Maximum Increase In Heart Rate Research Articles

HEART RATE RESPONSE TO AN I.V. TEST DOSE OF ADRENALINE AND LIGNOCAINE WITH AND WITHOUT ATROPINE PRETREATMENT

In order to evaluate the sensitivity of an adrenaline test dose for detecting intravascular injection and the effect of atropine pretreatment, 90 ASA physical status I and II patients were allocated randomly to two groups, to receive i.v. saline 1 ml (n = 46) or i.v. atropine 0.5 mg (n = 44). Five minutes later, all patients received an i.v. test dose of 2% lignocaine 3 ml with adrenaline 15 micrograms at a rate of 1 ml s-1. The groups were similar with respect to basal heart rate (HR). HR remained unchanged after saline injection, but increased slightly 5 min after atropine injection (mean 78 (SD 15) beat min-1 vs 87 (20) beat min-1 (P less than 0.05). After the test dose of lignocaine with adrenaline, HR increased significantly in both groups at 30 s, 1 and 2 min, and remained increased at 3 min in the atropine group. The maximum increase in HR was greater in the atropine group than in the saline group (31 (4) beat min-1 vs 26 (11) beat min-1 (P less than 0.05). However, when individual maximum HR changes are considered, five patients in the saline group and four in the atropine group had an increase less than or equal to 10 beat min-1, and three patients in the saline group had no change or a decrease in HR. Defining a positive result to a test dose as an increase in HR of greater than 10 beat min-1, the sensitivity of the adrenaline test dose was 83 (5.5)% in the saline group and 91 (3.5)% in the atropine group (ns).(ABSTRACT TRUNCATED AT 250 WORDS)

Microinjections of norepinephrine into the intermediolateral cell column of the spinal cord exert excitatory as well as inhibitory effects on the cardiac function

Cardiac responses to microinjections of norepinephrine (NE) into the intermediolateral column of the spinal cord (IML) at T 2 level were studied in pentobarbital-anesthetized, immobilized and artificially ventilated, male Wistar rats. For describing the effects of NE conveniently, the doses of NE were divided into two ranges. The small dose-range consisted of 20 nl volumes of 50, 75 and 100 micromolar (μM) solutions (i.e. 1, 1.5 and 2 pmole in 20 nl, respectively). The larger dose-range consisted of 20 nl volumes of 2.5, 25, 40 and 50 millimolar (mM) solutions (i.e. 0.05, 0.5, 0.8 and 1 nmole in 20 nl, respectively). Injections of small doses of NE (1–2 pmole) into the IML increased heart rate (HR); intravenous injections of these doses did not alter either blood pressure (BP) or HR. Larger doses of NE (0.05–1 nmole) elicited a decrease in HR; intravenous injections of these doses increased HR and BP. Maximum increase in HR was produced by injections of 1.5 pmole of NE into the IML; this effect was blocked by prior injections of prazosin (an α −1adrenergic receptor antagonist; 50 pmole) but not idazoxan (an α −2 adrenergic receptor blocker; 10 pmole) into the IML. Maximum decrease in HR was elicited by injections of 0.8 nmole of NE into the IML; this effect was blocked by idazoxan (10 pmole) but not prazosin (50 pmole). Microinjections of idazoxan (10 pmole) alone increased HR while prazosin (50 pmole) alone was ineffective. Intravenous injections of chlorisondamine (a ganglion blocker) blocked the increase in HR elicited by injections of 1.5 pmole of NE into the IML. Injections of NE, prazosin or idazoxan into the IML did not alter the responses to subsequent injections of glutamate at the same site. The effects of NE remained unchanged in midcollicular decerebrate rats. Vehicles in which NE, prazosin or idazoxan were dissolved, did not elicit a response when injected into the IML. Injections of NE outside the IML failed to elicit any response. These results suggest that NE may have a role to play as a neuromodulator/neurotransmitter in the IML. The pathways involved in these actions of NE in the IML remain to be identified.

