Modulation of AV nodal and Hisian conduction by changes in extracellular space.

Previous studies have demonstrated that the extracellular space (ECS) component of the atrioventricular (AV) node and His bundle region is larger than the ECS in adjacent contractile myocardium. The potential physiological significance of this observation was examined in a canine blood-perfused AV nodal preparation. Mannitol, an ECS osmotic expander, was infused directly into either the AV node or His bundle region. This resulted in a significant dose-dependent increase in the AV nodal or His-ventricular conduction time and in the AV nodal effective refractory period. Mannitol infusion eventually resulted in Wenckebach block (n = 6), which reversed with mannitol washout. The ratio of AV nodal to left ventricular ECS in tissue frozen immediately on the development of heart block (n = 8) was significantly higher in the region of block (4.53 +/- 0.61) compared with that in control preparations (2.23 +/- 0.35, n = 6, P < 0.01) and donor dog hearts (2.45 +/- 0.18, n = 11, P < 0.01) not exposed to mannitol. With lower mannitol rates (10% of total blood flow), AV nodal conduction times increased by 5-10% and the AV node became supersensitive to adenosine, acetylcholine, and carbachol, but not to norepinephrine. We conclude that mannitol-induced changes in AV node and His bundle ECS markedly alter conduction system electrophysiology and the sensitivity of conductive tissues to purinergic and cholinergic agonists.

Measurement of functional cholinergic innervation in rat heart with a novel vesamicol receptor ligand.

Regional differences in cholinergic activity in the cardiac conduction system have been difficult to study. We tested the utility of (+)-m-[125I]iodobenzyl)trozamicol(+)-[125I]MIBT), a novel radioligand that binds to the vesamicol receptor located on the synaptic vesicle in presynaptic cholinergic neurons, as a functional marker of cholinergic activity in the conduction system. The (+)-[125I]MIBT was injected intravenously into four rats. Three hours later, the rats were killed and their hearts were frozen. Quantitative autoradiography was performed on 20-micron-thick sections that were subsequently stained for acetylcholinesterase to identify specific conduction-system elements. Marked similarities existed between (+)-[125I]MIBT uptake and acetylcholinesterase-positive regions. Optical densitometric analysis of regional (+)-[125I]MIBT uptake revealed significantly greater (+)-[125I]MIBT binding (nCi/mg) in the atrioventricular node (AVN) and His bundle regions compared with other conduction and contractile elements (AVN: 3.43 +/- 0.37; His bundle: 2.16 +/- 0.30; right bundle branch: 0.95 +/- 0.13; right atrium: 0.68 +/- 0.05; right ventricle: 0.57 +/- 0.03; and left ventricle: 0.57 +/- 0.03; p < 0.05 comparing conduction elements with ventricular muscle). This study demonstrates that (+)-[125I]MIBT binds avidly to cholinergic nerve tissue innervating specific conduction-system elements. Thus, (+)-[125I]MIBT may be a useful functional marker in studies on cholinergic innervation in the cardiac conduction system.

Effect of parenteral d-sotalol on transvenous atrial defibrillation threshold in a canine model of atrial fibrillation.

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 <90% rate of successful defibrillation. At a dose associated with class III antiarrhythmic effects (5 mg/kg), d-sotalol significantly reduced atrial defibrillation threshold from 1.72 +/- 1.12 J to 0.59 +/- 0.60 J (p < 0.01). These results support the feasibility of using antiarrhythmic drug therapy with d-sotalol to minimize energy requirements for intracardiac electrical cardioversion of atrial fibrillation.

Improving active compression-decompression cardiopulmonary resuscitation with an inspiratory impedance valve.

BACKGROUND: Active compression-decompression (ACD) cardiopulmonary resuscitation (CPR) has recently been demonstrated to provide significantly more blood flow to vital organs during cardiac arrest. To further enhance the effectiveness of this technique, we tested the hypothesis that intermittent impedance to inspiratory gas exchange during the decompression phase of ACD CPR enhances vital organ blood flow. METHODS AND RESULTS: ACD CPR was performed with a pneumatically driven automated compression-decompression device in a porcine model of ventricular fibrillation (VF). Nine pigs were randomized to receive ACD CPR alone, while 8 pigs received ACD CPR plus intermittent impedance to inspiratory gas exchange with a threshold valve set to 40 cm H2O. Results comparing 2 minutes of ACD CPR alone versus ACD CPR with the inspiratory impedance threshold valve (ITV) revealed significantly higher mean (+/- SEM) coronary perfusion pressures (diastolic aortic minus diastolic right atrial pressures) in the ITV (31.0 +/- 2.3 mm Hg) group versus with ACD CPR alone (21 +/- 3.6 mm Hg) (P < .05). Total left ventricular and cerebral blood flows, determined by radiolabeled microspheres, were 0.77 +/- 0.095 and 0.47 +/- 0.06 mL/min per gram, respectively, with ACD CPR plus the ITV versus 0.45 +/- 0.1 and 0.32 +/- 0.016 mL/min per gram, respectively, with ACD CPR alone (P < .05). Similar improvements in the ITV group were observed after 7 minutes of ACD CPR. After 16 minutes of VF and 13 minutes of ACD CPR, 6 of 8 pigs in the ITV group were successfully resuscitated with less than three successive 150-J shocks, whereas only 2 of 9 pigs with ACD CPR alone were resuscitated with equivalent energy levels (P < .02). With up to three additional and successive 200-J shocks, all pigs in the ITV group and 7 of 9 pigs with ACD CPR alone were resuscitated (P = .18). CONCLUSIONS: Intermittent impedance to inspiratory flow of respiratory gases during ACD CPR significantly improves coronary perfusion pressures and vital organ blood flow and lowers defibrillation energy requirements in a porcine model of VF.

