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Cerebral perfusion is compromised during cardiopulmonary resuscitation (CPR). We hypothesized that beneficial effects of gravity on the venous circulation during CPR performed in the head-up tilt (HUT) position would improve cerebral perfusion compared with supine or head-down tilt (HDT).Twenty-two pigs were sedated, intubated, anesthetized, paralyzed and placed on a tilt table. After 6min of untreated ventricular fibrillation (VF) CPR was performed on 14 pigs for 3min with an automated CPR device called LUCAS (L) plus an impedance threshold device (ITD), followed by 5min of L-CPR+ITD at 0° supine, 5min at 30° HUT, and then 5min at 30° HDT. Microspheres were used to measure organ blood flow in 8 pigs. L-CPR+ITD was performed on 8 additional pigs at 0°, 20°, 30°, 40°, and 50° HUT.Coronary perfusion pressure was 19±2mmHg at 0° vs. 30±3 at 30° HUT (p0.001) and 10±3 at 30° HDT (p0.001). Cerebral perfusion pressure was 19±3 at 0° vs. 35±3 at 30° HUT (p0.001) and 4±4 at 30° HDT (p0.001). Brain-blood flow was 0.19±0.04mlmin(-1)g(-1) at 0° vs. 0.27±0.04 at 30° HUT (p=0.01) and 0.14±0.06 at 30° HDT (p=0.16). Heart blood flow was not significantly different between interventions. With 0, 10, 20, 30, 40 and 50° HUT, ICP values were 21±2, 16±2, 10±2, 5±2, 0±2, -5±2 respectively, (p0.001), CerPP increased linearly (p=0.001), and CPP remained constant.During CPR, HDT decreased brain flow whereas HUT significantly lowered ICP and improved cerebral perfusion. Further studies are warranted to explore this new resuscitation concept.

Objectives Emergency medical research performed under federal regulation 21 § CFR 50.24 provides a means to protect human subjects and investigate novel time-sensitive treatments. Although prospective individual consent is not required for studies conducted under this regulation, consent from a legally authorized representative (LAR) or the patient at the earliest feasible opportunity is required to obtain short- and long-term outcome data. The objective of this study was to determine which demographic, cardiac arrest, and patient outcome characteristics predicted the likelihood of obtaining informed consent following enrollment under exception from informed consent in a multicenter cardiac arrest study. Methods This investigation was an analysis of data collected during a multisite, randomized, controlled, out-of-hospital cardiac arrest clinical trial performed under 21 § CFR 50.24. Research personnel attempted to obtain informed consent from LARs and subjects for medical records review of primary outcome data, as well as consent for neurologic outcome assessments up to 1 year post–cardiac arrest. Hospital discharge and neurologic status were obtained from public records and/or medical records up until the time consent was formally denied, in accordance with federal regulations and guidance. Local institutional review boards also allowed medical records review for cases where consent was neither obtained nor declined despite multiple consent attempts. Patient demographic, cardiac arrest, and clinical outcome characteristics were analyzed in univariate multinomial regression models, with consent status (obtained, denied, neither obtained nor denied) as the dependent variable. A multivariate multinomial logistic regression was then performed. An exploratory secondary analysis following the same process was performed after assigning patients who neither consented nor declined to the declined consent group. Results Among a total study population of 1,655 cardiac arrest subjects, 457 were transported and had consent attempted (27.6%). The survival status and neurologic function at the time of hospital discharge were known in 440 of 457 (96%) subjects. In the multivariate analysis, initial rhythm of ventricular fibrillation/ventricular tachycardia (VF/VT) and survival with good neurologic outcome were strong predictors of obtaining consent (odds ratio [OR] = 3.15, 95% confidence interval [CI] = 1.73 to 5.75; OR = 7.64, 95% CI = 2.28 to 25.63, respectively). The exploratory secondary analysis also showed initial rhythm of VF/VT and survival with good neurologic outcome as strong predictors of obtaining consent (OR = 1.86, 95% CI = 1.17 to 2.95; OR = 4.52, 95% CI = 2.21 to 9.26, respectively). Conclusions Initial arrest rhythm and survival with good neurologic outcome were highly predictive of obtaining consent in this cardiac arrest trial. This phenomenon could result in underrepresentation of outcome data in the study arm with the worse outcome and represents a significant potential confounder in studies performed under 21 § CFR 50.24. Future revisions to the exception from informed consent regulations should allow access to critical survival data recorded as part of standard documentation, regardless of patient consent status.

The intraosseous route is an emergency alternative for the administration of drugs and fluids if vascular access cannot be established. However, in hemorrhagic shock or after vasopressors are given during resuscitation, bone marrow blood flow may be decreased, thus impairing absorption of intraosseously administered drugs. In this study, we evaluated the effects of vasopressin vs. high-dose epinephrine in hemorrhagic shock and cardiac arrest on bone marrow blood flow.Prospective, randomized laboratory investigation that used an established porcine model for measurement of hemodynamic variables and organ blood flow.University hospital laboratory.Fourteen pigs weighing 30 +/- 3 kg.Radiolabeled microspheres were injected to measure bone marrow blood flow during a prearrest control period and during hypovolemic shock produced by rapid hemorrhage of 35% of the estimated blood volume. In the second part of the study, ventricular fibrillation was induced; after 4 mins of untreated cardiac arrest and 4 mins of standard cardiopulmonary resuscitation, a bolus dose of either 200 microg/kg epinephrine (n = 6) or 0.8 units/kg vasopressin (n = 6) was administered. Defibrillation was attempted 2.5 mins after drug administration, and blood flow was assessed again at 5 and 30 mins after successful resuscitation.Mean +/- sem bone marrow blood flow decreased significantly during induction of hemorrhagic shock from 14.4 +/- 4.1 to 3.7 +/- 1.8 mL.100 g-1.min-1 in the vasopressin group and from 18.2 +/- 4.0 to 5.2 +/- 1.0 mL.100 g-1.min-1 in the epinephrine group (p =.025 in both groups). Five minutes after return of spontaneous circulation, mean +/- sem bone marrow blood flow was 3.4 +/- 1.1 mL.100 g-1.min-1 after vasopressin and 0.1 +/- 0.03 mL.100 g-1.min-1 after epinephrine (p =.004 for vasopressin vs. epinephrine). At the same time, bone vascular resistance was significantly (p =.004) higher in the epinephrine group when compared with vasopressin (1455 +/- 392 vs. 43 +/- 19 mm Hg. mL-1.100 g.min, respectively).Bone blood flow responds actively to both the physiologic stress response of hemorrhagic shock and vasopressors given during resuscitation after hypovolemic cardiac arrest. In this regard, bone marrow blood flow after successful resuscitation was nearly absent after high-dose epinephrine but was maintained after high-dose vasopressin. These findings emphasize the need for pressurized intraosseous infusion techniques, because bone marrow blood flow may not be predictable during hemorrhagic shock and drug therapy.

Midodrine hydrochloride is a peripheral -receptor agonist capable of inducing venous and arterial vasoconstriction.[1, 2, 3, 4, 5, 6, 7, 8, 9 and 10] As a result of this action, midodrine has been approved in the United States for treatment of orthostatic hypotension, and several reports attest to its effectiveness in that setting. [6 and 7] In addition, other studies suggest that, at least during short-term follow-up, midodrine may also be effective as a preventive measure in patients with vasovagal syncope. [3, 4, 5 and 10] This report extends prior experience with midodrine as a therapeutic measure in patients with refractory recurrent vasovagal syncope.

