Biomedical subjects

D E Euler

Publications and source records attributed to D E Euler.

At least 55 records · Page 3Linked to original sources

PubMed1988

Comparison of the effects of acute and chronic beta-blockade on infarct size in the dog after circumflex occlusion.

In order to compare the effects of acute and chronic beta-blockade on infact size, the left circumflex coronary artery was occluded for 6 hours in 33 anesthetized dogs. The dogs (18 to 22 kg) were divided into three groups; group 1 (N = 10) served as controls, group 2 received intravenous nadolol (average dose 1.25 mg/kg) just prior to coronary occlusion, and group 3 received oral nadolol (80 mg) twice daily for 16 days prior to coronary occlusion. To ensure equivalent degrees of beta-blockade at the time of occlusion, group 2 and 3 dogs were given incremental doses of intravenous nadolol to abolish the chronotropic response to isoproterenol (2 mu/kg IV). Left ventricular pressure, its first derivative (dP/dt), and heart rate were monitored. The anatomic risk region was determined antemortem by Evan's blue staining while the infarct zone was delineated postmortem by tetrazolium staining. Compared to Group 1, heart rate was 22% lower in group 2 and 15% lower in group 3 dogs 6 hours after occlusion (p less than 0.05). There were no differences among groups in peak left ventricular systolic pressure or mean arterial pressure. Infarct size as a function of the area at risk was 68 +/- 3% in group 1, 52 +/- 7% in group 2, and 44 +/- 8% in group 3. A significant difference was found only between groups 3 and 1. The data suggest that chronic beta-blockade provides greater protection against ischemic-induced necrosis than does acute beta-blockade. The greater protective effect of chronic beta-blockade may be due to chronic adaptive changes in either blood flow or metabolism.

Adrenergic beta-Antagonists↗

PubMed1988

Effect of propranolol on ventricular repolarization and refractoriness: role of beta-blockade versus direct membrane effects.

The purpose of this study was to define the role of beta-adrenergic blockade and direct membrane effects in the ability of dl-propranolol to alter ventricular repolarization and refractoriness in the intact heart. The effective refractory period (ERP) and the local Q-T interval were measured at an epicardial site in the left ventricle in 14 open-chest dogs anesthetized with alpha-chloralose. Beta-adrenergic influences were eliminated in seven dogs (group 1) by stellate transection and nadolol (0.5 mg/kg IV), and enhanced in seven dogs (group 2) by stellate transection and stimulation of the left ansae subclavia. Each dog received an initial beta-blocking dose of propranolol (0.5 mg/kg) followed by a second, cumulative dose of 5.0 mg/kg. In group 1 dogs, there was no significant change in either the ERP or local Q-T interval in response to the first dose of propranolol. In group 2 dogs, left stellate stimulation significantly shortened the ERP (20 +/- 2 msec) and the local Q-T interval (17 +/- 4 msec). The first dose of propranolol prolonged these parameters to values not different from prestimulation control values. There was no change in the H-V interval, QRS complex duration, or diastolic threshold (DT) in either group after the initial propranolol dose. The second dose of propranolol significantly shortened the ERP (5 +/- 1 msec) and the local Q-T interval (11 +/- 2 msec) in both groups. This dose also significantly increased the DT, H-V interval, and QRS complex duration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

PubMed1988

Comparative effects of antiarrhythmic drugs on the ventricular fibrillation threshold.

The purpose of this study was to compare the effects of several different antiarrhythmic drugs on the ventricular fibrillation threshold (VFT). Experiments were performed on open-chest dogs anesthetized with pentobarbital. The VFT was measured on the right ventricle by scanning the vulnerable period with a single 10-ms electrical stimulus. The following antiarrhythmic drugs were each given intravenously to eight different dogs: procainamide (25 mg/kg), lidocaine (2 mg/kg + 70 micrograms/kg/min), flecainide (3 mg/kg), timolol (0.1 mg/kg), clofilium (1 mg/kg), dl-sotalol (5 mg/kg), and bethanidine (4 mg/kg). The drugs resulted in the following increases in the VFT: procainamide, 33 +/- 13%; lidocaine, 21 +/- 5%; flecainide, 38 +/- 10%; timolol, 19 +/- 6%; clofilium, 14 +/- 6%; sotalol, 33 +/- 10%; and bethanidine, 69 +/- 15%. The changes in VFT were all significant (p less than 0.01) except for clofilium. Only procainamide and sotalol caused stimulus-induced runs of nonsustained polymorphic ventricular tachycardia that spontaneously reverted to sinus rhythm after 4 s or more. In individual experiments, the occurrence of nonsustained polymorphic tachycardia that resembled ventricular fibrillation could not be correlated with a change in the VFT. In addition, there appeared to be no relationship between a drug-induced increase of the VFT and alterations in the QRS duration, the QT interval, or the ventricular effective refractory period. Bethanidine had the greatest effect on the VFT, in spite of the fact that this drug shortened the ventricular effective refractory period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Effect of esmolol on the ventricular fibrillation threshold.

