Methylomic profiling and replication implicates deregulation of PCSK9 in alcohol use disorder.

Alcohol use disorder (AUD) is a common and chronic disorder with substantial effects on personal and public health. The underlying pathophysiology is poorly understood but strong evidence suggests significant roles of both genetic and epigenetic components. Given that alcohol affects many organ systems, we performed a cross-tissue and cross-phenotypic analysis of genome-wide methylomic variation in AUD using samples from 3 discovery, 4 replication, and 2 translational cohorts. We identified a differentially methylated region in the promoter of the proprotein convertase subtilisin/kexin 9 (PCSK9) gene that was associated with disease phenotypes. Biological validation showed that PCSK9 promoter methylation is conserved across tissues and positively correlated with expression. Replication in AUD datasets confirmed PCSK9 hypomethylation and a translational mouse model of AUD showed that alcohol exposure leads to PCSK9 downregulation. PCSK9 is primarily expressed in the liver and regulates low-density lipoprotein cholesterol (LDL-C). Our finding of alcohol-induced epigenetic regulation of PCSK9 represents one of the underlying mechanisms between the well-known effects of alcohol on lipid metabolism and cardiovascular risk, with light alcohol use generally being protective while chronic heavy use has detrimental health outcomes.

Nonlinear temperature modulation of sodium channel kinetics in GH(3) cells.

The effect of temperature on sodium channel function was examined in GH(3) cells, using the whole cell patch-clamp methodology. Specific parameters examined were current-voltage relationships, activation time, and inactivation time. For the temperature range studied, 23-37 degrees C, there was no change in the current-voltage relationship. A linear response to temperature was seen in the inactivation time constant, tau(h). The activation time constant, tau(m), was clearly nonlinear, with a sharp discontinuity at 28 degrees C. This nonlinearity was especially evident at lower membrane voltages. These findings are consistent with the hypothesis that membrane structural changes, which occur during the thermotropic phase transition, are capable of influencing the function of the intramembranous portion of the channel. Caution should, therefore, be exercised in extrapolating data on channel function obtained at room temperature to physiological temperatures.

Relationship of extent of revascularization with angina at one year in the Bypass Angioplasty Revascularization Investigation (BARI).

OBJECTIVES: To determine the relative degree of revascularization obtained with bypass surgery versus angioplasty in a randomized trial of patients with multivessel disease requiring revascularization (Bypass Angioplasty Revascularization Investigation [BARI]), one-year catheterization was performed in 15% of patients. BACKGROUND: Complete revascularization has been correlated with improved outcome after coronary artery bypass grafting (CABG) but not with percutaneous transluminal coronary angioplasty (PTCA). Relative degrees of revascularization after PTCA and surgery have not been previously compared and correlated with symptoms. METHODS: Consecutive patients at four BARI centers consented to recatheterization one year after revascularization. Myocardial jeopardy index (MJI), the percentage of myocardium jeopardized by > or =50% stenoses, was compared and correlated with angina status. RESULTS: Angiography was completed in 270 of 362 consecutive patients (75%) after initial CABG (n = 135) or PTCA (n = 135). Coronary artery bypass grafting patients had 3+/-0.9 distal anastomoses and PTCA patients had 2.4+/-1.1 lesions attempted at initial revascularization. At one year, 20.5% of CABG patients had > or =1 totally occluded graft and 86.9% of vein graft, and 91.6% of internal mammary artery distal anastomotic sites had <50% stenosis. One year jeopardy index in surgery patients was 14.1+/-11%, 46.6+/-20.3% improved from baseline. Initial PTCA was successful in 86.9% of lesions and repeat revascularization was performed in 48.4% of PTCA patients by one year. Myocardial jeopardy index one year after PTCA was 25.5+/-22.8%, an improvement of 33.8+/-26.1% (p<0.01 for greater improvement with CABG than PTCA). At one year, 29.6% of PTCA patients had angina versus 11.9% of surgery patients, p = 0.004. One-year myocardial jeopardy was predictive of angina (odds ratio 1.28 for the presence of angina per every 10% increment in myocardial jeopardy, p = 0.002). Randomization to PTCA rather than CABG also predicted angina (odds ratio 2.19, p = 0.03). CONCLUSIONS: In this one-year angiographic substudy of BARI, CABG provided more complete revascularization than PTCA, and CABG likewise improved angina to a greater extent than PTCA.

