Medication Adherence and Risk Factors for Non-adherence among Patients taking Highly Active Antiretroviral Therapy

Background: ART is a life long treatment and its effectiveness depends critically both on the efficacy of the antiretroviral drugs against the virus, and achieving a very high level of adherence (> 95 %) to the medications. Adherence poses a special challenge and requires commitment from the patient and the health care provider.Objectives: The study evaluated medication adherence, and identified risk factors for non-adherence in HIV-infected ART patients.Methods: In a cross-sectional survey, medication adherence of 118 HIV-infected ART patients who received pretreatment and ongoing adherence counseling and education for 6 months was evaluated using a self-administered studyspecific 16-item questionnaire. Self-reported adherence was calculated as the mean of patients' adherence to the medication schedule and the number of prescribed doses of medications missed. Chi-square statistics was used to test the association of adherence with occupation and education at 95 % CI.Results: The mean age of participants was 33.9 (95 % CI, 29.6-38.2) years; and 82.2 % of participants were aged 26-45years; 60.2 % females, 80.5 % attained secondary education at the least; and 77.1 % were employed. All participants reported been counseled on the benefits of ART and medication adherence at ART initiation. On assessment of participants' knowledge of the benefits of ART and medication adherence, 92.2 % were very knowledgeable, 2.9 %reported wrongly that ART is a cure for HIV. The self-reported adherence to medication schedule was 68.9 %(range: 0 % - 100 %), of which 83 (70.3 %) reported > 75 % adherence; while adherence to prescribed doses of medications was 89.2 % (range: 20 % - 100 %), of which 100 (84.7 %) participants reported > 80 % adherence. Mean self-reported adherence (±SD) was 79.1 % ± 14.4 %. Employment status was associated with poor adherence (P < 0.05), unlike the educational status. The major reasons reported for non-adherence were busy at work or school (33.1 %), forgetfulness (15.5 %), fasting (12.0 %), and travelled away from home (10.6%). Conclusion: The self-reported adherence was relatively poor compared to the desired value of > 95%. Employment status was associated with poor adherence and this may be corroborated by the major reason reported for non-adherence (busy at work or school). Routine adherence monitoring and multiple adherence interventions in clinical practice are recommended

Health-Related Quality of Life and CD4 Cells Status of Patients Receiving Antiretroviral Therapy in Nigeria

Background: The goals of antiretroviral therapy (ART) are to improve patient's health-related quality of life (HRQOL) and restore immunologic function among others. Objectives: The study evaluated HRQOL and CD4-cells response of HIV-infected patients at months 0 and 6 of receiving ART in Maitama District Hospital Abuja, Nigeria. Methods: HRQOL of a cohort of 150 HIV-infected patients was evaluated at months 0 and 6 of receiving ART using Medical Outcomes Study Short Form-36 (MOS SF-36) which has 8 domains. These include physical functioning, physically and emotionally related role limitations, social functioning, pain, energy/fatigue, emotional well-being and general health. A paired samples t-test was used to compare the HRQOL scores and CD4 cells count of participants at months 0 and 6. Wilcoxon's signed-ranks test was used to compare HRQOL of male and female participants. At two-tailed test, p value of <0.05 was considered significant. Results: The mean age (±SD) of the 150 participants at ART initiation was 34.3 ± 8.4 years; 59.3% were females. The mean (±SD) HRQOL of participants increased significantly from 71.9% ± 20.9 at ART initiation to 89.7% ± 10.6 after 6 months of ART (p<0.05). The change in all SF-36 domains was statistically significant (p<0.05) except for the domains of role limitation due to emotional problems, social functioning and pain. The improvement in the mental component score (MCS) was significant (p<0.05) unlike that of the physical component (PCS). The difference in the HRQOL of male and female participants at months 0 and 6 was not significant. The mean CD4 cell count (±SD) increased from 185.7 ±91.0 cells/mm3 at month 0 to 199.0 ±104.7 cells/mm3 after 6months of ART; though this increase was not statistically significant. Conclusion: There was significant improvement in the mean HRQOL scores of participants which was not associated with significant improvement in the CD4 cells status after six months of ART. The evaluation of HRQOL alongside the clinical and immunological parameters when monitoring treatment outcomes is recommended

CT findings following the cabrol composite graft procedure.