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 micrograms/kg followed by a continuous infusion of 300 micrograms/kg/min. After 15 min of infusion, the adequacy of beta-blockade was tested by the administration of 0.5 micrograms/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 less than 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 less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

PubMed1988

Effects of chronic beta-blockade on beta-receptors and adenylate cyclase activity in the canine heart.

To test the hypothesis that beta-receptors 'up-regulate' during chronic beta-blockade, myocardial beta-receptor density, affinity and functional sensitivity were examined in dogs before and after chronic beta-blockade. Membrane preparations from the left ventricle and right atrium were assayed for beta-receptors in 8 control dogs, and 8 dogs given oral nadolol (4 mg/kg) twice a day for 3 weeks. Beta-receptor density and affinity of membrane fractions were determined using 3H-dihydroalprenolol (0.5-20 nM), and Scatchard analysis. Beta-receptor densities after chronic beta-blockade were 419 +/- 28 (mean +/- SEM) and 436 +/- 47 fmol/mg protein in membranes from the left ventricle and right atrium respectively. These values were not significantly different from the left ventricle (412 +/- 25) or the right atrium (413 +/- 25) in control dogs. Beta-receptor affinities were 5.6 +/- 0.5 nM (left ventricle) and 8.5 +/- 1.1 nM (right atrium) after chronic beta-blockade, and not significantly different from control (6.9 +/- 0.7 nM, ventricle; 11.3 +/- 0.9 nM, atrium). Beta-receptor sensitivity was determined in membrane fractions from the left ventricle by analysis of the dose-response relationship between isoproterenol and the formation of c-AMP (pmol/min/mg protein). The concentration of isoproterenol that resulted in 50% of the maximal response was not significantly altered by chronic beta-blockade. Maximally stimulated adenylate cyclase with Gpp(NH)p or NaF was also unchanged by beta-blockade. These results suggest that in the canine heart, chronic beta-blockade does not lead to 'up-regulation' of beta-receptors nor catecholamine supersensitivity.

Adenylyl Cyclases↗

PubMed1987

Mechanisms responsible for countershock-induced ventricular tachycardia in the intact canine heart.

To determine the mechanism for postcountershock ventricular ectopy, internal and external shocks were delivered to 20 anesthetized dogs. Shock energies of 25 and 50 joules were employed internally while 100 and 200 joules were delivered externally. Experiments were performed in both the presence and absence of a nearly toxic dose of ouabain. All shocks resulted in the occurrence of nonsustained (less than 15 seconds) ventricular tachycardia. When bursts of rapid ventricular pacing were synchronized with a shock, the pacing stimuli invariably captured the ventricles and overdrove the shock-induced ventricular tachycardia. However, the burst pacing never appeared to break a tachycardia, since the termination of pacing was followed immediately by the resumption of the shock-induced ventricular tachycardia. The presence of ouabain did not alter the response of the ventricles to postshock burst pacing. Administration of verapamil (0.5 mg/kg) had no effect on the duration of shock-induced ventricular arrhythmia. Elevation of the serum potassium level to 8.5 +/- 0.6 mEq/L drastically reduced the duration of postshock ventricular tachycardia in both the presence and absence of ouabain. The results suggest that postshock ventricular ectopy results from an abnormality of impulse initiation rather than reentry.

Animals↗

PubMed1987

The effects of elevated intracranial pressure on the canine electrocardiogram.

Striking electrocardiographic abnormalities have been noted in some patients with central nervous system injury. To study the relationship between the electrocardiogram and intracranial pressure, intracranial pressure was elevated in 14 open chest pentobarbital-anesthetized dogs. The right vagus was stimulated to produce sinus slowing and the right atrium was paced at a constant cycle length fast enough to prevent arrhythmias and maintain heart rate constant (750 msec in 11 dogs and 600 msec in three dogs). In nine dogs, intracranial pressure was sequentially elevated to 100, 150, and 200 mmHg. Systolic arterial blood pressure consistently rose to exceed intracranial pressure (P less than 0.005). At a pressure of 150 and 200 mmHg, mean QT intervals shortened significantly in recorded leads II, X, Y, and Z from 0.01). T wave changes were also noted that consisted of increasing positivity in leads II, X, and Y and increasing negativity in lead Z. To delinate the role of the sympathetic nervous system, an additional five dogs were subjected to an intracranial pressure of 200 mmHg before and after bilateral stellate ganglionectomy and timolol (0.1 mg/kg IV). Elimination of sympathetic influences did not significantly alter the electrocardiographic effects of elevated intracranial pressure. Thus, intracranial hypertension results in significant QT shortening and T wave changes that are not entirely mediated by the sympathetic nervous system.