Is a strategy of intended incomplete percutaneous transluminal coronary angioplasty revascularization acceptable in nondiabetic patients who are candidates for coronary artery bypass graft surgery? The Bypass Angioplasty Revascularization Investigation (BARI).

OBJECTIVES: Our objective was to determine whether a strategy of intended incomplete percutaneous transluminal coronary angioplasty revascularization (IR) compromises long-term patient outcome. BACKGROUND: Complete angioplasty revascularization (CR) is often not planned nor attempted in patients with multivessel coronary disease, and the extent to which this influences outcome is unclear. METHODS: Before randomization, in the Bypass Angioplasty Revascularization Investigation, all angiograms were assessed for intended CR or IR via angioplasty. Outcomes were compared among patients with IR intended if assigned to angioplasty, randomized to coronary artery bypass graft surgery (CABG) versus angioplasty; and within angioplasty patients only, among patients with IR versus CR intended. RESULTS: At 5 years, there was a trend for higher overall (88.6% vs. 84.0%) and cardiac survival (94.5% vs. 92.1%) in CABG versus angioplasty patients with IR intended. The excess mortality in angioplasty patients occurred solely in diabetic subjects; overall and cardiac survival were similar among nondiabetic CABG and angioplasty patients. Freedom from myocardial infarction (MI) at 5 years was higher in nondiabetic CABG versus angioplasty patients (92.4% vs. 85.2%, p = 0.02), vet was similar to the rate observed (85%) in nondiabetic CABG and angioplasty patients with CR intended. Five-year rates of death, cardiac death, repeat revascularization and angina were similar in all angioplasty patients with IR versus CR intended. However, a trend for greater freedom from subsequent CABG was seen in CR patients (70.3% vs. 64.0%, p = 0.08). CONCLUSIONS: Intended incomplete angioplasty revascularization in nondiabetic patients with multivessel disease who are candidates for both angioplasty and CABG does not compromise long-term survival; however, subsequent need for CABG may be increased with this strategy. Whether the risk of long-term MI is also increased remains uncertain.

Study of condom integrity after brief exposure to over-the-counter vaginal preparations.

BACKGROUND: Latex condoms are used as contraceptives and as preventives against sexually transmitted diseases. Latex rapidly and significantly deteriorates when exposed to pure mineral oil and vegetable oil. We wanted to determine if short exposures to readily available over-the-counter (OTC) intravaginal preparations could affect latex condom integrity. METHODS: We compared the mean burst time of test latex condoms, which had 5-minute exposure to various OTC vaginal products, with the mean burst time of control (unexposed) condoms during pressurized air inflation. RESULTS: Baby oil reduced the mean burst time from nearly a minute to just over 11 seconds. One intravaginal moisturizer and two intravaginal antifungal preparations also adversely affected latex condom integrity. Products that weakened latex condoms contained either mineral oil or vegetable oil. CONCLUSIONS: Women who rely on latex condoms should exercise caution if using OTC vaginal products containing either mineral oil or vegetable oil. Such products apparently can decrease condom strength and potentially jeopardize efficacy.

Coronary revascularization in diabetic patients: a comparison of the randomized and observational components of the Aypass Angioplasty Revascularization Investigation (BARI).

