The effect of pentoxifylline on the lung during cardiopulmonary bypass

Abstract

Cardiopulmonary bypass (CPB) produces an inflammatory response due to the interaction of blood with a foreign body surface. The lungs are most affected by this inflammatory response. Pentoxifylline (PTX), a phosphodiesterase inhibitor and an inhibitor of leukocyte activation, is used to minimize damage in lungs where leukocytes play an important role. Twenty patients with mitral valve stenosis with planned mitral valve surgery were included in the study. The ten patients receiving pentoxifylline (PTX group) were administered 400 mg PTX orally TID for 3 days preoperatively and, following anesthetic induction, a 300 mg PTX infusion was given. The ten patients receiving no PTX were the control group (CT). Platelet and leukocyte counts, mean pulmonary arterial pressure (mPAP), pulmonary capillary wedge pressure (PCWP), cardiac index (CI), pulmonary vascular resistance (PVR), alveolar-arterial PO2 gradient (AaDO2) were measured just before and after CPB, and 2 h postoperatively. The number of the leukocytes increased in the blood samples drawn 15 min after CPB in both groups and 2 h postoperatively showed no statistical change. The number of platelets had decreased significantly at the end of the CPB in both groups and, 2 h postoperatively, there was a further decrease in the blood count in the control group (P < 0.05). There was no significant difference in either the preoperative or postoperative PAP, PAWP, and CI. Pulmonary vascular resistance increased in both groups following the CPB (CT, before: 136 +/- 44, after: 177 +/- 94 dyne. sec.cm-5; PTX, before: 151 +/- 82, after 182 +/- 43 dynes.sec.cm-5). Two hours postoperatively, a considerable increase continued in the control group (CT 219 +/- 170 dynes.sec. cm-5), while there was an insignificant increase in the PTX group (PTX 193 +/- 51 dynes.sec.cm-5) (P < 0.05). The alveolar-arterial PO2 gradient increased after the CPB in both groups but a moderate decrease was observed 2 h postoperatively. In lung biopsy specimens taken before and after the CPB, there was marked leukocyte sequestration in the control group, whereas the number of leukocytes was seen to be insignificant in the PTX group (P < 0.005). This dosage regimen of PTX inhibits the postoperative increase in PVR and greatly minimized leukocyte sequestration in the lung due to CPB.

Preoperative oral pentoxifylline in case of coronary artery bypass grafting with left ventricular dysfunction (ejection fraction equal to/less than 30%)

“…One of the most affected systems in this process is the respiratory system, which its dysfunction varies from least to most (3). In fact, deteriorating oxygen supply after cardiac surgery may be a prominent impediment, for which patients need prolonged mechanical ventilation (6). Involvement of the lungs in the inflammatory process after using CPB results from leukocyte activation, produced by pro-inflammatory mediators, like TNF-a and IL-6 (19).…”

“…Inhibition of TNF-a release is a probable mechanism by which Ptx abates the inflammatory response after cardiac surgery (14). One of the most prominent points in some previous studies is that Ptx was administered orally (6). …”

“…It also inhibits phosphodiesterase activity non-specifically, resulting in the accumulation of the intracellular signaling molecule cyclic adenosine monophosphate (cAMP) (13, 14), which, in turn, terminates the inhibition of the production and release of various cytokines, like tumor necrosis factor-α (TNF-α) (15). It has been suggested that in patients undergoing coronary artery bypass graft (CABG), Ptx administration prevents post-pump lung injury related to CABG surgery by 1) attenuating inflammatory cytokines (16) and 2) having a direct effect on pulmonary endothelial cells and their interactions (6). Furthermore, pre-operative administration of Ptx in patients undergoing cardiac surgery using CPB reduces potential complications and improves the outcomes (17).…”

Comparison of the Additive Effects of Intravenous Methyl Prednisolone with that of Intravenous Pentoxyfylline on Low Tidal Volume Normal Frequency Ventilation as a Lung Protection Strategy during Cardiopulmonary Bypass that Improves Immediate Postoperative Outcome

“…It inhibits formation of inflammatory cytokines, lowers leukocytes sensitivity to cytokines, and prevents neutrophil degranulation and lowers production of free radicals [28][29][30]. In a study, effect of 400mg Pentoxyfylline given orally thrice daily for 3 days preoperatively followed by 300mg Pentoxyfylline infusion after induction of anesthesia was studied on leukocyte sequestration in lung during post CPB period and leukocyte sequestration was lower in Pentoxyfylline group than control but, alveolar arterial pO 2 gradient was similar in both groups [31]. In the present study, 300 mg of intravenous Pentoxyfylline infusion was administered after induction and no adverse effect was seen.…”

Systemic Leukofiltration Does Not Attenuate Pulmonary Injury after Cardiopulmonary Bypass

“…Pharmacological approaches include the perioperative administration of aprotinin, a non-specific serine protease inhibitor shown to decrease CPB-induced leukocyte activation, 16,17 and pentoxifylline, a non-specific phosphodiesterase inhibitor, demonstrated to decrease both neutrophil activation 18 and pulmonary sequestration. 19 Technical strategies, such as temperature manipulation and heparin coated circuits have also had mixed trial results. 20 Over the last fifteen years, concurrent leukocyte removal from the perfusate using specialized filters has been proposed as a means of reducing CPB-associated inflammation.…”