Hibernating Myocardium

1998 ◽  
Vol 78 (4) ◽  
pp. 1055-1085 ◽  
Author(s):  
GERD HEUSCH
Keyword(s):  
Blood Flow ◽  
Myocardial Ischemia ◽  
Contractile Function ◽  
Myocardial Dysfunction ◽  
Experimental Studies ◽  
Reperfusion Therapy ◽  
Myocardial Contraction ◽  
Hibernating Myocardium ◽  
Short Term ◽  
Chronic Hibernation

Heusch, Gerd. Hibernating Myocardium. Physiol. Rev. 78: 1055–1085, 1998. — Decreased myocardial contraction occurs as a consequence of a reduction in blood flow. The concept of hibernation implies a downregulation of contractile function as an adaptation to a reduction in myocardial blood flow that serves to maintain myocardial integrity and viability during persistent ischemia. Unequivocal evidence for this concept exists in scenarios of myocardial ischemia that lasts for several hours, and sustained perfusion-contraction matching, recovery of energy and substrate metabolism, the potential for recruitment of inotropic reserve at the expense of metabolic recovery, and lack of necrosis are established criteria of short-term hibernation. The mechanisms of short-term hibernation, apart from reduced calcium responsiveness, are not clear at present. Experimental studies with chronic coronary stenosis lasting more than several hours have failed to continuously monitor flow and function. Nevertheless, a number of studies in chronic animal models and patients have demonstrated regional myocardial dysfunction at reduced resting blood flow that recovered upon reperfusion, consistent with chronic hibernation. Further studies are required to distinguish chronic hibernation from cumulative stunning. With a better understanding of the mechanisms underlying short-term hibernation, it is hoped that these adaptive responses can be recruited and reinforced to minimize the consequences of acute myocardial ischemia and delay impending infarction. Patients with chronic hibernation must be identified and undergo adequate reperfusion therapy.

Protamine inhibits coronary collateral development in a canine model of repetitive coronary occlusion

1995 ◽  
Vol 268 (2) ◽  
pp. H720-H728 ◽  
Author(s):  
J. R. Kersten ◽  
P. S. Pagel ◽  
D. C. Warltier
Keyword(s):  
Blood Flow ◽  
Myocardial Ischemia ◽  
Contractile Function ◽  
Regional Myocardial Blood Flow ◽  
Collateral Development ◽  
Coronary Collateral ◽  
Debt Repayment ◽  
Chronic Myocardial Ischemia

Protamine has been demonstrated to inhibit angiogenesis in vitro and in vivo; however, its effect on coronary collateral development has not been examined. The present investigation tested the hypothesis that subcutaneously administered protamine inhibits canine coronary collateral development in response to chronic myocardial ischemia. Dogs underwent daily, repetitive, 2-min, left anterior descending coronary artery (LAD) occlusions for 22 consecutive days. Regional myocardial blood flow (radioactive microspheres), LAD segment shortening, and coronary flow debt repayment were measured in saline-treated (n = 7) and protamine-treated (n = 6) dogs on days 1, 8, 15, and 22. Coronary collateral development in saline-treated dogs was demonstrated by time-dependent significant (P < 0.05) increases in collateral blood flow to ischemic myocardium [day 1 0.10 +/- 0.01 vs. day 22 0.88 +/- 0.05 (SE) ml.min-1.g-1], progressive normalization of myocardial contractile function during LAD occlusion, and successive reduction in flow debt repayment. In contrast, protamine treatment significantly attenuated, increases in collateral perfusion (day 1 0.13 +/- 0.02 vs. day 22 0.36 +/- 0.03 ml.min-1.g-1). Regional contractile dysfunction and postocclusive reactive hyperemic responses were sustained over time in protamine-treated compared with saline-treated dogs. The results demonstrate that protamine inhibits coronary collateral development in response to chronic myocardial ischemia.

