Functional and metabolic effects of bupivacaine and lidocaine in the perfused working rat heart

The effects of bupivacaine (2.5, 5, 10, and 12.5 mg/L) and lidocaine (12.5, 25, 40, and 50 mg/L), on spontaneous heart rate, mean pressure development, cardiac output, and coronary flow were compared after 15 minutes' exposure in the isolated perfused working rat heart preparation. In addition, myocardial oxygen consumption, glucose utilization, lactate production, tissue content of glycogen, adenine nucleotides, and creatine phosphate content were measured. The relative potency of bupivacaine to lidocaine, calculated from slopes of regression equations, as indicated by the four mechanical variables and oxygen consumption, was 4.59. When the bupivacaine concentration was "normalized" using this value, bupivacaine and lidocaine showed indistinguishable effects on glucose utilization, lactate production, and tissue glycogen. Neither of the local anesthetics had any influence on energy charge or creatine phosphate content.     

Homozygosity mapping of achromatopsia to chromosome 2 using DNA pooling

Achromatopsia is an autosomal recessive disease of the retina, characterized clinically by an inability to distinguish colors, impaired visual acuity, nystagmus and photophobia. A genome-wide search for linkage was performed using an inbred Jewish kindred from Iran. To facilitate the genome-wide search, we utilized a DNA pooling strategy which takes advantage of the likelihood that the disease in this inbred kindred is inherited by all affected individuals from a common founder. Equal molar amounts of DNA from all affected individuals were pooled and used as the PCR template for short tandem repeat polymorphic markers (STRPs). Pooled DNA from unaffected members of the kindred was used as a control. A reduction in the number of alleles in the affected versus control pool was observed at several loci. Upon genotyping of individual family members, significant linkage was established between the disease phenotype and markers localized on chromosome 2. The highest LOD score observed was 5.4 (theta = 0). When four additional small unrelated families were genotyped, the combined peak LOD score was 8.2. Analysis of recombinant chromosomes revealed that the disease gene lies within a 30 cM interval which spans the centromere. Additional fine-mapping studies identified a region of homozygosity in all affected individuals, narrowing the region to 14 cM. A candidate gene for achromatopsia was excluded from this disease interval by radiation hybrid mapping. Linkage of achromatopsia to chromosome 2 is an essential first step in the identification of the disease-causing gene.      

Serum levels of IL-1, IL-6 and tumour necrosis factors in patients undergoing coronary artery bypass grafts or cholecystectomy.

Plasma levels of biologically active IL-1, tumour necrosis factor (TNF) and IL-6 were measured before, during and after coronary artery bypass graftings (CABG) (n = 9) and cholecystectomy (CHO, n = 9), and in normal controls (nine healthy volunteers). Mean pre-operative IL-1 concentration in four of the nine CABG patients was 0.452 + 0.03 ng/ml, significantly (P less than 0.001) higher than that of the other five (0.045 +/- 0.009 ng/ml), CHO patients (0.035 +/- 0.005 ng/ml) and controls (0.029 +/- 0.008 ng/ml). Three of the four patients with high pre-operative IL-1 had functional capacity IV, while the other five had functional capacity IIa or IIb. Slight IL-1 elevation after anaesthesia, followed by reduction after initiation of bypass, elevation on completion of surgery and reduction to basal levels after 7 days was found in patients undergoing CABG. Mean basal TNF levels of CABG and CHO patients did not differ, but were higher than those of controls (2.85 +/- 0.5 ng/ml for CABG, 2.05 +/- 0.06 ng/ml for CHO, 0.72 +/- 0.07 ng/ml for normals, P less than 0.001). A unique kinetics of release during CABG was observed also for TNF. Mean pre-operative IL-6 levels were normal (50 +/- 3 ng/ml for CABG, 50 +/- 0.5 ng/ml for CHO and 65 +/- 10 ng/ml for controls). Gradual elevation to a mean peak of 725 +/- 100 ng/ml on completion of CABG was observed as compared with 275 +/- 50 ng/ml in CHO (P less than 0.01). On the seventh post-operative day mean IL-6 levels returned to normal. Two patients with post-operative low-grade fever (38 degrees C) had high, late cytokine levels. One of these two patients had leucocytosis, sterile discharge from the operative wound and was diagnosed as suffering from the Dressler syndrome. In this study elevated cytokine values and unique kinetics of release into the serum were found in patients undergoing CABG.     

Variability of Stickler syndrome.

Stickler syndrome is a dominantly inherited disorder characterized by ocular and nonocular manifestations. The phenotype of the affected patients is known to be variable. Our study of 3 families and a review of the literature show that the variability is mostly interfamilial while in each family less variability is present. In one family all the patients had high myopia and most developed a retinal detachment at a young age. In the second family the major symptoms were cleft palate and characteristic facial changes in presence of mild ocular changes. In the third family, all patients had a marfanoid habitus, high myopia, and mental retardation. Interfamilial variability coupled with intrafamilial similarities in clinical manifestation may indicate that the so-called Stickler syndrome represents in fact a phenotype and not a single genetic entity.     

Frequency and significance of complete atrioventricular block after coronary artery bypass grafting

Three hundred forty-eight consecutive patients were evaluated during 1985 and 1986 for the development of complete atrioventricular (AV) block after coronary artery bypass grafting. Cold (4 degrees) asanguineous potassium cardioplegia with temperature monitoring was used uniformly. AV block developed in 56 instances (16%). In 32 patients (group 1) the block was transient (less than 6 hours) and in 24 it was persistent (group 2). Left main coronary artery stenosis in conjunction with total obstruction of a dominant right coronary artery occurred more commonly in patients manifesting AV block (18 of 56, 32%) than in those without it (35 of 292, 12%) (p less than 0.05). Complete occlusion of a dominant right coronary artery was observed with equal frequency in patients with and without AV block. The presence of an ungraftable right coronary artery, however, was significantly more frequent in the AV block group: 16 of 37 (47%) vs 6 of 194 (3%) (p less than 0.01). Endarterectomy of the right coronary artery was performed in 8 of 24 patients (33%) with persistent AV block versus none in the patients with transient AV block (n = 32) or normal sinus rhythm postoperatively (n = 292) (p less than 0.0001). Persistent AV block (greater than 6 hours) was associated with myocardial infarction in 6 patients (25%) (p less than 0.05) and with low cardiac output in 18 patients (75%) (p less than 0.0001). In conclusion, AV block after myocardial revascularization was frequently associated with the presence of multivessel coronary disease and an ungraftable dominant right coronary artery. Persistent (greater than 6 hours) AV block was correlated with both perioperative myocardial infarction and low cardiac output.