Volume 106

Number 5, Part 1 Brief Communications 1159

tion of indocyanin dye for detection and assessment of right to left intercardiac shunting. Am J Cardiol 37:171, 1976.

4. Valdes-Crus LM, Pieroni DR, Ronald JA, Varghese PJ: Echocardiographic detection of intra-cardiac right to left shunts following peripheral vein injection. Circulation 54:558, 1976.

5. Kotler NM, Segal B: Clinical echocardiography. Philadel- phia, 1960, The F.A. Davis Company, p 331.

Intravenous nitroglycerin-induced abducens nerve palsy

Jay Alexander, M.D., Kerry Kaplan, M.D., Richard Davison, M.D., E. Richard Blonsky, M.D., and Jonathan Gilbert, M.D. Chicago, Ill.

Fig. 3. Two-dimensional contrast echocardiogram, api- cal four-chamber view. The microcavitations are shown in the right heart cavities and are also noticeable in the left ventricle (indicated by arrows).

nary pressures were 35/20 mm Hg (mean, 20 mm Hg). Using contrast echocardiography by injection of repetitive dose of 10 cc of normal saline into the antecubital vein, microcavitations could clearly be demonstrated in the LV with the M-mode echocardiography technique (Fig. 2). This phenomenon was also seen by a two-dimensional study in which the microcavitations were seen to enter the LV through a high ventricular septal defect (Fig. 3).

Contrast echocardiography has been widely reported in the diagnosis of atrial and ventricular septal defect.‘e4 It has also been proven unsuccessful in demonstrating shunts in patients with uncomplicated ventricular septal defect and normal pulmonary artery pressure(s) in our echocardiographic laboratory. Contrast echocardiography has not been reported as being used in patients with LV-to-RA shunt with either normal or high pulmonary artery pressures. The patient described here (having had this shunt) exhibited signs of transient right-to-left shunt at the ventricular level by contrast echocardiography. The exact mechanism of this kind of shunt as demonstrated here is not clearly understood, but it can be assumed that the explanation for this is the possible existence of a transient RA-to-LV flow occurring in late diastole with the possible additive effect of the Valsalva maneuver. To the best of our knowledge, this is the first report of this phenomenon in a patient with normal pulmonary artery pressures exhibiting this rare anomaly.

REFERENCES

1. Kronick G, Slany J, Moesslacher H: Contrast M-mode echo- cardiography in diagnosis of atrial septal defect in asymptomatic patients. Circulation 59:372, 1979.

2. Fraker TD, Harris PJ, Behar VS, Kisslo JA: Detection and exclusion of interatrial shunts by two-dimensional echocar- diography and peripheral venous injection. Circulation 59:379, 1979.

3. Seward JB, Tajik AJ, Guierrez F, Hagler DJ, Moodie DS, Ritter DG: Contrast echocardiography, peripheral vein injec-

Intravenous nitroglycerin was recently approved for use in refractory angina pectoris, congestive heart failure associ- ated with myocardial infarction, perioperative hyperten- sion, and production of hypotension in surgical proce- dures.‘,* This report describes a patient receiving intrave- nous nitroglycerin for postmyocardial infarction angina who developed a unilateral sixth nerve palsy that resolved when the nitroglycerin was discontinued.

A 4%year-old hypertensive black male with a 4-year history of stable exertional angina was admitted to the Coronary Care Unit at Northwestern Memorial Hospital complaining of frequent episodes of substernal chest pressure for the previous 2 days. The ECG demonstrated an acute inferior wall myocardial infarction which was confirmed by serum enzyme elevations, including a 13% MB fraction of creatine phosphokinase (CK). The hospital course was complicated by repeated episodes of angina at rest associated with ST depression and T wave inversions in the anterolateral leads. When these recurred in spite of the application of 4 inches of 2% nitroglycerin ointment every 4 hours, intravenous nitroglycerin was started at 50 rg/min. Within 2 hours, the patient complained of a throbbing headache that was exacerbated by coughing or lying flat. Following several episodes of angina the nitro- glycerin infusion was increased to 200 pg/min and shortly thereafter the patient complained of diplopia at distances of greater than 20 feet. An increase in the dose of nitroglycerin to 250 pg/min resulted in worsening of the diplopia to near vision and a left abducens nerve palsy was noted. Neurologic examination was otherwise unremark- able; skull x-ray views and computed tomography of the skull were normal. Cardiac catheterization revealed severe multivessel disease and a five-graft aortocoronary bypass procedure was performed. The nitroglycerin infusion was tapered after surgery and when it was discontinued there was prompt and nearly complete resolution of the abdu-

From the Department of Medicine, Section of Cardiology and Department of Neurology, Northwestern Memorial Hospital and Northwestern Univer- sity Medical School.

Reprint requests: Kerry Kaplan, M.D., Suite 628, Wesley, 250 E. Superior St., Chicago, IL 60611.

1160 Brief Communications November, 1983

Amertixn Heart Journal

tens palsy. A careful search was made for other possible etiologies for the sixth nerve palsy. The lack of associated neurologic findings and the normal computed tomography and skull x-ray views excluded nuclear lesions or mass effect. There was no history of alcohol abuse, diabetes mellitus, trauma, meningitis, petrositis, botulism, or other toxic metabolic causes. The temporal association between resolution of the palsy and discontinuation of nitroglycer- in suggests a causal relationship with this drug via its effects on cerebral vasculature and hence intracerebral pressure, rather than to other possible vascular etiologies such as hemorrhagic or occlusive lesions.

