Bacterial contamination of platelet components not detected by BacT/ALERT®.

OBJECTIVES: To investigate the possible causes for false negative results in BacT/ALERT® 3D Signature System despite bacterial contamination of platelet units. BACKGROUND: The Northern Ireland Blood Transfusion Service (NIBTS) routinely extends platelet component shelf life to 7 days. Components are sampled and screened for bacterial contamination using an automated microbial detection system, the BacT/ALERT® 3D Signature System. We report on three platelet components with confirmed bacterial contamination, which represent false negative BacT/ALERT® results and near-miss serious adverse events. METHODS: NIBTS protocols for risk reduction of bacterial contamination of platelet components are described. The methodology for bacterial detection using BacT/ALERT® is outlined. Laboratory tests, relevant patient details and relevant follow-up information are analysed. RESULTS: In all three cases, Staphylococcus aureus was isolated from the platelet residue and confirmed on terminal sub-culture using BacT/ALERT® . In two cases, S. aureus with similar genetic makeup was isolated from the donors. CONCLUSION: Risk reduction measures for bacterial contamination of platelet components are not always effective. Automated bacterial culture detection does not eliminate the risk of bacterial contamination. Visual inspection of platelet components prior to release, issue and administration remains an important last line of defence.

Angiotensin converting enzyme expression is increased in small pulmonary arteries of rats with hypoxia-induced pulmonary hypertension.

Previous studies suggest that while lung angiotensin converting enzyme (ACE) activity is reduced during chronic hypoxia, inhibitors of ACE attenuate hypoxic pulmonary hypertension. In an attempt to explain this paradox we investigated the possibility that whole lung ACE activity may not reflect local pulmonary vascular ACE expression. The experimental approach combined in vivo hemodynamic studies in control and chronically hypoxic rats, measurement of whole lung ACE activity, and evaluation of local pulmonary vascular ACE expression by in situ hybridization and immunohistochemistry. Total lung ACE activity was reduced to 50% of control activity by 5 d of hypoxia and remained low for the duration of the study. Immunohistochemistry showed a marked reduction of ACE staining in alveolar capillary endothelium. However, an increase in ACE staining was observed in the walls of small newly muscularized pulmonary arteries at the level of alveolar ducts and walls. In situ hybridization studies showed increased signal for ACE mRNA in the same vessels. Inhibition of ACE by captopril during chronic hypoxia attenuated pulmonary hypertension and markedly reduced distal muscularization of small pulmonary arteries. In addition, we demonstrated marked longitudinal variation in ACE expression along the normal pulmonary vasculature with the highest levels found in small muscular arteries associated with terminal and respiratory bronchioles. We conclude that local ACE expression is increased in the walls of small pulmonary arteries during the development of hypoxic pulmonary hypertension, despite a generalized reduction in alveolar capillary ACE expression, and we speculate that local arteriolar ACE may play a role in the vascular remodeling associated with pulmonary hypertension.

Effects of chronic hypoxia and altered hemodynamics on endothelial nitric oxide synthase expression in the adult rat lung.