Animals↗

PubMed1987

Acetylcholine release by a stimulus train lowers atrial fibrillation threshold.

This study was designed to evaluate the importance of local release of autonomic neuromediators when electrical stimuli are applied to the right atrium to measure the atrial fibrillation threshold (AFT). Experiments were performed in 16 open-chest dogs anesthetized with alpha-chloralose. The dogs were denervated by bilateral transection of the stellates and cervical vagi. The AFT was determined in 11 dogs by delivering either a train of stimuli (14 pulses, 4 ms, 100 Hz) or a single stimulus (10 ms) to the right atrium during its vulnerable period. In eight dogs, beta-adrenergic blockade with timolol (0.1 mg/kg) had no effect on the AFT determined with either method. Atropine (0.2 mg/kg), given after timolol, significantly increased the train-of-pulses AFT from 4.7 +/- 0.4 to 32.3 +/- 4.6 mA (P less than 0.001). The single-pulse AFT increased from 16.5 +/- 1.5 to 17.8 +/- 1.5 mA (P less than 0.05). Atropine had a similar effect on the AFT when it was given in the absence of timolol (n = 3). In five additional dogs, a monophasic action potential was recorded while a 10-mA train was delivered to the atrium during its absolute refractory period. There was marked shortening of the monophasic action potential duration (55 +/- 6 ms) in the first beat after the train. The shortening was totally abolished by atropine (0.2 mg/kg). The results suggest that a train of stimuli liberates local stores of acetylcholine, which cause a shortening of atrial repolarization time and a profound decrease in the current necessary to evoke fibrillation.

Acetylcholine↗

PubMed1986

Deleterious effects of bretylium on hemodynamic recovery from ventricular fibrillation.

To study the effects of bretylium on the restoration of circulatory function after resuscitation from ventricular fibrillation, closed-chest anesthetized dogs were electrically fibrillated for 1 minute followed by defibrillation (direct-current shock). After one control episode of fibrillation and defibrillation, 16 dogs received a bolus of bretylium (10 mg/kg intravenously). A second episode of fibrillation and defibrillation was induced in eight dogs 3 minutes after bretylium and in eight dogs 4 hours after bretylium. Prior to bretylium, mean arterial blood pressure spontaneously recovered to exceed 200 mm Hg by 2 minutes after defibrillation in all 16 dogs. However, after bretylium, 13 of 16 dogs were in electromechanical dissociation 2 minutes after defibrillation (p less than 0.001). Despite external chest compression, epinephrine, and sodium bicarbonate, a stable blood pressure could not be restored in 6 of 16 dogs. Clofilium, a bretylium analogue lacking sympathetic influences, did not alter the pattern of hemodynamic recovery following defibrillation in five of five dogs. The results suggest that the effects of bretylium on the sympathetic nervous system may profoundly influence the outcome of cardiac resuscitation from fibrillation.

Animals↗

PubMed1985

Mechanism of the effect of bretylium on the ventricular fibrillation threshold in dogs.

Experiments were performed to determine the importance of sympathetic blockade vs a direct myocardial effect as a mechanism for the antifibrillatory action of bretylium. The ventricular fibrillation (VF) threshold was determined in open-chest, anesthetized dogs by scanning the vulnerable period with either a single electrical stimulus (10 ms) or a train of electrical stimuli (14 pulses, 4 ms, 100 Hz). Using the train-of-pulses technique, the VF threshold increased from 6.8 +/- 0.6 mA to 29.7 +/- 6.4 mA 15 minutes after a 10-mg/kg intravenous bolus of bretylium (p less than 0.001, n = 8). There was no further significant change in the train-of-pulses VF threshold at 2 or 4 hours. Beta-adrenergic blockade with timolol (0.2 mg/kg) increased the train-of-pulses VF threshold from 6.7 +/- 1.6 mA to 24.5 +/- 5.2 mA (p less than 0.01 n = 8) and prevented any further significant change in response to bretylium. When single electrical pulses were used to scan the vulnerable period, bretylium at doses of 10 mg/kg (n = 8) and 100 mg/kg (n = 6) did not alter the VF threshold over a 4-hour observation period. The administration of timolol, alone or in combination with bretylium, did not significantly alter the single-pulse VF threshold. The failure of bretylium to alter the single-pulse VF threshold was not dependent on the site of stimulation. Stimulation of the right sympathetic cardiac nerves showed that 15 minutes of bretylium treatment was sufficient to completely inhibit adrenergic neuronal transmission to the myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Digoxin and the susceptibility of the canine heart to countershock-induced arrhythmia.

