Role of inducible nitric oxide synthase in myocardial ischemia-reperfusion injury in sleep-deprived rats

Introduction

REM sleep deprivation (SD) decreases tolerance of the rat heart to ischemia-reperfusion (IR) injury; the underlying mechanisms, however, are unknown. This study aimed at determining whether changes in iNOS, Bax, and Bcl-2 gene expression are involved in this detrimental effect.

Method

SD was induced by flowerpot technique for a period of 4 days. This method is simple and able to induce sleep fragmentation which occurs as one of the sleep disorder symptoms in clinical conditions. The hearts of control and SD rats were perfused in Langendorff apparatus and subjected to 30 min ischemia, followed by 90 min reperfusion. The hemodynamic parameters (left ventricular developed pressure (LVDP), and ± dp/dt), NOx (nitrite + nitrate) level, infarct size, and mRNA expression of iNOS, Bax, and Bcl-2 were measured after IR.

Results

SD rats had lower recovery of post-ischemic LVDP (32.8 ± 2.5 vs. 51.5 ± 2.1 mmHg; P < 0.05), + dp/dt (1555 ± 66 vs. 1119.5 ± 87 mmHg/s; P < 0.05) and ? dp/dt (1437 ± 65 vs. 888 ± 162 mmHg/s; P < 0.05). SD rats also had higher NOx levels (41.4 ± 3.1 vs. 22.4 ± 3.6 μmol/L; P < 0.05) and infarct size (64.3 ± 2.3 vs. 38.3 ± 1.6%; P < 0.05) after IR, which along with LVDP, ± dp/dt restored to near normal status in the presence of aminoguanidine, a selective iNOS inhibitor. Following IR, expression of iNOS and Bax increased and Bcl-2 decreased (502, 372, and 54%, respectively) in SD rats; whereas in the presence of aminoguanidine, expression of iNOS and Bax significantly decreased and Bcl-2 increased (165, 168, and 19%, respectively).

Conclusion

Higher expression of iNOS and subsequent increase in apoptosis in the hearts after IR may contribute to less tolerance to myocardial IR injury in SD rats.

     

A successful anticoagulation protocol for the first HeartMate II implantation in the United States

Bleeding and thrombus formation are common problems with life-threatening implications in patients receiving a left ventricular assist device. We describe the anticoagulation protocol for the 1st patient in the United States to undergo successful implantation of the HeartMate II left ventricular assist system.     

Impact of COVID-19 Pandemic on Training: Global Perceptions of Gastroenterology and Hepatology Fellows in the USA

Background

The COVID-19 pandemic has impacted numerous facets of healthcare workers’ lives. There have also been significant changes in Gastroenterology (GI) fellowship training as a result of the challenges presented by the pandemic.

Aims

We conducted a national survey of Gastroenterology fellows to evaluate fellows’ perceptions, changes in clinical duties, and education during the pandemic.

Methods

A survey was sent to Gastroenterology (GI) fellows in the USA. Information regarding redeployment, fellow restriction in endoscopy, outpatient clinics and inpatient consults, impact on educational activities, and available wellness resources was obtained. Fellows’ level of agreement with adjustments to clinical duties was also assessed.

Results

One hundred and seventy-seven Gastroenterology fellows responded, and 29.4% were redeployed to non-GI services during the pandemic. COVID-19 impacted all aspects of GI fellowship training in the USA (endoscopy, outpatient clinics, inpatient consults, educational activities). Fellows’ level of agreement in changes to various aspects of fellowship varied. 72.5% of respondents reported that their programs provided them with increased wellness resources to cope with the additional stress during the pandemic. For respondents with children, 17.6% reported no support with childcare.

Conclusions

Our results show that the COVID-19 pandemic has impacted GI fellowship training in the USA in multiple domains, including gastrointestinal endoscopy, inpatient consults, outpatient clinics, and educational conferences. Our study highlights the importance of considering and incorporating fellows’ viewpoints, as changes are made in response to the ongoing pandemic.

     

Hypertension exacerbates the effect of hypercholesterolemia on the myocardial microvasculature

OBJECTIVE: Hypercholesterolemia (HC) and hypertension (HT) are both major risk factors for the development and progression of atherosclerotic heart disease, and their co-existence has been associated with an increased incidence of cardiac events in clinical studies. HC and HT are individually associated with abnormal myocardial vascular function, but whether HT exacerbates the HC-induced myocardial vascular dysfunction remains unclear. METHODS: We studied in pigs the effect of renovascular HT superimposed on diet-induced HC (HC+HT) on myocardial perfusion and microvascular permeability in vivo (using electron-beam computed tomography) in response to cardiac challenge (i.v. adenosine and dobutamine). The involvement of systemic and myocardial tissue oxidative stress in vitro was assessed by oxidizability of LDL, levels of endogenous antioxidants, and tissue activities of radical-scavenger systems. RESULTS: While in normal animals myocardial perfusion increased in response to i.v. adenosine (+36+/-13%, P<0.05), in HC and HT alone the increase was blunted. In HC+HT myocardial perfusion response was further attenuated and significantly lower than normal, and myocardial vascular resistance failed to decrease (+7.6+/-8.8 vs. -21.0+/-5.8%, P=0.02 versus normal). HC+HT also showed blunted response to dobutamine, and augmented increases in microvascular permeability in vivo. These functional abnormalities were associated with increased systemic and myocardial tissue oxidative stress compared to HC or HT alone, and a synergistic decrease in endogenous antioxidant defenses in myocardial tissue. Furthermore, chronic antioxidant vitamin supplementation in combined HC and HT improved myocardial vascular responses. CONCLUSION: HT amplifies the HC-induced myocardial microvascular dysfunction in vivo and increased oxidative stress in vitro. These alterations may potentially play a role in the increased incidence of cardiac events observed when HC and HT co-exist.     

Fiducial-based fusion of 3D dental models with magnetic resonance imaging

Purpose

Magnetic resonance imaging (MRI) is widely used in study of maxillofacial structures. While MRI is the modality of choice for soft tissues, it fails to capture hard tissues such as bone and teeth. Virtual dental models, acquired by optical 3D scanners, are becoming more accessible for dental practice and are starting to replace the conventional dental impressions. The goal of this research is to fuse the high-resolution 3D dental models with MRI to enhance the value of imaging for applications where detailed analysis of maxillofacial structures are needed such as patient examination, surgical planning, and modeling.

Methods

A subject-specific dental attachment was digitally designed and 3D printed based on the subject’s face width and dental anatomy. The attachment contained 19 semi-ellipsoidal concavities in predetermined positions where oil-based ellipsoidal fiducial markers were later placed. The MRI was acquired while the subject bit on the dental attachment. The spatial position of the center of mass of each fiducial in the resultant MR Image was calculated by averaging its voxels’ spatial coordinates. The rigid transformation to fuse dental models to MRI was calculated based on the least squares mapping of corresponding fiducials and solved via singular-value decomposition.

Results

The target registration error (TRE) of the proposed fusion process, calculated in a leave-one-fiducial-out fashion, was estimated at 0.49 mm. The results suggest that 6–9 fiducials suffice to achieve a TRE of equal to half the MRI voxel size.

Conclusion

Ellipsoidal oil-based fiducials produce distinguishable intensities in MRI and can be used as registration fiducials. The achieved accuracy of the proposed approach is sufficient to leverage the merged 3D dental models with the MRI data for a finer analysis of the maxillofacial structures where complete geometry models are needed.