PubMed Health⌕ Search

Biomedical subjects

H P Grocott

Publications and source records attributed to H P Grocott.

At least 19 recordsLinked to original sources
PubMed2006

Inflammatory gene polymorphisms and risk of postoperative myocardial infarction after cardiac surgery.

BACKGROUND: The inflammatory response triggered by cardiac surgery with cardiopulmonary bypass (CPB) is a primary mechanism in the pathogenesis of postoperative myocardial infarction (PMI), a multifactorial disorder with significant inter-patient variability poorly predicted by clinical and procedural factors. We tested the hypothesis that candidate gene polymorphisms in inflammatory pathways contribute to risk of PMI after cardiac surgery. METHODS AND RESULTS: We genotyped 48 polymorphisms from 23 candidate genes in a prospective cohort of 434 patients undergoing elective cardiac surgery with CPB. PMI was defined as creatine kinase-MB isoenzyme level > or = 10x upper limit of normal at 24 hours postoperatively. A 2-step analysis strategy was used: marker selection, followed by model building. To minimize false-positive associations, we adjusted for multiple testing by permutation analysis, Bonferroni correction, and controlling the false discovery rate; 52 patients (12%) experienced PMI. After adjusting for multiple comparisons and clinical risk factors, 3 polymorphisms were found to be independent predictors of PMI (adjusted P<0.05; false discovery rate <10%). These gene variants encode the proinflammatory cytokine interleukin 6 (IL6 -572G>C; odds ratio [OR], 2.47), and 2 adhesion molecules: intercellular adhesion molecule-1 (ICAM1 Lys469Glu; OR, 1.88), and E-selectin (SELE 98G>T; OR, 0.16). The inclusion of genotypic information from these polymorphisms improved prediction models for PMI based on traditional risk factors alone (C-statistic 0.764 versus 0.703). CONCLUSIONS: Functional genetic variants in cytokine and leukocyte-endothelial interaction pathways are independently associated with severity of myonecrosis after cardiac surgery. This may aid in preoperative identification of high-risk cardiac surgical patients and development of novel cardioprotective strategies.

Aged↗
PubMed2005

The influence of xenon, nitrous oxide and nitrogen on gas bubble expansion during cardiopulmonary bypass.

BACKGROUND AND OBJECTIVE: Xenon may have favourable applications in the setting of cardiac surgery. Its advantages include a desirable haemodynamic profile as well as potential cardiac and neuroprotective properties. However, its low solubility may lead to enhanced diffusion into enclosed gas spaces. The purpose of this study was to compare the effects of xenon (Xe), nitrous oxide (N2O) and nitrogen (N2) on gas bubble size during cardiopulmonary bypass (CPB). METHODS: Rats were randomized to receive 70% Xe, 26% oxygen (O2), 4% carbon dioxide (CO2) (xenon group); 70% N2O, 26% O2, 4% CO2 (nitrous oxide group) or 70% N2, 26% O2, 4% CO2 (nitrogen group) during 90 min of normothermic CPB. Small gas bubbles (300-500 microL; n = 12 per group) were injected into a bubble chamber on the venous side of the bypass circuit. After 10 min of equilibration, they were removed for volumetric analysis. RESULTS: The increase in bubble size was 2 +/- 2% with nitrogen, 17 +/- 6% with xenon (P = 0.0192 vs. nitrogen) and 63 +/- 23% with nitrous oxide (P = 0.0001 vs. nitrogen). The nitrous oxide group had significantly increased bubble size compared to the xenon group (P = 0.0001). CONCLUSIONS: During CPB, xenon anaesthesia produced a small increase in gas bubble size compared to nitrogen. Nitrous oxide resulted in significantly larger bubbles compared to both nitrogen and xenon.

Analysis of Variance↗
PubMed2003

Cerebral embolization during cardiac surgery: impact of aortic atheroma burden.

BACKGROUND: Aortic atheromatous disease is known to be associated with an increased risk of perioperative stroke in the setting of cardiac surgery. In this study, we sought to determine the relationship between cerebral microemboli and aortic atheroma burden in patients undergoing cardiac surgery. METHODS: Transoesophageal echocardiographic images of the ascending, arch and descending aorta were evaluated in 128 patients to determine the aortic atheroma burden. Transcranial Doppler (TCD) of the right middle cerebral artery was performed in order to measure cerebral embolic load during surgery. Using multivariate linear regression, the numbers of emboli were compared with the atheroma burden. RESULTS: After controlling for age, cardiopulmonary bypass time and the number of bypass grafts, cerebral emboli were significantly associated with atheroma in the ascending aorta (R2=0.11, P=0.02) and aortic arch (P=0.013). However, there was no association between emboli and descending aortic atheroma burden (R2=0.05, P=0.20). CONCLUSIONS: We demonstrate a positive relationship between TCD-detected cerebral emboli and the atheromatous burden of the ascending aorta and aortic arch. Previously demonstrated associations between TCD-detectable cerebral emboli and adverse cerebral outcome may be related to the presence of significant aortic atheromatous disease.

