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PubMed1995

Hemodynamic recovery, atrial natriuretic peptide, and catecholamines during simulated ventricular tachycardia: effects of ventriculoatrial conduction.

Ventriculoatrial (VA) sequence and neurohumoral responses may be important modulators of hemodynamic recovery during VT. We studied the effects of VA conduction on blood pressure recovery, and levels of atrial natriuretic peptide (ANP), epinephrine, and norepinephrine during simulated VT. After diagnostic coronary angiography, VT was simulated by rapid right ventricular pacing (150 beats/min, 3 mins) in a consecutive series of patients. Whenever the patients demonstrated VA dissociation during ventricular pacing, they were included in the study. After 10 minutes of recovery, a group of nine patients then underwent an additional VA pacing (150 beats/min, 3 mins, VA delay of 150 msec). Intra-arterial blood pressure was continuously monitored, and plasma ANP and catecholamine levels were measured before, during, and after both pacing protocols. The mean arterial pressures declined rapidly by 26% and 30% after initiation of ventricular and VA pacing, respectively. The blood pressure then gradually recovered, the hemodynamic recovery being better during VA pacing. Plasma ANP and catecholamine levels increased toward the end of both pacing periods. The observed increase in ANP concentration was more prominent during VA pacing than ventricular pacing (P < 0.001), whereas catecholamine levels increased similarly. The results show that during simulated VT hemodynamic recovery is partially dependent on VA sequence. The increases in circulating ANP and catecholamines occur too slowly to account for the rapid changes in blood pressures observed after initiation of simulated VT. Therefore, other mechanisms, such as reflex stimulation of the sympathoadrenergic nervous system, must be involved, too. ANP release increases when atrial contraction frequency increases, but the exact determinants for this release remain unknown.

Adult↗
PubMed1986

Renal extraction of endogenous and radiolabelled catecholamines in the dog.

Efferent renal nerve activity can be studied by measurements of the renal venous outflow of noradrenaline and dopamine. Accurate estimates of the intrarenal release to plasma of these catecholamines, however, require determinations of the net contribution of the catecholamines in arterial plasma to their renal venous outflow. We therefore studied the extractions of endogenous noradrenaline, dopamine and adrenaline, as well as 3H-labelled tracer amounts of noradrenaline, and dopamine in innervated and denervated canine kidneys. Approximately two-thirds of noradrenaline and dopamine in arterial plasma were extracted in the kidney, while 80-90% of adrenaline in arterial plasma was extracted. The fractional extractions of the three catecholamines were not substantially altered when the sympathetic nervous system was moderately activated by bilateral carotid occlusion or when the renal nerve activity was abolished by acute denervation. It is concluded that biochemical assessment of renal sympathetic nerve activity by studies of the renal venous noradrenaline and dopamine outflow requires some estimate of the net arterial contribution to the renal venous outflow. Ideally, catecholamine extraction by the kidney should be evaluated by studies of the renal extraction of 3H-labelled noradrenaline and dopamine, but the extraction of endogenous adrenaline may also be useful for this purpose.

Animals↗
PubMed1967

The effect of ouabain on the secretion of catecholamines and on the intracellular concentration of potassium.

1. Perfusion of bovine adrenal glands with 0.1 mM ouabain is accompanied by a doubling of the spontaneous rate of release of catecholamines and by a 66% increase in the response to stimulation with carbamylcholine.2. Perfusion with ouabain (0.1 mM) reduces the intracellular content of potassium from 106 to 63 mM.3. The effect of ouabain on catecholamine secretion is dependent upon the presence of Ca(2+) ions in contrast to the effect upon the potassium content which is not dependent upon the presence of calcium.4. Ouabain has no effect on the release of catecholamines from isolated chromaffin granules both in the presence and absence of Ca(2+) ions.5. A possible relationship between the secretion of catecholamines and the concentration gradient of potassium across the cell membrane is discussed.

Journal Article↗
PubMed1981

Effects of catecholamines and cyclic amp on excitation--contraction coupling in isolated skeletal muscle fibres of the frog.