PURPOSE: Insertion of a composite graft and reimplantation of the coronary arteries through an intermediate Dacron tube (Cabrol composite graft procedure) has been used to treat ascending aortic aneurysms and dissections. The CT findings after the Cabrol composite graft procedure have not been previously described. METHOD: Retrospective review of 12 postoperative CT and CT angiography (CTA) studies both in the immediate postoperative period as well as during long-term follow-up was conducted. RESULTS: The Cabrol composite graft procedure produces typical CT findings consisting of a coronary conduit separate from the aortic graft. The presence of perigraft flow can be normal or abnormal depending on the time point of its occurrence and the extent of its hemodynamic consequences. CONCLUSION: Knowledge of the typical CT and CTA findings following a Cabrol composite graft procedure is essential for the correct interpretation of these studies.

Reperfusion injury significantly impacts clinical outcome after pulmonary transplantation.

BACKGROUND: Reperfusion injury after pulmonary transplantation can contribute significantly to postoperative pulmonary dysfunction. We hypothesized that posttransplantation reperfusion injury would result in an increase in both in-hospital mortality and morbidity. We also hypothesized that the incidence of reperfusion injury would be dependent upon the cause of recipient lung disease and the interval of donor allograft ischemia. METHODS: We performed a retrospective study of all lung transplant recipients at our institution from June 1990 until June 1998. One hundred patients received 120 organs during this time period. We compared two groups of patients in this study: those experiencing a significant reperfusion injury (22%) and those who did not (78%). RESULTS: In-hospital mortality was significantly greater in patients experiencing reperfusion injury (40.9% versus 11.7%, p < 0.02). Posttransplantation reperfusion injury also resulted in prolonged ventilation (393.5 versus 56.8 hours, p < 0.001) and an increased length of stay in both the intensive care unit (22.2 versus 10.5 days, p < 0.01) and in the hospital (48.8 versus 25.6 days, p < 0.03). The incidence of reperfusion injury could not be attributed to length of donor organ ischemia (221.5 versus 252.9 minutes, p < 0.20). The clinical impact of reperfusion injury was significantly greater in patients undergoing transplantation for preexisting pulmonary hypertension (6/14) than those with chronic obstructive pulmonary disease or emphysema alone (6/54) (42.9% versus 11.1%, p < 0.012). CONCLUSIONS: Clinically significant pulmonary reperfusion injury increased in-hospital mortality and morbidity resulting in prolonged ventilation, length of stay in the intensive care unit, and cost of hospitalization. The incidence of reperfusion injury was not dependent upon the duration of donor organ ischemia but increased with the presence of preoperative pulmonary hypertension. These findings suggest that recipient pathophysiology and donor allograft quality may play important roles in determining the incidence of reperfusion injury.

Enhanced visualization of parathyroid tissue by infusion of a visible dye conjugated to an antiparathyroid antibody.

BACKGROUND: The antiparathyroid antibody BB5-G1 conjugated to cibacron blue, a blue dye, was intravenously infused to enhance parathyroid visualization. Previously, we demonstrated selective staining of human parathyroid implants in athymic nude mice after infusion of the conjugate. METHODS: Mice possessing implanted parathyroid tissue were randomized into the following: group I, infused with cibacron blue alone; group II, infused with the antibody/dye conjugate; and group III, infused with radiolabeled BB5-G1 alone. Implants were surgically explored. Three blinded observers ranked parathyroid visualization in the operative fields, and corresponding histologic sections were computer analyzed. RESULTS: Group II implants were easily visualized; groups I and III showed no staining. Group III showed high gamma counts. Subjective rankings and computer rankings correlated well (p < .05). Group II showed a higher mean staining intensity of 27.45 picogram protein product (PPP)/cell compared with 7.76 PPP/cell of group I (p = .002). CONCLUSION: Cibacron blue/BB5-G1 consistently enhances visualization of implanted parathyroid tissue.

