Biomedical subjects

T Guarnieri

Publications and source records attributed to T Guarnieri.

At least 37 records · Page 2Linked to original sources

PubMed1993

Spontaneous myocardial calcium oscillations: are they linked to ventricular fibrillation?

The physiological oscillation of cytosolic [Ca2+] that underlies each heart beat is generated by the sarcoplasmic reticulum (SR) in response to an action potential (AP) and occurs relatively synchronously within and among cells. When the myocardial cell and SR Ca2+ loading become sufficiently high, the SR can also generate spontaneous, i.e., not triggered by sarcolemmal depolarization, Ca2+ oscillations (S-CaOs). The purpose of this review is to describe properties of S-CaOs in individual cells, myocardial tissue, and the intact heart, and to examine the evidence that may link S-CaOs to the initiation or maintenance of ventricular fibrillation (VF). The SR Ca2+ release that generates S-CaOs occurs locally within cells and spreads within the cell via Ca(2+)-induced Ca2+ release. The localized increase in cytosolic [Ca2+] due to S-CaOs may equal that induced by an AP and causes oscillatory sarcolemmal depolarizations of cells in which it occurs. These oscillatory depolarizations are due to Ca2+ activation of the Na/Ca exchanger and of nonspecific cation channels. Asynchronous occurrence of diastolic S-CaOs among cells within the myocardium causes inhomogeneity of diastolic SR Ca2+ loading; this leads to inhomogeneity of the systolic cytosolic [Ca2+] transient levels in response to a subsequent AP, which leads to heterogeneity of AP repolarization, due to heterogeneous Ca2+ modulation of the Na/Ca exchanger, nonspecific cation channels, and of the L-type Ca2+ channel. In a tissue in which asynchronous S-CaOs are occurring in diastole, the subsequent AP temporarily synchronizes SR Ca2+ loading and release within and among cells. Varying extents of synchronized S-CaOs then begin to occur during the subsequent diastole. The partial synchronization of this diastolic S-CaOs among cells within myocardial tissue produces aftercontractions and diastolic depolarizations. When S-CaOs are sufficiently synchronized, the resultant depolarizations summate and can be sufficient to trigger a spontaneous AP.S-CaOs occurrence within some cells during a long AP plateau also modulates the removal of voltage inactivation of L-type Ca2+ channels and increases the likelihood for "early afterdepolarizations" to occur in myocardial tissue. S-CaOs have an apparent modulatory role in the initiation of VF in the Ca2+ overload model and in the reflow period following ischemia. Likewise, in non-a priori Ca2+ overloaded hearts, S-CaOs modulate the threshold for VF induction (induced typically by alternating current) but may not be essential for VF induction.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1992

Anti-Ro/SS-A antibodies in the pathophysiology of congenital heart block in neonatal lupus syndrome, an experimental model. In vitro electrophysiologic and immunocytochemical studies.

OBJECTIVE: To determine whether anti-Ro/SS-A antibodies selectively bind to neonatal cardiac cells and alter membrane repolarization. METHODS: An in vitro electrophysiologic and immunocytochemical experimental model contrasting neonatal and rabbit cardiac tissue was employed. RESULTS: Sera and IgG-enriched fractions from anti-Ro/SS-A antibody-positive mothers of infants with neonatal lupus erythematosus and congenital heart block bind to neonatal, rather than adult, rabbit cardiac tissue and alter the transmembrane action potential (i.e., inhibit repolarization). The additional presence of anti-La/SS-B antibodies was not additive or synergistic for these immunocytochemical and electrophysiologic features. Sera containing other antibody specificities (i.e., anti-native DNA, cardiolipin, Sm, and nuclear RNP) failed to stain the neonatal cardiac tissue or produced alterations in membrane repolarization. CONCLUSION: Anti-Ro/SS-A antibodies may play a pathophysiologic role in the development of congenital heart block in neonatal lupus.

Action Potentials↗

PubMed1991

Testicular dysfunction with amiodarone use.

