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Shijie Sun

Publications and source records attributed to Shijie Sun.

At least 19 recordsLinked to original sources
PubMed2006

Cardiopulmonary resuscitation in a rat model of chronic myocardial ischemia.

Our group has developed a rat model of cardiac arrest and cardiopulmonary resuscitation (CPR). However, the current rat model uses healthy adult animals. In an effort to more closely reproduce the event of cardiac arrest and CPR in humans with chronic coronary disease, a rat model of coronary artery constriction was investigated during cardiac arrest and CPR. Left coronary artery constriction was induced surgically in anesthetized, mechanically ventilated Sprague-Dawley rats. Echocardiography was used to measure global cardiac performance before surgery and 4 wk postsurgery. Coronary constriction provoked significant decreases in ejection fraction, increases in left ventricular end-diastolic volume, and increases left ventricular end-systolic volume at 4 wk postintervention, just before induction of ventricular fibrillation (VF). After 6 min of untreated VF, CPR was initiated on three groups: 1) coronary artery constriction group, 2) sham-operated group, and 3) control group (without preceding surgery). Defibrillation was attempted after 6 min of CPR. All the animals were resuscitated. Postresuscitation myocardial function as measured by rate of left ventricular pressure increase at 40 mmHg and the rate of left ventricular pressure decline was more significantly impaired and left ventricular end-diastolic pressure was greater in the coronary artery constriction group compared with the sham-operated group and the control group. There were no differences in the total shock energy required for successful resuscitation and duration of survival among the groups. In summary, this rat model of chronic myocardial ischemia was associated with ventricular remodeling and left ventricular myocardial dysfunction 4 wk postintervention and subsequently with severe postresuscitation myocardial dysfunction. This model would suggest further clinically relevant investigation on cardiac arrest and CPR.

Animals↗
PubMed2006

One-shock versus three-shock defibrillation protocol significantly improves outcome in a porcine model of prolonged ventricular fibrillation cardiac arrest.

BACKGROUND: The success of resuscitation with a 1-shock versus the conventional 3-shock defibrillation protocol was investigated subject to the range of treatment variation imposed by automated external defibrillators (AEDs). METHODS AND RESULTS: Ventricular fibrillation was induced in 44 domestic pigs. After 7 minutes of untreated VF, animals were randomized among 4 groups representing all combinations of the 1- versus 3-shock protocol and 2 different AED regimens (AED1, AED2). Because few AEDs support a 1-shock protocol, manual defibrillators were used to replicate the AED treatment regimen: electrical waveform, dose sequence, and cardiopulmonary resuscitation (CPR) interruption intervals. Initial shock(s) were delivered, followed by 60 seconds of CPR, and the treatment was repeated until resuscitation was successful or for 15 minutes. The 1-shock protocol was associated with improved outcome, reducing CPR interruptions from 45% to 34% of total resuscitation time (P=0.019) and increasing survival from 64% to 100% (P=0.004). Survival was 91% for AED1 versus 36% for AED2 (P=0.024) with a 3-shock protocol but was increased to 100% for both by adoption of a 1-shock protocol. Improvements in postresuscitation left ventricular ejection fraction and stroke volume were observed with AED1 compared with AED2 (difference of means, 15% and 28% of baseline respectively, P<0.001) regardless of defibrillation protocol. CONCLUSIONS: Adoption of a 1-shock versus a 3-shock resuscitation protocol improved survival and minimized outcome differences imposed by variations in AED design and implementation. When a conventional 3-shock defibrillation protocol was used, however, the choice of AED had a significant impact on resuscitation outcome.

Animals↗
PubMed2006

Challenging the rationale of three sequential shocks for defibrillation.

