Leigh Ann Jenkins

Is ouabain an authentic endogenous mammalian substance derived from the adrenal

Ouabain has recently been reported to be an endogenous mammalian substance released by the adrenal cortex and present in normal plasma. We have attempted to confirm and extend this observation. Using a ouabain radioimmunoassay developed in this laboratory, we fractionated by high-performance liquid chromatography (HPLC) normal human plasma from healthy volunteers to determine the presence of ouabain immunoreactivity and compare this immunoreactivity with authentic ouabain. In most subjects no ouabain immunoreactivity that coeluted with authentic ouabain was observed. Some subjects had ouabain-immunoreactive material present at low levels, but it was largely attributable to cross-reactivity with diverse substances found not to be ouabain. Similar results were obtained after analysis of plasma collected from 10 patients entering a medical intensive care unit. Studies of serum-free medium conditioned by bovine adrenocortical cells showed some ouabain immunoreactivity. To determine whether this material might be a steroid product of cholesterol side-chain cleavage, we performed chemical blockade of steroidogenesis, which effectively suppressed progesterone production by these cells but had no consistent effect on ouabain immunoreactivity in this medium. Stimulation of steroidogenesis with 22-R-OH-cholesterol in bovine adrenocortical cells did not produce any increase in the ouabain immunoreactivity present in conditioned medium. Subsequent HPLC studies of ouabain immunoreactivity in bovine adrenocortical cell-conditioned medium indicated that authentic ouabain did not account for most of the ouabain immunoreactivity in serum-free medium. Studies with bovine adrenocortical cells incubated in a minimal salt and glucose medium indicated a small peak of immunoreactivity that may correspond to authentic ouabain.(ABSTRACT TRUNCATED AT 250 WORDS)

Synergistic interactions between Ca2+ entries through L‐type Ca2+ channels and Na+–Ca2+ exchanger in normal and failing rat heart

We used confocal Ca2+ imaging and the patch‐clamp technique to investigate the interplay between Ca2+ entries through L‐type Ca2+ channels (LCCs) and reverse‐mode Na+–Ca2+ exchange (NCX) in activating Ca2+‐induced Ca2+ release (CICR) from the sarcoplasmic reticulum (SR) in cardiac myocytes from normal and failing rat hearts. In normal myocytes exposed to N(6),2′‐O‐dibutyryl adenosine‐3′,5′‐cyclic monophosphate (db‐cAMP, membrane‐permeable form of cAMP), the bell‐shaped voltage dependence of cytosolic Ca2+ transients was dramatically broadened due to activation of SR Ca2+ release at high membrane potentials (30–120 mV). This broadening of Ca2+‐transient voltage dependence could be prevented by KB‐R7943, an inhibitor of the reverse‐mode NCX. Trans‐sarcolemmal Ca2+ entries were measured fluorometrically in myocytes during depolarizing steps to high membrane potentials. The total Ca2+ entry (ΔFTot) was separated into two Ca2+ entry components, LCC‐mediated (ΔFLCC) and NCX‐mediated (ΔFNCX), by exposing the cells to the specific inhibitors of LCCs and reverse‐mode NCX, nifedipine and KB‐R7943, respectively. In the absence of protein kinase A (PKA) stimulation the amplitude of the Ca2+‐inflow signal (ΔFTot) corresponded to the arithmetic sum of the amplitudes of the KB‐R7943‐ and nifedipine‐resistant components (ΔFTot=ΔFLCC+ΔFNCX). PKA activation resulted in significant increases in ΔFTot and ΔFLCC. Paradoxically, ΔFTot became ∼threefold larger than the sum of the ΔFNCX and ΔFLCC components. In myocytes from failing hearts, stimulation of PKA failed to induce a shift in Ca2+ release voltage dependence toward more positive membrane potentials. Although the total and NCX‐mediated Ca2+ entries were increased again, ΔFTot did not significantly exceed the sum of ΔFLCC and ΔFNCX. We conclude that the LCC and NCX Ca2+‐entry pathways interact synergistically to trigger SR Ca2+ release on depolarization to positive membrane potentials in PKA‐stimulated cardiac muscle. In heart failure, this new form of Ca2+ release is diminished and may potentially account for the compromised contractile performance and reduced functional reserve in failing hearts.

