Postischemic hyperthermia exacerbates neurologic injury after deep hypothermic circulatory arrest

BACKGROUND: Aggressive surface warming is a common practice in the pediatric intensive care unit. However, recent rodent data emphasize the protective effect of mild (2 degrees - 3 degrees C) hypothermia after cerebral ischemia. This study evaluates different temperature regulation strategies after deep hypothermic circulatory arrest with a survival piglet model. METHODS: Fifteen piglets were randomly assigned to 3 groups. All groups underwent 100 minutes of deep hypothermic circulatory arrest at 15 degrees C. Brain temperature was maintained at 34 degrees C for 24 hours after cardiopulmonary bypass in group I, 37 degrees C in group II, and 40 degrees C in group III. Neurobehavioral recovery was evaluated daily for 3 days after extubation by neurologic deficit score (0, normal; 500, brain death) and overall performance category (1, normal; 5, brain death). Histologic examination was assessed for hypoxic-ischemic injury (0, normal; 5, necrosis) in a blinded fashion. RESULTS: All results are expressed as mean +/- standard deviation. Recovery of neurologic deficit score (12.0 +/- 17.8, 47.0 +/- 49.95, 191.0 +/- 179.83; P = .05 for group I vs III), overall performance category (1.0 +/- 0.0, 1.4 +/- 0.6, 2.8 +/- 1.3; P < .05 for group I vs III), and histologic scores (0.0 +/- 0.0, 1.0 +/- 1.2, 2.8 +/- 1.8; P < .05 for group I vs III cortex) were significantly worse in hyperthermic group III. These findings were associated with a significantly lower cytochrome aa3 recovery determined by near-infrared spectroscopy in group III animals (P = .0041 for group I vs III). No animal recovered to baseline electroencephalographic value by 48 hours after deep hypothermic circulatory arrest. Recovery was significantly delayed in the hyperthermic group III animals, with a lower amplitude 14 hours after the operation, which gradually increased with time (P < .05 for group III vs groups I and II). CONCLUSIONS: Mild postischemic hyperthermia significantly exacerbates functional and structural neurologic injury after deep hypothermic circulatory arrest and should therefore be avoided.     

Aprotinin and recombinant human erythropoietin reduce the need for homologous blood transfusion in cardiac surgery

The effects of low dose aprotinin (Trasylol) and preoperative administration of recombinant human erythropoietin (EPO) were evaluated in 144 patients undergoing cardiopulmonary bypass divided into four groups. Group I (n = 43) received a subcutaneous administration of EPO (18,000 U) one week before operation and intraoperative administration of low-dose aprotinin (mean; 1.38 +/- 0.26 x 10(6) kallikrein inactivator units; KIU) from extracorporeal circulation, group II (n = 39) received only preoperative administration of EPO, group III (n = 28) received only intraoperative administration of low-dose aprotinin (mean; 1.46 +/- 0.25 x 10(6) KIU), and group IV (n = 34) were not administered either drug. Compared with group IV, the intraoperative blood loss was significantly lower in group I (p < 0.01), and in group II or III (p < 0.05). The postoperative drainage in 24 hours was significantly lower in groups I and III receiving aprotinin than in the other groups. The mean volume of total homologous blood transfusion and the percentage of cases not requiring a homologous blood transfusion in each group was, respectively, 74 +/- 235 ml and 88.4% in group I, 282 +/- 1289 ml and 87.2% in group II, 414 +/- 584 ml and 60.7% in group III, and 976 +/- 1931 ml and 44.1% in group IV. Significant differences were recognized between group I and group IV (p < 0.05). These findings indicate that when used in combination, both drugs reduce blood loss and the need for a homologous blood transfusion more effectively than either drug alone.     

Prognostic significance of silent myocardial ischaemia during maximal exercise testing after a first acute myocardial infarction

Clinical, exercise, and angiographic variables, and long-term follow-up were compared in patients, who, during maximal Bruce exercise testing after a first acute myocardial infarction (AMI), had positive responses to exercise testing (n = 116, 38% of 303) with (n = 23, group I) or without (n = 93, group II) angina. Group I patients more often (52 vs 19%, P < 0.001) had a history of pre-infarction angina. Group II had a greater proportion (75 vs 52%, P < 0.05) of inferior wall AMI, whereas group I had a greater proportion (30 vs 19%, P < 0.01) of non-Q wave AMI. Total exercise duration was significantly (P < 0.01) longer in group II (7.6 +/- 3.2 vs 5.5 +/- 3.1 min). Maximal exercise heart rate (144 +/- 22 vs 133 +/- 21, beats.min-1 P < 0.05) was also higher in group II. A greater proportion of group II patients (37 vs 9%, P < 0.05) had single-vessel disease, whereas multivessel disease was more common (91 vs 63%, P < 0.03) in group I. Left ventricular function was similar in both groups. During follow-up (48 +/- 22 months) the incidence of cardiac death (group I, 3.3%, group II, 4.8%), of recurrent infarction (group I, 4.8%, group II 3.3%), and of revascularization procedures (group I, 28.5%, group II, 19.8%) were similar in both groups. Although asymptomatic exercise-induced ischaemia was associated with better exercise performance and less extensive coronary disease than symptomatic ischaemia, it had the same long-term prognostic implications.     

