Oral-Mucosal PCO during hemorrhagic shock closely Monitors its time Course, Severity, and reversal outperforming blood lactate measurement.

Introduction: Given the redistribution of blood flow away from non-immediately vital territories during hemorrhagic shock, we investigate whether monitoring the oral mucosal PCO (PCO) as a surrogate of splanchnic circulation, could closely recognize the onset, assess severity, and identify reversal of hemorrhagic shock.

Material And Methods: The study was performed on six male pigs (38.4 ± 1.

From a pressure-guided to a perfusion-centered resuscitation strategy in septic shock: Critical literature review and illustrative case.

Purpose: To support a paradigm shift in the management of septic shock from pressure-guided to perfusion-centered, expected to improve outcome while reducing adverse effects from vasopressor therapy and aggressive fluid resuscitation.

Material And Methods: Critical review of the literature cited in support of vasopressor use to achieve a predefined mean arterial pressure (MAP) of 65 mmHg and review of pertinent clinical trials and studies enabling deeper understanding of the hemodynamic pathophysiology supportive of a perfusion-centered approach, accompanied by an illustrative case.

Results: Review of the literature cited by the Surviving Sepsis Campaign revealed lack of controlled clinical trials supporting outcome benefits from vasopressors.

Early and sustained vasopressin infusion augments the hemodynamic efficacy of restrictive fluid resuscitation and improves survival in a liver laceration model of hemorrhagic shock.

Background: Current management of hemorrhagic shock favors restrictive fluid resuscitation before control of the bleeding source. We investigated the additional effects of early and sustained vasopressin infusion in a swine model of hemorrhagic shock produced by liver laceration.

Methods: Forty male domestic pigs (32-40 kg) had a liver laceration inflicted with an X-shaped blade clamp, 32 received a second laceration at minute 7.

Adverse postresuscitation myocardial effects elicited by buffer-induced alkalemia ameliorated by NHE-1 inhibition in a rat model of ventricular fibrillation.

Major myocardial abnormalities occur during cardiac arrest and resuscitation including intracellular acidosis-partly caused by CO accumulation-and activation of the Na-H exchanger isoform-1 (NHE-1). We hypothesized that a favorable interaction may result from NHE-1 inhibition during cardiac resuscitation followed by administration of a CO-consuming buffer upon return of spontaneous circulation (ROSC). Ventricular fibrillation was electrically induced in 24 male rats and left untreated for 8 min followed by defibrillation after 8 min of cardiopulmonary resuscitation (CPR).

Cytochrome C in Patients with Septic Shock.

Purpose: Cytochrome c is an essential component of the electron transport chain, and circulating cytochrome c might be an indicator of mitochondrial injury. The objective of this study was to determine whether cytochrome c levels are elevated in septic patients, whether there is an association between cytochrome c levels and lactate/inflammatory markers, and whether elevated levels of cytochrome c are associated with poor outcomes.

Methods: This was a single-center, prospective, observational, pilot study within a randomized, placebo-controlled trial.

Ubiquinol (reduced Coenzyme Q10) in patients with severe sepsis or septic shock: a randomized, double-blind, placebo-controlled, pilot trial.

Introduction: We previously found decreased levels of Coenzyme Q10 (CoQ10) in patients with septic shock. The objective of the current study was to assess whether the provision of exogenous ubiquinol (the reduced form of CoQ10) could increase plasma CoQ10 levels and improve mitochondrial function.

Methods: We performed a randomized, double-blind, pilot trial at a single, tertiary care hospital.

Vasopressin Infusion with Small-Volume Fluid Resuscitation during Hemorrhagic Shock Promotes Hemodynamic Stability and Survival in Swine.

Introduction: Current management of hemorrhagic shock (HS) in the battlefield and civilian settings favors small-volume fluid resuscitation before controlling the source of bleeding. We investigated in a swine model of HS the effects of vasopressin infusion along with small-volume fluid resuscitation; with erythropoietin (EPO) and HS severity as additional factors.

Methods: HS was induced in 24 male domestic pigs (36 to 41 kg) by blood withdrawal (BW) through a right atrial cannula modeling spontaneous bleeding by a mono-exponential decay function.

