Atrial angiotensin-(1-12)/chymase expression data in patient of heart diseases.

The data presented here are related to the research article entitled "Differential expression of the angiotensin-(1-12) [Ang-(1-12)]/chymase axis in human atrial tissue [1]. We have showed that chymase gene transcripts, chymase activity, and immunoreactive- Ang-(1-12) expression levels were higher in left compared to right atrial tissue, irrespective of cardiac disease. This article presents the echocardiographic characteristics of 111 patients undergoing heart surgery for the correction of valvular heart disease, resistant atrial fibrillation or ischemic heart disease. Left atrial chymase mRNA expression and activity, and left atrial Ang-(1-12) levels were compared between patients with stroke vs. non-stroke, congestive heart failure vs. non-heart failure, and in cardiac surgery patients who had a history of postoperative atrial fibrillation vs. non-atrial fibrillation.

Differential Expression of the Angiotensin-(1-12)/Chymase Axis in Human Atrial Tissue.

BACKGROUND: Heart chymase rather than angiotensin (Ang)-converting enzyme has higher specificity for Ang I conversion into Ang II in humans. A new pathway for direct cardiac Ang II generation has been revealed through the demonstration that Ang-(1-12) is cleaved by chymase to generate Ang II directly. Herein, we address whether Ang-(1-12), chymase messenger RNA (mRNA), and activity levels can be differentiated in human atrial tissue from normal and diseased hearts and if these measures associate with various pathologic heart conditions. MATERIALS AND METHODS: Atrial appendages were collected from 11 nonfailing donor hearts and 111 patients undergoing heart surgery for the correction of valvular heart disease, resistant atrial fibrillation, or ischemic heart disease. Chymase mRNA was analyzed by real-time polymerase chain reaction and enzymatic activity by high-performance liquid chromatography using Ang-(1-12) as the substrate. Ang-(1-12) levels were determined by immunohistochemical staining. RESULTS: Chymase gene transcripts, chymase activity, and immunoreactive Ang-(1-12) expression levels were higher in left atrial tissue compared with right atrial tissue, irrespective of cardiac disease. In addition, left atrial chymase mRNA expression was significantly higher in stroke versus nonstroke patients and in cardiac surgery patients who had a history of postoperative atrial fibrillation versus nonatrial fibrillation. Correlation analysis showed that left atrial chymase mRNA was positively related to left atrial enlargement, as determined by echocardiography. CONCLUSIONS: As Ang-(1-12) expression and chymase gene transcripts and enzymatic activity levels were positively linked to left atrial size in patients with left ventricular heart disease, an important alternate Ang II forming pathway, via Ang-(1-12) and chymase, in maladaptive atrial and ventricular remodeling in humans is uncovered.

Use of the Reamer/Irrigator/Aspirator Decreases Carotid and Cranial Embolic Events in a Canine Model.

BACKGROUND: Approximately 2 million patients in the United States annually undergo total joint arthroplasty with reaming and placement of intramedullary nails, resulting in extravasation of bone marrow and fat into the circulatory system and potentially causing fat embolism syndrome. Acute and chronic changes in mental status documented after these procedures may be related to embolic events. The Reamer/Irrigator/Aspirator (RIA) device has been shown to decrease intramedullary pressure during reaming. We hypothesized that the use of the RIA in a canine model would reduce the number of microemboli detected in the carotid artery and brain compared with nailing either with or without reaming. METHODS: Twenty-four large canines underwent unreamed nailing (UR), sequentially reamed nailing (SR), or RIA-reamed nailing (RIA) of bilateral femora (eight dogs per group). During reaming and nailing, the number and size of microemboli transiting the carotid artery were recorded. After euthanasia, the brain was harvested for immunostaining and measurement of microinfarction volumes. RESULTS: Total embolic load passing through the carotid artery was 0.049 cc (UR), 0.045 cc (SR), and 0.013 cc (RIA). The number and size of microemboli in the UR and SR groups were similar; however, the RIA group had significantly fewer larger-sized (>200-µm) emboli (p = 0.03). Pathologic examination of the brain confirmed particulate emboli, and histologic analyses demonstrated upregulation of stress-related proteins in all groups, with fewer emboli and less evidence of stress for RIA reaming. CONCLUSIONS: RIA reaming decreased microemboli compared with traditional reaming and unreamed nailing, suggesting that intramedullary pressure and heat are important variables. The documented embolic events and brain stress may help to explain subtle neurobehavioral symptoms commonly seen in patients after undergoing long-bone reaming procedures. CLINICAL RELEVANCE: RIA reaming decreased cranial embolic events and may have an ameliorating effect on postoperative neurologic sequelae.

