Sequences of the coat protein gene of five peanut stripe virus (PStV) strains from Thailand and their evolutionary relationship with other bean common mosaic virus sequences.

The coat protein gene and part of the 3' non-coding region of five strains of peanut stripe virus (PStV) from Thailand have been cloned and sequenced. Phylogenetic comparisons of these strains, known as T1, T3, T5, T6 and T7, and related sequences showed that these strains are indeed strains of PStV. Further, PStV strains appear to be related to each other according to their geographic origin. That is, the Thai strains are more closely related to each other than they are to strains from the USA or Indonesia, despite the variety of symptoms caused by these strains and the overlap of symptom types between the strains from different locations. Like other PStV strains, PStV-Thai can be considered strains of bean common mosaic virus (BCMV) but can be distinguished from bean-infecting strains of BCMV and blackeye cowpea mosaic virus (B1CMV) through sequence and host range. No evidence was found that PStV-Thai strains, unlike PStV-Ib, are recombinants of PStV and B1CMV, although the T3 strain may be a recombinant of different PStV sequences. Phylogenetic analyses of viruses of the BCMV group suggest that acquisition of the ability to infect peanut may have occurred only once.

A divergent CFTR homologue: highly regulated salt transport in the euryhaline teleost F. heteroclitus.

The killifish, Fundulus heteroclitus, is a euryhaline teleost fish capable of adapting rapidly to transfer from freshwater (FW) to four times seawater (SW). To investigate osmoregulation at a molecular level, a 5.7-kilobase cDNA homologous to human cystic fibrosis transmembrane conductance regulator (hCFTR) was isolated from a gill cDNA library from SW-adapted killifish. This cDNA encodes a protein product (kfCFTR) that is 59% identical to hCFTR, the most divergent form of CFTR characterized to date. Expression of kfCFTR in Xenopus oocytes generated adenosine 3',5'-cyclic monophosphate-activated, Cl(-)-selective currents similar to those generated by hCFTR. In SW-adapted killifish, kfCFTR was expressed at high levels in the gill, opercular epithelium, and intestine. After abrupt exposure of FW-adapted killifish to SW, kfCFTR expression in the gill increased severalfold, suggesting a role for kfCFTR in salinity adaptation. Under similar conditions, plasma Na+ levels rose significantly after 8 h and then fell, although it is not known whether these changes are directly responsible for the changes in kfCFTR expression. The killifish provides a unique opportunity to understand teleost osmoregulation and the role of CFTR.

Detection of the t(2;5)(p23;q35) and NPM-ALK fusion in non-Hodgkin's lymphoma by two-color fluorescence in situ hybridization.

The non-Hodgkin's lymphoma (NHL) subset commonly referred to as large cell lymphoma (LCL) has historically been characterized by it's marked cytological, immunological, and clinical heterogeneity. One potential defining feature of these lymphomas, the t(2;5)(p23;q35), occurs in 25% to 30% of anaplastic LCLs and is also found in cases with diffuse large cell or immunoblastic morphology. We recently identified nucleophosmin (NPM) and anaplastic lymphoma kinase (ALK) as the genes on chromosomes 5 and 2, respectively, that are juxtaposed by this translocation. To provide a complementary approach to the use of classical cytogenetics or polymerase chain reaction-based methods for the detection of this abnormality, we have developed a two-color fluorescent in situ hybridization (FISH) assay for the t(2;5) that may be used for the analysis of both interphase nuclei and metaphase chromosomes. Three overlapping chromosome 5 cosmid clones located immediately centromeric to the NPM gene locus and an ALK P1 clone located telomeric to the chromosome 2 breakpoint were labeled with digoxigenin or biotin, respectively, and used to visualize the derivative chromosome 5 produced by the t(2;5), evident as juxtaposed or overlapping red and green fluorescent signals. This NPM-ALK FISH assay was initially validated by analysis of a series of cytogenetically characterized cell lines, with the presence of the der(5) chromosome showed specifically only in those lines known to contain the t(2;5). The assay was then applied in a blinded fashion to a series of eight cytogenetically t(2;5)-positive clinical specimens and seven known t(2;5)-negative cases, including three NHL and four Hodgkin's disease biopsy samples. Whereas the t(2;5)-negative cases were negative by FISH, all eight t(2;5)-positive cases were positive. One additional case, initially thought to be positive for the translocation by cytogenetics, was proven to not be a classic t(2;5) by interphase and metaphase FISH. These data indicate that the FISH assay described is a highly specific and rapid test that should prove to be a useful adjunct to the currently available methods for detection of the t(2;5).

