Stimulation of the right cervical vagosympathetic trunk in the chloralose-anesthetized, decentralized dog was followed by a two-component postvagal inotropic response: an initial return of contractility toward the control level, but significantly less than control and a secondary, more delayed, significant positive inotropic effect compared to control contractility. Maintenance of arterial pressure by ventricular pacing during vagal stimulation eliminated the late positive inotropic effect but not the early response. Occlusion of the inferior vena cava for 15-20 sec immediately following vagal stimulation delayed the late positive inotropic effect for a period equal to the duration of the occlusion. Blockade of muscarinic cholinergic receptors (atropine) eliminated the late response as did blockade of beta adrenergic receptors (propranolol). Block of catecholamine release from sympathetic endings (guanethidine) had no effect on the late response. It is concluded that adrenal medullary catecholamines, released presumably as a consequence of vagally-induced hypotension, are responsible for the late positive inotropic effect produced following vagal stimulation.
Pericardial Procainamide Delivery. Introduction: Procainamide delivery into the pericardial space may produce a greater and more prolonged electrophysiologic effect, particularly in thin superficial atrial tissue, compared with intravenous delivery. Methods and Results: Swine were randomized to sequential procainamide doses delivered intravenously ( n = 6 ) or into the pericardial space ( n = 7 ). The cumulative pericardial doses were 0.5, 1.5, and 3.5 mg/kg, and the intravenous doses were 2, 10, and 26 mg/kg. Pericardial procainamide prolonged right atrial effective refractory period from baseline by 22% ( P < 0.01 ) but only at the 3.5 mg/kg cumulative dose. This dose slowed interatrial conduction time by 14% ( P < 0.05 ) and raised atrial fibrillation threshold by 70 mA ( P < 0.05 ). Pericardial procainamide had minimal effect on ventricular electrophysiology. Similar results occurred with a single 2 mg/kg pericardial dose in a closed chest model. Intravenous 10 and 26 mg/kg cumulative doses prolonged atrial effective refractory period from baseline by 24% and 18% ( P < 0.01 ), respectively. The 26 mg/kg cumulative intravenous dose slowed interatrial and atrial‐ventricular conduction times by 27% and 17%, respectively ( P < 0.05 ), raised atrial fibrillation threshold, and slowed ventricular conduction time by 29% ( P < 0.05 ). Pericardial procainamide produced pericardial fluid concentrations ranging from 250 to 1,500 μ g/mL, but plasma concentrations were < 1 μ g/mL. Intravenous procainamide doses produced pericardial fluid concentrations similar to plasma trough concentrations 0 to 12 μ g/mL. Conclusion: The single 2 mg/kg and 3.5 mg/kg cumulative pericardial procainamide doses prolonged atrial refractoriness and raised atrial fibrillation threshold similar to the 26 mg/kg cumulative intravenous dose, but the duration of effect was similar between delivery methods. Pericardial procainamide did not affect global or endocardial ventricular electrophysiology nor was it associated with ventricular proarrhythmia.
The effects of vagal and sympathetic stimulation on canine ventricular refractoriness were studied in vivo. Sympathetic stimulation reduced the left ventricular refractory period to an extent linearly related to the logarithm of nerve stimulation frequency. Vagal stimulation had no effect in the absence of sympathetic stimulation but produced a frequency-dependent attenuation of sympathetic effects when the two systems were stimulated simultaneously. The effects of combined vagal and sympathetic stimulation were best described by a multilinear regression model using the logarithm of vagal and sympathetic frequency as covariates. The magnitude of vagal attenuation of sympathetic effects did not show any regional variation at the five widely spaced sites (2 right ventricular, 3 left ventricular) studied.
Abstract Both pentane and isoprene are excreted in human breath. Although pentane is considered an index of lipid peroxidation, the significance of isoprene is unknown. Having a similar boiling point, these two hydrocarbons are difficult to separate by gas chromatography. We separated pentane from isoprene on both a Poraplot Q and a Poraplot U column, injecting single-breath samples directly into a gas chromatograph. The breath samples were pressurized to 800 mmHg to increase the amount of sample volume delivered to the column. In a group of 43 healthy volunteers, the concentrations of end-expiratory pentane and isoprene were 0.57 +/- 0.3 and 7.05 +/- 3.53 nmol/L, respectively. There was a significant linear correlation (r = 0.57, P < 0.0001) between age and pentane concentration in expired air; isoprene showed no correlation with age or pentane concentrations. The age-related increase in pentane production suggests that oxidative stress may play a role in the aging process in humans. The method described should allow for rapid, inexpensive, serial measurement of expired pentane and isoprene.
Abstract The concentrations of acetone, isoprene, and pentane in alveolar breath were examined in 50 smokers and 50 nonsmokers by gas chromatography. The baseline pentane in smokers was 0.17 +/- 0.03 nmol/L (mean +/- SE), which was not different from pentane in nonsmokers (0.23 +/- 0.03 nmol/L). There were also no differences between smokers and nonsmokers in the concentrations of acetone and isoprene. Serial breath samples were obtained from 15 smokers before smoking and at 5, 15, and 60 min after smoking. Although acetone was not altered by smoking, isoprene increased by 86% +/- 26% 5 min after smoking (P <0.001) and returned to baseline 10 min later. Pentane increased by 456% +/- 156% 5 min after smoking (P <0.001) and remained increased 10 min later (204% +/- 73% of baseline, P <0.05). Isoprene concentrations in mainstream cigarette smoke were >5000 times greater than breath concentrations, whereas pentane could not be detected in mainstream smoke. Because pentane is produced from the peroxidation of n-6 polyunsaturated fatty acids, the results provide evidence that cigarette smoking causes an immediate increase in lipid peroxidation.