Differential expression of the angiotensin-(1-12)/chymase axis in human atrial tissue.

OBJECTIVE: Heart chymase rather than angiotensin converting enzyme has higher specificity for angiotensin (Ang) I conversion into Ang II in humans. A new pathway for direct cardiac Ang II generation has been revealed through the demonstration that Ang-(1-12) is cleaved by chymase to generate Ang II directly. We address here whether Ang-(1-12) and chymase gene expression and activity are detected in the atrial appendages of 44 patients (10 females) undergoing heart surgery for the correction of valvular heart disease, resistant atrial fibrillation or ischemic heart disease. METHODS AND RESULTS: Immunoreactive Ang-(1-12) expression was 54% higher in left atrial compared with right atrial appendages. This was associated with higher abundance of left atrial appendage chymase gene transcripts and chymase activity, but no differences in angiotensinogen mRNA. Atrial chymase enzymatic activity was highly correlated with left atrial but not right atrial enlargement as determined by echocardiography, while both tyrosine hydroxylase and neuropeptide Y atrial appendage mRNAs correlated with atrial angiotensinogen mRNAs. CONCLUSIONS: Higher Ang-(1-12) expression and upregulation of chymase gene transcripts and enzymatic activity from the atrial appendages connected to the enlarged left versus right atrial chambers of subjects with left heart disease defines a role of this alternate Ang II forming pathway in the processes accompanying adverse atrial and ventricular remodeling.

Longitudinal evaluation of neurobehavioral outcomes after carotid revascularization.

BACKGROUND: Carotid revascularization, including carotid endarterectomy (CEA) and carotid angioplasty and stenting (CAS), is performed for stroke risk reduction but may also impact cognitive function. Cognitive outcomes observed after carotid revascularization have been inconsistent, and mechanistic relationships with procedural factors are poorly understood. To further explore associations between carotid revascularization and cognitive outcomes, a prospective longitudinal evaluation was conducted of patients undergoing elective CEA or CAS for hemodynamically significant carotid stenosis. METHODS: Patients undergoing primary carotid artery revascularization for hemodynamically significant stenosis were evaluated with neurologic and neuropsychological testing at baseline and at 1 and 6 months after revascularization. A subgroup of patients was also studied with baseline and postoperative magnetic resonance imaging (MRI). Outcomes included neurologic or neuropsychological deficits and imaging findings (including quantitative assessment of cerebral blood flow). RESULTS: Sixteen patients underwent carotid revascularization with both preoperative and postoperative neurologic and neuropsychological testing; preoperative and postoperative MRIs were also performed on eight patients. Five of 16 treated carotid lesions (31%) were considered symptomatic, and severity of carotid stenosis was 60-79% for 6 of 16 lesions and 80% or more in all others. A single perioperative neurologic deficit was identified; all other patients (15/16) had no abnormalities detected by neurologic examination. Neuropsychological testing identified new postoperative deficits in 3 patients (19%), among whom 2 had a normal neurologic examination at all time points, whereas 1 had clinical evidence of stroke. Quantitative analysis of mean cerebral blood flow revealed postrevascularization increases for both gray matter (48.6 ± 13.9 mL per 100 g/min vs 75.3 ± 70.8 mL per 100 g/min) and white matter (31.8 ± 10.6 mL per 100 g/min vs 55.2 ± 30.1 mL per 100 g/min)(P = 0.04). New postoperative MRI foci of restricted diffusion were identified in 2 patients, both of whom had no neurologic or neuropsychological deficit. Among patients with postoperative neuropsychological deficits, MRI revealed globally increased cerebral perfusion without new postoperative abnormalities in 2 of 3. CONCLUSIONS: The relationship between carotid revascularization and cognitive function is complex, and cognitive deficits may occur in the presence of increased cerebral perfusion without detectable embolization.

Cannula design reduces particulate and gaseous emboli during cardiopulmonary bypass for coronary revascularization.

PURPOSE: The incidence of neurocognitive deficits after coronary bypass surgery remains problematic, with atheroembolism being one of the major causes. External manipulation of aorta and the "sandblasting" effect of the high-velocity perfusion jet can cause dislodgement of atheromatous debris. DESCRIPTION: A new arterial cannula features a tip configuration that diffuses the flow through multiple outlets, providing reduced velocity and shear with one central and three diverted flow streams. EVALUATION: Between March 2007 and July 2008 twenty patients having isolated coronary artery bypass operations were instrumented with an Embolus Detection and Classification transducer. These data were compared to 43 patients from a previous study using similar techniques except for a standard open-tip arterial cannula. Total embolic counts were markedly lower in the new cannula group (20±25 vs 174±378) as were both gaseous (11±15 vs 95±211) and particulate counts (9±11 vs 80±194). CONCLUSIONS: The select 3D cannula design reduces the sandblasting effect of the perfusion jet and, also, may direct emboli from the heart and cardiopulmonary bypass equipment away from the cerebral circulation.