Mechanisms that regulate endothelial nitric oxide synthase (eNOS) expression in normal and hypoxic pulmonary circulation are poorly understood. Lung eNOS expression is increased after chronic hypoxic pulmonary hypertension in rats, but whether this increase is due to altered hemodynamics or to hypoxia is unknown. Therefore, to determine the effect of blood flow changes on eNOS expression in the normal pulmonary circulation, and to determine whether the increase in eNOS expression after chronic hypoxia is caused by hemodynamic changes or low oxygen tension, we compared eNOS expression in the left and right lungs of normoxic and chronically hypoxic rats with surgical stenosis of the left pulmonary artery (LPA). LPA stenosis in normoxic rats reduced blood flow to the left lung from 9.8+/-0.9 to 0.8+/-0.4 ml/100 mg/min (sham surgery controls vs. LPA stenosis, P < 0.05), but there was not a significant increase in right lung blood flow. When compared with the right lung, eNOS protein and mRNA content in the left lung was decreased by 32+/-7 and 54+/-13%, respectively (P < 0.05), and right lung eNOS protein content was unchanged. After 3 wk of hypoxia, LPA stenosis reduced blood flow to the left lung from 5.8+/-0.6 to 1.5+/-0.4 ml/100 mg/min, and increased blood flow to the right lung from 5.8+/-0.5 to 10.0+/-1.4 ml/ 100 mg/min (sham surgery controls vs. LPA stenosis, P < 0.05). Despite reduced flow and pressure to the left lung and increased flow and pressure to the right lung, left and right lung eNOS protein and mRNA contents were not different. There were also no differences in lung eNOS protein levels when compared with chronically hypoxic sham surgery controls (P > 0.05). We conclude that reduction of pulmonary blood flow decreases eNOS mRNA and protein expression in normoxic adult rat lungs, and that hypoxia increases eNOS expression independently of changes in hemodynamics. These findings demonstrate that hemodynamic forces maintain eNOS content in the normoxic pulmonary circulation of the adult rat, and suggest that chronic hypoxia increases eNOS expression independently of changes in hemodynamics.

The pulmonary circulation of homozygous or heterozygous eNOS-null mice is hyperresponsive to mild hypoxia.

Acute hypoxic vasoconstriction and development of hypoxic pulmonary hypertension (PHTN) are unique properties of the pulmonary circulation. The pulmonary endothelium produces vasoactive factors, including nitric oxide (NO), that modify these phenomena. We tested the hypothesis that NO produced by endothelial nitric oxide synthase (eNOS) modulates pulmonary vascular responses to hypoxia using mice with targeted disruption of the eNOS gene (eNOS-/-). Marked PHTN was found in eNOS-/- mice raised in mild hypoxia when compared with either controls or eNOS-/- mice raised in conditions simulating sea level. We found an approximate twofold increase in partially and fully muscularized distal pulmonary arteries in eNOS-/- mice compared with controls. Consistent with vasoconstriction being the primary mechanism of PHTN, however, acute inhalation of 25 ppm NO resulted in normalization of RV pressure in eNOS-/- mice. In addition to studies of eNOS-/- mice, the dose-effect of eNOS was tested using heterozygous eNOS+/- mice. Although the lungs of eNOS+/- mice had 50% of normal eNOS protein, the response to hypoxia was indistinguishable from that of eNOS-/- mice. We conclude that eNOS-derived NO is an important modulator of the pulmonary vascular response to chronic hypoxia and that more than 50% of eNOS expression is required to maintain normal pulmonary vascular tone.

Value and limitation of biplane rest and exercise radionuclide angiography for assessing individual bypass grafts: a prospective study.

This prospective study evaluated the ability of serial biplane rest and exercise radionuclide angiography to predict the status of individual coronary bypass grafts in 20 patients 2 to 6 months after surgery. The preoperative coronary angiogram was used to assign vessels to 10 regions of distribution on the radionuclide angiogram. Predictions of graft adequacy for individual vessels were based on a detailed assessment of rest and exercise wall motion in their regions of supply. Of 59 grafts, 38 were judged adequate (patent with less than 75% stenosis) and 21 inadequate by postoperative catheterization. Radionuclide prediction of graft status was possible for 32 of the 59 grafts, including 19 of 24 left anterior descending, 7 of 19 circumflex and 6 of 16 right coronary artery grafts. The status of the remaining 27 grafts could not be assessed because of normal wall motion in their region of supply both pre- and postoperatively (22 vessels) or because a region of supply was not represented on the biplane radionuclide angiogram (5 vessels). Of the 32 predictions made, 25 (78%) were correct, including 13 (93%) of 14 predictions of graft adequacy and 12 (67%) of 18 predictions of graft inadequacy. The single incorrect prediction of graft adequacy resulted from improved exercise wall motion in a region supplied by a graft judged as having a 75% anastomotic stenosis. Most incorrect predictions of graft inadequacy were due to new septal or other rest wall motion abnormalities postoperatively. The comparison of pre- and postoperative studies was essential to maintain the predictive ability of the test. Thus, a detailed analysis of regional wall motion by rest and exercise radionuclide angiography can be used to predict the status of individual coronary artery bypass grafts. Reliable predictions can be made for most successful anterior descending grafts, and may permit cardiac catheterization to be deferred in certain cases. However, the method is limited by the need to perform preoperative exercise studies, by the low number of right and circumflex coronary artery grafts that can be evaluated and by the poor specificity of predictions of graft failure.

