Adrenomedullin (ADM) is a vasoactive peptide with potent dilatory effects. We studied whether perioperative myocardial injury could be altered by the presence of ADM. Blood samples from 19 children with congenital heart disease undergoing surgical repair were collected at six time points: preoperative, on cardiopulmonary bypass (CPB), and 0, 3, 6, and 12 hours after CPB. Blood levels of ADM (pg/ml) and troponin-I (Tn-I; ng/ml), a specific marker of myocardial injury, were measured. Patients were divided into three groups based on their 12-hour Tn-I levels (I, < 10, n = 6; II, 10-25, n = 6; III, >25, n = 7). Preoperative Tn-I levels were within the normal range for all patients. Preoperative ADM levels in group I (with little or no evidence of myocardial injury) were significantly greater than those of either group II or III (242.7 +/- 15.4 vs 83.8 +/- 18 and 85.2 +/- 5.5, respectively; p < or = 0.0001 for each). The 12-hour ADM levels in group I remained significantly lower than preoperative levels (242.7 +/- 15.4 vs 197.4 +/- 11.6, p < or = 0.03) but higher than in the other groups. In group III, ADM increased at the 12-hour time point (159.2 +/- 6.5, p < or = 0.0001 vs baseline). Higher preoperative ADM levels are associated with lower levels of myocardial injury (as assessed by troponin-I release) during congenital heart surgery.

Adrenomedullin↗

PubMedDate not supplied

In vitro and in vivo susceptibility of atypical mycobacteria to various drugs.

In vitro sensitivities to various drugs of a total of 106 strains of atypical mycobacteria were studied in modified Dubos Tween albumin liquid medium. Eight triple-drug combinations of antituberculous drugs were also evaluated in vitro for their potentiated activities. Minimal to moderate potentiation was demonstrated in the majority of the combination. From the results, the triple-drug combination--including rifampin, one of three aminoglycosides (streptomycin, kanamycin, viomycin), and either ethionamide or ethambutol--might be recommended for Mycobacterium kansasii infections. Against Mycobacterium avium-intracellulare infections, rifampin-kanamycin-ethionamide or rifampin-kanamycin-ethambutol might be the choice if we were to select any triple-drug regimen. None of the triple-drug regimens thus far tested on M. avium-intracellulare were active enough to recommend fully for clinical use. In vivo experimental chemotherapy of murine infection with Mycobacterium intracellulare (TMC 1469) on a five-drug regimen, kanamycin-rifampin-cycloserine-ethambutol-ethionamide, showed a moderate therapeutic effect but the infection was not eradicated.

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PubMedDate not supplied

Fasting plus prandial insulin supplements improve insulin secretory ability in NIDDM subjects.

To examine how insulin secretory ability is modified by strict glycemic control in non-insulin-dependent diabetes mellitus (NIDDM) subjects, basal and/or prandial insulin was supplemented for 4 wk in 24 diabetic subjects who were secondary failures to sulfonylurea treatment. One intermediate-acting insulin injection a day (n = 7) failed to suppress the rise in plasma C-peptide after meals and did not improve plasma C-peptide responses during a posttreatment oral glucose challenge. Continuous subcutaneous insulin infusion with a premeal bolus (n = 8) suppressed both fasting and meal-related rises in C-peptide and improved C-peptide response during the posttreatment oral glucose challenge. Daily insulin requirements during the 4 wk of treatment were reduced significantly by 52%. A short-acting insulin injection before each meal (n = 9) without basal supplementation suppressed the prandial rise in C-peptide and was associated with a significant reduction in daily insulin requirements during 4 wk of treatment by 28%. Diabetic subjects whose fasting and prandial hyperglycemia were less than 140 and less than 200 mg/dl, respectively, showed a significantly higher C-peptide response during oral glucose challenge after treatment than those whose insulin treatment only normalized (less than 200 mg/dl) prandial but not basal hyperglycemia (greater than 140 mg/dl). These results suggest that a short-term period of meal-related insulin treatment (which normalized prandial glycemia) increases residual beta-cell function in NIDDM subjects who failed long-term sulfonylurea administration. A basal insulin supplement alone was not effective. The effectiveness of a prandial insulin supplement may have been further improved by a combined basal and meal-related treatment program.

Acetohexamide↗

PubMedDate not supplied

Coronary blood flow does not decrease during allograft rejection in heterotopic heart transplants.