Adult↗
PubMed2001

Report of the substudy assessing the impact of neurocognitive function on quality of life 5 years after cardiac surgery.

BACKGROUND AND PURPOSE: The importance of perioperative cognitive decline has long been debated. We recently demonstrated a significant correlation between perioperative cognitive decline and long-term cognitive dysfunction. Despite this association, some still question the importance of these changes in cognitive function to the quality of life of patients and their families. The purpose of our investigation was to determine the association between cognitive dysfunction and long-term quality of life after cardiac surgery. METHODS: After institutional review board approval and patient informed consent, 261 patients undergoing cardiac surgery with cardiopulmonary bypass were enrolled and followed for 5 years. Cognitive function was measured with a battery of tests at baseline, discharge, and 6 weeks and 5 years postoperatively. Quality of life was assessed with well-validated, standardized assessments at the 5-year end point. RESULTS: Our results demonstrate significant correlations between cognitive function and quality of life in patients after cardiac surgery. Lower 5-year overall cognitive function scores were associated with lower general health and a less productive working status. Multivariable logistic and linear regression controlling for age, sex, education, and diabetes confirmed this strong association in the majority of areas of quality of life. CONCLUSIONS: Five years after cardiac surgery, there is a strong relationship between neurocognitive functioning and quality of life. This has important social and financial implications for preoperative evaluation and postoperative care of patients undergoing cardiac surgery.

Age Distribution↗
PubMed2001

Aortic dissection after angioplasty and stenting of an aortic coarctation: detection by intravascular ultrasonography but not transesophageal echocardiography.

In this case report, an iatrogenic dissection of the descending aorta occurred during balloon angioplasty and stenting of a recurrent coarctation. The dissection was not seen by transesophageal echocardiography, but intravascular ultrasonography, performed routinely during such procedures at this institution, identified the dissection and guided further therapeutic stent placement.

Adult↗
PubMed2001

Apolipoprotein E polymorphisms and age at first coronary artery bypass graft.

UNLABELLED: Apolipoprotein E (apoE) polymorphisms are heritable determinants of total and low-density lipoprotein cholesterol. The impact of apoE4 genotypes on the severity of atherosclerosis has been debated; however, recent studies have identified a correlation between apoE4 genotype and atherosclerosis. We assessed the impact of apoE4 genotype on age at first coronary artery bypass graft (CABG), hypothesizing that patients with the apoE4 allele are predisposed to coronary artery disease and present earlier for coronary revascularization. We assessed individual apoE genotypes and age in 560 patients undergoing primary CABG, by using analysis of variance (ANOVA) and controlling for gender. Because of the small number of patients in individual genotype groups, we compared patients with one or more copies of the apoE4 allele with those having no copies of the allele, again controlling for gender. A comparison of patients with one or more copies of the apoE4 allele with patients without the allele showed an earlier age at first CABG for those with the allele (P: = 0.032). Gene-dose analysis was also significant (P: = 0.012); patients with two copies of the allele presented at 54.2 +/- 6.9 yr. We report that the apoE4 allele is linked to age at first CABG. Identifying at-risk individuals may help prevent atherosclerosis. Further study is needed to define the mechanism of this association, and to define which coronary intervention is appropriate, based on long-term outcome. IMPLICATIONS: A correlation exists between apolipoprotein E (apoE) genotypes and the severity of atherosclerosis. We hypothesized that patients with the apoE4 allele are predisposed to coronary artery disease and present earlier for coronary artery bypass graft (CABG). Individuals with the apoE4 allele presented earlier for CABG, and the apoE4 allele is linked to age at first CABG.

Age Factors↗
PubMed2001

Prospective randomized trial of normothermic versus hypothermic cardiopulmonary bypass on cognitive function after coronary artery bypass graft surgery.

BACKGROUND: Despite significant advances in cardiopulmonary bypass (CPB) technology, surgical techniques, and anesthetic management, central nervous system complications occur in a large percentage of patients undergoing surgery requiring CPB. Many centers are switching to normothermic CPB because of shorter CPB and operating room times and improved myocardial protection. The authors hypothesized that, compared with normothermia, hypothermic CPB would result in superior neurologic and neurocognitive function after coronary artery bypass graft surgery. METHODS: Three hundred patients undergoing elective coronary artery bypass graft surgery were prospectively enrolled and randomly assigned to either normothermic (35.5-36.5 degrees C) or hypothermic (28-30 degrees C) CPB. A battery of neurocognitive tests was performed preoperatively and at 6 weeks after surgery. Four distinct cognitive domains were identified and standardized using factor analysis and were then compared on a continuous scale. RESULTS: Two hundred twenty-seven patients participated in 6-week follow-up testing. There were no differences in neurologic or neurocognitive outcomes between normothermic and hypothermic groups in multivariable models, adjusting for covariable effects of baseline cognitive function, age, and years of education, as well as interaction of these with temperature treatment. CONCLUSIONS: Hypothermic CPB does not provide additional central nervous system protection in adult cardiac surgical patients who were maintained at either 30 or 35 degrees C during CPB.

