Aprotinin improves myocardial recovery after ischemia and reperfusion Effects of the drug on isolated rat heartsThe effects of aprotinin, a protease inhibitor, on the ischemic and nonischemic isolated rat heart was investigated with the use of the modified Langendorlf model. During phase I of the study, hearts were perfused with either low-dose aprotinin (10 5 Kill/L), high-dose aprotinin (10 6 KIU /L), or normal saline solution added to modified Krebs-Henseleit solution. No statistically significant differences in contraction amplitude, contractility, coronary flow, and wet/dry heart weight ratio were observed among the three groups of hearts. In phase II, hearts were exposed to a 40-minute period of global ischemia at 31 0 C. Ischemic arrest was induced by warm cardioplegia. Before ischemia and during cardioplegia, hearts were perfused with either aprotinin 10 6 KIU/L (n = 10) or normal saline solution (n = 10) for .30 minutes. On reperfusion, recovery of hearts treated with aprotinin was significantly better than that of control hearts, as reflected by better contractility (analysis of variance, p = 0.011), higher coronary flow (p < 0.025), and lower creatine kinase levels (p <0.05). No statistically significant differences in contraction amplitude were observed between the two groups. When the effect of ischemia within each group of hearts was analyzed, the preserving effect of aprotinin was even more pronounced. In the control group, ischemia caused a decrease in contractility (p < 0.025) and a decrease in oxygen consumption (p = 0.006); by contrast, in the aprotinin group the preischemic values were maintained. Accordingly, we conclude that aprotinin at concentrations up to 10 6 KIU /L has no deleterious effect on normally perfused hearts and has a significant protective effect on the ischemic heart when used in high doses in the preischemic period. (J THoRAe CARDIOVASC SURG 1994;108:109-18)
A comprehensive analysis of the reporting of adverse events, withdrawals due to adverse events, and serious adverse events has been conducted on 2,010 patients treated with quinapril hydrochloride. An analysis of all events (from both double-blind and open label studies combined) showed no increase in the incidence of events reported in congestive heart failure (CHF) patients compared to hypertensive patients. When the data for all studies were combined, an age analysis showed no increase in the total reporting of adverse events in the 379 elderly patients studied. The incidence of events was lower in those patients who did not take concomitant diuretic therapy. A comparison of the double-blind phases showed quinapril to have a lower incidence of adverse events than captopril, enalapril, or chlorthalidone. An analysis of the onset of events, or withdrawals, did not show an increase with time on quinapril therapy, and no dose-relationship. A review of serious adverse events did not reveal an unexpected occurrence or a high incidence of serious events considered to be related to quinapril therapy. The proportion of patients who experienced "first-dose" hypotension, or symptomatic hypotension was similar to captopril or enalapril. Quinapril, a nonsulfhydryl ACE inhibitor, has been extensively studied and is equally well tolerated in the young and elderly for the treatment of hypertension and CHF.
Patients who undergo surgical repair of congenital heart defects, characterized by a hypoplastic right ventricle or high pulmonary vascular resistance, are at high risk for the development of postoperative right heart failure. This risk may discourage the surgical team from carrying out a biventricular or complete repair in such patients. To reduce the risk for right heart failure, we developed a one-way, valved, atrial septal patch to serve as an artificial one-way foramen ovale and tested it in an animal model. By permitting right-to-left shunt, this device decompresses the failing right ventricle and maintains systemic cardiac output. The device has been used in 15 patients divided into three different groups: group 1 (n = 8), patients with a hypoplastic right ventricle and pulmonic stenosis or atresia, seven of whom underwent a biventricular repair; group 2 (n = 5), patients with evidence of pulmonary disease after longstanding left-to-right shunt caused by a correctable atrial or ventricular septal defect, all of whom had a complete repair; group 3, two patients with acute right heart failure in whom the device was used as a last option of treatment to wean them from cardiopulmonary bypass. This article presents our data in regard to the use of the one-way, valved, atrial septal patch and the indications for its clinical use.
The effects of vitamin D depriva tion on the chick heart were investi gated from three aspects: cardiac contractility (±dP/dT), intracellular high-energy phosphorus compounds, and structural differences. Four- week-old vitamin D-deficient chicks were divided into four groups: Group A served as the normal group and re ceived subcutaneous injections of cholecalciferol; Groups B and C were vitamin D-deficient hearts but per fused differently; Group D received daily subcutaneous injections of 5 μg of 1,25(OH) 2D3. When the isolated spontaneously beating hearts (modi fied Langendorff preparation) were perfused with Krebs-Henseleit (KH) solution containing a calcium concen tration of 2.5mM, the myocardial contractility of the vitamin D-defi cient hearts was significantly in creased when compared with group A. After the isolated heart had beaten for one hour, the myocardial contractility in the vitamin D-defi cient hearts was found to decline to significantly lower values. Presacri fice administration of 1,25(OH) 2D3 improved cardiac performance. Vita min D deficiency resulted in an en hanced rate of decline of the intracellular high-energy phosphorus compounds. No differences were found in the microscopic study. These observations suggest that vitamin D has a role in cardiac function.
The present study compared the phosphorylation rate of 3'-azidothymidine (AZT) in isolated maternal and fetal peripheral blood mononuclear cells (PBMCs) with that in amniocytes obtained during gestation and at term. Maternal PBMCs were isolated from venous blood samples obtained from HIV-seronegative pregnant women during delivery. Immediately after delivery, cord blood specimens were collected, and fetal PBMCs were isolated. In a separate set of experiments, maternal and fetal PBMCs and amniocytes were obtained at 17-21 weeks of gestation. The fresh isolated PBMCs and amniocytes were maintained in RPMI 1640 medium until incubation with 10 microM tritiated AZT (10 microCi/mL). Thereafter, methanolic cell extracts were prepared for determination of AZT phosphates by high-performance liquid chromatography. Fetal PBMCs can efficiently convert AZT to its antivirally active metabolite. There were no significant differences after 6 or 12 hours of incubation with AZT between AZT phosphate levels in maternal and fetal PBMCs isolated at term or at 17-21 weeks of gestation: AZT monophosphate was found to be the major metabolite (about 95%). AZT phosphate levels in the amniocytes were up to sevenfold higher than those in the maternal or fetal PBMCs. These results show that during pregnancy and at term, fetal PBMCs-like maternal PBMCs-are able to take up AZT and to efficiently generate the active metabolite AZT triphosphate. These results are of major significance both in enabling efficient treatment of the fetuses of HIV-infected women and in the prediction and understanding of the efficacy and toxicity of AZT in pregnant women and their fetuses.
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