Comparison of two esmolol bolus doses on the haemodynamic response and seizure duration during electro-convulsive therapy

Twelve ASA physical status I-III patients were enrolled in a double-blind, prospective, randomized, three-way, within-patient crossover study designed to determine the effect of two standard esmolol bolus doses (100 and 200 mg) on the haemodynamic response and seizure duration during electro-convulsive therapy (ECT). Esmolol or placebo was administered one minute prior to induction of anaesthesia and exactly two minutes before ECT. Both the 100 and 200 mg bolus doses significantly blunted the maximum increase in heart rate (HR) and mean arterial pressure (MAP) following ECT in comparison with placebo. Compared with placebo, esmolol 100 mg decreased maximum HR by 23 +/- 3%, maximum MAP by 17 +/- 7% and maximum rate-pressure product (RPP) by 40 +/- 9%. Esmolol 200 mg decreased maximum HR by 25 +/- 3%, maximum MAP by 19 +/- 3% and maximum RPP by 42 +/- 5%. No significant difference was found between the two esmolol doses at corresponding measurement points before and after ECT. Treatment with esmolol 200 mg resulted in a significantly shorter mean seizure duration than with placebo. As the 200 mg dose caused a shorter seizure duration and the haemodynamic effects of 100 mg and 200 mg doses were similar, it was concluded that the 100 mg esmolol bolus dose was the better dose for ECT.

Bolus doses of esmolol for the prevention of postintubation hypertension and tachycardia

This study was designed to determine the safety and efficacy of 100-mg and 200-mg bolus doses of esmolol in the prevention of intubation-associated hypertension, tachycardia, ST depression, and dysrhythmias. Forty-five patients undergoing noncardiac surgery were randomly allocated to receive either placebo, esmolol, 100 mg, or esmolol, 200 mg, intravenously, 90 seconds prior to intubation. Both doses of esmolol decreased the mean maximum increase in heart rate and rate-pressure product by approximately 36% [ P < 0.01 y placebo), and attenuated these increases over the first 90 seconds postintubation. No effect on blood pressure was observed. Ventricular dysrhythmias occurred in 7 of 15 patients following placebo versus 4 of 30 patients receiving esmolol [ P < 0.05). No difference in any variable was detected between the two esmolol groups at any time. The incidence of hypotension and bradycardia was no greater following esmolol than after placebo, nor was esmolol associated with cardiac conduction disturbances or wheezing. It was concluded that bolus doses of esmolol safely attenuate the hemodynamic response to intubation and decrease the incidence of ventricular dysrhythmias.

Esmolol Bolus and Infusion Attenuates Increases in Blood Pressure and Heart Rate During Electro-Convulsive Therapy

To determine whether a standardized dose of can effectively attenuate the cardiovascular response to electroconvulsive therapy (ECT), 17 ASA physical status I-II patients were studied in a randomized within-patient, crossover design. Each patient received esmolol during one ECT and three to five days later crossed over to the alternative treatment receiving an 80 mg bolus followed by 24 mg.min-1 infusion two minutes prior to induction of anaesthesia and continued for five minutes after induction. Esmolol blunted the maximum increases in heart rate (HR) by 26 per cent, mean arterial pressure (MAP) by 14 per cent, and rate pressure product by 37 per cent with significant differences (P less than 0.05) noted at one, two, three and four minutes after ECT (minutes five, six, seven, and eight of the infusion). There was no significant difference in seizure duration between the two groups and no adverse reactions occurred.

