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Spectrum of autonomic cardiovascular neuropathy in diabetes.
Jacob G, Costa F, Biaggioni I
(2003) Diabetes Care 26: 2174-80
MeSH Terms: Arrhythmias, Cardiac, Autonomic Nervous System Diseases, Blood Pressure, Cardiovascular Diseases, Diabetic Angiopathies, Diabetic Neuropathies, Diastole, Epinephrine, Heart Rate, Hemodynamics, Humans, Middle Aged, Norepinephrine, Reference Values, Systole, Valsalva Maneuver
Show Abstract · Added December 10, 2013
OBJECTIVE - Diabetic patients with incapacitating orthostatic hypotension can have either a "hyperadrenergic" or "hypoadrenergic" presentation. Although the latter is related to overt autonomic neuropathy, the former is proposed to be explained by appropriate autonomic responses. We hypothesize, however, that both conditions are part of a spectrum of autonomic dysfunction.
RESEARCH DESIGN AND METHODS - We studied 16 consecutive diabetic patients with preserved renal function referred for incapacitating orthostatic hypotension and characterized their autonomic and neurohumoral cardiovascular regulation.
RESULTS - Six patients had a hyperadrenergic orthostatic response: systolic blood pressure fell 42 +/- 15 mmHg, heart rate increased 20 +/- 3 bpm, and plasma norepinephrine increased from 340 +/- 80 to 910 +/- 100 pg/ml. Ten patients had a hypoadrenergic response: systolic blood pressure fell 78 +/- 5 mmHg, heart rate increased only 7 +/- 3 bpm, and norepinephrine increased only from 130 +/- 28 to 230 +/- 40 pg/ml. Vagal (sinus arrhythmia, Valsalva ratio) and sympathetic (response to hyperventilation, postprandial hypotension) responses were impaired in both groups, but to a greater extent in the hypoadrenergic group. Notwithstanding severe orthostatic hypotension, the postural increase in plasma renin was blunted in both groups, more so in the hypoadrenergic group. Despite preserved renal function, patients had mild anemia due to impaired erythropoietin release, as seen in primary cases of autonomic failure.
CONCLUSIONS - Our results suggest that diabetic patients presenting with hyperadrenergic orthostatic hypotension have an initial stage of autonomic neuropathy, with overtly abnormal vagal function and early signs of sympathetic impairment. Furthermore, altered renin response can contribute to the patients' orthostatic hypotension.
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16 MeSH Terms
Kir6.2 is required for adaptation to stress.
Zingman LV, Hodgson DM, Bast PH, Kane GC, Perez-Terzic C, Gumina RJ, Pucar D, Bienengraeber M, Dzeja PP, Miki T, Seino S, Alekseev AE, Terzic A
(2002) Proc Natl Acad Sci U S A 99: 13278-83
MeSH Terms: Adaptation, Biological, Animals, Arrhythmias, Cardiac, Calcium, Death, Sudden, Electrophysiology, Hemodynamics, Homeostasis, Ions, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Myocardium, Neurons, Perfusion, Physical Conditioning, Animal, Physical Exertion, Potassium Channels, Inwardly Rectifying, Stress, Physiological, Time Factors
Show Abstract · Added February 21, 2015
Reaction to stress requires feedback adaptation of cellular functions to secure a response without distress, but the molecular order of this process is only partially understood. Here, we report a previously unrecognized regulatory element in the general adaptation syndrome. Kir6.2, the ion-conducting subunit of the metabolically responsive ATP-sensitive potassium (K(ATP)) channel, was mandatory for optimal adaptation capacity under stress. Genetic deletion of Kir6.2 disrupted K(ATP) channel-dependent adjustment of membrane excitability and calcium handling, compromising the enhancement of cardiac performance driven by sympathetic stimulation, a key mediator of the adaptation response. In the absence of Kir6.2, vigorous sympathetic challenge caused arrhythmia and sudden death, preventable by calcium-channel blockade. Thus, this vital function identifies a physiological role for K(ATP) channels in the heart.
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21 MeSH Terms
Inhibition of the Na(+)/H(+) exchanger attenuates phase 1b ischemic arrhythmias and reperfusion-induced ventricular fibrillation.
