Infusion Of Propranolol Research Articles

Mechanism of isoproterenol-induced angina pectoris in patients with obstructive hypertrophic cardiomyopathy and normal coronary arteries

In 14 patients with obstructive hypertrophic cardiomyopathy and angiographically normal coronary arteries, 8 with angina (group B) and 6 without (group A), the effects of intravenous isoproterenol, 2 to 4 μg/min, followed by intravenous propranolol, 0.2 mg/kg, were studied. An intraventricular systolic gradient <50 mm Hg, high-quality echocardiograms and cineangiograms and high-fidelity pressure tracings were selection criteria. Hemodynamic and metabolic variables were assessed during basal conditions, after 5 minutes of isoproterenol infusion or at angina and ST-segment depression, and 5 and 10 minutes after intravenous propranolol infusion. Isoproterenol increased the intraventricular systolic gradient more significantly in group B than in group A (102.4 ± 8.3 vs 52.2 ± 8.2, p < 0.0001). Group B also had higher left ventricular end-diastolic pressure (32.5 ± 3.9 vs 20.2 ± 5.7), lower mean arterial pressure (69.7 ± 3.5 vs 84.7 ± 4.8) and a smaller increase in coronary sinus flow (176.1 ± 9.2 vs 261.5 ± 33.9, all p < 0.0001), concomitant with lactate release and ST-segment depression. Propranolol promptly reversed hemodynamic and metabolic changes caused by isoproterenol, except for a further coronary sinus flow increase (from 176.1 ± 9.2 to 219 ± 14.2 ml/min, p < 0.001), and heart rate decrease below basal values (57.8 ± 7.5 vs 79.9 ± 9.8 beats/min, p < 0.001) in group B. In conclusion, in patients with angina, higher intraventricular systolic gradients develop during isoproterenol infusion, revealing the primary role of true left ventricular outflow obstruction in the pathophysiology of catecholamine-induced angina, and hyperresponse to β-adrenergic stimulation and β blockade could be suggested in angina patients with obstructive hypertrophic cardiomyopathy and normal coronary arteries.

Effect of severe burn injury on substrate cycling by glucose and fatty acids.

Increases in metabolic rate and core temperature are common responses to severe injury. We have investigated the hypothesis that these responses are due to increases in substrate cycling. A substrate cycle exists when opposing, nonequilibrium reactions catalyzed by different enzymes are operating simultaneously. At least one of the reactions must involve the hydrolysis of ATP. Thus, a substrate cycle both liberates heat and increases energy expenditure, yet there is not net conversion of substrate to product. In studies in volunteers (n = 18) and in patients with severe burns who were in a hypermetabolic state (n = 18), we used stable-isotope tracers to quantify substrate cycling in the pathways of glycolysis and gluconeogenesis and a cycle involving the simultaneous breakdown and synthesis of stored triglyceride (triglyceride-fatty acid cycle). The total rates of triglyceride-fatty acid and glycolytic-gluconeogenic cycling were elevated in the patients by 450 and 250 percent, respectively (P less than 0.01). An infusion of propranolol in the patients greatly reduced triglyceride-fatty acid cycling but did not affect gluconeogenic-glycolytic cycling. We conclude that increased substrate cycling contributes to the increased thermogenesis and energy expenditure following severe burns and that the increased triglyceride-fatty acid cycling is due to beta-adrenergic stimulation.

Increase of renal sympathetic nerve activity by metoprolol or propranolol in conscious spontaneously hypertensive rats.

1 Mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were recorded in conscious spontaneously hypertensive rats (SHR). 2 Infusion of metoprolol (4 mumol kg-1 h-1) or propranolol (1.5 mumol kg-1 h-1) reduced HR and significantly increased RSNA. 3 Administration of metoprolol caused a sustained decrease of MAP starting in the third hour of infusion. In contrast, administration of propranolol induced a biphasic response in MAP. It is suggested that the increase of RSNA after both beta-adrenoceptor blocking drugs is due to a decrease in arterial baroreceptor activity.

Acute effects of halothane anesthesia on arterial and venous concentrations of propranolol in the dog.