Exogenous vasopressin is a promising vasopressor when blood pressure is critically threatened, but the role of endogenous vasopressin during cardiopulmonary resuscitation (CPR) is unknown. We assessed the role of endogenous versus exogenous vasopressin in a porcine open chest CPR model. Seven minutes before induction of cardiac arrest, seven pigs received 10 microg/kg of a selective vasopressin V(1)-receptor-antagonist (Blocked Vasopressin group); another 12 pigs in two groups received saline administration only. After 4 min of untreated ventricular fibrillation followed by 3 min of basic life support CPR, six animals received 0.8 U/kg vasopressin (Exogenous Vasopressin group), whereas the blocked vasopressin group (n = 7), and the remaining six animals received saline placebo only (Endogenous Vasopressin group). Defibrillation was attempted after 14 min of CPR. During basic life support CPR, left ventricular myocardial blood flow was significantly (P < 0.05) decreased in the Blocked Vasopressin group compared with the Exogenous Vasopressin group and Endogenous Vasopressin group (42 +/- 5 compared with 64 +/- 6 and 66 +/- 6 mL x min(-1) x 100g(-1)). Left ventricular myocardial blood flow was significantly decreased in the Blocked Vasopressin group versus Exogenous Vasopressin group versus Endogenous Vasopressin group 90 s and 5 min after drug administration, respectively (38 +/- 4 and 27 +/- 3 vs 145 +/- 32 and 110 +/- 12 vs 62 +/- 4 and 56 +/- 6 mL x min(-1) x 100g(-1), respectively). None of seven Blocked Vasopressin animals, six of six Exogenous Vasopressin pigs, and six of six Endogenous Vasopressin swine had return of spontaneous circulation after 14 min of cardiac arrest including 10 min of CPR (P < 0.05). In conclusion, pigs with blocked endogenous vasopressin had poor coronary perfusion pressure and left ventricular myocardial blood flow during open chest CPR, and could not be successfully resuscitated. All pigs with effective endogenous vasopressin or pigs with effective endogenous vasopressin and additional exogenous vasopressin had good left ventricular myocardial blood flow during experimental CPR, and survived the 1-h postresuscitation phase. We conclude that endogenous vasopressin is an adjunct vasopressor to epinephrine and may serve as a back-up regulator to maintain cardiocirculatory homeostasis.

The use of an inspiratory impedance threshold valve (ITV) during active compression-decompression (ACD) cardiopulmonary resuscitation (CPR) improves perfusion pressures, and vital organ blood flow. We evaluated the effects of positive end-expiratory pressure (PEEP) on gas exchange, and coronary perfusion pressure gradients during ACD + ITV CPR in a porcine cardiac arrest model. All animals received pure oxygen intermittent positive pressure ventilation (IPPV) at a 5:1 compression-ventilation ratio during ACD + ITV CPR. After 8 min, pigs were randomized to further IPPV alone (n = 8), or IPPV with increasing levels of PEEP (n = 8) of 2.5, 5.0, 7.5, and 10 cm H(2)O for 4 consecutive min each, respectively. Mean +/- SEM arterial oxygen partial pressure decreased in the IPPV group from 150 +/- 30 at baseline after 8 min of CPR to 110 +/- 25 torr at 24 min, but increased in the PEEP group from 115 +/- 15 to 170 +/- 25 torr with increasing levels of PEEP (P0.02 for comparisons within groups). Mean +/- SEM diastolic aortic minus diastolic left ventricular pressure gradient was significantly (P0.001) higher after the administration of PEEP (24 +/- 0 vs 17 +/- 1 mm Hg with 5 cm H(2)O of PEEP, and 26 +/- 0 vs 17 +/- 1 mm Hg with 10 cm H(2)O of PEEP), whereas the diastolic aortic minus right atrial pressure gradient (coronary perfusion pressure) was comparable between groups. Furthermore, systolic aortic pressures were significantly (P0.05) higher with 10 cm H(2)O of PEEP when compared with IPPV alone (68 +/- 0 vs 59 +/- 2 mm Hg). In conclusion, when CPR was performed with devices designed to improve venous return to the chest, increasing PEEP levels improved oxygenation. Moreover, PEEP significantly increased the diastolic aortic minus left ventricular gradient and did not affect the decompression phase aortic minus right atrial pressure gradient. These data suggest that PEEP reduces alveolar collapse during ACD + ITV CPR, thus leading to an increase in indirect myocardial compression.Inspiratory impedance during active compression-decompression cardiopulmonary resuscitation improves perfusion pressures, and vital organ blood flow during cardiac arrest. Increasing levels of positive end-expiratory pressure during performance of active compression-decompression cardiopulmonary resuscitation with an inspiratory impedance valve improves oxygenation, and increases the diastolic aortic-left ventricular pressure gradient and systolic arterial blood pressure.

This study was designed to compare the effects of vasopressin vs. epinephrine vs. the combination of epinephrine with vasopressin on vital organ blood flow and return of spontaneous circulation in a pediatric porcine model of asphyxial arrest.Prospective, randomized laboratory investigation using an established porcine model for measurement of hemodynamic variables, organ blood flow, blood gases, and return of spontaneous circulation.University hospital laboratory.Eighteen piglets weighing 8-11 kg.Asphyxial cardiac arrest was induced by clamping the endotracheal tube. After 8 mins of cardiac arrest and 8 mins of cardiopulmonary resuscitation, a bolus dose of either 0.8 units/kg vasopressin (n = 6), 200 microg/kg epinephrine (n = 6), or a combination of 45 microg/kg epinephrine with 0.8 units/kg vasopressin (n = 6) was administered in a randomized manner. Defibrillation was attempted 6 mins after drug administration.Mean +/- SEM coronary perfusion pressure, before and 2 mins after drug administration, was 13 +/- 2 and 23 +/- 6 mm Hg in the vasopressin group; 14 +/- 2 and 31 +/- 4 mm Hg in the epinephrine group; and 13 +/- 1 and 33 +/- 6 mm Hg in the epinephrine-vasopressin group, respectively (p = NS). At the same time points, mean +/- SEM left ventricular myocardial blood flow was 44 +/- 31 and 44 +/- 25 mL x min-(1) x 100 g(-1) in the vasopressin group; 30 +/- 18 and 233 +/- 61 mL x min(-1) x 100 g(-1) in the epinephrine group; and 36 +/- 10 and 142 +/- 57 mL x min(-1) x 100 g(-1) in the epinephrine-vasopressin group (p.01 epinephrine vs. vasopressin; p.02 epinephrine-vasopressin vs. vasopressin). Total cerebral blood flow trended toward higher values after epinephrine-vasopressin (60 +/- 19 mL x min(-1) x 100 g(-1)) than after vasopressin (36 +/- 17 mL x min(-1) x 100 g(-1)) or epinephrine alone (31 +/- 7 mL x min(-1) x 100 g(-1); p = .07, respectively). One of six vasopressin, six of six epinephrine, and four of six epinephrine-vasopressin-treated animals had return of spontaneous circulation (p.01, vasopressin vs. epinephrine).Administration of epinephrine, either alone or in combination with vasopressin, significantly improved left ventricular myocardial blood flow during cardiopulmonary resuscitation. Return of spontaneous circulation was significantly more likely in epinephrine-treated pigs than in animals resuscitated with vasopressin alone.

