Cross-species and tissue variations in cyanide detoxification rates in rodents and non-human primates on protein-restricted diet.

We sought to elucidate the impact of diet, cyanide or cyanate exposure on mammalian cyanide detoxification capabilities (CDC). Male rats (~8 weeks old) (N=52) on 75% sulfur amino acid (SAA)-deficient diet were treated with NaCN (2.5mg/kg bw) or NaOCN (50mg/kg bw) for 6 weeks. Macaca fascicularis monkeys (~12 years old) (N=12) were exclusively fed cassava for 5 weeks. CDC was assessed in plasma, or spinal cord, or brain. In rats, NaCN induced seizures under SAA-restricted diet whereas NaOCN induced motor deficits. No deficits were observed in non-human primates. Under normal diet, the CDC were up to ~80× faster in the nervous system (14 ms to produce one µmol of thiocyanate from the detoxification of cyanide) relative to plasma. Spinal cord CDC was impaired by NaCN, NaOCN, or SAA deficiency. In M. fascicularis, plasma CDC changed proportionally to total proteins (r=0.43; p<0.001). The plasma CDC was ~2× relative to that of rodents. The nervous system susceptibility to cyanide may result from a "multiple hit" by the toxicity of cyanide or its cyanate metabolite, the influences of dietary deficiencies, and the tissue variations in CDC. Chronic dietary reliance on cassava may cause metabolic derangement including poor CDC.

Memory deficits associated with sublethal cyanide poisoning relative to cyanate toxicity in rodents.

Food (cassava) linamarin is metabolized into neurotoxicants cyanide and cyanate, metabolites of which we sought to elucidate the differential toxicity effects on memory. Young 6-8 weeks old male rats were treated intraperitoneally with either 2.5 mg/kg body weight (bw) cyanide (NaCN), or 50 mg/kg bw cyanate (NaOCN), or 1 µl/g bw saline, daily for 6 weeks. Short-term and long-term memories were assessed using a radial arm maze (RAM) testing paradigm. Toxic exposures had an influence on short-term working memory with fewer correct arm entries (F(2, 19) = 4.57 p < 0.05), higher working memory errors (WME) (F(2, 19) = 5.09, p < 0.05) and longer RAM navigation time (F(2, 19) = 3.91, p < 0.05) for NaOCN relative to NaCN and saline treatments. The long-term working memory was significantly impaired by cyanide with fewer correct arm entries (F(2, 19) = 7.45, p < 0.01) and increased working memory errors (F(2, 19) = 9.35 p < 0.05) in NaCN relative to NaOCN or vehicle treated animals. Reference memory was not affected by either cyanide or cyanate. Our study findings provide an experimental evidence for the biological plausibility that cassava cyanogens may induce cognition deficits. Differential patterns of memory deficits may reflect the differences in toxicity mechanisms of NaOCN relative to NaCN. Cognition deficits associated with cassava cyanogenesis may reflect a dual toxicity effect of cyanide and cyanate.

Age dependency in the timing of mitral annular motion in relation to ventricular filling in healthy subjects: Umea General Population Heart Study.

AIMS: Peak left ventricular (LV) relaxation normally precedes peak filling (E), which supports the hypothesis that LV suction contributes to early-diastolic filling. The significance of similar temporal discordance in late diastole has previously not been studied. We describe the time relationships between mitral annular motion and LV filling in early and late diastole and examine the effect of normal ageing on these time intervals. METHODS AND RESULTS: A total of 128 healthy subjects aged 25-88 years were studied. Transmitral and pulmonary venous flow reversals (Ar) were recorded by Doppler echocardiography. Mitral annular diastolic displacement-early (E(m)) and late (A(m))-were recorded by Doppler tissue imaging. With reference to electrocardiographic R and P-waves, the following measurements were made: R to peak E-wave (R-E) and E(m) (R-E(m)); onset P to peak A-wave (P-pA), A(m) (P-pA(m)), and Ar (P-pAr). The differences between [(R-E) and (R-E(m))] for early-diastolic temporal discordance (EDTD) and [(P-A) and (P-A(m))] for late-diastolic temporal discordance (LDTD) were calculated. Isovolumic relaxation time (IVRT) was also measured. Early-diastolic temporal discordance was approximately 26 ms in all age groups. Late-diastolic temporal discordance, however, was inversely related to age (r = -0.35, P < 0.001) and IVRT (r = -0.34, P < 0.001) and therefore decreased in the elderly vs. young (13 +/- 10 vs. 23 +/- 10 ms; P < 0.001). In multivariate analysis, age failed to predict LDTD in the presence of IVRT. A, A(m), and Ar were simultaneous at onset, and peak A(m) coincided with peak Ar in all age groups (r = 0.97, P < 0.001). No significant differences were noted in the RR intervals. CONCLUSIONS: Sequential prolongation of IVRT with ageing reduces LDTD, thus converging the peaks of A(m), A, and Ar (atrial mechanical alignment)-a potential novel method to identify subjects at increased dependency on atrial contraction for late-diastolic filling.

RETRACTED: Age dependency in the timing of mitral annular motion in relation to ventricular filling in healthy subjects - A pulsed and tissue Doppler study.

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Pulmonary venous flow reversal and its relationship to atrial mechanical function in normal subjects--Umeå General Population Heart Study.

AIMS: Although pulmonary venous flow reversal (Ar) is useful in the evaluation of left ventricular (LV) diastolic function, it is often difficult to study with transthoracic echocardiography (TTE). We determined the relationship between Ar and left atrial (LA) mechanical function and sought to define surrogate measurements for Ar. METHODS AND RESULTS: A total of 130 healthy subjects, mean age 54.3+/-18.3 years, 62 women, were studied and classified into three groups: [young (Y), 25-44 years; n=44], [middle-age (M), 45-64 years; n=43] and [elderly (E), > or =65 years; n=43]. Pulmonary venous flow and LV inflow studies were performed by TTE and LV basal free-wall motion was studied by Doppler tissue imaging (DTI). All images were acquired with a superimposed electrocardiogram. RR interval was similar in all groups while LA dimension and PR interval were increased in Group E vs. Y (P<0.001). LA contraction (A(m)) on DTI, transmitral A-wave (A) and Ar were simultaneous and started 84ms after onset of P wave and this interval increased with age (P=0.02). Similarly, the time intervals from the same landmark to peak A(m), A, and Ar were prolonged with age (all, P<0.001). Despite this prolongation, peak A(m) coincided with peak Ar in every age group (r=0.97, P<0.001) and Ar acceleration and deceleration times were consistently equal. CONCLUSION: The timing of A(m) obtained by DTI can be used to accurately estimate corresponding measurements of Ar recorded by TTE in subjects without cardiac disease.

Clinical outcome of coronary angioplasty in patients with ischaemic cardiomyopathy.

OBJECTIVE: To assess the clinical outcome of successful percutaneous transluminal coronary angioplasty (PTCA) in patients with poor ventricular function. METHODS: Analysis of angiographic, echocardiographic and clinical records of patients with severe LV dysfunction who underwent PTCA from January 1, 1995 to December 31, 1997 was undertaken. Forty-one patients aged 63+/-10 years, 36 men, all with significant coronary artery disease and impaired LV function (fractional shortening, FS