Control of tissue oxygenation by S-nitrosohemoglobin in human subjects.

S-Nitrosohemoglobin (SNO-Hb) is unique among vasodilators in coupling blood flow to tissue oxygen requirements, thus fulfilling an essential function of the microcirculation. However, this essential physiology has not been tested clinically. Reactive hyperemia following limb ischemia/occlusion is a standard clinical test of microcirculatory function, which has been ascribed to endothelial nitric oxide (NO). However, endothelial NO does not control blood flow governing tissue oxygenation, presenting a major quandary. Here we show in mice and humans that reactive hyperemic responses (i.e., reoxygenation rates following brief ischemia/occlusion) are in fact dependent on SNO-Hb. First, mice deficient in SNO-Hb (i.e., carrying C93A mutant Hb refractory to S-nitrosylation) showed blunted muscle reoxygenation rates and persistent limb ischemia during reactive hyperemia testing. Second, in a diverse group of humans-including healthy subjects and patients with various microcirculatory disorders-strong correlations were found between limb reoxygenation rates following occlusion and both arterial SNO-Hb levels (n = 25; P = 0.042) and SNO-Hb/total HbNO ratios (n = 25; P = 0.009). Secondary analyses showed that patients with peripheral artery disease had significantly reduced SNO-Hb levels and blunted limb reoxygenation rates compared with healthy controls (n = 8 to 11/group; P < 0.05). Low SNO-Hb levels were also observed in sickle cell disease, where occlusive hyperemic testing was deemed contraindicated. Altogether, our findings provide both genetic and clinical support for the role of red blood cells in a standard test of microvascular function. Our results also suggest that SNO-Hb is a biomarker and mediator of blood flow governing tissue oxygenation. Thus, increases in SNO-Hb may improve tissue oxygenation in patients with microcirculatory disorders.

Relationship of phasic left atrial volume and emptying function to left ventricular filling pressure: a cardiovascular magnetic resonance study.

BACKGROUND: Left atrial volume (LAV) and emptying fraction (LAEF) are phasic during cardiac cycle. Their relationships to left ventricular end diastolic pressure (LVEDP) have not been fully defined. METHODS: Forty one patients undergoing clinically indicated left heart catheterization were recruited for same day cardiovascular magnetic resonance (CMR). LAV and LAEF were assessed in cine images using biplane area and length method. Three phasic LAV was assessed at LV end systole (LAV(max)), LV end diastole (LAV(min)) and late LV diastole prior to LA contraction (LAV(ac)). LAEF was assessed as global LAEF (LAEF(Total)), passive (LAEF(Passive)) and active LAEF (LAEF(Contractile)). The relationships of phasic LAV and LAEF to LVEDP were assessed using Receiver operating characteristic comparing areas under the curves (AUC). RESULTS: The mean age of the patients was 59 years. A history of heart failure was present in 16 (39%) with NYHA functional class III or IV in 8 (20%) patients. Average LV ejection fraction was 49 ± 16% ranging from 10% to 74% and LVEDP by catheterization 14 ± 8 mmHg ranging from 4 mmHg to 32 mmHg. LAV(min) had the strongest association with LVEDP elevation (>12 mmHg) (AUC 0.765, p = 0.002), as compared to LAV(max) (AUC 0.677, p = 0.074) and LAV(ac) (AUC 0.735, p = 0.008). Among three phasic LAEF assessed, LAEF(Total) had the closest association with LVEDP elevation (AUC 0.780, p = 0.001), followed by LAEF(Contractile) (AUC 0.698, p = 0.022) and LAEF(Passive) (AUC 0.656, p = 0.077). CONCLUSIONS: Increased LAV(min) and decreased LAEF(Total) have the best performance in identifying elevated LVEDP among three phasic LAV and LAEF analyzed. Future studies should further characterize LA phasic indices in clinical outcomes.

Tirofiban Induced Thrombocytopenia: A Rare but Severe Adverse Effect.

With the advent of medical technology, coronary angiography is a common practice to evaluate patient for coronary artery disease. Normally, patients undergoing angiogram receive antiplatelets, anticoagulants, and platelet aggregation inhibitor agents. Glycoprotein IIb/IIIa receptor inhibitors are a type of platelets antiaggregant agents that can cause severe thrombocytopenia in very few cases. We present a case of a 69-year-old female who presented with chest pain, underwent an angiography and had two stents placed. She was administered tirofiban during angiogram that caused acute severe thrombocytopenia decreasing her platelets count from 224 to 2 k/mm3 within 1 day. Patients platelets gradually recovered after trial of steroid and platelets transfusion. Antiplatelets (Aspirin and Clopidogrel) were resumed; however, patient's platelets remained stable.

A Case Report of Dilated Biventricular Heart Failure from Hyperthyroidism: A Rare Presentation.

Hyperthyroidism is a common metabolic disorder with many cardiovascular manifestations. In rare cases, untreated hyperthyroidism can lead to thyrotoxic cardiomyopathy with severe left ventricular (LV) dysfunction. This case report aims to discuss the pathogenesis of heart failure in hyperthyroidism and the available treatment options. A 51-year-old male with a past history of untreated hyperthyroidism presented to our hospital for the evaluation of shortness of breath and dysphagia. Workup revealed atrial flutter and severe biventricular dilated cardiomyopathy. Stabilization thyroidectomy was performed due to dysphagia, and treatment with oral antithyroid medications was initiated. The patient was discharged on synthroid and beta-blockers. Untreated hyperthyroidism can lead to biventricular failure even in the young. Untreated hyperthyroidism leads to significant mortality and morbidity. Untreated hyperthyroidism is associated with atrial fibrillation, heart failure, pulmonary hypertension (PH), and angina-like symptoms. Further studies should be done to evaluate the pathogenesis of Graves/Goiter hyperthyroidism and the least-invasive, safe, and definitive treatment options should be discovered. Current treatment options are limited and include medication that needs to be taken lifelong; they are associated with toxicity. Radioactive iodine ablation comes with the drawback of long-term replacement therapy. The last option is surgery, which is invasive and has its own complications.

Anomalous Origin of Coronary Arteries Arising from the Right Coronary Cusp: A Rare Presentation.

The anomalous origin of coronaries is rare. The purpose of this case report is to show a rare anomalous origin of coronaries. A 64-year-old female presented with chest pain that was typical in nature. The patient had left heart catheterization that showed an anomalous origin of coronaries, where all the coronaries were arising from the right coronary cusp. The patient had a significant disease in the distal left anterior descending artery, but it was a small vessel. Medical management was chosen. This is a rare presentation of the coronary anatomy.