Ischemic cardiac myocytes

Studies by Kawata et al. (2001) showed that ischemic preconditioning (IP) enhances the expression of VEGF mRNA in ischemic cardiac myocytes and vascular ECs. They observed increase in capillary density in the infarcted area and a reduction in infarct size, 3 days after the onset of AMI preceded by IP. Several recent studies also provide evidence for an increased expression of VEGF triggered by IP (Fukuda et al. 2004). When rats with chronic MI were subjected to IP, an induction of survival factors including VEGF, Bcl-2, and survivin was observed (Fukuda et al. 2004). 

The use of bone marrow has also been explored in chronic ischemic disease [40 2]. Results are striking but with the small sample sizes of the studies, the results are difficult to interpret. There is a difficulty in choosing the correct cell line. An ideal cell population would (1) be readily and widely available, (2) have the ability to generate new cardiac myocytes, (3)... 

Martin, J.L., Mestril, R., Hilal-Dandan, R., Brunton, L.L., and Dillmann, W.H. 1997. Small heat shock proteins and protection against ischemic injury in cardiac myocytes. Circulation 96 4343-4348. 

Studies in various animal models and in human hearts suggest that apoptosis does occur in ischemia/reperfusion injury of the heart, though the relative contribution of apoptosis in comparison with necrosis to cell loss in ischemia/ reperfusion injury is still controversial. Cardiomyocyte apoptosis was first reported by Gottlieb et al. [107], who studied the ischemia/reperfusion in rabbit hearts and found the hallmark of apoptosis in ischemic/reperfused hearts but not in the normal or ischemic-only rabbit hearts. Identification of apoptosis was based on the presence of fragmented DNA in electrophoretic gels, on in situ nick end-labeling assays, and on electron microscopy. They concluded that apoptosis may be a specific feature of reperfusion injury in cardiac myocytes. Subsequent studies have shown that apoptosis probably occurs both in ischemia and reperfusion [108], It appears that apoptosis is more prominent after ischemia followed by reperfusion than after ischemia alone [109, 110],... 

IL-6 levels are elevated in patients with acute myocardial infarction. IL-6 is secreted by mononuclear cells in the ischemic area and is also produced by cardiac myocytes. IL-6 apart from its inflammatory effect regulates contractile function by its acute effect on calcium transients.37... 

Estimates show that nearly 6 million patients suffer from HF in the United States and about 23 million people are afflicted by HF worldwide (Lloyd-Jones et al., 2010, McMurray et al., 1998). Although these estimates include all causes of HF, ischemic heart disease is still the most common cause of HF. Several medical therapies improve hemodynamics in systohc HF and mortality. However, none of these medical therapies address the loss of cardiac myocytes. Due to a lack of availability of donor hearts, cardiac transplantation is usually not a viable option for most patients. 

Stem cells from a number of sources have been explored for regenerating the myocardium. Both multi-potent adult stem cells and pluripotent embryonic stem (ES) cells have been used to generate vascular cells and cardiac myocytes for therapy (Figure 34.3). A number of clinical studies have explored adult stem cells for their therapeutic potential in treating ischemic heart disease. While ES cells have only been investigated to date in preclinical models, a new clinical study is expected to assess safety of ES cell transplantation (Alper, 2009). In addition to stem cells, adult skeletal muscle cells have also been explored for clinical cardiac cell therapy. Each cell type is briefly reviewed in the context of myocardium regeneration. 

Mast cells are present in the normal human heart and even more abundant in diseased hearts [ 16-18,25,47]. Within heart tissue, mast cells he between myocytes and are in close contact with blood vessels. They are also found in the coronary adventitia and in the shoulder regions of coronary atheroma [20, 21], The density of cardiac mast cells is higher in patients with dilated and ischemic cardiomyopathy than in accident victims without cardiovascular diseases [25], Importantly, in some of these conditions there is in situ evidence of mast cell activation [16,34],... 

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