Jan-Petter Odden

The Effect of Arterial Pco2-Variations on Ocular and Cerebral Blood Flow in the Newborn Piglet

ABSTRACT: The response of ocular and cerebral blood flow to different arterial Pco2 levels was studied in ventilated paralyzed newborn piglets with the radionuclidelabeled microsphere method. The retina and the choroid have different blood flow responses to variations in arterial Pco2 levels. Retinal blood flow (ml/g/min) was increased during hypercarbia, from 0.26 ± 0.03 at baseline to 0.51 ± 0.07 (Paco2 8.7 ± 0.2 kPa) and 0.62 ± 0.07 (Paco2 11.0 ± 0.2 kPa). However, no significant change was found in choroidal blood flow during hypercarbia. Cerebral blood flow was more responsive to Paco2 than retinal blood flow, increasing from 0.71 ± 0.03 at baseline to 2.25 ± 0.25 (Paco2 8.7 ± 0.2) and 1.77 ± 0.13 (Paco2 11.0 ± 0.2). Hypocarbia did not influence either retinal or choroidal blood flow.

Regional blood flow during severe hypoxemia and resuscitation with 21% or 100% O2 in newborn pigs

Our aim was to determine whether the use of room air or 100% oxygen has different effects on the peripheral circulation during resuscitation from severe hypoxemia. Twenty-four piglets, 2-to 5-days old, were anesthetized with pentobarbital and randomized to control (n = 5, surgery only) or hypoxemia. Hypoxemia (FiO2 = 0.08) was continued until base excess reached - 20 mml/L. Resuscitation was then performed with 21% (n = 10) or 100% O2 (n = 9) for 25 min followed by 21% O2 in both groups. Regional blood flow was measured with radioactive microspheres. Both hypoxic groups showed marked hyperemia during resuscitation in cardiac and skeletal muscle, a moderate hyperemia in intestine and pancreas while kidneys, liver, spleen and skin showed no hyperemic response. There were no significant differences between the two treatment groups in blood flow to any organ. Arterial oxygen content was significantly higher in the 100% O2 group than in the 21% O2 at 5 and 20 min after onset of resuscitation (11.6 +/- 0.7 and 11.2 +/- 0.6 vs 8.6 +/- 0.3 and 8.7 +/- 0.3 ml/100 ml, p < 0.01). Oxygen delivery was, however, significantly higher in the 100% O2 group than in the 21% O2 group only to the intestine and pancreas at 5 min of resuscitation. We conclude that resuscitation with 21% or 100% oxygen produces similar changes in peripheral blood flow in this porcine model of neonatal hypoxemia.

Cerebral Blood Flow during Experimental Hypoxaemia and lschaemia in the Newborn Piglet

Odden, J.‐P., Stiris, T., Hansen, T. W. R. and Bratlid, D. (Neonatal Research Laboratory, Department of Paediatric Research, Institute for Surgical Research and Department of Paediatrics, Rikshospitalet, University of Oslo, Oslo, Norway). Cerebral blood flow during experimental hypoxaemia and ischaemia in the newborn piglet. Acta Paediatr Scand Suppl 360: 13, 1989.

Validity of Doppler measurements of superior mesenteric artery blood flow velocity: Comparison with blood flow measured by microsphere technique

Objective: To validate Doppler measurement of superior mesenteric artery blood flow velocity as a measurement of superior mesenteric artery blood flow. Method: The superior mesenteric artery blood flow velocity, measured by the Doppler ultrasound technique, was validated with simultaneous measurement of blood flow by the microsphere method. Six newborn piglets were studied during baseline conditions, after 10 min of hypoxaemia and during continuous calcium blocker infusion. Results: Mean blood flow velocity (r = 0.69, P < 0.0001), end-diastolic flow velocity (EDFV) (r = 0.81, P < 0.0001) and resistance index (r = 0.76, P < 0.0001) all correlated with superior mesenteric artery blood flow, whereas the peak systolic flow velocity did not correlate. Mean blood flow velocity did not significantly reflect all the changes in blood flow, probably because of changes in cross-sectional area of the superior mesenteric artery. The changes in EDFV followed the changes in blood flow more closely, although the decrease in EDFV (91% ± 12%) was of greater magnitude than the decrease in blood flow (55% ± 11%). Conclusions: Our results suggest that, although EDFV measurements in the superior mesenteric artery are not a predictor of quantitative changes in blood flow, it could be used to follow qualitative changes in intestinal blood flow under different clinical conditions.

Effect of hypoxemia and hypovolemia on retinal and choroidal blood flow in the newborn piglet

The effect of hypoxemia and/or hypovolemia on ocular blood flow was studied in paralyzed and mechanically ventilated newborn piglets with the isotope-labelled microsphere method. Twenty-six piglets were studied in four different groups. One group of piglets (n = 6) was made hypoxemic by breathing 10% O2, a second group (n = 7) and a third group (n = 7) were studied during hypoxemia (10% O2), followed by hypovolemia (bleeding 20 and 30% of estimated blood volume, respectively). A fourth group of piglets (n = 6) was made hypovolemic by bleeding 20% of estimated blood volume. Hypoxemia resulted in a 2- to 3-fold increase in retinal blood flow (RBF), while hypovolemia did not change RBF, not even when preceded by a period of hypoxemia. In the case of choroidal blood flow (ChBF), the increase caused by hypoxemia was only 10-40%. Although ChBF decreased significantly during hypovolemia, no significant correlation between mean arterial blood pressure and ChBF was found. The results indicate that autoregulation is normally seen in RBF, but probably not in ChBF. However, during hypoxemia autoregulation was found neither in RBF nor in ChBF.

