Lack of effect of antioxidant therapy during renal ischemia and reperfusion in dogs

Acute ischemic renal failure is of great clinical importance because of its frequent occurrence and the high mortality it causes. Recent observations indicate that reperfusion has its own dangers because of oxygenderived free radicals. To study this problem, ischemia was evoked in dogs in one kidney, by clamping the left renal artery for 45 min. This was followed by a 90-min period of reperfusion when diuresis, GFR, PAH clearance and sodium and potassium excretion were studied. Besides a control group (n=6), the following treatment groups were investigated. Allopurinol (n=7): 50 mg/kg for two days p.o. and 50 mg/kg in physiological saline infusion during the experiment; a small dose of SOD (n=6): 0.5 mg/kg in infusion, started 1 min before reperfusion and given continuously for 10 min; and a high dose of SOD (n=7): 5 mg/kg as above. In the first 15 min following reperfusion, the renal functions significantly worsened in all groups. Later on, the renal functions gradually improved and in the last period after reperfusion, GFR in the ischemic kidney was 64%, cPAH 59%, diuresis 60% and sodium and potassium excretion were 65% and 76%, respectively, of the basal values in the control group.Treatment with free radical scavengers did not cause any considerable changes in the renal functions. In some respects, the worst results were observed with low-level SOD treatment (cPAH, diuresis, as well as sodium and potassium excretion).At the end of reperfusion, there was a significant drop in sodium excretion by the right (intact circulation) kidney of the treated animals.     

Hepatic blood flow in acute myocardial ischemia

Hepatic blood flow was monitored in cats during myocardial ischemia (MI). Increased plasma CPK activity, the S-T segment of the electrocardiogram, and hepatic flow was reduced by 5 h to 40% of control. The results suggest that MI can influence organs distant from the original ischemic episode.     

Hepatic blood flow in acute myocardial ischemia

Summary Hepatic blood flow was monitored in cats during myocardial ischemia (MI). Increased plasma CPK activity, the S-T segment of the electrocardiogram, and hepatic flow was reduced by 5 h to 40% of control. The results suggest that MI can influence organs distant from the original ischemic episode.Supported in part by Research grant HL-17745 from the National Heart, Lung and Blood Institute of the National Institutes of Health.Acknowledgments. We gratefully acknowledge the expert technical assistance of Mary Ann Spath.     

Massive striatal dopamine release in acute cerebral ischemia in rats

Summary Extracellular dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and cerebral blood flow were simultaneously determined using in vivo brain dialysis and a hydrogen clearance method in the striatum of spontaneously hypertensive rats during ischemia and after recirculation. Massive striatal dopamine release was demonstrated in acutely induced ischemic brain.     

Ventricular fibrillation threshold during acute ischemia in hypertrophied rat hearts

Ventricular fibrillation threshold was significantly lower in hypertrophied hearts than in normal hearts. Ischemia produced by coronary occlusion reduced fibrillation threshold in both normal and hypertrophied hearts, but the maximum reduction in fibrillation threshold was observed earlier in hypertrophied hearts.     

Ventricular fibrillation threshold during acute ischemia in hypertrophied rat hearts

Summary Ventricular fibrillation threshold was significantly lower in hypertrophied hearts than in normal hearts. Ischemia produced by coronary occlusion reduced fibrillation threshold in both normal and hypertrophied hearts, but the maximum reduction in fibrillation theshold was observed earlier in hypertrophied hearts.     

Experimental approaches to study functional recovery following cerebral ischemia

Valid experimental models and behavioral tests are indispensable for the development of therapies for stroke. The translational failure with neuroprotective drugs has forced us to look for alternative approaches. Restorative therapies aiming to facilitate the recovery process by pharmacotherapy or cell-based therapy have emerged as promising options. Here we describe the most common stroke models used in cell-based therapy studies with particular emphasis on their inherent complications, which may affect behavioral outcome. Loss of body weight, stress, hyperthermia, immunodepression, and infections particularly after severe transient middle cerebral artery occlusion (filament model) are recognized as possible confounders to impair performance in certain behavioral tasks and bias the treatment effects. Inherent limitations of stroke models should be carefully considered when planning experiments to ensure translation of behavioral data to the clinic.     