To determine if the sympathetic nervous system exerts an arrhythmogenic effect on the ischemic myocardium independent of heart rate, the proximal circumflex coronary artery was occluded for 1 h in 62 open-chest, anesthetized dogs. The atrial rate was maintained at 200/min, and the vagosympathetic trunks were transected in all dogs. The total incidence of ventricular fibrillation was 35% in 20 dogs with intact stellates and not significantly different from the incidence of ventricular fibrillation (15%) in another 20 dogs in which both stellate ganglia had been decentralized. Electrical stimulation of the left ansae subclavia (3 Hz, 2 ms, 6-8 V) in the remaining 22 dogs significantly increased the incidence of ventricular fibrillation to 73% (P less than 0.05). The magnitude of S-T segment elevation in the lead II electrocardiogram 90 s after occlusion was 0.69 +/- 0.08 mV in the group with left ansae stimulation and significantly elevated (P less than 0.01) compared with dogs with intact stellates (0.35 +/- 0.06 mV) and with the denervated dogs (0.19 +/- 0.05 mV). The data indicate that the sympathetic nervous system is capable of a direct arrhythmogenic influence on the ischemic myocardium independent of heart rate. The rate-independent arrhythmogenic effects of the sympathetic nervous system may be mediated by an increase in severity of the ischemic insult.
The effect of esmolol on the ventricular fibrillation threshold (VFT) was determined in 11 open-chest dogs anesthetized with sodium pentobarbital. Since changes in VFT by antiarrhythmic drugs have been shown to depend on the method used to test vulnerability to fibrillation, two methods were studied. The vulnerable period was scanned with a train of pulses (100 Hz, 4 ms, 20 pulses) in nine experiments and a single pulse (10 ms) in eight experiments. Following control measurements, esmolol was administered as an intravenous bolus of 500 μg/kg followed by a continuous infusion of 300 μg/kg/min. After 15 min of infusion, the adequacy of beta-blockade was tested by the administration of 0.5 μg/kg of isoproterenol. Isoproterenol increased the heart rate by only 18 ± 2 beats/min following esmolol administration which was significantly less than the control response (79 ± 7 beats/min, p < 0.01). Although the VFT measured with the single-pulse technique did not change in response to esmolol (14.1 ± 1.1 mA vs. 14.3 ± 1.2 mA), the VFT measured with the train-of-pulses technique significantly increased (3.7 ± 0.5 mA to 14.5 ± 2.8 mA, p < 0.01). Twenty minutes after discontinuing esmolol, the VFT measurements were repeated and did not differ from control values with either technique. The increase in heart rate in response to isoproterenol also returned to control values (80 ± 6 beats/min). The results suggest that the ability of esmolol to raise VFT as measured by the train-of-pulses technique is due to beta-adrenergic blockade. The two methods may differ because of the relatively greater release of norepinephrine with the train-of-pulses technique.
Abstract Renografin‐76 (RG76) regularly depresses myocardial contractility during coronary angiography. Angiovist‐370 (AV370) is a contrast medium similar to RG76 except the calcium sequestering agents sodium citrate and EDTA in RG76 have been replaced by calcium EDTA (an additive that does not bind additional calcium). To determine if the calcium sequestering agents contribute to the mechanical depression produced by ionic contrast media, this study compared the inotropic response of RG76 to that of AV370. Additionally, saline solutions containing sodium citrate + EDTA and calcium EDTA at concentrations found in the respective contrast media were also compared. In 10 open chest dogs the percent change and duration of the inotropic response following intracoronary injections of RG76 and AV370, as well as solutions of sodium citrate + EDTA and calcium EDTA were compared using Walton‐Brodie strain gauges. Injections, 2 cc, of RG76 and AV370 produced a biphasic response characterized by an initial negative inotropic response followed by a more prolonged positive inotropic response. The magnitude (67 ± 3% vs 59 ± 2%; p < 0.001) and duration (34 ± 3 vs 24 ± 2 sec; p < 0.001) of the initial negative inotropic response was greater with RG76 than with AV370. The magnitude of the secondary positive inotropic response with RG76 was not different from that obtained with AV370 (31 ± 12% vs 28 ± 10%; p > 0.3). This positive response was not affected by b̃‐adrenergic blockage with 0.2 mg/kg of timolol. Similarly, 4 cc of sodium citrate + EDTA produced a significantly greater magnitude (56 ± 5%) and longer (42 ± 7 sec) negative inotropic response than calcium EDTA (17 ± 2% and 15 ± 3 sec) or 0.9% saline (18 ± 8% and 13 ± 2 sec; p < 0.001). The results suggest that the calcium sequestering agents sodium citrate + EDTA produce significant negative inotropic effects contributing to the mechanical depression produced by RG76. However, the calcium binding additives are not solely responsible for the depression in contractility produced by ionic contrast media. Contrast media lacking calcium binding additives may be preferable for coronary angiography.
