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Biomedical subjects

G Merin

Publications and source records attributed to G Merin.

At least 19 recordsLinked to original sources

High oxygen concentration exacerbates cardiopulmonary bypass-induced lung injury.

OBJECTIVE: To investigate the effect of ventilation with 100% oxygen on lung injury associated with surgery involving cardiopulmonary bypass (CPB). DESIGN: A prospective randomized study. SETTING: University hospital. PARTICIPANTS: Thirty patients undergoing coronary artery bypass graft surgery with CPB. INTERVENTIONS: Patients were randomized to receive 100% oxygen (Oxygen group) or 50% oxygen (Air group) throughout surgery. During CPB, patients' lungs in the Air group were flushed with air and in the Oxygen group with 100% oxygen. MEASUREMENTS AND MAIN RESULTS: Lung injury was evaluated by arterial oxygen tension-inspired oxygen concentration (PaO2-FIO2) ratio and cytokine levels (tumor necrosis factor-alpha and interleukin-8) in blood and bronchoalveolar lavage fluid measured before and after CPB. The lowest PaO2-FIO2 value was observed after 40 minutes following the completion of CPB in both groups. PaO2-FIO2 values 6 hours after CPB were not different from baseline in the Air group but remained lower (359+/-63 mmHg and 298+/-78 mmHg; p = 0.013) in the Oxygen group. Blood cytokine levels rose during surgery in both groups. Bronchoalveolar lavage levels of interleukin-8 did not change, whereas tumor necrosis factor-alpha increased only in the Oxygen group (p = 0.035). CONCLUSIONS: A significant decrease of oxygenation was observed in the early post-CPB period in both groups of patients, with delay in recovery in patients treated with 100% oxygen. A larger increase of the proinflammatory cytokines was found in patients treated with 100% oxygen. High oxygen concentrations during surgery with CPB should be used only when specifically required.

Bronchoalveolar Lavage Fluid↗

Postcardiopulmonary bypass hypoxemia: a prospective study on incidence, risk factors, and clinical significance.

OBJECTIVE: To evaluate the clinical significance of low arterial oxygen tension-inspired oxygen concentration (PaO2-FIO2) ratio, as a measure of hypoxemia, in the early period after cardiac surgery with cardiopulmonary bypass (CPB); and to evaluate the preoperative, intraoperative, and postoperative factors contributing to the development of hypoxemia within the first 24 hours after cardiac surgery with CPB. DESIGN: Prospective observational study. SETTING: University hospital. PARTICIPANTS: Patients who underwent elective or emergency cardiac surgery with CPB (n = 466). INTERVENTIONS: Preoperative clinical and laboratory data were recorded, as were intraoperative and postoperative data regarding the PaO2-FIO2 ratio, fluid and drug therapy, and chest radiograph. Data analysis evaluated hypoxemia as depicted by the PaO2-FIO2 ratios at 1, 6, and 12 hours after surgery. Thereafter, the effect of the PaO2-FIO2 ratios on time to extubation, lung injury, and length of hospital stay was evaluated. The risk factors were analyzed in 3 separate periods: preoperative, intraoperative, and postoperative. Univariate and multivariate analyses were performed on each period separately. All data were analyzed in 2 consecutive steps: univariate analysis and multivariate analysis. MEASUREMENTS AND MAIN RESULTS: PaO2-FIO2 ratios after CPB were significantly lower compared with baseline values. Six patients (1.32%) met the clinical criteria compatible with acute lung injury. All 6 patients had prompt recovery. Significant risk factors for hypoxemia were age, obesity, reduced cardiac function, previous myocardial infarction, emergency surgery, baseline chest radiograph with alveolar edema, high creatinine level, prolonged CPB time, decreased baseline PaO2-FIO2, use of dopamine after discontinuation of CPB, coronary artery bypass grafting, use of left internal mammary artery, higher pump flow requirement during CPB, increased level of hemoglobin or total protein content, persistent hypothermia 2 and 6 hours after surgery, requirement for reexploration, event requiring reintubation, and chest radiograph with alveolar edema 1 hour after surgery. Six hours after surgery, a lower PaO2-FIO2 ratio correlated significantly with time to extubation and lung injury. CONCLUSIONS: This study shows that despite improvements in the technique of CPB, hypoxemia depicted by low PaO2-FIO2 ratios is common in patients after CPB. It is short lived, however, and has minimal effect on the postoperative clinical course of these patients.