The present study determined the effect of halothane on arterial and venous propranolol concentrations during a continuous intravenous infusion of propranolol. Arterial and venous concentrations of propranolol remained constant during the experiment in the group of dogs anesthetized only with pentobarbital. However, there was a rapid increase in arterial propranolol concentration from 88 +/- 10 ng/ml (mean +/- SEM) prior to halothane to 116 +/- 12 ng/ml (P less than 0.05) and 130 +/- 7 ng/ml (P less than 0.05) 60 and 120 min, respectively, after starting halothane anesthesia (2.0 MAC 1.74%). The increase in venous propranolol concentration lagged substantially behind that of the arterial concentration, so that, 60 min after starting halothane, the arterial to venous (A/V) concentration ratio increased from 1.13 +/- 0.05 to a maximum of 1.48 +/- 0.08. In contrast to the changes following halothane, no significant change in the A/V ratio occurred following fentanyl. Both halothane and fentanyl administration produced a small but significant increase in the free fraction of propranolol (P less than 0.05). The results from this study emphasize the importance of the choice of sampling sites in pharmacokinetic experiments, as well as excluding subtle pharmacokinetic changes during anesthesia before ascribing changes in drug effect to changes in sensitivity to the drug.

Beta-adrenergic blockade and intravenous nutrient-induced thermogenesis in lean and obese women.

Continuous respiratory exchange measurements were performed in nine obese and eight lean women for 1 h before, 3 h during, and 1 h after the intravenous administration of a nutrient mixture infused at twice the postabsorptive resting energy expenditure (REE). This experiment was conducted without or with beta-adrenergic blockade (iv propranolol). Propranolol administration did not change the postabsorptive REE [i.e., 1.03 +/- 0.07 before vs. 1.01 +/- 0.02 kcal/min after administration in lean women and 1.16 +/- 0.04 vs. 1.15 +/- 0.03 kcal/min (NS) in obese women]. The mean overall thermogenic response expressed as a percentage of the infused energy was similar in both groups and was not significantly blunted after propranolol infusion [6.9 +/- 0.4 vs. 5.9 +/- 0.6% in the lean women and 7.5 +/- 0.5 vs. 7.1 +/- 0.6% (NS) in the obese women]. During beta-adrenergic blockade the rate of lipid oxidation decreased in the lean group but was unchanged in the obese group and the glycemic response to nutrient administration was significantly higher in both groups than without propranolol. It is concluded that beta-adrenergic blockade has no effect on REE and on intravenous nutrient-induced thermogenesis in both lean and obese women.

Mechanisms of cerebrovascular dilation by ether in monkeys.

We hypothesized that when the depth of ether anesthesia is increased from 2 to 5%, cerebral vessels dilate secondary to circulating catecholamine stimulation of cerebral metabolism. Cerebral blood flow (CBF) by 133Xe clearance and cerebral metabolic rate for oxygen (CMRO2) were measured on 2% and then 5% ether in air in two groups of seven monkeys each during mechanical ventilation. Propranolol, 0.5 mg/kg i.v., was infused over 5 min in one group, and the other received saline. All measurements were repeated on 5% and 2% ether. Cerebrovascular resistance (CVR) fell by 30%, from 2.28 +/- 0.61 (mean +/- SD) to 1.51 +/- 0.28 mm Hg ml-1 100 g-1 min-1 (p less than 0.01), with the increase in ether from 2 to 5%. CBF and CMRO2 were unaltered from values of about 45 ml 100 g-1 min-1 and 2.3 ml 100 g-1 min-1, respectively. During 5% ether anesthesia, propranolol had no effect on CBF, CMRO2, or CVR. On 2% ether, it increased CVR twofold, from 1.5 +/- 0.30 to 3.0 +/- 1.0 mm Hg ml-1 100 g-1 min-1, and decreased CBF by 33%, from 48 +/- 8 to 32 +/- 10 ml 100 g-1 min-1. Plasma epinephrine was two-fold higher on 2% compared to 5% ether, both before and after saline or propranolol infusion. In monkeys, cerebrovascular dilation by ether at 5% compared to 2% is not secondary to catecholamine stimulation of CMRO2. It may result from a direct effect of either plasma catecholamines or ether on the cerebrovasculature.

Validation of a new method for determination of free fatty acid turnover.