1. In skeletal muscle the presence of a positive inotropic effect induced by adrenaline has been a matter of controversy. If it exists, it could be due to catecholamines acting on the actomyosin system, on the sarcoplasmic reticulum (SR) Ca2+ pump or on the release or influx of Ca2+. We investigated these possibilities by using intact, split and skinned skeletal muscle fibres. We also investigated whether adrenaline acts directly or through cyclic AMP. 2. Catecholamines produced an increase in twitch tension and in maximum rates of tension development and tension decay. The inotropic effect took 3 min to appear and 8 min to reach its maximum level. With tetanic stimulations the extra force appeared only at the beginning of the tetanus while approaching the same maximum level, and tended to disappear faster, the higher the frequency of stimulation. At 4 shocks/sec the peak twitch tension with catecholamines decreased during the first seven to ten twitches and became steady afterwards at a level that was still greater than the control. 3. Resting and action potentials showed no important changes in the presence of adrenaline that could explain the inotropic effect. 4. In split fibres the force produced with the release of Ca2+ from the SR by caffeine was 60-100% larger when cyclic AMP was added to the previous loading solution. In skinned fibres adrenaline given directly to the interior of the cell produced no changes in contraction--relaxation cycles induced by fixed amounts of Ca2+ applied with a pipette. 5. These results strongly suggest that catecholamines through cyclic AMP stimulate the SR Ca2+ pump, increasing thereby the concentration of Ca2+ within the SR. This extra Ca2+ when released during subsequent activation may produce the increase in twitch tension.

Action Potentials↗
PubMed1982

Catecholamine synthesis in rabbit carotid body in vitro.

1. Catecholamine synthesis in rabbit carotid body was studied in vitro using [(3)H]DOPA and [(3)H]tyrosine as precursors. The effects of sympathectomy and transection of the carotid sinus nerve on [(3)H]dopamine ([(3)H]DA) and [(3)H]noradrenaline ([(3)H]NA) synthesis were investigated in chronically denervated carotid bodies.2. When [(3)H]DOPA was used as precursor, the synthesis of [(3)H]DA was linear for more than 6 hr. The carotid body synthesized larger amounts of [(3)H]catecholamines than when [(3)H]tyrosine was used as precursor, but most of this excess was liberated into the incubation media. Using 10 muM-[(3)H]DOPA as precursor, the synthesis rates were 6.76 and 1.51 n-mole/g per hr for [(3)H]DA and [(3)H]NA, respectively; with 40 muM-[(3)H]DOPA, these values increased to 19.22 and 3.23 n-mole/g per hr, respectively.3. The relationship between [(3)H]DOPA concentration and [(3)H]DA synthesis was linear throughout the range 5-40 muM-[(3)H]DOPA.4. Sympathectomy reduced the synthesis of [(3)H]NA by 90% and [(3)H]DA by 37% when [(3)H]DOPA was used as precursor.5. When [(3)H]tyrosine (40 muM) was used as precursor, synthesis of [(3)H]catecholamines was linear for at least 4 hr, with rates of 12.10 and 0.85 n-mole/g per hr for [(3)H]DA and [(3)H]NA, respectively.6. [(3)H]DA and [(3)H]NA synthesis from [(3)H]tyrosine exhibited the characteristics of saturable processes, with K(m) values of 16.8 and 17.6 muM, respectively.7. 6-methyltetrahydropterine (6-MPH(4), 100 muM), a synthetic analogue of the natural co-factor for tyrosine hydroxylase, increased [(3)H]DA and [(3)H]NA synthesis from [(3) H]tyrosine in both the carotid body and superior cervical ganglion, with the greatest effect seen in the carotid body.8. When [(3)H]tyrosine was used as precursor, sympathectomy of the carotid body reduced [(3)H]NA synthesis by 80%, but did not alter [(3)H]DA or [(3)H]tyrosine levels in the tissue. Transection of the carotid sinus nerve had no effect on [(3)H]catecholamine synthesis in the carotid body.

Animals↗
PubMed1986

Catecholamine secretion and adrenal nerve activity in response to movements of normal and inflamed knee joints in cats.