A single bolus dose of esmolol in the prevention of intubation-induced tachycardia and hypertension in an ambulatory surgery unit

The efficacy of a single bolus dose of esmolol in the prevention of intubation-induced tachycardia and hypertension was studied in a double-blind manner. Thirty patients, from the Ambulatory Surgery Unit at Rush-Presbyterian-St. Luke's Medical Center were prospectively randomized to receive a placebo, 100 mg of esmolol, or 200 mg of esmolol immediately prior to induction (2.5 to 3.0 minutes before intubation). The groups were similar in demographic characteristics and with regard to preoperative blood pressure (BP) and heart rate (HR). Anesthetic management was standardized for all patients. Fsmolol 100 mg (1.4 ± 0.3 mglkg) and 200 mg (2.6 ± 0.7 mglkg) significantly (p < 0.05) blunted the maximum increases in HR and BP following intubation. The average maximum HR increase in the placebo group was 40% as opposed to 16% in the esmolol 100 mg group and 14% in the esmolol 200 mg group. Both esmolol groups blunted the tachycardic response over a 4-minute postintubation time period. The average maximum BP increase was 47% in the placebo group versus 22% and 19% in. the esmolol 100 mg and esmolol 200 mg groups, respectively. There were no significant differences between the two esmolol groups. This study demonstrates the efficacy of a single bolus dose of esmolol in blunting the tachycardic and hypertensive responses to laryngoscopy and intubation in an ambulatory surgery setting.

Inotropic and Chronotropic Profile of MCI-154: Comparison with Isoproterenol and Imazodan in Guinea Pig Cardiac Preparations

Although recent studies indicate that MCI-154 exerts novel positive inotropic actions in heart muscle, the chronotropic properties of this new drug remain undefined. The present study compared the inotropic/chronotropic profile of MCI-154 with those of a nonselective beta 1/beta 2-agonist (isoproterenol, Iso) and a type III phosphodiesterase inhibitor (imazodan, CI-914) in cardiac preparations isolated from guinea pigs. The inotropic efficacy of MCI-154 was approximately equal to that of Iso and CI-194 in electrically paced (1 Hz) atrial muscle, with each agent increasing isometric contractile tension approximately 170% above basal (predrug) values. The inotropic EC50 for Iso (2.9 +/- 0.7 x 10(-9) M) was several orders of magnitude less than that for MCI-154 (1.4 +/- 0.4 x 10(-4) M) and CI-914 (1.1 +/- 0.2 x 10(-4) M). The inotropic potency of MCI-154 was equivalent in atrial and left ventricular myocardium. Both Iso and CI-194 substantially increased spontaneous beating frequency of sinoatrial preparations, and the inotropic/chronotropic potency ratio for each was unity. In contrast, MCI-154 exerted a slight negative chronotropic action on basal sinoatrial rate. Moreover, the negative chronotropic influence of MCI-154 was increased several-fold in the presence of Iso-stimulated maximal increases in heart rate (HR), and this inhibitory chronotropic action of MCI-154 was not prevented by muscarinic receptor blockade with atropine. These findings indicate that MCI-154 has a unique inotropic/chronotropic profile in cardiac tissues of guinea pigs in that this drug (a) efficaciously increased myocardial contractility, (b) had minimal effect on basal sinoatrial automaticity and yet (c) markedly inhibited sympathetically mediated sinus tachycardia.

The Effect of Advancing Age on the Sympathetic Response to Laryngoscopy and Tracheal Intubation

The effect of aging on the hemodynamic and sympathetic response to tracheal intubation was evaluated in 27 patients aged 18 to 80 years, ASA Class I and II, given atropine 0.4 mg and diazepam 10 mg as premedication and thiopental, 4.0 mg/kg, and succinylcholine 100 mg for anesthesia induction. Laryngoscopy and tracheal intubation was performed 60 seconds after induction. The elderly had significantly less chronotropic response to intubation 2, 3, 4, and 5 minutes after induction so that the maximum increase in heart rate above awake values was negatively correlated with age (R = -0.66, P less than 0.001). Baseline systolic blood pressure (SBP) and mean BP increased significantly with age (R = 0.81, P less than 0.001 and R = 0.76, P less than 0.001, respectively) but age was not significantly related to increases in SBP and mean BP following intubation. Baseline plasma norepinephrine (NE) levels increased with age ( R = 0.51, P less than 0.01). Following intubation, mean plasma NE concentrations were significantly higher in elderly patients than young patients, despite the diminished heart rate response. Heart rate (HR) per pg/ml of NE, a measure of cardiac sensitivity to beta stimulation, was therefore significantly less 2, 3, and 4 mins after induction in elderly patients than in younger patients. To determine if this alteration in cardiac sensitivity to endogenous catecholamines was reflected by changes in beta receptor function on lymphocytes, beta receptor density and the proportion of receptor binding agonist with high affinity (%RH) were measured. No significant correlation between beta-receptor affinity for agonist, %RH, or receptor density was found with age, HR, or HR per pg/ml NE.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma Elimination of Milrinone in Rats in Relation to Its Hemodynamic Effects

