Blood flow and high-energy phosphates in microregions of left ventricular subendocardium

1981 ◽  
Vol 240 (5) ◽  
pp. H804-H810 ◽  
Author(s):  
H. D. Kleinert ◽  
H. R. Weiss

Blood flow and high-energy phosphate (HEP) content were determined simultaneously in multiple microregions of left ventricular subendocardium in 29 normal anesthetized open-chest rabbits by use of a new micromethod to determine whether a direct linear relationship existed between these parameters. Tissue samples weighed 1-2 mg. ATP and creatine phosphate (CP) content were quantitated in quick-frozen hearts by fluorometry at sites where tissue perfusion was measured by H2 clearance by use of bare-tipped platinum electrodes. A series of validation studies were conducted to ensure that 1) no significant damage to the tissue surrounding the electrode occurred during the period of experimentation and 2) no significant loss of biochemical constituents had occurred due to labile processes during freezing or storage of the tissue. Blood flow, ATP, and CP values averaged 79.1 +/- 24.1 (SD) ml.min-1.100 g-1, 4.9 +/- 1.3 mumol/g tissue, and 8.0 +/- 3.0 mumol/g tissue, respectively, and are similar to those reported in studies using larger tissue samples. Correlation between the heterogeneous distribution of tissue perfusion and HEP revealed no direct linear relationship between these parameters in the normal unstressed rabbit subendocardium.

2008 ◽  
Vol 294 (6) ◽  
pp. H2680-H2686 ◽  
Author(s):  
Mohammad N. Jameel ◽  
Xiaohong Wang ◽  
Marcel H. J. Eijgelshoven ◽  
Abdul Mansoor ◽  
Jianyi Zhang

The heterogeneity across the left ventricular wall is characterized by higher rates of oxygen consumption, systolic thickening fraction, myocardial perfusion, and lower energetic state in the subendocardial layers (ENDO). During dobutamine stimulation-induced demand ischemia, the transmural distribution of energy demand and metabolic markers of ischemia are not known. In this study, hemodynamics, transmural high-energy phosphate (HEP), 2-deoxyglucose-6-phosphate (2-DGP) levels, and myocardial blood flow (MBF) were determined under basal conditions, during dobutamine infusion (DOB: 20 μg·kg−1·min−1 iv), and during coronary stenosis + DOB + 2-deoxyglucose (2-DG) infusion. DOB increased rate pressure products (RPP) and MBF significantly without affecting the subendocardial-to-subepicardial blood flow ratio (ENDO/EPI) or HEP levels. During coronary stenosis + DOB + 2-DG infusion, RPP, ischemic zone (IZ) MBF, and ENDO/EPI decreased significantly. The IZ ratio of creatine phosphate-to-ATP decreased significantly [2.30 ± 0.14, 2.06 ± 0.13, and 2.04 ± 0.11 to 1.77 ± 0.12, 1.70 ± 0.11, and 1.72 ± 0.12 for EPI, midmyocardial (MID), and ENDO, respectively], and 2-DGP accumulated in all layers, as evidenced by the 2-DGP/PCr (0.55 ± 0.12, 0.52 ± 0.10, and 0.37 ± 0.08 for EPI, MID, and ENDO, respectively; P < 0.05, EPI > ENDO). In the IZ the wet weight-to-dry weight ratio was significantly increased compared with the normal zone (5.9 ± 0.5 vs. 4.4 ± 0.4; P < 0.05). Thus, in the stenotic perfused bed, during dobutamine-induced high cardiac work state, despite higher blood flow, the subepicardial layers showed the greater metabolic changes characterized by a shift toward higher carbohydrate metabolism, suggesting that a homeostatic response to high-cardiac work state is characterized by more glucose utilization in energy metabolism.