Anesthetics, Intravenous↗
PubMed2001

Cardiopulmonary bypass induces neurologic and neurocognitive dysfunction in the rat.

BACKGROUND: Neurocognitive dysfunction is a common complication of cardiac surgery using cardiopulmonary bypass (CPB). Elucidating injury mechanisms and developing neuroprotective strategies have been hampered by the lack of a suitable long-term recovery model of CPB. The purpose of this study was to investigate neurologic and neurocognitive outcome after CPB in a recovery model of CPB in the rat. METHODS: Fasted rats (n = 10) were subjected to 60 min of normothermic (37.5 degrees C) nonpulsatile CPB using a roller pump and a membrane oxygenator. Sham-operated controls (n = 10) were not subjected to CPB. Neurologic outcome was assessed on days 1, 3, and 12 after CPB using standardized functional testing. Neurocognitive outcome, defined as the time (or latency) to finding a submerged platform in a Morris water maze (an indicator of visual-spatial learning and memory), was evaluated daily from post-CPB days 3-12. Histologic injury in the hippocampus was also evaluated. RESULTS: Neurologic outcome was worse in the CPB versus the sham-operated controls at all three measurement intervals (P < 0.001). The CPB group also had longer water maze latencies compared with the sham-operated controls (P = 0.004), indicating significant neurocognitive dysfunction after CPB. No difference in histologic injury between groups was observed. CONCLUSIONS: CPB caused both neurologic and neurocognitive impairment in a rodent recovery model. This model could potentially facilitate the investigation of CPB-related injury mechanisms and possible neuroprotective interventions.

Anesthesia↗
PubMed2001

Effect of apolipoprotein E genotype on cerebral autoregulation during cardiopulmonary bypass.

BACKGROUND AND PURPOSE: The presence of the apolipoprotein E epsilon4 (apoE4) allele has been associated with cognitive decline after cardiac surgery. We compared autoregulation of cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO(2)), and arterial-venous oxygen content difference [C(A-V)O(2)], during cardiopulmonary bypass (CPB) in patients with and without the apoE4 allele to help define the mechanism of association with cognitive decline. METHODS: One hundred fifty-four patients underwent coronary artery bypass grafting with CPB, nonpulsatile flow, and alpha-stat management. CBF was measured by using (133)Xe washout methods. C(A-V)O(2), CMRO(2), and oxygen delivery were calculated. Pressure-flow autoregulation was tested by using 2 CBF measurements at stable hypothermia: the first at stable mean arterial pressure (MAP) and the second 15 minutes later, when MAP had increased or decreased >/=20%. Metabolism-flow autoregulation was tested by varying the temperature and measuring the coupling of CBF and CMRO(2). RESULTS: In patients with (n=41) or without (n=113) the apoE4 allele, there were no differences in CBF, CMRO(2), C(A-V)O(2), pressure-flow and metabolism-flow autoregulation corrected for age, gender, non-insulin-dependent diabetes, hemoglobin, CPB time, and temperature. CONCLUSIONS: We conclude that apoE genotype does not affect global CBF and oxygen delivery/extraction during CPB, which suggests that other mechanisms are responsible for the apoE isoform-related neurocognitive dysfunction seen in patients undergoing CPB.

Apolipoproteins E↗
PubMed2001

Neurological injury during cardiopulmonary bypass in the rat.

Cerebral injury is a well-known complication of cardiac surgery. Investigations of both injury mechanisms and neuroprotective strategies have partially been limited by the lack of an adequate preclinical model of small animal cardiopulmonary bypass (CPB). We sought to determine if neurological injury could be demonstrated in a recovery model of complete CPB in the rat. Rats (n = 5) underwent 45 min of normothermic CPB followed by 24 h of recovery. Compared to sham-operated rats (n = 5), the CPB group showed a worse neurological outcome score (median, 25-75th percentile) compared to controls (5, 4-7 vs 9, 8-9, p = 0.016). This rat model of CPB may allow for the study of CPB-associated neurological injury.

Animals↗
PubMed2000

Beta(2)-adrenergic and several other G protein-coupled receptors in human atrial membranes activate both G(s) and G(i).