Promotion of folate for the prevention of neural tube defects: knowledge and use of periconceptional folic acid supplements in Western Australia, 1992 to 1995.

To assess changes in knowledge and use of folic acid supplements in relation to a statewide health promotion project for the prevention of neural tube defects, we surveyed general practitioners, pharmacists, women of child-bearing age and pregnant women in Western Australia. We also collected data on wholesale sales of folic acid supplements. By the end of the project, 56.5 per cent of general practitioner respondents knew that the recommended dose of folic acid was 0.5 mg and 70 per cent offered folic acid supplements to women planning pregnancy, 82.5 per cent of responding pharmacists knew the recommended dose, and 87.5 per cent reported an increase in sales of 0.5 mg folic acid. Wholesale sales of 0.5 mg folic acid increased markedly in Western Australia compared with other states. From shopping centre surveys of women of child-bearing age we estimated that their knowledge of the association between folate and spina bifida increased from 8.2 per cent before the project to 67.5 per cent 2.5 years later, and doctors were a major source of information for women. In a 1995 survey of a sample of pregnant women, 43.1 per cent with planned pregnancies had taken folic acid supplements periconceptionally, compared with 19.1 per cent in a similar survey in 1993.

The crystal structures of the oligopeptide-binding protein OppA complexed with tripeptide and tetrapeptide ligands.

BACKGROUND: The periplasmic oligopeptide-binding protein OppA has a remarkably broad substrate specificity, binding peptides of two or five amino-acid residues with high affinity, but little regard to sequence. It is therefore an ideal system for studying how different chemical groups can be accommodated in a protein interior. The ability of the protein to bind peptides of different lengths has been studied by co-crystallising it with different ligands. RESULTS: Crystals of OppA from Salmonella typhimurium complexed with the peptides Lys-Lys-Lys (KKK) and Lys-Lys-Lys-Ala (KKKA) have been grown in the presence of uranyl ions which form important crystal contacts. These structures have been refined to 1.4 A and 2.1 A, respectively. The ligands are completely enclosed, their side chains pointing into large hydrated cavities and making few strong interactions with the protein. CONCLUSIONS: Tight peptide binding by OppA arises from strong hydrogen bonding and electrostatic interactions between the protein and the main chain of the ligand. Different basic side chains on the protein form salt bridges with the C terminus of peptide ligands of different lengths.

AUR Memorial Award. Identification of myocardial cell death in reperfused myocardial injury using dual mechanisms of contrast-enhanced magnetic resonance imaging.

RATIONALE AND OBJECTIVES: Because the magnitude of dysprosium-induced signal loss depends on the microheterogeneity of its distribution (exclusion from intracellular space), we proposed that loss of myocardial cell integrity would be reflected by decreased potency of dysprosium in the injured compared with normal myocardium. We measured the effect of dysprosium on magnetic resonance (MR) imaging signal intensity of reperfused infarcted and nonischemic myocardium and related it to tissue concentration of the contrast media. METHODS: Rats were subjected to 1 hr coronary artery occlusion followed by 1 hr reperfusion. After 45 min of reflow, group 1 (n = 9) received 1.0 and 0.2 mmol/kg dysprosium diethylenetriamine pentaacetic acid-bismethylamide (Dy-DTPA-BMA) and gadodiamide (Gd-DTPA-BMA), respectively. Group 2 (n = 7) received no contrast agents. Excised hearts were imaged with spin-echo T1- and T2-weighted sequences. After imaging, hearts were stained (triphenyltetrazolium chloride) to define the injured zones. Concentrations of Dy-DTPA-BMA and Gd-DPTA-BMA in regional myocardial tissue were determined by induction coupled plasma-atomic emission spectrometry. Separate groups received one or the other contrast medium alone to control for potential error from the mixed effects of the two agents. RESULTS: Gd-DTPA-BMA delineated reperfused infarcted myocardium as a bright zone on T1-weighted images, thus indicating delivery of the agent and reperfusion at the tissue level. Dy-DTPA-BMA delineated the reperfused infarction as a bright region by decreasing the signal intensity of nonischemic myocardium significantly more than that of injured myocardium, despite being present in greater concentration (by 2.46-fold) in the injured myocardium. CONCLUSION: These findings are consistent with the hypothesis that the failure of myocardial cells to exclude the dysprosium compound is responsible for the diminished potency of dysprosium to cause MR imaging signal intensity loss in reperfused myocardial infarction. The combination of the two contrast media may define reperfusion of the myocardium at the tissue level (Gadolinium distribution) and the presence and extent of myocardial necrosis (diminished dysprosium effect) in reperfused myocardial infarctions.

