PubMed Health⌕ Search

Biomedical subjects

A Deussen

Publications and source records attributed to A Deussen.

At least 19 recordsLinked to original sources
PubMed2006

Metabolic coronary flow regulation--current concepts.

The concept of metabolic coronary flow control provides a rationale for the close relationship of coronary flow and myocardial metabolic rate of oxygen. The concept is based on the presence of an oxygen (metabolic) sensor coupled functionally to effector mechanisms, which control vascular tone. Four modes of metabolic control models have been proposed. 1) An oxygen sensor located in the wall of coronary vessels coupling to smooth muscle tension. Endothelial prostaglandin production may support this concept. 2) An oxygen sensing mechanism located in the myocardium and changing metabolism in response to changes of local pO(2). Adenosine is a metabolite produced at an accelerated rate when the supply-to-demand relationship for oxygen falls. 3) Sensing of oxygen turnover may be achieved by carbon dioxide production and, potentially, by mitochondrial production of reactive oxygen species. 4) The red blood cell might serve as an oxygen sensor in response to changes of haemoglobin oxygenation. A potential link to vessel relaxation may be red cell ATP release. A large body of experimental evidence supports the notion that K(ATP) channels play a significant role causing smooth muscle hyper-polarization. However, additional yet unknown effector mechanisms must exist, because block of K(ATP) channels does not lead to deterioration of coronary flow control under conditions of exercise. Thus, although several lines of evidence show that metabolic flow regulation is effective during hypoxic conditions,mechanisms mediating normoxic metabolic flow control still await further clarification.

Adenosine↗
PubMed2006

The influence of downstream arterial perfusion parameters on doppler pulsatility index and resistance index in an in-vitro perfusion model.

BACKGROUND: To investigate in vitro how downstream perfusion parameters influence pulsatility index (PI), resistance index (RI) and their constituting Doppler velocities. MATERIALS AND METHODS: We analyzed the influence of resistance, compliance, reflection coefficient and input impedance on PI and RI in an in-vitro model of arterial flow. RESULTS: The nominators of PI and RI were determined by resistance. The numerators were determined by compliance and by the reflection coefficient. There were close relationships of PI and RI with resistance under the condition of constant compliance, but not when compliance was variable. CONCLUSION: PI and RI consist of velocity terms which are independently influenced by different parameters of impedance: compliance, reflection coefficient and resistance. These findings explain the contradictory results reported for the relationship between the indices and peripheral resistance in studies where compliance and reflection effects were not considered.

Animals↗
PubMed2004

Myocardial ferritin content is closely related to the degree of ischaemia.

AIM: Ferritin acts as an iron scavenger and thereby may reduce iron catalysed oxygen radical production during reperfusion injury. We tested the hypothesis that the myocardial ferritin concentration is enhanced during ischaemia in proportion to the blood flow reduction. METHODS: In 10 anaesthetized, open chest Beagle dogs (six controls and four with 60 min coronary occlusion) regional myocardial blood flow (RMBF) was measured with the tracer microsphere technique and ferritin was determined in samples with an average mass of 125 mg (124-256 samples per heart). RESULTS: Under physiological conditions heart rate was 88 +/- 12 bpm, mean aortic pressure 98 +/- 8 mmHg, and RMBF 0.99 +/- 0.33 mL min-1 g-1. Data did not differ between experimental groups, P > 0.05. In the control group regional myocardial ferritin concentration averaged 11.76 +/- 3.54 ng mg-1 protein and exhibited a significant blood flow independent heterogeneity (CV(biol) = 0.27). However, between low and high flow areas (relative flow <0.5 and >1.5 times the average RMBF, respectively) no significant difference in ferritin was found, P > 0.05. In four experiments, in which regional blood flow was reduced by 40% to 0.60 +/- 0.23 mL min-1 g-1, regional ferritin content was significantly higher as compared with the control group 27.95 +/- 6.16 vs. 11.76 +/- 3.54 ng mg-1 protein, respectively. An inverse relationship was observed between ferritin and RMBF, r = -0.61, P < 0.001. Thus, a reduction of RMBF of >80% was associated with a 2.75-fold increase of the average ferritin content. Between subepicardium and subendocardium no significant difference in ferritin content was observed, neither in the control group nor in the group with induced ischaemia. Regions with control low and high flow responded similarly to the coronary constriction with regard to the local ferritin concentration: 27.88 +/- 15.22 vs. 30.10 +/- 14.91 ng mg-1, P > 0.05, respectively. A data analysis using Baye's theorem indicated that sensitivities were 0.28 and 0.94 for average flow reductions of 5 and 93%. In additional in vitro measurements (ischaemic incubation at 37 degrees C) myocardial ferritin content increased almost linearly within the first 60 min of incubation and thereafter remained unchanged. CONCLUSIONS: (1). Local physiological ferritin content in myocardium is heterogeneous and unrelated to control myocardial blood flow. (2). Ischaemia results in an enhanced ferritin content in relation to the degree of ischaemia. (3). The increase of myocardial ferritin requires a severe degree of ischaemia.