Estrogen fails to facilitate resuscitation from ventricular fibrillation in male rats.

Administration of 17β-estradiol has been shown to exert myocardial protective effects in hemorrhagic shock. We hypothesized that similar protective effects could help improve resuscitation from cardiac arrest. Three series of 18, 40, and 12 rats each, underwent ventricular fibrillation for 8 minutes followed by 8 minutes of chest compression and delivery of electrical shocks.

Effects of intraosseous erythropoietin during hemorrhagic shock in swine.

Objective: To determine whether erythropoietin given during hemorrhagic shock (HS) ameliorates organ injury while improving resuscitation and survival.

Methods: Three series of 24 pigs each were studied. In an initial series, 50% of the blood volume (BV) was removed in 30 minutes and normal saline (threefold the blood removed) started at minute 90 infusing each third in 30, 60, and 150 minutes with shed blood reinfused at minute 330 (HS-50BV).

Erythropoietin facilitates resuscitation from ventricular fibrillation by signaling protection of mitochondrial bioenergetic function in rats.

Objective: We previously reported beneficial myocardial effects during chest compression after administration of high-dose erythropoietin. We hypothesized that erythropoietin also elicits post-resuscitation myocardial benefits partly linked to protection of mitochondrial bioenergetic function.

Methods: Two series of 10 rats each underwent ventricular fibrillation for 10 minutes (series-1) and 8 minutes (series-2) and were randomized to erythropoietin (5,000 U/kg) or 0.

Protecting mitochondrial bioenergetic function during resuscitation from cardiac arrest.

Successful resuscitation from cardiac arrest requires reestablishment of aerobic metabolism by reperfusion with oxygenated blood of tissues that have been deprived of oxygen for variables periods of time. However, reperfusion concomitantly activates pathogenic mechanisms known as “reperfusion injury.” At the core of reperfusion injury are mitochondria, playing a critical role as effectors and targets of such injury.

Clinically plausible hyperventilation does not exert adverse hemodynamic effects during CPR but markedly reduces end-tidal PCO₂.

Aims: Ventilation at high respiratory rates is considered detrimental during CPR because it may increase intrathoracic pressure limiting venous return and forward blood flow generation. We examined whether ventilation at high, yet clinically plausible, tidal volumes could also be detrimental, and further examined effects on end-tidal pCO(2) (P(ET)CO(2)).

Methods: Sixteen domestic pigs were randomized to one of four ventilatory patterns representing two levels of respiratory rate (min(-1)) and two levels of tidal volume (ml/kg); i.

AVE4454B--a novel sodium-hydrogen exchanger isoform-1 inhibitor--compared less effective than cariporide for resuscitation from cardiac arrest.

We compared the efficacy of the novel sodium-hydrogen exchanger (NHE-1) inhibitor AVE4454B with cariporide for resuscitation from ventricular fibrillation (VF) assessing the effects on left ventricular myocardial distensibility during chest compression, myocardial function after the return of spontaneous circulation, and survival. Three groups of 10 rats each were subjected to 10 min of untreated VF and resuscitation attempted by providing chest compression for up to 8 min with the depth of compression adjusted to attain an aortic diastolic pressure between 26 and 28 mmHg (to secure a coronary perfusion pressure above 20 mmHg) followed by electrical shocks. Rats received AVE4454B (1 mg/kg), cariporide (1 mg/kg), or vehicle control immediately before chest compression.

Cariporide given during resuscitation promotes return of electrically stable and mechanically competent cardiac activity.

Unlabelled: Episodes of ventricular fibrillation (VF) and myocardial dysfunction commonly occur after cardiac resuscitation compromising the return of stable circulation. We investigated in a pig model of VF whether limiting Na(+)-induced cytosolic Ca(2+) overload using the sarcolemmal sodium-hydrogen exchanger isoform-1 (NHE-1) inhibitor cariporide promotes resuscitation with stable circulation.

Methods: VF was electrically induced in 20 male pigs and left untreated for 6 min after which CPR was initiated and continued for 8 min before attempting defibrillation.