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PubMed2006

Restrictive hemodynamics are present at the time of diagnosis of allograft coronary artery disease in children.

Clinical recognition of allograft coronary artery disease (ACAD) is challenging. We examined whether right heart hemodynamics can aid its diagnosis in pediatric recipients. We retrospective analyzed hemodynamic data of recipients with ACAD versus age and date-of-transplant matched controls. From 1982-2001, 18 cases fulfilled study entry criteria. Median age at transplant was 12 years for subjects and 8 years for controls. Median time to diagnosis of ACAD was 65 months (14.5-124 months) and 67 months (16-140 months) to arteriography for controls. The median right ventricular end-diastolic pressure (RVEDP) at diagnosis was 11.0 vs. 6.0 mmHg for controls (p = 0.003). Pulmonary capillary wedge pressure (PCWP) at diagnosis was 14.0 vs. 8.0 mmHg for controls (p = 0.001). When subdivided by severity of ACAD, the difference was greater in the moderate/severe group. Compared to the previous catheterization (median interval 10 months for subjects, 12.0 for controls ), there was an increase of 4.0 mmHg in RVEDP in ACAD subjects (n = 13, p = .003) versus 0 mmHg in controls (p = 0.042), and an increase in PCWP of 5.5 in subjects (p = .002) versus 0 mmHg in controls (p = 0.066). The presence of elevated filling pressures plus an interim increase should alert to the presence of ACAD and help guide further investigation.

Atrial Function, Right↗
PubMed2002

Evaluation of bi-atrial pacing and single site right atrial pacing for the prevention of atrial fibrillation.

Atrial resynchronization resulting from simultaneous pacing of the atria may adjust inter- or intra-atrial asynchrony and prevent atrial fibrillation (AF). The purpose of this study was to assess the efficacy of bi-atrial pacing (BAP) in preventing AF, and the safety of this system. The effect of BAP was compared with single site right atrial pacing (RAP) in 6 patients with sick sinus syndrome and paroxysmal AF in a prospective switchover trial. P wave duration was significantly reduced during BAP (p<0.01). Pacing threshold, atrial wave amplitude and the lead impedance presented no significant differences at implant, 1 week and 3 months after implantation, respectively (NS). The number of AF episodes significantly decreased during both RAP and BAP compared with the control (p<0.01). Although the number of premature atrial contractions was significantly less during BAP than RAP (p<0.05), there were no significant differences of AF episodes between the two. The percentage of pacing was achieved in only 70% during both pacing modes. BAP was safe and reliable in this follow-up period and can prevent AF. These findings provide encouragement for further study and observation of BAP to prevent AF.

Aged↗
PubMed2001

Optical mapping of activation patterns in an animal model of congenital heart block.

Congenital heart block (CHB) is associated with high mortality and affects children of mothers with autoantibodies (IgG) to ribonucleoproteins SSB/La and SSA/Ro. IgG from mothers of children with CHB (positive IgG) was used to assess activation patterns in both the right atrium (RA) and right ventricle (RV) of Langendorff-perfused young rabbit hearts. Optical action potentials (AP) were obtained by using a 124-site photodiode array with 4-[-[2-(di-n-butylamino)-6-naphthyl]vinyl]pyridinium. Optical APs were recorded to simultaneously image activation patterns from the RA and RV. Perfusion of positive IgG (800--1,200 micro resulted in sinus bradycardia and varying degrees of heart block. Activation maps revealed marked conduction delay at the sinoatrial junction but only minor changes in overall atrial and ventricular activation patterns. No conduction disturbances were seen in the presence of IgG from mothers with healthy children. In conclusion, besides atrioventricular (AV) block, positive IgG induces sinus bradycardia. These results establish that the sequelae of CHB are associated with impaired intrasinus and/or sinoatrial conduction. The findings raise the possibility that sinus bradycardia in the developing heart may indicate the potential for AV conduction disturbances.

Action Potentials↗
PubMed2003

Global dispersion of right atrial repolarization in healthy pigs and patients.

