Patrick McQuillan

Limb venous distension evokes sympathetic activation via stimulation of the limb afferents in humans

We have recently shown that a saline infusion in the veins of an arterially occluded human forearm evokes a systemic response with increases in muscle sympathetic nerve activity (MSNA) and blood pressure. In this report, we examined whether this response was a reflex that was due to venous distension. Blood pressure (Finometer), heart rate, and MSNA (microneurography) were assessed in 14 young healthy subjects. In the saline trial (n = 14), 5% forearm volume normal saline was infused in an arterially occluded arm. To block afferents in the limb, 90 mg of lidocaine were added to the same volume of saline in six subjects during a separate visit. To examine whether interstitial perfusion of normal saline alone induced the responses, the same volume of albumin solution (5% concentration) was infused in 11 subjects in separate studies. Lidocaine abolished the MSNA and blood pressure responses seen with saline infusion. Moreover, compared with the saline infusion, an albumin infusion induced a larger (MSNA: Δ14.3 ± 2.7 vs. Δ8.5 ± 1.3 bursts/min, P < 0.01) and more sustained MSNA and blood pressure responses. These data suggest that venous distension activates afferent nerves and evokes a powerful systemic sympathoexcitatory reflex. We posit that the venous distension plays an important role in evoking the autonomic adjustments seen with postural stress in human subjects.

The saphenous nerve and its relationship to the nerve to the vastus medialis in and around the adductor canal: An anatomical study

Recently, ultrasound‐guided saphenous nerve blocks within and distal to the adductor canal have shown success. However, a potential side effect is an unintentional block of branches of the nerve to the vastus medialis resulting in undesired motor weakness.

Release of cytokines and hemodynamic instability during the reperfusion of a liver graft

The objectives of this prospective, observational study were (1) to determine whether a transplanted liver graft releases proinflammatory cytokines into the systemic circulation upon reperfusion and (2) to determine whether they contribute to any subsequent hemodynamic instability observed after graft reperfusion (if this release occurs). Blood samples from 17 consecutive patients undergoing liver transplantation were analyzed for cytokines, including tumor necrosis factor α (TNF‐α), interleukin‐1β (IL‐1β), IL‐2, IL‐6, and IL‐8. Blood samples were obtained from the radial artery, portal vein, and flush blood (a sample taken from a catheter placed above the infrahepatic inferior vena cava clamp). The amount of catecholamines necessary to maintain a mean arterial pressure between 65 and 75 mm Hg during graft reperfusion was compared with the level of cytokines. A statistical analysis was performed with the least squares method, Kendalls tau‐b test, and regression analysis. We demonstrated that flush blood from the liver grafts contained a significant amount and variety of cytokines. Most of these were removed by graft irrigation. The concentration of TNF‐α in samples obtained from flush blood at the end of liver irrigation was significantly higher than the concentration in samples obtained from the radial artery (P = 0.0067) or portal vein (P = 0.0003) before reperfusion. This correlated directly with the amount of catecholamines used to treat hemodynamic instability. Although there were increased levels of IL‐1β, IL‐2, and IL‐8 in the flush blood, there was no statistically significant correlation between the levels of these cytokines and the amount of catecholamines used. Liver Transpl, 2011.

Sympathetic responses during saline infusion into the veins of an occluded limb

Animal studies have shown that the increased intravenous pressure stimulates the group III and IV muscle afferent fibres, and in turn induce cardiovascular responses. However, this pathway of autonomic regulation has not been examined in humans. The aim of this study was to examine the hypothesis that infusion of saline into the venous circulation of an arterially occluded vascular bed evokes sympathetic activation in healthy individuals. Blood pressure, heart rate, and muscle sympathetic nerve activity (MSNA) responses were assessed in 19 young healthy subjects during local infusion of 40 ml saline into a forearm vein in the circulatory arrested condition. From baseline (11.8 ± 1.2 bursts min−1), MSNA increased significantly during the saline infusion (22.5 ± 2.6 bursts min−1, P < 0.001). Blood pressure also increased significantly during the saline infusion. Three control trials were performed during separate visits. The results from the control trial show that the observed MSNA and blood pressure responses were not due to muscle ischaemia. The present data show that saline infusion into the venous circulation of an arterially occluded vascular bed induces sympathetic activation and an increase in blood pressure. We speculate that the infusion under such conditions stimulates the afferent endings near the vessels, and evokes the sympathetic activation.

Fatal hyperammonemia after renal transplant due to late-onset urea cycle deficiency: a case report.