Animals↗
PubMed2001

Plasma nitrite rather than nitrate reflects regional endothelial nitric oxide synthase activity but lacks intrinsic vasodilator action.

The plasma level of NO(x), i.e., the sum of NO(2)- and NO(3)-, is frequently used to assess NO bioavailability in vivo. However, little is known about the kinetics of NO conversion to these metabolites under physiological conditions. Moreover, plasma nitrite recently has been proposed to represent a delivery source for intravascular NO. We therefore sought to investigate in humans whether changes in NO(x) concentration are a reliable marker for endothelial NO production and whether physiological concentrations of nitrite are vasoactive. NO(2)- and NO(3)- concentrations were measured in blood sampled from the antecubital vein and brachial artery of 24 healthy volunteers. No significant arterial-venous gradient was observed for either NO(2)- or NO(3)-. Endothelial NO synthase (eNOS) stimulation with acetylcholine (1-10 microg/min) dose-dependently augmented venous NO(2)- levels by maximally 71%. This effect was paralleled by an almost 4-fold increase in forearm blood flow (FBF), whereas an equieffective dose of papaverine produced no change in venous NO(2)-. Intraarterial infusion of NO(2)- had no effect on FBF. NOS inhibition (N(G)-monomethyl-l-arginine; 4-12 micromol/min) dose-dependently reduced basal NO(2)- and FBF and blunted acetylcholine-induced vasodilation and NO release by more than 80% and 90%, respectively. In contrast, venous NO(3)- and total NO(x) remained unchanged as did systemic arterial NO(2)- and NO(3)- levels during all these interventions. FBF and NO release showed a positive association (r = 0.85; P < 0.001). These results contradict the current paradigm that plasma NO(3)- and/or total NO(x) are generally useful markers of endogenous NO production and demonstrate that only NO(2)- reflects acute changes in regional eNOS activity. Our results further demonstrate that physiological levels of nitrite are vasodilator-inactive.

Acetylcholine↗
PubMed2001

Heterogeneity of metabolic parameters in the left ventricular myocardium and its relation to local blood flow.