BACKGROUND: Patients with treated diabetes in the randomized-trial segment of the Bypass Angioplasty Revascularization Investigation (BARI) who were randomized to initial revascularization with PTCA had significantly worse 5-year survival than patients assigned to CABG. This treatment difference was not seen among diabetic patients eligible for BARI who opted to select their mode of revascularization. We hypothesized that differences in patient characteristics, assessed and unmeasured, together with the treatment selection in the registry, at least partially account for this discrepancy. METHODS AND RESULTS: Among diabetics taking insulin or oral hypoglycemic drugs at entry, angiographic and clinical presentations were comparable between randomized and registry patients. However, more registry patients were white, and registry diabetics tended to be more educated and more physically active and to report better quality of life. Procedural characteristics and in-hospital complications were comparable. The 5-year all-cause mortality rate was 34.5% in randomized diabetic patients assigned to PTCA versus 19.4% in CABG patients (P=0.0024; relative risk [RR]=1.87); corresponding cardiac mortality rates were 23.4% and 8.2%, respectively (P=0.0002; RR=3.10). The CABG benefit was more apparent among patients requiring insulin. In the registry, all-cause mortality was 14.4% for PTCA versus 14.9% for CABG (P=0.86, RR=1.10), with corresponding cardiac mortality rates of 7.5% and 6. 0%, respectively (P=0.73; RR=1.07). These RRs in the registry increased to 1.29 and 1.41, respectively, after adjustment for all known differences between treatment groups. CONCLUSIONS: BARI registry results are not inconsistent with the finding in the randomized trial that initial CABG is associated with better long-term survival than PTCA in treated diabetic patients with multivessel coronary disease suitable for either surgical or catheter-based revascularization.

Cognitive function 5 years after randomization to coronary angioplasty or coronary artery bypass graft surgery.

BACKGROUND: Coronary bypass surgery often leads to short-term cognitive dysfunction, whereas coronary angioplasty does not. Perioperative cognitive dysfunction usually resolves, although a subgroup of surgical patients may continue to exhibit long-term cognitive dysfunction. The purpose of this study was to compare cognitive function 5 years after randomization to a strategy of either initial coronary surgery or initial angioplasty. METHODS AND RESULTS: Five centers in the Bypass Angioplasty Revascularization Investigation participated in this ancillary study. Patients with multivessel coronary disease randomized to angioplasty or surgery were eligible at the time of their 5-year clinic visit. A battery of five measures previously shown to be sensitive to perioperative changes in cognitive function was administered, including the Logical and Figural Memory Scales from the Wechsler Memory Scale, the Digit Symbol and Digit Span subtests from the Wechsler Adult Intelligence Scale, and Part B of the Reitan Trail Making Test. The 125 study patients were generally similar to the 133 patients who were eligible but did not participate, although study participants were significantly younger (P=.003). The 64 patients randomly assigned to angioplasty had baseline characteristics similar to those of 61 patients randomly assigned to surgery. Cognitive function scores were not significantly different between angioplasty or surgery patients in an intention-to-treat analysis (P=.57). There also was no difference in cognitive function scores when the data were analyzed according to whether the patient had ever undergone bypass surgery (P=.59). CONCLUSIONS: Long-term cognitive function is similar after coronary bypass surgery and coronary angioplasty in the majority of patients.

Cause of death analysis in the NHLBI PTCA Registry: results and considerations for evaluating long-term survival after coronary interventions.