2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
P Mason McClatchey

Introduction: Impaired tissue oxygenation is observed in many disease states including congestive heart failure, diabetes, cancer and aging. Decreased tissue perfusion and heterogeneous distribution of blood flow in the microvasculature contributes to this pathology. The physiological mechanisms regulating homogeneity/heterogeneity of microvascular perfusion are presently unknown. We hypothesized that microfluidic properties of the glycocalyx would promote perfusion homogeneity. Methods: To test our hypothesis, we used established empirical formulations for modelling blood viscosity in vivo (blood vessels) and in vitro (glass tubes). We first assess distribution of blood flow in idealized arteriolar networks. We next simulated distribution of blood flow at an idealized capillary bifurcation. Finally, we simulated velocity profiles and pressure gradients within the vessel lumen with varying glycocalyx properties using a computational fluid dynamics approach. Results: We found that transit time heterogeneity (as assessed by STD to mean ratio) was increased approximately 9x (6.9x-10.6x) using in vitro formulations of blood viscosity relative to in vivo formulations. This effect was mathematically accounted for by increased effective blood viscosity in smaller arterioles. We also found that distribution of blood flow at an idealized microvascular bifurcation was more symmetric using the in vivo formulation than the in vitro formulation (approximately 2x greater disparity between flow in downstream vessels). This effect was mathematically accounted for by an increased hematocrit dependence of blood viscosity. Both the diameter- and hematocrit-based changes in blood viscosity were entirely predictable from fluid dynamics simulations incorporating a space-filling, semi-permeable glycocalyx layer. Summary: Our simulations indicate that the mechanical properties of the endothelial glycocalyx promote homogeneous microvascular perfusion. Conclusions: The literature provides evidence of both glycocalyx degradation and impaired tissue perfusion in the same disease states. Preservation or restoration of normal glycocalyx properties may be a viable strategy for improving tissue perfusion in a wide variety of diseases.


1982 ◽  
Vol 52 (6) ◽  
pp. 1629-1635 ◽  
Author(s):  
M. H. Laughlin ◽  
R. B. Armstrong ◽  
J. White ◽  
K. Rouk

A catheter-implantation procedure allowing use of the radiolabeled microsphere (MS) technique for measuring skeletal muscle blood flow (BF) in rats during high-speed treadmill running was desired. Attempts to use existing procedures were unsuccessful. We found that Silastic catheters (0.02 in. ID X 0.037 in. OD) placed in the ascending aorta (for MS infusions) and the renal artery (for reference sample withdrawal) minimized these exercise performance problems. It was then necessary to establish that aortic MS infusions result in good MS-blood mixing. We tested the method with the following: 1) the radioactivities found in reference withdrawal samples taken from two locations in the aorta were compared after left ventricular (LV) infusion and after aortic infusion; 2) BFs to bilaterally paired tissues were compared in anesthetized and conscious rats with LV and aortic infusions; 3) the distribution of MSs in the muscles was studied histologically; and 4) BFs in bilaterally paired tissues were compared in rats with aortic MS infusions during treadmill running. The results indicate that 1) the percent difference between the radioactivities found in the proximal and distal reference withdraw samples was the same for LV and aortic MS infusions; 2) BF to bilaterally paired tissue samples was the same with both LV or aortic MS infusions; 3) the MSs were distributed uniformly within muscles, and MS aggregation was not a significant problem; and 4) BFs to bilaterally paired tissue samples were the same in exercising rats. We conclude that this technique can be used to measure muscle BF in rats running on a treadmill.


1977 ◽  
Vol 232 (4) ◽  
pp. H441-H448 ◽  
Author(s):  
M. D. Stern ◽  
D. L. Lappe ◽  
P. D. Bowen ◽  
J. E. Chimosky ◽  
G. A. Holloway ◽  
...  