The effects of articular stimulation on adrenal catecholamine secretion and adrenal sympathetic nerve activity were studied using halothane anaesthetized cats. Various natural passive movements were applied to the normal and inflamed knee joints. Rhythmic flexions and extensions as well as rhythmic inward and outward rotation of normal knee joints within their physiological range of motion did not change nerve activity or the secretion of adrenal catecholamines. Static outward rotation in the normal working range was also ineffective. However, as soon as this static rotation was extended into the noxious range, significant increases in both of these variables were elicited. In the acutely inflamed knee joint, various passive movements produced increases in both adrenal sympathetic and catecholamine secretion. Especially noteworthy was the finding that movements of the inflamed knee joint that were within the normal range of motion produced increases in all variables. Articularly induced increases in adrenal sympathetic nerve activity were diminished by severing various hind-limb somatic afferent nerves and abolished by complete denervation of the knee joint. Additionally, section of the adrenal sympathetic nerves eliminated the catecholamine secretion response. From these data it was concluded that the responses observed in these experiments were reflexes having an afferent limb in hind-limb nerves and an efferent limb in the adrenal sympathetic nerves. A contribution of supraspinal structures was suggested for the reflex responses of sympatho-adrenal medullary function evoked by knee joint stimulations, since spinal transection at the C2 level completely abolished the responses.

Action Potentials↗
PubMed1994

Differential secretion of catecholamines in response to peptidergic and cholinergic transmitters in rat adrenals.

1. Rat adrenal medulla is stimulated by cholinergic and peptidergic transmitters released from splanchnic nerves. The peptidergic transmitter has been identified as vasoactive intestinal polypeptide (VIP) and its contribution in comparison to that of acetylcholine (ACh) is more prominent at low neuronal activity. The purpose of this study is to determine if ACh and VIP cause differential secretion of adrenaline and noradrenaline and whether the differential secretion also occurs when splanchnic nerves are stimulated at different frequencies. 2. Perfusion of the left adrenal gland with Krebs solution for several hours did not change adrenaline and noradrenaline contents (15.2 micrograms and 3.5 micrograms, respectively) and their ratio (4.4) from those of the unperfused right adrenal medulla (15.2 micrograms, 3.3 micrograms and 4.8, respectively). 3. Perfusion with ACh (10 microM for 4 min) resulted in the secretion of 109 ng of catecholamines and the ratio of adrenaline to noradrenaline was 3.8. Although the secretion increased with increased concentrations of ACh (30 and 100 microM), the ratios remained between 3 and 4. 4. Perfusion with VIP (10 microM for 4 min) resulted in the secretion of 27 ng of catecholamines and the ratio of adrenaline to noradrenaline was 9.7. A higher concentration of VIP (20 microM for 4 min) resulted in the secretion of greater amounts of catecholamines (102 ng) without significantly altering the ratio of adrenaline to noradrenaline (10.9). 5. Perfusion with as low as 0.01 microM pituitary adenylate cyclase-activating polypeptide (PACAP) increased the secretion of catecholamines to 31 ng and the secretion increased in a dose-dependent manner up to 0.3 microM.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1974

Reversal of catecholamine refractoriness by inhibitors of RNA and protein synthesis.

The generation of adenosine 3',5'-monophosphate (cyclic AMP) in response to catecholamines in the 2B subclone of RGC6 rat glioma cells previously exposed to norepinephrine and refractory to further norepinephrine addition is substantially increased by addition of inhibitors of RNA and protein synthesis. The time course of the effect of these inhibitors on cyclic AMP concentration suggests that rapid protein synthesis and turnover are involved in catecholamine refractoriness. Norepinephrine induction of cyclic nucleotide phosphodiesterase is demonstrable in RGC6 cells but not in the 2B subclone. Thus, catecholamine refractoriness cannot be attributed to induction of phosphodiesterase. This implies that induction of a protein or proteins, important in catecholamine refractoriness, affects the synthesis rather than the degradation of cyclic AMP.

Animals↗
PubMed1982

Rapid fluctuations in plasma catecholamines in monkeys under undisturbed conditions.

We have demonstrated in monkeys and in man sustained synchronous oscillations in plasma levels of insulin, C-peptide, glucagon, and glucose that have periods ranging from 8 to 11 min. To identify the mechanisms of these oscillations, we studied plasma levels of catecholamines in search for periodic fluctuations. Blood was obtained at 2-min intervals from fasting, undisturbed, chair-adapted male rhesus monkeys via chronically implanted central venous catheters. Plasma levels of epinephrine, norepinephrine, and dopamine were measured by a radioenzymatic assay. Large fluctuations in plasma epinephrine were observed with an average peak-to-trough amplitude of 34 pg/ml at a mean level of 122 pg/ml. Similar fluctuations in norepinephrine and dopamine occurred and were correlated to those of epinephrine: r = 0.51 and 0.35, respectively. The most common periodicity in all three catecholamines was 6-13 min/cycle as determined by spectral analyses. Cross-correlation analyses indicated that fluctuations in the catecholamines were significantly negatively correlated with oscillations in insulin and were unrelated to fluctuations in glucagon. These fluctuations in plasma catecholamines may be related to mechanisms controlling the periodicity observed in plasma insulin and glucose.