OBJECTIVES: We examined cause of death in relation to age, length of follow-up and other baseline characteristics in patients in the 1985-1986 National Heart, Lung, and Blood Institute Percutaneous Transluminal Coronary Angioplasty (NHLBI PTCA) Registry. BACKGROUND: The manner in which cardiac versus noncardiac mortality of patients with coronary revascularization varies in relation to patient and study characteristics has not been well documented. METHODS: Cause of death determined from a review of 5 years of annual follow-up forms and death certificates was analyzed in 2,127 patients who had coronary angioplasty (mean age 57.6 years) without acute myocardial infarction. RESULTS: Within 5 years of the initial procedure, there were 205 deaths (9.6%), with 52.7% attributed to cardiac causes. Patients with a low baseline ejection fraction, history of hypertension, previous bypass surgery, previous myocardial infarction, inoperable or high surgical risk or multivessel disease had significantly higher 5-year cardiac mortality. Patients with a history of diabetes, congestive heart failure or severe concomitant noncardiac disease had higher rates of both cardiac and noncardiac mortality. As length of follow-up increased, older patients died of noncardiac causes more often than cardiac causes. Age > or = 65 years was a strong independent predictor of 5-year noncardiac mortality (p < 0.001), but not cardiac mortality (p = 0.08). CONCLUSIONS: All-cause mortality rates may be high in elderly revascularized patients, yet cardiac mortality may be less than that expected because of a high risk of noncardiac death. Although all-cause mortality is a more reliable end point than cause-specific mortality, both cardiac and all-cause mortality should be considered in coronary intervention studies involving older patients and long-term follow-up.

Myocardial infarction and cardiac mortality in the Bypass Angioplasty Revascularization Investigation (BARI) randomized trial.

BACKGROUND: Cardiac mortality and myocardial infarction (MI) rates are used to evaluate the efficacy of coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA). We compared 5-year cardiac mortality and MI rates in 1829 patients with multivessel disease randomized to CABG or PTCA. METHODS AND RESULTS: The 5-year cardiac mortality rate was 8.0% in patients assigned to PTCA compared with 4.9% in those assigned to CABG (relative risk [RR] of 1.55 with a 95% confidence interval [CI] of 1.07 to 2.23; P=.022). In a subgroup of 1476 nondiabetic patients, there were no significant differences between treatment groups in cardiac mortality either overall (4.6% versus 4.2%; RR= 1.04, 95% CI, 0.65 to 1.66; P=.908) or in subgroups based on symptoms, left ventricular function, number of diseased vessels, or stenotic proximal left anterior descending artery. The two treatment groups had similar event rates for the combined end point of cardiac death or MI. The RR for cardiac mortality in 264 patients who sustained an MI compared with those who did not was 5.9 (P<.001). MIs were more common after CABG during index hospitalization (P=.004), but in the PTCA group, they were more common after discharge (P<.001). CONCLUSIONS: The Bypass Angioplasty Revascularization Investigation (BARI) trial indicates 5-year cardiac mortality in patients with multivessel disease was significantly greater after initial treatment with PTCA than with CABG. The difference was manifest in diabetic patients on drug therapy. There were no significant differences overall for the composite end point of cardiac mortality or MI between treatment groups or for cardiac mortality in nondiabetic patients regardless of symptoms, left ventricular function, number of diseased vessels, or stenotic proximal left anterior descending artery.

Contemporary practice of coronary revascularization in U.S. hospitals and hospitals participating in the bypass angioplasty revascularization investigation (BARI).

OBJECTIVES: To assess generalizability of the Bypass Angioplasty Revascularization Investigation (BARI), we conducted a separate study comparing revascularization in U.S. and BARI hospitals. BACKGROUND: The BARI trial is a multicenter investigation comparing initial revascularization with percutaneous transluminal coronary angioplasty and coronary bypass graft surgery in patients with symptomatic multivessel coronary disease. METHODS: All revascularization procedures during 5 consecutive workdays were surveyed at 75 U.S. hospitals offering coronary angioplasty and bypass surgery and at all BARI hospitals. Data collected were demographics, extent of disease and type of current and previous revascularization. RESULTS: At both U.S. and BARI hospitals, 57% of all revascularization procedures were coronary angioplasty and 43% were bypass surgery. The U.S. hospitals had more patients with single-vessel disease, acute myocardial infarction and primary procedures. Other characteristics were similar. The majority of revascularization procedures were angioplasty for single-vessel disease (U.S. 32% vs. BARI 25%) and bypass surgery for triple-vessel disease (U.S. 31% vs. BARI 31%). Overall, the choice between bypass surgery and angioplasty was similar in BARI and U.S. hospitals (adjusted odds ratio [OR] 1.0, p = 0.914). However, older patients were more likely and younger patients less likely to undergo bypass surgery in BARI versus U.S. hospitals (older patients: adjusted OR 1.6, p = 0.031; younger patients: adjusted OR 0.6, p = 0.028). The BARI protocol would have excluded 65% of all candidates for revascularization, for whom indications already exist for angioplasty or bypass surgery, and another 23%, for whom angioplasty would be contraindicated for individual lesions. CONCLUSIONS: Patients undergoing coronary revascularization in BARI and U.S. hospitals were generally similar, as was the choice between types of revascularization. Results from the BARI trial apply to approximately 300 (12%) candidates for coronary revascularization/workday.

