John Loesch and Harry Goldblatt: two great pioneers in circulation research.

TO THE EDITOR: Glodny and Glodny (1) state that first John Loesch and then our father, Harry Goldblatt, published papers with the same “central proposition”: “Renal ischemia causes persistent hypertension.” They also state that because of the “primacy” of his observations, Loesch should be recognized as the “discoverer of renovascular hypertension.” Earlier, Theodor Fahr suggested that “renal ischemia, by itself, may play an important part in the development of the hypertension that is associated with more or less diffuse vascular disease in man” (2). Several investigators who preceded both Loesch and Goldblatt deliberately interfered with the renal circulation, injuring the kidney, with some success in producing hypertension (2). Priority of publication, however, is irrelevant. The Glodnys’ term “Loesch–Goldblatt experiments” inappropriately joins the names of 2 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, and 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, Dr. Frederick Allen, an outspoken critic of Goldblatt, admitted that “[o]nly exceptional dogs develop hypertension with the number and duration of clampings which Loesch describes” (4). The parenchymal injury that Loesch produced included “necrosis with consequent inflammation.” Loesch called his model “experimental nephritis.” Findings in the urinary sediment in 5 dogs (microscopic hematuria from the first clamping onward and, in 2 animals, “abundant red and white blood corpuscles”) suggested that “nephritis” was an appropriate term (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 model, in which animals that developed hypertension usually died early because of renal insufficiency. Hypertension of this type resembles that of glomerulonephritis—the renal origin of which has never been seriously questioned since the time of Richard Bright. With the publication of Goldblatt’s work, a century after Bright’s work, 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). The Glodnys state that “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). However, Goldblatt’s actual statement is as follows: “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” (3). Goldblatt had explained why Loesch failed to prove his hypothesis. By omitting “persistent” from both sentences, the Glodnys completely pervert Goldblatt’s conclusions.