Animals↗
PubMed1986

Potentiation of hemorrhage-evoked catecholamine release by prior blood loss in cats.

The effect of prior blood loss on the plasma catecholamine response to acute hemorrhage (H) was assessed in alpha-chloralose-urethane anesthetized cats. Animals sustained an initial H period of 0 (samples only), 10, or 20% H total blood volume. Ninety minutes after reinfusion of the shed blood, all animals sustained a rapid 20% H. The catecholamine and arterial pressure responses to this second 20% H were assessed every 2 min for 20-min duration. Plasma norepinephrine increased modestly in the 0/20% group (+0.63 +/- 0.13 ng/ml) and 10/20% group (+0.66 +/- 0.07 ng/ml), whereas the 20/20% group showed a much larger (P less than 0.01) mean increase of 3.58 +/- 1.16 ng/ml. Plasma epinephrine did not increase after 0/20% (+0.05 +/- 0.02 ng/ml), increased slightly after 10/20% H (+0.10 +/- 0.05 ng/ml), and demonstrated a large significant increase after 20/20% H (+0.48 +/- 0.18 ng/ml). The differential effect of 20% H on catecholamine release, depending on the magnitude of prior blood loss, was not the result of altered mean arterial or pulse pressure responses to H. Correlation analyses revealed that the mean increases in epinephrine and norepinephrine during the post-H sampling period were well correlated in each animal (r = 0.864, P less than 0.001). The data indicate that the priming effect of prior blood loss on H evoked catecholamine release: requires an initial blood loss of 20% of total blood volume; occurs rapidly, as it is seen by 90 min after the initial H period; and affects epinephrine and norepinephrine similarly. We conclude that the immediate past secretory history of the sympathoadrenal system affects its responsiveness to subsequent blood loss.

Acute Disease↗
PubMed1988

Free and total catecholamines in critical illness.

The magnitude of circulating free and total (free plus conjugated) catecholamine responses to a strong and sustained stimulus was investigated in four groups of patients: traumatic brain injury (n = 24), vascular brain injury (n = 10), polysystem trauma (n = 7) and medical/surgical patients in an intensive care unit (n = 29). Despite significant three- to sevenfold elevations in both free and total norepinephrine (NE) and epinephrine (E), the ratio of free to total NE and E remained constant over a very broad range of values. The proportion of free E was twice normal (30.1-33.5 vs. 16.2%) in all but patients with polytrauma, whereas the percentage of free NE was unchanged in all patients (43.0%). All dopamine (DA) parameters remained generally normal. In the patients with traumatic or vascular brain injury, significant inverse correlations were present between the degree of neurological dysfunction, as indicated by the concomitant Glasgow coma score, and free NE, E, and DA and total NE and DA levels. Thus, during conditions of intense and prolonged catecholamine release, the proportion of free catecholamine remains constant and the total as well as free catecholamine concentration is proportional to the Glasgow coma score.

Critical Care↗
PubMed1988

Adrenal sympathetic efferent nerve and catecholamine secretion excitation caused by capsaicin in rats.

Capsaicin enhances adrenal medullary catecholamine secretion. The participation of the central nervous system on this enhancement by capsaicin was investigated in alpha-chloralose-urethan- or halothane-anesthetized rats. Intravenous administration of capsaicin caused a rapid and marked increase in adrenal sympathetic nerve activity. The nerve activity began to show an increase with the administration of capsaicin at a dosage of 20 micrograms/kg and significantly increased with a dosage of 200 micrograms/kg, i.e., capsaicin was found to cause a dose-dependent increase in adrenal nerve activity. Cholinergic blocking with hexamethonium bromide and atropine sulfate (1 and 5 mg/kg iv, respectively) attenuated the adrenal epinephrine secretion caused by capsaicin. The direct action of capsaicin on adrenal catecholamine secretion was examined using a retrograde perfusion system of left adrenal gland. Up to 8.2 X 10(-5) M capsaicin did not enhance catecholamine secretion from the adrenal gland. These results suggest that the enhancement of physiological catecholamine secretion by capsaicin is mainly through activation of the central nervous system.

Adrenal Glands↗
PubMed1996

Exercise stimulates interleukin-6 secretion: inhibition by glucocorticoids and correlation with catecholamines.