Temperature modulation of calcium channel function in GH3 cells.

The effect of temperature on calcium channel function was studied in GH3 cells, using the whole cell patch-clamp methodology. Specific parameters examined were peak current amplitude, activation time, and inactivation time. Over the temperature range studied (22-37 degree C), the peak current amplitude was found to be a non-linear function of temperature, with low-threshold currents more temperature dependent than high-threshold currents. Both activation time and inactivation time were faster at higher temperatures, but, whereas inactivation was a continuous function of temperature, activation was not, with a distinct discontinuity between 27 and 32 degrees C. These findings suggest that caution must be exercised in extrapolating data on channel function obtained at room temperature to physiological temperatures.

Inhibition of calcium channel activation in GH3 cells by static magnetic fields.

Voltage-activated calcium channel function was examined in cultured GH3 cells using the whole-cell patch clamp technique. Exposure to a 120 mT static magnetic field resulted in a slight reduction in the peak calcium current amplitude and shift in the current-voltage relationship. The most significant change was a slowing of the channel activation rate without any change in the inactivation rate. All changes in channel function were reversible, with return to pre-exposure values within 3 min after the field was turned off. These alterations in channel function were temperature-dependent. The present findings are consistent with a functional disruption of the intramembranous portion of the calcium channel by a magnetically induced membrane deformation.

Angiographic correlates of lesion relevance and suitability for percutaneous transluminal coronary angioplasty and coronary artery bypass grafting in the Bypass Angioplasty Revascularization Investigation study (BARI).

The Bypass Angioplasty Revascularization Investigation (BARI) randomized 1,829 patients to percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG). Clinical site angiographers categorized lesions of > or = 50% diameter stenosis (n = 4,977) as clinically significant (86.4%) or nonsignificant (13.6%), and as favorable or nonfavorable for PTCA or CABG. More lesions were considered favorable for revascularization by CABG than by PTCA (91.5% vs 78.4%; p <0.001), particularly in the subgroup of 99% to 100% lesions (77.6% for CABG vs 21.9% for PTCA, p <0.001). Lesion features, characterized by the BARI core laboratory, were correlated with clinical site angiographers' assessment of clinical importance and suitability for PTCA or CABG. By multivariate analysis, positive predictors of clinical importance for 50% to 95% stenoses were greater stenosis severity, more jeopardized myocardium, larger reference diameter, and proximal vessel location. For 99% to 100% occlusions, predictors were shorter duration of occlusion and more jeopardized myocardium. PTCA suitability for 50% to 95% stenoses was inversely related to lesion length, ostial location, location on a bend, difficult access, and age, and was directly associated with greater Thrombolysis in Myocardial Infarction (TIMI) trial flow rate and more jeopardized myocardium. Predictors of PTCA suitability for 99% to 100% lesions were a lower American College of Cardiology/American Heart Association class and higher TIMI grade. Predictors for 50% to 95% stenoses were more jeopardized myocardium, larger reference diameter, and more proximal vessel location, and for 99% to 100% occlusions, more jeopardized myocardium and shorter duration of occlusion. Suitability for PTCA depended on lesion potency (<99%) and multiple morphologic characteristics that contrasted with the few angiographic features that adversely affect CABG suitability.