It is well established that myocardial blood flow is heterogeneous on the local level. During recent years comprehensive studies have been undertaken to assess the relation between myocardial metabolism and spatial blood flow heterogeneity. Based on the type of measurements two major groups of studies have been performed: enzyme activity and tissue metabolite level assessments. Enzyme activity measurements have provided only limited insight into the coupling of local metabolism and flow. This is probably due to the fact that, in addition to estimated Vmax values, local substrate affinity (Km values) and substrate concentrations affect the metabolite fluxes. However, the latter two variables remain normally unknown. In contrast, valuable insight has been obtained concerning flow-metabolism matching from tissue metabolite measurements, especially when connected with mathematical model analyses. The latter permitted the calculation of metabolic flux rates (e.g., production of oxidation water, citric acid cycle flux, glucose uptake, fatty acid uptake) or the translation of the metabolic indexes into physiologically meaningful local metabolite concentrations (e.g., free cytosolic adenosine). The bottom line of the studies reported to date is that the broad range of myocardial flows observed under resting control conditions correlates with local metabolism possibly affected by spatial differences in adrenergic stimulation. Thus, high flow samples exhibit a higher oxidative metabolism than low flow samples. As a result the flow threshold below which local myocardial ischemia ensues is higher in control high flow samples. The importance of these findings with respect to local flow-metabolism matching is underlined by the finding that the probability of developing an infarction following ischemia/reperfusion is related to the functional state of the myocardium under control conditions, i.e., the local level of flow-metabolism matching.

Animals↗
PubMed2001

Spatial heterogeneity of energy turnover in the heart.

Local myocardial blood flow varies substantially in spite of a rather homogeneous morphology. To further elucidate this paradox, the spatial heterogeneity of tricarboxylic acid cycle turnover (J(TCA), micromol min(-1) g(-1)) and coronary flow was assessed at a high spatial resolution (6x6x6 mm3) in the open chest dog. Local flow differed more than 2.5-fold between individual samples in each heart (n=7). Out of 1,500 myocardial samples, 1/10 received less than 60% and another 1/10 more than 138% of the normalized mean. In low- and high-flow samples, pyruvate uptake and metabolism were analyzed by 13C NMR spectroscopy. Following [3-13C]pyruvate infusion (2 mM, 12 min), glutamate [4-13C]/[3-13C] was significantly greater in low-flow (2.21+/-0.75, 40 samples) than in high-flow (1.64+/-0.49, 39 samples) areas. This suggests that there are major differences in J(TCA). Glutamate, citrate and lactate content positively correlated with flow. Anaplerotic pathways contributed a fraction similar to J(TCA) in low- and high-flow areas, as demonstrated by isotopomer analysis after 60 min of [3-13C]pyruvate application. Mathematical model analysis of NMR data and relevant pool sizes revealed that J(TCA) and thus myocardial oxygen consumption (MVO2) in high-flow areas exceed values in low-flow areas at least threefold. Thus low and high metabolic states normally coexist within the well perfused heart, suggesting that there is considerable spatial heterogeneity of cardiac energy generation and work.

Alanine↗
PubMed2001

Significance of adenosine metabolism of coronary smooth muscle cells.

A detailed understanding of adenosine metabolism of vascular smooth muscle cells (VSMC) is highly desirable to critically evaluate possible autocrine effects of adenosine in this cell species. Therefore, this study quantified intra- and extracellular adenosine flux rates, the transmembrane concentration gradient, and the adenosine surface concentration in porcine VSMC and, for comparison, aortic endothelial cells (PAEC). Cell-covered microcarrier beads packed in a chromatography column were superfused with a HEPES buffer. With the use of specific inhibitors of adenosine kinase (iodotubericidine, 10 microM), adenosine deaminase [erythro-9-(2-hydroxy-3-nonyl)-adenine, 5 microM], ecto-5'-nucleotidase (alpha,beta-methylene-adenosine 5'-diphosphate, 50 microM), and adenosine membrane transport (n-nitrobenzylthioinosine, 1 microM), total production rates of 12.3 +/- 2.7 and 7.5 +/- 1.3 pmol x min(-1) x microl cell volume(-1) were obtained for VSMC and PAEC, respectively. Despite prevailing intracellular adenosine production (76 and 70% of total production, respectively), transmembrane concentration gradients under control conditions were directed toward the cytosol as a result of rapid intracellular adenosine rephosphorylation and continuous extracellular hydrolysis from 5'-AMP. Surface concentrations were approximately 18 nM in VSMC and PAEC under control conditions and increased to approximately 60 nM during partial inhibition of adenosine metabolism. Simultaneously, the transmembrane adenosine concentration gradient was reversed. We conclude that adenosine flux rates in VSMC and PAEC are quantitatively similar and that VSMC may influence the interstitial adenosine concentration under basal steady-state conditions.

