Digoxin toxicity with normal digoxin and serum potassium levels: beware of magnesium, the hidden malefactor.

BACKGROUND: In recent years, digoxin use has been on the decline, with decreased incidence of digoxin toxicity. Hence, digoxin toxicity, when it occurs, remains an elusive diagnosis to emergency physicians. OBJECTIVE: To present a case of digoxin toxicity with normal levels of digoxin and serum potassium, but with severe hypomagnesemia. CASE REPORT: A 66-year-old woman presented with junctional tachycardia and ectopic atrial tachycardia. She was known to have congestive cardiac failure on diuretic therapy. Her serum digoxin level was within the normal range (2.4 nmol/L [normal = 1.9-2.6]) along with a normal serum potassium level (3.9 mmol/L [normal = 3.5-5]). However, there was severe hypomagnesemia (0.39 mmol/L [normal = 0.65-1.25]) precipitating digoxin-induced dysrhythmia, which responded well to intravenous magnesium therapy. CONCLUSION: This case reiterates that digoxin toxicity can occur in patients with normal digoxin and potassium levels, and in such patients, magnesium needs to be checked and treated to prevent potentially life-threatening dysrhythmias.

Pericardial Effusion in a Patient with Non-ST-Elevation Myocardial Infarction: Beware of a Hidden Malefactor.

Pericarditis with pericardial effusion in acute coronary syndrome is seen in patients with ST-elevation myocardial infarction specifically when infarction is anterior, extensive, and Q wave. It is very uncommon to have pericardial effusion in a patient with non-ST-elevation myocardial infarction. We present an elderly hypertensive patient who was diagnosed as non-ST-elevation myocardial infarction with pericardial effusion that turned out to be acute aortic dissection with catastrophic end. We conclude that, in patients with suspected diagnosis of non-ST-elevation myocardial infarction or unstable angina, if pericardial effusion is detected on echocardiography, aortic dissection needs to be considered.

Predictive value of a 4-hour accelerated diagnostic protocol in patients with suspected ischemic chest pain presenting to an emergency department.

OBJECTIVES: Currently recommended risk stratification protocols for suspected ischemic chest pain in the emergency department (ED) includes point-of-care availability of exercise treadmill/nuclear tests or CT coronary angiograms. These tests are not widely available for most of the ED's. This study aims to prospectively validate the safety of a predefined 4-hour accelerated diagnostic protocol (ADP) using chest pain, ECG, and troponin T among suspected ischemic chest pain patients presenting to an ED of a tertiary care hospital in Oman. METHODS: One hundred and thirty-two patients aged over 18 years with suspected ischemic chest pain presenting within 12 hours of onset along with normal or non-diagnostic first ECG and negative first troponin T (<0.010 µg/l) were recruited from September 2008 to February 2009. Low-probability acute coronary syndrome (ACS) patients at 4-hours defined as absent chest pain and negative ECG or troponin tests were discharged home and observed for 30-days for major adverse cardiac events (MACE) (Group I: negative ADP). High-probability ACS patients at 4-hours were defined by recurrent or persistent chest pain, positive ECG or troponin tests and were admitted and observed for in-hospital MACE (Group II: positive ADP). RESULTS: One hundred and thirty-two patients were recruited and 110 patients completed the study. The overall 30-day MACE in this cohort was 15% with a mortality of less than 1%. 30-days MACE occurred in 8/95 of group I patients (8.4%) and 9/15 of the in-hospital MACE patients in group II. The ADP had a sensitivity of 52% (95% CI: 0.28-0.76), specificity of 93% (0.85-0.97), a negative predictive value of 91% (0.83-0.96), a positive predictive value of 60% (0.32-0.82), negative likelihood ratio of 0.5 (0.30-0.83) and a positive likelihood ratio of 8.2 (3.3-20) in predicting MACE. CONCLUSION: A 4-hour ADP using chest pain, ECG, and troponin T had high specificity and negative predictive value in predicting 30-day MACE among low probability ACS patients discharged from ED. However, 30-day MACE in ADP negative patients was relatively high in contrast to guideline recommendations. Hence, there is a need to establish ED chest pain unit and adopt new protocols especially adding a point-of-care exercise treadmill test in the ED.

