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In Response
The So-called Loesch-Goldblatt Experiments
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Bernhard Glodny, MD Department of Radiology, Innsbruck Medical University,, Dorothea E. Glodny, PhD, Münster, Germany.
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Bernhard.Glodny{at}uibk.ac.at Bernhard Glodny, et al.
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The Loesch-Goldblatt experiments We thank the Goldblatts for their letter, and appreciate their interest. We would like to respond as follows: Harry Goldblatt did not mention that the conclusions of his own work presented in 1934 had been reported previously. For this reason, we believe that John Loesch did not receive due recognition until he was recalled by us. The Goldblatts cited Fahr using their father’s article. Indirect quotation may result in changes, as in the case of P. Goldblatt’s statement on the lecture of 1932 (1). Loesch's article is actually in three parts. Loesch was familiar with Volhard's vasospasm hypothesis, but he did not test it (2). Goldblatt and Loesch both realized that they could generate persistent hypertension by means of ischemia, and both of them rightly received recognition for this. Loesch stated very clearly that he did not occlude the ureter. To prevent uremia, he successfully varied the occlusion intervals, and thus the extent of ischemia. He was therefore able to extend the animals' lives, and this fact should be acknowledged. Goldblatt also had to deal with the problem of animals dying due to uremia. Goldblatt, in contrast to Loesch, did not examine the urine sediment. At least two different "Goldblatt models" are known. We believe it would be appropriate to call them "Loesch-Goldblatt models", because Goldblatt had not yet fully realized the difference between the two in 1934. The "one kidney – one clip model" in a rabbit, for example, does not exhibit "the characteristics of benign human essential hypertension" because these animals die of malignant hypertension after a few weeks (3). The Loesch-Goldblatt models still puzzle us, but a solution to one of the greatest puzzles is now imminent: the structures of the lipid antihypertensive hormones, the "medullipins" and "angiolysins", which are released by the kidney into the bloodstream after “unclipping” or when perfusion pressure is increased (3), will be elucidated shortly. These are among the most potent antihypertensive agents and vasodilators known (4, 5). The means of achieving this are now available (4, 5). The paradigm will shift again, and then we will again remember two great researchers: Harry Goldblatt and John Loesch. Bernhard Glodny, MD, Department of Radiology, Innsbruck Medical University, and Dorothea E. Glodny, PhD, Münster, Germany. Bernhard.Glodny@uibk.ac.at 1. Goldblatt PJ. The Goldblatt experiment: a conceptual paradigm. In: Laragh JH, Brenner BM, eds. Hypertension: Pathophysiology, Diagnosis and Management. 2nd ed. New York: Raven Pr: 1995; 23-35 2. Loesch J. Ein Beitrag zur experimentellen Nephritis und zum arteriellen Hochdruck. I. Die Veränderungen im Blutdruck. II. Die Veränderungen in der Blutchemie. III. Die Veränderungen in den Geweben. Zentralblatt für Innere Medizin 1933; 7: 144-169; 8: 177-185 3. Muirhead EE. Renomedullary Vasodepressor Lipid: Medullipin. In: Swales ED, ed. Textbook of Hypertension. Oxford: Blackwell Scientific Publications; 1994: 341-359 4. Glodny B, Pauli GF. The vasodepressor function of the kidney: prostaglandin E2 is not the principal vasodepressor lipid of the renal medulla. Acta Physiol 2006; 187: 419-430 5. Glodny B, Pauli GF. The vasodepressor function of the kidney: further characterization of medullipin and a second hormone designated angiolysin. Hypertens Res 2006;29:533-544 Conflict of Interest:None declared |
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David Goldblatt, MD , Peter J. Goldblatt, MD, MPH
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dgoldblattmd{at}verizon.net David Goldblatt, et al.
