Ketone Ester D-β-Hydroxybutyrate-(R)-1,3 Butanediol Prevents Decline in Cardiac Function in Type 2 Diabetic Mice.

Background Heart failure is responsible for approximately 65% of deaths in patients with type 2 diabetes mellitus. However, existing therapeutics for type 2 diabetes mellitus have limited success on the prevention of diabetic cardiomyopathy. The aim of this study was to determine whether moderate elevation in D-β-hydroxybutyrate improves cardiac function in animals with type 2 diabetes mellitus.

PK11195 Protects From Cell Death Only When Applied During Reperfusion: Succinate-Mediated Mechanism of Action.

: Reperfusion after myocardial ischemia causes cellular injury, in part due to changes in mitochondrial Ca handling, oxidative stress, and myocyte energetics. We have previously shown that the 18-kDa translocator protein of the outer mitochondrial membrane (TSPO) can modulate Ca handling. Here, we aim to evaluate the role of the TSPO in ischemia/reperfusion (I/R) injury.

The Design and Implementation of a Heart Disease Reversal Program in the Veterans Health Administration: Before and During the COVID-19 Pandemic.

Background: Heart disease continues to be the leading cause of death in the US, and the number of people with cardiovascular disease (CVD) is rising. CVD is more prevalent among military veterans than nonveterans, and veteran status is associated with higher risk of incident heart disease after controlling for socioeconomic status, other medical diseases, depression, and lifestyle. Many patients seeking care in the Veterans Health Administration, including those who undergo cardiac catheterization, meet the criteria for multimorbidity (defined as ≥ 2 chronic diseases).

"Cool Knees" as a Measure of Systemic Vascular Resistance in Cardiac Patients.

Introduction: Clinical assessment of cardiac output (CO) and systemic vascular resistance (SVR) in cardiac patients is often inaccurate. Since the genicular arteries form a watershed zone accessible to physical examination, we hypothesized that "cool knees" would reflect abnormalities in central hemodynamics.

Methods: Nineteen patients with cardiac diagnoses, but without distributive shock, had a measurement of skin temperature over the thigh, knee, and foot in parallel with central hemodynamics derived from invasive monitoring.

Repurposing Ophthalmologic Timolol for Dermatologic Use: Caveats and Historical Review of Adverse Events.

Ophthalmic timolol solution is increasingly being repurposed as a topical therapeutic for a variety of dermatologic diseases, including pyogenic granulomas, infantile hemangiomas, and chronic wounds. There are no published guidelines or protocols for use in these indications in adults, and the dermatologic community may not be familiar with adverse events that have been extensively documented relating to its ophthalmic use. We review the evidence available relating to adverse events to topical timolol use to evaluate its safety in dermatologic applications and to alert clinicians to screening and monitoring that is needed when repurposing this drug for dermatologic use.

Beta-adrenergic antagonist for the healing of chronic diabetic foot ulcers: study protocol for a prospective, randomized, double-blinded, controlled and parallel-group study.

Background: Diabetic foot ulcers (DFUs) are the most common cause of leg amputations and their management is extremely challenging. Despite many advances and expensive therapies, there has been little success in improving outcomes of DFUs. In prior work our laboratory has examined the effects of beta-adrenergic antagonists (βAAs) on skin and skin-derived cells.

Mitochondrial Quality Control in Aging and Heart Failure: Influence of Ketone Bodies and Mitofusin-Stabilizing Peptides.

Aging and heart failure (HF) are each characterized by increased mitochondrial damage, which may contribute to further cardiac dysfunction. Mitophagy in response to mitochondrial damage can improve cardiovascular health. HF is also characterized by increased formation and consumption of ketone bodies (KBs), which may activate mitophagy and provide an endogenous mechanism to limit the adverse effects of mitochondrial damage.

Cardiac-specific Conditional Knockout of the 18-kDa Mitochondrial Translocator Protein Protects from Pressure Overload Induced Heart Failure.

Heart failure (HF) is characterized by abnormal mitochondrial calcium (Ca) handling, energy failure and impaired mitophagy resulting in contractile dysfunction and myocyte death. We have previously shown that the 18-kDa mitochondrial translocator protein of the outer mitochondrial membrane (TSPO) can modulate mitochondrial Ca uptake. Experiments were designed to test the role of the TSPO in a murine pressure-overload model of HF induced by transverse aortic constriction (TAC).

Age-Adjusted D-Dimer in the Prediction of Pulmonary Embolism: Does a Normal Age-Adjusted D-Dimer Rule Out PE?

Risk assessment for pulmonary embolism (PE) currently relies on physician judgment, clinical decision rules (CDR), and D-dimer testing. There is still controversy regarding the role of D-dimer testing in low or intermediate risk patients. The objective of the study was to define the role of clinical decision rules and D-dimer testing in patients suspected of having a PE.

Nicotinic acid is a common regulator of heat-sensing TRPV1-4 ion channels.

Nicotinic acid (NA, a.k.a.

TRPV1 channels are involved in niacin-induced cutaneous vasodilation in mice.

