Lipid peroxidation in healthy fetuses, preterm and fullterm neonates

Thrombolytic therapy has been accepted in the treatment of acute myocardial infarction. Given historical recommendations that thrombolytic therapy is contraindicated in patients receiving CPR, its potential clinical benefit for facilitating conversion of rhythm in patients in refractory cardiac arrest has not been investigated. We present three case reports in which patients with confirmed acute myocardial infarction had a witnessed cardiac arrest in the ED. Standard Advanced Cardiac Life Support measures failed in all three cases. A bolus infusion of tissue plasminogen activator was administered during CPR in refractory ventricular fibrillation (two cases) and pulseless ventricular tachycardia (one case). Patients were given tissue plasminogen activator and had defibrillation, followed by a spontaneous return of circulation, with resuscitation and subsequent discharge. No postarrest sequelae were observed as a result of thrombolytic use during the resuscitative process. We conclude that bolus thrombolytic infusions during CPR may facilitate spontaneous return of circulation in select patients with confirmed acute myocardial infarction, witnessed cardiac arrest in the ED, and refractory ventricular fibrillation or tachycardia.     

Comparison of sodium bicarbonate, Carbicarb, and THAM during cardiopulmonary resuscitation in dogs

OBJECTIVES: During cardiopulmonary resuscitation (CPR), elimination of CO2 was shown to be limited by low tissue perfusion, especially when very low perfusion pressures were generated. It has therefore been suggested that sodium bicarbonate (NaHCO3), by producing CO2, might aggravate the hypercarbic component of the existing acidosis and thereby worsen CPR outcome. The objectives of this study were to evaluate the effects of CO2 producing and non-CO2 producing buffers in a canine model of prolonged ventricular fibrillation followed by effective CPR. DESIGN: Prospective, randomized, controlled, blinded trial. SETTING: Experimental animal research laboratory in a university research center. SUBJECTS: Thirty-eight adult dogs, weighing 20 to 35 kg. INTERVENTIONS: Animals were prepared for study with thiopental followed by halothane, diazepam, and pancuronium. Ventricular fibrillation was electrically induced, and after 10 mins, CPR was initiated, including ventilation with an FIO2 of 1.0, manual chest compressions, administration of epinephrine (0.1 mg/kg every 5 mins), and defibrillation. A dose of buffer, equivalent to 1 mmol/kg of NaHCO3, was administered every 10 mins from start of CPR. Animals were randomized to receive either NaHCO3, Carbicarb, THAM, or 0.9% sodium chloride (NaCl). CPR was continued for up to 40 mins or until return of spontaneous circulation. MEASUREMENTS AND MAIN RESULTS: Buffer-treated animals had a higher resuscitability rate compared with NaCl controls. Spontaneous circulation returned earlier and at a significantly higher rate after NaHCO3 (in seven of nine dogs), and after Carbicarb (six of ten dogs) compared with NaCl controls (two of ten dogs). Spontaneous circulation was achieved twice as fast after NaHCO3 compared with NaCl (14.6 vs. 28 mins, respectively). Hydrogen ion (H+) concentration and base excess, obtained 2 mins after the first buffer dose, were the best predictors of resuscitability. Arterial and mixed venous Pco2 did not increase after NaHCO3 or Carbicarb compared with NaCl. CONCLUSIONS: Buffer therapy promotes successful resuscitation after prolonged cardiac arrest, regardless of coronary perfusion pressure. NaHCO3, and to a lesser degree, Carbicarb, are beneficial in promoting early return of spontaneous circulation. When epinephrine is used to promote tissue perfusion, there is no evidence for hypercarbic venous acidosis associated with the use of these CO2 generating buffers.     

Training in advanced cardiac life support

The nationally recognized training and certification program in Advanced Cardiac Life Support consists of lecture material and a new concept in training and testing for the practical skills of Advanced Cardiac Life Support. The course content follows closely the concepts of advanced life support as explained in the standards on cardiopulmonary resuscitation and emergency cardiac care.     

