Letters to the Editor which can be determined by omitting creatine phosphate, the specific substrate for CK, from the reaction medium. If one uses one of the column methods, the most likely explanation would be a carryover of MM into the MI3 fraction. Robert Roberts, M.D. Director, Coronary Care Unit Washington University School of Medicine 660 South Euclid Ave. St. Louis, MO. 63110 REFERENCES 1.
2.
3.
Klein, M. S., Ludbrook, P. A., Mimbs, J. W., Gafford, F. H., Gillespie, T. A., Weldon, C. S., Sobel, B. E., and Roberts, R.: Perioperative mortality rate in patients with unstable angina selected by exclusion of myocardial infarction, J. Thorac. Cardiovasc. Surg. 73253, 1977. Klein, M. S., Weiss, A. N., Roberts, R., and Coleman, R. E.: Technetium-99m stannous pyrophosphate scintigrams in normal subjects, patients with exercise induced ischemia and patients with calcified valves, Am. J. Cardiol. 39:360, 1977. Ahmed, S. A., Williamson, J. R., Roberta, R., Clark, R. E., and Sobel, B. E.: The association of increased plasma MB CPK activity and irreversible ischemic myocardial injury in the dog, Circulation 54:187, 1976.
to injury-spasm,b and thus is equivalent to post-ligation reduced flow. Studies’-’ showing prevention of post-ligation spasm by interference with the autonomic nervous system are evidence for the importance of a neural component of the control of coronary artery blood flow. A dual and cooperating system of coronary blood flow regulation, comprised of the autonomic nervous system and the anoxic feedback mechanism, has been proposed.” Coronary artery spasm usually is related solely to epicardial arteries. However, post-ligation spasm appears to be intramyocardial, and the occurrence of spasm involving small coronary arteries might have significant implications. For example, if these mural arteries are involved with spasm during the induction and acute course of infarction, and in angina, the importance of collateral channels in protecting against &hernia with attacks of spasm is lessened. Also, the absence of angina with catheter-induced spasm’ might be due to the lack of an intramyocardial component of this spasm. H. R. Hellstrom, M. D. V. A. Hospital University Drive Pittsburgh, Pa. 15240 REFERENCES 1.
Chronic cardiac and myocardial
denervation, blood flow
infarct
size, 2.
To the Editor: I read with interest the study by Dr. Jones and his group (AM. HEART J. 95738, 1978) which showed that chronic cardiac denervation in the dog resulted in a smaller infarct and a smaller area of non-perfused myocardium after coronary ligation.’ A likely reason for this is that after coronary occlusion, vasospasm of small coronary arteries obtains, and prior denervation prevented the development of this spasm. The occurrence of post-occlusion spasm is not in accord with current concepts, as dilation of mural coronary arteries is considered to occur invariably after coronary obstruction. However, prevention of post-occlusion spasm provides a reasonable explanation for the beneficial effects of cardiac denervation. The spasm would impede collateral flow into the ischemic zone, and its prevention would permit unimpaired Row from adjacent myocardium. This explanation was offered by Grayson and Lapin’ in 1966 for the prevention of infarction in the dog by prior procaine anesthesia of the coronary artery and its environs. Blood flow in the myocardium below the ligated and anesthetized artery returned to normal levels by four hours. Adrenergic neuron blockade yielded similar results.” Instead of the proposed spasm developing secondary to coronary ligation per se, it probably follows ischemic injury of the myocardium (injury-spasm).” The severe ischemia of ligation induced an injury reaction in intramyocardial arteries rather than the normal vasodilation. In favor of this, after coronary ligation alone,“. 3 the level of blood flow continued to fall for several hours, paralleling the development of myocardial necrosis. Also, in a reperfusion study,’ release of the coronary occlusion after two hours did not prevent further reduction in blood flow over the next four hours. It is likely that the “no-reflow” phenomenon of reperfusion studies is due
270
3.
4.
5.
6.
7.
Jones, C. E., Devous, M. D., Sr., Thomas, J. X., Jr., and DuPont, E.: The effect of chronic cardiac denervation on infarct size following acute coronary occlusion, AM. HEART J. 95:738, 1978. Grayson, J., and Lapin, B. A.: Observations on the mechanisms of infarction in the dog after experimental occlusion of the coronary artery, Lancet 1: 1284, 1966. Grayson, J., Irvine, M., Parratt, J. R., and Cunningham, J.: Vasospastic elements in myocardial infarction following coronary occlusion in the dog, Cardiovasc. Res. 2:54, 1968. Hellstrom, H. R.: Coronary artery stasis after induced myocardial infarction in the dog, Cardiovasc. Res. 5:371, 1971. Parker, P. E., Bashour, F. A., Downey, H. F., Kechejian, S. J., and Williams, A. G.: Coronary hemodynamics during reperfusion following acute coronary ligation in dogs, AM. HEART J. 90:593, 1975. Hellstrom, H. R.: The injury-vasospasm hypothesis of ischemic heart disease, revisited, AM. HEART J. 94:642, 1977. Heupler, F. A., Jr., Proudfit, W. L., Razavi, M., Shirey, E. K., Greenstreet, R., and Sheldon, W. C.: Ergonovine maleate provocative test for coronary arterial spasm, Am. J. Cardiol. 41:631, 1978.
Reply To the Editor: The comments of Dr. Hellstrom regarding our work on the chronically denervated heart were most sincerely appreciated. In previous publications Dr. Hellstrom has emphasized that a neurally mediated vasospasm, such as that known to be involved in Prinzmetal’s variant angina, may be operative in limiting collateral flow following acute coronary occlusion and myocardial infarction. Based on the studies cited in the above letter, this injury-spasm concept would appear to have substantial merit and presents an attractive explanation for the phenomenon observed by us. Indeed, when it first became apparent that chronic cardiac denervation afforded a protection to the heart after acute coronary occlusion, we were
February,
1979,
Vol. 97, No. 2
2.