In experimental animals, stress and catecholamines stimulate endogenous interleukin-6 (IL-6) secretion, whereas glucocorticoids inhibit it. To examine whether physical stress alters the secretion of IL-6 in humans, and to what extent this is correlated with catecholamines and modified by glucocorticoids, we performed high-intensity treadmill exercise test runs on 15 male volunteers, in a double-blind crossover design, after pretreatment with placebo, hydrocortisone, or dexamethasone. Plasma epinephrine and norepinephrine concentrations peaked 15 min after the start of exercise, whereas plasma IL-6 concentrations peaked twice, 15 min and 45 min after the onset of the test run. There was no difference in either the epinephrine or norepinephrine peaks among the three treatments, but the net area under the curve for IL-6 was smaller after hydrocortisone or dexamethasone than after placebo and smaller after dexamethasone than after hydrocortisone. A positive correlation was observed between peak plasma epinephrine or norepinephrine and IL-6 levels at 15 min. These findings suggest that IL-6 secretion is stimulated during exercise, possibly by catecholamines, whereas exogenous glucocorticoids attenuate this effect without affecting the catecholamine levels.

Adult↗
PubMed1980

Inhibition by adenosine of catecholamine-induced increase in rat atrial contractility.

Because adenosine has been shown to attenuate the catecholamine-induced increase in myocardial cAMP formation and glycogen phosphorylase activity (Circ. Res. 43: 785-792, 1978), the present study was undertaken to determine whether the nucleoside inhibits the catecholamine-elicited increase in cardiac contractile state. Isolated rat atria were bathed in oxygenated physiologic saline and stimulated to contract isometrically at 2/s. Isoproterenol (0.1 microM) increased peak contractile force (PCF) by 96% and the rate of force development (+dF/dt) by 107%. Adenosine (10 microM) alone had no effect on these contractile parameters. Isoproterenol in the presence of adenosine increased PCF and +dF/dt only 15 and 14%, respectively. Elevation of bathing medium Ca2+ or administration of dibutyryl cAMP (DBcAMP) increased PCF and +dF/dt, but these responses were not decreased by adenosine. Inosine, adenine, adenosine 5'-monophosphate, and guanosine inhibited the isoproterenol-induced responses 5-22%. The results indicate that adenosine markedly inhibits, whereas some related purines only mildly attenuate, the catecholamine-elicited, but not the Ca2+- or DBcAMP-elicited, increases in contractility. Thus, adenosine may antagonize catecholamine-elicited glycogenolysis and enhanced contractile state in the heart by exerting an effect at the level of, or proximal to, cAMP formation.

Acetylcholine↗
PubMed1985

Correlation between cardiac performance and plasma catecholamine levels in conscious dogs.

We correlated levels of circulating norepinephrine (NE) and epinephrine (Epi) induced by 1) infusions, 2) treadmill exercise, and 3) hemorrhage with left ventricular (LV) function in conscious dogs instrumented for the measurement of LV and arterial pressures, LV diameter, and calculations of indexes of myocardial contractility. With infusions of NE, significant hemodynamic changes were observed only when plasma levels of NE exceeded 1,000 pg/ml. While statistically significant, the increase in rate of rise of LV pressure (LV dP/dt) at these levels was relatively slight, i.e., 8 +/- 2.3%. With further increases in catecholamines (greater than 1,000 pg/ml) good correlations were observed with increases in arterial pressure and myocardial contractility. Similar results occurred with infusions of Epi. Moderate treadmill exercise doubled LV dP/dt, while NE and Epi rose by only 563 +/- 128 and 292 +/- 50 pg/ml, respectively. Hemorrhage (30 ml/kg) decreased all indexes of contractility but increased plasma NE by 1,108 +/- 206 pg/ml and Epi by 1,475 +/- 266 pg/ml. Despite arterial NE and Epi levels 10-20 times those during exercise, infusions were unable to reproduce the peak changes in contractility seen with exercise. Infusions of NE or Epi to equal the plasma levels during exercise increased contractility by only 5-10%. In view of the marked disparity between levels of circulating catecholamines and LV function during exercise, hemorrhage, and catecholamine infusion, we conclude that circulating catecholamines do not adequately reflect the degree of inotropic stimulation to the myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Sensitivities of cardiac O2 consumption and contractility to catecholamines in dogs.