The accuracy of tracer methods for estimating free fatty acid (FFA) rate of appearance (Ra), either under steady-state conditions or under non-steady-state conditions, has not been previously investigated. In the present study, endogenous lipolysis (traced with 14C palmitate) was suppressed in six mongrel dogs with a high-carbohydrate meal 10 h before the experiment, together with infusions of glucose, propranolol, and nicotinic acid during the experimental period. Both steady-state and non-steady-state equations were used to determine oleate Ra ([3H]oleate) before, during, and after a stepwise infusion of an oleic acid emulsion. Palmitate Ra did not change during the experiment. Steady-state equations gave the best estimates of oleate inflow approximately 93% of the known oleate infusion rate overall, while errors in tracer estimates of inflow were obtained when non-steady-state equations were used. The metabolic clearance rate of oleate was inversely related to plasma concentration (P less than 0.01). In conclusion, accurate estimates of FFA inflow were obtained when steady-state equations were used, even under conditions of abrupt and recent changes in Ra. Non-steady-state equations, in contrast, may provide erroneous estimates of inflow. The decrease in metabolic clearance rate during exogenous infusion of oleate suggests that FFA transport may follow second-order kinetics.

Inotropic responses of the left ventricle to changes in heart rate in anesthetized rabbits.

Factors known to influence left ventricular contractility include preload, afterload, circulating catecholamine concentration, efferent sympathetic discharge, and heart rate. Heart rate influences have been primarily determined in the dog, whereas the influence of heart rate in smaller mammals has not been determined. Eight pentobarbital-anesthetized rabbits were instrumented to measure electrocardiogram, heart rate, left ventricular pressure, end-diastolic pressure, dP/dt, and mean and pulsatile aortic pressures. Systematic bradycardia was induced by stimulating the peripheral end of the sectioned right vagus nerve. Between 293 and 235 beats/min, there was no change in (dP/dt)max as heart rate was decreased. Below this range there was a direct relationship between (dP/dt)max and heart rate. Preload remained unchanged down to 132 beats/min. There was a small but significant decrease in afterload (0.09 mmHg X beat-1 X min-1; 1 mmHg = 133.32 Pa) throughout the decrease in heart rate. Infusion of propranolol (2.0 mg/kg) produced no marked change in the heart rate - (dP/dt)max relationship, although both resting heart rate and (dP/dt)max were reduced. This study demonstrates that (dP/dt)max is not influenced by changes in heart rate above 235 beats/min in the pentobarbital-anesthetized rabbit. These results differ from findings in other animals, and demonstrate that species and heart rate ranges must be considered when drawing conclusions regarding (dP/dt)max as a reliable index of contractility.

The cardiovascular and adrenergic actions of verapamil or diltiazem in combination with propranolol during halothane anesthesia in the dog.

Continuous infusions of verapamil and diltiazem were established in halothane-anesthetized dogs (1.15-1.35% end tidal concentration) with or without a concomitant propranolol infusion to investigate changes: in cardiovascular function, in reflex activation as reflected in circulating catecholamine levels, and in the chronotropic response to the exogenously administered beta agonist, isoproterenol. Verapamil plasma levels of approximately 100 and 250 ng X ml-1, diltiazem plasma levels of approximately 140 and 325 ng X ml-1, and propranolol levels of approximately 70 ng X ml-1 were tolerated individually in the presence of halothane, although atrioventricular conduction was prolonged in the verapamil and diltiazem groups. Catecholamine levels were increased in the high verapamil group. However, when propranolol was combined with the lower levels of verapamil or diltiazem, the result was decreased heart rate, blood pressure, left ventricular maximum rate of tension development (dP/dt), and cardiac index with increased systemic vascular resistance. When the attempt was made to proceed to the increased plasma levels of verapamil or diltiazem in the presence of propranolol, 6/6 animals in the verapamil-propranolol group and 4/6 animals in the diltiazem-propranolol group were unable to maintain a mean arterial blood pressure of greater than 50 mmHg, and many developed 2 degrees or higher heart block.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of adrenergic receptors on ovarian progesterone secretion in the pseudopregnant cat and oestradiol secretion in the oestrous cat.

The infusion of isoprenaline or propranolol into the abdominal aorta of the pseudopregnant cat caused an increase or decrease respectively in the ovarian progesterone secretion rate. These observations suggest that the sympathetic innervation of the ovary has a physiological influence on normal progesterone secretion, and this mechanism may explain stress-related increases in progesterone concentrations. The infusion of isoprenaline or propranolol after the stimulation of follicular growth had no consistent or convincing effect on oestradiol secretion.