Postpartum Depression and Apical Ballooning Syndrome (Takotsubo Syndrome)

BACKGROUND Acute cardiac complications occur occasionally during pregnancy and in the immediate postpartum period. Some of these cardiac scenarios are rare and provide a diagnostic challenge. We report a case of apical ballooning syndrome (ABS), also known as takotsubo cardiomyopathy or broken-heart syndrome, in a postpartum patient. CASE A 32-year-old multigravid woman presented at 17 days after delivery with chest pain typical for cardiac ischemic pain. Her prior obstetrical history included two uncomplicated vaginal deliveries, and the current postpartum period had been uncomplicated until the time of presentation. Cardiac catheterization was performed and showed normal coronary blood vessels with no evidence of coronary artery occlusion. Left ventricular systolic function was moderately depressed, with an ejection fraction of 45%. The patient had full recovery of myocardial function in less than 40 days, with a subsequent echocardiogram during that time showing a normal ejection fraction of 65%. CONCLUSION Apical ballooning syndrome is a rare reversible cardiac condition that should be differentiated from ischemic and peripartum cardiomyopathy, especially in the immediate postpartum period.

Coronary artery aneurysms in Behçet's disease

Behçets disease is a rare chronic autoimmune vasculitis with characteristic skin findings. Vascular involvement generally affects veins more than arteries, and coronary arterial involvement is extremely uncommon. Here we report the significant coronary artery aneurysms detected in a 41-year-old man with Behçets disease who had been in remission for 13 years. Our case illustrates the necessity of initial non-invasive cardiac assessment of patients with Behçets disease.

Emotional Stress and Tako-Tsubo Cardiomyopathy: Observations on 2 Distinct Clinical Phenotypes

Background Tako-tsubo syndrome is a transient cardiomyopathy usually precipitated by an acute emotional or physiological stress. Our study objectives were to review and analyze the impact of emotional stress on clinical variables, echocardiographic characteristics, and short-term outcomes in patients with tako-tsubo syndrome. Methods Retrospective chart review. Results Eleven patients presented with tako-tsubo syndrome (1 man and 10 women) during the 8-year period (January 2000 to January 2008). The patients were split into 2 groups, defined by presenting either after emotional stress (6/11, 54.5%) or after idiopathic/physical stress (5/11, 45.5%). The mean age was 53.8 (12.6) years. The mean peak troponin T level was 0.54 ng/mL (range, 0.03-2.06 ng/mL), and the mean left ventricular end-diastolic pressure was 15.8 (8.1) mm Hg. Emotional stress was associated with younger age (P = 0.024), a lower left ventricular end-diastolic pressure (P < 0.05), more ST segment changes on electrocardiogram (66.7% vs 40%), and a higher ejection fraction (P = 0.012). The patients in the idiopathic/physical stress group required more frequent hemodynamic support. Conclusions We conclude that clinical, echocardiographic, and outcome characteristics can differentiate tako-tsubo patients presenting with emotional stress from those with idiopathic/physical stress into 2 distinct clinical phenotypes. Clinicians should monitor idiopathic/physically stressed tako-tsubo patients carefully for hemodynamic compromise.

Closure of a giant saphenous vein graft aneurysm with embolization coil.

Aneurysms of saphenous vein grafts (SVGs) to coronary arteries are rare, usually asymptomatic and found incidentally. We report a case of an 84-year-old female who was found to have 8.1 × 8.4 cm aneurysm of an SVG to obtuse marginal (OM) artery. The aneurysm was prior to the distal anastamosis but no flow into the OM artery was noted. Cook Tornado Embolization Coils were used successfully to occlude the SVG proximal to the aneurysm. No complications occurred. The use of embolization coils is an effective and safe method for aneurysm occlusion when the anatomy is suitable and especially when patient is high risk for repeat surgical intervention.

