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Biomedical subjects

W D Lazenby

Publications and source records attributed to W D Lazenby.

At least 19 recordsLinked to original sources
PubMed1997

Inflammatory cell-derived NO modulates cardiac allograft contractile and electrophysiological function.

We previously demonstrated that inhibition of inducible nitric oxide (NO) synthase (iNOS) ameliorated acute cardiac allograft rejection. This study used a rat cardiac transplant model to characterize contractile and electrophysiological dysfunction during early acute rejection, further examine the role of NO and iNOS in this process, and determine which cells expressed iNOS during early rejection. During early acute rejection, before significant myocyte necrosis, allograft papillary muscles had reduced tension development and rates of tension development and decline during beta-adrenergic, adenylate cyclase, and calcium stimulation compared with isograft and normals [e.g., tension of 36 (allograft) vs. 73 (isograft) mN/mm2 during calcium stimulation, P < 0.001]. Allografts had resting membrane potential depolarization and reduced action potential amplitude and upstroke velocity. iNOS mRNA was expressed in infiltrating inflammatory cells but not in allograft myocytes, endothelial cells, or isografts. Corticosteroids attenuated allograft contractile and electrophysiological dysfunction and inhibited iNOS enzyme activity. Direct iNOS inhibition with aminoguanidine inhibited NO production and prevented allograft contractile and electrophysiological dysfunction (e.g., tension of 64 mN/mm2 during calcium stimulation, P < 0.001). We conclude that 1) early allograft rejection caused contractile and electrophysiological dysfunction that was largely mediated by iNOS expression in infiltrating inflammatory cells, 2) corticosteroid-mediated amelioration of allograft contractile and electrophysiological dysfunction may reflect inhibition of iNOS, and 3) iNOS inhibition may offer an alternative in management of immune-mediated myocardial dysfunction.

Action Potentials↗
PubMed1995

Modulation of in vivo alloreactivity by inhibition of inducible nitric oxide synthase.

The role of nitric oxide in the immune response to allogeneic tissue was explored in an in vivo cardiac transplant model in the rat. Nitric oxide production during organ rejection was demonstrated by elevations in systemic serum nitrite/nitrate levels and by electron paramagnetic resonance spectroscopy. Messenger RNA for the inducible nitric oxide synthase enzyme was detected in the rejecting allografted heart, but not in the nonrejecting isografted heart. The enzyme was demonstrated to be biologically active by the in vitro conversion of L-arginine to L-citrulline and was immunohistochemically localized to the infiltrating inflammatory cells. Treatment with aminoguanidine, a preferential inhibitor of the inducible nitric oxide synthase isoform, prevented the increased nitric oxide production in the transplanted organ and significantly attenuated the pathogenesis of acute rejection. Aminoguanidine treatment prolonged graft survival, improved graft contractile function, and significantly reduced the histologic grade of rejection. These results suggest an important role for nitric oxide in mediating the immune response to allogeneic tissue. Inhibition of inducible nitric oxide synthase may provide a novel therapeutic modality in the management of acute transplant rejection and of other immune-mediated processes.

Amino Acid Oxidoreductases↗
PubMed1992

Effects of temperature and flow rate on regional blood flow and metabolism during cardiopulmonary bypass.

Eleven dogs were subjected to a 150-minute period of cardiopulmonary bypass that consisted of a high-flow, normothermic phase, a high-flow, hypothermic phase, a low-flow, hypothermic phase, and then a high-flow, rewarming phase. Regional blood flow and oxygen consumption to the brain, intestines, kidney, and hind limb were determined at baseline and at 10-minute intervals during cardiopulmonary bypass. Blood flow to the carotid artery, superior mesenteric artery, and renal artery declined significantly with hypothermic cardiopulmonary bypass whereas blood flow to the femoral artery increased significantly. Although total body oxygen consumption returned to baseline values at the end of the rewarming phase, oxygen consumption for these regions differed somewhat from their baseline values. We conclude that blood flow during hypothermic cardiopulmonary bypass is shunted to skeletal muscle, particularly with high pump flows. Additionally, the return of total body oxygen consumption to baseline after rewarming is not necessarily reflected at the regional level.

Animals↗
PubMed1992

Evaluation of an extraaortic counterpulsation device in severe cardiac failure.