Adenosine↗
PubMed2001

Screening of plasma homocysteine in peripheral arterial disease.

BACKGROUND: Homocysteine (HCY) was recently established as an independent risk factor for atherosclerosis. The prevalence of an increased homocysteine plasma concentration was reported to be up to 6-fold higher in patients with different locations of arterial occlusive diseases. AIM: This study evaluated critically whether the total HCY plasma concentration can be used as a screening marker for peripheral arterial disease in the general population. METHODS: Study subjects were 40 patients (51.8 +/- 7.5 years) with symptomatic lower limb peripheral arterial disease (PAD) (stage II) and 40 healthy volunteers (45.6 +/- 6.8 years, P< 0.05 vs PAD). The percentage of women in both groups was 30%. The plasma HCY concentration was determined by using derivatization techniques and subsequent fluorescence high-performance liquid chromatography. RESULTS: Total plasma HCY concentration was significantly higher in the PAD group than in controls (14.90 +/- 5.78 microM vs 11.32 +/- 2.95 microM, respectively, P< 0.001). Also, the coefficient of variation of plasma HCY in PAD was significantly higher than that in the control group, 0.38 vs 0.25 (P< 0.001), respectively, reflecting greater interindividual differences. In addition to a PAD-specific effect, the plasma HCY concentration was also dependent on gender and age (both P< 0.05). Sensitivity and specificity of HCY as a marker of PAD were 0.3 and 0.95, respectively. Positive and negative predictive values were 0.85 and 0.42, respectively. CONCLUSIONS: From these data it is concluded that HCY metabolism may have an influence on the development of PAD in one-third of all patients with PAD, and that total plasma HCY concentration may not be suited as a screening test for PAD in the general population but rather serves as a monitoring marker in certain risk groups.

Adult↗
PubMed2000

Metabolic flux rates of adenosine in the heart.

The quantitatively most important source of adenosine under well-oxygenated conditions is 5'-AMP hydrolyzed by cytosolic 5'-nucleotidase N-I. Hydrolysis of S-adenosylhomocysteine and extracellular dephosphorylation of 5'-AMP further contribute to total production. More than 90% of the total production occur intracellularly under well-oxygenated conditions. Besides cardiomyocytes, endothelial cells and smooth muscle contribute significantly to total cardiac adenosine production. Rapid enzymatic conversion of adenosine is provided by adenosine kinase and adenosine deaminase, keeping the cytosolic adenosine concentration in the nanomolar range. Due to the high intracellular rates of adenosine rephosphorylation and deamination the cytosolic is normally below the extracellular adenosine concentration, making the cytosol to a sink rather than a source of adenosine. It is for this reason that blockers of membrane transport enhance the plasma adenosine concentration. With increasing catabolism of adenine nucleotides the rate of intracellular adenosine production exceeds the rate of adenosine deamination and rephosphorylation. Thus, this condition will result in a concentration gradient from intra- to extracellular. Thence, membrane transport blockers would be expected to increase the intracellular adenosine concentration. A considerable insecurity on the importance of experimental data results from species differences of purine metabolism. Cardiac adenosine metabolism has recently been described in quantitative terms using mathematical model analysis. This analysis tool may prove useful in future when (1) clarifying the importance of various regulatory actions described for the different pathways of adenosine metabolism, (2) making quantitative comparisons of different experimental models possible and (3) deepening the insight from experimental data.

Adenosine↗
PubMed2000

Quantitative integration of different sites of adenosine metabolism in the heart.

