(Circulation. 1997;95:1357-1359.)
© 1997 American Heart Association, Inc.
Articles |
Transmural Channels as a Source of Blood Flow to Ischemic Myocardium?
Insights From the Reptilian Heart
The Heart Institute, Good Samaritan Hospital, and the Department of Medicine, Section of Cardiology, University of Southern California, Los Angeles.
Key Words: Editorials • myocardium • vasculature • lasers • blood flow
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Introduction |
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 Top Introduction De-Evolving the Human Heart:...The Acute Benefits of...Long-term Benefits of TMRReferences |
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Kohmoto et al1 have demonstrated, using several different techniques, that alligator hearts receive a significant amount of blood perfusion from the "inside out." That is, in addition to blood flow through the coronary arteries, blood flows directly into the myocardial tissue from the ventricular cavity. Such a circulation is possible because the inner two thirds of the alligator left ventricle is composed of tissue with a "spongelike" appearance. This tissue contains numerous trabecular spaces or "sinusoids" that have direct connections with the ventricular cavity. Similar architectural features have also been reported in fish hearts.2 The advantage of such a myocardial structure is that a significant degree of myocardial viability might be maintained even if the coronary arteries were completely occluded by atherosclerosis.
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De-Evolving the Human Heart: The Premise for Transmyocardial Revascularization |
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TopIntroductionDe-Evolving the Human Heart:...The Acute Benefits of...Long-term Benefits of TMRReferences |
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Why should the readership of Circulation have any interest in the coronary anatomy of alligators or fish? Although to the best of our knowledge these creatures do not require bypass surgery or angioplasty because of advanced coronary artery disease, humans do. Not all patients, however, are suitable candidates for these revascularization procedures, so in the quest for alternative therapies,3 efforts have been made to surgically mimic the reptilian circulation and exploit the concept that other conduits in addition to coronary arteries might be created to provide blood flow to the heart. Specifically, several groups have suggested that by making numerous channels through the myocardium (transmyocardial revascularization [TMR]), it might be possible to "de-evolve" mammalian hearts, restore a reptilian pattern of perfusion, and hence bypass diseased coronary vessels.4 5
In the initial test of this hypothesis, short-term experiments were performed in animal hearts that purported to demonstrate immediate protection against coronary artery occlusion, presumably through increased perfusion, even though blood flow was not directly measured.4 5 On the basis of these positive studies, the procedure was then performed on human hearts, and the results have been largely favorable.6 Importantly, however, this hypothesis indicates that mammalian hearts would have to possess a "sinusoid" system with connections to the existing vasculature for channels to supply blood flow immediately to the tissue. Unfortunately, a convincing micrograph of a mammalian cardiac sinusoid has, to the best of our knowledge, not been published, nor have we ever seen a sinusoid in a normal mammalian heart. We therefore concur with a recent editorial that the concept of sinusoids in mammalian hearts is a "phantom."7 Furthermore, there is a considerable amount of direct evidence, from studies that did measure blood flow, that channels fail to provide blood flow to surrounding myocardium in the first few hours after they have been made.8 9 10 These results present a paradox: if sinusoids are not present in mammalian hearts, what is the explanation for the immediate benefits, specifically a striking reduction in angina class,6 that have been reported in many of the clinical transmyocardial revascularization trials?
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The Acute Benefits of TMR May Not Be Flow Mediated |
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TopIntroductionDe-Evolving the Human Heart:...The Acute Benefits of...Long-term Benefits of TMRReferences |
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It might be argued that even in the absence of sinusoids, there might be a benefit from a "tidal flow" within the channels. That is, blood could pass to and fro within channels and hence supply oxygen to muscle cells immediately adjacent to the channels. However, such a supply would be limited by diffusion to a region, at most, a couple of cells thick. For example, in normal myocardium, oxygen diffusion distances require that each muscle cell be surrounded by an average of three capillaries.11 12 Thus, the number of channels required to provide an adequate oxygen supply solely through diffusion is clearly unrealistic, and in patients with compromised cardiac function, the removal of large amounts of muscle is unlikely to improve their status. Moreover, such a diffusion mechanism would require that the channels be directly in contact with muscle cells. This would not occur because the thermal and mechanical injuries incurred during channel making produce variable amounts of necrosis (and subsequent scarring) adjacent to the channel.13 14 Even the use of the "cold" excimer laser15 —and indeed a needle14 —fails to completely prevent local injury at the channel site. Because the ensuing scar tissue will provide a barrier for oxygen diffusion to muscle, "tidal" flow does not seem to be a likely mechanism for oxygen supply through the channels.