Comparison of exertion required to perform standard and active compression-decompression cardiopulmonary resuscitation.

OBJECTIVE: Active compression-decompression (ACD) cardiopulmonary resuscitation (CPR) utilizes a hand-held suction device with a pressure gauge that enables the operator to compress as well as actively decompress the chest. This new CPR method improves hemodynamic and ventilatory parameters when compared with standard CPR. ACD-CPR is easy to perform but may be more labor intensive. The purpose of this study was to quantify and compare the work required to perform ACD and standard CPR. METHODS: Cardiopulmonary testing was performed on six basic cardiac life support- and ACD-trained St. Paul, MN fire-fighter personnel during performance of 10 min each of ACD and standard CPR on a mannequin equipped with a compression gauge. The order of CPR techniques was determined randomly with > 1 h between each study. Each CPR method was performed at 80 compressions/min (timed with a metronome), to a depth of 1.5-2 inches, and with a 50% duty cycle. RESULTS: Baseline cardiopulmonary measurements were similar at rest prior to performance of both CPR methods. During standard and ACD-CPR, respectively, rate-pressure product was 18.2 +/- 3.0 vs. 23.8 +/- 1.7 (x 1000, P < 0.01); mean oxygen consumption 15.98 +/- 2.29 vs. 20.07 +/- 2.10 ml/kg/min or 4.6 +/- 0.7 vs. 5.7 +/- 0.6 METS (P < 0.01); carbon dioxide production 1115.7 +/- 110 vs. 1459.1 +/- 176 ml/min; respiratory exchange ratio 0.88 +/- 0.04 vs. 0.92 +/- 0.04 (P = NS); and minute ventilation 35.5 +/- 5.1 vs. 45.6 +/- 9.2 l/min (P < 0.01). CONCLUSIONS: Approximately 25% more work is required to perform ACD-CPR compared with standard CPR. Both methods require subanaerobic energy expenditure and can therefore be sustained for a sufficient length of time by most individuals to optimize resuscitation efforts. Due to the slightly higher work requirement, ACD-CPR may be more difficult to perform compared with standard CPR for long periods of time, particularly by individuals unaccustomed to the workload requirement of CPR, in general.

Active compression-decompression CPR improves vital organ perfusion in a dog model of ventricular fibrillation.

OBJECTIVES: This study was designed to assess whether a new method of cardiopulmonary resuscitation (CPR), termed active compression-decompression CPR, or ACD-CPR, improves organ perfusion when compared with standard (S) CPR in a dog model of ventricular fibrillation. BACKGROUND: ACD-CPR has recently been shown to improve hemodynamic and respiratory parameters during cardiac arrest when compared with standard CPR. However, to our knowledge, the effects of ACD-CPR on tissue perfusion have not been investigated. METHODS: Ventricular fibrillation was induced in eight anesthetized, intubated animals. ACD-CPR and standard CPR were each performed twice in alternating order. All interventions were preceded by 1 min of ventricular fibrillation, in which no CPR was performed, and consisted of 6 min of CPR with either technique during which tissue perfusion was measured. Compressions were performed at 80/min with a 50 percent duty cycle and 175 to 200 N downward force applied to the chest wall for both techniques. Epinephrine was administered at the beginning of each 6-min CPR interval. Hemodynamic monitoring of aortic and right atrial pressure was performed continuously and myocardial, cerebral, and renal blood flows were measured using the radiolabeled microsphere technique at baseline and during all interventions. RESULTS: Baseline organ perfusion and hemodynamics were similar for all dogs. Baseline left ventricular, brain, and renal blood flows were 62.0 +/- 5.5, 14.1 +/- 2.1, and 476.3 +/- 55.5 ml/min/100 g, respectively (mean +/- SEM). Compared with standard CPR, ACD-CPR resulted in higher global left ventricular (22.5 +/- 6.2 vs 14.1 +/- 4.0 ml/min/100 g, p < 0.01), cerebral (12.0 +/- 2.4 vs 8.5 +/- 2.3 ml/min/100 g, p < 0.01), and renal cortical (27.8 +/- 5.0 vs 17.5 +/- 5.0 ml/min/100 g, p < 0.05) blood flows. Regional flows to the epicardium, endocardium, and midmyocardium as well as to the frontal, parietal, and occipital lobes of the brain were all significantly improved by ACD-CPR. Aortic systolic (61.7 +/- 4.1 vs 49.5 +/- 3.1 mm Hg, p < 0.01), aortic mean (31.6 +/- 2.8 vs 27.2 +/- 2.2 mm Hg, p = 0.001), and myocardial perfusion pressure (12.9 +/- 3.4 vs 10.4 +/- 3.4 mm Hg, ACD-CPR vs standard CPR, p < 0.01) were all higher during ACD-CPR than during standard CPR. CONCLUSIONS: We conclude that ACD-CPR improves tissue perfusion and systemic hemodynamics compared with standard CPR.