The 2000 guidelines for cardiopulmonary resuscitation (CPR) recommend up to three sequential shocks for persistent ventricular fibrillation (VF). We hypothesized that the time consumed for repetitive rhythm analyses and recharging of the capacitor compromises the success of the second and third shock of each sequence. In 60 domestic pigs, VF was electrically induced and untreated for 7 min. After 1 min of CPR, which includes precordial compression and ventilation, up to three sequential shocks were delivered. All animals were resuscitated. For purposes of the present study we determined the outcomes of the first, the second, and the third shock of each sequence during attempted defibrillation. Our criterion of success was the restoration of spontaneous circulation (ROSC). Forty-eight of the 60 animals (80%) attained ROSC after the first shock, 9/60 (15%) after the second shock, and only 3/60 (5%) after the third shock. In confirmation of the earlier observations, ROSC was highly predictive when the coronary perfusion pressure (CPP) exceeded 12 mmHg and end-tidal CO(2) (ETCO(2)) exceeded 11 mmHg. However, these criteria were never achieved after the second shock. The present study supports the rationale of delivering only a single shock, or at the most two shocks, prior to resuming chest compression, to re-establish the threshold levels of CPP and ETCO(2) before delivery of a subsequent electrical shock.

Animals↗
PubMed2006

The characteristics of postcountershock pulseless electrical activity may indicate the outcome of CPR.

OBJECTIVES: When ventricular fibrillation is cardioverted to pulseless electrical activity (PEA), PEA has been regarded as a non-resuscitatable rhythm. Yet, recent reports and our earlier observations suggested otherwise. We therefore investigated outcomes after postcountershock PEA, and aimed to develop a scoring system for outcome classification at the onset of initial postcountershock PEA. METHODS: Data from 215 domestic pigs were retrospectively reviewed. VF was induced and untreated for 7 min. Defibrillation was attempted with up to three 150 J biphasic shocks. Failing to restore spontaneous circulation (ROSC), 1 min of CPR preceded subsequent sequences of shocks until animals were resuscitated or for a total of 15 min. Fifty-nine instances of PEA followed defibrillation, including 29 animals that attained ROSC. RESULTS: ROSC animals required a shorter interval between the first shock and the initial postcountershock PEA, fewer shocks prior to onset of initial postcountershock PEA, demonstrated a greater VF wavelet amplitude prior to onset of initial PEA, smaller QRS intervals, and higher heart rates. Using Fisher's linear discriminant analysis, 79.3% of the ROSC and 63.3% of non-ROSC cases were predicted correctly. A total of 71.2% of all cases were classified correctly. CONCLUSIONS: Animals in which postcountershock PEA was converted to ROSC required shorter intervals from first shock to initial postcountershock PEA, fewer shocks prior to onset of initial postcountershock PEA, had greater VF wavelet amplitude prior to initial postcountershock PEA, small QRS intervals, and higher heart rates. Fisher's discriminant analysis is helpful in predicting the likelihood of ROSC for an individual animal presenting with postcountershock PEA.

Animals↗
PubMed2006

Increases in tissue Pco2 during circulatory shock reflect selective decreases in capillary blood flow.

OBJECTIVES: Tissue Pco2 reflects metabolic alterations due to circulatory failure during circulatory shock. This study addresses simultaneous changes in gastric and buccal tissue Pco2 with changes in microcirculatory blood flow in a rat model of circulatory shock induced by cecal ligation and puncture. DESIGN: Prospective controlled laboratory study. SETTING: University-affiliated research laboratory. SUBJECTS: Male breeder Sprague-Dawley rats. INTERVENTIONS: Induction of polymicrobial, abdominal sepsis by cecal ligation and puncture. MEASUREMENTS AND MAIN RESULTS: Tissue Pco2 was continuously measured with the aid of a miniature carbon dioxide electrode. Using orthogonal polarization spectral imaging, recordings of the microcirculation were taken at baseline and hourly intervals until death and compared with sham-operated animals. Gastric and buccal tissue Pco2 values progressively increased in animals after cecal ligation and puncture and terminated in death. Microcirculatory blood flow in vessels >20 microm was well preserved during progression of shock, whereas there was an early and progressive decrease in microcirculatory blood flow in vessels <20 microm, mostly representing capillaries. Tissue Pco2, the tissue Pco2-Paco2 gradient, and blood flow in vessels <20 microm were highly correlated. This contrasted with sham control animals in which no significant hemodynamic, blood gas, lactate, microcirculatory, and tissue Pco2 abnormalities were observed. CONCLUSIONS: These observations suggest that microcirculatory failure in capillaries appears as an early defect in close association with anaerobic metabolism during progression of circulatory shock in an animal model of septic peritonitis.

