. Reprints: John A. Watts, PhD, Emergency Medicine Research, Carolinas Medical Center, Room 302, Cannon Research Center, 1542 Garden Terrace, PO Box 32861, Charlotte, NC 28232-2861 (e-mail: [email protected]). Journal of Cardiovascular Pharmacology: September 2009 - Volume 54 - Issue 3 - p 246-252 doi: 10.1097/FJC.0b013e3181b2b699 Buy Metrics Abstract Right ventricular (RV) damage contributes to poor clinical outcome after pulmonary embolism (PE). Our studies show that neutrophils contribute to RV dysfunction in rat PE. Present studies examine effects of the nonsteroidal anti-inflammatory drug, ketorolac, upon RV inflammation and dysfunction. RV inflammatory gene expression significantly increased 6 and 18 hours after PE [cytokine-induced neutrophil chemoattractant-1 (CINC-1) 18-fold and 24-fold; cyclooxygenase-2 21-fold and 32-fold]. Eighteen hours after PE, there was significant upregulation of adhesion molecules (selectin E 18-fold; intercellular adhesion molecule 1 14-fold), influx of neutrophils (myeloperoxidase activity 21-fold), depressed RV function (RV peak systolic pressure = 24 ± 3 vs. 40 ± 1 mm Hg; maximum rate of pressure development = 444 ± 79 vs. 1533 ± 146; maximum rate of pressure decrease = −357 ± 50 vs. −651 ± 44), and release of cardiac troponin I (7.8 ± 1.9 ng/mL) compared with vehicle. Ketorolac (10 mg/kg, intraperitoneally) significantly reduced expression of CINC-1, cyclooxygenase-2, selectin E, and intercellular adhesion molecule 1, lowered neutrophil influx, improved RV function (RV peak systolic pressure was 34 ± 3 mm Hg; maximum rate of pressure development = 1288 ± 146; maximum rate of pressure decrease = −611 ± 92), and marginally reduced cardiac troponin I release (P < 0.07) compared with PE alone. Ketorolac reduced CINC-1 stimulated chemotaxis of isolated neutrophils. PE converted cardiac tissue into a proinflammatory phenotype. Ketorolac reduced RV inflammatory genes, reduced neutrophil influx, and improved RV function in rat PE. © 2009 Lippincott Williams & Wilkins, Inc.