OBJECTIVE: To investigate the feasibility of monophasic action potential (MAP) mapping using an electroanatomical mapping system (CARTO) in obtaining information on global dispersion of atrial repolarization and to evaluate the role of dispersion of repolarization in the genesis of paroxysmal atrial fibrillation (PAF). METHODS AND RESULTS: Right atrial MAPs were recorded from 53 +/- 18 sites in 10 healthy pigs and 33 +/- 21 sites in 6 patients with and 4 patients without history of PAF. In pigs, the global dispersions of activation time (AT), MAP duration and end of repolarization time (EOR), 70 +/- 8, 95 +/- 18 and 121 +/- 28 ms, respectively, were significantly greater than those among 10, 20 and 30 sites. In patients with PAF, the global dispersions of MAP duration and EOR (128 +/- 10 and 149 +/- 31 ms) were significantly greater than those in patients without PAF (84 +/- 10 and 91 +/- 17 ms). CONCLUSION: MAP mapping using the CARTO system was feasible in experimental and clinical settings in obtaining information on global dispersion of atrial repolarization. The number of recording sites could significantly affect repolarization parameters. The dispersions of atrial repolarization were significantly greater in patients with PAF than those without, suggesting the involvement of an increased dispersion of repolarization in the genesis of PAF.

Action Potentials↗
PubMed1999

Atrial involvement in patients with progressive systemic sclerosis: relationship between ultrasonic tissue characterization of the atrium and interatrial conduction.

OBJECTIVE: The aim of this study was to assess atrial lesions using ultrasonic tissue characterization and to determine the contribution of atrial lesions to the interatrial electromechanical coupling conduction time in patients with progressive systemic sclerosis (PSS). METHODS: Twenty patients with PSS and 20 age-matched healthy controls were evaluated. The cyclic variation in integrated backscatter value (CV-IB) was measured at the interatrial septum (IAS) from apical four chamber view. M-modes of ventricular long axis motion along with phono- and electrocardiograms were recorded simultaneously at the right lateral (RT) and left lateral (LT) sites of the atrioventricular (AV) rings and central fibrous body (CFB) in the apical four-chamber view. Intervals from the P wave on ECG to the echocardiographic onset of atrial contraction as a point of inflection in long axis M-mode echocardiogram were measured at the RT and LT sites of AV rings and CFB (P-RT, P-LT, P-SEP, respectively). Interatrial electromechanical coupling conduction time was determined as [(P-LT) - (P-RT)]. RESULTS: In patients with PSS compared to normal controls, P-RT, P-SEP, P-LT, and interatrial conduction time were greater, while CV-IB in IAS decreased. Furthermore, CV-IB in IAS correlated well with interatrial conduction time (r = 0.7, p < 0.01) in patients with PSS. CONCLUSIONS: Interatrial electromechanical coupling times may be prolonged due to atrial tissue damage in patients with PSS.

Adult↗
PubMedDate not supplied

Measurements of hindlimb blood flow recorded using Doppler ultrasound during administration of vasoactive agents in halothane-anesthetized horses.

The purpose of the study was to determine the ability of Doppler ultrasound to detect changes in femoral blood flow during pharmacologic manipulation of arterial blood pressure. Doppler ultrasonography was performed in the femoral vessels of six halothane-anesthetized horses before and during administration of phenylephrine HCI and sodium nitroprusside. The time-averaged mean velocity and volumetric flow were calculated. The contour of the velocity waveform was assessed, and the early diastolic deceleration slope (EDDS) and pulsatility index (PI) were calculated. Administration of phenylephrine HCI resulted in increased mean aortic blood pressure (MABP) by 40% (29.3-53.0%). This caused significant decrease in cardiac output (26.8 to 13.5 l/min), femoral arterial velocity (left artery 7.20 to 4.00 cm/s; right artery 5.01 to 3.39 cm/s) and volumetric flow (left artery 556 to 221 ml/min; right artery 397 to 193 ml/min) in the femoral vessels and significant increase in systemic vascular resistance (163 to 433 dyn-s/cm5), EDDS (1a: 285 to 468: ra: 250 to 481) and PI (1a: 9.38 to 20.4; ra 17.1 to 29.1). Administration of sodium nitroprusside resulted in a decreased MABP of 27.2% (22.5-33%). This increased cardiac output (20.8 to 32.4 L/min), however, no significant changes were observed in femoral blood flow. Despite obvious changes in the waveform contour, no significant change occurred in EDDS or PI. These results suggest that Doppler ultrasound may be useful for measuring femoral blood flow in anesthetized horses. However, waveform analysis appears to be limited when multiple changes occur in central and peripheral haemodynamics.

Anesthetics, Inhalation↗
PubMed1992

Prediction of permanent atrial sensing by preoperative esophageal atrial wave evaluation.