Gumina RJ, Daemmgen J, Gross GJ
(2000) Eur J Pharmacol 396: 119-24
MeSH Terms: Animals, Anti-Arrhythmia Agents, Arrhythmias, Cardiac, Dogs, Female, Hemodynamics, Male, Myocardial Infarction, Myocardial Ischemia, Myocardial Reperfusion Injury, Sodium-Hydrogen Exchangers, Ventricular Fibrillation
Show Abstract · Added February 21, 2015
The sodium-hydrogen exchanger-isotype 1 (NHE-1) plays a critical role in myocardial ischemia-reperfusion injury. While studies employing less selective sodium-hydrogen inhibitors have demonstrated antiarrhythmic activity, only one study has examined the in vivo efficacy of selective NHE-1 inhibition in a canine model of ischemia-reperfusion-induced arrhythmia. In the present study, the antiarrhythmic activity of Benzamide, N-(aminoiminomethyl)-4-¿4-(2-furanylcarbonyl)-1-piperazinyl -3-(methy lsulfonyl), methanesulfonate (BIIB 513), a novel NHE-1 inhibitor, was examined. An in vivo canine model of myocardial ischemia-reperfusion injury in which 60 min of left anterior descending coronary artery (LAD) occlusion followed by 3 h of reperfusion was employed. BIIB 513 was infused either prior to ischemia or prior to reperfusion. Arrhythmias were quantified by single lead electrocardiogram. Infarct size, determined by triphenyltetrazolium staining, was expressed as a percent of the area-at-risk. In vivo, NHE-1 inhibition did not affect phase 1a arrhythmias, which occur within the first 10 min of occlusion, however, BIIB 513 significantly reduced the incidence of ischemia-induced phase 1b arrhythmias which occur between 10 and 30 min following occlusion and the incidence of reperfusion-induced ventricular fibrillation. Furthermore, NHE-1 inhibition significantly reduced infarct size, when the drug was administered either prior to ischemia or prior to reperfusion. NHE-1 inhibition selectively reduces both ischemia-induced phase 1b arrhythmias and reperfusion-induced ventricular fibrillation, and also markedly reduces myocardial infarct size when the drug is administered prior to ischemia or prior to reperfusion.
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12 MeSH Terms
Effects of procainamide and lidocaine on defibrillation energy requirements in patients receiving implantable cardioverter defibrillator devices.
Echt DS, Gremillion ST, Lee JT, Roden DM, Murray KT, Borganelli M, Crawford DM, Stewart JR, Hammon JW
(1994) J Cardiovasc Electrophysiol 5: 752-60
MeSH Terms: Aged, Arrhythmias, Cardiac, Combined Modality Therapy, Defibrillators, Implantable, Electrocardiography, Female, Humans, Lidocaine, Male, Middle Aged, Procainamide, Prospective Studies
Show Abstract · Added January 20, 2015
INTRODUCTION - In acute canine studies, lidocaine, but not procainamide, increases defibrillation energy requirements. We evaluated the effects of lidocaine or procainamide on defibrillation energy requirements in 27 patients undergoing intraoperative testing for implantable cardioverter defibrillator device placement.
METHODS AND RESULTS - Patients were tested off antiarrhythmic drugs and again following either lidocaine (200 to 250 mg loading and 3 mg/min maintenance infusions) or procainamide (1 gm loading and 3 to 4 mg/min maintenance infusions). The defibrillation testing protocol consisted of initial testing at 15 J, followed by higher or lower energies to determine the lowest energy producing three consecutive successful defibrillations. Overall, the mean defibrillation energy increased from 14 +/- 5 J to 18 +/- 7 J during lidocaine (plasma concentration 5.1 +/- 1.6 micrograms/mL; P < 0.02) but were similar at baseline (12 +/- 5 J) and during procainamide infusion (13 +/- 6 J) (plasma concentration: procainamide 10.7 +/- 7.2 micrograms/mL; N-acetyl procainamide 1.0 +/- 0.4 micrograms/mL). A positive linear correlation was found between lidocaine plasma concentration and percent change in defibrillation energy (lidocaine: r = 0.61; P = 0.01). Procainamide raised the defibrillation energy in three patients, two with supratherapeutic plasma concentrations. The increase in defibrillation energy equaled or exceeded 25 J in four patients after lidocaine and in one patient after procainamide.
CONCLUSION - The data suggest that at high plasma concentrations, lidocaine and procainamide adversely affect defibrillation energy requirements consistent with an adverse, concentration-dependent effect of sodium channel blockade on defibrillation energy requirements in patients.
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12 MeSH Terms
The effects of disobutamide on electrophysiologic properties of canine cardiac Purkinje fibers and papillary muscle.