We present a case of severe hyperammonemia with subsequent brain herniation in an adult man after renal transplantation. After successful surgery and an initially uneventful postoperative course, the patient developed significant mental status changes associated with seizure activity. His condition rapidly deteriorated, requiring mechanical ventilation and cardiovascular support. Laboratory studies at that time demonstrated an increased serum ammonia level without evidence of liver or kidney dysfunction. Further investigation revealed an increased orotic acid level in the urine, suggesting a urea cycle disorder (UCD). Despite aggressive therapy, the patients condition continued to deteriorate. Magnetic resonance imaging demonstrated severe brain edema with no cerebral perfusion; after consultation with the family, care was withdrawn. The combination of hyperammonemia and elevated urine orotic acid with normal liver and kidney function suggested a UCD. It is important to note that patients with a UCD may be free of symptoms for many years. Several factors are able to trigger the disease in adulthood, leading to encephalopathy and death. In this case, the patients seizures were initially assumed to be a side effect of immunosuppressive therapy. Further diagnostic measures were only performed late in the course of the disease, which delayed the diagnosis of UCD.

Local Prostaglandin Blockade Attenuates Muscle Mechanoreflex Mediated Renal Vasoconstriction during Muscle Stretch in Humans

During exercise, muscle mechanoreflex-mediated sympathoexcitation evokes renal vasoconstriction. Animal studies suggest that prostaglandins generated within the contracting muscle sensitize muscle mechanoreflexes. Thus we hypothesized that local prostaglandin blockade would attenuate renal vasoconstriction during ischemic muscle stretch. Eleven healthy subjects performed static handgrip before and after local prostaglandin blockade (6 mg ketorolac tromethamine infused into the exercising forearm) via Bier block. Renal blood flow velocity (RBV; Duplex Ultrasound), mean arterial pressure (MAP; Finapres), and heart rate (HR; ECG) were obtained during handgrip, post-handgrip muscle ischemia (PHGMI) followed by PHGMI with passive forearm muscle stretch (PHGMI + stretch). Renal vascular resistance (RVR, calculated as MAP/RBV) was increased from baseline during all paradigms except during PHGMI + stretch after the ketorolac Bier block trial where RVR did not change from baseline. Before Bier block, RVR rose more during PHGMI + stretch than during PHGMI alone (P < .01). Similar results were found after a saline Bier block trial (Delta53 +/- 13% vs. Delta35 +/- 10%; P < 0.01). However, after ketorolac Bier block, RVR was not greater during PHGMI + stretch than during PHGMI alone [Delta39 +/- 8% vs. Delta40 +/- 12%; P = not significant (NS)]. HR and MAP responses were similar during PHGMI and PHGMI + stretch (P = NS). Passive muscle stretch during ischemia augments renal vasoconstriction, suggesting that ischemia sensitizes mechanically sensitive afferents. Inhibition of prostaglandin synthesis eliminates this mechanoreceptor sensitization-mediated constrictor responses. Thus mechanoreceptor sensitization in humans is linked to the production of prostaglandins.

Upright posture reduces forearm blood flow early in exercise

The hypothesis that upright posture could modulate forearm blood flow (FBF) early in exercise was tested in six subjects. Both single (2-s duration) and repeated (1-s work/2-s rest cadence for 12 contractions) handgrip contractions (12 kg) were performed in the supine and 70° head-up tilt (HUT) positions. The arm was maintained at heart level to diminish myogenic effects. Baseline brachial artery diameters were assessed at rest in each position. Brachial artery mean blood velocity (MBV; Doppler) and mean arterial pressure (MAP) (Finapres) were measured continuously to calculate FBF and vascular conductance. MAP was not changed with posture. Antecubital venous pressure (Pv) was reduced in HUT (4.55 ± 1.3 mmHg) compared with supine (11.3 ± 1.9 mmHg) ( P < 0.01). For the repeated contractions, total excess FBF (TEF) was reduced in the HUT position compared with supine ( P < 0.02). With the single contractions, peak FBF, peak vascular conductance, and TEF during 30 s after release of the contraction were reduced in the HUT position compared with supine ( P < 0.01). Sympathetic blockade augmented the FBF response to a single contraction in HUT ( P < 0.05) and tended to increase this response while supine ( P = 0.08). However, sympathetic blockade did not attenuate the effect of HUT on peak FBF and TEF after the single contractions. Raising the arm above heart level while supine, to diminish Pv, resulted in FBF dynamics that were similar to those observed during HUT. Alternatively, lowering the arm while in HUT to restore Pv to supine levels restored the peak FBF and vascular conductance responses, but not TEF response, after a single contraction. It was concluded that upright posture diminishes the hyperemic response early in exercise. The data demonstrate that sympathetic constriction restrains the hyperemic response to a single contraction but does not modulate the postural reduction in postcontraction hyperemia. Therefore, the attenuated blood flow response in the HUT posture was largely related to factors associated with diminished venous pressures and not sympathetic vasoconstriction.