This study investigated the effects of therapeutic and subtoxic doses of digoxin on the risk of ventricular tachycardia (VT) after graded, transthoracic shocks in anesthetized dogs. A series of direct current shocks (5, 10, 25, 50, 75, 100, 150 and 200 J) was delivered to 33 normal dogs and 6 dogs with a healed (32 +/- 7 days) myocardial infarct (MI). In 10 untreated dogs, the duration of post-shock VT was highly reproducible when 3 separate series of shocks were delivered at 2-hour intervals. In 6 normal dogs treated with oral digoxin (0.5 mg/day for 5 to 7 days), a series of shocks delivered before and during treatment (serum levels 1.5 +/- 0.5 ng/ml) resulted in the same duration of post-shock VT. In 18 normal and 6 dogs with MI, a series of shocks was given before and 90 minutes after a therapeutic dose of digoxin (0.05 mg/kg intravenously). At this dose of digitalis (serum level 2.5 +/- 1.0 ng/ml), there was no difference in the duration of post-shock VT in either normal dogs or dogs with MI. A third series of shocks was given after achieving subtoxic digitalization with additional intravenous digoxin (0.01 mg/kg) every 30 minutes until a premature ventricular stimulus evoked a repetitive ventricular response. The subtoxic doses of digitalis (serum levels 13.9 +/- 4.7 ng/ml) increased the duration of post-shock VT in both normal dogs (100%) and dogs with MI (700%) (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Ventricular fibrillation during coronary angiography: an analysis of mechanisms.

To investigate the mechanisms of ventricular fibrillation (VF) during coronary angiography, we assessed ventricular automaticity, local QT intervals, local conduction characteristics, and the ability to induce arrhythmias with premature ventricular stimulation in 30 dogs after intracoronary injections of 4 to 6 cc of Renografin 76 (RG 76). Ventricular automaticity was measured in six dogs as the idioventricular escape rate following intense vagal stimulation and was unchanged (51 +/- 6 vs 52 +/- 6 bpm, p greater than 0.05) with 6 cc of RG 76. In addition, 8 of 10 injections of 6 cc of RG 76 produced VF at a heart rate of 200 bpm compared to only 2 of 10 injections at a heart rate of 80 bpm (p less than 0.05). Composite and bipolar plunge electrodes were placed in the region perfused by the left anterior descending coronary artery (LAD) and circumflex coronary artery to assess QT intervals and conduction characteristics. RG 76, 4cc, produced a 116 +/- 18 msec increase in the QT intervals recorded from the region perfused by the LAD, resulting in a marked dispersion in repolarization. Both local bipolar and composite electrograms showed minimal conduction delay, which rarely extended beyond the QRS of a lead II ECG during atrial paced rhythm. As premature beats (spontaneous or induced) conducted through the region of QT prolongation, marked conduction delay was recorded from bipolar electrograms, while composite electrograms recorded continuous fractionated electrical activity spanning the diastolic interval at the onset of VF.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗

PubMed1985

In vivo effects of acute changes in osmolality and sodium concentration on myocardial contractility.

Effects of acute changes in osmolality and sodium concentration (Na) on myocardial contractility (MC) were examined in anesthetized dogs. Using a carotid to left anterior descending bypass, 4 cc of NaCl and/or dextrose of varying osmolality as injected and the percentage of change in MC measured. At Na = O mEq/L, a positive inotropic response occurred, which varied inversely as osmolality increased from 300 (MC = 100 +/- 23%) to 700 mOsm/L (MC = 39 +/- 10%, p less than 0.01). Similar ranges of positive responses of lesser magnitude were noted at Na = 75 mEq/L. At Na = 150, 190, or 350 mEq/L, similar increments in osmolality caused an increasingly negative inotropic response. An inverse relationship between Na and MC was noted with osmolality held constant. Injections of the nonionic contrast agent, P297, in 5% dextrose or 0.9% NaCl, resulted in 28 +/- 3% or -17 +/- 4% (p less than 0.01) change in MC, respectively. Sodium concentration and osmolality have independent effects on MC. Hyperosmolality/hypernatremia causes a negative inotropic response while hyponatremia causes a positive one.

