Search

Although it is likely that, besides increases in fibroblast growth factors (FGFs) or vascular endothelial growth factor (VEGF), several factors may promote the development of collaterals in ischemic myocardium, it has become clear that administration of an angiogenic growth factor is itself sufficient to augment blood delivery. Several of these angiogenic growth factors have been tested in treatment of myocardial ischemia. This review will address the results of animal studies and then the first human trials.

Transmyocardial laser revascularization (TMLR) is indicated in chronic angina that is refractory to medical therapy and untreatable by coronary artery bypass graft (CABG) or percutaneous transluminal coronary angioplasty (PTCA).

In the early 1980s, Mirhoseini and Cayton were the first to propose using a laser for drilling channels through the myocardium to improve the blood supply directly from the left ventricular cavity to the ischemic areas. According to their initial report (Mirhoseini and Cayton 1981), which laid the basis for further clinical applications of transmyocardiallaser revascularization (TMLR), the authors applied CO2 laser technique to four groups of six dogs. The output power could be adjusted between o W and 400 Wand the duration of exposure or pulse width was approximately 100 msec. The spot size of the beam diameter was described as dependent upon the lens used and the repetition rate as varying from single pulse to continuous mode.

Although most morphological analyses raise serious doubts about channel patency, clinical studies (see Chap. 11) invariably show an improvement of angina symptomatology in end stage coronary artery disease patients. Therefore other mechanisms should be sought.

Transmyocardial laser revascularization (TMLR) was clinically performed soon after the first experimental report (Mirhoseini and Cayton 1981; Mirhoseini et al. 1983). Since then, experience with this technique has grown. This chapter will focus essentially on the studies which analyzed TMLR alone without concomitant coronary artery bypass grafting (CABG), to evaluate the particular effects of this procedure.

Atherosclerosis in the heart leads to progressive narrowing or occlusion of coronary arteries, finally resulting in regional myocardial ischemia. Nature has created mechanisms to adapt partially to this condition through “compensatory angiogenesis”, i.e., development of a functional collateral circulation, which is driven by angiogenic factors, most of which represent members of the peptide growth factor family. However, this adaptive process is rather slow and unable to compensate fully for the effects of ischemia induced by acute occlusion of a coronary artery. Therefore, it seems logical to apply the angiogenic factor where it is actually needed and other means of revascularization, such as coronary artery bypass grafts (CABG) or percutaneous transluminal coronary angioplasty (PTCA), are not applicable. This novel concept of the therapeutic induction of neovascularization, also denoted “therapeutic angiogenesis”, has been demonstrated in a number of different animal models to induce rapid collateralization in the ischemic area (i.e., revascularization) and thereby improve organ function.

The concept of myocardial revascularization by means other than through the normal coronary vasculature has a relatively long history dating back to the 1930S, when Beck made pericardial-myocardial adhesions to promote the development of an extracardiac myocardial blood supply (Beck 1935). Of the many techniques designed to augment the blood supply to ischemic myocardium, the Vineberg procedure, mainly involving implantation of the internal mammary artery (IMA) into the myocardial muscle, received the greatest attention, having been performed in an estimated 15,000 patients worldwide (Benson and McCallie 1979). Before it was abandoned because of the development of coronary artery bypass grafts (CABG) which became applicable to the vast majority of patients, much basic and clinical research concerning this procedure had been performed. The method is reviewed here because it is grounded on some principles, especially the neovascularization concept, which can be applied to new procedures of indirect myocardial revascularization designed to treat the growing number of patients suffering from angina despite maximal medical therapy and in whom traditional methods of revascularization, i.e., CABG and percutaneous transluminal coronary angioplasty (PTCA), cannot be applied. Procedures with possible or demonstrated involvement of vascular growth include mainly TMLR and therapeutic angiogenesis.

Initially, Mirhoseini et al. (1983) hypothesized that laser channels remained patent in the long term and could direct endocavitary blood to ischemic myocardium. Therefore, channel morphology is an important aspect in assessing the validity of transmyocardial laser revascularization (TMLR) theory. This chapter will analyze successively the experimental studies performed in normal and acutely ischemic myocardium in various animal models and postmortem reports of human hearts. The results are grouped according to the different types of laser.

The concept of the reptilian heart stimulated Sen et al. to perform the first transmyocardial revascularization procedures. The myocardial circulation of reptiles consists of channels radiating from the myocardial cavity that supply nearly the whole of the myocardium except for a thin shell on the outside comprising about 1/12 of the myocardial thickness. This external coat of muscle is disposed in a circular manner and receives its blood supply from the aorta through the external coronary arteries. Theoretically, this type of supply was lost in the mammalian heart as a result of evolution. Most of the heart muscle in man is supplied by the external coronary arteries - the exact opposite of the reptilian heart. The filling of reptilian myocardial channels occurs during systole and blood is forced into the myocardial “lake” under pressure (the three-chambered heart of the reptile pushing mixed blue blood into these vessels). In all mammals, including man, the filling takes place during diastole and the myocardial arterial and capillary tree is filled under lower pressure but with oxygenated blood.

When electromagnetic radiation impinges on a thin layer of tissues, part of the radiation is reflected, part is absorbed, and part is transmitted. The absorbed portion (i.e., the incidental radiation minus the sum of the reflected and transmitted portions) interacts with the tissue.