MR imaging of the myocardium using nonionic contrast medium: signal-intensity changes in patients with subacute myocardial infarction.

OBJECTIVE: Gadodiamide injection (Omniscan, Sanofi Winthrop Pharmaceuticals, New York) is a new nonionic MR contrast medium that has been shown in animal studies to provide persistent differential enhancement of myocardial infarction. Because differential enhancement of normal and infarcted myocardium may be useful for the diagnosis and sizing of myocardial infarctions, we assessed the effectiveness of gadodiamide injection in enhancing signal-intensity differences between infarcted and normal myocardium on spin-echo T1-weighted images. SUBJECTS AND METHODS: Signal intensity of normal and infarcted myocardium, contrast ratio, contrast-to-noise ratio, and signal-to-noise ratio were measured in 12 patients with subacute myocardial infarction (mean, 16 days after diagnosis) before and after injection of contrast medium. Precontrast T1-weighted and T2-weighted images were obtained with a 1.5-T MR imager. T1-weighted images were acquired 5, 15, and 30 min after gadodiamide injection (0.2 mmol/kg) and T1-weighted images with fat saturation were acquired 10 min after gadodiamide injection. RESULTS: Gadodiamide injection significantly increased signal intensity of normal (34 +/- %) and infarcted (90 +/- %) myocardium compared with their signal intensities on precontrast T1-weighted images. The contrast ratio was significantly increased, and the augmented ratios persisted throughout the 45-min observation period. The contrast ratio on T2-weighted images was comparable to that on contrast-enhanced T1-weighted images (with or without the use of fat saturation). However, the signal-to-noise and contrast-to-noise ratios of T2-weighted images were significantly lower than those of contrast-enhanced T1-weighted images. The maximum contrast-to-noise ratio for visualizing myocardial infarction was achieved on contrast-enhanced T1-weighted images with fat saturation. CONCLUSION: Improved and persistent contrast between infarcted and normal myocardium can be produced on MR images by injecting gadodiamide at a dose of 0.2 mmol/kg, which provides prolonged delineation of myocardial infarctions. Maximum contrast-to-noise ratios for detecting myocardial infarction can be produced by using fat-saturated T1-weighted imaging after a high dose of this nonionic contrast medium has been administered.

Genetic engineering of grain and pasture legumes for improved nutritive value.

This review describes work aimed at the improvement of the nutritive value of grain and forage legumes using gene transfer techniques. Two traits which are amenable to manipulation by genetic engineering have been identified. These are plant protein quality and lignin content. In order to increase the quality of protein provided by the legume grains peas and lupins, we are attempting to introduce into these species chimeric genes encoding a sunflower seed protein rich in the sulphur-containing amino acids methionine and cysteine. These genes are designed to be expressed only in developing seeds of transgenic host plants. Chimeric genes incorporating a similar protein-coding region, but different transcriptional controls, are being introduced into the forage legumes lucerne and subterranean clover. In this case the genes are highly expressed in the leaves of transformed plants, and modifications have been made to the sunflower seed protein-coding sequences in order to increase the stability of the resultant protein in leaf tissue. Another approach to increasing plant nutritive value is represented by attempts to reduce the content of indigestible lignin in lucerne.

The multidrug resistance and cystic fibrosis genes have complementary patterns of epithelial expression.

The cystic fibrosis gene product, CFTR, and the multidrug resistance P-glycoprotein (encoded by the MDR1 gene) are structurally related proteins and both are associated with epithelial chloride channel activities. We have compared their cell-specific expression in the rat by in situ hybridization. In all tissues examined the two genes were found to have complementary patterns of expression, demonstrating exquisite regulation in both cell-specific and temporal fashions. Additionally, a switch in expression from one gene to the other was observed in certain tissues. For example, expression in the intestine switches from CFTR to MDR1 as the cells migrate across the crypt-villus boundary. A switch from CFTR to MDR1 expression was also observed in the uterine epithelium upon pregnancy. These data suggest that CFTR and P-glycoprotein serve analogous roles in epithelial cells and provide additional evidence that P-glycoprotein has a physiological role in regulating epithelial cell volume. The patterns of expression suggest that the regulation of these two genes is coordinately controlled.