Laser light scattered from tissue in vivo is broadened in line width as a result of the Doppler shift produced by moving red cells in the microcirculation. A feasibility study was carried out to demonstrate use of this effect to measure and monitor tissue blood flow. Light from a helium-neon laser illuminated a 1-mm area of tissue (human skin or rat renal cortex), and the backscattered light was detected with a photomultiplier. The spectrum of the Doppler beat notes was analyzed directly with a digital spectrum analyzer, or processed by analog circuitry to yield a flow parameter based on the root-mean-square Doppler line width. This parameter was compared with 133Xe washout in the skin of volunteers subjected to UV-induced erythema and the skin of volunteers subjected to UV-induced erythema and was found to vary in an approximately linear manner with skin blood flow. The laser instrument provided continuous monitoring of blood flow fluctuations, including the pulsatile component. The instrument was used to monitor flow in the outer cortex of the rat kidney during administration of norepinephrine, angiotensin, hydralazine, dextran, dopamine, nitroprusside, and angiotensin blocked by saralasin. Dynamic and steady-state responses were consistent with known pharmacology and renal physiology, and with the assumption that vasoconstrictor angiotensin II receptors in the kidney are accessible to blood-borne inhibitors. The laser-Doppler method is a promising tool for rapid monitoring of dynamic changes in tissue perfusion.


1995 ◽  
Vol 15 (1) ◽  
pp. 88-96 ◽  
Author(s):  
Yuichi Maruki ◽  
Raymond C. Koehler ◽  
Jeffrey R. Kirsch ◽  
Kathleen K. Blizzard ◽  
Richard J. Traystman

Acidosis may augment cerebral ischemic injury by promoting lipid peroxidation. We tested the hypothesis that when acidosis is augmented by hyperglycemia, pretreatment with the 21-aminosteroid tirilazad mesylate (U74006F), a potent inhibitor of lipid peroxidation in vitro, improves early cerebral metabolic recovery. In a randomized, blinded study, anesthetized dogs received either tirilazad mesylate (1 mg/kg plus 0.2 mg/kg/h; n = 8) or vehicle (n = 8). Hyperglycemia (400–500 mg/dl) was produced prior to 30 min of global incomplete cerebral ischemia. Intracellular pH and high energy phosphates were measured by phosphorus magnetic resonance spectroscopy. During ischemia, microsphere-determined CBF decreased to 8 ± 4 ml min−1 100 g−1 and intracellular pH decreased to 5.6 ± 0.2 in both groups. During the first 20 min of reperfusion, ATP partially recovered in the vehicle group to 57 ± 21% of baseline, but then declined progressively in association with elevated intracranial pressure. By 30 min, ATP recovery was greater in the tirilazad group (77 ± 35 vs. 36 ± 19%), although postischemic hyperemia was similar. By 45 min, the tirilazad group had a higher intracellular pH (6.5 ± 0.5 vs. 5.9 ± 0.6) and a lower intracranial pressure (18 ± 6 vs. 52 ± 24 mm Hg). By 180 min, blood flow and ATP were undetectable in seven of eight vehicle-treated dogs, whereas ATP was >67% and pH was >6.7 in six of eight tirilazad-treated dogs. Thus, tirilazad acts during early reperfusion to prevent secondary metabolic decay associated with severe acidotic ischemia. If tirilazad acts by inhibiting lipid peroxidation, then these data are consistent with extreme acidosis limiting recovery by a mechanism involving lipid peroxidation.


Perfusion ◽  
2018 ◽  
Vol 34 (1) ◽  
pp. 67-75 ◽  
Author(s):  
Terje Aass ◽  
Lodve Stangeland ◽  
Christian Arvei Moen ◽  
Atle Solholm ◽  
Geir Olav Dahle ◽  
...  