Niacin is effective in treating dyslipidemias but causes cutaneous vasodilation or flushing, a side effect that limits its clinical use. Blocking prostaglandins in humans reduces but does not consistently eliminate flushing, indicating additional mechanisms may contribute to flushing. The transient receptor potential vanilloid 1 (TRPV1) channel, when activated, causes cutaneous vasodilation and undergoes tachyphylaxis similar to that seen with niacin.

Marked elevation of B-type natriuretic peptide in patients with heart failure and preserved ejection fraction.

Unlabelled: Marked elevations of B-type natriuretic peptide (BNP) are not generally seen in patients with heart failure and preserved ejection fraction (HFpEF). The objective of this study was to examine the clinical and laboratory characteristics of a large cohort of patients with HFpEF and markedly elevated BNP. A retrospective examination of 421 inpatients at a university hospital admitted with a diagnosis of HFpEF was performed.

Nicotinic acid activates the capsaicin receptor TRPV1: Potential mechanism for cutaneous flushing.

Objective: Nicotinic acid (also known as niacin or vitamin B3), widely used to treat dyslipidemias, represents an effective and safe means to reduce the risk of mortality from cardiovascular disease. Nonetheless, a substantial fraction of patients discontinue treatment because of a strong side effect of cutaneous vasodilation, commonly termed flushing. In the present study, we tested the hypothesis that nicotinic acid causes flushing partially by activating the capsaicin receptor TRPV1, a polymodal cellular sensor that mediates the flushing response on consumption of spicy food.

What lies beneath: Posterior ST elevation myocardial infarction with underlying right ventricular-paced rhythm.

A 66-year-old man with a history of coronary artery disease, stage V chronic kidney disease, peripheral arterial disease and a dual-chamber pacemaker experienced persistent chest and shoulder discomfort following his daily hemodialysis treatment. Treatment with clopidogrel had been discontinued three days previously due to impending vascular surgery. Electrocardiography revealed a right ventricular-paced rhythm with ST abnormalities indicative of posterior ST elevation myocardial infarction.

Progressive left ventricular noncompaction and systolic dysfunction.

Left ventricular noncompaction is a condition characterized by prominent ventricular trabeculations, often accompanied by systolic dysfunction. The present case involves an adult with a small ventricular septal defect, initially exhibiting mild systolic dysfunction and slightly prominent left ventricular trabeculations progressing over 13 years to severe dilated cardiomyopathy and overt noncompaction. The present case strongly suggests a correlation between the extent of noncompaction and the degree of systolic dysfunction.

Inhibition of soluble epoxide hydrolase limits niacin-induced vasodilation in mice.

Background: The use of niacin in the treatment of dyslipidemias is limited by the common side effect of cutaneous vasodilation, commonly termed flushing. Flushing is thought to be due to release of the vasodilatory prostanoids prostaglandin D2 (PGD2) and prostaglandin E2 from arachidonic acid metabolism through the cyclooxygenase pathway. Arachidonic acid is also metabolized by the cytochrome P450 system, which is regulated, in part, by the enzyme soluble epoxide hydrolase (sEH).

Myocardial uptake of 7'-(Z)-[(123)I]iodorotenone during vasodilator stress in dogs with critical coronary stenoses.

Background: There is a well-recognized need for a new generation of single photon emission computed tomography (SPECT) perfusion tracers with improved myocardial extraction over a wide flow range. Radiotracers that target complex I of the mitochondrial electron transport chain have been proposed as a new class of myocardial perfusion imaging agents. 7-(Z)-[(125)I]iodorotenone ((125)I-ZIROT) has demonstrated superior myocardial extraction and retention characteristics in rats and in isolated perfused rabbit hearts.

Comparative efficacy of ezetimibe/simvastatin, rosuvastatin, and atorvastatin in uncontrolled hyperlipidemia patients.

Objective: Treatment of dyslipidemia in high-risk patients specifies a low-density lipoprotein (LDL) cholesterol <100 mg/dL. The efficacy of higher-potency regimens in clinical practice in patients who have not achieved their LDL goal on generic therapy is not well characterized. The primary objective of this study was to determine the LDL-lowering efficacy of higher-potency strategies (ezetimibe/simvastatin, rosuvastatin, and atorvastatin) in high-risk patients who were switched from simvastatin therapy.

Phosphorylation of ARC is a critical element in the antiapoptotic effect of anesthetic preconditioning.

Background: Transient exposure to volatile anesthetics before cardiac ischemia/reperfusion (I/R), termed anesthetic preconditioning, limits myocardial injury and inhibits apoptosis. Apoptosis repressor with caspase recruitment domain (ARC) is a novel protein that has been demonstrated to protect cardiomyocytes from apoptosis induced by I/R and is regulated by phosphorylation. We therefore hypothesized that the antiapoptotic effect of anesthetic preconditioning is, in part, mediated by phosphorylation of ARC.

LDL = 5: Virtues and dangers of multidrug therapy of low-density lipoprotein cholesterol.

Multiple-drug therapy of dyslipidemia is frequently used to achieve treatment goals in high-risk patients with coronary artery disease. The authors report a case of a patient treated with a statin, fibrate, ezetimibe, and niacin in whom a calculated low-density lipoprotein cholesterol level of 5 mg/dL was achieved.