Ebstein anomaly in an adult presenting with wide QRS tachycardia: diagnostic and therapeutic dilemmas.

A 51-year-old man presented to the emergency department with sustained hemodynamically unstable wide QRS tachycardia and was revived successfully by immediate direct current (DC) cardioversion. There was evidence of previous open heart surgery, possibly atrial septal defect closure. Transthoracic echocardiography showed severe Ebstein anomaly with severe tricuspid regurgitation, no residual atrial septal defect, but with severe right ventricular dysfunction. Subsequent electrocardiograms showed transient atrial fibrillation with no manifest Wolff-Parkinson-White (WPW) accessory pathway during sinus rhythm. The cause of wide QRS tachycardia in this patient may be WPW related or ventricular tachycardia. This case illustrates the diagnostic and therapeutic dilemmas in patients with wide QRS tachycardia and suspected WPW syndrome. In addition, this case demonstrates that unoperated Ebstein anomaly can present in late adult life with tachyarrhythmias.

Aortic intramural hematoma with rupture and concomitant acute myocardial infarction: diagnostic and therapeutic dilemmas.

Aortic intramural hematoma is a contained aortic wall hematoma without a demonstrable intimal flap. It is similar to aortic dissection, but the pathology and pathophysiology are different. We report a patient with a chronic descending thoracic aortic intramural hematoma presenting with acute rupture and periaortic hematoma along with concomitant acute ST-elevation myocardial infarction that proved to be catastrophic without intervention. We discuss the diagnostic and therapeutic dilemma.

A large left atrial myxoma detected in emergency department using bedside transthoracic echocardiography.

We present a case of a 55-year-old woman with episodes of recurrent pulmonary edema that was diagnosed to have a large left atrial myxoma using bedside transthoracic echocardiography. This case illustrates the importance of a screening focused ultrasound examination of involved systems by emergency physicians in detecting causes for emergency clinical presentations.

Ischemic stroke secondary to aortic dissection following rifle butt recoil chest injury: a case report.

Ischemic stroke secondary to aortic dissection is not uncommon. We present a patient with left hemiplegia secondary to Stanford type A aortic dissection extending to the supra-aortic vessels, which was precipitated by rifle butt recoil chest injury. The diagnosis of aortic dissection was delayed due to various factors. Finally, the patient underwent successful Bentall procedure with complete resolution of symptoms. This case emphasizes the need for caution in the use of firearms for recreation and to take precautions in preventing such incidents. In addition, this case illustrates the need for prompt cardiovascular physical examination in patients presenting with stroke.

Adenosine 5'-triphosphate-sensitive potassium channel-mediated blood-brain tumor barrier permeability increase in a rat brain tumor model.

Brain tumor microvessels/capillaries limit drug delivery to tumors by forming a blood-brain tumor barrier (BTB). The BTB overexpresses ATP-sensitive potassium (K(ATP)) channels that are barely detectable in normal brain capillaries, and which were targeted for BTB permeability modulation. In a rat brain tumor model, we infused minoxidil sulfate (MS), a selective K(ATP) channel activator, to obtain sustained, enhanced, and selective drug delivery, including various sized molecules, across the BTB to brain tumors. Glibenclamide, a selective K(ATP) channel inhibitor, significantly attenuated the MS-induced BTB permeability increase. Immunocytochemistry and glibenclamide binding studies showed increased K(ATP) channel density distribution on tumor cells and tumor capillary endothelium, which was confirmed by K(ATP) channel potentiometric assay in tumor cells and brain endothelial cells cocultured with brain tumor cells. MS infusion in rats with brain tumors significantly increased transport vesicle density in tumor capillary endothelial and tumor cells. MS facilitated increased delivery of macromolecules, including Her-2 antibody, adenoviral-green fluorescent protein, and carboplatin, to brain tumors, with carboplatin significantly increasing survival in brain tumor-bearing rats. K(ATP) channel-mediated BTB permeability increase was also demonstrated in a human, brain tumor xenograft model. We conclude that K(ATP) channels are a potential target for biochemical modulation of BTB permeability to increase antineoplastic drug delivery selectively to brain tumors.