In an attempt to improve upon the currently poor outcomes for patients in cardiac arrest, new methods and devices have been developed to enhance the efficiency and efficacy of standard cardiopulmonary resuscitation (CPR). One new approach, active compression-decompression (ACD) CPR was developed to lower the intrathoracic pressure during the decompression phase of CPR, thereby enhancing venous blood return to the thorax. Over the past decade the ACD CPR device has been extensively evaluated in animals and humans. ACD CPR is the only new approach for improving CPR efficacy with a mechanical device that has achieved clinical relevance. More recently, an inspiratory impedance threshold valve (ITV ™ ) has been developed that causes a further reduction in intrathoracic pressures, augmenting the efficiency of both standard and ACD CPR. Consequently, ACD CPR and the impedance valve were recently recommended by the American Heart Association. Clinical trials are underway to determine the long-term, potential value of these new technologies.

This study evaluated ventricular fibrillation mean frequency and amplitude to predict defibrillation success in a porcine cardiopulmonary resuscitation (CPR) model using repeated administration of vasopressin or epinephrine. After 4 min of cardiac arrest and 3 min of CPR, 10 pigs were randomly assigned to receive either vasopressin (early vasopressin: 0.4, 0.4, and 0.8 units/kg, respectively, n 5 5) or epinephrine (early epinephrine: 45, 45, and 200 mg/kg, respectively, n 5 5). Another 11 animals were randomly allocated after 4 min of cardiac arrest and 8 min of CPR to receive every 5 min either vasopressin (late vasopressin: 0.4 and 0.8 units/kg, respectively, n 5 5) or epinephrine (late epinephrine: 45 and 200 mg/kg, n 5 6). Ventricular fibrillation mean frequency and amplitude on defibrillation were significantly higher in the vasopressin groups than in the epinephrine groups, respectively. In vasopressin versus epinephrine animals, mean frequency immediately before defibrillation was 9.6 6 1.5 Hz vs 7.0 6 0.7 Hz (P , 0.001), mean amplitude was 0.65 6 0.26 mV vs 0.21 6 0.14 mV (P , 0.001, and coronary perfusion pressure was 27 6 9m m Hg vs 86 4m m Hg (P , 0.00001), respectively. In contrast to no epinephrine animals, all vasopressin animals were successfully defibrillated and survive d1h( P , 0.05). Mean fibrillation frequency and amplitude predicted successful defibrillation and may serve as noninvasive markers to monitor continuing CPR efforts. Furthermore, vasopressin was superior to epinephrine in maintaining these variables above a threshold necessary for successful defibrillation. (Anesth Analg 2000;90:1067‐75)

Background —Blood pressure is severely reduced in patients in cardiac arrest receiving standard cardiopulmonary resuscitation (CPR). Although active compression-decompression (ACD) CPR improves acute hemodynamic parameters, arterial pressures remain suboptimal with this technique. We performed ACD CPR in patients with a new inspiratory threshold valve (ITV) to determine whether lowering intrathoracic pressures during the “relaxation” phase of ACD CPR would enhance venous blood return and overall CPR efficiency. Methods and Results —This prospective, randomized, blinded trial was performed in prehospital mobile intensive care units in Paris, France. Patients in nontraumatic cardiac arrest received ACD CPR plus the ITV or ACD CPR alone for 30 minutes during advanced cardiac life support. End tidal CO 2 (ETCO 2 ), diastolic blood pressure (DAP) and coronary perfusion pressure, and time to return of spontaneous circulation (ROSC) were measured. Groups were similar with respect to age, gender, and initial rhythm. Mean maximal ETCO 2 , coronary perfusion pressure, and DAP values, respectively (in mm Hg), were 13.1±0.9, 25.0±1.4, and 36.5±1.5 with ACD CPR alone versus 19.1±1.0, 43.3±1.6, and 56.4±1.7 with ACD plus valve ( P P Conclusions —Use of an inspiratory resistance valve in patients in cardiac arrest receiving ACD CPR increases the efficiency of CPR, leading to diastolic arterial pressures of >50 mm Hg. The long-term benefits of this new CPR technology are under investigation.

The concept that atrial fibrillation (or at least certain forms of the arrhythmia) may be amenable to reversal or amelioration by transcatheter ablation techniques has become increasingly accepted in recent years. As yet, however, the techniques being studied for ablation of atrial fibrillation address neither known critical anatomic elements nor well defined electrophysiologic markers. The approaches, although essentially empirical, are conceptually based on the 'multiple wavelet' or 'focal origin' hypotheses. To date, addressing 'focal origin' atrial fibrillation by transcatheter ablation has been the more encouraging. However, as technology evolves, both in terms of catheter design and possibly endocardial mapping techniques, approaches to wavelet or rotor mechanisms may become similarly effective. This communication examines concepts regarding the manner in which atrial fibrillation is initiated and maintained. The goals are to better understand the encouraging success of empirical ablation methods, and possibly derive insights which may help refine ablation targeting in the future.

A highly sensitive fluorometric assay technique was adopted in order to examine the adenylate cyclase activity in the minute right ventricular endomyocardial biopsy samples from patients with chronic congestive heart failure (n = 10). Norepinephrine (10(–4) M) and adenosine (10(–3) M) were incubated for 30 min with 10 μl of membrane preparation (1–2 mg protein/mg) to analyze the extent of the receptor‐coupled adenylate cyclase activity. Forskolin (10(–4) M) stimulation was used to estimate the maximum adenylate cyclase activity (pmol/mg protein/min, mean ± SE). The new microanalytical cyclic AMP assay involves four steps: enzymatic destruction of noncyclic adenine nucleotides and phosphorylated metabolites, conversion of cyclic AMP to ATP, amplification of ATP by enzymatic cycling, and fluorometric measurement of NADPH, which is generated in proportion to initial cyclic AMP levels. Basal and forskolin‐stimulated maximum adenylate cyclase activities were 75 ± 8 and 123 ± 15, respectively. Norepinephrine increased the adenylate cyclase activity to 107 ± 14, while adenosine tended to decrease it to 65 ± 7. In addition, elimination of adenosine by adenosine deaminase (10 U/ml) slightly increased the adenylate cyclase activity to 82 ± 9. These results indicate that the adenylate cyclase activity can be measured in minute endomyocardial biopsy samples. Use of this new approach shows promise of becoming a new and potentially important way to predict the efficacy of pharmacological treatment. J. Clin. Lab. Anal. 14:48–52, 2000. © 2000 Wiley‐Liss, Inc.

m-(Iodobenzyl)trozamicol (MIBT) is a recently discovered vesamicol analogue. It has been shown that radiolabelled [125I]MIBT can be used as a marker of cholinergic innervation in the heart as well as in the brain. The purpose of this study was to analyze the direct effects of MIBT on the atrioventricular and intraventricular conduction in addition to the coronary blood flow using the canine isolated, blood-perfused atrioventricular node preparation. Intracoronary administration of MIBT suppressed the atrioventricular and intraventricular conduction, while it increased the coronary blood flow. The effect and duration of action on the intraventricular conduction was less pronounced compared with other effects. Moreover, the doses of MIBT needed to cause negative dromotropic and coronary vasodilator effects in this study was much greater than those needed for imaging the cardiac cholinergic innervation. Pretreatment of the preparations with a muscarinic receptor antagonist, atropine, did not block these effects of MIBT, suggesting that MIBT may possess muscarinic receptor-independent ion channel activity in the cardiac conduction system and coronary arteries.

Use of an inspiratory impedance valve has recently been shown to increase the efficacy of standard and active compression-decompression cardiopulmonary resuscitation. We evaluated the effects of a prototypic impedance valve on the relationship between the active decompression and intra-thoracic pressure using a mechanical model lung system. Intermittent impedance to inspiratory flow of respiratory gases during the decompression phase of active compression-decompression cardiopulmonary resuscitation significantly decreased the intra-thoracic pressure, while the pressure was almost zero cm H2O during the cardiopulmonary resuscitation cycle when the impedance threshold valve was not functioning. Thus, this mechanical model will help in evaluating the valve as well as in optimizing its function by simulating various forms of lung disease.