Delineation of acute myocardial infarction with dysprosium DTPA-BMA: influence of dose of magnetic susceptibility contrast medium.

OBJECTIVES: The contrast enhancement of acutely infarcted myocardium produced by the nonionic magnetic susceptibility-enhancing agent dysprosium diethylenetriamine pentaacetic acid-bis-methylamide (DyDTPA-BMA [S-043 Injection]) was assessed in the current study to establish the lowest dose that would yield optimal contrast between normal and acutely infarcted myocardium. BACKGROUND: Magnetic susceptibility contrast agents enhance differences between normal and ischemic tissue by reducing the signal of the normally perfused tissue to which they distribute. METHODS: Acute myocardial infarctions were produced by ligation of the left coronary artery. At 3 to 4 h after occlusion, a dose of 0.1, 0.3 or 0.5 mmol/kg of DyDTPA-BMA was injected intravenously into eight rats each in group 1, 2 or 3, respectively; a fourth group of seven rats served as a control group. Nuclear magnetic resonance (NMR) transverse relaxation time (T2)-weighted images (electrocardiographically gated to every 5th beat, echo delay time [TE] = 60 ms) were acquired before and for 1 h after administration of contrast agent. RESULTS: Images obtained before the injection of contrast agent showed moderate differences in signal intensity between normal and infarcted myocardium (p < 0.05). The contrast enhancement and the duration of delineation between infarcted and normal myocardium produced by this agent were dose dependent. At doses of 0.1, 0.3 and 0.5 mmol/kg, DyDTPA-BMA produced signal loss in normal myocardium: 63 +/- 5%, 41 +/- 4% and 28 +/- 4% of the baseline values, respectively, without any significant reduction in signal intensity of the infarcted region. The reduction in signal of normal myocardium and delineation of the infarct persisted for 5 min at a dose of 0.1 mmol/kg, for 20 min at a dose of 0.3 mmol/kg and for 40 min at a dose of 0.5 mmol/kg. No change in signal intensity or signal intensity ratio between normal and infarcted myocardium was observed in the control group during the same observation period. CONCLUSIONS: These results suggest that low doses of this agent, comparable to those of longitudinal relaxation time (T1)-enhancing agents, can delineate acutely infarcted myocardium. A dose of 0.3 mmol/kg of DyDTPA-BMA (S-043 Injection) provides reasonably persistent demarcation of acute myocardial infarction. Because this dose dramatically suppresses the NMR signal of normal myocardium, it shows the infarcted region as a region of high intensity (bright spot) on NMR images.

Amelioration of cardiodepressive effects of gadopentetate dimeglumine with addition of ionic calcium.

Doses of gadopentetate dimeglumine of 0.1-0.5 mmol/kg cause cardiodepressive effects when injected as a rapid central bolus into the left jugular vein. This study evaluated the hemodynamic effects of this magnetic resonance imaging contrast medium with and without calcium supplementation in a rat model. Also, the potential of gadopentetate dimeglumine to bind ionized serum calcium was investigated in vitro. Addition of calcium ions resulted in dose-dependent attenuation of the hemodynamic depression induced by gadopentetate dimeglumine alone. The cardiodepressive response was negated for a 0.1-mmol/kg dose of the contrast agent by addition of 6 mumol/kg of calcium, for a 0.3-mmol/kg dose by addition of 12 mumol/kg of calcium, and for a 0.5-mmol/kg dose by addition of 18 mumol/kg of calcium. Concentrations of 2 and 4 mmol/L of gadopentetate dimeglumine were found to bind 5.1% and 10.1% of the ionized calcium in rat serum under in vitro conditions, respectively.

Occlusive and reperfused myocardial infarcts: MR imaging differentiation with nonionic Gd-DTPA-BMA.