Rapid liquid chromatography with tandem mass spectrometry-based screening procedures for studies on the biotransformation of drug candidates.

The accelerated pace of contemporary drug discovery and development in the pharmaceutical industry has generated increasing demands for early information on the metabolic fate of candidate drugs to guide the selection of new compounds for clinical evaluation. In response to these demands, we have developed a procedure for the rapid analysis of complex biological mixtures for the presence of drug-related materials and have embarked on the development of novel computer-based approaches whereby such procedures can be automated. The goal of this work was to rapidly identify drug metabolites (derived either from a single substrate or from a mixture of substrates) formed in vivo or in vitro. The approach that we have developed relies on the use of generic chromatographic and mass spectrometric methods for analysis of mixtures of drugs and metabolites and on correlation analysis of tandem mass spectrometry spectra to distinguish drug-related components from endogenous materials. Cross-correlation of the spectra also is used to identify the relationship between each metabolite and its respective parent drug in the mixture. In this manner, metabolites of a mixture of several drugs may be analyzed in the time it normally would take to analyze the products from a single substrate. We show that this rapid analytical approach can, with only minor sacrifices in the completeness of the data, significantly increase the number of compounds whose metabolic fate can be elucidated in a given time.

Simultaneous coronary artery bypass grafting and abdominal aneurysm repair decreases stay and costs.

BACKGROUND: Patients with large (> or = 5.0 cm) abdominal aortic aneurysms (AAA) frequently have marked associated coronary artery disease. We hypothesized that a single operation for coronary artery bypass grafting (CABG)/AAA would provide equivalent, if not improved, patient care while decreasing postoperative length of stay and hospital costs compared with staged procedures. METHODS: Eleven patients to date have undergone a combined procedure at our institution. Ten underwent CABG followed by AAA repair, whereas one patient received an aortic valve replacement before aneurysm repair. We performed a retrospective analysis comparing the postoperative length of stay and hospital costs for this single procedure to a combined cohort of 20 randomly selected patients who either received AAA repair (n = 10) or standard CABG (n = 10) during the same time period. RESULTS: No operative mortality has been reported. There were no episodes of neurologic deficit or cardiac complication after these procedures. The postoperative length of stay was significantly decreased for the CABG/AAA group compared with the combined postoperative length of stay for the AAA plus CABG group (7.44+/-0.88 days versus 14.10+/-2.00; p = 0.012). Total hospital costs were also significantly decreased for the CABG/AAA group compared with total hospital costs for the AAA plus CABG group ($22,941+/-$1,933 versus $34,076+/-$2,534; p = 0.003). CONCLUSIONS: A single operation for coronary revascularization and AAA repair is safe and effective. Simultaneous CABG and AAA repair substantially decreases postoperative length of stay and hospital costs while avoiding possible interim aneurysm rupture and repeat anesthesia.

Inhibition of inducible nitric oxide synthase after myocardial ischemia increases coronary flow.

BACKGROUND: The role of nitric oxide synthase in myocardial ischemia-reperfusion injury is complex. Our hypothesis was that inducible nitric oxide synthase has a role in the regulation of coronary flow after ischemia. METHODS: Four groups of isolated blood-perfused rabbit hearts underwent sequential periods of perfusion, ischemia, and reperfusion (20, 30, and 20 minutes). Two groups underwent 40 minutes of perfusion. Ischemic groups received saline vehicle, N omega-nitro-L-arginine methyl ester (L-NAME) or the highly specific inducible nitric oxide synthase inhibitor 1400W in low or high doses during reperfusion. Two nonischemic groups were treated with saline vehicle or 1400W during the last 20 minutes of perfusion. Left ventricular developed pressure and coronary flow were measured after each perfusion period. Ventricular levels of myeloperoxidase and cyclic guanosine monophosphate were measured at the end of the second perfusion period. RESULTS: Coronary flow was significantly increased in both 1400W groups versus L-NAME (p < 0.001) and in high-dose 1400W versus control (p < 0.001). Coronary flow was not significantly different between the nonischemic groups. Left ventricular developed pressure was not significantly different among the ischemic groups or between the two nonischemic groups. There were no differences in cyclic guanosine monophosphate levels in any of the ischemic hearts. Myeloperoxidase levels were significantly elevated in L-NAME versus high-dose 1400W, nonischemic 1400W, and nonischemic saline groups (p < 0.02). CONCLUSIONS: Highly selective inhibition of inducible nitric oxide synthase results in increased coronary flow after ischemia but not after continuous perfusion. This occurs with decreased neutrophil accumulation and a trend toward increased contractility without elevation of cyclic guanosine monophosphate levels.