Coronary artery bypass grafting with single cross-clamp results in fewer persistent neuropsychological deficits than multiple clamp or off-pump coronary artery bypass grafting.

BACKGROUND: In coronary artery bypass grafting (CABG) patients, neuropsychological deficits that are present from the time of the operation through 6 months postoperatively are considered permanent and represent organic brain damage related to the operation. We hypothesized that changes in our surgical method would reduce persistent deficits. METHODS: From 1999 to 2004, consenting CABG patients were randomly assigned to multiple aortic cross-clamp or single aortic cross-clamp technique. An additional contemporary group of patients treated with off-pump CABG was studied. All patients underwent an 11-part neuropsychologic examination preoperatively, and at 1 week, 6 weeks, and 6 months postoperatively. One hundred seven patients with no postoperative neurologic deficits had neuropsychologic examinations at all four testing periods. RESULTS: Off-pump CABG patients were significantly younger (60 +/- 11 years) than multiple aortic cross-clamp (66 +/- 8 years) and single aortic cross-clamp (64 +/- 9 years; p < 0.05) patients. At 6 months, 26% of 27 multiple aortic cross-clamp patients had neuropsychological deficits, 27% of 26 off-pump CABG patients had neuropsychological deficits, and only 9% of 54 single aortic cross-clamp patients had neuropsychological deficits (p = 0.067 versus multiple aortic cross-clamp and off-pump CABG). CONCLUSIONS: These results suggest that surgical technique is very important in determining cognitive outcome after CABG. Cardiopulmonary bypass is not the most important factor in determining outcome and when carefully performed with single cross-clamp and minimal aortic manipulation is equal or may be superior to off-pump operation. We suspect that mild hypothermia in on-pump surgery is additionally neuroprotective, a factor that should be taken into account when planning an operation.

Anesthetic preconditioning with sevoflurane does not protect the spinal cord after an ischemic-reperfusion injury in the rat.

Anesthetic preconditioning (APC) is a protective mechanism, whereby exposure to a volatile anesthetic renders a tissue resistant to a subsequent ischemic insult. We hypothesized that APC of the rat spinal cord with sevoflurane would reduce neurologic deficit after an ischemic-reperfusion injury. Rats were randomly assigned to 1 of 5 groups. The ischemic preconditioning (IPC) group (n = 14) had 3 min of IPC, 30 min of reperfusion, and 12 min of ischemia. The chronic APC (cSEVO) group (n = 14) had 1 h of APC with 3.5% sevoflurane on each of 2 days before ischemia. The acute APC (aSEVO) group (n = 14) had 1 h of APC with 3.5% sevoflurane followed by a 1-h washout period before the induction of ischemia. The controls (n = 14) underwent no preconditioning before ischemia. IPC attenuated the ischemia-reperfusion injury, whereas aSEVO and cSEVO groups were no better than control animals. Histologic evaluation of the spinal cord showed severe neurologic damage in all groups except for the IPC group and sham-operated rats. APC with sevoflurane did not reduce neurologic injury in a rat model of spinal cord ischemia. Traditional ischemic preconditioning had a strong protective benefit on neurologic outcome.

Single crossclamp improves 6-month cognitive outcome in high-risk coronary bypass patients: the effect of reduced aortic manipulation.