Myocardial hibernation: a delicate balance

2005 ◽  
Vol 288 (3) ◽  
pp. H984-H999 ◽  
Author(s):  
Gerd Heusch ◽  
Rainer Schulz ◽  
Shahbudin H. Rahimtoola
Keyword(s):  
Blood Flow ◽  
Contractile Function ◽  
Ischemia Reperfusion ◽  
Hibernating Myocardium ◽  
Regional Myocardial Blood Flow ◽  
Regional Energy ◽  
Myocardial Hibernation ◽  
Normal Blood Flow ◽  
Myocardial Ischemia Reperfusion ◽  
Regional Contractile Function

The pathophysiology of myocardial hibernation is characterized as a situation of reduced regional contractile function distal to a coronary artery stenosis that recovers after removal of the coronary stenosis. A subacute “downregulation” of contractile function in response to reduced regional myocardial blood flow exists, which normalizes regional energy and substrate metabolism but does not persist for more than 12–24 h. Chronic hibernation develops in response to one or more episodes of myocardial ischemia-reperfusion, possibly progressing from repetitive stunning with normal blood flow to hibernation with reduced blood flow. An upregulation of a protective gene program is seen in hibernating myocardium, putting it into the context of preconditioning. The morphology of hibernating myocardium is characterized by both adaptive and degenerative features.

Influence of insulin and free fatty acids on contractile function in patients with chronically stunned and hibernating myocardium

2005 ◽  
Vol 289 (2) ◽  
pp. H938-H946 ◽  
Author(s):  
Henrik Wiggers ◽  
Helene Nørrelund ◽  
Søren Steen Nielsen ◽  
Niels H. Andersen ◽  
Jens Erik Nielsen-Kudsk ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Steady State ◽  
Free Fatty Acids ◽  
Maximal Exercise ◽  
Contractile Function ◽  
Ischemic Myocardium ◽  
Hibernating Myocardium ◽  
Short Term ◽  
Metabolic Modulation ◽  
Substrate Supply

It is unknown whether short-term modulation of substrate supply affects cardiac performance in heart failure patients with chronic ischemic myocardium. The aim of this study was to determine whether modulation of myocardial substrate metabolism with insulin and free fatty acids (FFAs) affects contractile function of chronically stunned (CST) and hibernating (HIB) myocardium at rest and after maximal exercise. We studied eight nondiabetic patients with ejection fraction (EF) 30 ± 4% (SE) and CST/HIB in 49 ± 6% of the left ventricle: 36 ± 6% CST and 13 ± 2% HIB as determined by 99mTechnetium-Sestamibi single photon emission computed tomography (SPECT) and [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET). Each patient was subjected to a 3-h infusion of 1) saline, 2) insulin-glucose (i.e., euglycemic insulin clamp; high insulin, suppressed FFA), and 3) somatostatin-heparin (suppressed insulin, high FFA). Echocardiographic endpoints were global EF and regional contractile function [maximum velocity ( Vmax) and strain rate (εmax)] as determined by tissue Doppler imaging at steady state and after maximal exercise. EF was similar at baseline and steady state and increased after exercise to 36 ± 5% ( P < 0.05). Baseline regional Vmax and εmax were highest in control, intermediate in CST and HIB, and lowest in infarct regions ( P < 0.05). Steady-state EF, Vmax, and εmax were not affected by metabolic modulation in any region. After maximal exercise, contractile function increased in control, CST, and HIB ( P < 0.05), but not in infarct, regions. Exercise-induced contractile increments were unaffected by metabolic modulation. Metabolic modulation does not influence contractile function in CST and HIB regions. Chronic ischemic myocardium has preserved ability to adapt to extreme, short-term changes in substrate supply at rest and after maximal exercise.

Less afterload sensitivity in short-term hibernating than in acutely ischemic and stunned myocardium

2000 ◽  
Vol 279 (3) ◽  
pp. H1106-H1110 ◽  
Author(s):  
Rainer Schulz ◽  
Jochen Rose ◽  
Heiner Post ◽  
Andreas Skyschally ◽  
Gerd Heusch
Keyword(s):  
Contractile Function ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Negative Slope ◽  
Stunned Myocardium ◽  
Hibernating Myocardium ◽  
Wall Thickening ◽  
Short Term ◽  
The Relationship ◽  
Systolic Wall Thickening

