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.

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.

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.