We studied the effects of plasma catecholamines from the adrenal gland on systolic pressure-volume area (PVA)-independent O2 consumption (VO2) and contractility index (Emax) in the left ventricle of excised cross-circulated dog hearts. PVA is a measure of the total mechanical energy of contraction. Under baseline conditions, the PVA-independent VO2 correlated with plasma catecholamine level in the hearts (r = 0.84). Plasma epinephrine and norepinephrine levels increased gradually from 0.3 and 0.4 ng/ml to 10.3 and 2.7 ng/ml on average during adrenal sympathetic nerve stimulation of support dogs. Simultaneously, Emax and PVA-independent VO2 increased by 240 +/- 127 (SD) and 75 +/- 24%. Although their increases were monotonic in a given heart, their sensitivities to catecholamines were considerably variable among hearts. However, these two sensitivities were correlated (r = 0.96) with each other in the hearts, and the interheart variation of the sensitivity of the PVA-independent VO2 to Emax (i.e., oxygen cost of Emax) was smaller. We conclude that the oxygen cost of Emax is less variable among hearts despite large interheart variations of Emax and VO2 responses to plasma catecholamines.

Animals↗
PubMed1992

Catecholamine-mediated lymphatic constriction: involvement of both alpha 1- and alpha 2-adrenoreceptors.

It has been proposed that catecholamines may regulate lymphatic function by altering lymphatic resistance. In this study we perfused lymphatics in the paw of the anesthetized dog, administering catecholamines intralymphatically before and during intra-arterial administration of adrenoreceptor antagonists. Epinephrine and norepinephrine both increased lymphatic perfusion pressure. When the infusions were repeated during intra-arterial phentolamine, neither catecholamine significantly altered lymphatic perfusion pressure, thus implicating lymphatic adrenoreceptors. Intralymphatic infusion of these catecholamines during the intra-arterial infusion of prazosin significantly increased lymphatic perfusion pressure, but the increase was markedly less than that seen prior to prazosin. In these same animals, the lymphatic constriction produced by intralymphatic phenylephrine was completely blocked, indicating an effective blockade of the alpha 1-receptors. The intralymphatic infusion of phenylephrine or alpha-methylnorepinephrine both significantly increased lymphatic perfusion pressure, confirming the presence of both alpha 1- and alpha 2-receptors. These data demonstrate that the prenodal lymph vessels of the canine forelimb contain both alpha 1- and alpha 2-receptors and that epinephrine and norepinephrine interact with both classes of receptors to produce lymphatic constriction.

Animals↗
PubMed1993

Arrhythmogenic effects of catecholamines are decreased in heart failure induced by rapid pacing in dogs.

Increased circulating catecholamines are considered to be arrhythmogenic in heart failure. It is unclear whether increased circulating catecholamines contribute directly to ventricular arrhythmias or are only markers of the severity of heart failure. The present study determined the sensitivity of the failing heart to the arrhythmogenic effect of exogenous norepinephrine in a rapid pacing-induced model of heart failure in dogs (240 beats for 4 wk, n = 14). A similarly operated, non-paced group served as controls (n = 9). Cardiac sensitivity to the arrhythmogenic effect of catecholamines was determined by measuring the minimal dose of exogenous norepinephrine that induced ventricular tachycardia (arrhythmogenic threshold dose, ATD). ATD significantly increased after development of heart failure in heart-failure group (1.62 +/- 0.32 microgram/kg at baseline vs. 16.65 +/- 3.48 micrograms/kg at restudy, P < 0.01), whereas no significant change was noted in the control group (1.08 +/- 0.36 microgram/kg at baseline vs. 2.53 +/- 0.36 micrograms/kg at restudy, P > 0.10). Action potential duration was unchanged by superfusion with 10(-7) M isoproterenol in both ventricular muscles (230.2 +/- 6.1 vs. 229.7 +/- 5.3 ms, P = NS) and Purkinje fibers (273.2 +/- 6.5 vs. 283.8 +/- 4.2 ms, P = NS) from the failing hearts, although isoproterenol induced a shortening in the control group (204.8 +/- 0.9 vs. 181.3 +/- 1.6 ms in ventricular muscles, P < 0.01; 313.8 +/- 6.5 vs. 279.5 +/- 5.7 ms in Purkinje fibers, P < 0.01). We conclude that the failing heart has a decreased sensitivity to the arrhythmogenic effect of catecholamines.

Action Potentials↗