A valveless, single-orifice polyurethane ventricle with a maximum stroke volume of 60 mL was implanted on the brachiocephalic artery just above the aortic arch in sheep (n = 14) to act as an extraaortic counterpulsation device. In parallel, an intraaortic balloon was placed in the descending thoracic aorta. Both devices were pneumatically driven with an intraaortic balloon pump console that was gated by the electrocardiogram to provide aortic diastolic augmentation at a stroke volume of 40 mL. To compare the efficacy of counterpulsation for each device during severe cardiac failure, biventricular block was induced by continuous infusion of esmolol (100 to 600 micrograms.kg-1.min-1), titrated to reduce aortic flow and pressure to less than 75% of baseline. Pulsatile coronary and aortic flows were recorded with ultrasonic flow probes placed around their respective vessels. Aortic root and left ventricular pressures were recorded using micromanometers. The enhancement of hemodynamic variables for both devices were compared for optimal timing conditions, which were defined as inflation set just before the dicrotic notch and deflation bordering on isovolumetric systole. The extraaortic counterpulsation device was able to significantly augment aortic and coronary flows while simultaneously decreasing left ventricular tension time index and aortic end-diastolic pressure (p less than 0.02). The intraarotic balloon pump was able to significantly reduce only tension time index (p less than 0.002) to a lesser extent that the extraaortic counterpulsation device. All analysis was performed with the paired-samples t test. The extraaortic counterpulsation device greatly improves the myocardial oxygen supply-consumption ratio of the left ventricle by increasing diastolic coronary flow and reducing left ventricular wall tension during systole.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effects of shaving methods and intraoperative irrigation on suppurative mediastinitis after bypass operations.

To investigate the effects of the hair removal methods and intraoperative irrigation on suppurative mediastinitis after cardiopulmonary bypass operations, 1,980 consecutive adult patients over a 2-year period in our institution were prospectively randomized to manual shaving versus electrical clipping of hair before the skin incision, and to povidone-iodine solution (0.5%) versus saline solution mediastinal and subcutaneous irrigation before wound closure. The overall incidence of suppurative mediastinitis was 0.86% (17/1,980). The infectious rate was significantly higher in the manually shaven (13/990) than in the electrically clipped patients (4/990) with an odds ratio of 3.25 (95% confidence interval, 1.11 to 9.32; p = 0.024). It was also higher in the povidone-iodine group (11/990) than in the saline group (6/990), although the difference was not statistically significant (p = 0.16). Fourteen patients were treated with operative debridement with closed tube irrigation, with one failure requiring a conversion to an open wound. Two patients were successfully treated with primary open wound procedures followed by delayed muscular flap closures, and 1 patient succumbed to rapid and profound sepsis soon after open drainage. We conclude that electrical clipping is superior to manual shaving in the prevention of suppurative mediastinitis. The routine use of povidone-iodine (0.5%) irrigation was of no benefit in this study and may increase the incidence of infection due to its known suppressive effects on local leukocytes and fibroblasts. Furthermore, operative debridement with closed tube irrigation was successful in treating the majority of cases in this series.

Cardiopulmonary Bypass↗
PubMed1992

Compositional analysis of a modified University of Wisconsin solution for extended myocardial preservation. A study of the left ventricular pressure-volume relation.

BACKGROUND: The University of Wisconsin solution (UW) has been shown to be superior to the use of traditional types of simple crystalloids in extended heart preservation. This study was designed to determine the necessity of four potentially redundant components in UW. MATERIALS AND METHODS: Forty canine hearts (n = 8 in each group) were preserved for 6 hours under hypothermic (1-2 degrees C), nonperfused conditions in unmodified UW, UW with an extracellular or reversed composition of sodium and potassium (UW-E), UW with chloride instead of lactobionate (UW-L), UW without raffinose (UW-R), and UW without hydroxyethyl starch (UW-HS). The left ventricular functions were assessed in an isolated heart preparation equipped with a computerized servo-volume pump to measure the pressure-volume relation. The systolic function was expressed in elastance derived from the end-systolic pressure-volume relation, and total ventricular performance was expressed in preload recruitable stroke work area derived from the stroke work-end-diastolic volume relation. Diastolic compliance was derived from the end-diastolic pressure-volume pressure relation. The results were compared with a control group with no ischemia. There was no significant deterioration in left ventricular systolic contractile functions as demonstrated by the analysis of elastance and the preload recruitable stroke work area in any of the modifications of UW. However, significant deterioration in the diastolic compliance occurred in the UW-E and UW-HS groups. A similar trend was found in the UW-L group, although it was not statistically significant, whereas the diastolic compliance was preserved in the UW-R group. CONCLUSIONS: The intracellular electrolyte composition and the hydroxyethyl starch are important in the preservation of left ventricular diastolic function, whereas the omission of raffinose was inconsequential. The replacement of lactobionate by chloride had less untoward functional effects compared with studies of other solid organ preservation.