Mild hypothermia after cardiac arrest in dogs does not affect postarrest cerebral oxygen uptake/delivery mismatching

PURPOSE: To compare measurements of cerebral arteriovenous oxygen content differences (oxygen extraction ratios, oxygen utilization coefficients) in dogs after cardiac arrest, resuscitated under normothermia vs. mild hypothermia for 1-2 h or 12 h. METHODS: In 20 dogs, we used our model of ventricular fibrillation (no blood flow) of 12.5 min, reperfusion with brief cardiopulmonary bypass, and controlled ventilation, normotension, normoxemia, and mild hypocapnia to 24 h. We compared a normothermic control Group I (37.5 degrees C) (n = 8); with brief mild hypothermia in Group II (core and tympanic membrane temperature about 34 degrees C during the first hour after arrest) (n = 6); and with prolonged mild hypothermia in Group III (34 degrees C during the first 12 h after arrest) (n = 6). RESULTS: In Group I, the cerebral arteriovenous O2 content difference was 5.6 +/- 1.6 ml/dl before arrest; was low during reperfusion (transient hyperemia) and increased (worsened) significantly to 8.8 +/- 2.8 ml/dl at 1 h, remained increased until 18 h, and returned to baseline levels at 24 h after reperfusion. These values were not significantly different in hypothermic Groups II and III. The cerebral venous (saggital sinus) PO2 (PssO2) was about 40 mmHg (range 29-53) in all three groups before arrest and decreased significantly below baseline values, between 1 h and 18 h after arrest; the lowest mean values were 19 +/- 19 mmHg in Group I, 15 +/- 8 in Group II (NS), and 21 +/- 3 in Group III (NS). Postarrest PssO2 values of < or = 20 mmHg were found in 6/8 dogs in Group I, 5/6 in Group II and 4/6 in Group III. Among the 120 values of PssO2 measured between 1 h and 18 h after arrest, 32 were below the critical value of 20 mmHg. CONCLUSIONS: After prolonged cardiac arrest, critically low cerebral venous O2 values suggest inadequate cerebral O2 delivery. Brief or prolonged mild hypothermia after arrest does not mitigate the postarrest cerebral O2 uptake/delivery mismatching.     

Eosinophil surface antigen expression and cytokine production vary in different ocular allergic diseases

OBJECTIVES: Improving methods of donor heart preservation may permit prolonged storage and remote procurement of cardiac allografts. We hypothesized that continuous, sanguineous perfusion of the donor heart in the beating, working state may prolong myocardial preservation. METHODS: We developed a portable perfusion apparatus for use in donor heart preservation. Contractile, metabolic, and vasomotor functions were monitored simultaneously in an isolated swine heart. The metabolic state was monitored by myocardial tissue pH. Vasomotor function was assessed in isolated coronary ring chambers. Hearts were randomized into 3 groups: group I (n = 5), cardioplegic arrest, 12-hour storage at 4 degrees C with modified Belzer solution, and 2-hour sanguineous reperfusion in the working state; group II (n = 6), 12-hour continuous perfusion in the beating working state, 30 minutes of arrest (to simulate re-implantation time), and 2 hours of reperfusion, as above; group III (n = 7), coronary ring control hearts. RESULTS: At 2 hours of reperfusion, left ventricular developed pressure in group II was higher than in group I (mean +/- standard deviation: 90 +/- 6 mm Hg, 53 +/- 15 mm Hg, P = .005). Significantly less myocardial edema was observed in group II than in group I (73% +/- 4%, 80% +/- 1% water content, P = .01). Significantly less myocardial acidosis was noted in group II than in group I during preservation (pH 7.3 +/- 0.01, 6.1 +/- 0.03, P < .001) and reperfusion (pH 7.3 +/- 0.008, 6.8 +/- 0.05, P < .001). Coronary endothelial vasomotor function was better preserved in group II than in group I as evidenced by dose-response relaxation of coronary rings to 10(-8) mol/L bradykinin (37%, 55% delta baseline, P = .01). CONCLUSION: This new method extends the current preservation limit and avoids time-dependent ischemic injury, thereby allowing for distant procurement of donor organs.     

