Kurt G. Barringhaus

MicroRNAs Regulating a Change of Heart

MicroRNAs (miRNAs) are small RNAs, ∼22 nt long, that direct proteins to repress expression of mRNAs with which they are partially complementary. miRNAs are one of several classes of small RNA guides that provide sequence specificity to RNA silencing pathways (Reviewed in Ref. 1). In many respects, miRNAs are the normal cellular counterparts to small interfering RNAs (siRNAs), which guide RNA interference (RNAi), arguably the most famous RNA silencing pathway. With the exception of some ubiquitously expressed housekeeping genes, nearly every animal mRNA may, at some time in development and in one or more cell types, be repressed by one or more miRNAs. Thus, it is not surprising that miRNAs regulate key genetic programs in cardiovascular biology and are critical for cardiac development, endothelial function, lipid metabolism, ventricular hypertrophy, and post-infarction dysrhythmias. Here, we first review the key components of the RNA silencing pathway and then examine how RNA silencing regulates cardiovascular biology. Finally, we explore the opportunities miRNAs may provide for therapeutic intervention in human cardiac disease.

Outcomes from patients with multi-vessel disease following primary PCI: staged PCI imparts very low mortality

Background: CABG and PCI are effective means for revascularization of patients with multi‐vessel coronary artery disease, but previous studies have not focused on treatment of patients that first undergo primary PCI. Methods: Among patients enrolled in the global registry of acute coronary events (GRACE), clinical outcomes for patients presenting with STEMI treated with primary PCI were compared according to whether residual stenoses were treated medically, surgically, or with staged PCI. Clinical characteristics and data pertaining to major adverse cardiac events during hospitalization and 6 months after discharge were collected. Results: Of the 1,705 patients included, 1,345 (79%) patients were treated medically, 303 (18%) underwent staged PCI, and 57 (3.3%) underwent CABG following primary PCI. Hospital mortality was lowest among patients treated with staged PCI (Medical = 5.7%; PCI = 0.7%; CABG = 3.5%; P < 0.001 [PCI vs. Medical]), a finding that persisted after risk adjustment (Odds Ratio PCI vs. Medical = 0.16, [0.04–0.68]; P = 0.01). Six month postdischarge mortality likewise was lowest in the staged PCI group (Medical = 3.1%; PCI = 0.8%; CABG = 4.0%; P = 0.04 [PCI vs. Medical]). Patients revascularized surgically were rehospitalized less frequently (Medical = 20%; PCI = 19%; CABG = 6.3%; P < 0.05) and underwent fewer unscheduled procedures (Medical = 9.8%; PCI = 10.0%; CABG = 0.0%; P < 0.02). Conclusions: The results of this multinational registry demonstrate that hospital mortality in patients who undergo staged percutaneous revascularization of multivessel coronary disease following primary PCI is very low. Patients undergoing CABG following primary PCI are hospitalized less frequently and undergo fewer unplanned catheter‐based procedures.

Miniature Fabry–Perot Fiber Optic Sensor for Intravascular Blood Temperature Measurements

This paper presents a miniature fiber optic sensor for intravascular blood temperature measurements. Based on the Fabry–Perot interferometric principle, the sensor is fabricated by using chemical etching and thermal deposition. Before the animal test, static temperature calibration experiments are performed to characterize the sensors sensitivity, linearity, and hysteresis. A swine model is selected to perform the in-vivo experiment. During the in-vivo experiment, the swine intravascular blood temperature is measured at different locations in coronary arteries to demonstrate the sensors performance. The sensors usage in the thermal angioplasty application is successfully presented by capturing the rise and drop of local intravascular blood temperature variations.

A Study on Packaging of Miniature Fiber Optic Sensors for In-Vivo Blood Pressure Measurements in a Swine Model

Fiber optic sensors are potential techniques for diagnosis of coronary artery disease by measuring the blood pressure difference across a coronary artery stenosis. However, there is no available packaging method to accelerate the commercialization of the device from academic research. Obstacles that hinder the direct use of fiber optic sensors for this biomedical application were analyzed in this paper. Packaging requirements were summarized. A complete packaging solution to a miniature fiber optic sensor was designed accordingly, including fiber pretreatment, coating, tubing, and coil assembly, so that the packaged fiber optic sensor can work effectively and robustly in the coronary artery of a swine model. The successful blood pressure measurements in the aortic arch and the right coronary artery of the swine demonstrated that the reported packaging method provides effective protection and flexible steerability to fiber optic sensors for in-vivo blood pressure measurements.

Test of a novel miniature blood pressure sensor in the coronary arteries of a swine model

Fractional flow reserve (FFR) has proven to be very useful in diagnosis of narrowed coronary arteries. It is a technique that is used in coronary catheterization to measure blood pressure difference across a coronary artery stenosis in maximal flow. In-vivo blood pressure measurement is critical in FFR diagnosis. This paper presents a novel miniature all-optical fiber blood pressure sensor. It is based on Fabry-Perot (FP) interferometry principle. The FP cavity was fabricated by directly wet etching the fiber tip. Then, a diaphragm with well-controlled thickness was bonded to the end face of the fiber using the thermal bonding technique. Finally, the sensor was packaged with a bio-compatible and flexible coil for animal tests. A 25-50 kg Yorkshire swine model was introduced as the animal test target. The left anterior descending coronary artery (LAD) was exposed, and beyond the takeoff of the largest diagonal branch, a 3.0 mm vascular occluder was secured. Firstly, standard invasive manometry was used to obtain the blood pressure as baseline. Next, a guiding catheter was introduced into the ostium of the left main coronary artery, and the miniature blood pressure sensor was advanced into the LAD at a point beyond the vascular occlude. The blood pressure beyond the vascular occlude was recorded. The sensor successfully recorded the blood pressure at both near-end and far-end of the vascular occluder.

SAFETY OF SAME DAY DISCHARGE FOLLOWING PCI FOR NON-ST ELEVATION ACUTE CORONARY SYNDROMES

Background: Historically, patients undergoing percutaneous coronary intervention (PCI) remain hospitalized for observation overnight. However, with transradial approach, patients may be discharged during the day of procedure, although data supporting its safety is lacking. Methods: We analyzed data