Animals↗

PubMed1985

The use of programmed electrical stimulation to assess the fibrillatory propensity of ionic and nonionic contrast media.

Coronary angiography occasionally results in ventricular fibrillation. To compare the fibrillatory propensity of conventional ionic and nonionic contrast media, we measured QT intervals and performed programmed electrical stimulation during intracoronary injection of Renografin 76 (R76), Hypaque 76 (H76), and iopamidol (IOP) in 16 open chest dogs. In ten dogs the incidence of ventricular fibrillation following induction of a single premature ventricular beat after every fourth atrial paced beat was 19/20 with R76, 8/20 with H76, and 0/20 with IOP (P less than .001). When two premature beats were induced, the incidence of ventricular fibrillation was 20/20 with R76, 19/20 with H76, and 1/20 with IOP (P less than .001). In six additional dogs, the mean prolongation of the QT interval was 170 +/- 20 msec with R76, 105 +/- 14 msec with H76, and 63 +/- 9 msec with IOP (P less than .001). Thus, programmed electrical stimulation readily induces ventricular fibrillation during intracoronary injection of conventional ionic contrast media. The incidence of ventricular fibrillation parallels the amount of QT interval prolongation produced. H76, which lacks EDTA and sodium citrate, is less fibrillatory than R76. However, the nonionic medium IOP appears far less fibrillatory than either R76 or H76.

Angiography↗

PubMed1985

Effect of sympathetic tone on ventricular arrhythmias during circumflex coronary occlusion.

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.

Animals↗

PubMed1984

Ventricular fibrillation during coronary angiography in dogs: the role of calcium-binding additives.

Coronary angiography with Renografin 76 (RG76) occasionally results in ventricular fibrillation (VF). 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. To determine whether these sequestering agents contribute to contrast medium-induced VF, a comparison was made of the effects of intracoronary injections of RG76, AV370, and saline solutions containing sodium citrate and EDTA (CIT/EDTA) and calcium EDTA (CA EDTA) on myocardial conduction, local QT intervals, and incidence of spontaneous and induced VF in 32 dogs. Four milliliters of RG76 produced a 111 +/- 12-ms increase in local QT intervals, compared with a 73 +/- 8-ms increase with AV370 (p less than 0.001). Spontaneous VF occurred in 12 of 16 six-milliliter injections of RG76, compared with 4 of 16 injections of AV370 (p less than 0.02) An early-cycle premature impulse applied after every fourth beat induced VF in 15 of 16 four-milliliter injections of RG76 compared with 5 of 16 injections of AV370 (p less than 0.01). As the premature beat conducted through the left anterior descending region, conduction slowing and fractionation occurred, which was less with AV370 than with RG76. The CIT/EDTA solution produced a greater increase in QT intervals (77 +/- 5 ms) than the CA EDTA solution (29 +/- 3 ms) or 0.9% saline solution alone (28 +/- 2 ms) (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1984

Inotropic effects of ionic contrast media: the role of calcium binding additives.

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 less than 0.001) and duration (34 +/- 3 vs 24 +/- 2 sec; p less than 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 greater than 0.3). This positive response was not affected by beta-adrenergic blockage with 0.2 mg/kg of timolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1983

Effect of coronary occlusion on arrhythmias and conduction in the ovine heart.

The proximal left circumflex coronary artery was occluded for 1 h in 16 open-chest sheep anesthetized with pentobarbital sodium. Epicardial conduction was monitored at three or four sites within the ischemic zone and one site in the normal zone. Eight of the sheep developed ventricular fibrillation within the first 15 min of occlusion; the remaining sheep survived the 1-h observation period. In the sheep that developed spontaneous ventricular fibrillation, the circumflex perfused a significantly greater amount of the left ventricle (44 +/- 3 vs. 39 +/- 3%; P = 0.008). The occurrence of spontaneous ventricular fibrillation was invariably preceded by a period of sustained (0.5-4 min) ventricular tachycardia. Six of the surviving sheep developed episodes of sustained (2-10 min) tachycardia that were self-terminating. The ischemic zone electrograms showed continuous fractionated electrical activity during both self-terminating tachycardias and tachycardias ending in fibrillation. The continuous epicardial electrical activity did not appear to cause the tachycardias but rather occurred as a result of the tachycardias. The genesis of ventricular tachycardia and fibrillation in this model may involve mechanisms different from ischemia-induced ventricular tachycardia and fibrillation in canine and porcine hearts.

Animals↗