Replacing the atherosclerotic ascending aorta is a high-risk procedure.

BACKGROUND: Improved techniques in cerebral and myocardial protection have made replacement of the chronically aneurysmal ascending thoracic aorta a safe and effective procedure. We hypothesized that patients with severe ascending or aortic arch atherosclerosis were at greater risk for operative complications during ascending aortic replacement because of the diffuse nature of their atherosclerotic process. METHODS: We retrospectively analyzed the records of 17 patients who received ascending aortic replacement during elective coronary artery bypass grafting (CABG) because of the intraoperative finding of severe atherosclerosis. All 17 patients underwent tube graft replacement of the ascending aorta under hypothermic circulatory arrest and retrograde cerebral perfusion before coronary artery bypass grafting. The outcomes for these patients were compared with those of a control group of 89 consecutive patients who underwent replacement for ascending thoracic aortic aneurysm. RESULTS: The hospital mortality rate for replacement of the ascending thoracic aorta for severe atherosclerosis was 23.5% (4/17) versus 2.25% (2 of 89) for the control group (p=0.006). The incidence of cerebrovascular accident in the atherosclerotic group was 17.6% (3/17) and 3.37% (3/89) for the control group (p=0.051). Nine of 17 atherosclerotic patients (52.9%) had operative morbidity. Only 20.2% (18 of 89) of the control patients had nonfatal postoperative complications. CONCLUSIONS: The severely atherosclerotic ascending aorta is a marker of diffuse atherosclerosis. Despite improved techniques of myocardial and cerebral protection, we have been unable to duplicate our success with ascending thoracic aneurysm repair. Preoperative screening of the ascending aorta by chest computed tomography may be appropriate in select high-risk patients to determine operability.

Hypothermic circulatory arrest does not increase the risk of ascending thoracic aortic aneurysm resection.

OBJECTIVE: The purpose of this study was to investigate the safety and efficacy of a period of deep hypothermic circulatory arrest (DHCA) during elective replacement of the ascending thoracic aorta. SUMMARY BACKGROUND DATA: DHCA has been implemented in ascending thoracic aortic aneurysm resection whenever the anatomy or pathology of the aorta or arch vessels prevents safe or adequate cross-clamping. Profound hypothermia and retrograde cerebral perfusion have been shown to be neurologically protective during ascending aortic replacement under circulatory arrest. METHODS: The authors conducted a retrospective analysis of 91 consecutive patients who underwent repair of chronic ascending thoracic aortic aneurysms from 1986 to present. The authors hypothesized that patients undergoing DHCA with or without retrograde cerebral perfusion during aneurysm repair were at no greater operative risk than patients who received aneurysm resection while on standard cardiopulmonary bypass. RESULTS: There were no significant differences in hospital mortality, stroke rate, or operative morbidity between patients repaired on DHCA when compared to those repaired on cardiopulmonary bypass. CONCLUSIONS: DHCA with or without retrograde cerebral perfusion does not result in increased morbidity or mortality during the resection of ascending thoracic aortic aneurysms. In fact, this technique may prevent damage to the arch vessels in select cases and avoid the possible complications associated with cross-clamping a friable or atherosclerotic aorta.

Preservation with 8-bromo-cyclic GMP improves pulmonary function after prolonged ischemia.