Amiodarone, an antiarrhythmic drug approved for use in patients who survive cardiac arrest, has been associated with infiltration of or inflammatory changes in various tissues. To date thyroid dysfunction has been the only endocrine disturbance noted. In an initial group of seven amiodarone-treated men undergoing evaluation for sexual dysfunction, an elevation in serum gonadotropin concentration was detected, suggesting testicular dysfunction. Because of this finding, gonadal function was prospectively evaluated in 44 men (18 who had been treated with amiodarone for greater than 1 year and 26 survivors of cardiac arrest who had been treated with antiarrhythmic drugs other than amiodarone). Amiodarone-treated men had higher serum follicle-stimulating hormone (41.8 +/- 22.8 vs. 14.4 +/- 10.4 mIU/ml, p less than 0.001) and luteinizing hormone (34.8 +/- 26.4 vs. 10.1 +/- 5.2 mIU/ml, p less than 0.001) concentrations compared with control subjects. Although serum total and free testosterone levels were comparable between the two patient groups, these levels were inversely correlated (r = -0.53, p less than 0.05; r = -0.62, p less than 0.01, respectively) with cumulative amiodarone dose. Hyperresponsiveness to the administration of gonadotropin-releasing hormone was noted in the 10 amiodarone-treated men evaluated by this diagnostic test. Sexual dysfunction was common in both groups (70% of control subjects and 82% of amiodarone-treated subjects), although atrophic testes were more commonly observed in amiodarone-treated men (p less than 0.05). Because of the elevated serum gonadotropin level, it is concluded that testicular dysfunction may result from prolonged amiodarone treatment.

Adult↗

PubMed1991

Substance P in the habenulo-interpeduncular system of the goldfish.

The distribution of substance P (SP)-like immunoreactivity has been studied in the habenulo-interpeduncular system of the goldfish in normal conditions and after habenular ablation. In normal conditions intense SP-like immunoreactivity was observed in the neuropilar structure of the interpeduncular nucleus (IPN). No SP-like immunoreactive cell bodies were observed in the habenular nuclei (HBN), but some SP-like immunoreactive fibres were localized in the central core of the nucleus. Following surgical habenular ablation SP-like immunoreactivity was reduced in the IPN. The image analysis performed on the IPN showed clear-cut transmittance changes in the area examined. The results suggest that SP is involved in connecting HBN and IPN in goldfish, and are consistent with the data of mammals and other vertebrates.

Animals↗

PubMed1991

Long-term follow-up of patients with nonischemic dilated cardiomyopathy and ventricular tachyarrhythmias treated with implantable cardioverter defibrillators.

We analyzed our 10-year cumulative experience of 40 consecutive patients with idiopathic dilated cardiomyopathy and associated ventricular tachyarrhythmias, treated with implantable cardioverter defibrillators. Dilated cardiomyopathy was defined as left ventricular ejection fraction (EF) less than or equal to 50% with no defineable etiology. Patient characteristics included: 24 male, mean age 52 years, mean EF = 33%, New York Heart Association Class I-III, presenting syndrome--cardiac arrest (n = 28), syncope/near syncope (n = 12). At 2.5 years mean follow-up, there were 16 deaths: one operative, three sudden, two incessant ventricular tachycardia/ventricular fibrillation (VT/VF), six heart failure, and four noncardiac. The actuarial mortality at 1 and 4 years was 0% and 14% for sudden death, 11% and 34% for cardiac death. The projected mortality was 52% and 78% for same time intervals (P less than 0.01). No useful baseline variable predicted who would or would not receive an ICD shock in follow-up. ICD therapy appears effective in reducing sudden death mortality in this high risk population.

Cardiomyopathy, Dilated↗

PubMed1991

The interaction of antiarrhythmic drugs and the energy for cardioversion of chronic atrial fibrillation.

Antiarrhythmic drugs may alter the energy for cardioversion of ventricular arrhythmias. This study compares the energy necessary for cardioverting chronic atrial fibrillation in 57 patients taking type Ia, Ic, or type III antiarrhythmic drugs. Patients taking Ia (n = 22) or III (n = 14) drugs had a median energy for cardioversion of 100 joules, while the patients taking Ic (n = 17) drugs had a median energy of 200 joules (P = 0.03). There were no differences in the frequency of unsuccessful cardioversion. There were no serious adverse events in any of the three groups, although three patients in the Ic group had greater than 3 second pauses after the shock. The data suggest that the use of Ic antiarrhythmic drugs results in a higher energy for cardioversion of atrial fibrillation. However with higher energies, conversion is as successful as for type Ia and type III.

Amiodarone↗

PubMed1991

Predictors of first discharge and subsequent survival in patients with automatic implantable cardioverter-defibrillators.