Adenosine↗
PubMed1992

. . . and then some.

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American Medical Association↗
PubMed1992

Superiority of the University of Wisconsin solution over simple crystalloid for extended heart preservation. A study of left ventricular pressure-volume relationship.

To compare the effects of the University of Wisconsin solution with those of an extracellular crystalloid solution, Krebs-Ringer bicarbonate, as cardiac preservation media, we studied 35 adult dogs in an isolated heart preparation. Four groups of seven hearts were preserved in University of Wisconsin solution for 6 or 12 hours or in Krebs-Ringer bicarbonate solution for 6 or 12 hours. An additional group of seven hearts with no ischemia was used for a control group. In the four preservation groups, hearts were arrested by electrolyte solution (Normosol with potassium chloride, 20 mEq/L, added, 4 degrees C), flushed with 200 ml of the preservation solution, and then stored in the same solution at 1 degree to 2 degrees C. The hearts were mounted on an isolated heart preparation equipped with a computer-controlled servo-pump system that used a mock arterial system to modulate the aortic input impedance presented to the left ventricle. Left ventricular pressure-volume loops were measured on-line for 2 hours of reperfusion with autologous warm oxygenated blood. Elastance was derived from the end-systolic pressure-volume relationship, and diastolic compliance was derived from the end-diastolic pressure-volume relationship. The total left ventricular performance was assessed by the preload recruitable stroke work area, the slope, and its x-intercept, all of which derived from the stroke work (pressure-volume area)-end-diastolic volume relationship. Extended global ischemia had more deleterious effects on the end-diastolic than the end-systolic pressure-volume relationship. In confirmation with other studies, elastance did not accurately reflect the level of ventricular contractile dysfunction because of the significant amount of diastolic dysfunction. The preservation of myocardial systolic and diastolic functions, as demonstrated by the preload recruitable stroke work area and diastolic compliance, was better in the University of Wisconsin solution groups than in the Krebs-Ringer bicarbonate solution groups after 6 and 12 hours of preservation. In addition, 6 hours of preservation with University of Wisconsin solution maintained normal systolic and diastolic functions as compared with those of the control group. Preservation with University of Wisconsin solution prevented any myocardial edema formation; by contrast, this was significantly increased after 12 hours in Krebs-Ringer bicarbonate solution. Groups preserved with University of Wisconsin solution had less reperfusion injury as evidenced by the release of coronary sinus creatine kinase during reperfusion; they also had improved oxygen use during reperfusion.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine↗
PubMed1991

Isolated coronary artery bypass grafting in one hundred consecutive octogenarian patients. A multivariate analysis.

One hundred consecutive patients aged 80 or older underwent isolated coronary artery bypass grafting for New York Heart Association functional class III (24%) or IV (76%) disease in our institution from 1985 to 1989. The operations were elective in 36 patients, urgent in 52, and emergent in 12. Twenty-eight patients had significant disease of the left main coronary artery, with the remainder having an average of 2.8 diseased coronary vessels. Preoperative left ventricular ejection fraction was considered good (greater than 50%) in 62 patients, fair (30% to 50%) in 24 patients, and poor (less than 30%) in 14 patients. An average of 2.8 grafts were performed per patient, and the internal mammary artery was used in 10 patients. Univariate analysis of 36 perioperative factors followed by multivariate logistic regression analysis of the significant variables (p less than 0.05) revealed that the urgency of the operation and left ventricular ejection fraction were independent predictors of operative mortality. There were 12 in-hospital deaths, and the mortality was significantly lower in the elective cases (2.8%) than in the urgent (13.5%) and emergent cases (33.3%). Major complications occurred in 14% of the elective cases, in 21% of the urgent cases, and in 67% of the emergent cases. The operative mortality rates for good, fair, and poor left ventricular ejection fraction were 4.9%, 12.5%, and 42.9%, respectively. Long-term follow-up averaging 22 months revealed a 77% actuarial probability of survival at 24 months and 51% at 48 months, with only two cardiac-related deaths. We conclude that coronary artery bypass grafting can be performed in octogenarians with a favorable outcome when done electively in patients with normal to moderately depressed left ventricular function.

