Insights into the assessment of myocardial perfusion offered by different cardiac imaging modalities

Myocardial perfusion may be very broadly defined as the tightly regulated nutrient delivery to cardiac tissue. The different components of perfusion are myocardial blood flow, oxygen delivery, myocardial oxygen consumption, and myocardial blood volume. Historically, focus has been placed mostly on the assessment of blood flow. In many instances, knowledge of flow without information about these other aspects is inadequate. This review discusses the various cardiac imaging techniques used for the assessment of myocardial perfusion that represent diverse physiologic measures of “perfusion.” Their strengths and limitations are discussed as is their relevance to specific clinicopathologic conditions. Significant work still needs to be performed before all the aspects of myocardial perfusion can be precisely measured in human beings. Supported in part by a grant (R01-HL48890) from the National Institutes of Health, Bethesda, Md. Dr. Lindner is the recipient of a Fellowship Training Grant from the Virginia Affiliate of the American Heart Association, Glen Allen, Va. Dr. Kaul is an Established Investigator of the National Center of the American Heart Association, Dallas, Texas.     

Immunomodulatory effects of neem (Azadirachta indica) oil.

Immunomodulatory effects of neem oil were studied in mice. The animals were treated intraperitoneally (i.p.) with neem oil; control animals received the emulsifying agent with or without peanut oil. Peritoneal lavage, collected on subsequent days, showed a maximum number of leukocytic cells on day 3 following treatment with neem oil; peritoneal macrophages exhibited enhanced phagocytic activity and expression of MHC class-II antigens. Neem oil treatment also induced the production of gamma interferon. Spleen cells of neem oil-treated animals showed a significantly higher lymphocyte proliferative response to in vitro challenge with Con A or tetanus toxoid (TT) than that of the controls. Pre-treatment with neem oil, however, did not augment the anti-TT antibody response. The results of this study indicate that neem oil acts as a non-specific immunostimulant and that it selectively activates the cell-mediated immune (CMI) mechanisms to elicit an enhanced response to subsequent mitogenic or antigenic challenge.     

Surgical management and outcome of tuberculous atlantoaxial dislocation: a 15-year experience

OBJECTIVE: Tuberculous atlantoaxial dislocation is a rare disease entity. However, tuberculosis continues to be endemic in developing countries. Its earliest clinical presentation may be nonspecific, and delay in diagnosis may lead to irreversible neurological deficit. The management of tuberculous atlantoaxial dislocation includes ventral cervicomedullary decompression, occipitocervical arthrodesis, and administration of antituberculous medications. METHODS: Eighteen patients with tuberculous atlantoaxial dislocation who presented with neck pain and/or occipital headache, restriction of neck movement, difficulty swallowing, and signs of myelopathy were studied. Four patients had evidence of associated pulmonary tuberculosis. Plain x-rays of the cervical spine, computed tomographic scans, and magnetic resonance images were obtained in all patients for diagnosis and to assess the degree of dislocation and cervicomedullary compression. Simultaneous anterior neural decompression, via a transcervical retropharyngeal approach, and posterior arthrodesis were performed on all patients while they remained under anesthesia. Antituberculous chemotherapy was continued for 18 months. RESULTS: Histopathological analysis of excised tissue was consistent with tuberculosis in all patients. However, Ziehl-Neelsen staining for acid-fast bacilli was positive in two cases, and culture for Mycobacterium tuberculosis was negative in all patients. Patients with severe myelopathy experienced marked improvement. One patient died of fulminant resistant tuberculous meningitis. CONCLUSION: The transcervical retropharyngeal approach to the craniovertebral junction provides direct access to the lesion and avoids the potential bacterial contamination of the oral and pharyngeal cavity. It also prevents the development of persistent fistulae. Posterior stabilization should be performed directly after anterior neural decompression, while the patient remains under anesthesia, to prevent neurological deterioration before subsequent posterior fixation. This technique also is helpful for early mobilization of patients. The aim of surgical treatment should be to obtain biopsy tissue and to perform radical excision of epidural granulation tissue/abscess and infected bone using microsurgical technique. Antituberculous medication must be continued for 18 months with four drug regimens, and continuous monitoring of drug toxicity should be performed throughout the course of treatment.     

Influence of microbubble surface charge on capillary transit and myocardial contrast enhancement

OBJECTIVE: The goal of the study was to determine whether microbubble charge influences the microvascular retention of microbubble contrast agents. BACKGROUND: Interactions between serum proteins and lipid membranes are greater with anionic compared with neutral membranes. These interactions may influence the microvascular behavior of anionic lipid microbubbles. METHODS: Intravital microscopy of the cremaster muscle was performed in six wild-type mice and three C3-deficient mice during intravenous injection of lipid-shelled microbubbles with either a neutral or a negative charge. Both agents were prepared with and without a protective surface layer of polyethyleneglycol (PEG). Complement attachment to microbubbles was assessed by flow cytometry with flourescein isothiocyanate-conjugated anti-C3b monoclonal antibody. Myocardial contrast echocardiography was performed in six dogs to assess pulmonary and myocardial retention of microbubbles. RESULTS: Size-independent capillary retention of microbubbles, occurring for a few seconds to >10 min, was frequently observed with anionic, but rarely with neutral, microbubbles (4.3 +/- 0.3 vs. 0.4 +/- 0.1 mm(-3), p < 0.01). Anionic microbubble retention was reduced by 70% by surface PEG and was also markedly reduced in C3-deficient mice (1.4 +/- 0.1 mm(-3), p < 0.05 vs. wild-type). Flow cytometry demonstrated complement attachment to only anionic microbubbles. Contrast echocardiography indicated both pulmonary and myocardial retention of only anionic microbubbles, the latter evidenced by persistent opacification >10 min after bolus intravenous injection. CONCLUSIONS: Lipid microbubbles with a net negative charge can be retained within capillaries via complement-mediated attachment to endothelium. This property may be useful for the development of ultrasound contrast agents that can be imaged late after venous injection.     

Rhythm Control in Heart Failure Patients With Atrial Fibrillation : Contemporary Challenges Including the Role of Ablation

Because nonpharmacological interventions likely alter the risks and benefits associated with rhythm control, this paper reviews the role of current rhythm control strategies in atrial fibrillation. This report also focuses on the specific limitations of pharmacological interventions and the utility of percutaneous ablation in this growing population of patients with concomitant atrial fibrillation and heart failure.     

Multiplexed imaging of surface enhanced Raman scattering nanotags in living mice using noninvasive Raman spectroscopy

Raman spectroscopy is a newly developed, noninvasive preclinical imaging technique that offers picomolar sensitivity and multiplexing capabilities to the field of molecular imaging. In this study, we demonstrate the ability of Raman spectroscopy to separate the spectral fingerprints of up to 10 different types of surface enhanced Raman scattering (SERS) nanoparticles in a living mouse after s.c. injection. Based on these spectral results, we simultaneously injected the five most intense and spectrally unique SERS nanoparticles i.v. to image their natural accumulation in the liver. All five types of SERS nanoparticles were successfully identified and spectrally separated using our optimized noninvasive Raman imaging system. In addition, we were able to linearly correlate Raman signal with SERS concentration after injecting four spectrally unique SERS nanoparticles either s.c. (R² = 0.998) or i.v. (R² = 0.992). These results show great potential for multiplexed imaging in living subjects in cases in which several targeted SERS probes could offer better detection of multiple biomarkers associated with a specific disease.