Animals↗
PubMed2006

Mechanism by which activation of delta-opioid receptor reduces the severity of postresuscitation myocardial dysfunction.

OBJECTIVE: Postresuscitation myocardial dysfunction has been recognized as a leading cause of early death after initially successful cardiopulmonary resuscitation. We have previously demonstrated that opening adenosine triphosphate (ATP)-sensitive K (KATP) channels or activation of delta-opioid receptors minimized the severity of postresuscitation myocardial dysfunction and increased the duration of postresuscitation survival. In the present study, we investigated the potential mechanism of myocardial protection following delta-opioid receptor activation in a rat model of cardiac arrest and cardiopulmonary resuscitation. DESIGN: Randomized prospective animal study. SETTING: Animal research laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Ventricular fibrillation was induced in 24 Sprague-Dawley rats. Mechanical ventilation and precordial compression were initiated after 8 mins of untreated ventricular fibrillation. Defibrillation was attempted after 6 mins of cardiopulmonary resuscitation. The animals were randomized to four groups: a) pentazocine (0.3 mg/kg), a delta-opioid receptor agonist; b) pentazocine pretreated with KATP channel blocker, glibenclamide (0.3 mg/kg), administered 45 mins before induction of ventricular fibrillation; c) glibenclamide pretreated alone 45 mins before induction of ventricular fibrillation; and d) placebo. Pentazocine or saline placebo was injected into the right atrium after 5 mins of untreated ventricular fibrillation. MEASUREMENTS AND MAIN RESULTS: Postresuscitation myocardial function, as measured by the rate of left ventricular pressure increase at 40 mm Hg, left ventricular end-diastolic pressure, and cardiac index, was significantly improved in pentazocine-treated animals. This was associated with significantly prolonged duration of survival. Except for ease of defibrillation, the beneficial effects of pentazocine were abolished by pretreatment with the KATP channel blocker glibenclamide. CONCLUSIONS: The postresuscitation myocardial protective effects provided by activation of delta-opioid receptor may be mediated via opening KATP channels.

Adenosine Triphosphate↗
PubMed2006

Comparison of buccal microcirculation between septic and hemorrhagic shock.

OBJECTIVE: Microcirculatory perfusion is disturbed in sepsis, and global hemodynamics does not necessarily reflect microcirculatory blood flow. In this study, we investigated the effect of the same level of mean arterial pressure (MAP) or cardiac index on the changes in buccal microcirculation between septic and hemorrhagic shock. DESIGN: Prospective, controlled laboratory study. SETTING: University-affiliated research laboratory. INTERVENTIONS: A total of 20 Sprague-Dawley rats were divided into four groups: 1) septic shock induced by cecal ligation and perforation: when MAP decreased to 80 mm Hg, saline was infused at a rate of 25 mL.kg.hr for 2 hrs; 2) both time- and MAP-matched hemorrhagic shock: approximately 30% of total blood volume was withdrawn during the corresponding interval, followed by infusion aiming to restore MAP as required when MAP decreased to 80 mm Hg; 3) both time- and cardiac index-matched hemorrhagic shock: approximately 40% of total blood volume was withdrawn during the corresponding interval until MAP decreased to 50 mm Hg, which generally generated a cardiac index similar to those in septic animals, followed by infusion at the same rate for 2 hrs; and 4) sham control: animals underwent the same procedure except no cecal ligation and perforation, bleeding, and infusion. MEASUREMENTS AND MAIN RESULTS: Buccal microcirculation was visualized with the aid of an orthogonal polarization spectral image device. A semiquantitative score was calculated for vessels of <20 mum, primarily representing the capillaries. Impaired buccal capillary blood flows in septic animals were more severe than those in MAP-matched hemorrhagic animals and were similar to those in cardiac index-matched hemorrhagic animals during the hypoperfusion period before infusion. Significantly improved global hemodynamics after resuscitation cannot effectively improve the buccal capillary blood flows in septic animals, in contrast to those in MAP-matched and cardiac index-matched hemorrhagic animals. CONCLUSIONS: Impaired microcirculatory alteration in septic shock is more severe than hemorrhagic shock; microcirculation is relatively independent of improved systemic hemodynamics, in contrast to those in hemorrhagic shock.