Important microsatellite markers in the investigation of replication errors (RER) in colorectal carcinomas

PURPOSE: Our purpose was to assess the value of monitoring serum P and inhibin A to determine how values might improve the clinical monitoring of natural cycle in vitro fertilization (IVF)-embryo transfer (ET) patients. METHODS: All patients (n = 26) who underwent natural-cycle IVF-ET (n = 35) were analyzed. Groups were evaluated according to patients who had a spontaneous luteinizing hormone (LH) surge (group I) and women receiving human chorionic gonadotropin (hCG) who underwent subsequent oocyte aspiration (group II). Group II was further evaluated according to women who did (n = 10) and did not (n = 7) have an ET. All cycles were evaluated with serial transvaginal ultrasonography and serum estradiol, progesterone, and inhibin A. When follicle maturity was achieved, hCG, 10,000 IU, was administered intramuscularly if a LH surge was not detected. Transvaginal ultrasound-guided aspiration was performed 34-36 hr after hCG administration followed by a 48-hr transcervical ET. RESULTS: No differences were seen in cycles the day prior to (d-1) and the day of a spontaneous LH surge, (n = 18) or hCG (d-0)(n = 17) in group I or group II with respect to lead follicular diameter (d-1, 15.3 +/- 0.6 vs. 14.2 +/- 0.9 mm; d-0, 17.4 +/- 0.8 vs. 17.8 +/- 0.6 mm) and serum estradiol (d-1, 148 +/- 15 vs. 150 +/- 15 pg/ml; d-0, 218 +/- 15 vs. 199 +/- 16 pg/ml), respectively. However, serum progesterone was significantly elevated in group I compared with group II on d-1 (0.82 +/- 0.6 vs. 0.48 +/- 0.04 ng/ml; P < 0.05) and d-0 (1.1 +/- 0.12 vs. 0.63 +/- 0.08 ng/ml; P < 0.05). Inhibin A was significantly greater on d-1 in group I (24 +/- 2.5 vs. 15 +/- 2.2 pg/ml; P < 0.05). In group II, cycles that resulted in an ET (n = 10) compared with group II cycles that did not (n = 7) revealed a significant difference in serum progesterone (0.51 +/- 0.05 vs. 0.7 +/- 0.07 ng/ml; P < 0.05) and inhibin A (15 +/- 2.5 vs. 37.3 +/- 5 pg/ml; P < 0.05) the day of hCG. CONCLUSIONS: The possible application of serum progesterone and inhibin A in managing natural-cycle IVF-ET is suggested. These assays may predict women who should be set up for egg retrieval, while cancelling others in spite of the absence of an LH surge.     

Head-down-tilt bed rest alters forearm vasodilator and vasoconstrictor responses

To test the hypothesis that head-down-tilt bed rest (HDBR) for 14 days alters vascular reactivity to vasodilatory and vasoconstrictor stimuli, the reactive hyperemic forearm blood flow (RHBF, measured by venous occlusion plethysmography) and mean arterial pressure (MAP, measured by Finapres) responses after 10 min of circulatory arrest were measured in a control trial (n = 20) and when sympathetic discharge was increased by a cold pressor test (RHBF + cold pressor test; n = 10). Vascular conductance (VC) was calculated (VC = RHBF/MAP). In the control trial, peak RHBF at 5 s after circulatory arrest (34.1 +/- 2.5 vs. 48.9 +/- 4.3 ml . 100 ml-1 . min-1) and VC (0.34 +/- 0.02 vs. 0.53 +/- 0.05 ml . 100 ml-1 . min-1 . mmHg-1) were reduced in the post- compared with the pre-HDBR tests (P < 0. 05). Total excess RHBF over 3 min was diminished in the post- compared with the pre-HDBR trial (84.8 vs. 117 ml/100 ml, P < 0.002). The ability of the cold pressor test to lower forearm blood flow was less in the post- than in the pre-HDBR test (P < 0.05), despite similar increases in MAP. These data suggest that regulation of vascular dilation and the interaction between dilatory and constrictor influences were altered with bed rest.     