Evaluation of standard and active compression-decompression CPR in an acute human model of ventricular fibrillation.

BACKGROUND: The mechanisms that underlie cardiopulmonary resuscitation (CPR) in humans remain controversial and difficult to study. This report describes a new human model to evaluate CPR during the first 1 to 2 minutes after the onset of ventricular fibrillation (VF). With this model, standard CPR was compared with active compression-decompression (ACD) CPR, a method that uses a handheld suction device to actively compress and actively decompress the chest. METHODS AND RESULTS: During routine inductions of VF as part of a transvenous lead cardioverter/defibrillator implantation procedure, CPR was performed in 21 patients if the first defibrillation shock failed and until a successful rescue shock was delivered. Compressions during CPR were performed according to American Heart Association guidelines. For ACD CPR, decompression was performed with up to -30 lbs. Radial arterial and right atrial pressures were measured in all patients. Esophageal pressures, intratracheal pressures, or minute ventilation was measured in the last 13 patients. Application of both CPR techniques increased arterial and right atrial pressures. The mean coronary perfusion pressure was increased throughout the entire CPR cycle with ACD CPR (compression, 21.5 +/- 9.0 mm Hg; decompression, 21.9 +/- 8.7 mm Hg) compared with standard CPR (compression, 17.9 +/- 8.2 mm Hg; decompression, 18.5 +/- 6.9 mm Hg; P < .02 and P < .02, respectively). Ventilation per compression-decompression cycle was 97.3 +/- 65.6 mL with standard CPR and 168.4 +/- 68.6 mL with ACD CPR (n = 7, P < .001). Negative inspiratory pressure was -0.8 +/- 4.8 mm Hg with standard CPR and -11.4 +/- 6.3 mm Hg with ACD CPR (n = 6, P < .04). CONCLUSIONS: Patients undergoing multiple inductions of VF during cardioverter/defibrillator implantation with transvenous leads provide a well-controlled and reproducible model to study the mechanisms of CPR. Using this model, ACD CPR significantly increased arterial blood pressure, coronary perfusion pressure, minute ventilation, and negative inspiratory pressure compared with standard CPR.

Alteration of the pulsatile load in the high-altitude calf model of pulmonary hypertension.

We compared main pulmonary arterial elasticity and global pulmonary arterial compliance in control and high-altitude (HA) calves to determine whether 1) changes in pulmonary arterial elasticity are contributing to an increase in the oscillatory load of the right ventricle in this model of pulmonary hypertension and 2) measured changes in stiffness of the HA calves' arterial wall are the result of both an increase in pressure and an alteration of the material properties of the HA calves' arterial wall. Newborn calves were placed at 4,300 m simulated altitude for 14 days, and control calves were kept at 1,500 m. The HA calves were then reacclimatized to 1,500 m for 24 h so that baseline pressures of the two groups were similar. Open-chest main pulmonary arterial and right ventricular micromanometric pressures, ultrasonic main pulmonary arterial diameter, and green dye flow were measured under baseline conditions and then under moderate and severely hypoxic conditions to make measurements at both baseline and increased pulmonary pressures. At elevated pressures, the pressure-diameter relationship was noted to be nonlinear, and a characteristic late systolic peaking of the right ventricular pressure waveform was seen. The Peterson pressure-strain modulus, pulse wave velocity, characteristic impedance, and global compliance (3 element windkessel) were calculated. The calculated variables were all shown to be pressure dependent, and no intrinsic differences in stiffness were seen between the control and HA animals when mean pressure was taken into account. Pulmonary arterial histology demonstrated, however, a characteristic increase in wall thickness in the HA animals. Thus, in this model of pulmonary hypertension, major changes in elasticity and pulsatile load are primarily due to an increase in pulmonary pressure. The structural changes present in the HA calves' arterial wall did not separately produce any measurable changes in arterial distensibility or the oscillatory load.

Monocular diplopia accompanying ordinary refractive errors.

Monocular diplopia is commonly encountered in ophthalmic practice. We discovered that it could be induced in nine (82%) of 11 normal eyes with ordinary spherical or astigmatic defocus of the retinal image. Possible mechanisms responsible for this effect include retinal processing, diffraction effects, and spherical aberration. By employing geometric blur circle theory and using a simple optical model to photograph the effect, we concluded that monocular diplopia in the setting of ordinary refractive error is secondary to relatively minor optical irregularity such as spherical aberration. Contour enhancement properties of the retina probably accentuate this effect. Ordinary refractive error should therefore not be overlooked or discounted in patients with monocular diplopia.