The broad interest of my laboratory is to better understand the redistribution of cardiac output and altered hemodynamics when intact animals are exposed to "stressful" stimuli. Redistribution of cardiac output following various forms of trauma (i.e. endotoxin, hemorrhage, coronary occlusion, sepsis, anaphylaxis) and chemical intake (i.e. alcohol, morphine and cocaine) are studies with in vivo models. In line with the physiologic changes that these stimuli elicit, I am interested in the regional blood flow adjustments that occur. Even though different stresses may lead to common hemodynamic profiles, it has been demonstrated that regional vascular alterations can be quite dissimilar. We are trying to distinguish how local regulation of a vascular bed may be governed by numerous factors that change when the entire cardiovascular system is responding to the above stimuli. For example how does reproductive steroid biosynthesis (eg testosterone) interact with vasomediators (i.e. nitric oxide and endothelin) in sepsis.
In each of the model systems, we are first interested in whether the central hemodynamic profile of the animal has been disturbed. This is determined by measures of cardiac output, central venous pressure, systemic arterial pressure (i.e. pulsatile and mean), and left ventricular pressures. Other hemodynamic information such as total peripheral and local vascular resistances are calculated from the measured variables. Respiratory and metabolic functions are also assessed during the experimental procedures. At the same time, we are determining regional organ and tissue blood flows using radioactively labelled tracer microspheres.
As demonstrated in our laboratory, local vascular adjustments such as an increase in gastrointestinal blood flow following ethanol administration or a large drop in cerebral vascular resistance after an anaphylactic challenge likely have related local controls that are not dependent on centrally controlled function.
Publications:
1. Mourelatos, M.G., Enzer, N., Ferguson, J.L., Rypins, E.B., Burhop, K.E. and Law, W.R.: The Effects of Diaspirin Crosslinked Hemoglobin in Sepsis. Shock, 5(2):141-148, 1996.
2. Sharma, A.C., Bosmann, H.B., Motew, S.J., Hales, K.H., Hales, D.B. and Ferguson, J.L.: Steroid Hormone Alterations Following Induction of Chronic Intraperitoneal Sepsis in Male Rats. Shock, 6(2):150-154, 1996.
3. Law, W.R., Mourelatos, M.G., Krahmer, R., Dziki, A.J., Lynch, W.H. and Ferguson, J.L.: Effects of Phentolamine or Yohimbine on Naloxones Action During Endotoxin Shock in Rats. Shock, 7(3):217-224, 1997.
4. Sharma, A.C., Motew, S.J., Farias,S., Alden, K.J., Bosmann, H.B., Law, W.R. and Ferguson, J.L.: Sepsis Alters Myocardial and Plasma Concentrations of Endothelin and Nitric Oxide. J. Mol. Cell. Card., 29:1469-1477, 1997.
5. Motew, S.J., Mourelatos, M.G., Miller, R.N., Ferguson, J.L. and Law, W.R.: Evidence that Adenosine Maintains Hepatosplanhnic Blood Flow During Peritoneal Sepsis in rats. Shock, 7(6):439-446, 1997.
6. Sam II, A., Sharma, A.C., Law, W.R. and Ferguson, J.L.: Splanchnic Vascular Control During Sepsis and Endotoxemia. Frontiers in Bioscience, (Invited Review): 2e, 72-92, 1997.
7. Alden, K.J., Sharma, A.C., Motew, S.J. and Ferguson, J.L.: Effect of Aminoguanidine on Plasma Nitric Oxide By-products and Blood Flow During Chronic Peritoneal Sepsis. Shock, 9(4):289-295, 1998.
8. Sharma, A.C., Sam II, A.D., Lee, L.Y., Hales, D.B., Law, W.R., Ferguson, J.L. and Bosmann, H.B.: Effect of N–Nitro-L-Arginine Methyl Ester on Testicular Blood Flow and Serum Steroid Hormones During Sepsis. Shock, 9(6):416-421, 1998.
9. Fogelson, B.G., Nawas, S.I., Vigneswaran, W.T., Ferguson, J.L., Law, W.R. and Sharma, A.C.: Diabetic Patients Produce an Increase in Coronary Sinus Endothelin-1 after Coronary Artery Bypass Grafting. Diabetes, 47:1161-1163, 1998.
10. Motew, S.J., Sam II, A.D., Mourelatos, M.G., Sharma, A.C., Alden, K.J., Ferguson, J.L. and Law, W.R.: Adenosine receptor antagonism affects regional resting vascular resistance during rat peritoneal sepsis. J. Surgical Res., 80:326-332, 1998.
11. Sam II, A.D., Sharma, A.C., Lee, L.Y., Hales, D.B., Law, W.R., Ferguson, J.L. and Bosmann, H.B.: Sepsis produces depression of testosterone and Steroidogenic Acute Regulatory (StAR) protein. Shock, 11(4):298-301, 1999.
12. Sharma, A.C., Fogeleson, B.G., Nawas, S.I., Sam II, A.D., Alden, K.J., Vigneswaran, W.T., Ferguson, J.L. and Law, W.R.: Increased endothelin-I but not nitric oxide concentration following myocardial reperfusion in diabetics undergoing coronary artery bypass grafting. Annal Thoracic Surg., In Press, 1999.