Adolescent↗

Comparison of factors associated with 30-day mortality after coronary artery bypass grafting in patients with versus without diabetes mellitus. Israeli Coronary Artery Bypass (ISCAB) Study Consortium.

The purpose of this study was to identify factors associated with 30-day mortality after coronary artery bypass graft surgery (CABG) among diabetic patients, and to compare them with risk factors among nondiabetics. A subanalysis of a prospective national cohort study was performed which included patients who underwent CABG in 14 medical centers in Israel during 1994. Data including patient demographic and historical information, comorbidity, and cardiac catheterization results were collected by trained nurses. Data were derived from direct patient interviews, charts, catheterization reports, surgical reports, and national vital records. Multivariate logistic regression analysis was used to identify factors associated with a 30-day mortality in diabetic and nondiabetic patient populations. The results showed that crude mortality was 5.0% among diabetic patients (n = 1,034) and 2.5% among nondiabetics (n = 3,350; p < 0.001). The risk profile in diabetics was found to be worse. Multivariate logistic regression analysis identified female gender, 3-vessel disease, and left main disease as independent risk factors for 30-day, past-CABG mortality unique to diabetic patients. Left ventricular dysfunction was found to effect a greater risk among diabetic patients, whereas chronic renal failure was associated with greater risk among nondiabetics. In conclusion, we found differences in patterns of risk factors for post-CABG mortality between diabetics and nondiabetics. These findings may help physicians to identify patients at high risk for CABG mortality.

Aged↗

Estrogen induces nitric oxide-mediated vasodilation of human mammary arteries in vitro.

Human internal mammary arteries (IMA) are relatively protected from atherosclerosis. Estrogen plays a protective role in cardiovascular disease. It causes in vitro and in vivo vasodilatation, but the mechanisms are contradictory. To investigate the in vitro vasomotor effect of estrogen on IMA and the role of endothelium, we studied 30 IMA segments harvested from 10 men during coronary artery bypass grafting surgery. Patients with diabetes mellitus, hypercholesterolemia, hypertension, and smoking were excluded. Twenty IMA rings had intact endothelium ((+)Endo) and 10 rings were denuded of endothelium ((-)Endo). Vasomotor response of each ring was expressed as the percentage of maximal response to norepinephrine (NE). Acetylcholine (10(-8)-10(-5) M) given to (+)Endo and (-)Endo rings induced vasorelaxation of 72 +/- 30.4% and vasoconstriction of 48.5 +/- 20.1%, respectively. 17-Beta-estradiol (10(-8)-10(-5) M) given after maximal precontraction with NE induced marked relaxation in (+)Endo (80.9 +/- 39.2%), but no significant vasomotor effect in (-)Endo rings (P < 0.0001). Vasorelaxation to 17-beta-estradiol (10(-6) M) in (+)Endo rings was 64.5 +/- 18.4 and 8.6 +/- 8.4%, before and after 15-min treatment with nitric oxide synthase inhibitor, L-nitroarginine methyl ester, respectively (n = 14, P < 0.0001). Tamoxifen (10(-6) M) decreased 17-beta-estradiol (10(-7) M)-induced relaxation by 71%. In conclusion, 17-beta-estradiol induces endothelium-dependent NO-mediated vasodilation of human mammary arteries in vitro. This response is mediated through estrogen receptors.

Aged↗

New solution for prolonged myocardial preservation for transplantation.

