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VCU Pauley Heart Center

Basic science research

Dr. KukrejaThe VCU Pauley Heart Center basic research lab deals primarily with cardiovascular research on ischemia and reperfusion injury. This includes investigations on different approaches and therapeutic tools that have the potential to minimize the damage to the heart that occurs following a heart attack.

The major cause of cardiovascular disease involves inefficient delivery of oxygen and glucose to the cells of the heart, mainly the heart muscle cells or cardiomyocytes. These cells, after a period of stress, begin dying and the efficiency of the heart’s pumping action declines. This, in turn, can lead to complications in other organs and result in a compromised quality of life.

Preconditioning of the heart is a process by which either physiological or pharmacological stimuli may render the heart more resistant to such ischemic attacks. The concept, first introduced in 1986, remains of high interest to both scientists and clinicians because it may “warn” the heart prior to a cardiovascular event and allow it to be “ready” when the attack occurs, with less cell death as a result. More cells, as well as energy for the survival of these cells, would be preserved.

Our previous work has demonstrated that the induction of several endogenous proteins by various stimuli is protective to the ischemic heart. These include heat shock proteins, inducible and endothelial nitric oxide synthases, hypoxia inducible factor 1-α, etc.
We also have shown that many mediators are involved, such as bradykinin, adenosine, monophosphoryl lipid A, etc.

Most recently, we investigated the role of sildenafil citrate (Viagra) and vardenafil HCl (Levitra), the well-known and widely used erectile dysfunction drugs, in the protection of an ischemic heart.

Several projects are in progress in our laboratory. Some study preconditioning at the cellular level in a cell culture setting using cell lines or primary cells isolated from left ventricles of rats and mice. Other studies are concerned with ex-vivo settings utilizing our well-established Langendorff model of the isolated buffer-perfused heart. In addition, we have an in vivo model of myocardial infarction for further testing the drugs or physiological approaches and examining their potential effects on the entire living system.

In order to further understand the mechanism of action of these pharmacological or physiological tools, we conduct molecular and biochemical analyses of the hearts following treatments and examine the role(s) of several genes and proteins in the observed protection.

Our research is funded mainly by NIH (R01 grants to Dr. Rakesh C. Kukreja, Professor and P.I.) and also AHA (Dr. Lei Xi, Assistant Professor).

The major goal of our research is to establish novel strategies for cardioprotection against ischemia/reperfusion injury and to further investigate the underlying mechanism(s).
Projects include:

  • Sildenafil in cardioprotection
  • Vardenafil in cardioprotection
  • The role of hypoxia in preconditioning
  • Protein kinase G and its role in cardioprotection
  • KCa channel and its role in preconditioning
  • Cyclooxygenase inhibitors and their effect on the healthy and diseased heart
  • The role of inflammation in remodeling following a heart attack
  • The effect of rapamycin, the antibiotic used for coating stents to prevent restenosis, on the heart following myocardial infarction

Many other projects also are ongoing utilizing leading edge tools such as gene knock-out mice, small interfering RNA technology, micro-arrays, protein over-expression using delivery vectors, hemodynamic assessment and infarct size measurement.

All the above techniques are employed to provide a more general understanding of each observation and help us distinguish between true phenomena and artifacts.



Virginia Commonwealth University Medical Center
School of Medicine
VCU Health Pauley Heart Center
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