Several authors have reported transient increases in intracranial pressure (ICP) following boluses of intrave- nous nitroglycerin.3*5 Rogers et al3 found significant eleva- tions in intracranial pressure in cats following boluses of intravenous nitroglycerin. Cottrell et ah4 noted an increase in ICP in five patients given intravenous nitroglycerin to induce controlled hypotension during craniotomy. Gagnon et a1.5 described a patient with increased intracranial pressure secondary to a posterior fossa mass who had further transient elevations in ICP following the intrana- sal administration of nitroglycerin. This report describes a patient who developed a reversible abducens palsy that was temporally related to the administration of modest doses of intravenous nitroglycerin. We postulate that the nitroglycerin caused a dilatation of intracerebral capaci- tance vessels which resulted in an increased ICP and caused the headaches and nerve palsy. Physicians using intravenous nitroglycerin should be aware of the potential for this complication.

REFERENCES

1. Hill NS, Antman EM, Green LH, Alpert JS: Intravenous nitroglycerin, a review of pharmacology, indications, thera- peutic effects and complications. Chest 79:69, 1981.

2. Cottrell JE. Turndorf I-L Intravenous nitroelvcerin. AM HEART J 96/550, 1978.

I”

3. Rogers MC, Hamburger C, Owens K, Epstein MH: Intracra- nial pressure in the cat during nitroglycerin induced hypoten- sion. Anesthesiology 51~227, 1979.

4. Cottrell JE, Gupta B, Rappaport H, Turndorf H, Ransohoff J, Flamm ES: Intracranial pressure during nitroglycerin induced hypotension. J Neurosurg 53:309, 1930.

5. Gagnon RL, Marsh ML, Smith RW, Shapiro HM: Intracrani- al hypertension caused by nitroglycerin. Anesthesiology 51:86, 1979.

Fasting hypoglycemia associated with disopyramide

Jeffery D. Semel, M.D., Edward Wortham, M.D., and Diane M. Karl, M.D. Chicago, Ill.

A 75-year-old man was admitted for evaluation of chest pain. Five years previously the patient had suffered a left

From the Department of Internal Medicine, St. Joseph Hospital; and the Department of Internal Medicine, Northwestern University Medical School.

Reprint requests: Jeffery D. Semel, M.D., Dept. of Internal Medicine, St. Joseph Hospital, 2900 North Lake Shore Dr., Chicago, IL 60657.

cerebral hemisphere infarction; there was no history of diabetes mellitus. Physical examination disclosed a right hemiparesis. An ECG showed acute anterior myocardial infarction. The fasting plasma glucose (FPG) was 89 mgldl and serum creatinine was 4.2 mg/dl. On the eighth hospital day multifocal premature ventricular contrac- tions were noted and disopyramide was begun, 150 mg orally, every 6 hours. On the twenty-sixth hospital day FPG was 38 mg/dl. No unusual symptoms were noted. The FPGs on the next 4 days were 39 mgldl, 52 mg/dl, 35 mg/dl, and 30 mg/dl; while the postprandial plasma glucoses (PPPG) were 48 mg/dl to 77 mg/dl. An oral glucose tolerance test (following 100 gm glucose) showed an FPG of 29 mg/dl and subsequent plasma glucoses of 110 mg/dl (Yz hour), 125 mg/dl (1 hour), 124 mg/dl (2 hour), 122 mg/dl(3 hour), 96 mg/dl(4 hour), and 72 mg/dl (5 hour). Corresponding insulin levels were 19 $J/ml, 64 MU/ml, 62 &l/ml, 57 rU/ml, 56 rU/ml, 25 rU/ml, and 22 pU/ml. Disopyramide was discontinued on the thirty-first hospital day. The FPG on the thirty-third hospital day was 72 mg/dl, and 81 mg/dl to 91 mg/dl on the subsequent 4 days.

Asymptomatic fasting hypoglycemia (range 29 mg/dl to 52 mg/dl) was unexpectedly observed. One PPPG was 48 mg/dl; however, 10 other nonfasting determinations ranged from 64 mg/dl to 125 mg/dl. The patient was anorexic and lost 20 pounds of weight during hospitaliza- tion. The only other medications taken during the period of documented hypoglycemia were trimethoprim-sulfa- methoxazole and digoxin, neither of which is known to cause hypoglycemia.’ Trimethoprim-sulfamethoxazole can potentiate the effect of an oral hypoglycemic agent by displacing the agent from its binding site.’

The antiarrhythmic agent, disopyrtunide, has been associated with hypoglycemia in three patients. Quevedo et a1.3 reported symptomatic fasting hypoglycemia in two 72-year-old patients receiving disopyramide, which promptly resolved upon discontinuation of the drug. One patient became hypoglycemic again after inadvertently resuming disopyramide. Goldberg et al4 reported an g&year-old patient taking disopyramide who also had fasting hypoglycemia. The hypoglycemia responded to discontinuation of the drug and recurred upon rechallenge with a single dose of disopyramide. The latter patient was asymptomatic.

Our patient had an insulin level of 19 ~U/ml when his FPG was only 29 mg/dl. A fasting insulin level obtained after discontinuing disopyramide was < 3.2 kU/ml, with a corresponding FPG of 72 mg/dl. The insulin levels in the patient of Goldberg et al. were somewhat lower, but remained 10 rU/ml despite a plasma glucose of 41 mgldl.’ These data suggest that inappropriate secretion of insulin may play a role in the production of hypoglycemia by disopyramide. Other factors such as increased peripheral glucose utilization have not been excluded, and further studies are needed to fully define the etiologic factors. Disopyramide phosphate has a serum half-life of 4 to 10 hours and is excreted by the kidneys.5 Dosage modifica- tion is indicated for renal insufficiency (not done in our patient). Renal impairment existed in our patient and in