BACKGROUND: Cyclic guanosine monophosphate (cGMP) is a potent second messenger for the nitric oxide pathway in the pulmonary vasculature. Increased cytosolic cGMP levels elicit pulmonary vasodilatation resulting in decreased pulmonary vascular resistance and maximized pulmonary function after ischemia-reperfusion injury. We hypothesized that the addition of a membrane-permeable cGMP analogue (8-bromo-cGMP) to a Euro-Collins (EC) preservation solution would ameliorate pulmonary reperfusion injury better than prostaglandin E1 injection alone after prolonged hypothermic ischemia. METHODS: All lungs from New Zealand White rabbits (weight, 3 to 3.5 kg) were harvested en bloc, flushed with EC solution, and reperfused with whole blood for 30 minutes. Group 1 lungs (immediate control) were immediately reperfused. Group 2 lungs (control) were stored inflated at 4 degrees C for 18 hours before reperfusion. Groups 3 and 4 lungs were flushed with EC solution containing 200 micromol/L 8-bromo-cGMP and stored at 4 degrees C for 18 and 30 hours, respectively. Fresh, nonrecirculated venous blood was used to determine single-pass pulmonary venous-arterial oxygen gradients at 10-minute intervals. Assays for cGMP, cyclic adenosine monophosphate, nitric oxide synthase activity, and myeloperoxidase were performed on all lung tissue samples. Wet to dry weight ratios were determined after 2 weeks of passive desiccation. RESULTS: Oxygenation (venous-arterial oxygen gradient), pulmonary artery pressure, pulmonary vascular resistance, and edema formation were significantly improved in groups 3 and 4 (addition of 8-bromo-cGMP to EC plus 18 or 30 hours of hypothermic ischemia). Hypothermic storage (groups 2, 3, and 4) decreased both nitric oxide synthase activity and myeloperoxidase levels compared with immediate reperfusion (group 1). CONCLUSIONS: These results suggest that the addition of a membrane-permeable cGMP analogue to an EC pulmonary flush solution improves pulmonary function after prolonged storage compared with EC and prostaglandin (E1) preservation alone. The finding of myeloperoxidase reduced levels after hypothermic storage and subsequent reperfusion may suggest a more important role for pulmonary hemodynamic control in mitigating pulmonary reperfusion injury.

Acellular low-potassium dextran preserves pulmonary function after 48 hours of ischemia.

BACKGROUND: We previously have shown that extracellular preservation solutions provide superior pulmonary protection after 18 hours of cold ischemia at 4 degrees C in an isolated, whole-blood-perfused, rabbit lung model. We also reported that the addition of 20% whole blood to a low-potassium dextran solution (BLPD) conferred no discernible advantage over low-potassium dextran (LPD) alone in this same model. Our current study was aimed at documenting the importance of blood in buffering extracellular preservation solutions during 24 to 48 hours of hypothermic ischemia. METHODS: We studied three groups of lungs using an isolated, whole-blood-perfused, ventilated, rabbit lung model. Lungs were flushed with Euro-Collins, LPD, or BLPD solution, and then were reperfused after 24, 36, or 48 hours of hypothermic storage at 4 degrees C. Continuous measurements of pulmonary artery pressure, pulmonary vascular resistance, left atrial pressure, tidal volume, and dynamic airway compliance were obtained. Fresh, non-recirculated venous blood was used to determine single-pass pulmonary venous-to-arterial O2 gradients. RESULTS: The 24-hour Euro-Collins group could not be completed because of immediate reperfusion failure. The 36-hour LPD group oxygenated significantly better than the 36-hour BLPD group (363.3 +/- 65.1 versus 145.3 +/- 40.3 mm Hg, respectively; p = 0.015). The 48-hour LPD group also experienced significant improvements in oxygenation when compared with the 48-hour BLPD group (pulmonary venous-arterial O2 difference of 239.4 +/- 48.4 versus 70.7 +/- 19.5 mm Hg, respectively; p = 0.012). The 48-hour LPD group also displayed significant improvements in pulmonary artery pressure (34.72 +/- 0.96 versus 55.52 +/- 7.37 mm Hg, respectively; p = 0.031) and pulmonary vascular resistance (39,737 +/- 1,291 versus 67,594 +/- 9,467 dynes.s.cm-5, respectively; p = 0.027) when compared with the 48-hour BLPD group. There were no significant differences between the three LPD groups. CONCLUSIONS: Extracellular solutions provide improved pulmonary preservation in an isolated rabbit lung model after 48 hours of cold ischemia. The addition of blood to extracellular preservation solutions diminishes pulmonary function when combined with ischemic periods of 36 to 48 hours.