To increase the time during which effective contrast exists between normal and infarcted myocardium, a high dose (0.6 mmol/kg) of the nonionic contrast medium gadolinium diethylenetriaminepentaacetic acid bismethylamide (Gd-DTPA-BMA) was used to distinguish between occlusive and reperfused myocardial infarctions in rats. After administration of Gd-DTPA-BMA, there was clear and persistent demarcation of both occlusive and reperfused infarcts on T1-weighted MR images. In occlusive infarcts, normal, infarcted, and periinfarcted myocardium could be identified. High signal intensity was evident for 60 minutes in a band straddling the border between infarcted and normal myocardium, namely, the periinfarction zone. In the reperfused infarct, normal and infarcted myocardium could be identified. The reperfused zone was immediately enhanced after injection of Gd-DTPA-BMA. A differential pattern of enhancement between occlusive and reperfused myocardial infarcts was evident for 1 hour. Thus, Gd-DTPA-BMA has the potential to allow (a) depiction of occlusive and reperfused acute myocardial infarcts, (b) documentation of reperfusion of myocardial infarction, and (c) distinction between occlusive and reperfused infarction.

Postischemic recovery of mechanical performance and energy metabolism in the presence of left ventricular hypertrophy. A 31P-MRS study.

The present study was undertaken to define the effects of left ventricular hypertrophy on postischemic recovery of myocardial performance and high energy phosphate metabolism. Hemodynamics and 31P-magnetic resonance spectra were monitored simultaneously in the isolated Langendorff-perfused rat heart during 30 minutes of ischemia and 30 minutes of reperfusion. Left ventricular hypertrophy was produced by either suprarenal aortic constriction or chronic thyroxine administration. In chronic pressure overload hypertrophy, minimal coronary resistance was significantly higher (p less than 0.001) and the loss of purine nucleosides in the coronary effluent during early reperfusion significantly larger (p less than 0.001) compared with both normal hearts and thyroxine-induced hypertrophied hearts. Postischemic recovery of the baseline values for left ventricular developed pressure and phosphorylation potential was 43 +/- 4% and 82 +/- 4%, respectively, in chronic pressure overload hypertrophied hearts; 86 +/- 4% and 91 +/- 3%, respectively, in normal hearts (chronic pressure overload hypertrophy versus normal hearts, p less than 0.001 and p less than 0.05); and 100 +/- 4% and 98 +/- 2%, respectively, in thyroxine-induced hypertrophied hearts (normal hearts versus thyroxine-induced hypertrophied hearts, p less than 0.05 and p less than 0.05). Recovery after reperfusion was not related to intracellular pH, ATP, phosphocreatine, or inorganic phosphate levels during ischemia. Also, recovery was not related to developed pressure or oxygen consumption before ischemia. However, recovery was inversely related to coronary resistance and directly related to coronary flow before ischemia. Thus, functional and/or anatomic alterations of the coronary vascular bed and a greater loss of purine nucleosides during reperfusion are likely responsible for the attenuated compensatory response to ischemia and reperfusion in left ventricular hypertrophy induced by chronic pressure overload. On the other hand, the excess muscle mass per se does not seem to alter recovery, since thyroxine-induced myocardial hypertrophied hearts responded at least as well as normal hearts.

Magnetic resonance spectroscopy of the heart. Overview of studies in animals and man.

Magnetic resonance spectroscopy (MRS) has been used effectively in the evaluation of cardiac physiology. Studies have been done at various levels of complexity extending from isolated hearts to man. Correlation of high-energy phosphate compounds with contractile function is achieved by simultaneous or immediate sequential measurement of ventricular contractile function and the phosphorus-31 MR spectra. Studies in isolated hearts have monitored the response to ischemia of normal and hypertrophic hearts and the preservation of myocardial function and high- energy phosphate stores by drugs administered prior to the ischemic event. Regional myocardial ischemia has been evaluated by simultaneous monitoring of myocardial regional segment length by sonomicrometry and regional myocardial 31P MRS in the intact heart of larger animal models. Function and metabolism have been assessed in man by the combined application of cine MRI and 31P MRS acquired with a surface coil.

31P and 1H magnetic resonance spectroscopy of acute alcohol cardiac depression in rats.

