Tissue magnesium levels and the arrhythmic substrate in humans.

INTRODUCTION: Magnesium deficiency has been implicated in the pathogenesis of sudden death, but the investigation of arrhythmic mechanisms has been hindered by difficulties in measuring cellular tissue magnesium stores. METHODS AND RESULTS: To see if magnesium deficiency is associated with a propensity toward triggered arrhythmias, we measured tissue magnesium levels and QT interval dispersion (as an index of repolarization dispersion) in 40 patients with arrhythmic complaints. Magnesium was measured in sublingual epithelium using X-ray dispersive analysis. QT interval dispersion was assessed on 12-lead surface ECGs in all patients, and programmed stimulation was performed in 28. The sublingual epithelial magnesium level ([Mg]1), but the not the serum level, correlated inversely with QT interval dispersion in 40 patients (r = 0.58, P < 0.005); in 12 patients undergoing repeat testing on therapy, the change in magnesium also correlated inversely with the change in QT dispersion (r = 0.61, P < 0.05). Patients with left ventricular ejection fractions > 40% had significantly higher tissue magnesium and lower QT dispersion (34.5 +/- 0.5 mEq/L, 81 +/- 8 msec) than those with left ventricular ejection fractions < 40% (32.7 +/- 0.5 mEq/L, P < 0.01, and 114 +/- 9 msec, P < 0.05). There was no difference in either [Mg]1 or QT dispersion in the 16 patients with inducible monomorphic ventricular tachycardia versus the 12 noninducible patients. CONCLUSION: Reduced tissue magnesium stores may represent a significant risk factor for arrhythmias associated with abnormal repolarization, particularly in patients with poor left ventricular systolic function, but may not represent a risk for excitable gap arrhythmias associated with a fixed anatomic substrate (e.g., monomorphic ventricular tachycardia).

Provocation of hypotension and pain during upright tilt table testing in adults with fibromyalgia.

OBJECTIVE: Fibromyalgia is a common but poorly understood problem characterized by widespread pain and chronic fatigue. Because chronic fatigue has been associated with neurally mediated hypotension, we examined the prevalence of abnormal responses to upright tilt table testing in 20 patients with fibromyalgia and 20 healthy controls. METHODS: Each subject completed a symptom questionnaire and underwent a three stage upright tilt table test (stage 1:45 minutes at 70 degrees tilt; stage 2, 15 minutes at 70 degrees tilt with isoproterenol 1-2 micrograms/min; stage 3, 10 minutes at 70 degrees tilt with isoproterenol 3-4 micrograms/min). An abnormal response to upright tilt was defined by syncope or presyncope in association with a drop in systolic blood pressure of at least 25 mm Hg and no associated increase in heart rate. RESULTS: During stage 1 of upright tilt, 12 of 20 fibromyalgia patients (60%), but no controls had an abnormal drop in blood pressure (P < 0.001). Among those with fibromyalgia, all 18 who tolerated upright tilt for more than 10 minutes reported worsening or provocation of their typical widespread fibromyalgia pain during stage 1. In contrast, controls were asymptomatic (P < 0.001). CONCLUSION: These results identify a strong association between fibromyalgia and neurally mediated hypotension. Further studies will be needed to determine whether the autonomic response to upright stress plays a primary role in the pathophysiology of pain and other symptoms in fibromyalgia.

Transient time course of cocaine-induced cardiac depression versus sustained peripheral vasoconstriction.

OBJECTIVES: The goal of this study was to define in vivo the magnitude and temporal course of cocaine-induced cardiac depression separate from peripheral vascular loading changes. BACKGROUND: Cocaine administration immediately alters arterial pressure, ventricular filling, contractility and heart rate. These combined changes have complicated previous analyses of the cardiac effects of cocaine, because routine measures of function are influenced by all these factors. METHODS: Pressure-volume loops and relations were measured by conductance catheter technique in 10 intact chest anesthetized dogs before and up to 30 min after administration of cocaine (3 mg/kg intravenously). Heart rate was kept constant by atrial pacing, and data were obtained before and after ganglionic blockade. RESULTS: Cocaine decreased ejection fraction, cardiac output and maximal rate of rise of left ventricular pressure (dP/dtmax) and increased arterial vascular resistance (all p < 0.05). The maximal change occurred by 2 min and was fully sustained for the next 30 min. In contrast, contractile indexes based on pressure-volume analysis (e.g., end-systolic pressure-volume relation) decreased only briefly at 2 min (by -19%) and returned to control value after 5 to 10 min. Reflex blockade with hexamethonium eliminated cocaine-induced vasoconstriction, but the magnitude and brevity of cardiac depression were unaltered. Ejection fraction, dP/dtmax and cardiac output now also decreased transiently, suggesting that the sustained changes observed before blockade in these variables were load related. Analogous load effects also explained changes in peak filling rate. CONCLUSIONS: Cocaine induces brief direct cardiac depression that is temporally dissociated from more sustained peripheral vasoconstriction. This dissociation is not measured by traditional left ventricular function analysis because of simultaneous load change. The transience of cardiac depression suggests that it probably does not play a major role in late adverse sequelae of cocaine administration.

Effects of vasopressin on pulmonary and systemic vascular mechanics.

The direct effects of vasopressin on the resistance and capacitance properties of the pulmonary and systemic vasculature were studied in nine aneural dogs on systemic and pulmonary bypass. The systemic and pulmonary pressure-flow, the systemic and pulmonary arterial pressure-volume, and the systemic and pulmonary venous pressure-volume relationships were determined for five levels of infused vasopressin. Vasopressin levels of approximately 10, 30, 150, 300, and 500 pg/ml were achieved by intravenous infusions. Samples of venous blood were drawn before and after each set of pressure-flow and pressure-volume relationships for the determination of vasopressin level by radioimmunoassay. A linear relationship was found between vasopressin level and systemic vascular resistance. Systemic vascular resistance increased 0.072 +/- 0.011 mmHg.kg.min.ml-1 for a change in vasopressin level of 100 pg/ml. Vasopressin did not affect pulmonary vascular resistance or any vascular compliance. High doses of infused arginine vasopressin were necessary to elicit substantial vasoconstriction.