Background We previously observed that short-term survival after out-of-hospital cardiac arrest was greater with active compression–decompression cardiopulmonary resuscitation (CPR) than with standard CPR. In the current study, we assessed the effects of the active compression–decompression method on one-year survival. Methods Patients who had cardiac arrest in the Paris metropolitan area or in Thionville, France, more than 80 percent of whom had asystole, were assigned to receive either standard CPR (377 patients) or active compression–decompression CPR (373 patients) according to whether their arrest occurred on an even or odd day of the month, respectively. The primary end point was survival at one year. The rate of survival to hospital discharge without neurologic impairment and the neurologic outcome were secondary end points. Results Both the rate of hospital discharge without neurologic impairment (6 percent vs. 2 percent, P=0.01) and the one-year survival rate (5 percent vs. 2 percent, P=0.03) wer...

Active compression decompression resuscitation (ACD-CPR) has been developed as an alternative to standard cardiopulmonary resuscitation (S-CPR). To determine the effect of ACD-CPR on survival and neurologic outcome in patients with out-of-hospital cardiac arrest, this combined analysis involved individual patient data from 2866 patients from seven separate randomized prospective prehospital studies who had received ACD-CPR or S-CPR after out-of-hospital cardiac arrest in seven international sites. Significant improvement in 1-h survival (odds ratio (OR) = 0.83; confidence interval (CI): 0.695-0.99; P0.05) was found with ACD-CPR (n = 1410) versus S-CPR (n = 1456). The odds ratio for hospital discharge after ACD-CPR was similar (OR = 0.82; CI: 0.609-1.107, P = NS), but this finding was not statistically significant. Using the chi2-test for trend, there was a significant improvement in overall survival with ACD-CPR (P0.05) versus S-CPR. This improvement was largely due to the influence of results from one study site. Neurological outcome and complication rates were comparable between groups. Further study is needed to determine which emergency medical services systems may benefit from out-of-hospital use of ACD-CPR.

Syncope is a common problem in medical practice. Of the various types of syncope, the neurally mediated syncopal syndromes (of which vasovagal syncope is the most common) predominate. In most cases, neurally mediated syncope is a solitary event that can be managed with only reassurance, but certain patients (those with multiple recurrences or those who have been injured as a result of syncope) need further investigation and therapy. Dietary and lifestyle changes are crucial and often overlooked aspects of therapy that may be sufficient to control symptoms. Pharmacologic therapy, which usually starts with beta-blockers or fludrocortisone, can also be effective. Finally, certain patients may continue to have recurrences despite the use of both nonpharmacologic and pharmacologic therapy. It was recently demonstrated that permanent pacing may be effective in preventing recurrent syncopal episodes in some of these patients.

Although a benefit of vasopressin when compared with epinephrine was shown during cardiopulmonary resuscitation (CPR) after a short duration of ventricular fibrillation cardiac arrest, the effect of vasopressin during prolonged cardiac arrest with pulseless electrical activity is currently unknown.Prospective, randomized laboratory investigation using an established porcine model with instrumentation for measurement of hemodynamic variables, vital organ blood flow, blood gases, and return of spontaneous circulation.University hospital laboratory.Eighteen domestic pigs.After 15 mins of cardiac arrest and 3 mins of chest compressions, 18 animals were randomly treated with either 0.8 units/kg vasopressin (n = 9) or 200 microg/kg epinephrine (n = 9).Compared with epinephrine, vasopressin resulted, at both 90 secs and 5 mins after drug administration, in significantly higher (p.05) median (25th-75th percentiles) left ventricular myocardial blood flow (120 [range, 96-193] vs. 54 [range, 11-92] and 56 [range, 41-80] vs. 21 [range, 11-40] mL/min/100 g, respectively) and total cerebral blood flow (85 [78-102] vs. 24 [18-41] and 50 [44-52] vs. 8 [5-23] mL/min/100 g, respectively). Spontaneous circulation was restored in eight of nine animals in the vasopressin group and in one of nine animals in the epinephrine group (p = .003).Compared with a maximum dose of epinephrine, vasopressin significantly increased left ventricular myocardial and total cerebral blood flow during CPR and return of spontaneous circulation in a porcine model of prolonged cardiac arrest with postcountershock pulseless electrical activity.

Acute passive fixation atrial lead dislodgment occurred due to an unexpected and marked postural descent of the heart after permanent pacemaker implantation in two patients. Sagging of the heart in these two individuals may have been related to a history of morbid obesity followed by weight loss of over 100 pounds. Lead replacement with active fixation leads was required in both cases. The term "sagging heart syndrome" is proposed to describe this clinical entity. In certain adult populations, such as in patients with a history of significant weight loss, the "sagging heart syndrome" may represent a previously unrecognized cause of acute lead dislodgment.

Prehospital discharge defibrillation testing is often performed to verify the function of newly implanted cardioverter defibrillators (ICDs). To determine whether elimination of predischarge testing could reduce costs without placing patients at additional risk, 31 patients were randomized in this prospective clinical evaluation to either receive or not receive a predischarge ICD defibrillation test. Expenses associated with postimplant care was the primary endpoint. All patients underwent induction of ventricular fibrillation after 6 months to evaluate ICD function. The groups were well matched in terms of patient characteristics, initial lead implant parameters, and defibrillation thresholds. Elimination of prehospital discharge testing resulted in a savings of $1,800/patient after 6 months, with no difference between groups in terms of ICD complication rates or unanticipated hospital admissions. Further studies are needed to better define the most appropriate time to assess defibrillation thresholds in the first year after implantation.

We prospectively studied the efficacy of pindolol, a beta-adrenergic blocker with intrinsic sympathomimetic activity (ISA), for the prevention of syncope recurrences in 31 patients with recurrent neurocardiogenic syncope. Pindolol proved to be an effective treatment, even in patients who had previously failed treatment with conventional beta blockers, suggesting a clinical benefit from addition of ISA to beta blockade in this setting.

Lasnier, Joseph M., David H. Ingbar, Ethan P. Carter, Kirk Wilson, Scott McKnite, Keith G. Lurie, and O. Douglas Wangensteen.Perfusion technique determines alveolar fluid resorption rate in the isolated perfused rat lung. J. Appl. Physiol. 84(2): 740–745, 1998.—The isolated perfused lung (IPL) preparation is a well-established model for the study of alveolar epithelial sodium transport. We noted that preparations of normal fluid-filled rat lungs with recirculated perfusate reproducibly lost weight, whereas preparations in which the perfusate was discarded after a single pass through the lungs had a variable and lesser weight change. To confirm this, we performed IPL experiments by using male Sprague-Dawley specific-pathogen-free rats (175–225 g). In 10 IPLs, perfusate initially was discarded after passing through the lungs and then was recirculated continuously. During the single-pass period, the rate of weight change was +0.7 ± 2.0 mg/min compared with −9.0 ± 1.3 mg/min for the recirculating period. Adenosine 3′,5′-cyclic monophosphate (cAMP) accumulated during recirculation. The weight loss induced by recirculation was reproduced by perfusion with 8-bromoadenosine 3′,5′-cyclic monophosphate or terbutaline in single-pass fashion and blocked when the kinase inhibitor H-8 or phosphodiesterase was present in the recirculating perfusate. In summary, perfusate recirculation in the IPL stimulates fluid resorption at least partially via cAMP. This should be factored into the design and interpretation of IPL experiments.