Cardiac depression in the isolated rat heart perfused with 4% ethanol was correlated with intracellular phosphate energetics and tissue water distributions. Energy metabolites were assessed using 31P magnetic resonance spectroscopy (MRS) and correlated to the mitochondrial redox state using epicardial surface fluorometry. Changes in myocardial water compartmentation were measured by using 1H NMR spectroscopy with an extracellular chemical-shift reagent (DyTTHA) and correlated to results of 2D echocardiography (2DE). During alcohol perfusion there was a significant decrease in developed pressure and in coronary flow. No change was seen in ATP, PCr, pHi, Pi, or NADH. After withdrawal of alcohol from the perfusate cardiac function reverted to control values without a depletion of energy levels. During alcohol perfusion 1H MRS showed a marked redistribution of water from the intra- to the extracellular space, corresponding to a 35% left ventricular wall thinning confirmed by 2DE. The results indicate that acute alcohol cardiac depression is related to a dehydration of myocardial cells, but is not associated with intracellular acidosis or energy depletion.

Reversibility of acute alcohol cardiac depression: 31P NMR in hamsters.

Isolated hamster hearts were perfused with 2% ethanol for 30 min and then reequilibrated with control medium. One group of hamsters was pretreated with verapamil. Another group received diltiazem. Myocardial verapamil levels were 9.5 +/- 0.7 mg/g dry wt; diltiazem levels were 22 +/- 7 mg/g dry wt. Energy metabolites were assessed by using 31P NMR standardized with high-pressure liquid chromatography of freeze-clamped tissue. Intracellular calcium was measured by atomic absorption spectrophotometry, marking the extracellular space with K(CoEDTA). After 30 min of perfusion, untreated hamster hearts showed a 74% decrease in developed pressure, a marked increase in end-diastolic pressure, a decrease of ATP from 9.8 to 8.8 mmol, and an increase of Pi from 6.7 to 9.8 mmol, but no change of phosphocreatine (PCr) or intracellular pH (pHi). Verapamil pretreatment partially prevented cardiac depression during alcohol perfusion. Whereas diltiazem had no protective effect. After reequilibration, developed pressure and oxygen consumption significantly exceeded control values. ATP decreased to 8 mmol; pHi, PCr, and Pi showed no significant change. Verapamil-pretreated hearts showed better performance than untreated hearts without change in PCr and Pi, whereas ATP dropped slightly to 8.7 mmol. Thus, functional cardiac depression resulting from acute alcohol exposure is reversible. Increased intracellular calcium levels during alcohol exposure normalized after the removal of alcohol. There was no major change in high-energy phosphates during alcohol exposure or after the removal of alcohol. Verapamil protects the heart from functional depression during alcohol exposure without affecting energy resources.

Beneficial effects of verapamil during metabolic acidosis in isolated perfused rat hearts.

Metabolic acidosis was produced in two groups of isolated, glucose-perfused beating rat hearts. The first group (control) was untreated whereas the second group was pretreated for 48 h by the addition of verapamil (1.2 g/L) to the drinking water. Untreated hearts all developed asystole during a 30 min perfusion with an acidotic substrate (pH = 6.8) or during subsequent reequilibration with physiologic substrate (pH = 7.4). Prior to asystole, all untreated hearts showed evidence of severe mechanical and biochemical deterioration evaluated by 31 P NMR spectroscopy. In contrast, hearts of treated rats showed less mechanical and metabolic deterioration, and all recovered during reequilibration. The mechanism of protection of verapamil against the effects of metabolic acidosis is unclear but appears to be related to preserved mitochondrial function by the drug and not to a reduced demand for energy.

Influence of heart rate on metabolic and hemodynamic parameters in the Syrian hamster cardiomyopathy.

The effect of varying heart rate in 155- to 170-day-old isolated, perfused cardiomyopathic Syrian hamster hearts was evaluated by 31P nuclear magnetic resonance spectroscopy. At a low paced heart rate of 170 bpm, cardiomyopathic hearts did not differ from normal hearts except for a lower developed left ventricular pressure. As pacing rate was increased progressively to 270/min, cardiomyopathic hearts showed prolongation of contraction, which led to a pronounced rise in diastolic pressure as the interstimulus interval shortened. This was accompanied by a marked decrease in energy-rich phosphorus compounds. By contrast, increasing heart rate in normal hearts did not change left ventricular pressure and caused only a mild reduction in energy-rich phosphorus compounds. Intracellular pH of cardiomyopathic animals paced at 270 bpm was significantly lower than in normal animals. Thus, indices reflecting mitochondrial function of 155- to 170-day-old cardiomyopathic hamsters appear adequate at low heart rate. Increasing the heart rate unmasks latent mitochondrial dysfunction.