Striatopallidal and thalamic dystonia. A magnetic resonance imaging anatomoclinical study

The effects of manual and a new mechanical chest compression device (Heartsaver 2000) during prolonged CPR with respect to haemodynamics and outcome were tested in a prospective, randomized, controlled experimental trial during ventricular fibrillation in 12 dogs of 9-13 kg body weight after 1 min of cardiac arrest. During the first 10 min of CPR the dogs were resuscitated according to the Basic Life Support (BLS) algorithm, followed by 20 min of Advanced Life Support (ALS) algorithm. After 30 min of CPR both manual and mechanical CPR groups were resuscitated following a standardized ALS protocol. During CPR, coronary perfusion pressure and end tidal CO2 were greater with mechanical CPR. All animals were successfully resuscitated and neurological deficit scores were not different. The CPR trauma score was less in the mechanical group. Mechanical external chest compression provided better haemodynamics than the manual technique, though outcome did not differ. Both optimally performed manual and mechanical techniques produce flow sufficient to maintain organ viability for 30 min of CPR after a 1 min arrest interval.     

Current concepts in cardiopulmonary resuscitation

The "chain of survival" is important in the resuscitation of a patient who has had a cardiac arrest. The provision of Basic Life Support (BLS) and Advanced Cardiac Life Support (ACLS) is essential in this "chain of survival." Both BLS and ACLS have undergone several revisions since their initial inception. This article reviews (1) the current established and investigational issues of cardiopulmonary resuscitation, (2) the incidence and outcomes of anesthesia-related cardiac arrest, (3) the use of cardiopulmonary bypass in resuscitation, and (4) cerebral protection during and after resuscitation.     

Interaction of the Na(+)-Ca2+ exchanger with small molecules on cell Ca2+ signaling

BACKGROUND: Evaluation of outcome after CPR in severe hypothermic patients. DESIGN: Perspective study from October 1995 to April 1996. SETTING: First aid team of Italian Red Cross, Busto Arsizio (Varese), Italy. METHODS: A population of 22 patients in cardiac arrest in which CPR was performed immediately after rescue team's arrival is studied. ECG, core temperature, SpO2 and MAP were monitored whereas vital parameters were present during Basic Life Support. Outcome after CPR was evaluated with GOS scale. RESULTS: It has been observed that severe hypothermia and time of cardiac arrest impact on the clinical outcome after CPR. The high mortality rate after CPR with BLS standard is worsened by a core temperature < or = 33 degrees C. CONCLUSIONS: Severe hypothermia seems to have a dangerous effect upon outcome after cardiopulmonary resuscitation; heating systems for body temperature could prevent this situation improving CPR results.     

Future directions for resuscitation research. IV. Innovative advanced life support pharmacology

The topics discussed in this session include a partial review of laboratory and clinical studies examining the effects of adrenergic agonists on restoration of spontaneous circulation after cardiac arrest, the effects of varying doses of epinephrine, and the effects of novel vasopressors, buffer agents (NaHCO3, THAM, 'Carbicarb') and anti-arrhythmics (lidocaine, bretylium, amiodarone) in refractory ventricular fibrillation. Novel therapeutic approaches include titrating electric countershocks against electrocardiographic power spectra and of preceding the first countershocks with single or multiple drug treatments. These approaches need to be investigated further in controlled animal and patient studies. Epidemiologic data from randomized clinical outcome studies can give clues, but cannot document pharmacologic mechanisms in the dynamically changing events during attempts to achieve restoration of spontaneous circulation from prolonged cardiac arrest. Also, rapid drug administration by the intraosseous route was compared with intratracheal and intravenous (i.v.) drug administration. Many studies on the above treatments have yielded conflicting results because of differences between healthy hearts of animals and sick hearts of patients, differences in arrest (no-flow) times and cardiopulmonary resuscitation (CPR) (low-flow) times, different pharmacokinetics, different dose/response requirements, and different timing of drug administration during low-flow CPR versus during spontaneous circulation. The need to stabilize normotension and prevent rearrest by titrated novel drug administration, once spontaneous circulation has been restored, requires research. Most of the above topics require some re-evaluation in clinically realistic animal models and in cardiac arrest patients, especially by titration of old and new drug treatments against variables that can be monitored continuously during resuscitation.     