Animals↗
PubMed2006

delta-Opioid-induced pharmacologic myocardial hibernation during cardiopulmonary resuscitation.

OBJECTIVES: Cardiac arrest and cardiopulmonary resuscitation is an event of global myocardial ischemia and reperfusion, which is associated with severe postresuscitation myocardial dysfunction and fatal outcome. Evidence has demonstrated that mammalian hibernation is triggered by cyclic variation of a delta-opiate-like compound in endogenous serum, during which the myocardial metabolism is dramatically reduced and the myocardium tolerates the stress of ischemia and reperfusion without overt ischemic and reperfusion injury. Previous investigations also proved that the delta-opioid agonist elicited the cardioprotection in a model of regional ischemic intact heart or myocyte. Accordingly, we were prompted to search for an alternative intervention of pharmacologically induced myocardial hibernation that would result in rapid reductions of myocardial metabolism and therefore minimize the myocardial ischemic and reperfusion injury during cardiac arrest and cardiopulmonary resuscitation. DESIGN: Prospective, controlled laboratory study. SETTING: University-affiliated research laboratory. INTERVENTIONS: In the series of studies performed in the established rat and pig model of cardiac arrest and cardiopulmonary resuscitation, the delta-opioid receptor agonist, pentazocine, was administered during ventricular fibrillation. MEASUREMENTS AND MAIN RESULTS: : The myocardial metabolism reflected by the concentration of lactate, or myocardial tissue PCO2 and PO2, is dramatically reduced during cardiac arrest and cardiopulmonary resuscitation. These are associated with less severe postresuscitation myocardial dysfunction and longer duration of postresuscitation survival. CONCLUSIONS: delta-Opioid-induced pharmacologic myocardial hibernation is an option to minimize the myocardial ischemia and reperfusion injury during cardiac arrest and cardiopulmonary resuscitation.

Animals↗
PubMed2006

Role of buccal PCO2 in the management of fluid resuscitation during hemorrhagic shock.

Arterial pressure is a widely used measurement for estimating the severity of hemorrhagic shock and to guide its management. However, this capability is reduced when very low arterial pressure values cannot be reliably measured by noninvasive methods. Moreover, hypoperfusion may be masked by compensatory hemodynamic changes, and therefore, in the presence of near normal blood pressure, tissue hypoperfusion may progress undetected. Accordingly, hypercarbia is a general phenomenon of perfusion failure, which occurs in coincidence of the onset of hypotension and is promptly reversed with restoration of normal blood flows. Increases in buccal mucosa PCO2 are highly correlated with increases in gastric wall and sublingual mucosa PCO2 and decreases in tissue blood flows during hemorrhagic shock. In both clinical and experimental settings, tissue PCO2 measured in the oral mucosa proved to be a practical and reliable measurement for the diagnosis of circulatory failure states and an indicator of its severity. In contrast to intraarterial pressure, buccal PCO2 discriminated between short- and long-term survival after large-volume blood loss. Buccal PCO2 measurement therefore emerges as a useful predictor for survival and outcome and a useful guide to manage fluid resuscitation during hemorrhagic shock.