Mature pulmonary lobar transplants grow in an immature environment.

OBJECTIVE: Mature lobar transplantation will increase the pediatric donor organ pool, but it remains unknown whether such grafts will grow in a developing recipient and provide adequate long-term support. We hypothesized that a mature pulmonary lobar allograft implanted in an immature recipient would grow. METHODS: We investigated our hypothesis in a porcine orthotopic left lung transplant model using animals matched by the major histocompatibility complex to minimize the effects of chronic rejection. Twenty-three immature animals (< 12 weeks of age and < 10 kg total body weight) received either sham left thoracotomy (SH control, n = 4), left upper lobectomy to study compensatory growth (UL control, n = 4), age-matched immature whole left lung transplants (IWL TXP, n = 6), mature (donor > 1 yr in age and > 40 kg in total body weight) left lower lobe transplants (MLL TXP, n = 5), or mature left upper lobe transplants (MUL TXP, n = 4). Twelve weeks after implantation, functional residual capacity of the left lung was measured and arterial blood gas samples were obtained after the native right lung had been excluded. The graft was excised and weighed, and samples for microscopy and wet/dry ratios were collected. RESULTS: Initial and final graft weights were as follows: IWL TXP group (34.6 +/- 1.5 and 107.8 +/- 5.9 gm, p < 0.0001), MLL TXP group (72.4 +/- 6.8 and 111.4 +/- 8.7, p < 0.001), and MUL TXP group (32.8 +/- 1.3 and 92.8 +/- 7.1 gm, respectively, p < 0.004). No significant differences between groups were demonstrated when functional residual capacity, wet/dry ratios, or oxygenation were compared. Immunohistochemical staining for the nuclear antigen Ki-67 demonstrated dividing pneumocytes. CONCLUSIONS: We conclude that a mature lobar graft implanted into an immature recipient grows by pneumocyte division in this model. Mature lobar transplants can be expected to grow and provide adequate long-term function in developing recipients.

Use of over-sized mature pulmonary lower lobe grafts results in superior pulmonary function.

BACKGROUND: Mature lobar transplantation will increase the pediatric donor organ pool; however, issues regarding size discrepancy between donor grafts and recipient lungs remain unresolved. We hypothesized that an oversized mature pulmonary lobar allograft implanted into an immature recipient would provide adequate longterm pulmonary function versus a size-matched mature lobar graft or an immature whole lung. METHODS: We investigated our hypothesis in a porcine orthotopic left lung transplant model in which 19 immature animals made up one control and three recipient groups. Group I underwent sham left thoracotomy (control, n = 4). Group II received age- and size-matched immature whole left lung transplant (n = 6). Group III received mature size-matched left upper lobe transplants (n = 4). Group IV received mature over-sized left lower lobe transplants (n = 5). Twelve weeks after implantation, data were collected after the native right lung was excluded. RESULTS: Graft weight was significantly elevated in group IV as compared with the explanted lung (72.4 +/- 6.8 versus 38.3 +/- 4.5 g; p = 0.003). Pulmonary artery pressure and pulmonary vascular resistance were significantly elevated in group III as compared with the over-sized mature lower lobe transplants (51.8 +/- 2.2 versus 40.4 +/- 2.5 mm Hg [p < 0.0001] and 1,605.9 +/- 117.5 versus 857.6 +/- 133.6 dynes.s.cm-5 [p < 0.0005], respectively). A trend toward decreased oxygenation was identified in group II. CONCLUSIONS: Over-sized mature lobar grafts provide improved hemodynamics as compared with size-matched grafts. Mature left lower lobe grafts are superior to size-matched upper lobe grafts in this model, probably as a result of an augmented vascular bed.

