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Microvascular/Exercise Studies
- Effects of botulinum neurotoxin A on the microvasculature
- Botulinum neurotoxin A blocks the pre-synaptic release of neurotransmitter by cleaving the molecules that are responsible for tethering of the neurotransmitter vesicles with the pre-synaptic neuronal membrane during the neurally-mediated release of neurotransmitter following an action potential. These studies are using an acute striated muscle preparation (the rat cremaster muscle) to examine the effects of BoNTA on the release of norepinephrine from the sympathetic neurons innervating the microcirculation.
- Mechanism of action of the hemodynamic effects of Peroxisome Proliferator Activated Receptor (PPAR) gamma (subtype) agonists
PPAR gamma agonists (ex. Avandia) restore the sensitivity of insulin receptors and improve the plasma lipid profile in Type 2 diabetes. Clinicians are reluctant to use these compounds in patient populations that may be a risk for heart failure because of the observed edema accompanying PPAR gamma administration. Initial hemodynamic studies in rats chronically instrumented with ascending aortic flow probes and blood pressure telemetry devices suggest that these compounds elicit a significant (25-30%) increase in cardiac output due to an equivalent decrease in systemic vascular resistance. Further studies suggest that this decreased resistance occurs at the microvascular level in striated muscle. Additional studies examining the microvasculature of striated muscle as well as hindlimb perfusion studies in chronically instrumented rats are underway.
- Current research suggests that endothelial mechanisms are important mediators of the hemodynamic responses to the PPAR gamma agonists. The laboratory currently is utilizing an endothelial PPAR gamma knockout mouse strain to pursue some of these questions.
- Cardiac output and arterial pressure changes during exercise in chronically instrumented mice Recent advances in gene targeted mouse strains need physiologic interventions such as exercise to be evaluated fully. These studies utilize techniques developed in this laboratory to monitor cardiac output and arterial pressure chronically in mice. These animals then are subjected to treadmill exercise and maximal cardiac output, stroke volume and systemic vascular resistance can be calculated. The effect of exercise of the muscles can also be studied.
- Effects of anesthetic agents on mouse hemodynamics
- Mice are increasingly used for studying the genetic control mechanisms of the cardiovascular system. Many of these studies involve an integrative assessment of the impact of specific gene targeting that requires in-vivo hemodynamic measurements. Too often, these studies are performed in anesthetized mice, without assessments of the effects of anesthetics on the hemodynamics of interest. Current research indicates that commonly used anesthetics can have profound effects on the hemodynamics under study and that mice require several days (5-7) of post-surgical recovery before the hemodynamic parameters become stabilized to pre-surgical levels. This information is critical in studies of the effect of certain factors on exercise and muscle activity.
- Macro-Microcirculatory relationships
- The relationship between the systemic circulation and the microcirculation is being studied in several of the cardiovascular experiments. These studies relate changes in the resistance blood vessels (both diameter and number) to observed alterations in the systemic vascular resistance. These studies are important to understand pathological states that affect blood flow in the hands and fingers and feet and toes.
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