Research

 

Cardiovascular Research

Our research group focuses on translational research that is relevant to common cardiovascular disorders that cause mortality and morbidity in millions. We study the pathophysiology of heart attack, heart failure, shock, stroke, and potential therapies for these conditions.

Transverse left ventricular slices from a preclinical heart attack model. ​​​​A & D: Ischemic risk zone is the pink area. B & E: Area of no reflow is the nonfluorescent area after thioflavin injection (arrows). It is more extreme after nicotine. C & F: Red area=viable heart muscle. Pale area (arrows) represents the heart attack (dead heart cells). The size of the heart attack is greater in the nicotine group.
Schematic of causes of the no-reflow phenomenon whereby the microvasculature is not adequately perfused following opening up of an occlusion in the proximal coronary artery as treatment for a heart attack.
Transverse slices of the left ventricle weeks after an experimental heart attack in a preclinical model. Yellow=heart muscle; red=scar tissue. The experimental drug, Bendavia, was associated with smaller scar circumference and less dilation of the LV cavity in this example.

 

The effect of electronic cigarettes on fluid removed from the lungs in an experimental model. Left is lung lavage from an air treated subject. Right is lung lavage from an e-cigarette plus nicotine treated subject showing marked inflammatory cells. 

 

Cardiovascular Research Laboratory led by Robert A. Kloner, MD, PhD

This laboratory includes participation by Wangde Dai, MD who heads experimental cardiovascular surgery, Jianru Shi, PhD who carries out studies on genetic, biochemical, and histologic analysis, Juan Carreno, DVM who runs the Vivarium at HMRI and participates in surgical procedures, and our new Boswell Fellow, Rashid Alavi, PhD who works with our visiting scientist, Niema Pahleva, PhD to develop ways of analyzing the carotid artery waveform to predict cardiac events as well as AI projects.  

Current projects include studies designed to reduce the amount of damage that occurs during experimental myocardial infarction (heart attack). In the United States, there are about 800,000 heart attacks per year, and this remains a major cause of morbidity and mortality. One month mortality can be as high as 10% and nearly a quarter of older people suffering heart attack develop heart failure. Limiting the number of cells that die after coronary occlusion is one way of reducing mortality and morbidity after a heart attack and this approach remains a major focus of the laboratory. The laboratory has had success with some treatments: preconditioning, hypothermia, pharmacologic therapies such as mitochondrial protective proteins, a delta opioid antagonist, and others. We are currently exploring the effect of NAD+ in our experimental models in collaboration with Dr. Abdala Elkhal. Other studies have also explored therapies to prevent or treat heart failure and left ventricular dilatation after a heart attack.  

The no-reflow phenomenon refers to the inability to perfuse the microvasculature after re-opening the large occluded epicardial coronary artery which is the primary cause of a heart attack. We have studied the no-reflow phenomenon on its effect on adverse left ventricular remodeling following a heart attack and have also been working on therapies to reduce this devastating consequence of a heart attack. The presence of no-reflow is now recognized as an independent risk factor that predicts poor clinical outcomes, and it is independent of the size of a heart attack. We are exploring a unique therapy that involves iron nanoparticles in which the movement and spin of the particles, controlled by a specially designed magnet, may help to open clogged micro-vessels and improve no-reflow and/or help to deliver drugs to hard-to-reach areas in the wall of the heart.  

The laboratory has also been involved in cardio-toxicology studies, exploring the effects that electronic cigarettes (vaping) have on heart and lung function and pathology. These studies, carried out with our collaborators at UCI, have suggested that e-cigarettes may not be as safe as originally thought and may have adverse effects on the heart and lungs. Recent studies have found that exposure to e-cigarettes with nicotine impairs the ability of blood vessels to dilate normally; and may suppress the immune response of the heart.  

Dr. Kloner is involved in epidemiological studies exploring the effect of the class of drugs, called phosphodiesterase-5 (PDE-5) inhibitors on cardiovascular outcomes in men being treated with these drugs for erectile dysfunction. Recent studies from their research group have suggested that this class of drugs may have cardioprotective effects and is associated with lower rates of adverse major cardiac events in a population of men taking these drugs. These drugs were also associated with a lower rate of overall mortality and cardiovascular mortality. A current study is analyzing the results of a long- acting phosphodiesterase-5 inhibitor on cardiovascular outcomes.  

In collaboration with Dr. Niema Pahlevan in the engineering department of USC, Dr. Kloner’s group is exploring potentially non-invasive ways of assessing heart function and the diagnosis of coronary artery occlusion by a mathematical analysis of the carotid artery waveform shape. The shape of this waveform can be assessed by a cell phone application; and was shown to predict reduced left ventricular function in heart failure patients. 

In collaboration with Dr. Xianghong Arakaki and the neuroscience group, Dr. Kloner and collaborators at UCI are studying the effect of heart rate variability and its relationship to early signs of dementia, such as Alzheimer’s Disease, and correlation to other neurologic abnormalities including the volume of certain regions of the brain, Neuro-psychological abnormalities, and EEG findings.   

For additional information please contact the Cardiovascular lab at: 

robert.kloner@hmri.org or 626-389-3413