HLA class I expression on human ovarian carcinoma cells correlates with T-cell infiltration in vivo and T-cell expansion in vitro in low concentrations of recombinant interleukin-2

This study was carried out to determine whether HLA class I or class II expression on ovarian tumor cells and lymphocytic infiltration of the epithelial ovarian carcinoma (EOC) tissues were responsible for the ability to expand tumor-infiltrating lymphocytes (TIL) in vitro in low concentrations of recombinant interleukin-2 (rIL-2). Immunohistochemical analysis was performed using monoclonal antibodies that recognize framework determinants of either HLA class I or HLA class II or leukocyte differentiation antigens (LCA, CD3, CD4, and CD8). Cryostat sections of EOC had HLA class I and HLA class II expression on at least 5% of tumor cells in 18 of 20 specimens (90%). From another portion of the same tumor specimens T-cell lines were developed from TIL in low concentrations of rIL-2 (200-600 IU/ml) in 7 of 17 patients. Tumors from which TIL were expanded in vitro with rIL-2 had significantly higher proportions of HLA class I-positive tumor cells (73 +/- 10%) compared to tumors from which TIL failed to grow (40 +/- 10%) (P = 0.036). However, there was no difference in the proportions of HLA class II-positive tumor cells between the two groups. Tumor specimens of patients whose TIL were expanded in rIL-2 had significantly higher numbers per field (423 +/- 114 vs 154 +/- 20; P = 0.005) and proportions (90 +/- 3% vs 77 +/- 4%; P = 0.023) of infiltrating CD3+ cells, significantly higher numbers per field (115 +/- 44 vs 19 +/- 5; P = 0.003) and proportions (25 +/- 5% vs 11 +/- 2%; P = 0.017) of CD8+ cells and significantly higher numbers per field of CD4+ cells (318 +/- 101 vs 113 +/- 18; P = 0.025), in comparison to tumor specimens from patients whose TIL did not grow in vitro. Significant correlations were observed between the proportions of HLA class I-positive EOC tumor cells and the numbers of infiltrating LCA-positive cells (r = 0.67; P = 0.005) CD3+ cells (r = 0.70; P = 0.002), CD4+ cells (r = 0.69; P = 0.003), and CD8+ cells (r = 0.82; P = 0.001). The proportions of HLA class II-positive tumor cells correlated positively (r = 0.45; P = 0.049) only with the numbers of CD8+-infiltrating cells. In conclusion, we report here that HLA class I expression on EOC cells correlates with T-cell infiltration in vivo and T-cell expansion in vitro, in low concentrations of rIL-2.     

Aprotinin reduces homologous blood transfusions when pediatric cardiac surgery must be redone

The hemostatic effect of aprotinin in pediatric cardiac surgery is controversial. This study demonstrated the usefulness of aprotinin in cases undergoing additional surgery. In a retrospective study, three groups of children were investigated. In group I (n = 10), no aprotinin or Cell saver was used (control). In group II (n = 12), Cell saver was used intraoperatively. In group III (n = 14), aprotinin 30,000 KIU/kg was added to the prime of cardiopulmonary bypass, and another 10,000 KIU/kg was given every hour during extracorporeal circulation. Both blood loss and use of homologous blood during operation were significantly (p < 0.01) reduced in group III compared to those in the other two groups. In group III, blood loss both 12 and 48 hours postoperatively were one-third less than those in group I (no significant difference). The use of homologous blood 48 hours postoperatively was significantly reduced in group III compared to that in group I (p < 0.01) or group II (p < 0.05). We conclude that aprotinin administration during cardiopulmonary bypass reduced blood loss and homologous blood requirements both operatively and postoperatively when pediatric cardiac surgery must be redone.     

Mechanics of avian fibrous periosteum: tensile and adhesion properties during growth

Aprotinin is a proteinase inhibitor that reduces blood loss in total hip arthroplasty when administered in large doses. Little is known about the capability of smaller doses of aprotinin in reducing blood loss and transfusion needs in this surgical setting. We reviewed the medical records of 372 patients who had undergone unilateral primary total hip arthroplasty under general anaesthesia during a 6-year period (1989 to 1994) at our institution. Successively, 193 patients had and 179 patients had not received aprotinin in a dose of 20,000 kallikrein inhibitor units per kilogram body weight intravenously before surgery. Neither the volume of red blood cells lost nor that of red blood cells transfused during hospitalization differed significantly between the patients who had and those who had not received aprotinin (520 +/- 406 vs. 549 +/- 394 mL and 463 +/- 379 vs. 475 +/- 367 mL; P = 0.49 and P = 0.76 respectively). These results suggest that small-dose aprotinin was not effective in reducing blood loss and transfusion needs in patients undergoing unilateral primary total hip replacement.     