To evaluate changes in coronary blood flow during allograft rejection, 16 beagles with cervical cardiac allografts from mongrel donors were immunosuppressed postoperatively for 7 days with cyclosporine (20 mg/kg orally) and prednisone (0.5 mg/kg orally). They were weaned from immunosuppression over 3 days and then treated with methylprednisolone (30 mg/kg/day IV), cyclosporine (20 mg/kg orally), and prednisone (0.5 mg/kg orally) for 4 days. Previous experiments with this model have suggested the utility of phosphorus 31 nuclear magnetic resonance spectroscopy (31P NMR) in the diagnosis of rejection. Therefore in 10 dogs (NMR group) bioenergetic changes during rejection were assessed using the 31P NMR index of the ratio of phosphocreatine to inorganic phosphate (PCr/Pi). To correlate coronary blood flow and graft ischemia with allograft rejection, six dogs (FLOW group) underwent placement of a magnetic flow probe on the left anterior descending coronary artery to determine mean and peak coronary flow. In both NMR and FLOW groups, grafts were evaluated by endomyocardial biopsy (grading 0 to 8 for increasing rejection), and measurement of lactate production and left ventricular end-diastolic pressure. During the initial 7 days of immunotherapy, cellular rejection was effectively suppressed, and the bioenergetic status of the grafts remained stable (day 7: PCr/Pi = 70% of baseline, biopsy score = 2.0). During weaning of immunotherapy, however, the metabolic profile of the grafts decayed (day 10: PCr/Pi = 45% of baseline, biopsy score = 5.8; p less than 0.05 vs day 0). After 4 days of augmented immunosuppression, PCr/Pi recovered to 83% of baseline; this metabolic recovery corresponded with an improvement in mean biopsy score to 3.2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Twelve-hour cardiopulmonary preservation using donor core cooling, leukocyte depletion, and liposomal superoxide dismutase.

Because leukocytes and oxygen radical species contribute to ischemic and reperfusion injury during organ preservation, we examined the effects of a long-acting liposomal superoxide dismutase (liposomal SOD) and mechanical filtration of leukocytes on cardiopulmonary graft function after 12 hours of static preservation. Bovine heart-lung blocks were harvested, core cooled to 15 degrees C, stored in 4 degrees C donor blood for 12 hours, and then orthotopically transplanted (control group, n = 6). In the leukocyte-depletion group (n = 6), a leukocyte filter was incorporated in the bypass circuits of the donor and recipient. In the SOD group (n = 6), liposomal SOD (5000 U/kg) was administered in the cardioplegic solution, in the prime of the bypass circuits of donor and recipient, and immediately before recipient heart-lung reperfusion. In the combination group (n = 6), both leukocyte depletion (LD) and liposomal SOD were used. Only four of six control animals survived more than 2 hours after weaning from bypass, whereas all LD, SOD, and LD + SOD animals survived to be studied at 6 hours. Pulmonary function was assessed at 6 hours by arterial oxygen tension on 100% inspired oxygen (PO2), pulmonary vascular resistance (PVR), and postmortem wet/dry lung weight ratios. Arterial pO2 values (mm Hg) were as follows: control, 102 +/- 51; LD, 437 +/- 60*; SOD, 278 +/- 83; and LD + SOD, 504 +/- 54* (*p less than 0.05 vs controls). PVR values (dynes . sec . cm5) were as follows: control, 1975 +/- 697; LD, 682 +/- 131*; SOD, 607 +/- 191*; and LD + SOD 367 +/- 87* (*p less than 0.05 vs controls).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Extended cardiopulmonary preservation for heart-lung transplantation: a comparative study of superoxide dismutase.

We examined an 8-hour cardiopulmonary preservation technique and the role of free radical-induced injury during cardiopulmonary preservation and transplantation. Hence, donor dogs were placed on cardiopulmonary bypass, rapidly cooled to 15 degrees C, and heterotopic heart-unilateral left lung transplantations were performed. In group 1 (n = 5), hearts and lungs were transplanted immediately after core-cooling and cardioplegic arrest. In groups 2 to 5 (n = 5 in each group), heart-lung blocks were excised and stored at 4 degrees C for 8 hours before transplantation. During preservation hearts were perfused (20 mm Hg) with oxygenated extracellular solution (pH 7.4, 410 m0sm/L) and the lungs immersed in the same solution. In groups 3 through 5 recombinant human superoxide distumase (r,h-SOD, total 40 mg/kg) was administered during either donor cooling, donor preservation, or just before and during reperfusion, respectively. Load independent analysis of myocardial function was assessed by determining the ratio of the end-systolic pressure to end-systolic dimension. Pulmonary preservation was evaluated by determination of extravascular lung water of the implanted left lung, arterial oxygenation on 40% inspired oxygen, and pulmonary vascular resistance. Although arterial oxygenation was similar in each group, pulmonary vascular resistance was increased in groups 2 through 4 after implantation. Furthermore, in groups 2 and 4 impaired myocardial function and increased extravascular lung water were observed. Administration of r,h-SOD, however, just before and during reperfusion significantly enhanced cardiopulmonary preservation. These results indicate that free radical-induced injury is primarily the result of reperfusion. Thus the best time for administration of r,h-SOD is before and during reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