Background Multisite ventricular pacing has recently been proposed as an additional treatment for patients with severe congestive heart failure. To further assess the potential value of this technique, we compared the acute hemodynamic changes associated with pacing the right ventricular apex (RVA) or outflow tract (RVOT) alone, the left ventricle (LV) alone, or biventricular (BIV) pacing of the RVA and LV together. Methods and Results Acute hemodynamic findings were measured in 27 patients with severe heart failure despite optimal therapy and either first-degree AV block and/or an intraventricular conduction defect. In the 23 patients with a high pulmonary capillary wedge pressure (PCWP) (>15 mm Hg), data were collected after transvenous pacing at different ventricular sites in either the VDD mode (AV delay=100 ms) or the VVI mode in patients with atrial fibrillation (n=6). The mean baseline cardiac index was 1.82 L · min −1 · m −2 . Mean±SD baseline systolic blood pressure (SBP) (118.5±15.2 mm Hg), PCWP (26.4±6.6 mm Hg), and V-wave amplitude (39.1±14.6 mm Hg) were similar before and after either RVA or RVOT pacing. In contrast, LV-based pacing (either LV alone or BIV pacing) resulted in higher SBP ( P P P Conclusions In patients with severe congestive heart failure, both LV pacing alone and BIV pacing resulted in a similar and significant acute improvement in SBP, PCWP, and V-wave amplitude compared with baseline measurements and RV pacing alone. These results provide a strong basis for initiating long-term studies examining the chronic effects of LV-based pacing in patients with medically refractory congestive heart failure.

Both epinephrine (Epi) and vasopressin (VP) increase coronary perfusion pressure (CPP) when administered during cardiac arrest. Given their different mechanisms of action we tested the hypothesis that during cardiopulmonary resuscitation (CPR) a combination of VP plus Epi would be superior to either agent alone. Epi(40 microg/kg), VP(0.3 U/kg) and the combination of both agents were assessed in a porcine model of ventricular fibrillation (VF). Maximum CPP (diastolic aortic-right atrial pressures) during CPR was similar among the groups but the time course of action was different in each group: with Epi + VP the increase in CPP was significantly more rapid than with VP alone whereas the CPP remained significantly higher for a longer periods of time with VP or VP + Epi versus Epi alone. Left ventricular blood flow (ml/min per g) determined during CPR two min after drug administration was similar between groups: Epi 1.06 +/- 0.16; VP 0.82 +/- 0.26; Epi + VP 0.83 +/- 0.14 (P = N.S.). Post drug administration. 2 min, cerebral blood flow (ml/min per g) in the VP group (0.76 +/- 0.15) was more than two times higher compared with Epi alone (Epi:0.30 +/- 0.08, P0.01 versus VP) and Epi plus VP (Epi + VP:0.23 +/- 0.03, P0.01 versus VP). We conclude that combination of VP + Epi during cardiac arrest results in a more rapid rise in CPP when compared with VP alone and a more sustained elevation in CPP than observed with Epi alone. Thus, the synergistic effects of these two potent vasopressor agents may be of benefit during CPR.

Atrial fibrillation is the most common cardiac arrhythmia requiring treatment. Limitations of medical treatment have prompted development of nonpharmacologic therapies for this arrhythmia. These are aimed at ventricular rate control during atrial fibrillation, termination of the arrhythmia, and/or prevention of recurrences. Ventricular rate control can be achieved with transcatheter ablation or modification of the atrioventricular node. The MAZE operation is effective in preventing arrhythmia recurrence, but because it requires cardiac surgery, its appeal is limited. Development of the technique for direct transcatheter ablation of atrial fibrillation is eagerly anticipated and may represent the standard curative treatment of the future. In appropriately selected patients, implantable device therapy may play an important role in the treatment of paroxysmal atrial fibrillation.

Background Intravenous administration of vasopressin during cardiopulmonary resuscitation (CPR) has been shown to be more effective than optimal doses of epinephrine. This study evaluated the effect of endobronchial vasopressin during CPR. Methods After 4 min of untreated ventricular fibrillation and 3 min of CPR, 21 pigs were randomized to be treated with 0.8 U/kg intravenous vasopressin (n = 7), 0.8 U/kg endobronchial vasopressin (n = 9), or an endobronchial placebo of normal saline (n = 5). Defibrillation was performed 5 min after drug administration to attempt return of spontaneous circulation. Results All animals in the intravenous and endobronchial vasopressin group were resuscitated successfully, but only two of five animals in the placebo group were. At 2 and 5 min after drug administration, coronary perfusion pressure in the intravenous and endobronchial vasopressin group was significantly higher than in the placebo group (50 +/- 10, 34 +/- 5 vs. 16 +/- 6 mmHg, respectively; and 35 +/- 10, 39 +/- 10 vs. 19 +/- 5 mmHg, respectively; P < 0.05). Conclusions Endobronchial vasopressin is absorbed during CPR, coronary perfusion pressure is increased significantly within a short period, and the chance of successful resuscitation is increased in this porcine model of CPR. Endobronchial vasopressin may be an alternative for vasopressor administration during CPR, when intravenous access is delayed or not available.

Mechanical measures intended to increase blood flow to vital organs are the mainstay of therapy for patients in cardiac arrest. Several new cardiopulmonary resuscitation techniques and devices have been developed and tested since the first report of manual closed-chested cardiopulmonary resuscitation nearly four decades ago. These include vest cardiopulmonary resuscitation, active compression-decompression cardiopulmonary resuscitation, an intra-aortic perfusion balloon pump, and an inspiratory impedance threshold valve, interposed abdominal counterpulsation cardiopulmonary resuscitation, and phased thoracic-abdominal compression and decompression. Many of these new mechanical advances in the treatment of cardiac arrest are currently undergoing clinical evaluation in patients in cardiac arrest. Although some of those new methods and techniques have shown promise in small human clinical trials, none have yet to be found to be conclusively superior to manual closed-chested cardiopulmonary resuscitation.

Although it is essential to cardiac conduction, little is known about the biochemistry underlying postreceptor adrenergic, cholinergic and purinergic processes in the AV node. To study these mechanisms, we adapted a new and highly sensitive fluorometric assay for cyclic adenosine monophosphate (AMP) to characterize regional adenylylcyclase activity (cyclic AMP production in pmol/min/mg of protein) in membrane preparations made from 20-50 pieces of freeze-dried, 20-microm thick, microdissected samples of tissue from canine right atrium, the AV nodal region, and left ventricle. Basal and NaF-stimulated adenylylcyclase activity (mean +/- SEM, n = 6) were 7.2 +/- 0.4 and 72.4 +/- 7.5 in atrial, 15.6 +/- 1.3 and 58.8 +/- 4.7 in AV nodal, and 6.4 +/- 0.9 and 66.7 +/- 5.0 in ventricular tissues, respectively. Isoproterenol (10(-7)-10(-4) M) increased adenylylcyclase activity in a dose-dependent fashion in three different regions. The isoproterenol (10(-6) M)-stimulated adenylylcyclase activity (n = 6) was 14.4 +/- 1.3 in atrial, 21.9 +/- 1.6 in AV nodal and 13.4 +/- 1.4 in ventricular tissues. Adenosine (10(-3) M) and carbachol (10(-5) M) inhibited isoproterenol (10(-6) M)-stimulated adenylylcyclase activity to 10.1 +/- 1.1, 12.9 +/- 1.3 in atrial, 15.1 +/- 1.6, 15.5 +/- 1.2 in AV nodal, and 7.5 +/- 0.7, 11.9 +/- 1.2 in ventricular tissues, respectively. The results demonstrate that there are regional differences in adenylylcyclase activity under basal conditions and after adrenergic, purinergic, and cholinergic stimulation in the heart. Unlike adenosine, the inhibitory effects of cholinergic stimulation appear to be more specific for the AV node.