Fibronectin in the ascitic fluid of cirrhotic patients: correlation with biochemical risk factors for the development of spontaneous bacterial peritonitis

Cirrhotic patients (23 with alcoholic cirrhosis, 5 with posthepatitic cirrhosis and 2 with cryptogenic cirrhosis) with ascites and portal hypertension were studied and divided into two groups corresponding to high or low risk to develop spontaneous bacterial peritonitis (SBP) related to the concentration of total protein in the ascitic fluid (A-TP): group I (high risk): A-TP < or = 1.5 g/dl and group II (low risk): A-TP > 1.5 g/dl. Fibronectin (FN), C3 and C4 concentrations were measured by radial immunodiffusion while total protein was measured by the biuret method. The mean values (group I vs group II) of C3 (12.59 +/- 4.72 vs 24.53 +/- 15.58 mg/dl), C4 (4.26 +/- 3.87 vs 7.26 +/- 4.14 mg/dl) and FN (50.47 +/- 12.49 vs 75.89 +/- 24.70 mg/dl) in the ascitic fluid were significantly lower (P < 0.05) in the group considered to be at high risk for SBP. No significant difference was observed in the plasma/ascites fibronectin ratio (3.91 +/- 1.21 vs 3.80 +/- 1.26) or gradient (131.46 +/- 64.01 vs 196.96 +/- 57.38) between groups. Fibronectin in ascites was significantly correlated to C3 (r = 0.76), C4 (r = 0.58), total protein (r = 0.73) and plasma FN (r = 0.58) (P < 0.05). The data suggest that the FN concentration in ascites is related to the opsonic capacity of this fluid, and that its concentration in the ascitic fluid may be a biochemical risk factor indicator for the development of spontaneous bacterial peritonitis.     

Comparison of patterns of pulmonary venous blood flow in the functional single ventricle heart after operative aortopulmonary shunt versus superior cavopulmonary shunt

In this study we investigated the patterns of pulmonary venous flow in children with functional single ventricles to obtain a better understanding of the determinants of transpulmonary blood flow. Sixty-eight patients with functional single ventricles and aortopulmonary shunt (n = 34, group I), or superior cavopulmonary connection (n = 34, group II) underwent transesophageal Doppler echocardiographic assessment of flow in the left upper pulmonary vein before undergoing the next stage of surgery. Twelve patients from group II also underwent simultaneous evaluation of superior vena caval flow. Biphasic forward pulmonary venous flow was noted in 62 patients in sinus rhythm (S wave in systole, D wave in diastole); in 6 patients with junctional rhythm, significant early systolic reversal of flow was present. Both the S- and D-wave velocity-time integrals (VTI) were greater in group I than in group II (S(VTI) 9.9 +/- 4.2 vs 8.0 +/- 2.6, p = 0.02; D(VTI) 8.0 +/- 3.5 vs 4.2 +/- 2.6, p <0.001). In both groups, pulmonary venous flow was predominantly systolic; however, the proportion of flow during ventricular systole was significantly greater in group II than in group I (S(VTI)/D(VTI) group II: 2.4 +/- 1.5; group I 1.4 +/- 0.5, p = 0.001; percent systolic fraction of pulmonary venous flow group II = 67%, group I = 56%, p <0.001). Analysis of superior vena caval flow in group II revealed a single predominant wave with onset at early systole and peak in late systole at a mean of 150 ms after the pulmonary venous S-wave peak. Our data suggest that ventricular systole (i.e., atrial relaxation, atrioventricular valve descent) asserts great influence on transpulmonary blood flow in the functional single ventricle.     

Outcome of cardiac valve ring abscesses after medical treatment: attempt to identify criteria of favorable prognosis

OBJECTIVES: Identify factors predicting favorable outcome after medical management of valve ring abscesses in order to propose a surveillance schedule for conservative treatment. METHODS: A multicentric study conducted from July 1989 to February 1996 included 28 patients (mean age 64 +/- 16 years, range 26-83) hospitalized for active endocarditis and valve ring abscesses diagnosed at transthoracic or transesophageal echography. Conservative medical therapy was given because of a decision of the medico-surgical team (n = 9), high surgical risk (n = 12), or patient refusal of surgery (n = 7). Outcome was favourable in 18 patients (Group I) and unfavorable in 10 (Group II) due to death (n = 9) or subsequent surgery (n = 1). Univariate and multivariate analysis were used to determine differences between the groups in terms of clinical and laboratory data. RESULTS: Mean follow-up in Group I was 33 +/- 18 months and 15 +/- 10 months in Group II. Univariate analysis showed significant differences between Group I and II respectively for age (59 +/- 18 yr vs 72 +/- 10, p = 0.04), delay to apyrexia after antibiotics (4.3 +/- 2.8 vs 8.3 +/- 2.4 days, p < 0.0008), heart failure (5% vs 70%, p = 0.003), grade III or IV valvular regurgitation (5% vs 60%, p < 0.04), and mean surface area of the abscess (1.5 +/- 1.2 vs 5.4 +/- 6.4 cm2, p < 0.03). Independent factors at multivariate analysis were by decreasing order: lack of heart failure at admission, delay to apyrexia, abscess surface area, and age. Outcome was favorable (mean follow-up 33 +/- 10 months) in all patients with an abscess surface area < 1.5 cm2, no signs of heart failure, no grade III or IV valvular regurgitation, apyrexia after less than 8 days on antibiotics and no staphylococcus positive blood culture. CONCLUSION: Medical management of valve ring abscesses may be indicated in selected patients in care units with rigorous surveillance facilities. Further studies are needed to precisely identify surveillance and treatment criteria.     