Dohrmann ML, Harrell FE, Strauss HC
(1981) J Pharmacol Exp Ther 217: 549-54
MeSH Terms: Animals, Anti-Arrhythmia Agents, Arrhythmias, Cardiac, Dogs, Heart, Heart Rate, In Vitro Techniques, Membrane Potentials, Ouabain, Papillary Muscles, Potassium, Purkinje Fibers
Added February 28, 2014
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12 MeSH Terms
Prognostic value of ventricular arrhythmias associated with treadmill exercise testing in patients studied with cardiac catheterization for suspected ischemic heart disease.
Califf RM, McKinnis RA, McNeer JF, Harrell FE, Lee KL, Pryor DB, Waugh RA, Harris PJ, Rosati RA, Wagner GS
(1983) J Am Coll Cardiol 2: 1060-7
MeSH Terms: Arrhythmias, Cardiac, Cardiac Catheterization, Coronary Disease, Exercise Test, Humans, Prognosis
Show Abstract · Added February 28, 2014
The prognostic information provided by ventricular arrhythmias associated with treadmill exercise testing was evaluated in 1,293 consecutive nonsurgically treated patients undergoing an exercise test within 6 weeks of cardiac catheterization. The 236 patients with simple ventricular arrhythmias (at least one premature ventricular complex, but without paired complexes or ventricular tachycardia) had a higher prevalence of significant coronary artery disease (57 versus 44%), three vessel disease (31 versus 17%) and abnormal left ventricular function (43 versus 24%) than did patients without ventricular arrhythmias. Patients with paired complexes or ventricular tachycardia had an even higher prevalence of significant coronary artery disease (75%), three vessel disease (39%) and abnormal left ventricular function (54%). In the 620 patients with significant coronary artery disease, patients with paired complexes or ventricular tachycardia had a lower 3 year survival rate (75%) than did patients with simple ventricular arrhythmias (83%) and patients with no ventricular arrhythmias (90%). Ventricular arrhythmias were found to add independent prognostic information to the noninvasive evaluation, including history, physical examination, chest roentgenogram, electrocardiogram and other exercise test variables (p = 0.03). Ventricular arrhythmias made no independent contribution once the cardiac catheterization data were known. In patients without significant coronary artery disease, no relation between ventricular arrhythmias and survival was found.
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6 MeSH Terms
Prognostic implications of ventricular arrhythmias during 24 hour ambulatory monitoring in patients undergoing cardiac catheterization for coronary artery disease.
Califf RM, McKinnis RA, Burks J, Lee KL, Harrell FE, Behar VS, Pryor DB, Wagner GS, Rosati RA
(1982) Am J Cardiol 50: 23-31
MeSH Terms: Adrenergic beta-Antagonists, Ambulatory Care, Angina Pectoris, Arrhythmias, Cardiac, Cardiac Catheterization, Cardiac Output, Coronary Disease, Death, Sudden, Digoxin, Electrocardiography, Female, Heart Ventricles, Humans, Male, Middle Aged, Myocardial Contraction, Myocardial Infarction, Prognosis
Show Abstract · Added February 28, 2014
The prognostic importance of ventricular arrhythmias detected during 24 hour ambulatory monitoring was evaluated in 395 patients with and 260 patients without significant coronary artery disease. Ventricular arrhythmias were found to be strongly related to abnormal left ventricular function. A modification of the Lown grading system (ventricular arrhythmia score) was the most useful scheme for classifying ventricular arrhythmias according to prognostic importance. When only noninvasive characteristics were considered, the score contributed independent prognostic information, and the complexity of ventricular arrhythmias as measured by this score was inversely related to survival. However, when invasive measurements were included, the ventricular arrhythmia score did not contribute independent prognostic information. Furthermore, ejection fraction was more useful than the ventricular arrhythmia score in identifying patients at high risk of sudden death.
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18 MeSH Terms
Evidence for an inhibition of thyroid hormone effects during chronic treatment with amiodarone.