Another possibility is that because the capillary density in human myocardium is 
2200 per square millimeter,16 it is inevitable that a channel made through the ventricular wall will intersect a considerable number of vessels. Could blood flow from the channels into these transected capillaries and arterioles? Again, thermal injury (in effect, cautery) to the tissue surrounding the channels makes this possibility highly unlikely.
Even though an acute increase in blood flow to the tissue via the channels appears unlikely, there are other possible explanations for the reduction in angina class reported clinically. For example, the laser-mediated thermal injury may destroy nerve fibers, the ablation of muscle from the treated region may have a positive effect on the oxygen supply-and-demand balance in the remaining tissue, and the possibility of a psychosomatic or "placebo" reaction to the surgery exists.
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Long-term Benefits of TMR |
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TopIntroductionDe-Evolving the Human Heart:...The Acute Benefits of...Long-term Benefits of TMRReferences |
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Even though there does not appear to be blood flow through the channels immediately after they are made, there have been clinical reports that myocardial perfusion (assessed by PET and thallium scans) in patients treated with a carbon dioxide laser improved over time after the channels were made.6 17 18 This observation, together with the finding in one patient of blood vessels connected to an open laser channel,19 raises the possibility that there may be a progressive development of blood flow through the channels. It is likely that in response to the injury caused by the initial channel making, the resulting inflammatory response results in the growth of new blood vessels.20 Such vessel growth would take some time to complete; thus, an improvement in flow would not occur immediately. Although angiogenesis is a well-documented response to injury, to be useful, the new blood vessels should presumably connect to the channel. In addition, it appears desirable that the channels remain patent and maintain direct connections to the ventricular cavity. Nevertheless, it has been suggested that an open channel is not necessary. Rather, some investigators have speculated that laser injury might stimulate vessel growth not only in the region of injury but throughout the heart, thereby allowing blood to enter the region of compromised flow from other remote regions. However, if the channel does not remain patent and stimulation of vessel growth in distant regions is the only benefit of the channel making, then one could question the rationale of subjecting a patient to surgery when there are pharmacological agents, eg, basic fibroblast growth factor, that could have the same effect.21 22
As mentioned, patent channels have been reported in a postmortem histological study of one patient19 ; however, closed channels have also been found.23 There also are conflicting reports from animal experiments.13 14 24 25 For example, Kohmoto and colleagues13 25 found that channels made with holmium:YAG and carbon dioxide lasers in canine hearts became completely occluded with scar tissue within 2 weeks. Interestingly, the channels were made with the same parameters as those used to make channels in the clinical trials. On the other hand, we have found that channels made in rat hearts, with either a hypodermic syringe needle or an excimer laser, were still open when examined 2 months later and, perhaps more importantly, had direct connections to both blood vessels and the ventricular cavity.14 15 In addition, when these hearts were subjected to an ischemic challenge in the form of a 90-minute coronary artery occlusion, we found that there was less muscle necrosis in excimer-laser and needle-treated hearts versus controls.14 15 These observations are consistent with blood flow to the ischemic tissue through the channels; however, they do not provide direct evidence of improved perfusion. Unequivocal evidence of flow through channels is also lacking in patients, despite the circumstantial evidence mentioned earlier. In both animal and human studies, direct evidence of blood flow must be provided if the current enthusiasm for transmyocardial revascularization is to be translated into a viable treatment.
In summary, the observations of Kohmoto et al1 suggest that the original rationale proposed for making channels through the myocardium is flawed: converting human hearts to a reptilian circulation appears highly unlikely, if not impossible. That does not mean, however, that transmyocardial revascularization cannot provide long-term improvements in blood flow, perhaps through new vessel growth. It is clear that we still have a great deal to learn about the procedure. What is the mechanism for the apparent reduction in angina? Do the channels provide a conduit for blood flow? How should the channels be made? Is there such a thing as an optimal laser wavelength, or can the channels be made with mechanical methods? Time will tell whether the promising clinical results that have been obtained in the initial trials, despite our lack of knowledge regarding mechanisms, indicate that even greater clinical success is possible in the future.
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Footnotes |
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Reprint requests to Peter Whittaker, PhD, The Heart Institute, Good Samaritan Hospital, 1225 Wilshire Blvd, Los Angeles, CA 90017-2395.
The opinions expressed in this editorial are not necessarily those of the editor or of the American Heart Association.
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References |
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TopIntroductionDe-Evolving the Human Heart:...The Acute Benefits of...Long-term Benefits of TMRReferences |
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3.
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13.
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14.
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21.
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23.
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