SUMMARY In eight humans with coarctation, fresh aortic tissue was examined pharmacodynamically. In four of these patients, and in 12 additional patients, the aorta above and below the coarctation was studied morphologically and compared with eight control aortas. By in vitro stimulation with potassium (127 mM), noradrenaline (18 usM), and prostaglandin F,. (28 M), postcoarctational aortic ring preparations-showed a significantly greater contractility than precoarctational rings (p < 0.05). Volumetric analysis showed significantly more collagen (p < 0.01) and less smooth muscle mass (p < 0.01) in the aorta above than below the coarctation. No significant differences were found between sections from the arch and distal to the ligamentum arteriosum in the normal aortas.We conclude that the precoarctational aortic wall is more rigid than the postcoarctational wall. (25-30°C) and transported to the laboratory, where they were cleaned of connective tissue and cut into rings. The macroscopically identified coarctation was isolated in one ring preparation, and two preparations of about the same weight were isolated above and below the stenosis. MethodThe isometric tension changes in both rat and human ring segments were recorded by the "ring" method described by Bevan and Osher7 and others.8-'0 The ring preparations were mounted in 30-ml jacketed organ baths that contained Krebs solution ( fig. 1). The temperature of the solution was maintained at 37°C and was constantly aerated with 95% oxygen and 5% carbon dioxide. The isometric contractions were recorded using Grass Ft 03 transducers connected to a Beckman R6 11 polygraph.During a 1-2-hour period, the resting length was adjusted (by stepwise depression of the rod) ( fig. 1) to the level at which maximal contraction force by depolarization could be generated. During this period, anesthetics possibly left in the tissue were also washed out. The resulting resting length -and corresponding resting tension -for a ring preparation were kept constant throughout the experiment, and a drug was not applied before the resting tension was reached again.The repeated isometric contractions were induced by potassium depolarization (127 mM) until responses were reproducible. Thereafter, the responses to supra-

Renal ischemia-reperfusion injury is the state of which a tissue experiences injury after a phase of restrictive blood supply and recirculation. Ischemia-reperfusion injury (I/R-I) is a leading cause of acute kidney injury (AKI) in several disease states, including kidney transplantation, sepsis, and hypovolemic shock. The most common methods to evaluate AKI are creatinine clearance, plasma creatinine, blood urea nitrogen, or renal histology. However, currently, there are no precise methods to directly assess renal injury state noninvasively. Hyperpolarized C-pyruvate MRI enables noninvasive accurate quantification of the in vivo conversion of pyruvate to lactate, alanine, and bicarbonate. In the present study, we investigated the in situ alterations of metabolic conversion of pyruvate to lactate, alanine, and bicarbonate in a unilateral I/R-I rat model with 30 min and 60 min of ischemia followed by 24 h of reperfusion. The pyruvate conversion was unaltered compared with sham in the 30 min I/R-I group, while a significant reduced metabolic conversion was found in the postischemic kidney after 60 min of ischemia. This indicates that after 30 min of ischemia, the kidney maintains normal metabolic function in spite of decreased kidney function, whereas the postischemic kidney after 60 min of ischemia show a generally reduced metabolic enzyme activity concomitant with a reduced kidney function. We have confidence that these findings can have a high prognostic value in prediction of kidney injury and the outcome of renal injury.

We have investigated the active, passive and myogenic tension-internal circumference relations of rat intramural coronary and, as controls, mesenteric small arteries (internal diameter ca. 200 micron) using an isometric myograph. The active tensions of the vessels (when fully activated with 30 microM serotonin in K-saline) reached a maximum (2.54 N/m, coronary; 3.39 N/m, mesenteric) at an internal circumference, L0, where the passive tensions (measured in Ca-free solution) were 0.80 N/m (coronary) and 0.74 N/m (mesenteric). Below 0.8 L0 and above 1.2 L0 the active tensions fell linearly, the zero tension intercepts being 0.37 L0 and 1.74 L0 (coronary) and 0.40 L0 and 1.72 L0 (mesenteric). The passive wall tensions of the vessels rose exponentially as a function of internal circumference, the wall tension at 1.5 L0 being 10.0 N/m (coronary) and 8.5 N/m (mesenteric). In normal physiological salt solution, the coronary vessels had a Ca2+ dependent myogenic tone which was also dependent on the internal circumference. Maximum myogenic tone (0.54 N/m) was obtained at 1.18 L0. The mesenteric vessels had no such myogenic tone. Histological examination showed that the media/lumen ratios of both vessel types were the same, and that the smooth muscle content of the media was greater in the coronary (81%) than in the mesenteric (72%) vessels. The smaller active tension of the coronary vessels could not therefore be ascribed to a reduced smooth muscle content, but possibly in part to an observed heterogeneous arrangement of the smooth muscle cells in the coronary vessels.

After furosemide 40 mg i. v. its plasma concentration was significantly higher during an 8-hour period in 6 patients with left sided heart failure than in 8 normal subjects. The plasma clearance was significantly lower in the patients than in the normal subjects--1.23 and 2.34 ml/kg/min, respectively. The apparently smaller volume of distribution in the cardiac patients (0.140 1/kg and 0.181 1/kg, respectively) was not significantly different. In the group of normal subjects, whose ages ranged from 27 to 74 years, no correlation was found between age and either plasma clearance or volume of distribution. In all the patients, the renal clearance of furosemide rose from the first to the second hour after the injection (average +/- SD)--39 +/- 17 and 77 +/- 51 ml/min. In normal subjects, the average values did not change--116 +/- 79 and 117 +/- 54 ml/min. The urinary excretion of furosemide and a metabolite (probably a glucuronide) was measured in 16 individuals. 24-hour urines from all the subjects investigated contained between 20 and 30 mg unchanged furosemide (average 25.2 mg). In addition, between 2.7 and 11.2 mg (average 6.7 mg) furosemide was excreted as the metabolite in five patients who had been treated with furosemide for at least the preceding 6 months. An average of 0.8 +/- 0.8 mg of the metabolite was found in 11 subjects who had not previously been treated with furosemide.