Beck-Peccoz P, Volpi A, Maggioni AP, Cattaneo MG, Piscitelli G, Giani P, Landolina M, Tognoni G, Faglia G
(1986) Horm Metab Res 18: 411-4
MeSH Terms: Adolescent, Adult, Aged, Amiodarone, Antithyroid Agents, Arrhythmias, Cardiac, Benzofurans, Female, Heart Function Tests, Humans, Hypothalamo-Hypophyseal System, Male, Middle Aged, Thyroid Function Tests, Time Factors
Show Abstract · Added November 13, 2013
The effects of chronic amiodarone treatment on several thyroid and cardiac function parameters were studied in 50 euthyroid patients with refractory ventricular arrhythmias, divided in responders and nonresponders according to their sensitivity to the antiarrhythmic action of the drug. No differences in the severity of cardiac disease and blood amiodarone concentrations were found in the two groups. Amiodarone induced a significant inhibition of peripheral T4 monodeiodination, more pronounced in responders compared to nonresponders. On the contrary, only in responsive patients, elevated basal and TRH-stimulated TSH levels were observed (despite serum T3 levels were not different from those in nonresponders) and the indirect indices of cardiac performance, particularly the systolic time intervals, fell in a range usually observed in the hypothyroid states. These findings suggest that amiodarone, besides the well-known inhibition of T4 to T3 conversion, also induces a partial resistance to the thyroid hormones, which is probably involved in the therapeutical effectiveness of the drug.
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15 MeSH Terms
Effects of different paced heart rates on canine coronary occlusion and reperfusion arrhythmias.
Lederman SN, Wenger TL, Harrell FE, Strauss HC
(1987) Am Heart J 113: 1365-9
MeSH Terms: Animals, Arrhythmias, Cardiac, Cardiac Pacing, Artificial, Coronary Circulation, Coronary Disease, Dogs, Heart Rate, Hemodynamics
Show Abstract · Added February 28, 2014
Little information exists regarding the effect of heart rate on arrhythmias induced by coronary reperfusion. We therefore evaluated the effects of different heart rates on arrhythmias following canine coronary artery occlusion and reperfusion. Dogs were paced at either 350 msec cycle length (171 bpm; n = 30) or 480 msec cycle length (125 bpm; n = 30). They were then subjected to a 20-minute occlusion of the proximal left anterior descending coronary artery, followed by sudden reperfusion. Ligated vessel perfusion bed size (myocardial "at risk") was measured with monastral blue and red dyes. The incidence of both occlusion and reperfusion arrhythmias correlated with the myocardium at risk. Dogs paced at 171 bpm had more ventricular ectopic depolarizations (37/1000 beats vs 8/1000 beats, p less than 0.01) and a higher incidence of ventricular tachycardia during occlusion than those paced at 125 bpm (67% vs 33%, p less than 0.05). Dogs paced at the faster rate also had a higher incidence of ventricular tachycardia (83% vs 60%, p = 0.08) and ventricular fibrillation (70% vs 40%, p less than 0.05) after reperfusion. Thus, heart rate can have a substantial effect on occlusion and reperfusion arrhythmias and should be considered when making therapeutic interventions and risk assessments in this setting.
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8 MeSH Terms
Prognostic effect of bundle branch block related to coronary artery bypass grafting.
Chu A, Califf RM, Pryor DB, McKinnis RA, Harrell FE, Lee KL, Curtis SE, Oldham HN, Wagner GS
(1987) Am J Cardiol 59: 798-803
MeSH Terms: Adult, Age Factors, Aged, Arrhythmias, Cardiac, Bundle-Branch Block, Coronary Artery Bypass, Female, Humans, Male, Middle Aged, Postoperative Complications, Prognosis, Stroke Volume, Time Factors
Show Abstract · Added February 28, 2014
The incidence and prognostic effect of the development of new perioperative ventricular conduction abnormalities were examined in all patients undergoing coronary artery bypass surgery at Duke University Medical Center between 1976 and 1981. Of the 913 patients included, transient (resolved before discharge) ventricular conduction abnormalities developed in 156 (17%) and persistent (until discharge) changes developed in 126 (14%). Complete right bundle branch block (BBB) was the most frequent type of new ventricular conduction abnormality, followed by left anterior hemiblock and incomplete right BBB (found in 60%, 26%, and 9%, respectively, of all patients with transient changes and 29%, 33% and 26% of all patients with persistent changes). Development of new ventricular conduction abnormalities was most strongly related to date of operation (p less than 0.0001, univariate chi 2 = 122), increasing from 2% transient and 7% persistent in 1976 to 36% transient and 22% persistent in 1981. The incidence was also higher in older patients. Preoperative ejection fraction and number of diseased vessels were related to development of perioperative ventricular conduction abnormalities but were not independently related after adjustment for other baseline characteristics. Contrary to findings in other studies, development of new perioperative ventricular conduction abnormalities, including isolated new left BBB, did not worsen the survival rate in patients followed up to 3 years after surgery.
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14 MeSH Terms