Ashok Gowda

Heat shock improves recovery and provides protection against global ischemia after hypothermic storage

BACKGROUNDnImproved methods of donor heart preparation before preservation could allow for prolonged storage and permit remote procurement of these organs. Previous studies have shown that overexpression of heat-shock protein 72 provides protection against ischemic cardiac damage. We sought to determine whether rats subjected to heat stress with only 6-hour recovery could acquire protection to a subsequent heart storage for 12 hours at 4 degrees C.nnnMETHODSnThree groups of animals (n = 10 each) were studied: control, sham-treated, and heat-shocked rats (whole-body hyperthermia 42 degrees C for 15 minutes). After 12-hour cold ischemia hearts were reperfused on a Langendorff column. To confirm any differences in functional recovery, hearts were then subjected to an additional 15-minute period of warm global ischemia after which function and lactate dehydrogenase enzyme leakage were measured.nnnRESULTSnHeat-shocked animals showed marked improvements compared with controls in left ventricular developed pressure (63+/-4 mm Hg versus 44+/-4 mm Hg, p<0.05) heart rate x developed pressure (13,883+/-1,174 beats per minute x mm Hg versus 8,492+/-1,564 beats per minute x mm Hg, p<0.05), rate of ventricular pressure increase (1,912+/-112 mm Hg/second versus 1,215+/-162 mm Hg/second, p<0.005), rate of ventricular pressure decrease (1,258+/-89 mm Hg/second versus 774+/-106 mm Hg/second, p<0.005). Diastolic compliance and lactate dehydrogenase release were improved in heatshocked animals compared with controls and sham-treated animals. Differences between heat-shocked animals and control or sham-treated animals were further increased after the additional 15-minute period of warm ischemia. Western blot experiments confirmed increased heat-shock protein 72 levels in heat-shocked animals (>threefold) compared with sham-treated animals and controls.nnnCONCLUSIONSnHeat shock 6 hours before heart removal resulted in marked expression of heat-shock protein 72 and protected isolated rat hearts by increased functional recovery and decreased cellular necrosis after 12-hour cold ischemia in a protocol mimicking that of heart preservation for transplantation. Protection was further confirmed after an additional 15-minute period of warm ischemia.

Development of an endoscopic fluorescence image-guided OCT probe for oral cancer detection

Oral squamous cell carcinoma is a disease which progresses through a number of well-defined morphological and biochemical changes. Optical coherence tomography (OCT) is a rapidly-evolving, non-invasive imaging modality which allows detailed probing of subsurface tissue structures with resolution on the order of microns. While this technique offers tremendous potential as a diagnostic tool for detection and characterization of oral cancer, OCT imaging is presently associated with a field of view on the order of millimeters, and acquisition time on the order of seconds. Thus, OCTs utility as a rapid cancer screening technique is presently limited. On the other hand, imaging of tissue autofluorescence provides a very rapid, high-throughput method for cancer screening. However, while autofluorescence measures may be sensitive to cancer, they are often non- specific and lead to a large number of false positives. In the present work, we have developed a fluorescence image guided optical coherence tomographic (FIG-OCT) probe in which tissue autofluorescence images are simultaneously used to guide OCT image acquisition of suspicious regions in real time. We have begun pre-clinical pilot studies with this instrument in a DMBA-induced model of oral cancer in the hamster cheek pouch. Initial results indicate that the FIG- OCT approach shows promise as a rapid and effective tool for screening of oral cancer.

Closed-loop feedback control of laser therapy using magnetic resonance imaging

In the destructive treatment of tumors or other lesions, laser therapies such as laser induced thermal therapy (LITT) or interstitial laser phototherapy (ILP) offer tremendous potential to minimize surgical complications, reduce recovery time and hospital stays, and decrease associated health care costs. While laser procedures have gained wide popularity in dermatology and ophthalmology, their potential has yet to be fully realized in treatment of deep tissues where the damage front created by the laser can not be readily visualized. In the present work, we facilitate this visualization by producing an image of spatial temperature distribution via non-invasive magnetic resonance imaging (MRI). Further, we have implemented a control strategy which allows us to utilize this information for the feedback control of laser thermal therapies. We have begun to explore the feasibility of using this system for improving the safety and efficacy oflaser thermal surgery.