Cardiac G protein-coupled receptors that couple to Galpha(s) and stimulate cAMP formation (eg, beta-adrenergic, histamine, serotonin, and glucagon receptors) play a key role in cardiac inotropy. Recent studies in rodent cardiac myocytes and transfected cells have revealed that one of these receptors, the beta(2)-adrenergic receptor (AR), also couples to the inhibitory G protein Galpha(i) (activation of which inhibits cAMP formation). If beta(2)ARs could be shown to couple to Galpha(i) in the human heart, it would have important ramifications, because levels of Galpha(i) increase with age and in failing human heart. Therefore, we investigated whether beta(2)ARs in the human heart activate Galpha(i). By photoaffinity labeling human atrial membranes with [(32)P]azidoanilido-GTP, followed by immunoprecipitation with antibodies specific for Galpha(i), we found that Galpha(i) is activated by stimulation of beta(2)ARs but not of beta(1)ARs. In addition, we found that other Galpha(s)-coupled receptors also couple to Galpha(i), including histamine, serotonin, and glucagon. When coupling of these receptors to Galpha(i) is disrupted by pertussis toxin, their ability to stimulate adenylyl cyclase is enhanced. These data provide the first evidence that beta(2)AR and many other Galpha(s)-coupled receptors in human atrium also couple to Galpha(i) and that abolishing the coupling of these receptors to Galpha(i) increases the receptor-mediated adenylyl cyclase activity.

Adenylate Cyclase Toxin↗
PubMed2000

Post-ischemic RSR13 amplifies the effect of dizocilpine on outcome from transient focal cerebral ischemia in the rat.

In a recent study of focal cerebral ischemia in rats, pre-ischemic administration of the synthetic allosteric hemoglobin modifier RSR13 (2-[4-[[3,5-dimethylanilino) carbonyl] methyl] phenoxy]-2-methylproprionic acid) reduced cerebral infarct size when combined with the NMDA receptor antagonist dizocilpine (MK-801) but not when given alone. We hypothesized that post-ischemic RSR13 administration would enhance neuroprotection afforded by NMDA receptor antagonism in a rat model of transient middle cerebral artery occlusion (MCAO). Fasted normothermic Wistar rats underwent 75 min of temporary MCAO. At onset of reperfusion, rats randomly received: (1) 0.9% NaCl (vehicle) i.v. alone (n=16); (2) 0.9% NaCl+dizocilpine (0.25 mg/kg) i.v. (n=16); or (3) RSR13 (150 mg/kg)+dizocilpine (0.25 mg/kg) i.v. (n=17). Seven days later, neurologic deficit and cerebral infarct size were determined. Dizocilpine alone compared to vehicle reduced mean+/-S.D. subcortical (52+/-24 mm(3) vs. 122+/-64 mm(3), P=0.003) and cortical (35+/-35 mm(3) vs. 125+/-72 mm(3), P=0.00074) infarct volumes. When compared to dizocilpine alone, the combination of RSR13+dizocilpine further reduced subcortical (37+/-14 mm(3) vs. 52+/-24 mm(3), P=0. 034) and cortical (8+/-19 mm(3) vs. 35+/-35 mm(3), P=0.018) infarct size. RSR13+dizocilpine improved neurologic scores vs. either dizocilpine alone (P=0.0014) or vehicle (P=10(-7)). The combination of NMDA receptor antagonism and a RSR13 mediated rightward shift of the oxy-hemoglobin dissociation curve improved outcome from MCAO. Because this occurred after reperfusion, our results suggest that the post-ischemic brain continues to suffer from hypoperfusion defects, which are amenable to therapy by enhanced O(2) delivery. The results also support the concept that neuroprotective strategies, which combine drugs with different mechanisms of action, may yield cumulative benefits.

Aniline Compounds↗
PubMed2000

Intraoperative physiologic variables and outcome in cardiac surgery: Part II. Neurologic outcome.

BACKGROUND: The impact of alterable physiologic variables on neurologic outcome after coronary artery bypass grafting procedures is unknown. The purpose of this study was to determine whether minimum intraoperative hematocrit, maximum glucose concentration, or mean arterial pressure during cardiopulmonary bypass influences risk-adjusted neurologic outcome after coronary artery bypass grafting. METHODS: Outcome data from 2,862 patients undergoing coronary artery bypass grafting were merged with intraoperative physiologic data. A preoperative stroke risk index was calculated for each patient. Variables found significant by univariate logistic regression were tested in a multivariable model to determine association with outcome. RESULTS: The incidence of stroke or coma in the study population was 1.3%. After controlling for stroke risk and bypass time, only an index of low mean arterial pressure during bypass retained a significant inverse association with outcome (p = 0.0304). CONCLUSIONS: This study found no evidence that glucose concentration or minimum hematocrit are associated with major adverse neurologic outcome. The association between lower pressure during bypass and decreased incidence of stroke or coma persisted in all risk groups. This points to mechanisms other than hypoperfusion as the primary cause of neurologic injury associated with cardiac surgery.

Aged↗