ECG of the Month

Shannon N. Larrabee 1Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN 55108

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Christopher D. Stauthammer 1Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN 55108

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A 13-year-old 2.4-kg (5.3-lb) spayed female domestic shorthair cat was examined by a referring veterinarian because of lethargy, inappetence, and signs of right forelimb pain when ambulating. Radiographic findings for the right forelimb were suggestive of lameness as a result of historic trauma. The owners of the cat elected for conservative workup of the problem, and supportive pain management was instituted with administration of buprenorphine hydrochloride. Nine days later, the cat was taken to a veterinary teaching hospital's emergency service for evaluation of persistent lethargy, inappetence, and lameness. On examination of the cat, there was concern for shock with hypothermia (rectal temperature, 36.7°C [98.1°F]), and borderline bradycardia (heart rate, 140 beats/min) and dull mentation were noted. A cardiac arrhythmia or murmur was not detected, and femoral pulses were reported as fair and synchronous with the heartbeat bilaterally. The cat was assessed as being 5% dehydrated and had mild generalized muscle wasting.

The initial diagnostic evaluation included a CBC and serum biochemical analysis. The results of the CBC were unremarkable. Serum biochemical abnormalities included moderate azotemia (BUN concentration, 106 mg/dL [reference range, 12 to 39 mg/dL]; creatinine concentration, 3.2 mg/dL [reference range, 0.5 to 2.1 mg/dL]), moderate hyperphosphatemia (8.9 mg/dL; reference range, 3.3 to 7.8 mg/dL), and severe hypermagnesemia (6.6 mg/dL; reference range, 1.6 to 2.4 mg/dL). Abdominal ultrasonography revealed an infiltrative kidney lesion, a jejunal mass, and a hepatic mass. Microscopic examination of ultrasound-guided fine-needle aspirate specimens of the kidney and liver lesions revealed a predominantly lymphocyte population. The lymphocytes were medium to large, consistent with lymphoma. During the diagnostic workup, 6-lead ECG was performed. The cat was subsequently euthanized by IV injection of pentobarbital sodium, and postmortem examination confirmed a diagnosis of lymphoma. There were no pathological changes in the heart identified during postmortem examination.

ECG Interpretation

The 6-lead ECG recording (Figure 1) obtained from the cat revealed a regular sinus rhythm with a ventricular rate of 140 beats/min. Each QRS complex of the lead II tracing had an R-wave amplitude of 0.1 mV (reference range, < 0.9 mV), markedly prolonged duration of 0.06 seconds (reference range, < 0.04 seconds), and deep S waves. The QT intervals were markedly prolonged (duration, 0.24 seconds; reference range, 0.12 to 0.18 seconds). The overall mean electrical axis was −180° indicative of a right axis shift. In light of the mean electrical axis and other ECG findings, a diagnosis of right bundle branch block was made.

Figure 1—
Figure 1—

A 6-lead ECG recording obtained from a 13-year-old domestic shorthair cat that was evaluated because of signs of right forelimb pain when ambulating and persistent inappetence and lethargy. The cat was severely hypermagnesemic (6.6 mg/dL; reference range, 1.6 to 2.4 mg/dL). In this initial tracing, there is normal sinus rhythm with a calculated heart rate of 140 beats/min. The overall mean electrical axis is −180° with deep S waves with prolonged QRS-complex duration (0.06 seconds; reference range, < 0.04 seconds), indicative of a right-axis shift and right bundle branch block. The QT interval is markedly prolonged (0.24 seconds; reference range, 0.12 to 0.18 seconds). Paper speed 50 mm/s; 1 cm = 1 mV.

Citation: Journal of the American Veterinary Medical Association 256, 1; 10.2460/javma.256.1.56

Discussion

In humans, mild hypermagnesemia results in nonspecific clinical signs such as flushing, warmth, or lightheadedness. However, circulating magnesium concentrations of 6 to 12 mg/dL (5 to 10 mEq/L) result in characteristic ECG changes including prolongation of the PR interval, increased duration of the QRS complex, prolonged QT interval, delayed intraventricular conduction, bradycardia, and increased amplitude of the T wave.1,2 Circulating magnesium concentrations of 9 to 12 mg/dL (7.5 to 10 mEq/L) can induce somnolence and hypotension; concentrations > 12 mg/dL (10 mEq/L) may potentially result in sinoatrial and atrioventricular block, ventricular arrhythmias, hypoventilation, and paralysis, and those exceeding 15.6 mg/dL (13 mEq/L) can result in cardiac asystole or respiratory arrest.1,3 On the basis of clinical and ECG similarities, hypermagnesemia is commonly misdiagnosed as hyperkalemia, thereby making the true incidence of ECG and clinical abnormalities associated with hypermagnesemia-related derangements difficult to quantify. For the cat of the present report, ECG characteristics included QRS-complex prolongation, right bundle branch block, and QT-interval prolongation. When ventricular conduction disturbances result in QRS-complex prolongation, assessment of the terminal forces late in the QRS complex can help indicate force vector directionality and further support an axis shift. In this cat, the late terminal forces of the QRS complexes were negative, further supporting a right axis shift and presence of right bundle branch block. In this case, the right bundle branch block may have been an incidental finding or secondary to interventricular conduction disturbances caused by the high serum magnesium concentration.