Minimally invasive coronary artery bypass grafting decreases hospital stay and cost.

OBJECTIVE: The authors performed a retrospective cost analysis for patients undergoing revascularization of their left anterior descending (LAD) coronary artery either by standard coronary artery bypass grafting (CABG), percutaneous transluminal coronary angioplasty (PTCA), or minimally invasive coronary artery bypass grafting (MICABG). SUMMARY BACKGROUND DATA: Minimally invasive CABG has become a safe and effective alternative treatment for single-vessel coronary artery disease. However, the acceptance of this procedure as a routine alternative for the treatment of coronary artery disease will depend on both long-term graft patency rates as well as a competitive market cost. METHODS: The authors conducted a retrospective analysis of three patient groups undergoing LAD coronary revascularization from January 1995 to July 1996. Ten patients were selected randomly from this period after PTCA of an LAD lesion with or without stenting. Nine patients underwent standard CABG on cardiopulmonary bypass with a left internal mammary artery. Nine patients received MICABG via a limited left anterior thoracotomy and left internal mammary artery to LAD grafting without the use of cardiopulmonary bypass. RESULTS: Percutaneous transluminal coronary angioplasty (n = 10) was unsuccessful in two patients. One patient in the MICABG group (n = 9) was converted successfully to conventional CABG because of an intramyocardial LAD and dilated left ventricle. There was no operative morbidity or mortality in any group. Average length of stay postprocedure was decreased significantly for both the MICABG and PTCA groups when compared with that of conventional CABG (n = 9) (2.7 + 0.26, p = 0.009, and 2.6 + 0.54, p = 0.006, vs. 4.8 + 0.46, respectively). Total hospital costs for the MICABG and PTCA groups were significantly less when compared with those of standard CABG ($10,129 + 1104, p = 0.0028, and $9113 + 3,039, p = 0.0001, vs. $17,816 + 1043, respectively). There were no statistically significant differences between the MICABG and PTCA groups. CONCLUSIONS: The final role of minimally invasive CABG is unclear. This procedure is clearly cost effective when compared with that of PTCA and conventional CABG. The long-term patency rates for MICABG will determine its overall efficacy.

Intravenous phenylephrine preconditioning of cardiac grafts from non-heart-beating donors.

BACKGROUND: Hypoxia and warm ischemia produce severe injury to cardiac grafts harvested from non-heartbeating donors. To potentially improve recovery of such grafts, we studied the effects of intravenous phenylephrine preconditioning. METHODS: Thirty-seven blood-perfused rabbit hearts were studied. Three groups of non-heart-beating donors underwent intravenous treatment with phenylephrine at 12.5 (n = 8), 25 (n = 7), or 50 microg/kg (n = 7) before initiation of apnea. Non-heart-beating controls (n = 8) received saline vehicle. Hypoxic cardiac arrest occurred after 6 to 12 minutes of apnea, followed by 20 minutes of warm in vivo ischemia. A 45-minute period of ex vivo reperfusion ensued. Nonischemic controls (n = 7) were perfused without antecedent hypoxia or ischemia. RESULTS: Phenylephrine 25 microg/kg significantly delayed the onset of hypoxic cardiac arrest compared with saline controls (9.6 +/- 0.5 versus 7.7 +/- 0.4 minutes; p = 0.00001), yet improved recovery of left ventricular developed pressure compared with saline controls (57.1 +/- 5.3 versus 41.0 +/- 3.4 mm Hg; p = 0.04). Phenylephrine 25 microg/kg also yielded a trend toward less myocardial edema than saline vehicle (p = 0.09). CONCLUSIONS: Functional recovery of nonbeating cardiac grafts is improved by preconditioning. We provide evidence that the myocardium can be preconditioned with phenylephrine against hypoxic cardiac arrest.

Low-dose sodium nitroprusside reduces pulmonary reperfusion injury.