BACKGROUND: A solution for prolonged cold storage of the heart has been developed. The Jerusalem-Cape Town Solution (JCT) is an "intracellular" type cardioplegic solution and is formulated to (1) minimize hypothermic-induced cell swelling, (2) diminish intracellular acidosis, (3) prevent the expansion of the interstitial space during the reperfusion, (4) protect against oxygen free radical injury during early reperfusion, and (5) provide substrates for regenerating high-energy phosphates. METHODS: With a Langendorff model, rat hearts were subjected to 15 minutes of perfusion with Krebs-Henseleit, 10 minutes of cardioplegic infusion and 20 hours of cold storage (5 degrees to 6 degrees C). Hearts were reperfused for 60 minutes and hemodynamic recovery was assessed. The hearts were assigned to three groups (eight hearts in each), according to the cardioplegic solution used: group 1, JCT; group 2, Bretschneider's HTK cardioplegic solution; and group 3 University of Wisconsin cold storage solution. RESULTS: After 60 minutes of reperfusion, the recovery of the coronary artery flow in group 1 (JCT) was significantly better than in group 2, and slightly better than in group 3 (64% +/- 8.9%, 47.2% +/- 11.6%, 52.5% +/- 19.9%, mean +/- SD, respectively; group 1 versus group 2, p < 0.01). The recovery of the left ventricular developed pressure (LVDP) was significantly better in group 1 compared with group 2 and group 3 (60.2% +/- 14.5%, 41.1% +/- 12.6% and 36.5% +/- 10.1%, respectively; p < 0.01). The recovery of the heart contractility expressed by the product of LVDP and the heart rate (LVDP x heart rate) was significantly higher in group 1 than in group 2 and group 3 (47.5% +/- 3.4%, 23.6% +/- 9.6%, and 28.7% +/- 8.3%, respectively, p < 0.001). In hearts stored for 12 hours in JCT or HTK, the recovery of the heart contractility did not differ significantly (73.4% +/- 12.7% or 70.8% +/- 30.8%, respectively). Modified reperfusion aimed to improve postischemic heart recovery did not bring significant changes in cardiac mechanical function but resulted in an increase in postischemic coronary artery flow recovery in hearts reperfused with amino acid-enriched buffer. CONCLUSIONS: The JCT solution is effective (as well as HTK) in preserving the ischemic hearts for up to 12 hours. It is superior to HTK or University of Wisconsin solution at 20 hours of isolated ischemic storage.

Adenosine Triphosphate↗

Cardioprotective effect of L-arginine in myocardial ischemia and reperfusion in an isolated working rat heart model.

BACKGROUND: Studies in myocardial ischemia and reperfusion have demonstrated damage to endothelium, impaired production and release of vasoactive substances such as nitric oxide, and marked alteration in endothelium-dependent relaxatin of the coronary vasculature. This study was designed to examine the cardioprotective effect of exogenous administration of L-arginine, a precursor of nitric oxide, during ischemia and reperfusion, particularly using oxygenated crystalloid cardioplegia. METHODS: Seventy energy-depleted isolated working rat hearts were arrested by cardioplegia and subjected to 60 min normothermic global ischemia followed by 10 min nonworking and 30 min working reperfusion (Gr 1). L-arginine (3mM or 10mM) was added to the cardioplegic solution (Gr 2,3 respectively), reperfusion (Gr 6,7 respectively), throughout the experiment (Gr 4,5 respectively), and with Nw-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of nitric oxide synthase (Gr 8). RESULTS: At 30 min of working heart reperfusion, compared to control all arginine containing groups (Gr 2-7) exhibited a significant improved recovery of cardiac output (64.7+/-21.2, 98.1+/-21.1, 90.9+/-11.7, 88.9+/-16.2, 83.1+/-7.4, and 90.8+/-10.6, mean +/- SD% Gr 2 to 7 respectively, vs Gr 1 36.3+/-20%, p<0.01). Significant recovery improvement was observed also in other hemodynamic parameters (coronary flow, aortic peak pressure), as well as biochemical recovery assessed by O2 consumption ratio, release of lactic dehydrogenase at reperfusion and regeneration of ATP. The L-NAME group had a significant poorer hemodynamic and biochemical recovery. L-arginine had no effect on the preischemic hemodynamic parameters. CONCLUSIONS: These results support the cumulative data considering L-arginine as a cardioprotective agent in postischemic reperfusion injury.