Animals↗
PubMed2006

Effects of biphasic waveforms on outcomes of cardiopulmonary resuscitation in a porcine model of prolonged cardiac arrest.

OBJECTIVES: The effects of two clinically available biphasic waveforms on the success of defibrillation and postresuscitation myocardial dysfunction after prolonged ventricular fibrillation were compared with two newly designed dual-path sequential and simultaneous rectilinear biphasic waveforms. Defibrillation via sequential pulses and encircling, overlapping multiple pathway may depolarize a larger myocardial mass and facilitate transthoracic defibrillation. DESIGN: Animal study. SETTING: Experimental laboratory. SUBJECTS: Thirty-two 40 +/- 3 kg pigs. INTERVENTIONS: Ventricular fibrillation was ischemically induced in 32 pigs. After 7 mins of untreated ventricular fibrillation, cardiopulmonary resuscitation was initiated and continued for 5 mins. Animals were then randomized to receive up to three shocks with a) single-path rectilinear biphasic waveform; b) single-path biphasic truncated exponential waveform; c) dual-path rectilinear biphasic sequential defibrillation; or d) dual-path rectilinear biphasic simultaneous defibrillation. MEASUREMENTS AND MAIN RESULTS: Rectilinear biphasic, dual-path sequential defibrillation, and simultaneous defibrillation had significantly fewer shocks (1.1 +/- 0.4, 1.4 +/- 0.5, 1.3 +/- 0.7, respectively) before restoration of spontaneous circulation than biphasic truncated exponential waveform (2.6 +/- 1.4, p < .005) and less postresuscitation myocardial dysfunction (p < .05). Also, dual-path sequential defibrillation had higher postresuscitation ejection fraction than rectilinear biphasic and dual-path simultaneous defibrillation (p < .005). CONCLUSIONS: The energy requirements for terminating ischemically induced ventricular fibrillation were significantly lower and minimized early postresuscitation myocardial dysfunction in the rectilinear biphasic, dual-path sequential defibrillation, and simultaneous defibrillation than the biphasic truncated exponential waveform. Dual-path sequential defibrillation had less postresuscitation myocardial dysfunction than rectilinear biphasic and dual-path simultaneous defibrillation, but at 72 hrs these differences were no longer significant.

Animals↗
PubMed2005

Buccal capnometry to guide management of massive blood loss.

In both clinical and experimental settings, tissue P(CO2) measured in the oral mucosa is a practical and reliable measurement of the severity of hypoperfusion. We hypothesized that a threshold level of buccal tissue P(CO2) (P(CO2) BU)) would prognosticate the effects of volume repletion on survival. Twenty pentobarbital-anesthetized Sprague-Dawley male breeder rats, each weighing approximately 0.5 kg, were randomly assigned to one of four groups. Animals were bled over an interval of 30 min in amounts estimated to be 25, 30, 35, or 40% of total blood volume. One-half hour after the completion of bleeding, each animal received an infusion of Ringer lactate solution over the ensuing 30 min in amounts equivalent to two times the volume of blood loss. P(CO2) BU) was measured continuously with an optical P(CO2) sensor applied noninvasively to the mucosa of the left cheek. Arterial pressure and end-tidal CO2 were measured over the same interval. Neurological deficit and 72-h survival were recorded. Aortic pressures were restored to near baseline values for each of the four groups after fluid resuscitation. This contrasted with the improvement of P(CO2) BU), which differentiated between animals with short and long durations of postintervention survival. After electrolyte fluid resuscitation in rats subjected to rapid bleeding, noninvasive measurement of P(CO2) BU) was predictive of outcomes. Neither noninvasive end-tidal P(CO2) nor invasive aortic pressure measurements achieved such discrimination. Accordingly, P(CO2) BU) fulfills the criterion of a noninvasive and reliable measurement to guide fluid management of hemorrhagic shock.