Adenosine is a biologically active metabolite that evokes numerous potent actions in the heart and other tissues. A better understanding of the regulation of the local adenosine concentration seems mandatory to permit specific manipulation of the adenosine tissue concentration. To achieve this a combined experimental and model analysis approach was developed. Experiments carried out in isolated perfused guinea pig hearts, coronary endothelial, and smooth muscle cells and data were analyzed with an axially distributed, 4-region mathematical model of adenosine metabolism and transport. This approach permitted us to obtain a comprehensive parameter set that adequately described cardiac adenosine metabolism. The parameter values that gave the optimal fits to experimental results indicated that adenosine production was largest in the cytosol, while extracellular adenosine production accounted for approximately 8% of total cardiac adenosine production. However, despite the much higher intracellular rate of adenosine production, the concentration gradient of adenosine across cell membranes was directed toward the cytosol under physiological conditions, i.e., when the cytosolic adenosine concentration was low. This was due to the high rate of intracellular adenosine removal which exceeded intracellular production. The endothelial region contributed approximately 5% to total cardiac adenosine production. Despite this small contribution endothelial cells may effectively control the vascular adenosine concentration over a wide concentration range (5-500 nM). In conclusion, a combination of experimental and modeling approaches may provide unique insights into capillary-tissue exchange and metabolism of adenosine. In the future this may reveal realistic concentration-effect relationships for adenosine in the heart. These achievements seem critical in order to design strategies which permit a specific manipulation of substrates with high turnover rates in biological tissues.

Adenosine↗
PubMed2000

Heterogeneity of local myocardial flow and oxidative metabolism.

In mammalian hearts, local myocardial flow (LMF) varies between 20 and 200% of the mean. It is not clear whether oxidative metabolism has a similar degree of heterogeneity. Therefore, we investigated the relation between LMF and local oxidative metabolism in isolated rabbit hearts. Buffer oxygenation with (18)O(2) resulted in labeled myocardial oxidation water (H(2)(18)O). In four hearts, myocardial oxygen consumption (MVO(2)) was calculated from the H(2)(18)O production and compared with that calculated according to Fick. In eight additional hearts, LMF was measured using microspheres. Coronary venous H(2)(18)O kinetics and local H(2)(18)O residues were determined and analyzed by mathematical modeling. MVO(2) recovery from H(2)(18)O was >93% compared with that according to Fick. LMF ranged from 1.91 to 11.24 ml. min(-1). g(-1), and local H(2)(18)O residue ranged from 0.41 to 1.04 micromol/g. Both variables correlated (r = 0.62, n = 64, P < 0.001). Measurements in nine hearts were fitted by modeling using capillary permeability-surface area products (PS(c)) from 2 to 10 ml. min(-1). g(-1). With flow-proportional PS(c), a 3.33-fold difference in LMF was associated with a 6.45-fold difference in local MVO(2). Both LMF and local oxidative metabolism are spatially heterogeneous, and they correlate to one another.

Animals↗
PubMed1999

Quantification of extracellular and intracellular adenosine production: understanding the transmembranous concentration gradient.

BACKGROUND: Inhibitors of adenosine membrane transport cause vasodilation and enhance the plasma adenosine concentration. However, it is unclear why the plasma adenosine concentration rises rather than falls when membrane transport is inhibited. We tested the hypothesis that the cytosolic adenosine concentration exceeds the interstitial concentration under well-oxygenated conditions. METHODS AND RESULTS: In isolated, isovolumically working guinea pig hearts (n=50), the release rate of adenosine and accumulation of S-adenosylhomocysteine (after 20 minutes of 200 micromol/L homocysteine), a measure of the free cytosolic adenosine concentration, were determined in the absence and presence of specific and powerful blockers of adenosine membrane transport (nitrobenzylthioinosine 1 micromol/L), adenosine deaminase (erythro-9-hydroxy-nonyl-adenine 5 micromol/L), and adenosine kinase (iodotubericidine 10 micromol/L). Data analysis with a distributed multicompartment model revealed a total cardiac adenosine production rate of 2294 pmol. min-1. g-1, of which 8% was produced in the extracellular region. Because of a high rate of intracellular metabolism, however, 70.3% of extracellularly produced adenosine was taken up into cellular regions, an effect that was effectively eliminated by membrane transport block. The resulting approximately 2.8-fold increase of the interstitial adenosine concentration evoked near-maximal coronary dilation. CONCLUSIONS: We rejected the hypothesis that the cytosolic adenosine concentration exceeds the interstitial. Rather, there is significant extracellular production, and the parenchymal cell represents a sink, not a source, for adenosine under well-oxygenated conditions.