Atrial undersensing is a common problem in permanent atrial and dual chamber pacing. The purpose of this study was to evaluate the relationship between transesophageal atrial wave (EsAW) and right atrial endocavitary (RA). Forty-seven patients 72 +/- 9.7 years of age, with symptomatic bradyarrhythmias were studied. The EsAW was filtered with a high pass filter of 10 Hz (Arzco preamplifier-filter), using 1, 2, and 3 cm bipolar transesophageal catheters. Atrial bipolar floating 1, 2, and 3 cm electrograms from the high RA (HRA) and from the mid RA (MRA), as well as unipolar electrograms from the right auricle (RAUR) were recorded 1 day later. Comparison by paired t-test showed no significant differences between EsAW and bipolar sensing in RA, but significant differences between EsAW and RAUR (P = 0.0001). The results of the Spearman correlation coefficient for sensing (mV) for EsAW, HRA, and MRA, respectively, were: 1 cm, 1.8 +/- 0.9, 1.7 +/- 0.9, and 1.9 +/- 0.9 (z > 3.5; P < 0.0003); 2 cm, 2.2 +/- 0.9, 1.9 +/- 0.8, and 2.1 +/- 0.9 (z > 2.3; P < 0.03); 3 cm, 2.1 +/- 1, 2 +/- 0.9, and 2.2 +/- 1.0 (z > 2.9; P < 0.003); and the result for the monopolar RAUR was 3.0 +/- 1.0 (z < 1.4; P > 0.17). These findings, if confirmed in more patients, indicate that preoperative EsAW recording could be useful in estimating the quality of bipolar floating electrograms from the RA but not of unipolar RAUR.

Aged↗
PubMed1996

Comparison of isoflurane, halothane and fentanyl in patients with decreased ejection fraction undergoing coronary surgery.

The aim of the study was to compare three anaesthetic agents in patients with ejection fraction below 0.40 subjected to coronary revascularization surgery. Twenty five elective coronary surgical patients with ejection fraction below 0.40 were prospectively studied. Premedication was pethidine 1 mg/kg and induction was fentanyl 0.03 mg/kg and pancuronium 0.1 mg/kg. The patients were randomized to one of three maintenance techniques (fentanyl, isoflurane or halothane). Radial arterial pressure, heart rate, right atrial pressure, pulmonary arterial and occluded pressures, and thermodilution cardiac output were measured, and cardiac index and resistance calculated, at the following times: before induction; 5 min after intubation; 2 min after sternotomy; immediately after discontinuation of bypass; 15 min afterwards; immediately after sternal closure; during suture of the skin; 5 min after arrival in the postoperative care unit; and 60 min postoperatively. Mean arterial pressure decreased significantly in the isoflurane group and nonsignificantly in the halothane group after induction. Cardiac index decreased significantly in the isoflurane group and nonsignificantly in the halothane group after induction and after sternotomy. Neither pressure nor flow decreased in patients receiving fentanyl. Following weaning from cardiopulmonary bypass, systemic vascular resistance decreased significantly in all groups. Cardiac index, however, did not increase above control values and arterial pressure consequently decreased; there was no significant difference between groups.

Adjuvants, Anesthesia↗
PubMed2000

Inotropic, chronotropic, and dromotropic effects mediated via parasympathetic ganglia in the dog heart.

Some parasympathetic ganglionic cells are located in the epicardial fat pad between the medial superior vena cava and the aortic root (SVC-Ao fat pad) of the dog. We investigated whether the ganglionic cells in the SVC-Ao fat pad control the right atrial contractile force, sinus cycle length (SCL), and atrioventricular (AV) conduction in the autonomically decentralized heart of the anesthetized dog. Stimulation of both sides of the cervical vagal complexes (CVS) decreased right atrial contractile force, increased SCL, and prolonged AV interval. Stimulation of the rate-related parasympathetic nerves to the sinoatrial (SA) node (SAPS) increased SCL and decreased atrial contractile force. Stimulation of the AV conduction-related parasympathetic nerves to the AV node prolonged AV interval. Trimethaphan, a ganglionic nicotinic receptor blocker, injected into the SVC-Ao fat pad attenuated the negative inotropic, chronotropic, and dromotropic responses to CVS by 33 approximately 37%. On the other hand, lidocaine, a sodium channel blocker, injected into the SVC-Ao fat pad almost totally inhibited the inotropic and chronotropic responses to CVS and partly inhibited the dromotropic one. Lidocaine or trimethaphan injected into the SAPS locus abolished the inotropic responses to SAPS, but it partly attenuated those to CVS, although these treatments abolished the chronotropic responses to SAPS or CVS. These results suggest that parasympathetic ganglionic cells in the SVC-Ao fat pad, differing from those in SA and AV fat pads, nonselectively control the atrial contractile force, SCL, and AV conduction partially in the dog heart.