Calcium-dependent potassium channels as a target protein for modulation of the blood-brain tumor barrier.

Even though the blood-brain tumor barrier (BTB) is more permeable than the blood-brain barrier (BBB), the BTB still significantly restricts the delivery of anticancer drugs to brain tumors. Brain tumor capillaries that form the BTB, however, express certain unique protein markers that are absent or barely detectable in normal brain capillaries. We were able to biochemically modulate one such protein marker, the calcium-dependent potassium (K(Ca)) channel, by using a specific K(Ca) channel agonist, NS-1619, to obtain sustained enhancement of selective drug delivery, including molecules of varying sizes, to tumors in rat syngeneic and xenograft brain tumor models. Immunolocalization and potentiometric studies showed increased K(Ca) channel distribution on tumor cells compared with normal cells, suggesting that tumor cell-specific signals might induce overexpression of K(Ca) channels in capillary endothelial cells, leading to increased BTB permeability. We also demonstrated that the cellular mechanism for K(Ca) channel-mediated BTB permeability increase is due to accelerated formation of pinocytotic vesicles, which can transport therapeutic molecules across the BTB. This concept was investigated by using NS-1619 to facilitate increased delivery of carboplatin to brain tumor leading to enhanced survival in rats with brain tumors. Additionally, we showed that K(Ca) channel modulation resulted in enhanced permeability to macromolecules, including Her-2 monoclonal antibody and green fluorescent protein-adenoviral vectors, in a human, primary brain-tumor xenograft model. Therefore, K(Ca) channels are a potential, promising target for biochemical modulation of BTB permeability to increase antineoplastic drug delivery selectively to brain tumors.

Regulation of blood-brain tumor barrier permeability by calcium-activated potassium channels.

The blood-brain tumor barrier (BTB) limits the delivery of therapeutic drugs to brain tumors. We demonstrate in a rat brain tumor (RG2) model an enhanced drug delivery to brain tumor following intracarotid infusion of bradykinin (BK), nitric oxide (NO) donors, or agonists of soluble guanylate cyclase (sGC) and calcium-dependent potassium (K(Ca)) channels. We modulated K(Ca) channels by specific agonists and agents that produce NO and cGMP in situ to obtain sustained enhancement of selective drug delivery to brain tumors. Intracarotid infusion of BK or 1,3-dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2H-benzimidazol-2-one (NS-1619) significantly enhanced BTB permeability (K(i)) to [(14)C]alpha-aminoisobutyric acid in the brain tumor area but not in normal brain tissue. The K(i) increase achieved by BK, NS-1619, NO donors, or the sGC activator 3-(5'-hydroxymethyl-2'furyl)-1-benzylindazole (YC-1) was significantly attenuated when coinfused with a K(Ca) channel antagonist, iberiotoxin. Immunoblot and immunolocalization studies demonstrate overexpression of K(Ca) channels in tumor cells and capillaries compared with normal brain. The potentiometric assays demonstrate the functional activity of K(Ca) channels in rat brain endothelial and glioma cells. Additionally, we show that BK and NS-1619 significantly increased the density of transport vesicles in the cytoplasm of brain tumor capillary endothelia and tumor cells. The cleft indices and cleft area indices in rat tumor capillaries were significantly higher than in normal brain capillaries, and BK infusion did not alter these indices. These data demonstrate that the cellular mechanism for K(Ca) channel-mediated BTB permeability increase is due to accelerated formation of pinocytotic vesicles, which can transport drugs across BTB. We conclude that K(Ca) channels serve as a convergence point in the biochemical regulation of BTB permeability.