Short-term hibernating myocardium is characterized by reduced contractile function during persistent moderate ischemia, the recovery of metabolic parameters, and the absence of necrosis. To study the afterload dependence of regional wall excursion in short-term hibernating myocardium, in 11 enflurane-anesthetized swine the left anterior descending coronary artery was cannulated and hypoperfused for 90 min to reduce anterior systolic wall thickening (WT, sonomicrometry) by 60%. Under control conditions, at 5 and 90 min ischemia the descending thoracic aorta was acutely constricted to increase left ventricular (LV) pressure by 30 mmHg. Under control conditions, increased LV pressure resulted in decreased WT [i.e., a negative slope of the relationship between WT and LV end-systolic pressure: −11.2 ± 4.2 (SD) μm/mmHg]. This slope was further significantly decreased at 5 min ischemia (−26.5 ± 8.8 μm/mmHg) but returned toward control values in short-term hibernating myocardium at 90 min ischemia (−17.2 ± 6.6 μm/mmHg). At 30 min reperfusion, the slope was once more significantly decreased (−27.8 ± 8.1 μm/mmHg). In conclusion, WT in short-term hibernating myocardium is less afterload dependent than in acutely ischemic and reperfused myocardium.

Regional short-term myocardial hibernation in swine does not involve endogenous adenosine or KATP channels

1995 ◽  
Vol 268 (6) ◽  
pp. H2294-H2301 ◽  
Author(s):  
R. Schulz ◽  
J. Rose ◽  
H. Post ◽  
G. Heusch
Keyword(s):  
Contractile Function ◽  
Myocardial Necrosis ◽  
Katp Channels ◽  
Creatine Phosphate ◽  
Hibernating Myocardium ◽  
Phosphate Content ◽  
Short Term ◽  
Endogenous Adenosine ◽  
Myocardial Hibernation ◽  
The Impact

Short-term hibernating myocardium is characterized by reduced contractile function during persistent ischemia, the recovery of metabolism over time, a recruitable inotropic reserve, and the lack of necrosis. The mechanisms underlying myocardial hibernation are unclear. The present study addressed the role of endogenous adenosine and that of activation of ATP-dependent potassium (KATP) channels. In 22 enflurane-anesthetized swine, coronary inflow was reduced to decrease regional myocardial work (W, measured by sonomicrometry) by 60-70% at 5 min of ischemia; this flow reduction has previously been shown to be compatible with the development of myocardial hibernation. Systemic hemodynamics, W, subendocardial blood flow (measured by microspheres), and the myocardial creatine phosphate content (measured by biopsies, mumol/g wet wt) were measured under control conditions and during 90 min of ischemia, with an intracoronary dobutamine infusion during the last 5 min of ischemia. The impact of endogenous adenosine was eliminated by infusion of intracoronary adenosine deaminase (ADA), and the impact of activation of KATP channels by glibenclamide. Creatine phosphate content recovered in the placebo-treated swine (n = 8, 3.8 +/- 1.9 to 5.8 +/- 2.0 mumol/g wet wt) as well as in swine receiving ADA (n = 7, 4.1 +/- 1.2 to 6.0 +/- 1.7 mumol/g wet wt) or glibenclamide (n = 7, 2.8 +/- 1.3 to 6.7 +/- 1.6 mumol/g wet wt) when ischemia was prolonged from 5 to 85 min. At the end of 90 min of ischemia, W increased during intracoronary dobutamine in all three groups to a comparable extent, and myocardial necrosis was absent in all three groups of swine.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Myocardial ischemia: lack of coronary blood flow, myocardial oxygen supply-demand imbalance, or what?

2019 ◽  
Vol 316 (6) ◽  
pp. H1439-H1446 ◽  
Author(s):  
Gerd Heusch
Keyword(s):  
Blood Flow ◽  
Myocardial Ischemia ◽  
Myocardial Blood Flow ◽  
Coronary Blood Flow ◽  
Oxygen Supply ◽  
Contractile Function ◽  
Historical Background ◽  
Prevailing Paradigm ◽  
And Function ◽  
Myocardial Oxygen Supply

This opinionated article reviews current concepts of myocardial ischemia. Specifically, the historical background is briefly presented. Then, the prevailing paradigm of myocardial oxygen-supply-demand imbalance is criticized since demand is a virtual parameter that cannot be measured and data on measurements of myocardial blood flow and contractile function rather support matching between flow and function. Finally, a concept of myocardial ischemia that focusses on the reduction of coronary blood flow to below 8–10 µl/g per beat with consequences for myocardial electrical, metabolic, contractile and morphological features is advocated.