OBJECTIVE: We hypothesized that a strategy that reduced aortic manipulation would reduce the incidence of cognitive deficits in patients undergoing coronary artery bypass grafting compared with the "traditional" approach and that neurobehavioral outcomes with the reduced aortic manipulation strategy would approach those obtained with off-pump coronary artery bypass surgery. METHODS: Consenting high-risk patients (those with older age, diabetes, or hypertension) scheduled for coronary artery bypass grafting and cardiopulmonary bypass were randomly assigned to 1 of 2 aortic management protocols: (1) a traditional approach in which distal anastomoses were accomplished while the aorta was crossclamped but in which proximal anastomoses were sewn while a partial occlusion clamp was applied to the aorta (multiple aortic clamping group) or (2) a reduced aortic manipulation approach in which the aorta was clamped a single time with a reduced-pressure clamp (single aortic clamping group) and the partial occlusion clamp was not used. A contemporaneous group of patients undergoing off-pump coronary artery bypass surgery without cardiopulmonary bypass was also enrolled. Subjects in all 3 groups underwent neurologic and neuropsychological testing before and after surgery. After randomization, patients assigned to either approach could be changed to another strategy if the attending surgeon determined that patient safety demanded this change. The study design anticipated that surgical techniques would evolve over the course of patient enrollment and anticipated that some patients would have intraoperative echocardiographic findings that would demand that the traditional approach (eg, severe aortic atherosclerosis) or the reduced manipulation protocol (eg, severe ischemia or poor left ventricular function) be abandoned. Thus, an unequal distribution of patients was expected. By surgeon decision, 20 of 84 multiple aortic clamping patients crossed over to single aortic clamping, and 3 of 85 single aortic clamping patients switched to multiple aortic clamping. Eligible patients had a battery of neuropsychological tests before surgery and at 6 months after surgery. A 20% decrement in 2 or more tests was defined as a neuropsychological deficit. RESULTS: [table: see text]. CONCLUSIONS: A surgical strategy designed to minimize aortic manipulation can significantly reduce the incidence of cognitive deficits in coronary artery bypass grafting patients compared with traditional techniques. In this series, the results of the reduced aortic manipulation strategy were not significantly different from those in patients having off-pump coronary artery bypass surgery, thus emphasizing surgical technique as the primary cause of brain damage in coronary artery bypass grafting patients.

Spinal cord blood flow after ischemic preconditioning in a rat model of spinal cord ischemia.

Spinal cord blood flow after ischemic preconditioning is poorly characterized. This study is designed to evaluate spinal cord blood flow patterns in animals after acute ischemic preconditioning. Experiment 1: After a laminectomy and placement of a laser Doppler probe over the lumbar spinal cord to measure spinal cord blood flow, 16 male Sprague-Dawley rats were randomized into two groups: ischemic preconditioning (IPC, n = 8), and control (CTRL, n = 8). Rats in the CTRL and the IPC groups were subjected to 12 min of ischemia directly followed by 60 min of reperfusion. IPC rats received 3 min of IPC and 30 min of reperfusion prior to the 12-min insult period. Experiment 2: After instrumentation, the rats were randomized into three groups: control (CTRL, n = 7), ischemic preconditioning (IPC, n = 7), and time control (TC, n = 4). Rats in the CTRL and the IPC groups were subjected to the same ischemia and reperfusion protocol as above. The TC group was anesthetized for the same time period as the CTRL and the IPC groups, but had no ischemic intervention. Microspheres were injected at baseline and at 15 and 60 min into the final reperfusion. All rats were euthanized and tissue harvested for spinal cord blood flow analysis. In Experiment 1, there was a slight, significant difference in spinal cord blood flow during the ischemic period; however, this difference soon disappeared during reperfusion. In experiment 2, there was no difference in blood flow at any experimental time. The results of these experiments demonstrate that IPC slightly enhances blood flow to the spinal cord during ischemia; however, this effect is not sustained during the reperfusion period.

Does local anesthetic stereoselectivity or structure predict myocardial depression in anesthetized canines?

BACKGROUND AND OBJECTIVES: It is unclear whether the susceptibility to myocardial depression from an accidental intravascular local anesthetic (LA) administration is associated with LA stereoselectivity or structure. By using direct left ventricular pressure monitoring and echocardiographic indices of contractile function in anesthetized, ventilated dogs, we compared the cardiac depressant effects of bupivacaine, ropivacaine, levobupivacaine, and lidocaine. METHODS: Open-chest dogs were randomized to receive escalating incremental infusions of the 4 local anesthetics until cardiovascular collapse. We assumed a concentration relationship for potency of 4:1 for lidocaine/bupivacaine, ropivacaine, and levobupivacaine. RESULTS: All LAs produced concentration-dependent increases in left ventricular end diastolic pressure (LVEDP) and decreases in dP/dtmax, ejection fraction % (EF), fractional shortening (%) (FS), and cardiac output (CO). When comparing the long-acting agents, the effect was least for ropivacaine. The effective concentration estimates for ropivacaine that produced 35% reductions in dP/dtmax and FS were 4.0 micro g/mL (95% confidence intervals [CI(95)]: 3.1 to 5.2 micro g/mL) and 3.0 micro g/mL (CI (95): 2.1 to 4.2 micro g/mL), respectively. The concentrations of levobupivacaine that produced these same end points of contractile dysfunction were significantly less: 2.4 micro g/mL (CI(95): 1.9 to 3.1 micro g/mL) and 1.3 micro g/mL (CI(95): 0.9 to 1.8 micro g/mL), respectively, and these were not different from bupivacaine. As expected, the concentrations of lidocaine that produced 35% reductions in dP/dtmax and FS were significantly greater than the longer acting agents; 8.0 micro g/mL (CI(95): 5.7 to 11.0 micro g/mL) and 5.5 micro g/mL (CI(95): 3.5 to 8.7 micro g/mL), respectively. CONCLUSIONS: This study suggests that smaller molecular size and possibly a piperidine-free structure as opposed to stereoselectivity may be the more important factor in reducing the risk of LA-induced myocardial depression.