Alveolar expansion itself but not continuous oxygen supply enhances postmortem preservation of pulmonary grafts

OBJECTIVE: If lungs could be retrieved for transplant after circulatory arrest, the shortage of donors might be significantly alleviated. Great controversy still exists concerning the optimal mode of preservation of pulmonary grafts in these non-heart-beating donors. METHODS: Graft function was measured in an isolated room air-ventilated rabbit lung model during reperfusion with homologous, diluted (Hb +/- 8.0 g/dl) and deoxygenated (PaO2 +/- 40 mmHg) blood up to 4 h. Five groups of cadavers (n = 4 in each group) were studied: In the control group, lungs were immediately reperfused. In the other groups, cadavers were left at room temperature for 4 h after death with lungs either deflated (group 1), inflated with room air (group 2), or ventilated with room air (group 3) or 100% nitrogen (group 4). RESULTS: After 1 h of reperfusion, significant differences were noted between group 1 and groups 2, 3, and 4 in peak airway pressure (27 +/- 5 cm H2O vs. 15 +/- 1 cm H2O, 17 +/- 2 cm H2O, and 16 +/- 1 cm H2O, respectively; P < 0.05), in weight gain (137 +/- 24 vs. 31 +/- 7, 30 +/- 3, and 30 +/- 2%, respectively; P < 0.05), and in veno-arterial oxygen pressure gradient (9 +/- 5 vs. 95 +/- 13, 96 +/- 7 and 96 +/- 4 mmHg, respectively; P < 0.05). Also, wet-to-dry weight ratio at end of reperfusion was significantly different (10.2 +/- 1.0 vs. 6.0 +/- 0.3. 5.2 +/- 0.3 and 5.4 +/- 0.5, respectively; P < 0.05). No significant differences in any of these parameters were observed between groups 2, 3, and 4. CONCLUSIONS: These data suggest that: (1) pulmonary edema will develop in atelectatic lungs if reperfusion is delayed for 4 h after death; (2) postmortem room air-inflation is as good as ventilation in prolonging warm ischemic tolerance; (3) ventilation with room air is no different from that with nitrogen; (4) therefore, prevention of alveolar collapse appears to be the critical factor in protecting the warm ischemic lung from reperfusion injury independent of continuous oxygen supply.     

Glutamate excitotoxicity: a mechanism of neurologic injury associated with hypothermic circulatory arrest

Glutamate, the major central nervous system neurotransmitter, may have potent neurotoxic activity under conditions of metabolic stress. By receptor autoradiography, we have demonstrated that brain regions most vulnerable to injury during prolonged hypothermic circulatory arrest have the highest density of glutamate receptors. To test the hypothesis that such injury could be mediated by glutamate excitotoxicity, we used dizocilpine (MK-801), a selective N-methyl-D-aspartate-glutamate receptor antagonist in a canine survival model of hypothermic circulatory arrest. Eighteen male dogs (20 to 25 kg) were supported by closed-chest cardiopulmonary bypass, subjected to 2 hours of hypothermic circulatory arrest at 18 degrees C, and rewarmed on cardiopulmonary bypass. All were mechanically ventilated and monitored for 20 hours before extubation and survived for 3 days. Group A dogs (n = 9) received a prearrest intravenous bolus of dizocilpine (0.75 mg/kg) followed by continuous infusion (75 micrograms/kg per hour), resulting in electroencephalographic silence. Dizocilpine was weaned before extubation. Group B dogs received vehicle only. According to a species-specific behavior scale that yielded a neurologic deficit score ranging from 0 (normal) to 500 (brain dead), all animals were neurologically assessed every 12 hours. After the dogs were killed at 72 hours, brains were examined by receptor autoradiography and histologically for patterns of selective neuronal necrosis; they were scored blindly from 0 (normal) to 100 (severe injury). Group A dogs had better neurologic function than group B (neurologic deficit score 21 +/- 15 versus 192 +/- 40, p < 0.001) and had less neuronal injury (7.3 +/- 3 versus 48.3 +/- 9, p < 0.0001). Densitometric receptor autoradiography revealed preservation of neuronal N-methyl-D-aspartate-glutamate receptor expression in group A only. These results represent the first direct evidence of a role for glutamate excitotoxicity in the development of hypothermic circulatory arrest-induced brain injury and suggest that selective glutamate receptor antagonists may have a neuroprotective capacity in prolonged periods of hypothermic circulatory arrest.     