Animals↗
PubMed2005

Development of autoimmunity against transcriptionally unrepressed target antigen in the thymus of Aire-deficient mice.

Autoimmune regulator (AIRE) gene mutation is responsible for the development of organ-specific autoimmune disease with monogenic autosomal recessive inheritance. Although Aire has been considered to regulate the elimination of autoreactive T cells through transcriptional control of tissue-specific Ags in thymic epithelial cells, other mechanisms of AIRE-dependent tolerance remain to be investigated. We have established Aire-deficient mice and examined the mechanisms underlying the breakdown of self-tolerance. The production and/or function of immunoregulatory T cells were retained in the Aire-deficient mice. The mice developed Sjogren's syndrome-like pathologic changes in the exocrine organs, and this was associated with autoimmunity against a ubiquitous protein, alpha-fodrin. Remarkably, transcriptional expression of alpha-fodrin was retained in the Aire-deficient thymus. These results suggest that Aire regulates the survival of autoreactive T cells beyond transcriptional control of self-protein expression in the thymus, at least against this ubiquitous protein. Rather, Aire may regulate the processing and/or presentation of self-proteins so that the maturing T cells can recognize the self-Ags in a form capable of efficiently triggering autoreactive T cells. With the use of inbred Aire-deficient mouse strains, we also demonstrate the presence of some additional factor(s) that determine the target-organ specificity of the autoimmune disease caused by Aire deficiency.

Animals↗
PubMed2005

Levosimendan improves postresuscitation myocardial dysfunction after beta-adrenergic blockade.

In earlier studies, we found that a nonselective beta-adrenergic blocking agent, propranolol, facilitated cardiac resuscitation, reduced postresuscitation myocardial ectopy, and improved postresuscitation survival. However, the potential adverse effects and specifically the negative inotropic actions of propranolol prompted our further investigation of the potential value of a non-beta-adrenergic inotropic drug, levosimendan, in conjunction with propranolol, for minimizing postresuscitation myocardial dysfunction after successful resuscitation from cardiac arrest. Ventricular fibrillation was induced and untreated for 7 minutes in 15 domestic pigs, which were divided into propranolol, propranolol plus levosimendan, and control groups. Propranolol was administered as a bolus dose of 0.1 mg/kg during cardiac arrest. Electrical defibrillation was attempted after 12 minutes of cardiac arrest including 5 minutes of precordial compression. Levosimendan was administered at 10 minutes after successful resuscitation in a dose of 20 microg/kg and followed by infusion of 0.4 microg/kg/min over the ensuing 220 minutes. Propranolol reduced energies or numbers of defibrillatory shocks and postresuscitation myocardial ectopy, and it improved postresuscitation myocardial dysfunction. When levosimendan was added, postresuscitation myocardial contractile function was improved even more.

Adrenergic beta-Antagonists↗
PubMed2005

Levosimendan improves postresuscitation outcomes in a rat model of CPR.