Cerebral blood flow autoregulation after moderate hypoxemia in the newborn piglet.

The isotope-labelled microsphere method was used to study blood flow autoregulation in the brainstem (BS), cerebellum (CBL), cerebrum (CBR) and choroid plexus (ChPl) in 21 newborn piglets exposed to hypoxemia and/or hypovolemia. One group of piglets (n = 7) was made hypoxemic by breathing 10% O2 for 10 min, a second group (n = 8) was studied during hypoxemia (10% O2, 10 min), followed by hypovolemia (bleeding 20% of estimated blood volume). A third group of piglets (n = 6) was made hypovolemic by bleeding 20%. Hypoxemia significantly impaired the autoregulatory capacity in CBL and CBR resulting in a pressure-passive flow pattern. Hypovolemia alone did not produce any significant cerebral vascular response in BS, CBL and CBR, not even when hypovolemia was preceded by hypoxemia, indicating a rapid restoration of the autoregulatory capacity of the cerebral vasculature after hypoxemia of moderate duration. The hypotension seen both during hypoxemia and hypovolemia was gradually compensated for and normalized within 60 min. However, animals exposed to both hypoxemia and hypovolemia were still hypotensive 60 min after the hypoxemic insult. Cardiac output (CO) was not affected by hypoxemia, but was consistently reduced in hypovolemia. We therefore speculate that in the newborn a reduced CO might be a more specific parameter for hypovolemia than a low blood pressure.

Effect of Light and Hyperoxia on Ocular Blood Flow in the Newborn Piglet

Ocular blood flow was studied in newborn piglets during light exposure and light combined with hyperoxia. Light caused a significant increase in ocular blood flow which returned to values not significantly different from baseline levels during superimposed hyperoxia. None of these experimental conditions changed total cerebral blood flow or cardiac output. The findings indicate that light might be a regulator of ocular blood flow. This influence of light on ocular blood flow may be of importance in the pathophysiology of retinopathy of prematurity.

Effect of Intraventricular Hemorrhage on Pulmonary Function in Newborn Piglets

Intracranial hemorrhage in the premature infant is often associated with respiratory failure and need for mechanical ventilation. We therefore addressed the question of possible interactions with and pulmonary consequences of intraventricular hemorrhage. Newborn piglets were studied during intraventricular hemorrhage simulated by intraventricular blood infusion. Infusion volume amounted to 8% of estimated brain weight. Respiratory rate, minute ventilation, lung resistance and dynamic lung compliance, as well as arterial blood gases, arterial and intraventricular pressures were measured. The piglets were mechanically ventilated with a low basal rate of 20 breaths per minute throughout the study. All piglets experienced significant rise in intraventricular pressure and respiratory failure during the study. Respiratory failure was mainly a result of a reduction in respiratory frequency and minute ventilation until apnea. However, a rise in lung resistance was also noted while lung compliance did not change. We conclude that increased need for mechanical ventilation during intracranial hemorrhage is primarilty a consequence of hypoventilation. The increase seen in lung resistance could also suggest that intraventricular hemorrhage causes an element of bronchiolar constriction. Furthermore, these effects are not only a result of the increase in intraventricular pressure, but specific effects of blood components within the central nervous system must be considered.

Effect of nimodipine on cerebral and organ blood flow in normal and posthypoxemic newborn piglets

Using the isotope-labelled microsphere method, blood flow to the brain, the heart and the kidneys were studied in newborn piglets during nimodipine infusion. Twenty piglets were studied in two different groups. Group 1 (n = 8) was kept normoxic and given a continuous nimodipine infusion (15 micrograms/kg/min). Group 2 (n = 12) was made hypoxemic by breathing 10% O2 for 10 min followed by an identical nimodipine infusion as group 1. In spite of a significant systemic hypotension, nimodipine infusion alone significantly increased blood flow in the brain stem and right cardiac ventricle at 30-60 min of infusion, while blood flow to cerebellum, cerebrum and the left cardiac ventricle did not change. Blood flow to the kidneys decreased significantly. In posthypoxemic piglets nimodipine infusion gave almost similar flow patterns, however, the changes appeared at an earlier time. We conclude that in spite of a significant reduction in blood pressure, cerebral and cardiac blood flow is preserved both in normal and posthypoxemic animals even at high doses of nimodipine. However, because of the decreased blood flow to the kidneys further dose-response studies are needed before clinical use in asphyctic newborns.

Retinal and choroidal blood flow response to hyperoxemia after severe hypoxemia in the newborn Piglet

To investigate the effect of hyperoxemia on the ocular circulation after a severe hypoxemic insult (8% O2 until base excess reached -20 mmol/l), we randomly reoxygenated newborn piglets with 100% (study group, n = 8) or 21% O2 (control group, n = 10). Retinal (RBF) and choroidal blood flow (ChBF) were measured with radioactive microspheres. The hypoxemic insult did not change RBF, while ChBF significantly decreased. However, a marked reduction in both retinal (RDO2) and choroidal oxygen delivery (ChDO2) was observed, probably resulting in hypoxia both in the inner and outer retina. At 5 and 20 min of reoxygenation a similar hyperemic response in the retina was seen in both groups. RDO2 also increased significantly and no significant differences between the 2 groups could be demonstrated. We found no indication of retinal vasoconstriction during hyperoxemia. We speculate that the vasodilating effect of the preceding hypoxemia overrules the vasoconstrictive effect of the retinal vessels normally found during hyperoxemia.