Effects of Esmolol on Airway Function in Patients with Asthma

In a double-blind, randomized, crossover study in ten patients with asthma, the effects on specific airway resistance of esmolol, a new ultra-short-acting beta 1-selective adrenoceptor blocker, were compared with those of placebo. Specific airway resistance was measured during increasing doses of esmolol infusion, during dry air provocation tests, and following isoproterenol inhalation. These same studies were later carried out on six of ten patients following intravenous propranolol infusion. All patients were able to tolerate the maximum dose of esmolol (300 micrograms/kg/min); treatment differences between esmolol and placebo were not found. In contrast, intravenous propranolol produced marked symptomatic bronchoconstriction after the lowest dose (1 mg) in two of six patients. Esmolol produced slight but statistically significant enhancement of patients' sensitivity to dry air provocation. Similarly, a slight but significant inhibition of bronchomotor sensitivity to isoproterenol was noted during esmolol infusion. After infusion of 5 mg of intravenous propranolol, one of four patients had a clinically significant increase in sensitivity to dry air. It is concluded that esmolol, because of its short duration of action and relative lack of effect on airway resistance, may be preferred over propranolol in patients with asthma who require treatment with an intravenous beta-blocking agent.

Effect of propranolol on cortical electrical activity in conscious and anesthetized rats

The effect of propranolol on electrocorticographic (ECoG) activity was studied in conscious and anesthetized rats. Cortical electrodes and femoral venous cannulae were implanted 5 days before the experiments. The ECoG was recorded continuously and analyzed to different frequency bands, 2 hr before and 4 hr after the administration of propranolol. After a single infusion of 2 and 5 mg/kg or 5 consecutive daily doses of 2 mg/kg propranolol, frequent bursts of large amplitude 6–7 c/sec wave in the ECoG were observed. This ECoG phenomenon lasted between 60–100 min after the infusion of propranolol and was entirely abolished by pentobarbital anesthesia. Frequency analysis of the ECoG showed an immediate shift from predominantly delta (Δ 0.5–4 c/sec) activity to overwhelmingly theta (θ4–8 c/sec) activity following the infusion of propranolol. It is suggested that these changes in ECoG induced by propranolol are related to the sleep-enhancing and tranquilizing effects of propranolol.

The influence of nutrient administration on energy expenditure in man

Recent data on the thermic effect of nutrients are presented. When given intravenously (i.v.), glucose (+ insulin) induces an increase of energy expenditure (EE) of 7% of energy infused, whereas lipid (Intralipid ®) infusion stimulates EE by 3% of energy infused. The stimulation of EE due to amino acid infusion in depleted patients is 30–40% of the energy infused as amino acids. Glucose induced thermogenesis includes an ‘obligatory thermogenesis’ which accounts for the energy cost of storing the nutrient and a ‘facultative thermogenesis’ which is mainly due to a stimulation of sympathetic activity; the latter is suppressed by propranolol infusion. Comparison of nutrient induced thermogenesis during continuous administration of nutrients between the enteral and parenteral routes reveal similar responses. This shows that the energy costs of digestion and absorption of nutrients is low in comparison with the cost of nutrient storage. However, when given by the enteral route, the net efficiency of energy utilisation is also dependent on the co-efficient of nutrients absorption. Oral administration of nutrients (bolus) induces a larger thermogenic response than continuous enteral administration, due to a larger nutrient storage for the former. It is therefore advisable to allow for the thermic effect of nutrients when assessing the efficiency of energy utilisation in patients.

The Effect of ??-Adrenergic Blockade on the Cardiovascular Response to Diltiazem or Verapamil in Dogs

Diltiazem or verapamil were each given at two different infusion rates to pentobarbital-anesthetized dogs with or without a concurrent infusion of propranolol. Changes in cardiovascular function, in reflex activation as reflected by circulating catecholamine levels, and in the chronotropic response to an exogenous beta-adrenergic agonist, isoproterenol, were measured. When administered alone, diltiazem or verapamil, at plasma concentrations of 160 and 370 ng/ml, or 230 and 500 ng/ml, respectively, prolonged atrioventricular conduction and caused systemic vasodilation with a decrease in mean arterial pressure. Cardiac index increased, associated with an increase in arterial norepinephrine level. Heart rate increased with the lower level of verapamil; left ventricular dP/dt increased with both levels of verapamil and at the higher level of diltiazem. Plasma propranolol levels of approximately 35 ng/ml were well tolerated in the absence of diltiazem or verapamil. When added to diltiazem or verapamil, propranolol resulted in an increase in systemic vascular resistance to near control values; a decrease in cardiac index, left ventricular dP/dt, and heart rate; and worsened atrioventricular conduction. Three of nine animals in the high verapamil-propranolol group were unable to maintain a mean arterial pressure greater than 50 mm Hg, and developed a low cardiac index with an elevated systemic vascular resistance, despite very high levels of circulating catecholamines. Compared to the anesthetized state, greater amounts of isoproterenol were needed to effect the same increase in heart rate with the addition of diltiazem, verapamil, or propranolol alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Beta-adrenergic contribution to glucagon-induced glucose production and insulin secretion in uremia.

