ABSTRACT. Previous work in a neonatal lamb model has demonstrated abnormalities in cerebral blood flow (CBF) and oxygen consumption (CMROZ) after asphyxia. Immediately after resuscitation, there was a marked increase in CBF and a significant decrease in CMR02 compared to control. During the late period after asphyxia (30 min to 4 h), both CBF and CMR02 were significantly depressed.The same postasphyxia model (n = 16) was used to examine the hypothesis that generation of oxygen free radicals during cerebral reperfusion may be involved in the genesis of late postasphyxia hypoperfusion and depressed CMR02. Before asphyxia, the animals were pretreated with either inactivated (n = 8) or active (n = 8) polyeth-

Experiments were performed to determine whether furosemide, given in doses high enough to induce a strong diuresis and to inhibit the mechanism of tubuloglomerular feedback, offers any protection from acute renal failure induced by a nephrotoxin or ischaemia. Microperfusion of the loop of Henle revealed that a tubular furosemide concentration of 5 x 10(-5) mol x 1(-1) was necessary to fully inhibit the tubuloglomerular feedback response to a raised sodium chloride concentration at the macula densa. The infusion of furosemide systemically to achieve such concentrations in the tubule resulted in an improvement in renal function when given before or after the nephrotoxin but was without effect when given before or after ischaemia. Measurements of furosemide concentrations in the urine, however, confirmed that sufficient amounts were applied to inhibit the feedback mechanism. It is concluded from this and similar studies that furosemide is only beneficial in models of acute renal failure with an obstructive or nephrotoxic pathogenesis, in which it acts by flushing out the noxious material and not by inhibiting the mechanism of tubuloglomerular feedback.

We examined mitochondrial oxidative function 5 minutes and 2 hours after a gradual asphyxia! insult in newborn lambs. We subjected 16 ventilated newborn lambs to 75-90 minutes of hypoxia and hypercarbia that resulted in bradycardia and systemic hypotension over the final 15 minutes of the insult. At the end of asphyxia, the lambs were resuscitated and returned to control ventilator settings. Samples of brain were removed 5 minutes (n=8) and 2 hours 0 = 8 ) after asphyxia. Each group of eight lambs was subdivided into those < 3 or > 3 days old to evaluate the effect of age on postasphyxia mitochondrial function. After classification into nonsynaptk and synaptlc mitochondria, mitochondria] respiration (oxygen consumption) was measured using five different substrates. Data from asphyxiated lambs were compared with that from a control group of ventilated nonasphyxiated lambs (n=8). In the lambs < 3 days old, there was significant depression of mean±SEM nonsynaptic mitochondria state 3 (adenosine diphosphate-dependent) respiration to 29.5±5.2% of control with four of the five substrates and of state 4 respiration to 33.7±0.9% of control with three of the five substrates 5 minutes after asphyxia. By 2 hours after asphyxia, mean±SEM nonsynaptic mitochondria state 3 respiration increased to 70.4±6.4% of control while state 4 respiration increased to 58.2±4.5% of control. In contrast, lambs > 3 days old exhibited no inhibition of nonsynaptic mitochondria function after asphyxia. In synaptic mitochondria, mean±SEM state 3 respiration was significantly decreased to 45.5±4.0% of control with four of the five substrates 5 minutes after asphyxia, with a return to 81.8±11.9% of control 2 hours after asphyxia. Synaptic mitochondria state 4 respiration significantly decreased 5 minutes after asphyxia with only one of the five substrates used. Again, no inhibition of mitochondrial respiration was seen in lambs > 3 days old either 5 minutes or 2 hours after asphyxia. We have demonstrated reversible inhibition of mitochondrial respiratory function after asphyxia in lambs < 3 days old. In lambs > 3 days old, no inhibition of mitochondrial respiration was noted after asphyxia. (Stroke 1989;20:674-679) P revious work in a newborn lamb postasphyxia model has demonstrated abnormalities in postasphyxia cerebral blood flow (CBF) and oxygen consumption (CMRO2). Recovery from asphyxia was associated with an early hyperperfusion followed by a delayed hypoperfusion, during which CMRO2 was persistently depressed.1 Although mitochondrial respiratory function has been studied in a variety of adult postischemia models, Received May 10, 1988; accepted November 9, 1988. CMR0 2 after asphyxia previously demonstrated in this model was due to an inhibition of mitochondrial respiratory function. We used the newborn lamb asphyxia model to evaluate postasphyxia mitochondrial respiratory activity. Nonasphyxiated lambs were compared with lambs exposed to an asphyxia! insult followed by 5 minutes or 2 hours of recirculation. Furthermore, the groups were ...