BACKGROUND: Two hundred eighteen patients were evaluated in a two-phase approach (time to first appropriate discharge, survival after discharge) to identify factors that may be related to maximal benefit derived from use of an automatic implantable cardioverter-defibrillator (AICD). METHODS AND RESULTS: One hundred ninety-seven patients survived implantation of AICD, with or without concomitant cardiac surgery. One hundred five patients had an AICD discharge associated with syncope, presyncope, documented sustained ventricular tachycardia or fibrillation, or sleep at 9.1 +/- 11.1 months after implantation. Patients survived 23.8 +/- 18.0 months after AICD discharge. Left ventricular dysfunction (p = 0.008 for ejection fraction less than 25%) was associated with earlier AICD discharge and shortened survival after AICD discharge (p = 0.008 for ejection fraction less than 25%; p = 0.01 for New York Heart Association functional class III and IV). beta-Blocker administration (p = 0.006) and coronary bypass surgery (p = 0.06) were associated with later AICD discharge. Coronary bypass surgery (p = 0.035) but not beta-blockers was associated with more prolonged survival after AICD discharge. CONCLUSIONS: These data suggest that a relatively easy algorithm can be applied to predict which patient will benefit most from AICD implantation.

Electric Countershock↗

PubMed1991

Cardiac disturbances during the administration of taxol.

The clinical development of taxol, a new antimicrotubule agent with a unique mechanism of cytotoxic action, has proceeded slowly due to serious hypersensitivity reactions (HSRs) and shortages in its supply. Nevertheless, large-scale phase II trials have been initiated as taxol has recently demonstrated impressive activity in advanced and cisplatin-refractory ovarian carcinoma. Furthermore, the incidence of HSRs has been reduced substantially with premedications and modifications in the administration schedule. However, various manifestations of potential cardiotoxicity have been observed in several patients who participated in four phase I and II studies of taxol. Asymptomatic bradycardia has occurred in a high proportion of patients, including 29% of ovarian cancer patients who were treated with maximally tolerated doses of taxol in a phase II study. More profound cardiac disturbances, including a range of atrioventricular conduction blocks, left bundle branch block, ventricular tachycardia (VT), and manifestations of cardiac ischemia, have been observed in seven of 140 patients (5%) who received taxol. Descriptions of these events are presented in this report to alert investigators to the potential for these adverse effects. Although these disturbances did not result in serious sequelae in most patients, investigators should continue to maintain a high degree of caution until precise risk factors, frequency, and clinical significance of these adverse cardiac effects are determined.

Aged↗

PubMed1990

Effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in goldfish brain.

The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which selectively damages dopaminergic neurons in mammals, caused a marked depletion of tyrosine hydroxylase (TH) immunoreactivity in the goldfish brain. The concomitant ultrastructural observations showed the neurotoxic effect of MPTP on telencephalic, diencephalic and medullar neurons. The affected neurons revealed darkening of the cytoplasm and swelling of the mitochondria and the endoplasmic reticulum. Concomitant significant decreases in dopamine (DA) and noradrenaline (NA) levels were determined in the brain areas where morphological observations were performed. The loss of catecholamine levels was completely prevented by the treatment with the monoamine oxidase (MAO) inhibitor pargyline to prevent MPTP oxidation. The results indicate that in goldfish brain, acute MPTP administration causes selective catecholamine depletion, without altering the serotoninergic system.

Animals↗

PubMed1990

Clinical interactions between pacemakers and automatic implantable cardioverter-defibrillators.

Concomitant use of a pacemaker and an automatic implantable cardioverter-defibrillator (AICD) is common. Seventeen percent of patients receiving an AICD at The Johns Hopkins Hospital also had a permanent pacemaker implanted before (16 patients), at the same time as (2 patients) or after (12 patients) AICD implantation. Four types of interactions were noted: 1) transient failure to sense or capture immediately after AICD discharge (seven patients); 2) oversensing of the pacemaker stimulus by the AICD, leading to double counting (one patient); 3) AICD failure to sense ventricular fibrillation resulting from pacemaker stimulus oversensing (three patients, one only at high asynchronous output); and 4) pacemaker reprogramming caused by AICD discharge (three patients). No clinical sequelae of these interactions were noted during follow-up study. Thus, potentially adverse clinical interactions are common and routine screening is recommended. With proper attention to lead placements and programming of the devices, clinical consequences of these interactions can be avoided.

Anti-Arrhythmia Agents↗

PubMed1990

Role of calcium and the calcium channel in the initiation and maintenance of ventricular fibrillation.