In this study we sought to determine whether a calcium sensitizer, levosimendan, would have a more favorable effect on postresuscitation myocardial function and, consequently, postresuscitation survival than beta-adrenergic dobutamine. The extreme decrease in survival before hospital discharge of resuscitated victims is attributed, in part, to postresuscitation myocardial failure, and dobutamine has been recommended for the management of postresuscitation myocardial failure. We studied a total of 15 animals. Ventricular fibrillation was induced in Sprague-Dawley rats weighing 450 to 550 g. Cardiopulmonary resuscitation (CPR), including chest compressions and mechanical ventilation, was begun after 8 minutes of untreated cardiac arrest. Electrical defibrillation was attempted after 6 minutes of CPR. Each animal was resuscitated. Animals were randomized to undergo treatment with levosimendan, dobutamine, or saline-solution placebo. These agents were administered 10 minutes after the return of spontaneous circulation. Levosimendan was administered in a loading dose of 12 microg kg(-1) over a 10-minute period, followed by infusion of 0.3 microg kg(-1) min(-1) over the next 230 minutes. Dobutamine was continuously infused at a dosage of 3 microg kg(-1) min(-1). Saline-solution placebo was administered in the same volume and over the same amount of time as levosimendan. Levosimendan and dobutamine produced comparable increases in cardiac output and rate of left-ventricular pressure increase. However, administration of levosimendan resulted in lower heart rates and lesser increases in left ventricular diastolic pressure compared with both dobutamine and placebo. The duration of postresuscitation survival was significantly greater with levosimendan (16 +/- 2 hours), intermediate with dobutamine (11 +/- 2 hours) and least with saline-solution placebo (8 +/- 1 hour). Levosimendan and dobutamine both improved postresuscitation myocardial function. However, levosimendan produced more favorable postresuscitation myocardial function and increased the duration of postresuscitation survival.

Adrenergic beta-Agonists↗
PubMed2005

Comparison between dobutamine and levosimendan for management of postresuscitation myocardial dysfunction.

OBJECTIVE: To investigate the effects of levosimendan, a nonadrenergic inotropic calcium sensitizer, in comparison with adrenergic dobutamine for the management of postresuscitation myocardial dysfunction following resuscitation from prolonged cardiac arrest. DESIGN: Randomized prospective animal study. SETTING: Animal research laboratory. SUBJECTS: Male Yorkshire-cross domestic pigs INTERVENTIONS: Ventricular fibrillation was induced in male domestic pigs weighing between 35 and 40 kg. Cardiopulmonary resuscitation, including precordial compression and mechanical ventilation, was started after 7 mins of untreated cardiac arrest. Electrical defibrillation was attempted after 5 mins of cardiopulmonary resuscitation. Each animal was successfully resuscitated without pharmacologic intervention. Resuscitated animals were randomized to treatment with levosimendan, dobutamine, or saline placebo. The inotropic agents or an equivalent volume of placebo diluents was administered 10 mins after restoration of spontaneous circulation. Levosimendan was administered in a loading dose of 20 microg.kg over 10 mins followed by a 220-min infusion of 0.4 microg.kg.min. Dobutamine was infused into the right atrium in an amount of 5 microg.kg.min. Treatment was continued for a total of 230 mins. MEASUREMENTS AND MAIN RESULTS: Levosimendan and dobutamine produced comparable increases in cardiac output. However, levosimendan produced significantly greater left ventricular ejection fraction and fractional area changes compared with dobutamine and saline placebo. CONCLUSIONS: Levosimendan has the potential of improving postresuscitation myocardial function. It is likely to serve as an alternative to dobutamine as an inotropic agent for management of postresuscitation myocardial dysfunction.

Analysis of Variance↗
PubMed2005

Increases in both buccal and sublingual partial pressure of carbon dioxide reflect decreases of tissue blood flows in a porcine model during hemorrhagic shock.