Coronary responses to cold air inhalation following afferent and efferent blockade

Cardiac ischemia and angina pectoris are commonly experienced during exertion in a cold environment. In the current study we tested the hypotheses that oropharyngeal afferent blockade (i.e., local anesthesia of the upper airway with lidocaine) as well as systemic β-adrenergic receptor blockade (i.e., intravenous propranolol) would improve the balance between myocardial oxygen supply and demand in response to the combined stimulus of cold air inhalation (-15 to -30°C) and isometric handgrip exercise (Cold + Grip). Young healthy subjects underwent Cold + Grip following lidocaine, propranolol, and control (no drug). Heart rate, blood pressure, and coronary blood flow velocity (CBV, from Doppler echocardiography) were continuously measured. Rate-pressure product (RPP) was calculated, and changes from baseline were compared between treatments. The change in RPP at the end of Cold + Grip was not different between lidocaine (2,441 ± 376) and control conditions (3,159 ± 626); CBV responses were also not different between treatments. With propranolol, heart rate (8 ± 1 vs. 14 ± 3 beats/min) and RPP responses to Cold + Grip were significantly attenuated. However, at peak exercise propranolol also resulted in a smaller ΔCBV (1.4 ± 0.8 vs. 5.3 ± 1.4 cm/s, P = 0.035), such that the relationship between coronary flow and cardiac metabolism was impaired under propranolol (0.43 ± 0.37 vs. 2.1 ± 0.63 arbitrary units). These data suggest that cold air breathing and isometric exercise significantly influence efferent control of coronary blood flow. Additionally, β-adrenergic vasodilation may play a significant role in coronary regulation during exercise.

Use of a Third-Generation Perfluorocarbon for Preservation of Rat DCD Liver Grafts

BACKGROUND Cold storage in any of the commonly used preservation solutions is not always adequate for donation after cardiac death (DCD) liver grafts due to prolonged warm ischemic time. In this study, we used a third-generation perfluorocarbon (PFC), Oxycyte, for DCD liver graft preservation in a rat model. MATERIALS AND METHODS Twenty-eight rats (14 in each group) were used. Thirty minutes after cardiopulmonary arrest, livers were harvested and flushed with a cold and pre-oxygenated solution of either University of Wisconsin (UW) or UW + 20% PFC. After 8 h of cold preservation in either of the investigated solutions, liver graft specimens were analyzed for evidence of ischemic injury. Hemotoxylin and eosin staining (H and E), as well as immunohistochemical analysis with anti-cleaved caspase 3 antibody, was performed. Levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the preservation solution were analyzed at 1 and 8 h during preservation. RESULTS In the PFC group, the degree of cell congestion, vacuolization and necrosis were all significantly less than in the UW group (P = 0.002-0.004). The number of cells with a positive cleaved caspase 3 antibody reaction was reduced by about 50% in comparison with the UW group (P < 0.006). The AST level in the PFC group was significantly less than in the UW group after 8 h of preservation (P < 0.048). CONCLUSION The addition of PFC to UW solution significantly decreases the degree of histologic damage in rat DCD liver grafts. This preservation strategy can be potentially helpful for organ preservation after prolonged warm ischemia.

Presentation of diaphragmatic herniae during pregnancy and labour

We report two cases of pregnancy-related diaphragmatic hernia. Case one was a 36-year-old woman who presented in her ninth pregnancy, after eight vaginal deliveries. Eight months after a stab wound to the chest, she developed persistent vomiting. The diagnosis was made by chest X-ray after a contralateral central line had been inserted for parenteral nutrition. A 6 x 4 cm stab-induce defect in the diaphragm was repaired. Close by was a second healed diaphragmatic stab wound. Case two involved a 32-year-old woman with a history of repaired childhood diaphragmatic hernia. She developed atypical shoulder and precordial chest pain during labour. Delivery was achieved by the vaginal route, ventouse-assisted. Persistent pain and vomiting led to insertion of a nasogastric tube and the diagnosis was made on the subsequent chest X-ray. The omentum was very adherent to the lung and could only be mobilised via a thoracotomy, at which significant air leaks occurred but settled rapidly. The difficulties of diagnosis are discussed along with the embryology, mechanisms and management of this condition.