The 5-HT1A and 5-HT2A/2C receptor antagonists WAY-100635 and ritanserin do not attenuate D-fenfluramine-induced fos expression in the brain

In a prospective randomised study we investigated end-tidal carbon dioxide levels during standard versus active compression-decompression (ACD) cardiopulmonary resuscitation (CPR) assuming that the end-tital carbon dioxide reflects cardiac output during resuscitation. In each group 60 patients with out-of-hospital cardiac arrest were treated either with the standard or the ACD method. End-tidal CO2 (p(et)CO2, mmHg) was assessed with a side-stream capnometer following intubation and then every 2 min up to 10 min or restoration of spontaneous circulation (ROSC). There was no difference in p(et)CO2 between both patient groups. However, CO2 was significantly higher in patients who were admitted to hospital as compared to patients declared dead at the scene. All of the admitted patients had a p(et)CO2 of at least 15 mmHg no later than 2 min following intubation, none of the dead patients ever exceeded 15.5 mmHg. From these data we conclude that capnometry adds valuable information to the estimation of a patient's prognosis in the field (threshold, 15 mmHg), but we could not detect any difference in p(et)CO2 between ACD and standard CPR.     

Similarities in coronary flow between external counterpulsation and intra-aortic balloon pumping

The ability of external counterpulsation (Cardiassist) and intra-aortic balloon pumping (AVCO) to influence collateral coronary blood flow in ischemic myocardium was measured in anesthetized dogs. Cardiac output and heart rate (atrial pacing) were held constant on right-heart bypass. Both external counterpulsation and balloon pumping augmented peak diastolic pressure (30 mmHg and 38 mmHg, respectively), while mean aortic pressure, peak left-ventricular pressure, left-ventricular end-diastolic pressure, maximum left-ventricular dp/dt, hematocrit, and osmolality remained unchanged. Regional coronary blood flow was measured using 9-mum radioactive microspheres. External counterpulsation and balloon pumping begun immediately following ligation of the left-anterior descending coronary artery significantly increased collateral coronary blood flow 29 +/- 7.5% (SE, P is less than .01) and 20 +/- 8% (P is less than .05), respectively, to ischemic myocardium. This redistribution of collateral coronary blood flow produced by both methods of counterpulsation was primarily to the subepicardial region of the ischemic myocardium. The mechanism responsible for the measured increases in collateral coronary blood flow appears most likely to be an increased pressure gradient produced by diastolic augmentation.     

Dopexamine improves liver oxygenation during crystalloid resuscitation from experimental hemorrhagic shock

OBJECTIVE: To evaluate the effects of dopexamine administration on hemodynamic variables and tissue oxygen tensions during crystalloid resuscitation from hemorrhagic shock. DESIGN: Randomized, control trial. SETTING: An animal laboratory at a university center. SUBJECTS: Twelve piglets, mean weight 22 kg. INTERVENTIONS: The animals were anesthetized and bled to a state of hemorrhagic shock and resuscitated, using a crystalloid solution infused at a rate of approximately 2.6 mL/min/kg (total amount 208 mL/kg). Cardiac output and mean arterial pressure (MAP were measured as indicators of volume filling during the 20- to 30-min resuscitation period and during the follow-up period until 80 mins from the start of resuscitation. Dopexamine was administered by infusion at 6 micrograms/kg-min from the start of volume replacement (dopexamine group, n = 6). The rest of the animals (control group, n = 6) were given volume replacement only. MEASUREMENTS AND MAIN RESULTS: Systemic oxygen transport variables were calculated. Tissue oxygen tensions were continuously recorded from the liver, conjunctival layer, and via subcutaneous and transcutaneous electrodes in the abdominal region. MAP decreased from 119 +/- 2 (SEM) to 44 +/- 2 mm Hg and cardiac output decreased by 77% during the shock period. During resuscitation, cardiac output was restored in both groups. MAP increased close to the baseline during the early resuscitation period and decreased slowly during follow-up. Oxygen delivery remained at 46% of baseline, whereas systemic oxygen consumption was restored during resuscitation in both groups. Liver tissue oxygen tension increased well above baseline during resuscitation in the dopexamine group, and liver tissue oxygen tension was significantly higher than in the control group. After 60 mins of resuscitation, the liver oxygen tension decreased to control group values. None of the other tissue oxygen tensions showed any differences between groups. CONCLUSIONS: Dopexamine administration during crystalloid resuscitation from hemorrhagic shock was well tolerated and resulted in significant and specific, although transient, improvement in liver oxygenation.     