Milrinone (1, 6-dihydro-2-methyl-6-oxo[3, 4′-bipyridine]-5-carbonitrile) is a cardiotonic drug, currently under clinical investigation for the treatment of congestive heart failure.Its positive inotropic properties and its strong vasodilative action contribute to a favorable therapeutic effect. Plasma elimination of milrinone is generally by renal excretion of the unchanged drug. Since hemodynamic effects might influence the pharmacokinetics of renally eliminated drugs, we have investigated the plasma elimination of milrinone after different iv bolus doses of the compound in healthy rats. Half-times were 20.6 ± 5.5 min (0.3 mg/kg milrinone), 17.0 ± 1.8 min (1.0 mg/kg), 31.4 ± 4.5 min (3.0 mg/kg), and 95.5 ± 18.4 min (10.0 mg/kg). Clearances of milrinone showed a positive correlation with doses. Hemodynamic effects were dose dependent and (plasma) concentration dependent, and the maximum decrease in diastolic blood pressure was 54.5 ± 0.5 mmHg. The half-effective plasma concentration of milrinone was 1.0 ± 0.2 μM. The maximum increase in heart rate was 15%. We conclude that milrinone plasma elimination in rats is dose dependent, probably resulting from its strong vasodilator properties.

Single doses of ritodrine delay orocaecal transit in patients with irritable bowel syndrome.

The lactulose hydrogen breath test was used to assess the effect of a single dose of the beta 2-adrenoceptor agonist ritodrine on orocaecal transit time in 11 patients (three men) with irritable bowel syndrome. Transit time (median values, range) was significantly longer (P less than 0.01) after ritodrine than after placebo (120, 50-200 vs 75, 40-100 min). Median heart rate was similar before treatments whereas the maximal increase in heart rate was significantly greater (P less than 0.01) after ritodrine than after placebo.

Central mechanisms of action involved in cocaine-induced tachycardia

The present study was designed to determine the central effects of cocaine on heart rate and blood pressure in Wistar Kyoto rats (WKY) and to evaluate mechanisms involved in the response. Cocaine (0.025 – 4 mg/kg) was administered to unanesthetized, unrestrained rats via a cannula placed into the lateral ventricle. Procaine (0.1 and 4 mg/kg) was also administered centrally. Cocaine did not significantly alter blood pressure at doses of 0.025, 0.1, or 0.5 mg/kg, icv. Only the highest dose, 4 mg/kg, icv produced a significant pressor response. Cocaine produced significant dose-dependent tachycardia, with the maximum increase in heart rate occurring within 5 min. Procaine (4 mg/kg, icv) produced tachycardia, but the effect was significantly less than that produced by cocaine (4 mg/kg, icv). Cocaine also produced tachycardia at a dose of 0.1 mg/kg, but procaine did not significantly alter heart rate at the same dose. Central phentolamine pretreatment (0.1 mg/kg, icv) significantly attenuated the increase in heart rate produced by cocaine. These results indicate that the centrally mediated tachycardia produced by cocaine is partly due to its local anesthetic activity and to indirect stimulation of α receptors.