The cellular events during the initiation and maintenance of ventricular fibrillation (VF) are poorly understood. We developed a nonischemic, isolated, perfused rabbit Langendorff preparation in which sustained VF could be induced by alternating current (AC) and which allowed changes in perfusate composition. We also used Na(+)-K+ pump inhibition (10 microM ouabain or K(+)-free perfusate) to induce VF. AC stimulation or Na(+)-K+ pump inhibition always initiated VF. Calcium channel blockade by verapamil or nitrendipine uniformly inhibited the initiation of VF in both models. During Na(+)-K+ pump inhibition, 1) VF was prevented by calcium channel blockade, despite evidence of Ca2+ overload, and 2) abolition of spontaneous sarcoplasmic reticulum-generated cytosolic Ca2+ oscillations by ryanodine or Na+ channel blockade with tetrodotoxin did not prevent VF initiation. Lowering extracellular [Ca2+] to 80 microM uniformly prevented the initiation of VF due to Na(+)-K+ pump inhibition but not that due to AC stimulation. VF maintenance also was studied using 1) reduction in perfusate [Ca2+], 2) blockade of Ca2+ channels, or 3) electrical defibrillation. Decreasing the perfusate [Ca2+] to 80 microM resulted in defibrillation during VF whether induced by AC or Na(+)-K+ pump inhibition. Verapamil or nitrendipine also resulted in defibrillation regardless of the initiation method. Electrical defibrillation was successful only in AC-induced VF. The results demonstrate that VF can be initiated and maintained in a nonischemic rabbit Langendorff preparation. The data suggest that increases in slow channel Ca2+ flux, as opposed to increases in cytosolic Ca2+ per se, were necessary for the initiation and maintenance of VF. The data, however, do not exclude an important role for cytosolic Ca2+ in the modulation of VF.

Animals↗

PubMed1990

Mechanism of myocardial contractile depression by clinical concentrations of ethanol. A study in ferret papillary muscles.

Moderate alcohol intoxication in man, a ubiqitious social event, causes acute but reversible myocardial depression, the mechanism of which is unknown. We investigated whether this depression could be due to a direct effect of ethanol on the process of electromechanical coupling by simultaneously measuring the transmembrane action potential and contraction, or the cytosolic calcium transient (via aequorin photoluminescence) and contraction in isolated ferret right ventricular papillary muscle. Ethanol, in concentrations that are similar to plasma levels in man during intoxication (0.15 vol %), depressed the force of contraction approximately 10%. The step in the electromechanical process that was affected appeared to be the calcium-myofilament interaction, as there was no change in the transmembrane action potential or cytosolic calcium transient. This inhibition was quickly reversed by removal of the ethanol from the perfusate. On the other hand, higher concentrations of ethanol produced changes in contraction, the calcium transient, and the action potential, suggesting multiple levels of inhibition of electromechanical coupling. Increasing the perfusate calcium or use of the calcium channel agonist, BAY-K 8644, increased cytosolic calcium to near maximum but had little effect on contractility, confirming that the relationship between calcium and the myofilaments had been altered. These data suggest that the acute depression in ventricular function seen with alcohol consumption may be due to a direct effect on electromechanical coupling through inhibition of the calcium myofilament interaction.

Action Potentials↗

PubMed1989

Tyrosine hydroxylase immunohistochemistry in the normal and 1-methyl-4-phenyl-tetrahydropyridine (MPP+)-treated retina of goldfish.

Dopaminergic interplexiform neurons have been identified in the inner nuclear layer of goldfish retina, with tyrosine hydroxylase (TH) immunocytochemistry in whole-mounted retinae and in cryosections. The neurotoxin 1-methyl-4-phenylpyridinium ion (MPP+), which selectively damages dopaminergic neurons in mammals, caused a marked depletion of TH immunoreactivity in goldfish retina. Three days after intravitreal injection, retinae showed no significant decrease in the number of TH-positive neurons. However most of the TH-immunoreactive cell bodies showed an evident depletion of TH immunoreactivity and their processes, ramified in the inner and outer plexiform layers, disappeared almost completely.

1-Methyl-4-phenylpyridinium↗

PubMed1989

High-grade atrioventricular heart block in an adult with systemic lupus erythematosus: the association of nuclear RNP (U1 RNP) antibodies, a case report, and review of the literature.

High-grade atrioventricular heart block (HGAVB) occurring as a manifestation of systemic lupus erythematosus is an exceedingly rare event. We describe a patient with HGAVB who had myositis and antibodies to nuclear RNP (previously associated with myocarditis). A review of the literature on HGAVB associated with systemic lupus erythematosus is also presented.

Adult↗

PubMed1989

Serial lung function testing in patients treated with amiodarone: a prospective study.