Cardiac output during cardiopulmonary resuscitation at various compression rates and durations

Cardiac output during cardiopulmonary resuscitation (CPR) was measured by a modified indicator-dilution technique in 20 anesthetized dogs (6-12 kg), during repeated 1- to 2-min episodes of electrically induced ventricular fibrillation, by a mechanical chest compressor and ventilator. With compression rates from 20 to 140/min and compression durations (duty cycles) from 10 to 90% of cycle time, cardiac output (CO) was predicted by the equation: CO = CR . SVmax . [DC/(k1 . CR + DC)] . [(1 -- DC)/k2 . CR + 1 - DC)], where CR is compression rate, DC is duty cycle, SVmax (19 ml) is the effective capacity of the pumping chamber, and k1 (0.00207 min) and k2 (0.00707 min) are ejection and filling constants. This expression predicts maximal CO for DC = 0.40 and cR = 126/min and 90-100% of maximal CO for 0.3 less than DC less than 0.5 and 70 less than CR less than 150/min. Such mathematical analysis may prove useful in the optimization of CPR.     

Optimizing resuscitation outcomes with pharmacologic therapy

Pharmacologic therapy plays a key role in the emergency resuscitation of patients with cardiac arrest. The Advanced Cardiac Life Support guidelines sanctioned by the American Heart Association provide flexible treatment protocols (algorithms) that serve as a valuable tool for clinicians. Vasoactive (vasopressive) therapy with epinephrine is of primary importance in all patients with nonperfusing rhythms (for example, ventricular fibrillation [VF], pulseless ventricular tachycardia [VT], electromechanical dissociation [EMD], and asystole) because it raises myocardial and cerebral perfusion pressures, thereby increasing the likelihood of successful resuscitation. Antiarrhythmic drugs play a secondary role to electrocardioversion in the treatment of VF and pulseless VT. Despite continued investigation and recent advances in our understanding of the role of drugs and other therapeutic interventions, the short-term and long-term prognoses of patients with cardiac arrest, especially out-of-hospital arrest, remain dismal. Clearly, much study into the prevention and treatment of sudden cardiac death is desperately needed.     

Vasopressin can increase coronary perfusion pressure during human cardiopulmonary resuscitation

OBJECTIVES: To determine the hemodynamic effect of vasopressin on coronary perfusion pressure (CPP) in prolonged human cardiac arrest. METHODS: A prospective, open-label clinical trial of vasopressin during cardiac resuscitation was performed. Ten patients presenting in cardiac arrest initially received resuscitative measures by emergency physicians according to Advanced Cardiac Life Support (ACLS) guidelines. A central venous catheter for fluid and drug administration and a femoral artery catheter for measurement of CPP (aortic minus right atrial relaxation phase pressures) were placed. When each patient was deemed nonsalvageable, 1.0 mg epinephrine was given and CPP was measured for 5 minutes, followed by a dose of vasopressin (1.0 U/kg). CPP measurements were continued for another 5 minutes. RESULTS: The mean duration of cardiac arrest (out-of-hospital interval plus duration of ED ACLS) was 39.6 +/- 16.5 min. There was no improvement in CPP after 1.0 mg of epinephrine. Vasopressin administration resulted in a significant increase of CPP in 4 of the 10 patients. Patients responding to vasopressin had a mean increase in CPP of 28.2 +/- 16.4 mm Hg (range: 10-51.5), with these peak increases occurring at 15 seconds to 4 minutes after administration. The increases in the vasopressin levels after administration did not differ between the responders and nonresponders. CONCLUSIONS: In this human model of prolonged cardiac arrest, 40% of the patients receiving vasopressin had a significant increase in CPP. This pilot study suggests that investigation of earlier use of vasopressin as a therapeutic alternative in the treatment of cardiac arrest is warranted.     