Randomized, Double-Blind Trial of Midazolam and Diazepam for Endoscopic Sedation in Children

We performed a prospective, randomized, double-blind study of 41 children (6-18 years of age) who were undergoing esophagogastroduodenoscopy (EGD) to compare the efficacy of diazepam and midazolam with respect to quality of sedation and amnesia. The endoscopist assessed the patients for control of salivation, gag reflex, vomiting and cooperation after intravenous injection of either 0.1-0.15 mg/kg of midazolam or 0.2-0.4 mg/kg of diazepam. The patients answered a questionnaire at 1 and 24 h after the procedure to assess recall of procedure details, pain and/or discomfort, and their medication choice for future procedures. Vital signs were monitored for 1 h after injection. Although midazolam caused greater mean maximum increase in heart rate than diazepam (30 vs. 14/min), no difference was found between the two treatment groups with respect to other vital signs. There was also no difference in physician's assessment or patient recall of specific events during the procedure. However, significantly fewer patients recalled pain or discomfort with midazolam at both 1 and 24 h following the procedure (p = 0.02). In addition, more patients receiving midazolam indicated preference for the same sedation for future procedures. We conclude that midazolam may provide better amnesia in children undergoing endoscopic procedures.

Drug plasma levels and coronary vasodilation after isosorbide dinitrate chewing capsules

Five, ten and fifteen min after sublingual administration of 10mg isosorbide dinitrate (ISDN) in chewing capsules, in 10 patients with coronary artery disease, ISDN plasma levels were correlated with the dilation of epicardial coronary arteries as well as with changes in aortic blood pressure and heart rate. Due to the rapid and extensive drug absorption, maximal ISDN plasma levels averaged 138 +/- 73 ng ml-1 and were already obtained after 5 min; they declined to 102 +/- 76 and 62 +/- 34 ng ml-1 in the 10th and 15th min respectively. In 7 patients isosorbide mononitrate plasma levels were still negligibly low (less than 30 ng ml-1). Mean diameters of 'normal' coronary segments increased by an average of 20 +/- 10%, 26 +/- 11% and 27 +/- 13% (P less than 0.001) at 5, 10 and 15 min respectively compared to control. The maximal drop in systolic aortic pressure (147 +/- 19 to 115 +/- 15 mmHg; P less than 0.01) as well as the maximal increase in heart rate (66 +/- 4 to 80 +/- 11 beats min-1; P less than 0.01) were observed in the 15th min; diastolic aortic pressure and double product remained constant. Due to the long persistence of coronary dilation and haemodynamic changes, none of these drug effects correlated significantly with the ISDN plasma levels. In addition, the minimal diameters of 10 coronary stenoses were measured in 7 patients; with ISDN 7 stenoses showed dilation ranging from 23% to 98%.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular responses to a newly developed phosphodiesterase inhibitor, DN-9693 (7-pyperidinyl-1,2,3,5-tetrahydroimidazo (2,1-b)-quinazolin-2-oneHCl) in dog cross-circulated atrial and ventricular preparations.

The cardiovascular effects of DN-9693, a newly synthesized cyclic AMP phosphodiesterase inhibitor, and sulmazole were investigated in an isolated right atrial or left ventricular preparation which was cross-perfused with blood from another support dog. Each substance dose-dependently increased heart rate and decreased blood pressure of the support dog when administered i.v. The hypotensive effects of DN-9693 were about 40 times more potent than those of sulmazole. The positive chronotropic effect of DN-9693 was about 10 times more potent, but the maximal increase in heart rate was much less than that produced by sulmazole. Each substance dose-dependently increased the sinus rate, the right atrial and the left ventricular developed tension in isolated preparations when administered selectively into cannulated arteries. The effects of DN-9693 were about 10-30 times more potent than those of sulmazole, although the maximal positive chronotropic response to DN-9693 was significantly smaller. Positive chrono- and inotropic effects induced by both substances in the isolated, blood-perfused right atrial preparation were not inhibited by treatment with propranolol, but they were consistently attenuated by electrical stimulation of intramural vagal nerve fibers. These results suggest that DN-9693 and sulmazole produce cardiotonic effects by directly increasing the cyclic AMP level in the dog heart. DN-9693 possesses more potent cardiotonic and vasodilating effects than sulmazole, and has a smaller effect on heart rate.

