International survey on the perioperative management of pulmonary endarterectomy: the perfusion perspective.

INTRODUCTION: Pulmonary endarterectomy (PEA) is the most effective treatment available for chronic thromboembolic pulmonary hypertension (CTEPH). Patient selection, surgical technique and perioperative management have improved patient outcomes, which are traditionally linked to surgical and center experience. However, optimal perfusion care has not been well defined. The goal of the international survey was to better characterize the contemporary perfusion management of PEA and highlight similarities and controversies. METHOD: The combined caseload of 15 participating centers was 5,066 cases. Topics queried included materials and types of cardiopulmonary bypass (CPB) equipment, choice of prime, fluid management, deep hypothermia strategy, temperature management, treatment of acid-base abnormalities and intraoperative hematocrit as well as anticoagulation management for heparin-induced thrombocytopenia. CONCLUSION: Our assessment could provide a base for further advancement and may help design future studies to elucidate the impact of perfusion in this challenging field.

Is There a Relationship between Pressure Gradients through Contemporary Oxygenators and Immune Cell Proliferation during Cardiopulmonary Bypass? A Pilot Study.

There have been many advances in the perfusion equipment used for cardiopulmonary bypass (CPB) surgery. A key component, the membrane oxygenator, has had a number of modifications in recent years and a recent clinical evaluation demonstrated disparity in various aspects of device performance. One difference among oxygenators, which to-date has received little attention, was the impact on the patient's immune cells, with some oxygenators producing a significantly greater increase in immune cell numbers after cross clamp. Such increases in immune cell proliferation may contribute to the development of a systemic inflammatory response (SIR), which has been demonstrated to have a negative impact on patient outcomes. Although factors contributing to immune cell proliferation during CPB are recognized to be multi-factorial, the goal of the current communication was to perform an ad hoc analysis of these raw data for evidence that pressure gradients through an oxygenator contributes to this outcome. Despite the observation that higher-pressure gradient oxygenators appeared to associate with increased immune cell proliferation, no correlation was detected in this analysis. This finding, however, provides further evidence for the complex nature of inflammation during CPB, which deserves ongoing discussion and investigation.

Clinical evaluation of contemporary oxygenators.

Advances in cardiopulmonary bypass equipment have played a critical role in improving outcomes for cardiac surgery patients. Recent advancements include reduced priming volumes, biocompatible coatings and gaseous microemboli handling, as well as the incorporation of an arterial filter into the oxygenator.The purpose of this study was to conduct a comprehensive clinical evaluation of adult oxygenators on the market. Oxygenators assessed included the Sorin Synthesis(®) (n = 30), the Sorin Inspire 6F(®) (n = 10) and Inspire 8F(®) (n = 30), the Terumo FX15(®) (n = 13) and FX25(®) (n = 30), the Maquet Quadrox-i(®) (n = 30) and the Medtronic Fusion(®) (n = 30). Parameters assessed included functional prime volumes, gas exchange, pressure gradients and the effects on patient hematology.The Synthesis had the largest functional prime volume (1426 ml), the FX15 the lowest (956 ml). The Inspire 6F, 8F and Fusion had the greatest O2 transfer. The Sorin oxygenators required the lowest sweep gas flows to obtain a PaCO2 of 40 mmHg. The Sorin oxygenators had the largest pressure gradients. While no differences were observed for hemoglobin and platelet levels post cross-clamp removal, the Sorin Synthesis and Inspire 8F had the largest increases in white blood cell (WBC) counts (122% and 141% of baseline, respectively) and neutrophils (162% and 185% of baseline, respectively).The data demonstrate that no single product is superior in all aspects. The choice of ideal oxygenator depends on the aspect(s) of oxygenator performance the perfusion team believes most clinically acceptable based on available data.

Mitogenic factors promoting intestinal smooth muscle cell proliferation.