BACKGROUND: Reperfusion injury is a significant cause of early allograft dysfunction after lung transplantation. We hypothesized that direct pulmonary arterial infusion of an intravascular nitric oxide donor, sodium nitroprusside (SNP), would ameliorate pulmonary reperfusion injury more effectively than inhaled nitric oxide without causing profound systemic hypotension. METHODS: Using an isolated, ventilated, whole-blood-perfused rabbit lung model, we studied the effects of both inhaled and intravascular nitric oxide during lung reperfusion. Group I (control) lungs (New Zealand White rabbits, 3 to 3.5 kg) were harvested en bloc, flushed with Euro-Collins solution, and then stored inflated for 18 hours at 4 degrees C. Lungs were then reperfused with whole blood and ventilated with 60% oxygen for 30 minutes. Groups II, III, and IV received pulmonary arterial infusions of SNP at 0.2, 1.0, and 5.0 micrograms.kg-1.min-1, respectively, whereas group V was ventilated with 60% oxygen and nitric oxide at 80 ppm during reperfusion. RESULTS: Pulmonary arterial infusions of SNP even at 0.2 microgram.kg-1.min-1 (group II) showed significant improvements in pulmonary artery pressure (31.35 +/- 0.8 versus 40.37 +/- 3.3 mm Hg; p < 0.05) and pulmonary vascular resistance (38,946 +/- 1,269 versus 52,727 +/- 3,421 dynes.s/cm-5; p < 0.05) when compared with control (group I) lungs after 30 minutes of reperfusion. Infusions of SNP at 1.0 microgram.kg-1.min-1 (group III) showed additional significant improvements in dynamic airway compliance (1.98 +/- 0.10 versus 1.46 +/- 0.02 mL/mm Hg; p < 0.05), venous-arterial oxygenation gradient (116.00 +/- 24.4 versus 34.43 +/- 2.5 mm Hg; p < 0.05), and wet-to-dry ratio (6.9 +/- 0.9 versus 9.1 +/- 2.2; p < 0.05) when compared with control (group I) lungs. Lungs that received inhaled nitric oxide at 80 ppm (group V) were significantly more compliant (1.82 +/- 0.13 versus 1.46 +/- 0.02 mL/mm Hg; p < 0.05) than control (group I) lungs. CONCLUSIONS: Pulmonary arterial infusion of low-dose SNP during lung reperfusion significantly improves pulmonary hemodynamics, oxygenation, compliance, and edema formation. These effects were achieved at doses of SNP that did not cause profound systemic hypotension. Direct intravascular infusion of SNP via pulmonary arterial catheters could potentially abate reperfusion injury immediately after allograft implantation.

Electrospray sample preparation for improved quantitation in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

The goal of this work is the development of a rapid and objective matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) method for the quantitation of peptides and proteins in human plasma suitable for use in the Good Laboratory Practices (GLP) environment, where the analytical method, validation and pharmacokinetic parameters derived from concentration data will be scrutinized by global regulatory agencies. Electrospray deposition has traditionally been used to prepare thin, uniform samples for a number of techniques, including Cf-252 plasma desorption and secondary ion mass spectrometry. Here the electrospray process of sample application is used to reduce the segregation of analyte from matrix during the sample drying step. The small droplets formed during the electrospray process are found to significantly improve the homogeneity of the sample surface prepared. Experiments comparing the traditional air dried and electrosprayed methods of sample preparation show that the increase in sample homogeneity from electrosprayed samples decreases both the within-sample spot and between-sample spot variability, resulting in a decrease in percent coefficient of variation (%CV) for the recorded MALDI mass spectra. The increase in sample homogeneity permits a more objective use of MALDI-TOFMS as a quantitative analytical method and has led to the development of an assay for the determination of desamino-[8-D-arginine] vasopressin (DDAVP) using arginine vasopressin (AVP) as internal standard in human plasma. The range of quantitation observed (2.0-10 micrograms/mL) is of limited value for bioanalytical application; however, the analysis of neat standards shows lower quantitation limits are easily achieved.