Effective management of the syncope patient is critically dependent on excluding conditions in which altered consciousness is not due to syncope (e.g., seizure and sleep disorders) then establishing the basis for syncopal symptoms. The initial diagnostic step in syncope patients is differentiation of those individuals with normal cardiovascular status from those with structural heart disease. In the former, tilt-table testing and related studies of autonomic nervous system function are usually the most productive direction in which to proceed. In patients with structural heart disease, a functional assessment of the suspected structural disturbance (i.e., hemodynamic, angiographic, imaging as appropriate) and evaluation for susceptibility to symptomatic arrhythmias by monitoring or conventional electrophysiologic testing is appropriate. Autonomic function testing should follow if the diagnosis remains unclear. In only a few instances should specialized neurologic studies be undertaken as an initial step. The ultimate objective is always to obtain a sufficiently strong correlation between syncopal symptoms and detected abnormalities to feel confident in the diagnosis, permit an accurate assessment of prognosis, and develop an appropriate treatment plan.

Vasovagal syncope is characterized by transient failure of usually reliable physiologic mechanisms responsible for maintaining both systemic arterial pressure and cerebral blood flow. Two circulatory phenomena are almost universally present: systemic arterial vasodilation and bradycardia. A third phenomenon, cerebrovascular constriction, has also been described but its contribution to the faint is less well established. The neural reflex pathways responsible for triggering the circulatory changes in the vasovagal faint are incompletely understood, but have recently been the subject of renewed interest. In part, this interest probably stems from the frequency with which vasovagal symptoms are now recognized to be the cause of fainting spells. Additionally, however, there is an increasingly recognized need to develop treatment strategies for those affected patients in whom recurrent vasovagal symptoms are particularly troublesome. It is the goal of this discussion to focus on those aspects of circulatory control, and in particular on potential interactions among certain neural and humoral systems, which may contribute to the inappropriate physiologic responses associated with the vasovagal faint.

Implantable cardioverter-defibrillator (ICD) pulse generators are now routinely positioned in a pectoral location, either submuscularly (under the pectoralis muscles) or subcutaneously (over the pectoralis muscles). Furthermore, in current ICDs, the generator shield usually participates in the defibrillation energy pathway ("hot can"). Consequently, the precise generator location could affect defibrillation system efficacy. To assess this issue, we compared high voltage pathway impedance and defibrillation threshold (DFT) in 20 patients undergoing submuscular and 46 patients undergoing subcutaneous pectoral implantation of an Angeion Sentinel ICD and an AngeFlex dual-coil defibrillation lead. Measurements were performed at time of ICD implant, pre-hospital discharge, and 1, 3 and/or 6 months later. Following induction of ventricular fibrillation, 569 biphasic waveform shocks were delivered between the generator shield and either the distal defibrillation coil (RV/can configuration) or both proximal and distal coils (RV/SVC/can configuration). Impedance differences between submuscular and subcutaneous implants were approximately 3-4 Ohms (p value of 0.132 to < 0.001 depending on time of follow-up and lead configuration). A significant increase in impedance over time was noted independent of implant location and lead configuration. The DFT at implant or pre-discharge was assessed in 27 individuals, and was 9.9 +/- 3.8 J in 8 patients in the submuscular group, and 7.4 +/- 3.3 J in 19 patients in the subcutaneous group (p = 0.057). In conclusion, anatomic location of a "hot can" ICD generator (submuscular versus subcutaneous) influences impedance to defibrillation current, but the impact is of small magnitude and does not appear to result in clinically important differences in DFT.

One approach to improve outcomes after trauma and hemorrhage is to follow the principles of permissive hypotension by avoiding intravascular overpressure and thereby preventing dislodgement of platelet plugs early in the clotting process. We hypothesized that augmentation of negative intrathoracic pressure (nITP) by treatment with an impedance threshold device would improve hemodynamics without compromising permissive hypotension or causing hemodilution, whereas aggressive fluid resuscitation with normal saline (NS) would result in hemodilution and SBPs that are too high for permissive hypotension and capable of clot dislodgement.Thirty-four spontaneously breathing anesthetized female pigs (30.6 ± 0.5 kg) were subjected to a fixed 55% hemorrhage over 30 minutes; block randomized to nITP, no treatment, or intravenous bolus of 1-L NS; and evaluated over 30 minutes. Results are reported as mean ± SEM.Average systolic blood pressures (SBPs) (mm Hg) 30 minutes after the study interventions were as follows: nITP, 82.1 ± 2.9; no treatment, 69.4 ± 4.0; NS 89.3 ± 5.2. Maximum SBPs during the initial 15 minutes of treatment were as follows: nITP, 88.0 ± 4.3; no treatment, 70.8 ± 4.3; and NS, 131 ± 7.6. After 30 minutes, mean pulse pressure (mm Hg) was significantly higher in the nITP group (nITP, 32.3 ± 2.2) versus the no-treatment group (21.5 ± 1.5 controls) (p0.05), and the mean hematocrit was 25.2 ± 0.8 in the nITP group versus 19 ± 0.6 in the NS group (p0.001).In this porcine model of hemorrhagic shock, nITP therapy significantly improved SBP and pulse pressure for 30 minutes without overcompensation compared with controls with no treatment. By contrast, aggressive fluid resuscitation with NS but not nITP resulted in a significant rise in SBP to more than 100 mm Hg within minutes of initiating therapy that could cause a further reduction in hematocrit and clot dislodgment.

Background Survival after out-of-hospital cardiac arrest (OHCA) remains poor. Acute coronary obstruction is a major cause of OHCA. We hypothesize that early coronary reperfusion will improve 24 h-survival and neurological outcomes. Methods Total occlusion of the mid LAD was induced by balloon inflation in 27 pigs. After 5 min, VF was induced and left untreated for 8 min. If return of spontaneous circulation (ROSC) was achieved within 15 min (21/27 animals) of cardiopulmonary resuscitation (CPR), animals were randomized to a total of either 45 min (group A) or 4 h (group B) of LAD occlusion. Animals without ROSC after 15 min of CPR were classified as refractory VF (group C). In those pigs, CPR was continued up to 45 min of total LAD occlusion at which point reperfusion was achieved. CPR was continued until ROSC or another 10 min of CPR had been performed. Primary endpoints for groups A and B were 24-h survival and cerebral performance category (CPC). Primary endpoint for group C was ROSC before or after reperfusion. Results Early compared to late reperfusion improved survival (10/11 versus 4/10, p = 0.02), mean CPC (1.4 ± 0.7 versus 2.5 ± 0.6, p = 0.017), LVEF (43 ± 13 versus 32 ± 9%, p = 0.01), troponin I (37 ± 28 versus 99 ± 12, p = 0.005) and CK-MB (11 ± 4 versus 20.1 ± 5, p = 0.031) at 24-h after ROSC. ROSC was achieved in 4/6 animals only after reperfusion in group C. Conclusions Early reperfusion after ischemic cardiac arrest improved 24 h survival rate and neurological function. In animals with refractory VF, reperfusion was necessary to achieve ROSC.