Randomized comparison of the cost and effectiveness of iopamidol and diatrizoate as contrast agents for cardiac angiography.

To evaluate the effectiveness and cost of low osmolarity, nonionic contrast agents for cardiac angiography, 443 patients were randomized to receive either iopamidol or diatrizoate. All adverse events that occurred within 24 h of the procedure were recorded prospectively by study personnel and classified according to previously determined criteria. Major events were defined as life threatening or requiring a procedure to treat, or both. Costs of the catheterization procedure, pharmacy, hospital laboratory and treatment of adverse events were determined on the basis of actual resource use. A total of 20 patients (8.5%) had major and 143 (61%) had minor adverse events with diatrizoate use; 10 patients (4.8%) had major and 53 (25%) had minor adverse events with iopamidol (p = 0.12 for major events; p less than 0.001 for total events). Most adverse events were treated fairly easily and inexpensively. The median overall cost was $186 higher for patients after iopamidol use compared with diatrizoate (p less than 0.0001), but all costs except the cost of the contrast agent were not significantly different between the two groups. Thus, patients who received iopamidol for cardiac angiography had a significantly lower rate of adverse events than those who received diatrizoate, but this difference was achieved at a considerably high overall cost.

Survival and cardiac event rates in the first year after emergency coronary angioplasty for acute myocardial infarction.

One year survival and event-free survival rates were analyzed in 342 patients with acute myocardial infarction who were consecutively enrolled in a treatment protocol of early intravenous thrombolytic therapy followed by emergency coronary angioplasty. Ninety-four percent of the patients achieved successful reperfusion, including 4% with failed angioplasty whose perfusion was maintained by means of a reperfusion catheter before emergency bypass surgery. The procedural mortality rate was 1.2% and the total in-hospital mortality rate was 11%. Ninety-two percent of surviving nonsurgical patients who underwent repeat cardiac catheterization were discharged from the hospital with an open infarct-related artery. The related cumulative 1 year survival rate for all patients managed with this treatment strategy was 87%, and the cardiac event-free survival rate was 84%. The 1 year survival for hospital survivors was 98% and the infarct-free survival rate was 94%. Multivariable analysis identified the following factors as independent predictors of subsequent cardiovascular death: cardiogenic shock, greater age, lower ejection fraction, female gender and a closed infarct-related vessel on the initial coronary angiogram. Among patients with cardiogenic shock, despite a 42% in-hospital mortality rate, only 4% died during the first year after hospital discharge. Similarly, the in-hospital and 1 year postdischarge mortality rates were 19 and 4%, respectively, for patients with an initial ejection fraction less than 40, and 25 and 3%, respectively, for patients greater than 65 years. An aggressive treatment strategy including early thrombolytic therapy, emergency cardiac catheterization, coronary angioplasty and, when necessary, bypass surgery resulted in a high rate of infarct vessel patency.(ABSTRACT TRUNCATED AT 250 WORDS)

Criteria for early discharge after acute myocardial infarction: validation in a community hospital.