Animals↗
PubMed1997

Electrical and mechanical modulations by oxygen-derived free-radical generating systems in guinea-pig heart muscles.

The effects of free-radical generating systems and angiotensin-converting enzyme (ACE) inhibitors on the action potentials and contractile force in guinea-pig cardiac muscles were examined using conventional microelectrode and whole-cell voltage-clamp methods at 36 degrees C. Hydrogen peroxide (30-100 microM) prolonged 50%, 75% and 90% repolarization of action-potential duration (APD) approximately 15-25 min after its application. But the longer exposure reversed the APD shortening in a concentration-dependent manner. Other action-potential parameters were not altered to a significant extent. The contractile force was increased. Longer exposure inhibited the enhanced force (but it was still larger than control). The effects on the spontaneous action potential from right atrial muscle were almost the same. In whole-cell voltage-clamp experiments, H2O2 (100 microM) inhibited L-type Ca2+ current and enhanced delayed rectifier K+ current. The effects of light-activated rose bengal (10-100 nM) on the APD were similar to, but more potent than, those of H2O2. The response was observed rapidly after a light illumination. During exposure to rose bengal (100 nM), abnormal spontaneous action potentials or arrhythmias such as a bigeminy occurred, presumably because of early and delayed afterdepolarizations. The responses were irreversible. At 300 microM ACE inhibitors, captopril and enalapril, protected the changes induced by these free radicals. These results indicate that H2O2 has a dual, time-dependent, action on the APD and rose bengal with light illumination produced the responses rapidly. The oxygen-derived free radicals increased [Ca]i and then cellular Ca2+ overload occurred. These responses were protected by ACE inhibitors.

Action Potentials↗
PubMed2006

Non-Newtonian blood flow in human right coronary arteries: transient simulations.

This study looks at pulsatile blood flow through four different right coronary arteries, which have been reconstructed from biplane angiograms. A non-Newtonian blood model (the Generalised Power Law), as well as the usual Newtonian model of blood viscosity, is used to study the wall shear stress in each of these arteries over the entire cardiac cycle. The difference between Newtonian and non-Newtonian blood models is also studied over the whole cardiac cycle using the recently generalised global non-Newtonian importance factor. In addition, the flow is studied by considering paths of massless particles introduced into the flow field. The study shows that, when studying the wall shear stress distribution for transient blood flow in arteries, the use of a Newtonian blood model is a reasonably good approximation. However, to study the flow within the artery in greater detail, a non-Newtonian model is more appropriate.

Atrial Function, Right↗
PubMed1994

Assisted circulation without systemic heparinization.

The need for improvements in materials and equipment for extracorporeal circulation has been obvious for years. Among the surfaces with biologically active compounds, those with heparin binding have been found sufficiently thromboresistant and particularly suitable for different types of artificial perfusion. Partial left heart bypass (LHBP) was performed in 10 anesthetized, acutely instrumented, and open-chested mongrel dogs (weight 23 to 50 kg) with a servo-controlled roller pump. The pump flow was maintained at 50 mL/kg/min for 6 hours. Heparin surface-coated equipment was used without additional heparin. For LHBP with a standard circuit, the total amount of heparin during the study period was (mean +/- SD) 487 +/- 124 IU/kg. The right atrial, pulmonary artery, and left ventricular end-diastolic pressures, cardiac output, left ventricular output, right and left ventricular stroke work, pulmonary gas exchange, and acid-base balance changed similarly with both systems. Blood loss (204 +/- 78 v 1,240 +/- 586 mL, P < 0.0005), volume substitution requirements (647 +/- 48 v 1,860 +/- 764 mL, P < 0.0025), and oxygen extraction ratio (mean 25.4 to 32.0 v 25.4 to 56.4%, P < 0.025) were significantly lower, and mean aortic pressure (mean 65 to 69 v 62 to 38 mmHg, P < 0.025) and hemoglobin concentration (mean 9.1 to 8.1 v 9.4 to 3.9 g/dL, P < 0.05) were significantly higher during 6 hours of LHBP without systemic heparinization. Low but stable oxygen delivery was provided with heparin-coated LHBP, whereas it showed a descending trend (mean 14.0 to 10.8 v 13.4 to 5.5 mL/kg/min, P < 0.1) with the standard circuit.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2001

The in vitro effects of remifentanil, sufentanil, fentanyl, and alfentanil on isolated human right atria.

