Expression of diverse Na+ channel messenger RNAs in rat myocardium. Evidence for a cardiac-specific Na+ channel.

This study examined the diversity of Na+ channel gene expression in intact cardiac tissue and purified myocardial cells. The screening of neonatal rat myocardial cell cDNA libraries with a conserved rat brain Na+ channel cDNA probe, resulted in the isolation and characterization of a putative rat cardiac Na+ channel cDNA probe (pCSC-1). The deduced amino acid sequence of pCSC-1 displayed a striking degree of homology with the eel, rat brain-1, and rat brain-2 Na+ channel, thereby identifying pCSC-1 as a related member of the family of Na+ channel genes. Northern blot analysis revealed the expression of a 7-kb CSC-1 transcript in rat cardiac tissue and purified myocardial cells, but little or no detectable expression of CSC-1 in rat brain, skeletal muscle, denervated skeletal muscle, or liver. Using RNase protection and Northern blot hybridization with specific rat brain Na+ channel gene probes, expression of the rat brain-1 Na+ channel was observed in rat myocardium, but no detectable expression of the rat brain-2 gene was found. This study provides evidence for the expression of diverse Na+ channel mRNAs in rat myocardium and presents the initial characterization of a new, related member of the family of Na+ channel genes, which appears to be expressed in a cardiac-specific manner.

Regional cardiac adrenergic function using I-123 meta-iodobenzylguanidine tomographic imaging after acute myocardial infarction.

The effect of acute myocardial infarction (AMI) on regional cardiac adrenergic function was studied in 27 patients mean +/- standard deviation 10 +/- 4 days after AMI. Regional adrenergic function was evaluated noninvasively with I-123 meta-iodobenzylguanidine (MIBG) using a dedicated 3-detector tomograph. Four hours after its administration, there was reduced MIBG uptake in the region of infarction, 0.38 +/- 0.31 counts/pixel/mCi x 103 compared with 0.60 +/- 0.30 counts/pixel/mCi x 103 and 0.92 +/- 0.35 counts/pixel/mCi x 103 in the zones bordering and distant from the infarct area, respectively, p less than 0.001. In all patients, the area of reduced MIBG uptake after 4 hours was more extensive that the associated thallium-201 perfusion defect with defect scores of 52 +/- 22 and 23 +/- 18%, respectively, p less than 0.001. After anterior wall AMI, the 4-hour MIBG defect score was 70 +/- 13% and the degree of mismatch between myocardial perfusion and MIBG uptake was 30 +/- 9% compared with 39 +/- 17 and 21 +/- 17% after inferior AMI, p less than 0.001 and p = 0.016, respectively. The 4-hour MIBG defect score correlated inversely with the predischarge left ventricular ejection fraction, r = -0.73, p less than 0.001. Patients with ventricular arrhythmia of greater than or equal to 1 ventricular premature complexes per hour, paired ventricular premature complexes or ventricular tachycardia detected during the late hospital phase had higher 4-hour MIBG defect scores, 62.5 +/- 15.0%, than patients with no detectable complex ventricular ectopic activity and a ventricular premature complex frequency of less than 1 per hour, 44.6 +/- 23.4%, p = 0.036.(ABSTRACT TRUNCATED AT 250 WORDS)

Prolonged hypoglycemic crisis associated with glyburide.

An elderly patient taking glyburide 5 mg/day for noninsulin-dependent diabetes mellitus was hospitalized because of severe hypoglycemia. Laboratory results indicated both renal and hepatic abnormalities were present at the time of admission. Despite infusion of 10% dextrose and supplemental boluses of 50% dextrose, the hypoglycemic crisis persisted for 3 days. After it resolved, the patient's diabetes was controlled by diet alone. The patient's age and the presence of hepatic and/or renal impairment must be taken in account in prescribing glyburide. Recognizing patients who may require dosage changes, and educating them on the signs and symptoms of hypoglycemia, may help prevent hospitalizations resulting from this complication associated with glyburide.

Ethanol-induced coronary vasodilation in patients with and without coronary artery disease.