ABSTRACT. The effect of preasphyxia blood glucose concentration on postasphyxia (PA) cerebral hemodynamics was examined in 21 newborn lambs. Glucose was unregulated in one group (n = 7), and controlled throughout the study by glucose clamp in hyperglycemic (n = 7) and hypoglycemic (n = 7) groups. Cerebral blood flow, determined using radiolabelled microspheres, and arterial and sagittal sinus Oz contents were measured at control, 5 min, 1, 2, and 4 h after resuscitation from an asphyxia1 insult.Preasphyxia blood glucoses were 6.48 f 0.55 mM (mean f SEM), 12.08 f 0.80, and 2.66 f 0.14 in the three study groups. In all three groups, 5 min PA cerebral blood flow was significantly increased from control. In the late period after asphyxia, the unregulated group had decreased cerebral blood flow compared with control, 53.2 f 3.8 mL. 100 g-' . min-I, mean f SEM, p < 0.01; 49.6 f 2.0, p < 0.005; 53.4 2 3.0, p < 0.01, at 1, 2, and 4 h PA, respectively, versus 85.7 + 6.9 at control, whereas both the hyper-and hypoglycemic groups did not differ significantly from control measurements. Cerebral oxygen consumption (CMR02) was significantly decreased in all three groups 5 min PA and remained decreased in the late period after asphyxia in both the unregulated and hypoglycemic groups. In the unregulated group, CMRO? was 191 2 14 pM. 100 g-' . min-I, mean 2 SEM, p < 0.05; 200 +. 4; and 181 + 10, p < 0.05 at 1, 2, and 4 h, respectively, PA versus 251 + 12 at control. In the hypoglycemic group, CMRO? was 170 + 9 pM. 100 g-' . min-I, mean + SEM, p < 0.05; 174 f 14, p < 0.05; and 183 f 17 at 1, 2, and 4 h PA, respectively, versus 231 f 15 at control. CMRO? did not differ from control in the hyperglycemic group at 1, 2, and 4 h PA. In our newborn lamb postasphyxia model, CMRO? was best maintained PA when the lambs were hyperglycemic before asphyxia and throughout the recovery period. To the extent that more rapid recovery of CMROz postasphyxia is a favorable outcome, these data may have implications for clinical management. Previous studies in a newborn lamb postasphyxia model have demonstrated abnormalities in PA CBF and CMR02. Immediately after resuscitation from asphyxia, there was a marked increase in CBF. However, despite this overperfusion, CMR02 was decreased. Thirty min to 4 h after resuscitation, both CBF and CMROl were decreased ( 1-3).One of the variables that may influence the response to perinatal asphyxia is preasphyxia blood glucose concentration. Myers and Yamaguchi (4) found that food-deprived juvenile monkeys recovered with minimal damage after a 10-14 min cardiorespiratory arrest, whereas fed or glucose-pretreated animals developed signs of increased intracranial pressure and died. Considerable data exist in adult ischemia models demonstrating worse neurologic outcome (5), increased pathologic damage and cerebral edema (5-7), impaired cerebral perfusion (8), and poorer recovery of brain energy metabolism (9, 10) with glucose administration prior to asphyxia. However, data from newborn rats and mice have demonstrate...