Aged↗
PubMed1991

Keep the faith.

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Alabama↗
PubMed1991

Myocardial reperfusion injury. Platelet-activating factor stimulates polymorphonuclear leukocyte hydrogen peroxide production during myocardial reperfusion.

To study the roles of platelet-activating factor, polymorphonuclear leukocytes, and oxygen free radicals in myocardial reperfusion injury, we subjected 10 sheep to 90 minutes of mid-left anterior descending coronary artery followed by 6 hours of reperfusion. Stainings with gentian violet and tetratriphenyl ammonium chloride demonstrated 20% +/- 3% of the left ventricular mass at risk for ischemia, of which 75% +/- 10% underwent infarction. Coronary sinus blood was assayed for platelet-activating factor and neutrophil hydrogen peroxide production before and during coronary occlusion and during reperfusion. Platelet-activating factor was isolated by column chromatography and lipid extraction and quantified by radioimmunoassay. Neutrophil hydrogen peroxide production was measured by a 2',7'-dichlorofluorescein flow-cytometric assay. Platelet-activating factor was elevated to 899 +/- 210 pg/ml at 15 minutes of reperfusion, compared with the preocclusion level of 271 +/- 55 pg/ml and coronary occlusion level of 359 +/- 64 pg/ml (p less than 0.05; analysis of variance). Neutrophil hydrogen peroxide production, measured on a relative fluorescence scale, was also elevated to a level of 141 +/- 27 at 1 hour of reperfusion, compared with the preocclusion level of 103 +/- 6 and the coronary occlusion level of 114 +/- 13 (p less than 0.01; analysis of variance). Both of these parameters returned toward baselines at the end of 6 hours of reperfusion. Histologic examination revealed infiltration of polymorphonuclear leukocytes into the interstitium of the reperfused myocardium. Neutrophils isolated from unoperated and healthy sheep demonstrated a graded dose response in hydrogen peroxide production when stimulated by purified platelet-activating factor in vitro. These findings suggest that platelet-activating factor is released in the coronary circulation and is a mediator of oxygen free radical production in polymorphonuclear leukocytes during myocardial reperfusion.

Animals↗
PubMed1991

Commitment.

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Career Choice↗
PubMed1991

HCFA blinks.

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Budgets↗
PubMed1990

Treatment with desmopressin acetate in routine coronary artery bypass surgery to improve postoperative hemostasis.

Desmopressin acetate (DDAVP) has been shown to decrease blood loss and transfusions in complex cardiac operations with long extracorporeal times. Its use in routine cardiac valve operations has been shown not to be beneficial, but its role in routine coronary artery bypass grafting operations has not been defined. We examined the effect of DDAVP in a prospective study of 60 patients undergoing uncomplicated primary coronary artery bypass grafting operations. Thirty consecutive patients received DDAVP (0.3 micrograms/kg) after cardiopulmonary bypass and were compared with 30 consecutive patients who did not receive DDAVP. No significant differences were seen in 12-hour mediastinal blood loss (465 +/- 207 ml with DDAVP versus 511 +/- 221 ml without DDAVP) or 12-24-hour mediastinal blood loss (236 +/- 127 ml with DDAVP versus 260 +/- 112 ml without DDAVP). Transfusion of blood products were similar for both groups. Platelet aggregometry at intraoperative and postoperative time points using ADP, collagen, and ristocetin was not significantly different from baseline values in either group. In a subgroup of patients with poor initial ristocetin-induced platelet aggregometry, a significant increase (p less than 0.05) in ristocetin-induced platelet aggregometry was seen postoperatively only in those patients who had received DDAVP. A decrease in blood loss and transfusions, however, was not demonstrable. In those patients who had been on aspirin or nonsteroidal anti-inflammatory drugs preoperatively, DDAVP did not improve mediastinal blood loss or transfusion needs.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1983

Breast necrosis complicating anticoagulation therapy.

Two patients had breast necrosis after sodium warfarin (Coumadin) therapy. This well recognized, but rare, complication of anticoagulation therapy also occurs in other areas of the body. The cause is not known. We present these cases and discuss the literature.

Aged↗