Prospective, randomized trial comparing blood and oxygenated crystalloid cardioplegia in reoperative coronary artery bypass grafting.

OBJECTIVES: Reoperative coronary artery bypass grafting presents unique challenges for myocardial preservation. The purpose of this study was to compare oxygenated blood cardioplegia with oxygenated crystalloid cardioplegia during reoperative coronary artery bypass grafting using transesophageal echocardiography to assess regional wall motion of the left ventricle before and after cardiopulmonary bypass. METHODS: Sixty-one patients undergoing reoperative coronary artery bypass grafting were prospectively randomized to receive oxygenated blood cardioplegia or oxygenated crystalloid cardioplegia delivered with a combined antegrade-retrograde technique. Transgastric short axis views of the left ventricle were made with transesophageal echocardiography during the operation before cardiopulmonary bypass and immediately after cardiopulmonary bypass. Regional wall motion was graded by a blinded observer, and before cardiopulmonary bypass scores were compared with after cardiopulmonary bypass scores. RESULTS: No significant differences were found in the change in regional wall motion score from before cardiopulmonary bypass to after cardiopulmonary bypass between the blood and crystalloid cardioplegia groups. CONCLUSIONS: This study found blood and crystalloid cardioplegia to be equally efficacious for myocardial preservation during reoperative coronary artery bypass grafting.

Should the freehand allograft be abandoned as a reliable alternative for aortic valve replacement?

Cryopreserved aortic allografts were used for aortic valve replacement in 80 patients between 1986 and 1994 (infracoronary in 46 and complete root replacement in 34). Hospital mortality was 6.3% (5/80) with all deaths occurring in the infracoronary group. Three of five deaths were in patients with endocarditis and valve ring abscess. Left ventricular-aortic mean pressure gradients across the allograft valves were significantly lower for root replacement patients (mean, 9.0 +/- 6.9 mm Hg versus 18.1 +/- 8.7 mm Hg for infracoronary patients) (p = 0.0001). No patient having root allograft replacement had early echocardiographic aortic insufficiency greater than grade 1 versus 28% of those having infracoronary implantations. Late aortic insufficiency of grade 2 or greater was seen in 46% of patients having infracoronary implantation versus 17% of patients having root implantation. Nine patients had explantation of an aortic allograft (eight infracoronary and one root). Reasons for explantation were as follows: endocarditis (three infracoronary, one root), technical (three infracoronary), undiagnosed idiopathic hypertrophic subaortic stenosis (1 patient), and prolapsing infracoronary leaflet (1 patient). Actuarial freedom from grade 3 and 4 aortic insufficiency or explantation was 77% at 7 years for infracoronary implantations. We conclude that the infracoronary aortic allograft has an unacceptable frequency of late insufficiency and its use in this position should be abandoned. The substantial incidence of late endocarditis in the infracoronary (free-hand) aortic allograft was surprising.(ABSTRACT TRUNCATED AT 250 WORDS)

Interleukin 1 regulates secretion of zinc-thymulin by human thymic epithelial cells and its action on T-lymphocyte proliferation and nuclear protein kinase C.

Thymic epithelial cells (TEC) are known to secrete thymic hormones that influence maturation of T lymphocytes. One of these peptides, thymulin, requires zinc in an equimolar ratio for biological activity. A previous study [Cousins, R. J. & Leinart, A. S. (1988) FASEB J. 2, 2884-2890] showed that interleukin 1 (IL-1) in vivo stimulates zinc uptake by the thymus. Both the alpha and beta forms of IL-1, which stimulate proliferation of human TEC, also stimulate their uptake of zinc in vitro, and this latter stimulation is both dependent and independent of proliferation. Zinc induces zinc accumulation without proliferation. Two other stimulants of proliferation, bovine pituitary extract and epidermal growth factor, stimulate zinc uptake by TEC, but only in a manner dependent on proliferation. Utilizing in situ hybridization, we show that the IL-1 alpha and beta forms and zinc induce metallothionein mRNA expression TEC. Metallothionein is thought to be involved in the transfer of zinc to thymulin. IL-1 was shown to stimulate the secretion of thymulin as measured both by its ability to stimulate induction of IL-2 receptor-positive lymphocytes from human peripheral blood lymphocytes and by the azathioprine-sensitive rosette assay. In addition, the zinc-thymulin complex in the presence, but not absence, of IL-1 stimulates nuclear protein kinase C in isolated lymphocyte nuclei. IL-1 apparently regulates the synthesis or secretion and delivery of zinc-thymulin complex to the T-lymphocyte system.

Effect of endotoxin to differentially affect cytochrome P-450 monooxygenase activities of untreated rats and animals induced with phenobarbital or 3-methylcholanthrene.

The effect of endotoxin in decreasing the cytochrome P-450-dependent metabolism of aniline, aminopyrine and ethoxycoumarin was examined in untreated rats, and in rats pretreated with either phenobarbital or 3-methylcholanthrene. Ethoxycoumarin metabolism was determined at two substrate concentrations (5 microM and 500 microM) to determine the effect of endotoxin on the high and low affinity enzyme activities. In untreated animals, endotoxin depressed both aniline and ethoxycoumarin metabolism by the high and low affinity enzymes by approximately 70%, but aminopyrine was decreased by only 47%. In phenobarbital pretreated rats, endotoxin decreased enzyme activities less than in untreated animals. Aniline metabolism and low affinity ethoxycoumarin metabolism were decreased by only 24%, and aminopyrine metabolism was decreased by 35%. The high affinity ethoxycoumarin metabolism was least affected, being decreased by only 12%. In 3-methycholanthrene pretreated rats, aniline and ethoxycoumarin (500 microM) metabolism were decreased by approximately 45%, but aminopyrine metabolism was only decreased by 20%. In these animals, endotoxin did not significantly affect the activity of ethoxycoumarin metabolism assayed with the low substrate concentration. Endotoxin decreased total cytochrome P-450 level of untreated rats by 32%, of phenobarbital pretreated rats by 39%, and in 3-methylcholanthrene pretreated animals the decrease was only 21%. Heme oxygenase activity of untreated animals was induced most by endotoxin administration and least in phenobarbital treated rats. The data suggest that endotoxin may differentially affect the various isozymes of cytochrome P-450 associated with the metabolism of aniline, aminopyrine and ethoxycoumarin. The results also suggest that the isozymes associated with these activities in untreated, phenobarbital or 3-methylcholanthrene pretreated rats may differ in their sensitivity to the effect of endotoxin.