Adenine↗
PubMed1999

[How much blood flow is required by the myocardium?].

OBJECTIVES: The myocardium of the left ventricle exhibits spatial heterogeneity of blood flow under physiological conditions. This study was designed to investigate, whether oxygen supply is jeopardized in low flow areas (blood flow < 50% of mean) under physiological conditions and whether areas of high flow (> 150% of mean) exhibit perfusion in excess of demand ("luxury perfusion"). METHODS: The study was performed in anesthetized and ventilated beagle dogs. Local blood flow was reduced by mechanically narrowing of the r. circumflexus of the left coronary artery; myocardial blood flow was measured by the tracer-microsphere technique, free concentrations cellular adenosine by the SAH-technique, regional metabolism of substrates by the desoxyglucose-technique. RESULTS: Low flow areas exhibited normal oxygenation of the myocardium, while in high flow areas no luxury perfusion could be demonstrated. CONCLUSION: Myocardial blood flow and metabolism demonstrate significant spatial heterogeneity. There appears to be no absolute threshold of blood flow, where regional myocardial ischemia develops. Probably biochemical evidence of myocardial ischemia is determined by a local ratio of oxygen supply and demand.

Adenosine↗
PubMed1998

Coronary reserve of high- and low-flow regions in the dog heart left ventricle.

BACKGROUND: Left ventricular myocardial blood flow is spatially heterogeneous. The hypothesis we tested was whether myocardial areas with a steady-state flow <0.5 times mean flow are underperfused and areas with flow > 1.5 times mean flow are overperfused. METHODS AND RESULTS: In anesthetized beagle dogs (n=10), the relationship between local blood flow versus S-adenosylhomocysteine (SAH) concentration, a measure of the free intracellular adenosine concentration, and lactate, a measure of the myocardial NADH/NAD+ ratio, were determined under control conditions and after coronary constriction. Control local myocardial blood flow was 0.99+/-0.46 mL x min(-1) x g(-1), with a coefficient of variation of 0.36+/-0.12 (n=256 per heart; sample wet mass, 125+/-30 mg). Tissue concentrations of SAH (3.4+/-2.5 nmol/g) and lactate (1.88+/-0.80 micromol/g) were not elevated in low-flow samples. However, after coronary artery constriction, poststenotic blood flow decreased from 1.00+/-0.27 to 0.49+/-0.22 mL x min(-1) x g(-1) (P<0.04), with significant correlation between local SAH and flow (r=-0.59) and lactate and flow (r = -0.50). Although nearly all samples from control high-flow regions showed increased SAH concentrations if relative flow after stenosis was <1.0, control low-flow samples frequently displayed low SAH concentrations. The percent reduction in flow determined the changes in the local SAH and lactate concentration, independent of the local control blood flow. CONCLUSIONS: When the coronary inflow is unrestricted, the oxygen supply to control low-flow regions meets metabolic demand. Flow to control high-flow regions reflects a higher local demand rather than overperfusion. Thus, blood flow heterogeneity most likely reflects differences in aerobic metabolism.

Animals↗
PubMed1998

[Metabolic aspects of myocardial ischemia].

Myocardial ischemia can be described as an imbalance of energy demand and energy supply. Even during ischemia, energy metabolism is predominantly aerobic. Only during the most severe underperfusion (residual flow less than 5%) anaerobic metabolism exceeds aerobic metabolism quantitatively. ATP synthesis and ATP metabolism are in a steady state during myocardial ischemia, albeit on a reduced level. A locally low blood flow rate may exist under physiological conditions without the presence of ischemia. The basis for the underlying flow heterogeneity is functional. While experimental data have been widely obtained during acute ischemia, metabolic rates have scarcely been determined during conditions of chronic myocardial ischemia. First experimental studies, however, show that uptake of fluoro-deoxyglucose is enhanced for hours after induction of myocardial stunning and even for months during myocardial hibernation.

