Restoration of antigen-specific CD4 T-cell response against Mycobacterium tuberculosis in HIV-infected people.

Again, our emphatic statements about the NO pathway and endothelium function may have led to this interpretation. We agree that cardiac surgery vasoplegia has multiple mechanisms, including drug interactions, as Poullis4 discussed in his excellent letter, which was motivated by the article of Argenziano et al5 on vasodilatory shock after cardiac surgery. Their third comment rejects the notion that low systemic vascular resistance is “the main problem with protamine administration.” In our opinion, this is really the main hemodynamic protamine effect. These effects are closely related to infusion rate. Pulmonary hypertension and systemic hypotension routinely occur in most animal models when protamine or any other polycation is given by rapid injection. Many reports have suggested that there may be advantages to the intra-aortic (IA) administration vs the IV administration of protamine due to the reversal of heparin at the end of cardiopulmonary bypass. The cardiac surgical practice is consistent in presenting similar good results if protamine is infused by the IV or IA route. However, there is significant hypotension when protamine is infused by the IA route.1 NO release is mainly responsible for this effect, because the arterial endothelium is more adapted to this function than is the venous endothelium. Their fourth comment focuses on the unpredictability of the endothelium function of different organs and animal species, and the unpredictability of NO donors and blockers effects. We completely agree with this comment. We did not emphasize these points, but they are relevant. When low systemic vascular resistance occurs during or after protamine infusion, NO release is a transitory consequence of the constitutive NO-synthase expression. However, if protamine evokes an anaphylactic/anaphylactoid or inflammatory reaction, it causes massive overproduction of NO as consequence of inducible NO-synthase isoform expression.4 We agree that isolated pulmonary vasodilatation may increase cardiac output and BP by increasing left ventricular filling. This is true and happens when using inhaled NO to treat patients with pulmonary hypertension. However, even in the setting of pulmonary hypertension, and considering the possibility of hypovolemia, isolated pulmonary vasodilatation may cause systemic hypotension by volume redistribution. Finally, we would like to emphasize the three known vasodilatation mechanisms, as follows: guanosine monophosphatecyclic-dependent, adenosine monophosphate cyclic-dependent, and hyperpolarization-dependent. These three mechanisms are synergistic. Beside these three mechanisms, an arginine vasopressin deficiency also has been reported. From our point of view, a better understanding of this synergism is mandatory. If the vasoplegic hypotension is unresponsive to catecholamines (adenosine monophosphate cyclic), methylene blue (guanosine monophosphate cyclic) infusion would be logical. In our opinion, this synergism is strongly suggested by the faster decrease of catecholamines after methylene blue infusion. Arginine vasopressin deficiency is a particular and individual possibility, because, in general, vasopressin levels remain increased until 48 to 72 h after cardiopulmonary bypass.