Do advanced cardiac life support drugs increase resuscitation rates from in-hospital cardiac arrest? The OTAC Study Group

STUDY OBJECTIVE: The benefit of Advanced Cardiac Life Support (ACLS) medications during cardiac resuscitation is uncertain. The objective of this study was to determine whether the use of these medications increased resuscitation from in-hospital cardiac arrest. METHODS: A prospective cohort of patients undergoing cardiac arrest in 1 of 5 academic hospitals was studied. Patient and arrest factors related to resuscitation outcome were recorded. We determined the association of the administration of ACLS drugs (epinephrine, atropine, bicarbonate, calcium, lidocaine, and bretylium) with survival at 1 hour after resuscitation. RESULTS: Seven hundred seventy-three patients underwent cardiac resuscitation, with 269 (34. 8%) surviving for 1 hour. Use of epinephrine, atropine, bicarbonate, calcium, and lidocaine was associated with a decreased chance of successful resuscitation (P <.001 for all except lidocaine, P <.01). While controlling for significant patient factors (age, gender, and previous cardiac or respiratory disease) and arrest factors (initial cardiac rhythm, and cause of arrest), multivariate logistic regression demonstrated a significant association between unsuccessful resuscitation and the use of epinephrine (odds ratio . 08 [95% confidence interval .04-.14]), atropine (.24 [.17-.35]), bicarbonate (.31 [.21-.44]), calcium (.32 [.18-.55]), and lidocaine (.48 [.33-.71]). Drug effects did not improve when patients were grouped by their initial cardiac rhythm. Cox proportional hazards models that controlled for significant confounders demonstrated that survivors were significantly less likely to receive epinephrine (P <. 001) or atropine (P <.001) throughout the arrest. CONCLUSION: We found no association between standard ACLS medications and improved resuscitation from in-hospital cardiac arrest. Randomized clinical trials are needed to determine whether other therapies can improve resuscitation from cardiac arrest when compared with the presently used ACLS drugs.     

Documenting life-support preferences in hospitalized patients

PURPOSE: The purpose of this article was to determine the extent to which patients at high risk of hospital death who undergo cardiopulmonary resuscitation (CPR) have previously had their life support preferences addressed and documented. MATERIALS AND METHODS: We conducted a retrospective chart review of all patients older than 18 years of age hospitalized for more than 24 hours who sustained a cardiac arrest with attempted CPR at our tertiary care university teaching hospital during 1994 (n = 71). We searched all hospital charts specifying ICD-9 codes: Cardiac arrest, ventricular fibrillation, ventricular tachycardia, asystole, electromechanical dissociation, defibrillation, or CPR. Patients were selected if (1) they had a true cardiac arrest (abrupt cessation of spontaneous circulation) and (2) had attempted CPR or defibrillation. Patients were classified as "high risk" if they satisfied at least one of the following: modified prearrest morbidity index > or = 7, moderate/severe dementia, day 1 APACHE II score > 24 or > or = 4 dysfunctional organ systems. RESULTS: We searched 147 charts; of 71 patients meeting inclusion criteria, 53 were high risk. Of patients at high risk of sustaining a cardiopulmonary arrest during the index hospital admission, 3 (6%) had preferences addressed within the first 24 hours of hospitalization, 7 (13%) had delayed discussion of preferences before arrest, 23 (43%) had preferences addressed post arrest, and 20 (38%) had no documented discussions. Of the 23 high-risk patients initially surviving cardiac arrest, all were subsequently given "do not resuscitate" orders. Univariate analysis of factors associated with life-support discussion before cardiac arrest were previous cardiac arrest (OR, 5.9) and APACHE II score > 24 (OR, 1.1), although neither reached statistical significance. None of the 32 patients with a modified PAM index > or = 7 (32 of 71) survived hospitalization. Only 3 patients survived to hospital discharge. CONCLUSIONS: Early communication regarding life-support preferences is important in high-risk patients so that inappropriate or unwanted treatment is not implemented. Given that optimal care includes addressing and documenting life-support preferences in high-risk patients early in their hospitalization, this standard was infrequently met.     