Clinical and operative characteristics of patients randomized to coronary artery bypass surgery in the Bypass Angioplasty Revascularization Investigation (BARI).

The surgical cohort of the Bypass Angioplasty Revascularization Investigation (BARI) is the largest group of patients with multivessel coronary artery disease randomly assigned to surgical treatment. This report presents baseline and operative characteristics of the cohort and describes some aspects of the variability in surgical practice among the 14 primary clinical centers and 4 co-investigational sites participating in BARI. Preoperative clinical and angiographic data and intraoperative variables were reviewed in 892 patients who were randomly assigned to coronary artery bypass grafting (CABG) and underwent operation. Associations between patient/lesion variables and operative characteristics are described. Of patients assigned to CABG, 87% underwent an operation within 2 weeks of randomization, as recommended in the protocol. Mean age of the 892 patients was 61 years, and mean age of the 235 women was greater than that of men (64 years vs 60 years); 64% of the surgical patients were classified as having unstable angina during the 6 weeks prior to randomization. Coronary angiography demonstrated 3-vessel disease (50% diameter narrowing by caliper measurement) in 41% of patients, and disease of the left anterior descending coronary artery was present in 87% of patients. A mean of 3.1 coronary arteries per patient were bypassed, and 82% of patients received 1 (70%) or 2 (12%) internal thoracic artery grafts. Prevalence of internal thoracic grafts was lower in elderly patients (74% of patients > or = 70 years), in women (72% vs 85% in men; p < 0.01), and in black participants (65%).(ABSTRACT TRUNCATED AT 250 WORDS)

Bypass Angioplasty Revascularization Investigation (BARI): baseline clinical and angiographic data.

This report presents baseline clinical and angiographic data from the Bypass Angioplasty Revascularization Investigation (BARI), a multicenter international trial assessing the relative efficacy of percutaneous transluminal coronary angioplasty (PTCA) versus coronary artery bypass graft surgery (CABG) in selected patients with multivessel coronary artery disease. PTCA is commonly performed in patients with multivessel coronary artery disease, yet its long-term efficacy in comparison to CABG is unknown. From August 1988 through August 1991, 1,829 qualifying patients with multivessel disease suitable for either procedure were randomized to PTCA or CABG; sample size estimates were based on anticipated 5-year mortality. Two registry populations were also defined for follow-up: (1) 2,013 patients eligible for randomization but not randomized; and (2) 422 patients considered by angiography as unsuitable for randomization. Patients randomized in BARI were at relatively high risk for subsequent cardiac events: 39% were > or = 65 years old, 55% had prior myocardial infarction, 69% presented with unstable angina or non-Q wave myocardial infarction, and 43% had 3-vessel coronary artery disease. Patients randomized to PTCA and CABG were equally matched in all the important baseline variables. The randomized and the eligible but not randomized groups were similar in most respects. However, the nonrandomized group had a higher proportion with college education; fewer with a history of myocardial infarction, heart failure, diabetes, and smoking; and a somewhat better average ejection fraction. At the 3-month follow-up, PTCA had been performed more commonly in the nonrandomized eligible patients, especially those with 2-vessel disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Threshold and limits of magnetic field action at the presynaptic membrane.

The relationship of field intensity and exposure duration to the inhibitory effect of static magnetic fields on presynaptic membrane function was examined in order to further define the mechanism of action of these fields. Miniature endplate potentials (MEPPs) were recorded from the isolated murine neuromuscular junction, maintained at a temperature of 35.5 degrees C, during exposure to static magnetic fields of varying duration and intensity. Inhibition of MEPP generation correlated well with the product of the square of the flux density and exposure time. At lower product values the relationship was linear with an absolute flux density threshold of 37.9 mT. Higher product values were associated with deviation from linearity indicative of a limit on the extent of inhibition. These findings are consistent with the hypothesis that static magnetic fields induce a reorientation of diamagnetic molecular domains within the membrane but with a restriction on the degree of reorientation imposed by the membrane's cytoskeleton.