Adenosine↗
PubMed1998

Blood flow heterogeneity in the heart.

Local deposition density of microspheres is heterogeneous in histologically homogeneous myocardium under physiological conditions. The underlying biological heterogeneity must be distinguished from a methodological heterogeneity which depends preferentially on the number of microspheres injected, blood flow to a particular myocardial region and sample mass. As the variables space (spat), time (temp), and method (meth) are independent of each other, the observed (obs) variability may be approximated using the coefficients of variation (CV) of the individual variables: CVobs = (CV2spat+CV2temp+CV2meth)0.5. Studies in which these different variables have been quantified indicate that the largest fraction of the observed variability of microsphere deposition density is contributed by spatial flow heterogeneity which exists independent of the myocardial layer. Spatial flow heterogeneity increases with decreasing sample mass and decreasing mean flow. Fractal and autocorrelation analyses have shown that adjacent myocardial flows are spatially correlated and nonrandom. Local blood flow was shown to correlate with various metabolic and transport rates, while no differences were found between low and high flow regions with respect to several metabolic markers of tissue hypoxia. In conclusion, the evidence available to date indicates that 1) in histologically homogeneous myocardium there exists a spatial blood flow heterogeneity which 2) is temporally stable, 3) resolution dependent, 4) largely layer-independent, 5) nonrandom, and 6) related to local aerobic metabolism.

Aerobiosis↗
PubMed1998

Regional myocardial heat-shock protein (HSP70) concentrations under different blood flow conditions.

The concentration of heat-shock proteins of 70 kD (HSP70) in heart tissue has been shown to increase during transient myocardial ischaemia and to persist during several hours of reperfusion. In this study the relationship between the local myocardial HSP70 concentration and blood flow was addressed for control physiological conditions and acute myocardial ischaemia. A specific aim of this study was to address the question of whether low flow areas under control physiological conditions have undergone a transient ischaemia during the preceding hours and thus may be in a state of hibernation or stunning. In 12 anaesthetized, open-chest beagle dogs (6 control and 6 with 60-min coronary artery stenosis) heart rate, mean aortic pressure, mean arterial partial pressure of O2 and partial pressure of CO2 averaged 85+/-16 beats/min, 94+/-14 mmHg, 102+/-17 mmHg and 39+/-6 mmHg, respectively. Regional HSP70 and myocardial blood flow (RMBF) were measured using an HSP70-enzyme-linked immunosorbent assay and the tracer microsphere technique, respectively, in samples of 250 mg wet mass. In the control group the mean RMBF was 1.06+/-0.59 ml.min-1.g-1 and the local HSP70 concentration was 7.08+/-1.03 microg/mg cytosolic protein. Myocardial HSP70 showed a blood flow-independent regional biological heterogeneity, equivalent to a coefficient of variation of 0.31. Local HSP70 concentrations did not differ (P>0.05) between control low and high flow samples, 6.16+/-1.0 vs 6.08+/-0.75 microg/mg cytosolic protein, respectively. However, after 60 min of coronary artery occlusion the local HSP70 concentration increased from 7.08 +/-1.03 to 13.43+/-3.19 microg/mg cytosolic protein (P<0. 001). There was a significant inverse relationship between the percent reduction of local blood flow and HSP70 (r=-0.56, P<0.001). From these results it is concluded that: (1) low flow samples under control physiological conditions are unlikely to be in a state of hibernation or stunning since their HSP70 concentration is normal and (2) the increase in the local HSP70 concentration during myocardial ischaemia reflects the degree of impairment of O2 delivery.

Animals↗