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To the Editor: Bernhard and Dorothea E. Glodny state that first John Loesch and then our father, Harry Goldblatt, published papers with the same “central proposition”: “Renal ischemia causes persistent hypertension.” Because of the “primacy” of his observations, Loesch should be recognized as the “discoverer of renovascular hypertension.” (1) Earlier, Fahr suggested “that renal ischemia, by itself, may play an important part in the development of the hypertension which is associated with more or less diffuse vascular disease in man” and several investigators deliberately interfered with the renal circulation, injuring the kidney, with some success in producing hypertension. (2) Priority of publication, however, is irrelevant: the Glodnys’ coinage “Loesch-Goldblatt experiments” inappropriately joins the names of two independent investigators whose aims, experimental methods, and results were fundamentally different. Loesch investigated the hypothesis that vasospasm causes human hypertension. His model involved intermittent cross-clamping of the renal pedicle. His hypothesis remains unproved. His findings have not been reliably replicated. Goldblatt, who observed the high correlation between intrarenal vascular disease found at autopsy and “essential” hypertension—hypertension without obvious renal origin—during life, hypothesized that intrarenal vascular disease causes benign human essential hypertension. By persistently constricting the renal artery of the dog, he produced sustained hypertension that closely resembled the human disorder. His technique and results have been replicated throughout the world. Loesch reported that intermittent clamping of the pedicle of a dog’s kidney explanted beneath the skin caused sustained hypertension. Goldblatt repeated Loesch’s work with the kidney in situ and in a way that avoided compressing the ureter and renal vein with the artery. He demonstrated that intermittent occlusion of the renal artery does not produce elevation of the blood pressure. (3) Even Loesch’s mentor, Allen, an outspoken critic of Goldblatt, admitted, “Only exceptional dogs develop hypertension with the number and duration of clampings which Loesch describes.” (4) The parenchymal injury Loesch produced included “necrosis with consequent inflammation.” Loesch called his model “experimental nephritis.” Findings in the urinary sediment in 5 dogs suggested that “nephritis” was an appropriate term: microscopic hematuria from the first clamping on and, in 2 animals, “abundant red and white blood corpuscles.” (5) The Glodnys omit this information. Goldblatt’s model conformed to the characteristics of benign human essential hypertension and differed from preceding models, including Loesch’s, in which animals that developed hypertension usually died early as a result of renal insufficiency. Hypertension of this type resembles that of glomerulonephritis, about the renal origin of which there has never been any serious question since the time of Richard Bright. With the publication of Goldblatt’s work, a century after Bright’s, the paradigm shifted. The Glodnys assert that Goldblatt did not test the efficacy of his technique when he disproved Loesch’s findings. That testing and its results are detailed in Goldblatt’s paper.(3) Glodnys: “Goldblatt finally acknowledged that Loesch had succeeded in inducing ischemia and that Loesch had produced chronic, sustained hypertension. He stated, “The positive results obtained by Loesch . . . may well have been due . . . to . . . renal ischemia. So, in the end, Goldblatt acknowledged that Loesch had produced sustained hypertension by renal ischemia.” (1) Goldblatt’s actual statement: “The positive results obtained by Loesch in the other two dogs may well have been due to persistent [and unintended] constriction, of lesser degree, of one or all of the components of the renal pedicle, with resultant persistent renal ischemia.” Goldblatt had explained why Loesch failed to prove his hypothesis. By omitting “persistent” from both sentences, the Glodnys completely pervert Goldblatt’s conclusions. The Glodnys’ article contains additional misquotation, misattribution, and historical error, which reviewers should have detected. Its central proposition is insupportable. Its publication baffles us. • David Goldblatt, MD Professor Emeritus of Neurology and the Medical Humanities, University of Rochester (New York) School of Medicine and Dentistry Peter J. Goldblatt, MD, MPH Professor and Chairman Emeritus of Pathology and former Dean of Graduate Studies, Medical University of Ohio References 1. Glodny G, Glodny DE. John Loesch, Discoverer of Renovascular Hypertension, and Harry Goldblatt: Two Great Pioneers in Circulation Research. Ann Intern Med. 2006;144:286-95. 2. Goldblatt H, Lynch J, Hanzal RF, Summerville WW. Studies on Experimental Hypertension I. The production of persistent elevation of the systolic blood pressure by means of renal ischemia. J Exper Med. 1934;59:347-79. 3. Goldblatt H, Weinstein H, Kahn JR. Studies on Experimental Hypertension. XIV. The effect of intermittent renal arterial occlusion on the blood pressure of the dog. J Exp Med. 1941;73:439-51. 4. Allen FM. Experimental production of various renal-vascular disorders. J Urol. 1943;49:512-23. 5. Loesch J. Ein Beitrag zur experimentellen Nephritis und zum arteriellen Hochdruck. I. Die Veränderungen im Blutdruck. II. Die Veränderungen in der Blutchemie. Zentralblatt für Innere Medizin. 1933;7:144-69. |
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