How effective are cardiopulmonary bypass circuits at removing gaseous microemboli?

An association has been demonstrated between intravascular microemboli and organ injury during cardiopulmonary bypass (CPB). Air may be inadvertently introduced into the venous line during CPB resulting in the formation of gaseous microemboli (GME). We studied the ability of CPB circuits, from five different manufacturers, to remove GME originating from the introduction of air into the venous line. Using an in vitro model of adult CPB, 60 ml of air was introduced into the venous line and the progression of GME through the circuit components was monitored at 5 locations. In all circuits GME were detected in the arterial line following the introduction of air into the venous line. There was a wide variation between manufacturers in the ability of the circuit to remove GME. Air introduced into the venous line during CPB results in the formation of GME that are able to pass through all the circuit components including the arterial filter. The quantity of GME detected in the arterial line is influenced by the design of the circuit components and varies between manufacturers. Air in the venous line should be avoided and if present it must be dealt with promptly.

Comparing dual-stream and standard cardiopulmonary bypass in pigs.

BACKGROUND: Dual-stream (DS) and standard cardiopulmonary bypass (CPB) were compared. METHODS: A DS catheter inserted into the distal ascending aorta across the arch pumps blood through an upper lumen (maximum 2.25 L/min) directed by a bloodstreaming baffle toward the arch vessels. A separate lower lumen pumps blood (maximum 3.75 L/min) into the aorta caudad to the inflated baffle. The baffle is flat and horizontal along the catheter. When the baffle is collapsed the heart or both lumens may perfuse all organs. For 30 minutes 8 randomized CPB pigs had corporeal cooling to 32 degrees C and for 30 minutes had rewarming to 36 degrees C. Eight randomized DS pigs had 25 degrees C upper lumen cooling for 60 minutes. Lower lumen blood flow was streamed at 32 degrees C for 30 minutes, then rewarmed to 36 degrees C for 30 minutes. RESULTS: The change in relative lower lumen to brain blood flow as determined by brain-counted microspheres (15 micron) injected into the ascending aorta was less for DS brains than controls during full flow (DS 63.4+/-129.5 versus CPB 2,585.4+/-250.8, p < 0.001), and when injected into the ejecting-heart left atrium just after weaning off only lower lumen blood flow (DS 250.8+/-297.3 versus CPB 1,159.1+/-782.3, p < 0.001). DS brain temperatures were lower at an equal pump-off core temperature of 36 degrees C+/-0.5 degrees C (DS 31.6 degrees C+/-3.2 degrees C versus CPB 36.5 degrees C+/-1.7 degrees C, p < 0.025). Jugular O2 saturations were not different. CONCLUSIONS: DS-CPB prioritizes pump-filtered separate cold blood flow to the brain over a blood-streaming baffle to wash away potentially surgery related air and particulate matter arising from the heart or ascending aorta.

Does vacuum-assisted venous drainage increase gaseous microemboli during cardiopulmonary bypass?

BACKGROUND: Vacuum-assisted venous drainage enables adequate drainage through small-diameter cannulas but concerns are that it results in more gaseous microemboli delivered to the patient. METHODS: Five identical embolus detectors monitored the propagation of entrained air through a cardiopulmonary bypass (CPB) model. The ability of the CPB circuit to remove gaseous microemboli was studied with vacuum-assisted venous drainage and gravity siphon venous drainage using different pump speeds and rates of gaseous microemboli delivery. RESULTS: Under all conditions entrained venous air resulted in the detection of gaseous microemboli in the perfusate after the arterial filter. In blood-primed circuits, increased flow rates and higher levels of vacuum-assisted venous drainage were independently associated with increased gaseous microemboli counts in the arterial line. Vacuum-assisted venous drainage at -40 mm Hg did not significantly increase gaseous microemboli activity when compared with gravity siphon venous drainage at 4 L/min flow rate. CONCLUSIONS: Vacuum-assisted venous drainage at -40 mm Hg does not statistically reduce the ability of the CPB circuit to remove gaseous microemboli at lower pump rates. High levels of vacuum and increased pump flow rates should be avoided. Air should not be introduced into the venous line.