Introduction: This experimental study compares myocardial function after prolonged arrest by St. Thomas’ Hospital polarizing cardioplegic solution (esmolol, adenosine, Mg2+) with depolarizing (hyperkalaemic) St. Thomas’ Hospital No 2, both administered as cold oxygenated blood cardioplegia. Methods: Twenty anaesthetized pigs on tepid (34°C) cardiopulmonary bypass (CPB) were randomised to cardioplegic arrest for 120 min with antegrade, repeated, cold, oxygenated, polarizing (STH-POL) or depolarizing (STH-2) blood cardioplegia every 20 min. Cardiac function was evaluated at Baseline and 60, 150 and 240 min after weaning from CPB, using a pressure-conductance catheter and epicardial echocardiography. Regional tissue blood flow, cleaved caspase-3 activity and levels of malondialdehyde were evaluated in myocardial tissue samples. Results: Preload recruitable stroke work (PRSW) was increased after polarizing compared to depolarizing cardioplegia 150 min after declamping (73.0±3.2 vs. 64.3±2.4 mmHg, p=0.047). Myocardial tissue blood flow rate was high in both groups compared to the Baseline levels and decreased significantly in the STH-POL group only, from 60 min to 150 min after declamping (p<0.005). Blood flow was significantly reduced in the STH-POL compared to the STH-2 group 240 min after declamping (p<0.05). Left ventricular mechanical efficiency, the ratio between total pressure-volume area and blood flow rate, gradually decreased after STH-2 cardioplegia and was significantly reduced compared to STH-POL cardioplegia after 150 and 240 min (p<0.05 for both). Conclusion: Myocardial protection for two hours of polarizing cardioplegic arrest with STH-POL in oxygenated blood is non-inferior compared to STH-2 blood cardioplegia. STH-POL cardioplegia alleviates the mismatch between myocardial function and perfusion after weaning from CPB


1999 ◽  
Vol 91 (5) ◽  
pp. 1349-1349 ◽  
Author(s):  
Sanjiv Mathur ◽  
Parviz Farhangkhgoee ◽  
Morris Karmazyn

Background Sodium ion-hydrogen ion (Na(+)-H(+)) exchange inhibitors are effective cardioprotective agents. The N(+)-H(+) exchange inhibitor HOE 642 (cariporide) has undergone clinical trials in acute coronary syndromes, including bypass surgery. Propofol and sevoflurane are also cardioprotective via unknown mechanisms. The authors investigated the interaction between propofol and HOE 642 in the ischemic reperfused rat heart and studied the role of adenosine triphosphate-sensitive potassium (K(ATP)) channels in the myocardial protection associated with propofol and sevoflurane. Methods Isolated rat hearts were perfused by the Langendorff method at a constant flow rate, and left ventricular function and coronary pressures were assessed using standard methods. Energy metabolites were also determined. To assess the role of K(ATP) channels, hearts were pretreated with the K(ATP) blocker glyburide (10 microM). Hearts were then exposed to either control buffer or buffer containing HOE 642 (5 microM), propofol (35 microM), sevoflurane (2.15 vol%), the K(ATP) opener pinacidil (1 microM), or the combination of propofol and HOE 642. Each heart was then subjected to 1 h of global ischemia followed by 1 h of reperfusion. Results Hearts treated with propofol, sevoflurane, pinacidil, or HOE 642 showed significantly higher recovery of left ventricular developed pressure and reduced end-diastolic pressures compared with controls. The combination of propofol and HOE 642 provided superior protection toward the end of the reperfusion period. Propofol, sevoflurane, and HOE 642 also attenuated the onset and magnitude of ischemic contracture and preserved high-energy phosphates (HEPs) compared with controls. Glyburide attenuated the cardioprotective effects of sevoflurane and abolished the protection observed with pinacidil. In contrast, glyburide had no effect on the cardioprotection associated with propofol treatment. Conclusion HOE 642, propofol, and sevoflurane provide cardioprotection via different mechanisms. These distinct mechanisms may allow for the additive and superior protection observed with the combination of these anesthetics and HOE 642.


1987 ◽  
Vol 252 (5) ◽  
pp. E581-E587 ◽  
Author(s):  
M. M. Jepson ◽  
M. Cox ◽  
P. C. Bates ◽  
N. J. Rothwell ◽  
M. J. Stock ◽  
...  