Because some clinical studies have suggested that opioids used in anesthesia may have different deleterious hemodynamic effects, we compared the direct myocardial effects of cumulative concentrations of remifentanil, sufentanil, fentanyl, and alfentanil on inotropic and lusitropic variables of isolated human myocardium in vitro. Human right atrial trabeculae, obtained from patients scheduled for coronary bypass surgery or aortic valve replacement, were suspended vertically in an oxygenated (95% oxygen/5% CO(2)) Tyrode's modified solution ([Ca(2+)](o) = 2.0 mM, 37 degrees C, pH 7.40, stimulation frequency 1 Hz). The effects of cumulative concentrations (10(-11), 10(-10), 10(-9), 10(-8), 10(-7), and 10(-6) M) of remifentanil (n = 8), sufentanil (n = 8), fentanyl (n = 8), and alfentanil (n = 8) on inotropic and lusitropic variables of isometric twitches were measured. Remifentanil, sufentanil, and fentanyl did not modify active isometric force and peak of the positive force derivative as compared with the Control group. Alfentanil induced a dose-dependent decrease in active isometric force and peak of the positive force derivative. This effect was abolished in the presence of [Ca(2+)](o) = 4.0 mM. None of these opioids altered lusitropic variables.

Aged↗
PubMed1996

Exercise induced sympathetic influences do not change interatrial conduction times in VDD and DDD pacing.

Using telemetry, right atrial electrogram (RA), and marker channel of atrial sense events (MA) in combination with the left atrial electrogram (LA), recorded by a filtered bipolar esophageal lead, interatrial conduction during submaximal exercise and at rest was examined in 46 DDD pacemaker patients. The RA-LA and MA-LA conduction times measured in the presence of atrial sensing (VDD) as well as the conduction time SA-LA from atrial stimulus (SA) to LA, determined during atrial pacing (DDD) were found to be individual constants independent of exercise induced sympathetic influences. Thus, having determined an optimal mechanical interval (LA-LV)mech/opt from left atrium to ventricle by other methods, the optimal AV delay for DDD as well as for VDD operation can be calculated by the sum of the appropriate interatrial conduction time (SA-LA, respectively MA-LA) and the (LA-LV)mech/opt interval. Due to the constant SA-LA and MA-LA, the difference between these two values (AV delay correction interval) is a constant as well, which remains unchanged during exercise. Therefore, in selecting the rate responsive AV delay, only hemodynamic and not electrophysiological measurements need to be considered.

Aged↗
PubMed1996

A new method for analysis of atrial activation during chronic atrial fibrillation in man.

To further clarify the mechanisms maintaining chronic atrial fibrillation (CAF), a method identifying preferable activation patterns of the atria during fibrillation, by time averaging of multiple discrete excitation vectors, was developed. Repeated recordings, each of 56 atrial bipolar electrograms simultaneously acquired during 8 s, were made at multiple sites in the right atrial free wall and the left atrial appendage in 16 patients with CAF using a 2.17 x 3.54 cm electrode array. The local activation times (LAT's) in each recording were estimated as the median activation time at the respective measurement point. By calculating the time difference between the LAT's at adjacent measurement points in two spatial dimensions, a direction vector was created for each activation wave passing each set of measurement points, a total of 42 sets. By time averaging of the individual direction vectors (typically n = 55) at each set of measurement points, preferable activation patterns were determined. Three types of activation patterns were found: 1) inconsistent activation (n = 5), 2) consistent activation with preferential propagation directions (n = 7) and 3) consistent activation with impulses originating from a localizable site within the recording area (n = 4). All activation patterns were reproducible and the two latter patterns were proven significant using statistical tests. We conclude that this new method is useful in further clarification of the mechanisms involved in the maintenance of atrial fibrillation.

Aged↗
PubMed1998

Electrical atrial remodeling assessed by monophasic action potential and atrial refractoriness in patients with structural heart disease.