Noncoordinate regulation of cardiac Gs protein and beta-adrenergic receptors by a physiological stimulus, chronic dynamic exercise.

We used a physiological stimulus, chronic dynamic exercise, in pigs to examine resultant changes in chronotropic responsiveness to catecholamine and biochemical features of cardiac beta-adrenergic receptors and the stimulatory guanine nucleotide-binding protein, GS. Long-term treadmill running resulted in a substantial (44%) down-regulation of right atrial beta-adrenergic receptors, but the dose of isoproterenol yielding a 50% maximal increase in heart rate was decreased by 57% (from 0.07 +/- 0.03 to 0.03 +/- 0.01 microgram/kg; P less than 0.02) despite this decrease in receptor number. This disparity between receptor number and physiological responsiveness suggested altered signal transduction. We therefore quantitated GS in myocardial membranes obtained before and after chronic exercise in a competitive ELISA based on an antipeptide antibody developed to the alpha S portion of GS. We found a 42% increase in the amounts of GS in right atrial membranes (from 11.4 +/- 0.8 to 16.2 +/- 2.0 pmol/mg; P less than 0.05) and a 76% increase in the amounts of GS in left ventricular membranes (from 15.6 +/- 2.6 to 27.4 +/- 5.2 pmol/mg; P = 0.02) after chronic running. These data suggest that in the heart physiological perturbations can result in changes in the levels of GS, that GS and beta-adrenergic receptor number are not coordinately regulated, and that GS may contribute to altered adrenergic responsiveness independently of changes in beta-adrenergic receptor number.

The influence of infusion rate on the pharmacokinetics and haemodynamic effects of nisoldipine in man.

1. The pharmacokinetics and haemodynamic effects of nisoldipine on long term i.v. infusion of 2.40 mg and 9.59 mg in 25 h were studied in six healthy subjects. Liver blood flow at 0.8 and 24 h was assessed by measuring indocyanine green (ICG) clearance. 2. After high-dose nisoldipine, systemic clearance was 0.99 +/- 0.16 1 min-1, volume of distribution was 5.8 +/- 1.5 1 kg-1 and elimination half-life was 10.7 +/- 2.4 h. The pharmacokinetic parameters were similar after low-dose nisoldipine. 3. No significant changes in apparent liver blood flow were observed after either high-dose or low-dose nisoldipine. 4. Systolic blood pressure did not change, whereas diastolic blood pressure decreased by approximately 10% during both treatments. Maximal increase in heart rate was approximately 37% at high-dose infusion, whereas this was one half lower during the low-dose regimen. 5. Increased infusion rate results in an unfavourable shift in the haemodynamic effect profile of nisoldipine.

Combined effects of 5-hydroxytryptamine and filling pressure on the isolated heart of the lobster,Panulirus japonicus

1. The effects of a pericardial neurohormone, 5-hydroxytryptamine (5-HT), were investigated on the isolated and pumping heart of the spiny lobsterPanulirus japonicus. 2. Under low filling pressure, 5-HT (1–1000 nM) increased the rate and amplitude of heartbeat in a dose-dependent manner. 3. When filling pressure was raised, the first systolic contraction (FSC) was greatly enhanced while the second systolic contraction (SSC) was reduced or eliminated. Increased SSC by 5-HT was dose-dependent while the increase in FSC was mild. The maximum increase in heart rate by 5-HT was below 1 Hz though higher pressures increased the rate above 1 Hz. 4. A combination of 5-HT and pressure acted synergistically on heart rate and amplitude. The degree of increase in both rate and FSC by this synergistic action decreased with increasing pressure. The combined actions on SSC were related to a facilitated increase of beat amplitude. 5. 5-HT increased the burst rate of cardiac ganglion cells without decreasing burst duration. 5-HT also increased firing frequency even in divided ganglia. In the divided ganglion, the effects of 5-HT on large cells were mild while the actions on small cells were strong. 6. 5-HT enhanced slow sustained potentials, which drive impulse bursts of the ganglion cells. 5-HT had no effect on junction potentials evoked in cardiac muscle cells. Therefore, enhancement of sustained potentials is related to the augmentation of FSC and SSC.