Time to awakening after out-of-hospital cardiac arrest (OHCA) and post-resuscitation therapeutic hypothermia (TH) varies widely. We examined the time interval from when comatose OHCA patients were rewarmed to 37°C to when they showed definitive signs of neurological recovery and tried to identify potential predictors of awakening.With IRB approval, a retrospective case study was performed in OHCA patients who were comatose upon presentation to a community hospital during 2006-2010. They were treated with TH (target of 33°C) for 24h, rewarmed, and discharged alive. Comatose patients were generally treated medically after TH for at least 48h before any decision to withdraw supportive care was made. Pre-hospital TH was not used. Data are expressed as medians and interquartile range.The 89 patients treated with TH in this analysis were divided into three groups based upon the time between rewarming to 37°C and regaining consciousness. The 69 patients that regained consciousness in ≤48h after rewarming were termed "early-awakeners". Ten patients regained consciousness 48-72h after rewarming and were termed "intermediate-awakeners". Ten patients remained comatose and apneic72h after rewarming but eventually regained consciousness; they were termed "late-awakeners". The ages for the early, intermediate and late awakeners were 56 [49,65], 62 [48,74], and 58 [55,65] years, respectively. Nearly 67% were male. Following rewarming, the time required to regain consciousness for the early, intermediate and late awakeners was 9 [2,18] (range 0-47), 60.5 [56,64.5] (range 49-71), and 126 [104,151]h (range 73-259), respectively. Within 90 days of hospital admission, favorable neurological function based on a Cerebral Performance Category (CPC) score of 1 or 2 was reported in 67/69 early, 10/10 intermediate, and 8/10 late awakeners.Following OHCA and TH, arbitrary withdrawal of life support48h after rewarming may prematurely terminate life in many patients with the potential for full neurological recovery. Additional clinical markers that correlate with late awakening are needed to better determine when withdrawal of support is appropriate in OHCA patients who remain comatose48h after rewarming.

We investigated the effects of ischemic postconditioning (IPC) with and without cardioprotective vasodilatory therapy (CVT) at the initiation of cardiopulmonary resuscitation (CPR) on cardio-cerebral function and 48-h survival.Prospective randomized animal study. Following 15 min of ventricular fibrillation, 42 Yorkshire farm pigs weighing an average of 34 ± 2 kg were randomized to receive standard CPR (SCPR, n=12), SCPR+IPC (n=10), SCPR+IPC+CVT (n=10), or SCPR+CVT (n=10). IPC was delivered during the first 3 min of CPR with 4 cycles of 20s of chest compressions followed by 20-s pauses. CVT consisted of intravenous sodium nitroprusside (2mg) and adenosine (24 mg) during the first minute of CPR. Epinephrine was given in all groups per standard protocol. A transthoracic echocardiogram was obtained on all survivors 1 and 4h post-ROSC. The brains were extracted after euthanasia at least 24h later to assess ischemic injury in 7 regions. Ischemic injury was graded on a 0-4 scale with (0=no injury to 4 ≥ 50% neural injury). The sum of the regional scores was reported as cerebral histological score (CHS). 48 h survival was reported.Post-resuscitation left ventricular ejection (LVEF) fraction improved in SCPR+CVT, SCPR+IPC+CVT and SCPR+IPC groups compared to SCPR (59% ± 9%, 52% ± 14%, 52% ± 14% vs. 35% ± 11%, respectively, p0.05). Only SCPR+IPC and SCPR+IPC+CVT, but not SCPR+CVT, had lower mean CHS compared to SCPR (5.8 ± 2.6, 2.8 ± 1.8 vs. 10 ± 2.1, respectively, p0.01). The 48-h survival among SCPR+IPC, SCPR+CVT, SCPR+IPC+CVT and SCPR was 6/10, 3/10, 5/10 and 1/12, respectively (Cox regression p0.01).IPC and CVT during standard CPR improved post-resuscitation LVEF but only IPC was independently neuroprotective and improved 48-h survival after 15 min of untreated cardiac arrest in pigs.

The autonomic nervous system plays a central role in the maintenance of hemodynamic stability. Dysfunction of this complex regulatory system can lead to the development of loss of consciousness. This article summarizes our current understanding of the role of the autonomic nervous system in maintaining a stable blood pressure and heart rate under normal and abnormal physiologic conditions. The role of baroreceptors, mechanoreceptors, chemoreceptors, vascular reactivity, and the interaction of these sensor systems with the central nervous system as a whole are reviewed. Current concepts related to the mechanisms of unexplained syncope and the "state-of-the-art" diagnostic and treatment options are also discussed.

In an effort to reduce energy requirements for atrial defibrillation to a level low enough to perform painless electrical cardioversion with an implantable atrial defibrillator, we tested the hypothesis that drug therapy with the class III agent d-sotalol, when used concurrently with a low-energy shock, reduces atrial defibrillation threshold. In a nonthoracotomy canine model of atrial fibrillation, intracardiac shocks were delivered between the distal coronary sinus and the mid-right atrium. Based on a step-up energy delivery protocol the atrial defibrillation threshold was defined as the least amount of energy that resulted in a >10% and

Objective: This study was designed to assess whether median frequency of ventricular fibrillation (VF) correlates with myocardial blood flow and defibrillation success during cardiopulmonary resuscitation (CPR) after epinephrine or vasopressin administration. Methods and results: After 4 min of VF and 3 min of CPR, 14 pigs received 0.045 mg/kg epinephrine or 0.4 U/kg vasopressin. Using radio-labeled microspheres, median myocardial blood flow during CPR before, and 90 s and 5 min after drug administration (DA) was 15.5 (12.6, 23.1; 25th percentile, 75th percentile), 26.4 (18.5, 29.1), 16.9 (14.9, 19.1) ml min−1 100 g−1, respectively, in the epinephrine, and 16.9 (15.4, 18.9), 48.1 (36.9, 68.9) (P < 0.05 vs. before DA), 52.3 (38.5, 65.0) ml min−1 100 g−1,respectively, in the vasopressin group. Using spectral analysis of VF, median frequency of VF was 11.0(10.7, 11.8), 11.3(9.6, 13.1), 10.2, (8.8, 11.4) Hz, respectively, in the epinephrine, and 10.1 (10.0, 10.5), 11.7 (11.1, 14.2) (P < 0.05 vs. before DA), 13.2 (11.5, 13.9) Hz, respectively, in the vasopressin group at the same points in time. Median frequency correlates significantly with myocardial blood flow in the epinephrine (n = 21; rs = 0.772; P < 0.001) and in the vasopressin group (n = 21; rs = 0.905; P < 0.001). Median fibrillation frequency before the first defibrillation was 13.0 (12.2, 13.2) Hz in resuscitated (n = 8) and 9.2 (8.3, 10.2) Hz (n = 6) in non-resuscitated animals (P < 0.01). Conclusions: We conclude that median frequency of VF reflects myocardial blood flow and the chance of successful defibrillation during closed-chest CPR after vasopressor treatment in a porcine model of VF.

This study compared alterations in arterial catecholamine concentrations associated with tilt-induced vasovagal syncope that differed in older (>65 years) and younger patients (

A retrospective review of patients evaluated at a university-based referral hospital was performed to assess the basis for syncope associated with exercise in young patients. Over an 8-year period, 54 consecutive young patients (aged 12 to 30 years) were referred for evaluation of frank syncope. Twelve patients had syncope associated with exercise (group I) and 42 patients had syncope not associated with exercise (group II). Patients underwent physical examination, chest x-ray, 2-dimensional echocardiography, and in selected cases, cardiac catheterization. Head-up tilt-table testing was performed in 11 of 12 group I patients. Ten group I patients had no evidence of structural heart disease: 9 of these 10 (90%) developed syncope with tilt-table testing. Head-up tilt-table testing was performed in 41 of 42 group II patients: 34 (83%) developed syncope with tilt-table testing. Standard cardiac electrophysiologic study was performed in 9 of 12 group I and in 30 of 42 group II patients, and identified a basis for syncope in only 2 group I and 1 group II patients. Among 9 group I patients with a positive result on head-up tilt-table testing and no evidence of structural heart disease (mean follow-up 4.3 years), 7 are without further episodes of syncope; 3 have discontinued medication and 5 have resumed at least limited exercise. In conclusion, susceptibility to tilt-induced syncope was the most frequent finding in young patients without structural heart disease referred for evaluation of exercise-associated syncope. Tilt-table testing may be an important diagnostic tool for the evaluation of these patients.