UNLABELLED: The present study was performed to assess the effect of induced atrial fibrillation (AF) on atrial monophasic action potentials (MAPs) and atrial refractory period (ERP) in patients with structural heart disease. An electrode MAP catheter was placed in the right atrium to continuously measure atrial potential duration (APD90) in 13 patients (coronary artery disease, 10 patients; dilated cardiomyopathy, 2 patients; hypertrophic cardiomyopathy, 1 patient) without spontaneous AF episodes. AF was induced by rapid atrial stimulation (300-1500/min). If sinus rhythm returned within 10 minutes, AF was reinduced. The atrial ERP was measured during atrial pacing at a basic cycle length of 550 ms before AF induction and after its conversion. RESULTS: The mean atrial ERP and the atrial APD90 before AF was 242 +/- 34 ms and 256 +/- 23 ms, respectively. ERP and APD90 shortening was observed after 3 minutes of AF. After 11 +/- 0.5 min (10 min 20 s-13 min 10 s) of AF, ERP and APD90 reached their minimal values of 72% +/- 13% and 71% +/- 10% of baseline, respectively. ERP and APD90 returned to their initial values within 10 minutes after conversion of AF. A tendency toward longer duration of consecutive AF episodes and facilitation of their induction was observed. CONCLUSION: The present study confirms that short episodes of AF modify the electrophysiological properties of the atria in humans. In patients with structural heart disease, induced atrial fibrillation shortens the atrial ERP as well as the atrial APD90. The changes were reversible within 10 minutes after arrhythmia termination.

Action Potentials↗
PubMed1998

Mitral inflow and pulmonary venous Doppler measurements do not predict pulmonary capillary wedge pressure in heart transplant recipients.

BACKGROUND: Noninvasive estimation of pulmonary capillary wedge pressure (PCWP) with Doppler-derived mitral inflow pattern has been shown to correlate well with invasively measured PCWP; however, it has not yet been determined whether Doppler-derived mitral inflow pattern can be used to estimate PCWP accurately in heart transplant recipients. METHODS: To determine if mitral and pulmonary venous inflow data can be applied to calculate PCWP in heart transplant recipients, some-day echocardiograms and right heart catheterizations were reviewed and 83 echocardiograms with adequate mitral inflow patterns in 53 patients were studied. Twenty-eight studies that also had adequate pulmonary venous inflow patterns were selected for offline analysis. RESULTS: Using a previously published formula [PCWP = 17 + (5.3 x E/A) - (0.11 x IVRT)], where E/A is the ratio of early to late mitral inflow velocities and IVRT is the isovolumic relaxation time, we derived a calculated PCWP, the results of which compared poorly with the measured PCWP (r = 0.33; p = 0.002). Linear regression analysis of measured PCWP versus mitral inflow Doppler flow velocity parameters also revealed poor to modest correlation. Adding parameters derived from the pulmonary venous inflow patterns failed to improve this correlation. CONCLUSION: Doppler-derived estimation of PCWP with mitral and pulmonary venous inflow patterns cannot be used to reliably predict PCWP in heart transplant recipients.

Adolescent↗
PubMed1997

Diabetes with and without ketoacidosis on right atrial pacemaker rate and autonomic responsiveness.

Experiments were designed to determine whether insulin-dependent diabetes mellitus (IDDM) alters direct chronotropic effects of adrenergic and cholinergic agonists and whether the observed changes are associated with hyperglycemia or combined hyperglycemia and ketoacidosis. Diabetes was induced by intravenous administration of 45, 50, or 65 mg/kg streptozotocin (STZ). Rats treated with 65 mg/kg STZ had higher levels of blood glucose and ketones compared with the levels of the other groups. Right atria were isolated 12 wk after administration of STZ and bathed in Krebs-Henseleit solution. Basal spontaneous pacemaker rate was diminished in preparations isolated from diabetic rats. The maximum pacemaker rate observed during exposure to isoproterenol or norepinephrine was also depressed in preparations from diabetic animals; however, the increase in rate and half-maximal effective concentration values for each agent were not affected. The sensitivity to the negative chronotropic action of acetylcholine was enhanced by IDDM, whereas the response to carbachol (a cholinergic agonist not readily metabolized by acetylcholinesterase) was not changed. No significant differences were observed when we compared preparations isolated from diabetic animals with and without ketoacidosis. In summary, these data suggest 1) that IDDM is associated with a diminished basal spontaneous pacemaker without changes in the responsiveness to adrenergic and cholinergic receptor activation and 2) that ketoacidosis does not play a role in the observed alterations.

Acidosis↗