PURPOSE: Amiodarone has proven to be effective in many cases of cardiac arrhythmias, refractory ventricular tachycardia, and ventricular fibrillation. Pulmonary toxicity is a possible side effect of the drug, with a reported incidence of 2 to 15 percent per year. To determine the effect of amiodarone on lung function, we prospectively studied serial lung function tests in a cohort of 91 patients with refractory cardiac arrhythmias treated with this agent. PATIENTS AND METHODS: Spirometry and carbon monoxide diffusing capacity (DLCO) were measured at zero, three, six, 12, 18, and 24 months, with a mean follow-up of 351 days. RESULTS: For the whole population taking a mean dose of amiodarone of 367 mg daily (range: 136 to 512 mg), there was no accelerated rate of decline in spirometric indices or DLCO. Analysis of lung function changes by multivariate analysis demonstrated that an accelerated decline in DLCO values occurred in elderly patients (p less than 0.05) but not in patients with pre-existing lung disease or cigarette smokers. In four patients (4.5 percent), clinical evidence of amiodarone pulmonary toxicity developed that was associated with a fall in DLCO of greater than 20 percent. All four patients recovered after the drug was stopped. Another 15 patients, without clinical evidence of pulmonary toxicity, had a sustained decline in DLCO of greater than 20 percent. These 15 patients remained asymptomatic over the next 11 months without interruption of therapy. A greater than 20 percent fall in DLCO was a sensitive test for clinically evident amiodarone pulmonary toxicity, but had a positive predictive value of only 21 percent. CONCLUSION: An isolated fall in DLCO, in the absence of clinical evidence of toxicity, does not necessitate stopping amiodarone. An unchanged DLCO value appears to be a reliable negative predictor of pulmonary toxicity.

Adult↗

PubMed1989

Anti-SS-A/Ro SS-B/La antibodies bind to neonatal rabbit cardiac cells and preferentially inhibit in vitro cardiac repolarization.

The neonatal lupus syndrome is the most common cause of isolated congenital heart block. There is, at present, little information about the putative role of anti-SS-A/Ro SS-B/La antibodies in the pathogenesis of congenital heart block in the neonatal lupus syndrome. Using an in vitro experimental model, the present study was designed to test the hypothesis that IgG antibodies in the sera of anti-SS-A/Ro SS-B/La-positive mothers of infants with isolated congenital heart block bind to and affect the transmembrane action potential of rabbit cardiac tissue. The results demonstrate a preferential inhibition of membrane repolarization (ADP-50 and ADP-90) and staining of cardiac cells within the neonatal, in contrast to the adult, rabbit heart by sera and IgG-enriched fractions from anti-SS-A/Ro SS-B/La-positive individuals. The results of the electrophysiologic studies demonstrate a pathophysiologic role for the IgG fraction of anti-SS-A/Ro SS-B/La-positive maternal sera in inhibiting neonatal rabbit cardiac repolarization. It is possible that antibodies to similar determinants expressed on the cell membrane of cardiac-conducting cells also may play a pathophysiologic role in the development of idiopathic congenital heart block in humans.

Animals↗

PubMed1989

Alternating sequence of retrograde atrial activation in patients with dual AV nodal physiology.

Patients with dual AV nodal physiology have been demonstrated to have earliest retrograde activation sequence of the fast pathway in the lower septal right atrium and slow pathway in the proximal coronary sinus, and the posterior atrial septum. This case report describes a patient with dual AV nodal physiology demonstrating a dual sequence of retrograde activation with 2:1 block occurring in the fast pathway causing the conduction to proceed alternately via fast then slow pathway. This sequence was abolished by atropine allowing conduction to proceed via fast pathway. Surgical cure of patients with reentrant AV nodal tachycardia suggests the presence of two anatomically distinct AV nodal-like pathways. This case report confirms this observation and further suggests preferential autonomic modulation of the fast pathway.

Adult↗

PubMed1989

Hypothalamic target cells of endogenous sexual steroids in female rat. An immunocytochemical approach utilizing antiestradiol antiserum.

The immunostaining proposed in this study identifies cells containing endogenous estrogens in the Central Nervous System, in the presence of both very high and very low serum estrogen levels. Ten adult rats, seven normal and three ovariectomized females, were used for this study. Paraffin sections of hypothalamus and ovary of each female were stained using Avidin-Biotin Complex method and antiestradiol antiserum. Two different antiestradiol antisera were tested in this work: tests for method and antisera specificity are described. The immunostaining used here shows to be specific and sensitive revealing a higher number of labeled hypothalamic areas than those revealed by other techniques.

Animals↗