Animals↗

[Limited axillary thoracotomy for recurrent spontaneous pneumothorax].

Recurrent spontaneous pneumothorax often requires surgical intervention. Recently, less invasive thoracic surgical techniques, such as video-assisted thoracoscopy (VAT) and limited axillary thoracotomy (LAT), have been developed and used for different thoracic procedures. We describe our results with limited axillary thoracotomy, as compared with those of video-assisted thoracoscopy as reported in the literature. From October 1994 to May 1996, 14 patients with recurrent spontaneous pneumothorax, aged 16-33 years, underwent limited axillary thoracotomy, resection of blebs and apical pleurectomy, using multifire GIA 80 staplers (Auto Suture Inc.). There were no complications or recurrences during 5-17 months of follow-up. Mean operative time was 52.2 minutes and mean hospital stay 2.3 days postoperatively. Full activity was regained within 12.1 days. In comparison with over 75 cases of VAT from the literature, LAT is safe and offers the potential benefits of decreased operative time, hospital stay and cost.

Adolescent↗

Endogenous basic fibroblast growth factor displaced by heparin from the lumenal surface of human blood vessels is preferentially sequestered by injured regions of the vessel wall.

BACKGROUND: Proliferation of smooth muscle cells (SMCs) of the arterial wall in response to local injury is an important factor in vascular proliferative disorders. Among the growth factors that promote SMC proliferation is basic fibroblast growth factor (bFGF), which is characterized by a high affinity for heparin and is associated with heparan sulfate on cell surfaces and extracellular matrices. We investigated whether heparin can displace endogenous active bFGF from the lumenal surface of blood vessels, whether bFGF is preferentially bound to injured blood vessels, and whether a synthetic, polyanionic, heparin-mimicking compound (RG-13577) can prevent sequestration of bFGF by the vessel wall. METHODS AND RESULTS: Injured and noninjured saphenous vein segments were perfused with or without heparin, in the absence or presence of 125I-bFGF and/or RG-13577 (a polymer of 4-hydroxyphenoxy acetic acid). Heparin displaced bFGF from the lumenal surface of the vein, and the released bFGF stimulated proliferation of SMCs. Likewise, systemic administration of heparin during open heart surgery resulted in a marked increase in plasma bFGF levels. Injured veins sequestered 125I-bFGF to a much higher extent than noninjured vein segments, both in the absence and presence of heparin. This sequestration was inhibited by compound RG-13577. CONCLUSIONS: Despite its beneficial effects, heparin may displace active bFGF, which subsequently may be preferentially deposited on injured vessel walls, thus contributing to the pathogenesis of restenosis. This effect may be prevented by a synthetic heparin-mimicking compound.

3T3 Cells↗

[Volume reduction surgery in emphysema].

Volume reduction surgery (VRS) is a new procedure based on the concept that relieving hyperinflation in emphysema improves diaphragmatic and chest wall mechanics and ventilation perfusion mismatch. We present our early experience with 16 patients who underwent VRS from August 1995 to June 1996. Patient selection was based on: PFT, CT scan, V/Q scan, ABG's and 6-min walk. After pulmonary rehabilitation, operation was by median sternotomy and bilateral lung shaving. Pulmonary function improved significantly. FEV1 increased from 0.68 +/- 0.2 to 1.0 +/- 0.2 L (p < 0.01) and FVC increased from 1.7 +/- 0.5 to 2.7 +/- 0.5 L (p < 0.017). Total lung capacity decreased from 129% +/- 24% to 108% +/- 20% (p < 0.03). 6-min walk increased from 221 +/- 90 to 404 +/- 123 meters (p < 0.001). Complications included 1 death, prolonged air leak in 7 cases and infection in 2. Quality of life improved substantially in 12 of the 16 cases; in 3 cases there was only slight improvement and in 1 the condition became worse. Volume reduction surgery is a promising surgical solution in selected patients with advanced emphysema.