All patients admitted to a community hospital coronary care unit during an 18-month-period were studied to validate previously reported criteria for early hospital discharge after myocardial infarction. Factors present during the first four hospital days, which predict subsequent complications requiring urgent medical attention, were classified as either urgent or prognostic. Patients whose initial four days were marked by either no complications (81 patients) or prognostic complications (51 patients) are described. Only one patient in the group of 81 patients had a subsequent urgent complication. Four of 55 patients had late urgent complications. Persistent sinus tachycardia occurred during the first four days in all four of these 55 patients. Early hospital discharge would be feasible in the group with neither urgent nor prognostic complications. Further study of persistent sinus tachycardia is required to improve its predictive ability.

Right ventricular angiotensin converting enzyme activity and expression is increased during hypoxic pulmonary hypertension.

OBJECTIVE: To determine whether local cardiac angiotensin converting enzyme (ACE) expression is upregulated during the development of hypoxia-induced right ventricular hypertrophy. METHODS: ACE activity was measured in membrane preparations from the right ventricle and left ventricle plus septum in normoxic rats and animals exposed to chronic hypoxia for 8 and 14 days. Local cardiac ACE expression was studied by immunohistochemistry using a monoclonal antibody to ACE (9B9). RESULTS: In the normal rat heart, ACE expression was confined to vascular endothelium, the valvular endocardium, and localized regions of parietal endocardium. We found that the development of pulmonary hypertension and right ventricular hypertrophy were associated with 2.6- and 3.4-fold increases in membrane-bound right ventricular ACE activity by 8 and 14 days of hypoxia, respectively. Right ventricular ACE activity was positively correlated with the degree of right ventricular hypertrophy (r = 0.83, P < 0.001). In contrast, left ventricular plus septal ACE activity was significantly reduced by approximately 40 and 60% by 8 and 14 days of hypoxia, respectively, compared to controls. In the right ventricle of chronically hypoxic rats, immunohistochemistry demonstrated increased ACE expression in areas of myocardial fibrosis. Interestingly, increased ACE expression was noted in the right ventricular epicardium in chronically hypoxic rats. In the free wall of the left ventricle there was a significant reduction in the number of myocardial capillaries which expressed ACE in chronically hypoxic rats. CONCLUSION: Chronic hypoxia has a differential effect on left and right ventricular ACE activity and that the sites of altered ACE expression are highly localized. We speculate that locally increased right ventricular ACE activity and expression may play a role in the pathogenesis of right ventricular hypertrophy secondary to hypoxic pulmonary hypertension.

Hemodynamic effects of the antiarrhythmic drug pirmenol.

We examined the hemodynamic effects of pirmenol, a new antiarrhythmic drug, for the first time in man. Right and left heart pressures, Fick cardiac output, and radionuclide ejection fraction were measured before and during infusion of pirmenol in 10 patients with coronary artery disease who were undergoing routine diagnostic cardiac catheterization. Pirmenol was given as a 50-mg IV injection over 2 min followed by a constant infusion of 2.5 mg/min for up to 36 min. Plasma pirmenol levels were within or near the previously determined therapeutic range in all patients. There were no significant changes in systolic blood pressure or cardiac output. Diastolic blood pressure rose from a mean (+/- SD) 78 +/- 7 during the control period to 82 +/- 6 during the infusion, heart rate rose from 66 +/- 6 during the control period to 75 +/- 7 during infusion and ejection fraction fell from 60 +/- 8 during control to 55 +/- 12 during infusion. Although the left ventricular end-diastolic pressure rose from 6 +/- 2 during control to 8 +/- 3 during the infusion, the left ventricular stroke work index fell and the left ventricular work index per minute did not change. The fall in ejection fraction did not correlate with the control ejection fraction, plasma pirmenol levels, or the change in heart rate. The decline in ejection fraction and the failure of the left ventricular work index per minute to rise despite a small rise in left ventricular end-diastolic pressure may indicate a potential myocardial depressant effect of pirmenol.