Possible reasons for the variability of human responses to IAC-CPR

OBJECTIVE: To propose reasons for the variability of the hemodynamic responses and survival data observed when interposed abdominal compression cardiopulmonary resuscitation (IAC-CPR) is performed on humans in cardiac arrest. METHODS: Critical content review of all studies performed in the United States examining IAC-CPR in humans and of selected animal studies addressing hemodynamic mechanisms of CPR. Articles in the English language dealing with human IAC-CPR studies from 1970-1993 were retrieved using the MEDLINE database of the National Library of Medicine. RESULTS: IAC-CPR does not consistently improve coronary perfusion pressure (CPP) over standard CPR in humans and is capable of decreasing as well as increasing CPP. This variability does not seem dependent on the manner in which abdominal compressions are performed. Because of the limited response to standard CPR, significant increases in return of spontaneous circulation would be expected with IAC-CPR if a large percentage of patients were to have favorable increases in CPP. However, other patients may be adversely affected by decreases in CPP during IAC-CPR, with unsuccessful resuscitation of those individuals. Return of spontaneous circulation also may be enhanced using IAC-CPR due to other factors reflected in the initial arrest rhythm and in arrest-population demographics. CONCLUSION: IAC-CPR should not be recommended for routine use until the mechanism of its beneficial effects is known and until those patients who are likely to benefit from the technique can be better identified.     

Dose-dependent character of the effect of hydrocortisone on energy metabolism of rat thymocytes

OBJECTIVES: Pancreatic hypoxia/ischemia, as a consequence of shock-induced microcirculatory failure, is considered a causative factor in the initiation and/or progression of pancreatic tissue injury. The aim of this study was to compare the effects of "small volume resuscitation" with conventional isovolemic colloid and hypervolemic crystalloid resuscitation on pancreatic microcirculation after hemorrhagic shock. DESIGN: Randomized, controlled intervention trial. SETTING: University laboratory. SUBJECTS: Twenty-three male Sprague-Dawley rats anesthetized with á-chloralose mechanically and ventilated. Interventions: Rats subjected to 1 hr of hemorrhagic shock (mean arterial pressure of 40 mm Hg) were resuscitated with lactated Ringer's solution (four-fold shed volume/20 mins), 10% hydroxyethyl starch (shed volume/5 mins), or 7.2% sodium chloride-10% hydroxyethyl starch (10% shed volume/2 mins). MEASUREMENTS AND MAIN RESULTS: The microcirculation of pancreatic acinar tissue was studied by means of intravital fluorescence microscopy and laser Doppler flowmetry. At 1 hr after resuscitation, mean arterial pressure, pancreatic capillary erythrocyte velocity, and erythrocyte flux were found to be significantly increased when compared with those values in the shock state. However, mean arterial pressure, pancreatic capillary erythrocyte velocity, and erythrocyte flux did not completely return to preshock values, regardless of the type of fluid used for resuscitation. At 15 mins and 1 hr after resuscitation, shock-induced capillary perfusion failure (reduction of functional capillary density) was restored to 91% to 94% of baseline values in all groups. Pancreatic capillary narrowing, indicating microvascular endothelial cell swelling, was abolished by resuscitation with both isotonic hydroxyethyl starch and hypertonic hydroxyethyl starch (p<.05 vs. lactated Ringer's solution). CONCLUSIONS: Despite replacement of only 10% of actual blood loss, small-volume resuscitation with hypertonic hydroxyethyl starch is as effective as the ten-fold volume of isotonic hydroxyethyl starch and, due to prevention of microvascular endothelial cell swelling, superior to the 40-fold volume of isotonic lactated Ringer's solution in regard to restoration of the shock-induced microcirculatory disturbances of rat pancreatic acinar tissue.     

Adenosine in wide-complex tachycardia

The use of adenosine as a therapeutic and diagnostic tool in wide-complex tachycardia is suggested in the current Advanced Cardiac Life Support (ACLS) guidelines. The ACLS guidelines are now 4 years old, and new information on the safety and efficiency of adenosine in wide-complex tachycardia is available. We review the ACLS recommendations in light of the current available literature. In general, the ACLS recommendations remain reasonable with some important caveats.     