3.
Klein, M. S., Ludbrook, P. A., Mimbs, J. W., Gafford, F. H., Gillespie, T. A., Weldon, C. S., Sobel, B. E., and Roberts, R.: Perioperative mortality rate in patients with unstable angina selected by exclusion of myocardial infarction, J. Thorac. Cardiovasc. Surg. 73253, 1977. Klein, M. S., Weiss, A. N., Roberts, R., and Coleman, R. E.: Technetium-99m stannous pyrophosphate scintigrams in normal subjects, patients with exercise induced ischemia and patients with calcified valves, Am. J. Cardiol. 39:360, 1977. Ahmed, S. A., Williamson, J. R., Roberta, R., Clark, R. E., and Sobel, B. E.: The association of increased plasma MB CPK activity and irreversible ischemic myocardial injury in the dog, Circulation 54:187, 1976.
to injury-spasm,b and thus is equivalent to post-ligation reduced flow. Studies’-’ showing prevention of post-ligation spasm by interference with the autonomic nervous system are evidence for the importance of a neural component of the control of coronary artery blood flow. A dual and cooperating system of coronary blood flow regulation, comprised of the autonomic nervous system and the anoxic feedback mechanism, has been proposed.” Coronary artery spasm usually is related solely to epicardial arteries. However, post-ligation spasm appears to be intramyocardial, and the occurrence of spasm involving small coronary arteries might have significant implications. For example, if these mural arteries are involved with spasm during the induction and acute course of infarction, and in angina, the importance of collateral channels in protecting against &hernia with attacks of spasm is lessened. Also, the absence of angina with catheter-induced spasm’ might be due to the lack of an intramyocardial component of this spasm. H. R. Hellstrom, M. D. V. A. Hospital University Drive Pittsburgh, Pa. 15240 REFERENCES 1.
Chronic cardiac and myocardial
denervation, blood flow
infarct
size, 2.
To the Editor: I read with interest the study by Dr. Jones and his group (AM. HEART J. 95738, 1978) which showed that chronic cardiac denervation in the dog resulted in a smaller infarct and a smaller area of non-perfused myocardium after coronary ligation.’ A likely reason for this is that after coronary occlusion, vasospasm of small coronary arteries obtains, and prior denervation prevented the development of this spasm. The occurrence of post-occlusion spasm is not in accord with current concepts, as dilation of mural coronary arteries is considered to occur invariably after coronary obstruction. However, prevention of post-occlusion spasm provides a reasonable explanation for the beneficial effects of cardiac denervation. The spasm would impede collateral flow into the ischemic zone, and its prevention would permit unimpaired Row from adjacent myocardium. This explanation was offered by Grayson and Lapin’ in 1966 for the prevention of infarction in the dog by prior procaine anesthesia of the coronary artery and its environs. Blood flow in the myocardium below the ligated and anesthetized artery returned to normal levels by four hours. Adrenergic neuron blockade yielded similar results.” Instead of the proposed spasm developing secondary to coronary ligation per se, it probably follows ischemic injury of the myocardium (injury-spasm).” The severe ischemia of ligation induced an injury reaction in intramyocardial arteries rather than the normal vasodilation. In favor of this, after coronary ligation alone,“. 3 the level of blood flow continued to fall for several hours, paralleling the development of myocardial necrosis. Also, in a reperfusion study,’ release of the coronary occlusion after two hours did not prevent further reduction in blood flow over the next four hours. It is likely that the “no-reflow” phenomenon of reperfusion studies is due
270
3.
4.
5.
6.
7.
Jones, C. E., Devous, M. D., Sr., Thomas, J. X., Jr., and DuPont, E.: The effect of chronic cardiac denervation on infarct size following acute coronary occlusion, AM. HEART J. 95:738, 1978. Grayson, J., and Lapin, B. A.: Observations on the mechanisms of infarction in the dog after experimental occlusion of the coronary artery, Lancet 1: 1284, 1966. Grayson, J., Irvine, M., Parratt, J. R., and Cunningham, J.: Vasospastic elements in myocardial infarction following coronary occlusion in the dog, Cardiovasc. Res. 2:54, 1968. Hellstrom, H. R.: Coronary artery stasis after induced myocardial infarction in the dog, Cardiovasc. Res. 5:371, 1971. Parker, P. E., Bashour, F. A., Downey, H. F., Kechejian, S. J., and Williams, A. G.: Coronary hemodynamics during reperfusion following acute coronary ligation in dogs, AM. HEART J. 90:593, 1975. Hellstrom, H. R.: The injury-vasospasm hypothesis of ischemic heart disease, revisited, AM. HEART J. 94:642, 1977. Heupler, F. A., Jr., Proudfit, W. L., Razavi, M., Shirey, E. K., Greenstreet, R., and Sheldon, W. C.: Ergonovine maleate provocative test for coronary arterial spasm, Am. J. Cardiol. 41:631, 1978.
Reply To the Editor: The comments of Dr. Hellstrom regarding our work on the chronically denervated heart were most sincerely appreciated. In previous publications Dr. Hellstrom has emphasized that a neurally mediated vasospasm, such as that known to be involved in Prinzmetal’s variant angina, may be operative in limiting collateral flow following acute coronary occlusion and myocardial infarction. Based on the studies cited in the above letter, this injury-spasm concept would appear to have substantial merit and presents an attractive explanation for the phenomenon observed by us. Indeed, when it first became apparent that chronic cardiac denervation afforded a protection to the heart after acute coronary occlusion, we were
February,
1979,
Vol. 97, No. 2
