| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Ann Thorac Surg 1995;60:744-745
© 1995 The Society of Thoracic Surgeons
Department of Anesthesiology, CHU Dupuytren, 2 ave M. Luther King, 87042 Limoges, France, and Laboratoire d'Hématologie Expérimentale, Facultéde Médecine, 2 Rue Dr Marcland, 87025 Limoges, France
To the Editor:
We read with interest the work of Zehr and associates [1] reporting the effects of platelet-activating factor (PAF) inhibition on lung injury after cardiopulmonary bypass (CPB) in a porcine model. Several points deserve to be underlined. Increased blood PAF levels have been found in humans at the cessation of CPB [2], after protamine reversal of heparin [3], and several hours after CPB [4]. The effects of a PAF receptor antagonist (BN 52021) have been already investigated in humans during and after CPB. BN 52021 is unable to prevent hematologic alterations (such as leukopenia, thrombocytopenia, and blood loss) induced by CPB or after protamine reversal of heparin [5]. In contrast, we observed in the BN 52021--treated patients improved pulmonary vascular resistance immediately at the end of CPB and a subsequent lower right ventricle systolic work index, which could be related to lower transpulmonary pressure gradients [6, 7]. Unfortunately this improvement was brief and disappeared after protamine infusion. The clinical importance of the results of Zehr and associates would have been more convincing if they had observed persistent improved hemodynamics after protamine reversal of heparin.
In this porcine model, the effects of the PAF receptor antagonist on the pulmonary arterial and the left atrial pressures and cardiac index should have been assessed immediately after infusion to exclude an effect of this compound before CPB. Detailed hemodynamics after CPB should explain whether the low pulmonary vascular resistances in the treated pigs resulted from a decrease of the pulmonary arterial pressure or of the transpulmonary gradient or from an increased cardiac index.
References
Division of Cardiac Surgery, The Johns Hopkins Hospital, Blalock 618, 600 N Wolfe St, Baltimorel, Md 21287
To the Editor:
We appreciate the comments of Drs Nathan and Denizot on our study [1] and agree that the clinical relevance of our findings is uncertain because we did not reverse heparin with protamine at the conclusion of the experiment. This was intentional, as protamine induces marked pulmonary hypertension and decreased cardiac output in the porcine model [2]. Furthermore, the protamine--heparin interaction leads to neutrophil activation, pulmonary leukocyte sequestration, and altered hemodynamics, which would confound our assessment of the effects of PAF inhibition.
It is noteworthy that the effects seen in the PAF inhibition group were stable for some time after CPB. The lower pulmonary vascular resistance in the treated animals was the result of decreased mean pulmonary arterial pressure and a lower transpulmonary pressure gradient; left atrial pressure and cardiac index were not significantly different between groups. Although protamine might have blunted the beneficial effect of PAF inhibition, we doubt it would have eliminated it. There were no immediate hemodynamic changes after administration of HUL 412 before CPB.
The work cited by Nathan and associates [3, 4] used the ginkolide compound BN 52021. There is considerable experience with this compound, both experimental and clinical, in Europe [5]. We have also studied the compound in our porcine model (Zehr KJ, Cameron DE; unpublished data). In BN 52021--treated animals (n = 8), we found somewhat lower post-CPB pulmonary vascular resistance when compared with controls (n = 7) (531 ± 177 dynes • s • cm-5 [mean ± standard deviation] versus 781 ± 310 dynes • s • cm-5 at 15 minutes after CPB and 884 ± 419 dynes • s • cm-5 versus 1,336 ± 362 dynes • s • cm-5 at 120 minutes after CPB; p = not significant). There was a marked alveolar--arterial gradient after CPB in both groups: at 120 minutes after CPB with an inspired oxygen fraction of 1, the arterial oxygen tension in treated animals was 218 ± 167 mm Hg compared with 234 ± 202 mm Hg in controls. Pulmonary compliance was significantly better in BN 52021--treated animals, but there was no difference in pulmonary edema as measured by lung wet weight. There was a trend toward decreased pulmonary leukosequestration in treated animals: lung myeloperoxidase activity was 118% ± 87% of pre-CPB levels in treated animals compared with 197% ± 59% in controls (p = not significant). CD18 upregulation increased a similar extent in both groups during CPB (treated = 17% ± 19% versus control = 24% ± 5.2%) but trended toward a lower level 120 minutes after CPB in treated animals (68% ± 45% versus 118% ± 28%; p = not significant). BN 52021 did not prevent neutropenia. These changes were not as striking as those we observed with HUL 412. Thus, in our porcine model of CPB, BN 52021 was less effective than HUL 412 in reducing pulmonary injury. The difference in efficacy of these compounds may relate to differences in bioavailability or to an effect of HUL 412 on receptors unrelated to PAF.
Whether PAF inhibition will have clinical utitity in cardiac surgery has yet to be determined, but we believe these studies contribute to a better understanding of the pathophysiology of postperfusion syndrome [6].
References
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ANN THORAC SURG | ASIAN CARDIOVASC THORAC ANN | EUR J CARDIOTHORAC SURG |
| J THORAC CARDIOVASC SURG | ICVTS | ALL CTSNet JOURNALS |