Intrathoracic pressure regulation (IPR) has been used to treat hypotension and states of hypoperfusion by providing positive pressure ventilation during inspiration followed by augmentation of negative intrathoracic pressure during expiration. This therapy augments cardiac output and lowers intracranial pressure, thereby providing greater circulation to the heart and brain. The effects of IPR on microcirculation remain unknown.Using a hemorrhagic model, hemodynamics and sublingual microcirculation were evaluated after a 55% blood loss over a 30 min timeframe in 10 female farm pigs (30 kg) previously anesthetized with isoflurane.After hemorrhage the mean arterial pressure was 27 ± 4 mm Hg. Blood cell velocity, the key indicator of microcirculation, was significantly reduced after the bleed from 1033 ± 175 μm/s pre-bleed to 147 ± 60 μm/s (p0.0001). Application of an IPR device reduced airway pressure during expiration to -9 mm Hg after each positive pressure breath (10 mL/kg, 10 breaths/min) and resulted in a rapid increase in systemic hemodynamics and microcirculation. During IPR treatment, average mean arterial pressure increased by 59% to 43 ± 6 mm Hg (p = 0.002) and blood cell velocity increased by 344% to 506 ± 99 μm/s (p = 0.001).In this animal model, we observed that microcirculation and systemic blood pressures are correlated and may be significantly improved by using IPR therapy.

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 porcine model 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 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.

Within the last several years a new method of CPR, termed active compression-decompression (ACD) CPR was developed. Based upon the theory that active rather than passive chest wall decompression would augment venous return and ventilation by causing an increase in negative intrathoracic pressure during the decompression phase of CPR, a hand-held device was designed and is now being used clinically. Studies in dogs and pigs in ventricular fibrillation have demonstrated a significant improvement in systolic blood pressure, coronary perfusion pressure and total brain and myocardial blood flow with ACD CPR compared with standard CPR. Animal and human studies suggest that the mechanism of ACD CPR is complex, with coronary perfusion occurring during both the compression and decompression phases. Clinical studies comparing ACD to standard CPR in patients in cardiac arrest demonstrate that immediate resuscitation rates are nearly doubled when ACD CPR is started within 10 min after cardiac arrest. The potential long term benefits of ACD CPR remain under investigation.

The effects of aging on atrioventricular (AV) nodal and right and left ventricular beta-adrenergic receptor (beta-AR) characteristics were studied in Fischer 344 rat hearts using quantitative autoradiography. Twenty-micrometer-thick cardiac sections containing the compact AV node from 16 mature (4-6 mo old) rats, 6 middle-aged (12 mo old) rats, and 16 old (24 mo old) rats were incubated with [125I]iodocyanopindolol, [125I]iodocyanopindolol plus atenolol, or ICI 118551. Saturation experiments revealed a significant age-related decrease in AV nodal beta-AR density (mature: 190 +/- 46, middle-aged: 165 +/- 27, old: 133 +/- 34 amol/mm2; P < 0.01), with no change in affinity (mature: 106 +/- 62, middle-aged: 132 +/- 46, old: 128 +/- 66 pM). No age-related changes in AV nodal beta-AR subtype ratio (55% beta 1, 45% beta 2) or estimated compact AV node volume were detected (mature: 66 +/- 17, old: 65 +/- 23 microns 3). No difference in beta-AR density or affinity was detected between mature and old rats in either left (LV) or right (RV) ventricular tissue (LV, mature: 60 +/- 11, middle-aged: 59 +/- 11, old: 62 +/- 11 amol/mm2; RV, mature: 65 +/- 9, middle-aged: 65 +/- 11, old: 58 +/- 10 amol/mm2). beta-AR subtype ratios for the left ventricle (64% beta 1, 36% beta 2) and right ventricle (63% beta 1, 37% beta 2) did not significantly differ between mature and old rats. To summarize, aging from 4 to 24 mo in the Fischer 344 rat is associated with 1) a decrease in AV nodal beta-AR density with no change in affinity; 2) no change in volume of the compact region of the AV node; 3) no change in beta-AR subtype ratio in the AV node, left ventricle, or right ventricle; and 4) no change in either RV or LV beta-AR density.

Prevention of recurrent atrial fibrillation and flutter remains a difficult clinical problem. Consequently, development of an easily implantable automatic atrial cardioverter defibrillator is appealing. In this context we have examined the feasibility of intracavitary low-energy shocks delivered via transvenously positioned electrodes for termination of induced atrial tachyarrhythmias in canine models. This study extends these observations with use of single-pathway (5 msec pulse duration) and dual-pathway sequential (55msec, 0.2 msec separation) shocks of varying leading edge voltages (100 to 400 V) in a closed-chest canine talc-pericarditis model. Bipolar 9.5 French electrode catheters (electrode surface areas, 0.62 cm 2 ) were positioned at the superior vena cava-right atrium (SVC-RA) junction (labeled SVC) and right ventricular (RV) apex, with a subcutaneous plate over the chest wall. For single-pathway shocks, overall treatment effectiveness was comparable among the three vectors tested (RV apex to SVC, 35%; RV apex to subcutaneous plate, 17%; and SVC to subcutaneous plate, 35%). Furthermore, there was no evident relationship between leading edge voltage and shock effectiveness. In conrast, although each of the dual-pathway shock vector combinations tested also showed similar overall effectiveness, there was an apparent dose-response effect as leading edge voltage increased. The SVC (common) to RV apex (pulse 1) and subcutaneous plate (pulse 2) achieved 60% effectiveness at 400 V (approximately 4 joules). Thus this study provides additional evidence favoring feasibility of low-energy transvenous atrial cardioversion defibrillation. However, further refinement of energy delivery is essential for the implantable automatic atrial cardioverter defibrillator concept to become clinically accepted.

An enzymatic assay for adenosine 3':5'-monophosphate (cAMP) is described. Current measurement techniques can be expensive, time-consuming, and lack versatility. The critical step of this new method is the enzymatic destruction of endogenous purinergic noncyclic nucleotides. The diester linkage of cAMP is then cleaved and AMP is phosphorylated to ATP. Newly formed ATP is amplified using ATP-ADP cycling reactions and NADPH is measured fluorometrically. cAMP was measured in neonatal rat ventricular myocytes cultured on standard 100-mm dishes and treated with 2 microM 3-isobutyl-1-methylxanthine +/- 1 microM isoproterenol. When the enzymatic fluorometric assay was compared with an immunocolorimetric assay and a radioimmunoassay, cAMP content (pmol/plate mean +/- SE) was 124.3 +/- 6.7, 130.6 +/- 3.9, and 144.0 +/- 4.4 without isoproterenol and 656.4 +/- 23.5, 659.5 +/- 54.1, and 677.1 +/- 48.9 with isoproterenol, respectively. The standard curve with the enzymatic fluorometric assay is linear, in contrast to the curves of the nonlinear immunocolorimetric assay and radioimmunoassay. The enzymatic fluorometric assay can be used to detect < 20 fmol of cAMP/sample and can be adapted to measure < 1 fmol/sample. It can also be used to measure the activities of adenylate cyclase and phosphodiesterase. In summary, this enzymatic cAMP assay is sensitive, safe, versatile, and inexpensive and has multiple potential applications.