A proposed mechanism for the action of strong static magnetic fields on biomembranes.

Experimental studies have demonstrated a temperature dependent effect by strong static magnetic fields on synaptic function. It is proposed that these findings may be explained by the diamagnetic properties of membrane phospholipids. The change in diamagnetic anisotropy coincidental with membrane thermotropic phase transition is responsible for the temperature dependence of this phenomenon and provides insight into the mechanism of action of these fields. At the prephase transition temperature highly diamagnetic anisotropic gel phase domains exist within a more fluid liquid-crystal phase. The partial magnetic reorientation of these domains results in membrane distortion and, thereby, functional impairment of contiguous ion specific channels. This mechanism adequately explains observations of the effects of static magnetic fields both on the central nervous system and at the neuromuscular junction. It is suggested that the same mechanism may be operative in other biosystems.

Membrane response to static magnetic fields: effect of exposure duration.

The time-course for the reversible alteration in presynaptic membrane function associated with exposure to a 123 mT static magnetic field was examined in an attempt to help define the mechanism whereby these fields influence biomembranes. Miniature endplate potentials (MEPPs) were recorded in the isolated murine neuromuscular junction preparation, maintained at a temperature of 35.5 degrees C. A minimum field duration of 50 s was found to be necessary for MEPP inhibition, with the efficacy of the field in inducing further inhibition being a function of its duration, but only for periods up to 150 s. Longer durations were not associated with additional inhibition. The time required for MEPP frequency to return to baseline, following deactivation of the field, was found to be linear for field durations up to 150 s. At and above this limit, recovery time remained constant at 135 s. These findings are consistent with the slow reorientation of diamagnetic molecular domains within the membrane and suggest tight coupling to the mechanism responsible for neurotransmitter release. The limits on this effect are compatible with the mechanical constraints imposed by the membrane's cytoskeleton.

Magnetic field influence on acetylcholine release at the neuromuscular junction.

The effects of a static magnetic field on the frequency of miniature end-plate potentials (MEPPs), recorded from the murine phrenic nerve-diaphragm preparation, were studied. In the presence of a 1,200-G field, statistically significant changes in MEPP frequency were observed. There was a modest increase in frequency at temperatures at and below 34 degrees C and a prominent decrease in frequency at temperatures above 35 degrees C. This temperature-dependent phenomenon was not seen in the absence of calcium in the perfusate. These results suggest that, at its phase transition temperature, the diamagnetic anisotropy of the presynaptic membrane is sufficient to influence neurotransmitter release by altering the function of the transmembrane calcium transfer mechanism.

Modification of spontaneous unit discharge in the lateral geniculate body by a magnetic field.

The effects of a 1230-G static magnetic field on spontaneous discharge frequency and discharge pattern of principle cells in the cat's lateral geniculate body (LGB) were examined. In 45% of cells studied, a decrease in frequency was seen after the field was turned on. This progressed, even after the field was turned off, with return to baseline after an average duration of 250 s. Onset typically was 75 s after the field was activated, with maximum effect occurring 135 sec thereafter. In 67% of those cells which exhibited a decrease in frequency and in 50% of those which did not, a change in discharge pattern, as reflected by the interspike interval histogram, was seen. When present, this was manifested as a decrease in short interspike intervals. The change in the interspike interval histogram usually persisted longer than the change in frequency. The gradual onset and prolonged time course of changes in LGB cell activity suggest either an alteration in the synaptic ionic environment or in neurotransmitter availability. It is hypothesized that strong magnetic fields produce a partial realignment of diamagnetically anisotropic molecules within the cell membrane, thereby distorting ion-specific channels sufficiently to alter their function.