Tissue catecholamines following renal denervation in spontaneously hypertensive rats

Summary The delay in blood pressure increase observed in spontaneously hypertensive rats following bilateral renal denervation appeared to be due to a temporary reduction of the renal catecholamines content.This work was supported by grants from the Institut National de la Santé et de la Recherche Médicale (ATP 32-76-64, and AU 79-35) and from the Fonds National Suisse de la Recherche Scientifique (3.033.76)     

Urinary renin and norepinephrine excretion in dogs after unilateral renal artery constriction

Zusammenfassung Nach einseitiger Drosselung der Nierenarterie beim Hund fanden sich höhere Renin-Aktivität und Norepinephrin-Konzentration im Urin der ischämischen Niere als im Urin der Gegenseite. In der Rinde der gedrosselten Niere waren Renin-Aktivität und Granulationsindex der juxtaglomerulären Zellen höher als in der Rinde der ungeklemmten Niere, während der Natriumgehalt niedriger war.     

Brain glycogen following experimental cerebral ischemia in gerbils (Meriones unguiculatus)

Summary Cortical glycogen levels decreased after both 1 and 3 h of unilateral ischemia. After 1 h of recirculation, the levels of glycogen were restored to control values in both groups. Subsequently, glycogen increased above normal levels after 1 week of recirculation in the 1 h ischemic groups, and after 5 h in the 3 h ischemic group. Thus, the onset of the excess glycogen accumulation appears to be dependent on the intensity of the ischemic insult.     

Baroreceptor reflex sensitivity after acute blood volume expansion in anesthetized dogs

Summary Changes in heart rate resulting from mechanically induced changes in arterial blood pressure were used as a measure of baroreflex sensitivity. This sensitivity was shown to be decreased after volume expansion.This work was supported in part by PHS grant HL-23239 and a grant from the Central Ohio Heart Chapter of the American Heart Association.     

Postischemic ATP levels predict hepatic function 24 hours following ischemia in the rat

Summary Hepatic function was assessed by the aminopyrine breath test (ABT) in male Sprague Dawley rats 24 h after partial hepatic ischemia. ABT decreased progressively to 26.3 (p<0.05) and 19.7% of dose (p<0.05) after 90 and 120 min of ischemia, respectively. ABT at 24 h after injury was correlated to the concentration of ATP in the ischemic lobes 1 h after the onset of reperfusion (r²=0.971) but not to ALT activity in plasma at 1 h (r²=0.391). We conclude that postischemic ATP levels are a better index of subsequent hepatic function than ALT.     

Postischemic ATP levels predict hepatic function 24 hours following ischemia in the rat

Hepatic function was assessed by the aminopyrine breath test (ABT) in male Sprague Dawley rats 24 h after partial hepatic ischemia. ABT decreased progressively to 26.3 (p less than 0.05) and 19.7% of dose (p less than 0.05) after 90 and 120 min of ischemia, respectively. ABT at 24 h after injury was correlated to the concentration of ATP in the ischemic lobes 1 h after the onset of reperfusion (r2 = 0.971) but not to ALT activity in plasma at 1 h (r2 = 0.391). We conclude that postischemic ATP levels are a better index of subsequent hepatic function than ALT.     

Acute effect of hypophysectomy on the natriuresis following saline infusion in dogs.

The natriuresis following an i.v. isotonic saline loading corresponding to 10% of body wt. was markedly decreased after acute hypophysectomy, due to lowered urinary sodium concentration, in anaesthetized dogs. A role of the pituitary in such a homeostatic natriuresis is suggested.     

Examination of the fundus of the eye of renal hypertensive dogs

Summary Only 1 of 7 dogs with long-standing renovascular hypertension showed clear changes in the fundus. No distinct retinopathy was seen in the others. Ophthalmoscopy alone is thus of limited value in assessing the progress of benign hypertension in the dog.