To assess the influence of ethanol on coronary arterial blood flow and dimensions, we measured coronary sinus blood flow in 35 subjects (23 men and 12 women, aged 38 to 69 years; (29 with and 6 without coronary artery disease) before and during a 15- to 30-minute intracoronary infusion of (1) 5% dextrose in water (n = 15, controls) or (2) 5% dextrose in water (n = 20). In the controls heart rate, arterial pressure, and coronary sinus blood flow were unchanged. In those receiving ethanol at a rate that produced a concentration in coronary sinus blood of 285 +/- 102 (mean +/- SD) mg/dl, heart rate-systolic arterial pressure product was unchanged; coronary sinus blood flow rose 27 +/- 36%, and coronary vascular resistance fell 17 +/- 22% (p less than 0.05 in comparison to baseline); arterial-coronary sinus oxygen content difference fell (p less than 0.05), and epicardial coronary arterial dimensions were unchanged. Thus intracoronary ethanol increases coronary blood flow and decreases resistance without inducing a change in epicardial coronary dimensions, suggesting that its effect results from dilatation of the intramyocardial resistance vessels.

Quantitative rotational tomography with 201Tl and 99mTc 2-methoxy-isobutyl-isonitrile. A direct comparison in normal individuals and patients with coronary artery disease.

We tested the hypothesis that 99mTc 2-methoxy-isobutyl-isonitrile (99mTc MIBI), a new radiopharmaceutical for myocardial perfusion imaging, provides accurate noninvasive detection of coronary artery disease (CAD). Imaging in patients after exercise and at rest with 99mTc MIBI was compared with imaging after exercise and redistribution with 201Tl in 12 normal subjects and 38 patients with angiographic documentation of CAD (greater than or equal to 50% diameter stenosis). We used single-photon emission computed tomography (SPECT) and computer quantitation of regional tracer distribution. The quality of reconstructed images with 99mTc MIBI judged visually was superior to that of 201Tl in 88% of all studies performed and was comparable in the others. With the limits of normal as 2.5 SD below the mean of gender-matched normal volunteers, 201Tl SPECT identified 32 and 99mTc MIBI identified 36 patients with CAD (p = 0.2). 201Tl SPECT identified 45 of 75 (60%) and 99mTc MIBI identified 59 of 75 (79%) stenosed coronary arteries (p less than 0.05). The quantitative severity of perfusion defects was similar for the two tracers. 201Tl SPECT identified 104 reversibly ischemic myocardial segments compared with 134 with 99mTc MIBI (p less than 0.05). Thus, SPECT myocardial perfusion imaging with 99mTc MIBI and computer quantitation provides an accurate method for the noninvasive detection of significant coronary artery disease. Furthermore, image quality is generally superior to 201Tl, and reversibly ischemic myocardial segments may be better identified with 99mTc MIBI.

Cocaine-induced coronary-artery vasoconstriction.

Intranasal cocaine is used frequently as a local anesthetic during many rhinolaryngologic procedures. Although its "recreational" use in high doses has been associated with chest pain and myocardial infarction, this association has not been established when cocaine is used in low doses as a topical anesthetic, and its effect on the coronary vasculature of humans is unknown. We studied the effects of intranasal cocaine (10 percent cocaine hydrochloride; 2 mg per kilogram of body weight) on the blood flow in and dimensions of the coronary arteries and on myocardial oxygen demand in 45 patients (34 men and 11 women, 36 to 67 years of age) who were undergoing cardiac catheterization for the evaluation of chest pain. Heart rate, arterial pressure, blood flow in the coronary sinus (measured by thermodilution), and the dimensions of the epicardial left coronary artery (measured by quantitative arteriography) were measured before and 15 minutes after the intranasal administration of saline (in 16 patients) or cocaine (in 29). No variables changed after the administration of saline. After cocaine was administered, the heart rate and arterial pressure rose, the coronary-sinus blood flow fell (from a mean [+/- SD] of 149 +/- 59 ml per minute to 124 +/- 53 ml per minute), and the diameter of the left coronary artery decreased by 8 to 12 percent (P less than 0.01 for all comparisons). No patient had chest pain or electrocardiographic evidence of myocardial ischemia after the administration of cocaine. Subsequently, the administration of the alpha-adrenergic blocking agent phentolamine caused all these values to return to base-line levels. There was no difference in response between the patients found to have disease of the left coronary artery (n = 28) and those without such disease (n = 17). We conclude that the intranasal administration of cocaine near the dose used for topical anesthesia causes vasoconstriction of the coronary arteries, with a decrease in the coronary blood flow, despite an increase in myocardial oxygen demand, and that these effects are mediated by alpha-adrenergic stimulation. It is reasonable to assume that these effects would be more pronounced at the much higher doses associated with the recreational use of cocaine.