Contractile dysfunction caused by normothermic ischaemia and KCL arrest in the isolated pig heart: a 31P NMR study

The aims of this study were to assess (1) whether contractile dysfunction caused by ischaemia under hyperkalaemic conditions ("cardioplegic ischaemia") is associated with impaired energy production or abnormalities in regulation of contractility and (2) whether hyperkalaemia itself contributes to contractile dysfunction. We used 31P and 23Na NMR spectroscopy in conjunction with measurements of mechanical function and oxygen consumption in Langendorff perfused pig hearts to evaluate the mechanism of contractile failure caused by (1) total global cardioplegic (17 mM [K+]) ischaemia (36 degrees C, 50 min KCl arrest, 45 min ischaemia, 20 min reflow with high KCl) and (2) KCl arrest alone (115 min) without flow cessation. KCl arrest plus ischaemia and subsequent reperfusion (Group I) resulted in decreases in ATP (mean +/- S.D.; 61 +/- 13% of initial, n = 5; P < 0.01) and pressure-rate product (PRP) (31 +/- 9%, n = 17; P = 0.0001) while phosphocreatine (PCr), Pi, total creatine (Cr) and intracellular Na+ levels were unaffected. KCl arrest itself (Group II, n = 6) did not affect PCr, ATP or total Cr levels but decreased the PRP to 59 +/- 12% (P < 0.001). Oxygen consumption rates (Vo2) were reduced in both groups to similar levels (67 +/- 18, P < 0.01 and 77 +/- 13%, P < 0.02, respectively). The efficiency of energy conversion to mechanical work (PRP/delta VO2) decreased to 51 +/- 15 (P < 0.001) and 67 +/- 13% (P < 0.012) of initial levels, respectively. To assess metabolic and contractile reserves of post-ischaemic (n = 7) and KCl-treated (n = 3) hearts, the effects of isoproterenol (Iso) and increased Ca2+ were compared with those in normal beating hearts (Group III, n = 3). In all groups treatment with Iso (0.1 micron) greatly increased PRP (to 526 +/- 116, 203 +/- 16 and 198 +/- 8% of the level prior to stimulation (baseline), P < 0.01, respectively) and Vo2 (162 +/- 9, 153 +/-16 and 128 +/-10% of baseline, P < 0.05, Respectively). Increasing [Ca2+] from 1 to 1.66 mM produced less stimulation than Iso: PRP increased to 195 +/- 23, 156 +/- 13 and 163 +/- 22% (P < 0.05) and Vo2 increased to 138 +/- 22 (P < 0.05), 115 +/- 4 and 120 +/- 10% of baseline in Groups I, II and III, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)     

Coronary vasoreactivity to ergonovine after angioplasty: difference between the infarct-related coronary artery and the noninfarct-related coronary artery

BACKGROUND: The vasoreactivity after direct percutaneous transluminal coronary angioplasty (PTCA) in patients with previous myocardial infarction remains unknown. We examined the constrictor response to ergonovine of the infarct-related coronary artery in comparison with that of noninfarct-related coronary artery after angioplasty. METHODS: Ergonovine was administered intravenously to 17 patients with previous myocardial infarction (group I) and to 21 patients with stable angina (group II) 1 year after PTCA. The effects of ergonovine on lumen diameter were analysed quantitatively at the PTCA segment, nonPTCA segment (proximal to the PTCA segment), and nonPTCA artery. RESULTS: The ergonovine-induced decrease in minimal lumen diameter at the PTCA segment was significant in group I (decrease from 2.12 +/- 0.56 to 1.39 +/- 0.74 mm, P < 0.01), but not in group II (decrease from 1.60 +/- 0.35 to 1.43 +/- 0.33 mm, NS). Patients in group I showed a constrictor response at the nonPTCA artery (decrease in diameter from 2.54 +/- 0.90 to 1.94 +/- 0.77 mm, P < 0.01), and a tendency to constrict at the nonPTCA segment (2.56 +/- 0.67 to 2.11 +/- 0.66 mm, P = 0.06), whereas those in group II showed no significant constrictor response to ergonovine at any of the three segments examined. The changes in diameter at the three segments in patients in group I were significantly greater than those in group II (all P < 0.01). Subtotal coronary spasm at the PTCA segment was provoked only in three patients in group I (18%). CONCLUSIONS: The constrictor response to ergonovine of the infarct-related coronary artery was enhanced compared with that of the noninfarct-related coronary artery. This difference in coronary vasoreactivity at the angioplasty segment may be due to previous hypersensitivity of the smooth muscle.     