Adult↗

Israeli women were at a higher risk than men for mortality following coronary bypass surgery.

As part of a national study of surgical departments is Israel, cardiac surgery patients undergoing open heart surgery between 1987 and 1989 were followed-up prospectively. Of these, 1,046 patients had coronary artery bypass grafting (CABG) and are the subject of this report. The six-months mortality after surgery was 12.9% among 202 women and 4.1% among 844 men. Female gender was an independent predictor of mortality even after controlling for the effect of 14 putative risk factors. The adjusted relative risk for mortality in women compared to men was 2.79 (1.5-5.2). In an attempt to understand this excessive mortality among women, a detailed analysis in one of the participating hospitals revealed differences associated with surgical technique by gender, such as proportion of patients with entirely venous grafting vs internal mammary artery grafts (IMA). Thirty percent of women vs 4.8% of men had entirely venous grafting. Adjusting the data for differences in the proportion of venous grafting has obliterated the difference in mortality between the genders in that hospital. We suggest that interventions to reduce mortality among women should involve a more careful choice of female candidates for CABG surgery, as well as introduction of modifications in the operating technique.

Adult↗

Danaparoid for cardiopulmonary bypass in patients with previous heparin-induced thrombocytopenia.

Anticoagulation for cardiopulmonary bypass in patients with heparin-induced thrombocytopenia requires the use of other anticoagulants. We report a case in whom this was achieved using the heparinoid danaparoid (Orgaran). Based on our experience and a review of the literature, we provide guidelines for managing these rare patients. A danaparoid dose substantially lower than that recommended by the manufacturer may minimize bleeding complications.

Anticoagulants↗

Naturally produced extracellular matrix is an excellent substrate for canine endothelial cell proliferation and resistance to shear stress on PTFE vascular grafts.

PURPOSE: Successful development of a vascular prosthesis lined with endothelial cells (EC) may depend on the ability of the attached cells to resist shear forces after implantation. The present study was designed to investigate EC detachment from extracellular matrix (ECM) precoated vascular prostheses, caused by shear stress in vitro and to test the performance of these grafts in vivo. METHODS: Bovine aortic endothelial cells were seeded inside untreated polytetrafluoro-ethylene (PTFE) vascular graft (10 x 0.6 cm), PTFE graft precoated with fibronectin (FN), or PTFE precoated with FN and a naturally produced ECM (10(6) cells/graft). Sixteen hours after seeding the medium was replaced and unattached cells counted. The strength of endothelial cell attachment was evaluated by subjecting the grafts to a physiologic shear stress of 15 dynes/cm2 for 1 h. The detached cells were collected and quantitated. PTFE or EC preseeded ECM coated grafts were implanted in the common carotid arteries of dogs. RESULTS: While little or no differences were found in the extent of endothelial cell attachment to the various grafts (79%, 87% and 94% of the cells attached to PTFE, FN precoated PTFE, or FN+ECM precoated PTFE, respectively), the number of cells retained after a shear stress was significantly increased on ECM coated PTFE (20%, 54% and 85% on PTFE, FN coated PTFE, and FN+ECM coated PTFE, respectively, p <0.01). Implantation experiments in dogs revealed a significant increase in EC coverage and a reduced incidence of thrombus formation on ECM coated grafts that were seeded with autologous saphenous vein endothelial cells prior to implantation. CONCLUSION: ECM coating significantly increased the strength of endothelial cell attachment to vascular prostheses subjected to shear stress. The presence of adhesive macromolecules and potent endothelial cell growth promoting factors may render the ECM a promising substrate for vascular prostheses.

Animals↗

[Pulmonary thrombo-endarterectomy].

Chronic pulmonary thromboembolism is an underdiagnosed condition with major morbidity and mortality. Over the past year and a half, we diagnosed 6 new cases of which 3 underwent successful, pulmonary thrombo-endarterectomy (2 in San Diego, 1 in Jerusalem). All recovered fully and returned to normal, active life. We conclude that pulmonary thrombo-endarterectomy is a viable option for patients with chronic pulmonary thromboembolism.

Adult↗