BACKGROUND: Earlier studies had demonstrated that gastric partial pressure of carbon dioxide (PCO2) of the gastric wall is an early indication of perfusion failure. Because hypercarbia is a general phenomenon of perfusion failure, this study investigated whether sublingual and buccal mucosal tissue PCO2 also serve as a sensitive indicator of systemic blood flow during hemorrhagic shock. METHODS AND RESULTS: Hemorrhagic shock was induced in five male domestic pigs. Buccal and sublingual PCO2 increased from 60 to 129 mm Hg (p < 0.01) in parallel with average decreases in cardiac output to 44% (from 6.1 to 2.8 L/minute; p < 0.01), and mean arterial pressure to 47% (from 115 to 57 mm Hg; p < 0.01), over the 2-hour interval of shock. According to colored microspheres used for measurements, buccal mucosal flow decreased to 35% (from 6.3 to 2.2 mL/minute/100 g; p < 0.01) in close parallel with sublingual blood flow, which decreased to 34% (from 7.2 to 2.5 mL/minute/100 g; p < 0.01). Liver flow decreased to 56% (from 152 to 85 mL/minute/100 g;p < 0.01), and renal flow to 47% (from 272 to 128 mL/minute/100 g;p < 0.01) of baseline values. The procedure yielded to overall comparable volume exchanges in different animals. After reinfusion of shed blood, buccal PCO2, like sublingual PCO2, was restored to approximately baseline values (respectively, from 56 to 71 mm Hg and from 60 to 71 mm Hg; p = not significant), together with arterial pressure, cardiac output, and end-tidal CO2 (EtCO2) (respectively, from 115 to 115 mm Hg, from 6.1 to 6.3 L/minute, and from 35 to 39 mm Hg; p = not significant), but there was delayed reversal of lactic acidosis (from 0.7 to 2.5 mmol/L;p < 0.01). In five unbled control animals, no significant changes were observed over the same interval. CONCLUSION: The current study extends the rationale for noninvasive measurements to both buccal and sublingual mucosa for diagnosis and quantitation of hemorrhagic shock severity.

Animals↗
PubMed2005

Carvedilol mitigates adverse effects of epinephrine during cardiopulmonary resuscitation.

INTRODUCTION: Earlier studies have implicated the adverse effects of beta- and alpha(1)-adrenergic receptors during cardiopulmonary resuscitation (CPR). Because carvedilol is both a nonselective beta- and alpha1-selective adrenergic receptor-blocking agent, we hypothesized that pretreatment with carvedilol would convert the actions of epinephrine to that of a selective alpha2-agonist. METHODS: Ventricular fibrillation (VF) was induced in Sprague-Dawley rats weighing approximately 500 g. Animals were randomized to 4 groups of 5 animals each: (1) placebo pretreatment and epinephrine treatment, (2) carvedilol pretreatment and placebo treatment, (3) carvedilol pretreatment and epinephrine treatment, and (4) placebo pretreatment and placebo treatment. Carvedilol (50 microg/kg) was injected as a bolus into the right atrium 15 minutes before VF was induced. VF was untreated for 8 minutes, after which CPR (chest compression and mechanical ventilation) was begun. Epinephrine (30 microg/kg) was injected into the right atrium 2 minutes after the start of CPR. Electrical defibrillation was attempted after 14 minutes of VF. RESULTS: All but 2 animals were successfully resuscitated. Approximately equivalent increases in coronary perfusion pressure from 23 +/- 1 mm Hg to 30 +/- 3 mm Hg were observed after the injection of epinephrine independently of carvedilol pretreatment. Carvedilol pretreatment followed by epinephrine treatment reduced early postresuscitation ventricular ectopy (116 +/- 147 vs 834 +/- 380, P < .01) and minimized increases in arterial blood lactate at 5 minutes after resuscitation (10.9 +/- 2.1 mmol/L vs 17.4 +/- 3.5 mmol/L, P < .01). The postresuscitation cardiac index measured 4 hours later was increased (307 +/- 43 mL x min(-1) x kg(-1) vs 210 +/- 6 mL x min(-1) x kg(-1), P < .05). Left ventricular diastolic pressures were decreased (6 +/- 1 vs 14 +/- 1 mm Hg, P < .05). Animals pretreated with carvedilol survived longer (71 +/- 1 vs 45 +/- 22 hours, P < .05) and with less postresuscitation neurologic deficit. CONCLUSION: After beta- and alpha1-adrenergic blockade with carvedilol before inducing cardiac arrest, epinephrine administered during CPR yielded better postresuscitation myocardial and neurologic functions and significantly increased postresuscitation survival.

Adrenergic Agonists↗