Prevention of the hemorrhagic hypotension-induced hepatic arterial vasoconstriction by L-arginine and naloxone.

The possible involvement of the L-arginine-nitric oxide pathway and endogenous opioid mechanisms in the hemorrhagic hypotension- (HH) induced changes of hepatic arterial blood flow and vascular resistance was studied in cats. During HH hepatic arterial blood flow was significantly higher both in L-arginine- and naloxone-treated animals than in controls. Furthermore, HH induced a significant increase of the hepatic vascular resistance in the control group, which was prevented by L-arginine or naloxone treatment. Because inhibition of the nitric oxide synthesis by N(G)-nitro-L-arginine in normotensive cats induced a similar increase of the hepatic vascular resistance to that observed during HH in the control group, our results indicate that impairment of the endothelial function may be responsible for the hemorrhage-induced L-arginine- and naloxone-reversible hepatic arterial vasoconstriction. This hypothesis is consistent with our previous observations demonstrating the development of endothelial dysfunction in the feline hepatic artery during HH.

Effect of superoxide dismutase on hemorrhagic hypotension and retransfusion-evoked middle cerebral artery endothelial dysfunction.

UNLABELLED: Middle cerebral artery rings (MCA) were prepared from control and hemorrhagic hypotension and retransfusion-subjected (HHR) cats, with or without superoxide dismutase (SOD) treatment. Two-mm-long MCA segments were suspended in organ chambers containing Krebs-Henseleit solution (37 degrees C, gassed with 95% O2-5% CO2) for isometric force measurements. HHR was produced by bleeding to 90, 70, and 50 mmHg MAP and maintained for 15 min at each level, followed by retransfusion. HHR resulted in a marked attenuation of the acetylcholine- and ATP-induced endothelium-dependent relaxations of the MCA in vitro. Relaxations induced by the nitric oxide (NO) donor SIN-1 remained unaltered. In vitro treatment of the vessels with SOD (150 U/ml), facilitated the acetylcholine-induced relaxations both in the control arteries and in the vessels after HHR. In the vessel rings from cats that received in vivo SOD (10 mg/kg initial bolus, followed by 0.1-mg/kg/min infusion) during HHR, cholinergic relaxations were more pronounced than in the HHR untreated cats. The ATP-induced relaxations, however, remained attenuated after SOD treatment, except for the highest dose (10(-5) M) that was applied. CONCLUSION: Superoxide release attenuates the endothelium-dependent relaxation by acetylcholine both in control arteries and after HHR in vitro. The protective effect of in vivo SOD treatment on cerebrovascular endothelium-dependent reactivity in cats suggests that superoxide free radicals contribute to the development of the endothelium dysfunction in MCA rings after HHR.

31P NMR spectroscopy of brain and heart.

31P NMR technique was applied to monitor changes in the energy metabolism of the brain and heart of unanesthetized cats during shock, stroke, hypoxia and increased functional activity. The results show that in these tissues content of inorganic phosphate, sugar phosphates, phosphocreatine and of ATP can be measured decently in awake animals. At the same time this technique has the great advantage over the disruptive biochemical methods that it gives a semi-continuous reading and it is non-invasive. Our findings are summarized as follows: Hemorrhagic shock resulted in an irreversible deterioration of the energy state of the brain. Our stroke model led to a very marked increase in Pi and a decrease CP in the brain but these changes were reversible. The ATP levels of the brain as it was indicated by 31p NMR spectra were not affected by hemorrhagic shock and stroke which can be attributed probably by the reduced rate of ATP consumption. The verification of this hypothesis needs further work. During increased mechanical performance the levels of SP, and Pi increased, ATP decreased, while CP was not influenced in the heart.

Local blood flow of the hypothalamus in haemorrhagic hypotension.