Reactive Thrombocytosis Associated with Acute Myocardial Infarction following STEMI with Percutaneous Coronary Intervention.

The etiology of thrombocytosis can be classified into reactive and essential forms. The rate of thromboembolic events is higher in essential thrombocytosis, and these events include strokes, transient ischemic attacks, retinal artery or retinal vein occlusions, digital ischemia, and acute coronary syndrome. In a study of 732 medical and surgical patients with thrombocytosis, 88% had reactive thrombocytosis. Patients with reactive thrombocytosis do not require cytoreductive medications or antiplatelet treatment. We report a healthy 40-year-old man without any medical problems who developed a new episode of myocardial infarction associated with thrombocytosis after an episode of myocardial infarction followed by percutaneous coronary intervention. He had thrombocytosis, and his platelet function test did not reveal adequate inhibition. To treat his acute coronary syndrome, therapeutic enoxaparin was added, and clopidrogel was substituted with ticagrelor. We decided to start hydroxyurea to reduce platelets counts. Enoxaparin and hydroxyurea were discontinued when platelet count returned to baseline. JAK-2 and BCR/ABL mutations were negative. This case report highlights a clinical dilemma (reactive thrombocytosis), which is challenging in terms of management and pathophysiology.

LASER endovascular atherectomy with secondary stenting of technically challenging calcified celiac trunk stenosis

Endovascular therapy for chronic mesenteric ischemia is a proven, feasible alternative approach to open surgical repair with significantly lower morbidity and mortality. A clinical dilemma is encountered when technically challenging lesions are encountered during the procedure. We present here an 86 year‐old woman who had intractable abdominal pain with postprandial exacerbation. The patient had successful endovascular light amplification by stimulated emission of radiation atherectomy of a highly calcified celiac truck, showing the feasibility of this technique.

Left circumflex coronary artery to hepatic vein fistula: a case report and brief review of coronary vasculogenesis.

Coronary artery fistulas are rare coronary artery anomalies. Their clinical significance varies from a long asymptomatic course to overt heart failure and death. They are often detected incidentally with diagnostic coronary angiograms. Cardiologists increasingly encounter coronary artery fistulas secondary to recent improvements in cardiovascular imaging modalities. Management is still controversial, especially in asymptomatic cases with less significant shunts. Here, we describe a 62-year-old woman with a left circumflex artery to hepatic vein fistula found on coronary angiography. The patient is being managed conservatively using nuclear imaging studies and echocardiographic evaluation.

Hypertensive Heart Disease and the Role of Aldosterone Antagonists

Hypertensive heart disease (HHD) encompasses a spectrum of abnormalities resulting from structural and functional adaptations to chronic pressure overload. The clinical manifestations of HHD range from asymptomatic left ventricular hypertrophy (LVH) to symptomatic heart failure. HHD has been associated with increased risk of cardiovascular morbidity and all cause mortality. However, regression of LVH by antihypertensive therapy has been associated with improved outcome. The pathogenesis of HHD involves various hemodynamic and nonhemodynamic factors including neurohormone, aldosterone. Aldosterone enhances myocardial fibrosis through its direct effect on mineralocorticoid and angiotensin II receptors leading to excessive collagen deposition within the myocardium. Increased myocardial fibrosis is a major determinant of hypertensive remodeling and the transition to heart failure. Aldosterone antagonists are effective antihypertensive agents. Additionally, they have been shown to improve LV structural remodeling, systolic and diastolic function in patients with HHD independent of its effect on blood pressure. Data on long-term benefit of these agents have thus far been limited to patients with advanced systolic heart failure and post-acute myocardial infarction LV systolic dysfunction. The potential benefit of aldosterone antagonists in patients with heart failure and preserved LV systolic function is currently being investigated in large scale clinical trials.