The interactions of PI-PLC with nonsubstrate zwitterionic [phosphatidylcholine (PC)] and anionic [phosphatidylmethanol (PMe), phosphatidylserine, phosphatidylglycerol, and phosphatidic acid] interfaces that affect the catalytic activity of PI-PLC have been examined. PI-PLC binding is strongly coupled to vesicle curvature and is tighter at acidic pH for all of the phospholipids examined. PI-PLC binds to small unilamellar vesicles (SUVs) of anionic lipids with much higher affinity (K(d) is 0.01-0.07 microM for a site consisting of n = 100 +/- 25 lipids when analyzed with a Langmuir adsorption isotherm) than to zwitterionic PC SUVs (K(d) is 5-20 microM and n = 8 +/- 3). The binding to PC surfaces is dominated by hydrophobic interactions, while binding to anionic surfaces is dominated by electrostatic interactions. The contributions of specific cationic side chains and hydrophobic groups at the rim of the alpha beta-barrel to zwitterionic and anionic vesicle binding have been assessed with mutagenesis. The results are used to explain how PC activates the enzyme for both phosphotransferase and cyclic phosphodiesterase activities.

Purpose of the study To describe a new method of CPR that optimizes vital organ perfusion pressures and carotid blood flow. We tested the hypothesis that a combination of high dose sodium nitroprusside (SNP) as well as non-invasive devices and techniques known independently to enhance circulation would significantly improve carotid blood flow (CBF) and return of spontaneous circulation (ROSC) rates in a porcine model of cardiac arrest. Methods 15 Isofluorane anesthetized pigs (30±1Kg), after 6 minutes of untreated ventricular fibrillation, were subsequently randomized to receive either 15 minutes of standard CPR (S-CPR) (8 animals) or 5 minute epochs of S-CPR followed by active compression-decompression (ACD) +inspiratory impedance threshold device (ITD) CPR followed by ACD+ITD+abdominal binding (AB) with 1mg of SNP administered at minutes 2, 7, 12 of CPR (7 animals). Primary endpoints were CBF and ROSC rates. ANOVA and Fisher’s exact test were used for comparisons. Results/Conclusion There was significant improvement in the hemodynamic parameters in the SNP animals. ROSC was achieved in 7/7 animals that received SNP and in 2/8 in the S-CPR (p=0.007). CBF and end tidal CO2 (ETCO2) were significantly higher in the ACD+ITD+AB+SNP (SNPeCPR) animals during CPR. Bolus doses of SNP, when used in conjunction with ACD+ITD+AB CPR, significantly improve CBF and ROSC rates compared to S-CPR.

Objective Sodium nitroprusside-enhanced CPR (SNPeCPR) consists of active compression decompression (ACD), impedance threshold device (ITD), abdominal binding (AB), and large intravenous doses of sodium nitroprusside (SNP). We hypothesize SNPeCPR will significantly increase carotid blood flow and return of spontaneous circulation compared to standard CPR after prolonged ventricular fibrillation (VF) and pulseless electrical activity (PEA) cardiac arrest. Design Prospective randomized animal study. Setting Hennepin County Medical Center Animal Laboratory. Subjects 40 Yorkshire female farm-bred pigs weighing 32 ± 2kg. Interventions In protocol A, 24 isoflurane anesthetized pigs underwent 15 minutes of untreated VF and were subsequently randomized to receive S-CPR (n=6), ACD CPR +ITD (n=6), or SNPeCPR (n=12) for up to 15 minutes. First defibrillation was attempted at minute 6 of CPR. In protocol B, a separate group of 16 pigs underwent 10 minutes of untreated VF followed by 3 minutes of chest compression only CPR followed by counter-shock induced PEA after which animals were randomized to S-CPR (n=8) or SNPeCPR (n=8). Measurements and Main Results The primary endpoint was carotid blood flow during CPR and return of spontaneous circulation (ROSC). Secondary endpoints included end-tidal CO2 (ETCO2) as well as coronary (CPP) and cerebral perfusion pressure (CerPP). After prolonged untreated VF, SNPeCPR demonstrated superior rates of ROSC when compared to S-CPR and ACD CPR+ITD (12/12, 0/6, 0/6 respectively, p<0.01). In animals with PEA, SNPeCPR increased ROSC rates when compared to S-CPR. In both groups, carotid blood flow, CPP, CerPP, and ETCO2 were increased with SNPeCPR. Conclusions In pigs, SNPeCPR significantly increased ROSC rates as well as carotid blood flow and ETCO2, when compared to S-CPR or ACD CPR+ITD.

Aim of study Sodium nitroprusside-enhanced CPR, or SNPeCPR, consists of active compression-decompression CPR with an impedance threshold device, abdominal compression, and intravenous sodium nitroprusside (SNP). We hypothesize that SNPeCPR will improve post resuscitation left ventricular function and neurological function compared to standard (S) CPR after 15 min of untreated ventricular fibrillation in a porcinemodel of cardiac arrest. Methods Pigs (n = 22) anesthetized with isoflurane underwent 15 min of untreated ventricular fibrillation, were then randomized to 6 min of S-CPR (n = 11) or SNPeCPR (n = 11) followed by defibrillation. The primary endpoints were neurologic function as measured by cerebral performance category (CPC) score and left ventricular ejection fraction. Results SNPeCPR increased 24-hour survival rates compared to S-CPR (10/11 versus 5/11, p = 0.03) and improved neurological function (CPC score 2.5± 1, versus 3.8 ± 0.4, respectively, p = 0.004). Left ventricular ejection fractions at 1, 4 and 24 hours after defibrillation were 72± 11, 57± 11.4 and 64 ± 11 with SNPeCPR versus 29 ± 10, 30 ± 17 and 39 ± 6 with S-CPR, respectively (p < 0.01 for all). Conclusions In this pig model, after 15 min of untreated ventricular fibrillation, SNPeCPR significantly improved 24-hour survival rates, neurologic function and prevented post-resuscitation left ventricular dysfunction compared to S-CPR.