Local blood flow of the hypothalamus (HBF) was measured by the hydrogen clearance method in anaesthetized dogs. The average value for HBF in normal controls was 0.64 +/- 0.05 ml/g/min, which compares favourably with values available in the literature. During haemorrhagic hypotension induced by a modified Wiggers method there occurred a marked reduction of HBF to 52% of the initial control value at a mean arterial blood pressure (MABP) of 55--60 mm Hg and to 44% at 35--40 mm Hg. Prevention of concomitant extracellular acidosis by infusion of sodium bicarbonate solution during the hypotensive period resulted in a significantly smaller decrease in HBF as compared to an untreated control group, and a significant protection of HBF was also found at 55--60 mm Hg MABP in the bicarbonate treated group, but not in controls treated with physiologic saline. Hypothalamic tissue hypoxia was inevitable in untreated bled animals due to insufficient circulatory transport, while evidence suggested that the metabolism might have remained unaltered in the group protected against acidosis during haemorrhage. Analysis of the control of local hypothalamic blood flow revealed a significant correlation (r = 0.7026, p less than 0.001) between HBF and arterial blood pH in severe hypotension which is outside the autoregulatory blood pressure domain.

Hypothalamic and thalamic blood flow during somatic afferent stimulation in dogs.

The effect of somatic afferent C fiber stimulation on regional cerebral blood flow (rCBF) and cerebral tissue available oxygen (aO2) was studied in 20 dogs under chloralose anesthesia. Mean arterial blood pressure, arterial Pco2, and pH were stabilized before and during the 3-min stimulation of the sciatic nerves (20 V, 300 ms, 15 Hz). Combined gold+platinum electrodes were chronically implanted into the ventral posterolateral nucleus of the thalamus, ventromedial nucleus of the hypothalamus, and into the white matter. Tissue aO2 and rCBF of these regions were measured polarographically, the latter by the H2-gas clearance technique. Blood flow changed from 42 +/- 2.1 to 28 +/- 1.7 ml/100 g per min (cerebrovascular resistance (CVR), from 2.91 +/- 0.29 to 4.31 +/- 0.52 resistance units (RU) in the thalamus, from 59 +/- 5.0 to 47 +/- 5.0 ml/100 g per min (CVR: from 2.46 +/- 0.28 to 2.92 +/- 0.35 RU) in the hypothalamus, and from 21 +/- 1.0 to 17 +/- 0.8 ml/100 g per min (CVR: from 6.367 +/- 0.35 to 7.672 +/- 0.40 RU) in the white matter during ipsilateral stimulation. Contralateral stimulation of the sciatic nerves caused a more moderate but likewise significant drop in rCBF and an increase in CVR except in the white matter. Parallel to these changes, tissue aO2 decreased by 25 +/- 2% in the thalamic and by 19 +/- 2% in the hypothalamic area, relative to the prestimulation level.

Cerebral blood flow and brain function during hypotension and shock.

In conclusion, the reviewed results clearly suggest that vital functions of the brain -in spite of the well-developed autoregulatory mechanisms-are impaired during long-lasting hypovolemic and other shock conditions. The insufficiency of the cerebrocortical and hypothalamic regulatory mechanisms can contribute to the development of the irreversible shock. In other words, failure of the body suffering from shock to restore the homeostatic equilibrium can be attributed to the inadequacy of the central nervous servocontrol system. According to the available results, the regional cerebral microcirculatory defect develops through sludge formation. The unevenly distributed local brain damage could be the background of the functional impairment. The focal appearance suggest that, in addition to generalized (bloody borne) changes, local factors play an important role in the production of patchy ischemic areas in the brain.

[Changes in the blood supply and oxygen tension of the brain following afferent somatic stimulation]. / Izmeneniia krovotoka i napriazheniia kisloroda v golovnom mozge pri afferentnoi somaticheskoi stimuliatsii

Effect of somatic afferent C fibres stimulation on rCBF (H2 - clearance method) and cerebral tissue pO2 was studied in 20 dogs. MABP and partial pressure of the arterial blood gases were stabilized before and during 3 min stimulation of the sciatic nerves. The blood flow was changed by 32% in the thalamus and by 17% in the hypothalamus during ipsilateral stimulation. Contralateral sciatic nerve stimulation caused smaller but still a significant fall of the rCBF and increase of the CVR in both regions. Parallel to these changes, tissue pO2 decreased by 19% in the hypothalamic and by 25% in the thalamic areas as compared with the prestimulation level.