Spontaneous or propranolol-induced hypoglycemia can occur in uremic humans. We studied glucose kinetics (using [3-3H]glucose) in five uremic humans 24 h after hemodialysis and in seven normal controls. The effect of glucagon infusion at rates of 3, 6, 12, and 18 ng X kg-1 X min-1 at 60-min intervals was compared with either saline or beta-adrenergic blockade (propranolol infusion). In uremics, plasma glucose increased by 20-25% and by 40-50% at the 3 and 6 ng X kg-1 X min-1 glucagon doses, respectively, with no further increases at higher infusion rates. Glucose production increased transiently and in tandem with glucose uptake at each glucagon increment (P less than 0.0001). During beta-adrenergic blockade, the effect of glucagon in stimulating glucose production was blunted by 14-24% at the 6-18 ng X kg-1 X min-1 doses (P less than 0.05). During saline infusion, plasma insulin concentrations increased progressively to peak levels fourfold above basal at the 18 ng X kg-1 X min-1 dose. This increase in plasma insulin was virtually abolished by concomitant beta-adrenergic blockade (P = 0.0002). In contrast to uremic subjects, normal controls exhibited lesser degrees of hyperglycemia and hyperinsulinemia at all glucagon infusion rates. Propranolol infusion had no effect on the increments in glucose production and uptake nor on the plasma insulin response. These results suggest that in uremic humans propranolol independently reduces the hepatic response to glucagon and the insulin secretory response to hyperglycemia and/or hyperglucagonemia. These observations provide a possible mechanism for the adrenergic regulation of glucose homeostasis in uremia.

Modulation of insulin secretion by pancreatic ganglionic nicotinic receptors.

Autonomic ganglia may be regulated, in part, by nicotinic receptors. To test whether basal insulin secretion may be modulated by an endogenous pancreatic ganglionic mechanism, the effects of ganglionic pre- and postsynaptic nicotinic receptor antagonism were studied in the in vitro canine pancreas. Combined infusion of atropine, phentolamine, and propranolol had no affect on insulin secretion (P less than .30). Presynaptic nicotinic receptor blockade by beta-bungarotoxin (beta-BuTX) in combination with atropine and phentolamine reduced mean insulin secretion (78 +/- 18 U/ml, P less than .0025) from preinfusion concentrations (287 +/- 43 U/ml). The decrease in insulin secretion resulting from BuTX, atropine, and phentolamine was prevented by the addition of either specific postsynaptic nicotinic receptor blockade by alpha-bungarotoxin (P less than .05) or propranolol (P less than .005). Because it is known that postsynaptic nicotinic receptor agonism may stimulate the intraganglionic release of norepinephrine, these results suggest that nicotinic receptors are present at the ganglionic level in the pancreas and modulate insulin secretion by a complex intraganglionic mechanism. The postulated ganglionic nicotinic receptor-mediated mechanism may operate by the interaction of a beta-adrenergic inhibitory component, which may be activated by intraganglionic norepinephrine, and a stimulatory nonmuscarinic nonadrenergic (possibly peptidergic) component, which may be activated in the absence of intraganglionic norepinephrine.

The automatic computation of pressure‐derived maximal shortening velocity (Vmax) of the unloaded contractile element in the intact canine heart left ventricle