Intestinal smooth muscle cells are normally quiescent, but in the widely studied model of trinitrobenzene sulfonic acid (TNBS)-induced colitis in the rat, the onset of inflammation causes proliferation that leads to increased cell number and an altered phenotype. The factors that drive this are unclear and were studied in primary cultures of circular smooth muscle cells (CSMC) from the rat colon. While platelet-derived growth factor (PDGF)-AA, fibroblast growth factor (FGF), and epidermal growth factor (EGF) were ineffective, PDGF-BB and insulin-like growth factor-1 (IGF-1) caused significant increase in [(3)H]thymidine incorporation, bromodeoxyuridine uptake, and increased CSMC number, with PDGF-BB (≥0.2 nM) substantially more effective than IGF-1. Surprisingly, CSMC lacked expression of PDGF receptor-ß (PDGF-Rß) upon isolation but by 4 days in vitro, CSMC gained expression of PDGF-Rß as shown by quantitative PCR, Western blot analysis, and immunocytochemistry; these CSMC responded to PDGF-BB but not IGF-1. PDGF-BB caused PDGF-Rß phosphorylation and mobilization from the surface membrane, leading to activation of both Akt and ERK signaling pathways, which were essential for subsequent proliferation. In contrast, PDGF-AA, FGF, EGF, and IGF-1 were ineffective. In vivo, control CSMC lacked expression of PDGF-Rß. However, this changed rapidly with TNBS-colitis, and by day 2 when CSMC proliferation in vivo is maximal, freshly isolated CSMC showed on-going PDGF-Rß phosphorylation that was further increased by exogenous PDGF-BB. This suggests that the onset of PDGF-Rß expression is a key factor in CSMC growth in vitro and in vivo, where inflammation may damage intrinsic inhibitory mechanisms and thus lead to hyperplasia.

Nerve growth factor sensitivity is broadly distributed among myenteric neurons of the rat colon.

Nerve growth factor (NGF) acts on the two-receptor system of trkA and p75 to mediate neuroprotection and influence phenotype and function in the peripheral nervous system, but the effects of NGF on the enteric nervous system (ENS) are virtually unknown. To establish a basis for enteric responsiveness to NGF, we studied the presence and distribution of NGF-sensitive receptors in the myenteric neurons of the normal rat colon and examined their activation via trkA phosphorylation. Fluorescent immunocytochemistry on wholemounts showed that the two NGF receptors were abundantly present in the ENS, with 71% of all neurons positive for trkA and 78% for p75. More thanr 60% of the myenteric neurons expressed both receptors, and exogenous application of NGF resulted in trkA phosphorylation, evidence for high NGF sensitivity within the ENS. trkA was co-expressed with choline acetyltransferase (61% of trkA-positive neurons), neuronal nitric oxide synthase (22%), or calbindin (10%), suggesting widespread potential for NGF action. We conclude that functional receptors for NGF are widely distributed among the diverse enteric phenotypes and argue for a novel NGF-mediated regulatory system within the ENS.

Inflammation causes expression of NGF in epithelial cells of the rat colon.

Nerve growth factor (NGF) is a neurotrophin implicated in intestinal pathophysiology, such as impaired barrier function, altered motility and a lowered threshold to noxious stimuli in colitis. We evaluated the cellular source of NGF and determined the effect of inflammation on its expression in TNBS-induced colitis in the rat. Receptors for NGF were studied by immunocytochemistry, showing that submucosal neurons expressed both trkA and p75(NTR). NGF presence and activity was assessed by bioassay, ELISA, western blotting and immunocytochemistry. Bioassay of colonic mucosa using the PC12 cell line showed low levels in control tissue but a marked increase in NGF activity with inflammation. Western blotting showed the appearance of 13 kDa NGF in inflamed mucosa by 6 h, declining over time to become similar to control by 35 days. Semi-quantitative PCR showed minimal mRNA for NGF in control mucosa that increased sharply by 6 h post-TNBS. Laser-capture microdissection was used to collect colonic epithelial cells, where mRNA for NGF was markedly increased by 6 h post-TNBS. While the epithelium of the inflamed colon was positive for NGF by immunocytochemistry, other cell types remained negative. A potential precursor form of NGF, but not 13 kDa NGF itself, was detected in several epithelial cell lines and a mucosal mast cell line. We conclude that NGF is principally synthesized by epithelial cells in the inflamed colon, where the presence of specific receptors suggests the potential for wide-spread action.