ABSTRACT
BACKGROUND: Cardiac damage triggered by severe hypocalcemia is well known. However, the role of chronic hypoparathyroidism (HP) and pseudohypoparathyroidism (PHP) in cardiac health is still unclear. We investigated the effect of chronic HP and PHP on cardiac structure and conductive function in patients compiling with treatment. METHODS: The study included 18 patients with HP and eight with PHP aged 45.4 ± 15.4 and 22.1 ± 6.4 years, respectively with a previously regular follow-up. In addition, 26 age- and sex-matched healthy controls were included. General characteristics and biochemical indices were recorded. Cardiac function and structure were assessed by estimation of myocardial enzymes, B-type natriuretic peptide (BNP), and echocardiography. The 12-lead electrocardiogram and 24-h Holter electrocardiography were performed to evaluate the conductive function. RESULTS: Levels of serum calcium in HP and PHP were 2.05 ± 0.16 mmol/L and 2.25 ± 0.19 mmol/L, respectively. The levels of myocardial enzyme and BNP were within the normal range. Adjusting for age at evaluation and body mass index, all M-mode measurements, left ventricular mass (LVM), LVM index (LVMI) and relative wall thickness (RWT) were comparable between patients and controls. Prolongation of corrected QT (QTc) intervals occurred in 52.6% (10/19) of patients, and 6.7% (1/15) of patients manifested more than 100 episodes of supraventricular and ventricular extrasystoles, as well as supraventricular tachycardia. None of the above arrhythmias was related to a severe clinical event. CONCLUSIONS: From this pilot study, patients diagnosed with HP and PHP and well-controlled serum calcium levels manifested normal cardiac morphology and ventricular function, except for prolonged QTc intervals, and a small percentage of mild arrhythmias needing further investigation.
Subject(s)
Arrhythmias, Cardiac/physiopathology , Hypoparathyroidism/physiopathology , Pseudohypoparathyroidism/physiopathology , Ventricular Dysfunction, Left/physiopathology , Adolescent , Adult , Arrhythmias, Cardiac/etiology , Arrhythmias, Cardiac/metabolism , Atrial Premature Complexes/etiology , Atrial Premature Complexes/metabolism , Atrial Premature Complexes/physiopathology , Calcium/metabolism , Case-Control Studies , Chronic Disease , Echocardiography , Electrocardiography , Electrocardiography, Ambulatory , Female , Humans , Hypoparathyroidism/complications , Hypoparathyroidism/metabolism , Long QT Syndrome/etiology , Long QT Syndrome/metabolism , Long QT Syndrome/physiopathology , Male , Middle Aged , Natriuretic Peptide, Brain/metabolism , Pilot Projects , Pseudohypoparathyroidism/complications , Pseudohypoparathyroidism/metabolism , Tachycardia, Supraventricular/etiology , Tachycardia, Supraventricular/metabolism , Tachycardia, Supraventricular/physiopathology , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/metabolism , Ventricular Premature Complexes/etiology , Ventricular Premature Complexes/metabolism , Ventricular Premature Complexes/physiopathology , Young AdultABSTRACT
BACKGROUND: Recent evidence indicates that spontaneous sarcoplasmic reticulum (SR) calcium (Ca) release underlies the mechanism of sinoatrial node (SAN) acceleration during beta-stimulation, indicating the importance of the Ca clock in SAN automaticity. Whether or not the same mechanism applies to atrial ectopic pacemakers (AEPs) remains unclear. OBJECTIVE: The purpose of this study was to assess the mechanism of AEP. METHODS: We simultaneously mapped intracellular calcium (Ca(i)) and membrane potential in 12 isolated canine right atria. The late diastolic Ca(i) elevation (LDCAE) was used to detect the Ca clock activity. Pharmacological interventions with isoproterenol (ISO), ryanodine, and ZD7288, a blocker of the I(f) membrane current, were performed. RESULTS: Ryanodine, which inhibits SR Ca release, reduced LDCAE in SAN, resulting in an inferior shift of the pacemaking site. Cycle length increased significantly in a dose-dependent way. In the presence of 3 to 10 mumol/l of ryanodine, ISO infusion consistently induces AEPs from the lower crista terminalis. All ectopic beats continuing over 30 seconds were located at the lower crista terminalis. These AEPs were resistant to ryanodine treatment even at high doses. Subsequent blockade of I(f) inhibited the AEP and resulted in profound bradycardia. CONCLUSION: Spontaneous SR Ca release underlies ISO-induced increase of superior SAN activity. As compared with SAN, the AEP is less dependent on the Ca clock and more dependent on the membrane clock for its automaticity. AEPs outside the SAN can effectively serve as backup pacemakers when the Ca clock functionality is reduced.
Subject(s)
Atrial Premature Complexes/etiology , Calcium/metabolism , Heart Atria/physiopathology , Sarcoplasmic Reticulum/metabolism , Sinoatrial Node/physiopathology , Adrenergic beta-Agonists/pharmacology , Animals , Atrial Premature Complexes/metabolism , Calcium Channels, L-Type/drug effects , Calcium Channels, L-Type/metabolism , Cardiotonic Agents/pharmacology , Dogs , Heart Atria/drug effects , Heart Atria/innervation , Heart Conduction System/drug effects , Heart Rate/drug effects , Isoproterenol/pharmacology , Membrane Potentials/drug effects , Pyrimidines/pharmacology , Risk Assessment , Risk Factors , Ryanodine/pharmacology , Sarcoplasmic Reticulum/drug effects , Sinoatrial Node/drug effects , Sinoatrial Node/metabolism , Time FactorsABSTRACT
INTRODUCTION: The funny current (I(f)) contributes to phase IV spontaneous depolarization in cardiac pacemaker tissue. Enhanced I(f) activity in myocardial tissue may lead to increased automaticity and therefore tachyarrhythmia. We measured the amount of I(f) activity in the messenger ribonucleic acid (mRNA) in human atrial tissue and correlated the mRNA amount to left atrial filling pressure and atrial fibrillation (AF). METHODS AND RESULTS: A total of 34 patients undergoing open heart surgery were included (15 men and 19 women, aged 55+/-10 years). Atrial tissue was obtained from the right atrial free wall, the right atrial appendage, the left atrial free wall, and the left atrial appendage, respectively. The mRNA amount of the I(f) channel was measured by reverse transcription polymerase chain reaction and was normalized to the mRNA levels of glyceraldehyde 3-phosphate dehydrogenase. We found that the I(f) channel mRNA was present at all the atrial sampling sites. A higher left atrial filling pressure, an indicator of congestive heart failure, was associated with a higher I(f) mRNA level (r2 = 0.446, P < 0.01 by linear regression). We also found that the mRNA amount was significantly higher in patients with AF than in patients without AF (1.68+/-0.49 vs 1.27+/-0.43; P < 0.05). Age, sex, right atrial filling pressure, left atrial dimension, and left ventricular ejection fraction had no significant effect on the mRNA level. CONCLUSION: The mRNA of the I(f) channel is present in the free-wall area and appendage area from both atria. Increased left atrial filling pressure and clinical AF are associated with increased I(f) mRNA level.