Magnesium is the fourth most abundant cation and the second most abundant intracellular electrolyte (after potassium) in humans.1,2 Although it is abundant intracellularly, there is no major Mg2+ concentration gradient across the cellular membrane. One study4 demonstrated that free intracellular Mg2+ concentrations range from 0.6 to 1.3 mmol/L, with extracellular concentrations ranging from 0.8 to 1.1 mmol/L in the liver, kidney, and brain cells of rats.5 The physiologic concentration of free intracellular Mg2+ in rat ventricular myocytes ranges from 0.8 to 1.0 mmol/L.6 Therefore, the ECG changes observed secondary to hypermagnesemia are not directly attributable to alterations in resting membrane potential. However, magnesium may be indirectly contributing to observed ECG changes via off-target effects on other electrolyte-associated processes such as sodium-potassium membrane transport and interference with calcium release within the sarcoplasmic reticulum of myocardial cells.

Bradycardia is a common clinical finding in humans with hypermagnesemia.3 Results of a study7 that evaluated the effect of magnesium in the sinus node of dogs indicate Mg2+ likely interferes with the slow inward Na+ current, which ultimately has a negative chronotropic effect. In another study,8 a negative chronotropic effect of magnesium on the sinus node of rabbits was evident. In addition to possible direct interference with electrolyte currents in these cells, magnesium ions also have an indirect effect on resting membrane potential through effects on the Na+/K+ ATPase pump. The primary ions involved in determining the resting membrane potential and rapid depolarization of the myocardium and pacemaker tissues include Na+, K+, and Ca2+. A crucial component of maintaining an appropriate resting membrane potential and subsequent cellular depolarization is the Na+/K+ ATPase pump. The function of the Na+/K+ ATPase pump is to reestablish the appropriate ion gradients of Na+ and K+ after an action potential is propagated, resulting in repolarization of the cellular membrane.9 For the Na+/K+ ATPase pump to function appropriately, Mg2+ ions are required to bind to ATP, thereby inducing its biologically active state.2,10 It can be inferred marked hypermagnesemia or hypomagnesemia could indirectly cause appreciable conduction disturbances through alterations in resting membrane potential secondary to the effects of Mg2+ on Na+ and K+ membrane concentrations.

The underlying cause of QT-interval prolongation in patients with a high serum magnesium concentration is not well understood, and further research is indicated. Long QT syndrome is a well-established condition in humans for which genetic (inherited) channelopathies are cited as the most common cause. Some individuals with a genetic predisposition may also develop acquired long QT syndrome secondary to treatment with certain medications. For clinical long QT syndrome to develop, either the repolarizing K+ ion currents must be inhibited or the inward Na+ ion currents must be prolonged.11 In humans, long QT syndrome is the result of mutations in 1 of the 3 major susceptibility genes: LQT1, LQT2, and LQT3. In long QT syndrome type 1, there is a defect in the slow component of the repolarizing potassium current. In long QT syndrome type 2, the human ether-a-go-go-related gene (hERG) is defective.11 The hERG gene encodes for the pore-forming subunit of the rapidly activating delayed potassium channel (IKr), which is crucial for myocardial repolarization.12 The long QT syndrome type 2 hERG mutation has been further evaluated, and it was determined that magnesium ions do not play a role in hERG inactivation because the presence or absence of magnesium in solution made no difference on the rate or extent of gene inactivation.13 Lastly, mutations responsible for long QT syndrome type 3 cause abnormalities in a sodium channel (SCN5A), which allow for increased inward Na+ ion currents and prolonged depolarization.11 Acquired QT-interval prolongation has also been associated with other electrolyte disturbances such as hypokalemia, hypocalcemia, and hypomagnesemia.14

Magnesium also has a negative inotropic effect through interference with Ca2+ release from the sarcoplasmic reticulum of cardiac myocytes. It has been identified that magnesium can interfere with Ca2+ release from the sarcoplasmic reticulum through 2 separate mechanisms (types I and II) on ryanodine receptors (RyRs). Type I is characterized by Mg2+ binding to the high-affinity Ca2+ site on the RyRs, whereas type II is characterized by Mg2+ binding to the low-affinity Ca2+ site on the RyRs.15 When intracellular Mg2+ concentrations are markedly elevated, the probability that more RyR channels will be closed because of Mg2+ ions outcompeting Ca2+ ions for activation site binding increases. This inhibition ultimately blocks the calcium-induced calcium-release pathway and decreases overall intracellular Ca2+ concentration. The amount of available intracellular Ca2+ ions directly influences the peak contractile force generated by the myocardium.16 These effects have been postulated as the pathophysiologic mechanism underlying the negative inotropic effect commonly identified in humans with hypermagnesemia. Although magnesium can have an appreciable inhibitory effect on overall sarcoplasmic release of Ca2+, these changes do not affect phases 1 and 2 of the myocyte action potential. Therefore, at this time, the reason for QRS-complex prolongation in cases of hypermagnesemia is unclear.

The treatment of hypermagnesemia involves identification and management of the underlying cause, such as kidney failure, constipation, poor gastrointestinal tract motility, exogenous sources, or some type of endocrinopathy. In mild cases, removal of any exogenous sources of magnesium is generally sufficient for effective treatment. Calcium gluconate may be administered IV to stabilize a patient in critical condition because of the antagonizing effects of Ca2+. In severe cases that are secondary to chronic kidney disease, serial hemodialysis is required to lower blood magnesium concentration.3 The cat of the present report was given an IV 40-mL bolus of lactated Ringer solution and subsequently maintained on an IV infusion of LRS (9 mL/h) for an unspecified time prior to euthanasia.

References

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