Potential renal protective benefits of intra-operative BNP infusion during cardiac transplantation.

BACKGROUND: Recombinant BNP (nesiritide) is known to reduce endothelin levels, cause afferent arteriole vasodilation, and increase natriuresis and diuresis. We hypothesized that intraoperative infusion of BNP may benefit renal function in cardiac transplant patients. METHODS: From June 2003 to September 2005, 22 consecutive heart transplant patients received BNP at a dose of 0.01 microg/kg/min before initiation of cardiopulmonary bypass (group A). BNP infusion was continued for a mean of 3.3 +/- 1.9 days. Hemodynamics, urine output, and serum creatinine levels were prospectively collected and compared with 22 consecutive patients who underwent heart transplantation between May 2002 and June 2003 following the identical transplant protocol, but without BNP infusion (group B). RESULTS: At 24 hours postoperatively, mean blood pressure was comparable between groups (87 +/- 11 mm Hg vs 89 +/- 17 mm Hg, P = .7), but pulmonary artery pressure (18 +/- 5 mm Hg vs 24 +/- 5 mm Hg, P = .001) and central venous pressure (12 +/- 5 mm Hg vs 16 +/- 4 mm Hg, P = .01) were lower with BNP infusion, whereas cardiac index was augmented (2.8 +/- 0.5 vs 2.4 +/- 0.6, P = .03). Requirement of low-dose inotropic and vasopressor support was equally distributed between groups (P > or = .72). Postoperative urine output for the initial 24 hours was higher in group A (84 +/- 15 vs 55 +/- 36 mL/h, P = .01). None of the patients with BNP infusion required additional diuretics or renal replacement therapy during the first week after transplantation. Mean postoperative serum creatinine levels as compared with preoperative values remained unchanged within group A (P = .12), but increased significantly in group B (P < .001). CONCLUSIONS: Intraoperative BNP infusion in heart transplant recipients was associated with favorable postoperative hemodynamics, significantly improved urine output, and stable serum creatinine levels. A prospective, randomized, multicenter trial is warranted to evaluate the potential renal protective benefits of intraoperative BNP infusion in this patient population.

Autoradiographic localization of N-type VGCCs in gerbil hippocampus and failure of omega-conotoxin MVIIA to attenuate neuronal injury after transient cerebral ischemia.

In the mammalian central nervous system, transient global ischemia of specific duration causes selective degeneration of CA1 pyramidal neurons in hippocampus. Many of the ischemia-induced pathophysiologic cascades that destroy the neurons are triggered by pre- and postsynaptic calcium entry. Consistent with this, many calcium channel blockers have been shown to be neuroprotective in global models of ischemia. omega-Conotoxin MVIIA, a selective N-type VGCC blocker isolated from the venom of Conus magus, protects CA1 neurons in the rat model of global ischemia, albeit transiently. The mechanism by which this peptide renders neuroprotection is unknown. We performed high-resolution receptor autoradiography with the radiolabeled peptide and observed highest binding in stratum lucidum of CA3 subfield, known to contain inhibitory neurons potentially important in the pathogenesis of delayed neuronal death. This finding suggested that the survival of stratum lucidum inhibitory neurons might be the primary event, leading to CA1 neuroprotection after ischemia. Testing of this hypothesis required the reproduction of its neuroprotective effects in the gerbil model of global ischemia. Surprisingly, we found that omega-MVIIA did not attenuate CA1 hippocampal injury after 5 min of cerebral ischemia in gerbil. Possible reasons are discussed. Lastly, we show that the peptide can be used as a synaptic marker in assessing short and long-term changes that occur in hippocampus after ischemic injury.