Right ventricular overload causes the decrease in cardiac output after nitric oxide synthesis inhibition in endotoxemia

OBJECTIVE: To determine whether the decrease in cardiac output after nitric oxide synthase inhibition in endotoxemia is due to increased left ventricular afterload or right ventricular afterload. DESIGN: Prospective, randomized, unblinded study. SETTING: Research laboratory at an academic, university medical center. SUBJECTS: Nonanesthetized, sedated, mechanically ventilated pigs. INTERVENTIONS: Pigs were infused with 250 microg/kg of endotoxin over 30 mins. Normal saline was infused to maintain pulmonary artery occlusion pressure (PAOP) at a value not exceeding 1.5 times the baseline value. Left ventricular dimensions and function were studied using echocardiography. Right ventricular volumes and ejection fraction were determined via a rapid thermistor pulmonary artery catheter. We also measured mean arterial pressure (MAP), cardiac output, pulmonary arterial pressure, and calculated pulmonary and systemic resistances. Gastric tonometry was used as an index of gastric mucosal oxygenation and peripheral oxygenation. When MAP had decreased to < or =60 mm Hg or had decreased 30 mm Hg from baseline, nine animals received NG-nitro-L-arginine methyl ester (L-NAME) at 15 mg/kg to restore MAP to baseline. A second group of animals (n = 6) continued to receive normal saline, ensuring that PAOP did not exceed 1.5 times its baseline value. A third group of pigs (n = 5) did not receive endotoxin and served as the time control. In this group, a balloon was used to occlude the descending thoracic aorta and to increase MAP by approximately the same amount as in the L-NAME group. MEASUREMENTS AND MAIN RESULTS: Endotoxin caused an increase in pulmonary arterial pressure and right ventricular volumes, and a decrease in gastric mucosal pH. Cardiac output was maintained in the animals receiving the saline infusion. By 2 hrs, pulmonary arterial pressure had decreased but was still notably higher than baseline. However, by this time, MAP had decreased to < or =60 mm Hg. L-NAME administration restored MAP to its baseline value but resulted in worsening pulmonary hypertension, increased right ventricular volumes, and decreased cardiac output, compared with the saline group. Three animals that received L-NAME died of right ventricular failure. We did not observe any evidence of left ventricular dysfunction with increased left ventricular afterload. Moreover, the restoration of MAP with L-NAME infusion did not correct gastric mucosal acidosis. No changes were noted in the time-control group. Occlusion of the thoracic aorta increased MAP but did not change cardiac output. This finding demonstrates that increases in left ventricular afterload of the magnitude seen with the infusion of L-NAME do not lead to decreases in cardiac output. CONCLUSION: The decrease in cardiac output after nitric oxide synthase inhibition in endotoxemia is due to increased right ventricular afterload and not to left ventricular afterload.     

Concentration dependence of sodium permeation and sodium ion interactions in the cyclic AMP-gated channels of mammalian olfactory receptor neurons

We explored the hypothesis that brain damage after cardiac arrest caused by ventricular fibrillation (VF) needs different therapies than that after asphyxiation, which has been studied less thoroughly. In 67 healthy mongrel dogs of both sexes cardiac arrest (at normothermia) by ventricular fibrillation (no blood flow lasting 10 min) or asphyxiation (no blood flow lasting 7 min) was reversed by normothermic external cardiopulmonary resuscitation, followed by intermittent positive-pressure ventilation for 20 h, and intensive care to 96 h. To ameliorate ischemic brain damage, the calcium entry blocker lidoflazine or a solution of free radical scavengers (mannitol and L-methionine in dextran 40) plus magnesium sulphate, was given intravenously immediately upon restoration of spontaneous circulation. Outcome was evaluated as functional deficit, brain creatine kinase (CK) leakage into the cerebrospinal fluid (CSF) and brain morphologic changes. Lidoflazine seemed to improve cerebral outcome after VF but not after asphyxiation. Free radical scavengers plus magnesium sulphate seemed to improve cerebral outcome after asphyxiation, but not after VF. After VF, scattered ischemic neuronal changes in multiple brain regions dominated, and total brain histopathologic damage scores correlated with final neurologic deficit scores at 96 h (r = 0.66) and with peak CK levels in CSF (r = 0.81). After asphyxiation, in addition to the same ischemic neuronal changes, microinfarcts occurred, and there was no correlation between total brain histopathologic damage scores and neurologic deficit scores or CK levels in CSF. CONCLUSIONS: Different mechanisms of cardiac arrest, which cause different morphologic patterns of brain damage, may need different cerebral resuscitation treatments.