Rapid and Persistent Decrease in Brain Tissue Oxygenation in Ovine Gram-negative Sepsis

The changes in brain perfusion and oxygenation in critical illness, which are thought to contribute to brain dysfunction, are unclear due to the lack of methods to measure these variables. We have developed a technique to chronically measure cerebral tissue perfusion and oxygen tension in unanesthetised sheep. Using this technique, we have determined the changes in cerebral perfusion and PO2 during the development of ovine sepsis. In adult Merino ewes, fibre-optic probes were implanted in the brain, renal cortex and renal medulla to measure tissue perfusion, oxygen tension (PO2) and temperature and flow probes were implanted on the pulmonary and renal arteries. Conscious sheep were infused with live Escherichia coli for 24-hr, which induced hyperdynamic sepsis; mean arterial pressure decreased (85.2±5.6 to 71.5±8.7 mmHg), while cardiac output (4.12±0.70 to 6.15±1.26 L/min) and total peripheral conductance (48.9±8.5 to 86.8±11.5 mL/min/mmHg) increased (n=8, all P<0.001) and arterial PO2 decreased (104±8 to 83±10 mmHg; P<0.01). Cerebral perfusion tended to decrease acutely, although this did not reach significance, but there was a significant and sustained decrease in cerebral tissue PO2 (32.2±10.1 to 18.8±11.7 mmHg) after 3 h and to 22.8±5.2 mmHg after 24-hr of sepsis (P<0.02). Sepsis induced large reductions in both renal medullary perfusion and PO2 but had no effect in the renal cortex. In ovine sepsis, there is an early decrease in cerebral PO2 that is maintained for 24-hours despite minimal changes in cerebral perfusion. Cerebral hypoxia may be one of the factors causing sepsis-induced malaise and lethargy.

Do I dream of conscious sheep: On self as a mental construct

I give some demonstrations for philosophy on the self and make connection to contemporary spirituality.

Activation of the carotid body increases directly recorded cardiac sympathetic nerve activity and coronary blood flow in conscious sheep

Activation of the carotid body (CB) using intracarotid potassium cyanide (KCN) injection increases coronary blood flow (CoBF). This increase in CoBF is considered to be mediated by co-activation of both the sympathetic and parasympathetic nerves to the heart. However, whether cardiac sympathetic nerve activity (cardiac SNA) actually increases during CB activation has not been determined previously. We hypothesized that activation of the CB would increase directly recorded cardiac SNA, which would cause coronary vasodilatation. Experiments were conducted in conscious sheep implanted with electrodes to record cardiac SNA and diaphragmatic electromyography (dEMG), flow probes to record CoBF and cardiac output and a catheter to record arterial pressure. Intracarotid KCN injection was used to activate the CB. To eliminate the contribution of metabolic demand on coronary flow, the heart was paced at a constant rate during CB chemoreflex stimulation. Intra-carotid KCN injection resulted in a significant increase in directly recorded cardiac SNA frequency (from 24±2 to 40±4 bursts/minute; p<0.05) as well as a dose-dependent increase in mean arterial pressure (79±15 to 88±14 mmHg; p<0.01) and CoBF (75±37 Vs 86±42 mL/min; p<0.05). The increase in CoBF and coronary vascular conductance to intracarotid KCN injection was abolished after propranolol infusion, suggesting that the increased cardiac SNA mediates coronary vasodilatation. The pressor response to activation of the CB was abolished by pre-treatment with intravenous atropine but there was no change in the coronary flow response. Our results indicate that CB activation increases directly recorded cardiac SNA which mediates vasodilatation of the coronary vasculature.

Renal hemodynamics and oxygenation during experimental cardiopulmonary bypass in sheep under total intravenous anesthesia

Renal medullary hypoxia may contribute to the pathophysiology of acute kidney injury, including that associated with cardiac surgery requiring cardiopulmonary bypass (CPB). When performed under volatile (isoflurane) anesthesia in sheep, CPB causes renal medullary hypoxia. There is evidence that total intravenous anesthesia (TIVA) may preserve renal perfusion and renal oxygen delivery better than volatile anesthesia. Therefore, we assessed the effects of CPB on renal perfusion and oxygenation in sheep under propofol/fentanyl-based TIVA. Sheep ( n = 5) were chronically instrumented for measurement of whole renal blood flow and cortical and medullary perfusion and oxygenation. Five days later, these variables were monitored under TIVA using propofol and fentanyl and then on CPB at a pump flow of 80 mL·kg−1·min−1 and target mean arterial pressure of 70 mmHg. Under anesthesia, before CPB, renal blood flow was preserved under TIVA (mean difference ± SD from conscious state: −16 ± 14%). However, during CPB renal blood flow was reduced (−55 ± 13%) and renal medullary tissue became hypoxic (−20 ± 13 mmHg versus conscious sheep). We conclude that renal perfusion and medullary oxygenation are well preserved during TIVA before CPB. However, CPB under TIVA leads to renal medullary hypoxia, of a similar magnitude to that we observed previously under volatile (isoflurane) anesthesia. Thus use of propofol/fentanyl-based TIVA may not be a useful strategy to avoid renal medullary hypoxia during CPB.

Systemic angiotensin II does not increase cardiac sympathetic nerve activity in normal conscious sheep

While it is well established that centrally injected angiotensin II (Ang II) has potent actions on sympathetic nervous activity (SNA), it is less clear whether peripheral Ang II can immediately stimulate SNA. In particular, the contribution of cardiac sympathetic nerve activity (CSNA) to the acute pressor response is unknown. We therefore examined the effect of incremental doses of intravenous Ang II (3, 6, 12, 24, and 48 ng/kg/min each for 30 min) on CSNA in eight conscious sheep. Ang II infusions progressively increased plasma Ang II up to 50 pmol/l above control levels in dose-dependent fashion (P<0.001). This was associated with the expected increases in mean arterial pressure (MAP) above control levels from <10 mmHg at lower doses up to 23 mmHg at the highest dose (P<0.001). Heart rate and cardiac output fell progressively with each incremental Ang II infusion achieving significance at higher doses (P<0.001). There was no significant change in plasma catecholamines. At no dose did Ang II increase any of the CSNA parameters measured. Rather, CSNA burst frequency (P<0.001), burst incidence, (P=0.002), and burst area (P=0.004) progressively decreased achieving significance during the three highest doses. In conclusion, Ang II infused at physiologically relevant doses increased MAP in association with a reciprocal decrease in CSNA presumably via baroreceptor-mediated pathways. The present study provides no evidence that even low-dose systemic Ang II stimulates sympathetic traffic directed to the heart, in normal conscious sheep.