Endotoxins induce muscle wasting in part as a result of depressed protein synthesis. To investigate whether these changes reflect impaired energy transduction, blood flow, O2 extraction, and high-energy phosphates in muscle and whole-body O2 consumption (VO2) have been measured. VO2 was measured for 6h after an initial sublethal dose of endotoxin (Escherichia coli lipopolysaccharide 0.3 mg/100 g body wt sc) or saline and during 6h after a second dose 24 h later. In fed or fasted rats, VO2 was either increased or better maintained after endotoxin. In anesthetized fed rats 3-4 after the second dose of endotoxin VO2 was increased, and this was accompanied by increased blood flow to liver (hepatic arterial supply), kidney, and perirenal brown adipose tissue and a 57 and 64% decrease in flow to back and hindlimb muscle, respectively, with no change in any other organ. Hindlimb arteriovenous O2 was unchanged, indicating markedly decreased aerobic metabolism in muscle, and the contribution of the hindlimb to whole-body VO2 decreased by 46%. Adenosine 5'-triphosphate levels in muscle were unchanged in endotoxin-treated rats, and this was confirmed by topical nuclear magnetic resonance spectroscopy, which also showed muscle pH to be unchanged. These results show that although there is decreased blood flow and aerobic oxidation in muscle, adenosine 5'-triphosphate availability does not appear to be compromised so that the endotoxin-induced muscle catabolism and decreased protein synthesis must reflex some other mechanism.


Angiology ◽  
2020 ◽  
Vol 72 (1) ◽  
pp. 9-15
Author(s):  
Pavel Poredos ◽  
Mateja K. Jezovnik ◽  
Rajko Radovancevic ◽  
Igor D. Gregoric

The endothelium plays a crucial role in maintaining cardiovascular homeostasis. Shear stress generated by flowing blood regulates the release of substances that provide adequate tissue perfusion. The extent of damage to endothelial cells depends on locally disturbed shear stress caused by the deteriorated flow. Patients with heart failure have reduced cardiac output, which results in reduced blood flow and negative shear stress. Reduced shear stress also affects microcirculation and reduces tissue perfusion. Consequently, the production of free oxygen radicals is increased and bioavailability of nitric oxide is additionally decreased. Therefore, endothelial dysfunction is involved in the progression of heart failure and cardiovascular events. Left ventricular assist devices (LVAD) are used for the treatment of patients with advanced heart failure. Older pulsatile flow LVADs were mostly substituted by continuous-flow LVADs (cf-LVADs). Despite the advantages of the cf-LVADs, the loss of pulsatility leads to different complications on the micro- and macrovascular levels. One of the pathogenetic mechanisms of cardiovascular complications with cf-LVADs may be endothelial dysfunction, which after the implantation of the device does not improve and may even deteriorate. In contrast, the pulsatile pattern of LVADs on blood flow could preserve endothelial function.


1997 ◽  
Vol 273 (1) ◽  
pp. H418-H425 ◽  
Author(s):  
T. Tsukube ◽  
J. D. McCully ◽  
K. R. Metz ◽  
C. U. Cook ◽  
S. Levitsky

Previously, we have shown that potassium and magnesium (K-Mg, 20 mM each) cardioplegia ameliorated cytosolic calcium ([Ca2+]i) accumulation and was associated with enhanced functional recovery after surgically induced global ischemia in the aged heart. K-Mg cardioplegia was also shown to enhance cytosolic cytochrome oxidase I activity and mRNA levels, suggesting that enhanced functional recovery may involve the preservation of high-energy phosphates. To investigate this hypothesis, 31P nuclear magnetic resonance was used to measure serial alterations in phosphocreatine (PCr), inorganic phosphate, nucleoside triphosphate (NTP), intracellular free magnesium (Mgf), and intracellular pH (pHi) in Langendorff-perfused, aged (135 wk) rabbit hearts during preischemia, global ischemia (30 min), and reperfusion (30 min). K-Mg cardioplegia retarded PCr depletion (P <0.05) and significantly enhanced NTP preservation (P < 0.05) during ischemia and reperfusion. K-Mg cardioplegia also attenuated the increase in Mgf during ischemia (P < 0.05). These results were correlated with amelioration of [Ca2+]i accumulation during ischemia and preservation of left ventricular function after reperfusion and suggest that optimal functional recovery from surgically induced ischemia is provided by K-Mg cardioplegia in the aged myocardium.


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