Tracheal versus intravenous atropine

Atropine 600 micrograms was given either intravenously or intratracheally and the change in heart rate noted in a double-blind, randomised study of 40 anaesthetised patients. There was no significant difference between the two groups in the maximum increase in heart rate, 20.3 beats/minute in the tracheal compared to 21.4 beats/minute in the intravenous group. However, the maximum increase occurred significantly earlier in the tracheal group, 45.5 seconds after administration compared to 95.5 seconds in the intravenous group (p less than 0.01, 95% confidence interval 36.8-63.2 seconds). This study supports the clinical observation that tracheal and intravenous atropine are equally effective and suggests that the trachea should be the route of choice when a rapid response is required.

Decreased exercise heart rate and blood pressure response in diabetic subjects with cardiac autonomic neuropathy.

Abnormal hemodynamic responses to exercise have been observed in diabetic subjects, but the pathogenesis and significance remain uncertain. We used maximal treadmill exercise to study 32 subjects with long-term insulin-dependent diabetes without clinical evidence of cardiac disease. Two of the 32 had occult ischemic heart disease revealed by stress electrocardiography and myocardial-perfusion scintigraphy and were excluded from subsequent analysis. In the remaining 30 subjects, we compared the responses to exercise of the 17 subjects with cardiac autonomic neuropathy diagnosed by noninvasive maneuvers (group 1) with the 13 without (group 2). At rest, the pressure-rate product (PRP) was higher in group 1 (114.0 +/- 5.7 vs. 95.9 +/- 5.3, P less than .05). With maximal exercise the increase in heart rate (44.6 +/- 4.8 vs. 79.0 +/- 5.4 beats/min, P less than .001), systolic blood pressure (36.8 +/- 5.9 vs. 55.0 +/- 5.8 mmHg, P = .02), and the PRP (102.0 +/- 7.3 vs. 182.0 +/- 8.2, P less than .001) were all lower in group 1 than in group 2, despite similar total treadmill times (631 +/- 47 vs. 587 +/- 40 s, P greater than .1). At each stage of exercise, the increase in heart rate and systolic blood pressure was lower in group 1 patients. The severity of cardiac autonomic neuropathy correlated inversely with the maximal increase in heart rate (r = -.68, P less than .001) and the PRP (r = -.58, P less than .005). Age, duration of diabetes, and the presence and severity of microvascular disease did not correlate with any of the hemodynamic parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduced chronotropic responsiveness of the heart in experimental uremia.

Cardiac beta-adrenoceptor responsiveness was evaluated in experimental uremia by in vivo and in vitro techniques. Uremia was induced in rats by bilateral nephrectomy for 48 h. In rats with chronic intra-arterial and intravenous catheters, cardiovascular reflexes and the renin-angiotensin system were blocked with atropine, pentolinium, and a converting-enzyme inhibitor, respectively. Blood pressure (BP) and heart rate (HR) were continuously recorded. Cumulative doses of isoproterenol were injected intravenously. In uremic rats, the dose-response curve for the HR response showed a lower maximal response (P less than 0.01) and no significant difference in 50% effective dose values compared with controls, whereas the BP decrease caused by isoproterenol was similar in control and uremic rats. When forskolin was injected intravenously to stimulate adenylate cyclase in a receptor-independent manner, the maximal HR increase was lower in uremic rats (P less than 0.01). beta-Adrenoceptor density and affinity, measured by 125I-cyanopindolol binding to sarcolemmal membranes, was not different between control and uremic rats. Also binding affinities for the agonist isoproterenol were not different between groups. Basal adenylate cyclase activity, as well as activity after maximal stimulation by isoproterenol and by forskolin were lower in uremic than in control rats (P less than 0.01). The results show that the chronotropic response of the heart is reduced in uremia. Such hyporesponsiveness may be due, at least in part, to a reduced activity of cardiac adenylate cyclase.