Factors associated with an atherogenic lipid profile in premenopausal women without clinical cardiovascular disease

BACKGROUND: To investigate different factors associated to a non desirable lipid profile in premenopausal women without cardiovascular disease. To determine the independent factors of lipid profile as a whole of the sample, for planning preventive studies. PATIENTS AND METHODS: We study (March 1994 to June 1996) premenopausal women with alcohol consumption less than 14 g/day and normal serum level of glucose. Group I: women with a non desirable lipid profile (total cholesterol [TCH, mg/dl]/high density lipoprotein cholesterol [HDL-C, mg/dl] > or = 5). Group II: with a desirable lipid profile (TCH/HDL-C < 5). The following factors were analyzed: age, body mass index (BMI), waist/hip ratio (W/H), systolic blood pressure (SBP, mmHg), fasting plasma insulin (fpI, microU/ml), cigarette smoke (CS) and presence of parents with history of non insulin dependent diabetes mellitus (NIDDM) or hypertension. Statistical methods: Mann-Whitney and Student statistics. Contingency-table analysis (chi 2 statistic). Pearson correlation and multiple linear regression. RESULTS: We analyzed 126 women (age = 30 +/- 8.2; 95% CI, 29-32; TCH = 197 +/- 36; 95% CI, 190-203 mg/dl), with 20 women (group I) and 106 (group II). Women from group I had higher values of W/H (0.83 +/- 0.04 vs 0.78 +/- 0.06; p < 0.001), BMI (29.9 +/- 9 vs 24.6 +/- 4.9; p < 0.03), fpI (12.9 +/- 10.4 vs 7.8 +/- 3.5; p < 0.05), SBP (125.9 vs 117; p < 0.02), as well as higher percentage of smokers (75 vs 40%; p < 0.01) and parents with NIDDM (60 vs 26%; p < 0.01) or hypertension (60 vs 49%; NS). No differences of age were detected (32 +/- 7.3 vs 30 +/- 8.3; NS). BMI (0.32; p < 0.01), W/H (0.50; p < 0.01), SBP (0.27; p < 0.01) and fpI (0.33; p < 0.01) were positively correlated with TCH/HDL-C ratio (n = 126). In multiple regression analysis (n = 126), W/H (regression coefficient = 6.1; 95% CI, 3.1-9.1), fpI (regression coefficient = 0.045; 95% CI, 0.018-0.072) and CS (regression coefficient = 0.5; 95% CI, 0.336-0.667) were the only independent predictors (p < 0.01) of the TCH/HDL-C ratio, controlling a 46% of the variance (R2 = 0.46). CONCLUSIONS: Our data indicates that central obesity, hyperinsulinemia and cigarette smoke are independently associated to a high risk cardiovascular lipid profile in premenopausal women without cardiovascular disease. This study suggests the importance of these factors in the management of early lipid control in these women.     

Lidocaine prolongs the safe duration of circulatory arrest during deep hypothermia in dogs

PURPOSE: To test the hypothesis that lidocaine prolongs the safe period of circulatory arrest during deep hypothermia. METHODS: Sixteen dogs were subjected to cooling, first surface cooling to 30 degrees C and then core cooling to 20 degrees C rectal temperature). The circulation was then stopped for 90 min. In the lidocaine group, 4 mg.kg-1 lidocaine was injected into the oxygenator two minutes before circulatory arrest and 2 mg.kg-1 at the beginning of reperfusion and rewarming. The control group received equivalent volumes of normal saline. Post-operatively, using a neurological deficit scoring system (maximum deficit score-100; minimum-zero indicating that no scored deficit could be detected). Neurological function was evaluated hourly for six hours and then daily for one week, the pharmacokinetic parameters were calculated using one compartment model. RESULTS: On the seventh day, the neurological deficit score and overall performance were better in the lidocaine (0.83 +/- 2.04) than in the control group (8.33 +/- 4.08 P < 0.05). During the experiment, the base excess values were also better in the lidocaine than in the control group (at 30 min reperfusion: -4.24 +/- 1.30 vs -8.20 +/- 2.82 P < 0.01, at 60 min reperfusion was -3.34 +/- 1.87 vs -7.52 +/- 2.40 (P < 0.01). On the eighth day the extent of pathological changes were milder in the lidocaine group than that in the control group. The elimination half life of lidocaine was 40.44 +/- 7.99 during hypothermia and 2.01 +/- 4.56 during rewarming. CONCLUSIONS: In dogs lidocaine prolongs the safe duration of circulatory arrest during hypothermia.