Estimation of the maximum velocity (Vmax) of the contractile element of the intact left ventricular wall muscle demands extrapolation of the force-velocity curve to zero load. The present paper describes our on-line computation system for measuring and analysing pressure derived Vmax using both linear (Vmax-lin) and exponential (Vmax-exp) extrapolation methods. The developed pressure during isovolumetric phase of systole was used as an equivalent of the force. Testing on anaesthetized artificially ventilated dogs showed the exponential function to fit pressure-velocity data better than the straight line did. The Vmax-exp attained 15-35% greater values than Vmax-lin, but both responded almost equally when considered on the basis of linear regression analysis (r = 0.991, n = 725). Changes of contractility caused by i.v. infusion of isoproterenol, calcium chloride or propranolol were practically similar when assessed by either method of Vmax computation, or by dP/dtmax. Volume loading by dextran infusion increased not only dP/dtmax, by 33 +/- 13%, but also Vmax, up to 24 +/-. When arterial pressure was raised by phenylephrine infusion, or heart rate by atrial pacing, dP/dtmax increased significantly while Vmax remained unaltered. Hence, the linear and exponential dP/dtmax increased significantly while Vmax remained unaltered. Hence, the linear and exponential extrapolation procedures provided comparable values for Vmax, but the linear one due to its simplicity is more suited for on-line computation. The Vmax thus obtained is, however, not independent of the changes in preload.

Chemical dependencies of learning in the rabbit olfactory bulb: acquisition of the transient spatial pattern change depends on norepinephrine.

Intracerebral cannulas were implanted in both olfactory bulbs of 6 rabbits. A surface electrode-array (8 X 8) was implanted epidurally on the lateral surface of the left bulb. Each rabbit was conditioned to respond to sniffing to an odor paired with cutaneous shock while receiving continuous intrabulbar infusion of either vehicle or propranolol (100 microM at 1 microliter/hr) in vehicle. After two training sessions to the original odor, a response to a new odor was conditioned under the influence of the alternate infusate. Electroencephalographic (EEG) activity was sampled on inspirations before and during odor presentations. During vehicle infusion a transient alteration in the pattern of activity was acquired that occurred during the second and third inspirations following presentation of the reinforced odor. The acquisition did not occur when propranolol was infused. No significant pattern changes occurred with unreinforced odors in either condition. There was no local anesthetic effect of the racemic mixture of propranolol found for any type of electric activity, including antidromic spike activity observed in an independent control group. Intrabulbar norepinephrine injection (100 microM, 10 microL) resulted in an amplitude increase of the bulbar 40-80-Hz EEG and a potentiation of the transient spatial pattern change to a novel odor, when compared with those observed during vehicle infusion. It is concluded that norepinephrine released under centrifugal control may act to prevent or delay habituation that otherwise occurs rapidly to unreinforced odors.

Plasma histamine concentration during propranolol induced bronchoconstriction.

The mechanism of propranolol induced bronchoconstriction in asthma is uncertain, as airway beta adrenoceptors are not innervated by sympathetic nerves and circulating adrenaline concentrations are not raised. Propranolol 10 mg was infused over 27 minutes in 14 subjects with mild asthma. Peak expiratory flow (PEF) decreased by 80-235 l/min (17-51% of baseline) in nine subjects, who were called "responders," and by less than 50 l/min (12% of baseline) in five "non-responders". These two groups did not differ in baseline ventilatory function or in any clinical characteristic. In "responders" mean PEF had decreased significantly from 440 to 390 l/min after infusion of propranolol 2.1 mg, though the maximum fall in PEF occurred during or within five minutes of the end of the infusion. In nine of the subjects (six "responders" and three "non-responders") the possibility that propranolol induced bronchoconstriction is due to blockade of mast cell beta receptors leading to increased mediator release was examined by measurement of plasma histamine concentration as an index of mast cell degranulation. There was no consistent change in plasma histamine concentration in either group. No evidence of increased mast cell mediator release has been found in association with propranolol induced bronchoconstriction.

Electromechanical delay in the intact dog heart

A computer method was developed for the determination of electromechanical delay defined as the time between the onset of Q-wave and the onset of the left ventricular systolic pressure rise. It was validated for heart catheterization studies on 56 intact anaesthetized beagle dogs in 86 sessions. The mean basal value of the electromechanical delay was 22 ± 4 msec. Heart rate, contractility, preload and afterload were changed by atrial pacing and by infusions of calcium chloride, isoproterenol, propranolol, dextran and phenylephrine. Increase of heart rate by pacing from the spontaneous rate of 90 per min to 240 per min prolonged the electromechanical delay from 21 ± 5 to 33 ± 14 msec ( P < 0.001). Otherwise the duration of electromechanical delay changed independently of the heart rate. If it changed, the direction of the change followed that of the pre-ejection period. Its proportion of the pre-ejection period varied from 26 to 52%. The electromechanical delay shortened when a positive inotropic effect was noticed or the presystolic fibre length increased.