EXPERIMENTAL STUDIES OF CAR PROPERTIES ON A PHYSICAL MODEL

2019 ◽  
pp. 10-16
Author(s):  
Oleksii Timkov ◽  
Dmytro Yashchenko ◽  
Volodymyr Bosenko
Keyword(s):  
Mathematical Model ◽  
Remote Control ◽  
Physical Model ◽  
Model Experiment ◽  
Experimental Studies ◽  
Electrical Energy ◽  
Short Term ◽  
Motor Current ◽  
Memory Card ◽  
The Mathematical Model

The article deals with the development of a physical model of a car equipped with measuring, recording and remote control equipment for experimental study of car properties. A detailed description of the design of the physical model and of the electronic modules used is given, links to application libraries and the code of the first part of the program for remote control of the model are given. Atmega microcontroller on the Arduino Uno platform was used to manage the model and register the parameters. When moving the car on the memory card saved such parameters as speed, voltage on the motor, current on the motor, the angle of the steered wheel, acceleration along three coordinate axes are recorded. Use of more powerful microcontrollers will allow to expand the list of the registered parameters of movement of the car. It is possible to measure the forces acting on the elements of the car and other parameters. In the future, it is planned to develop a mathematical model of motion of the car and check its adequacy in conducting experimental studies on maneuverability on the physical model. In addition, it is possible to conduct studies of stability and consumption of electrical energy. The physical model allows to quickly change geometric dimensions and mass parameters. In the study of highway trains, this approach will allow to investigate the various layout schemes of highway trains in the short term. It is possible to make two-axle road trains and saddle towed trains, three-way hitched trains of different layout. The results obtained will allow us to improve not only the mathematical model, but also the experimental physical model, and move on to further study the properties of hybrid road trains with an active trailer link. This approach allows to reduce material and time costs when researching the properties of cars and road trains. Keywords: car, physical model, experiment, road trains, sensor, remote control, maneuverability, stability.

The capacity of short term memory from an evolutionary perspective

2019 ◽  
Author(s):  
Majid Manoochehri
Keyword(s):  
Short Term Memory ◽  
Memory Span ◽  
Critical Role ◽  
Experimental Studies ◽  
Cognitive System ◽  
Evolutionary Approach ◽  
Evolutionary Perspective ◽  
Short Term ◽  
Term Memory

Memory span in humans has been intensely studied for more than a century. In spite of the critical role of memory span in our cognitive system, which intensifies the importance of fundamental determinants of its evolution, few studies have investigated it by taking an evolutionary approach. Overall, we know hardly anything about the evolution of memory components. In the present study, I briefly review the experimental studies of memory span in humans and non-human animals and shortly discuss some of the relevant evolutionary hypotheses.

Effect of alkali therapy with NaHCO3 or THAM on cardiac contractility

1996 ◽  
Vol 270 (5) ◽  
pp. R955-R962
Author(s):  
C. D. Mazer ◽  
B. Naser ◽  
K. S. Kamel
Keyword(s):  
Myocardial Ischemia ◽  
Contractile Function ◽  
Venous Blood ◽  
Systolic Pressure ◽  
Ischemic Myocardium ◽  
Stroke Work ◽  
Length Relationship ◽  
Alkali Therapy ◽  
Myocardial Contractile ◽  
The Impact

We examined the impact of alkali therapy on myocardial contractility in a model of myocardial ischemia in dogs using direct measurements of myocardial contractile function. Myocardial ischemia in the left anterior descending (LAD) artery territory was induced using a perfusion circuit from the internal carotid artery to the LAD artery. Myocardial contractile function was assessed using sonomicrometry for measurement of percent systolic shortening (%SS), preload recruitable stroke work (PRSW) slope, and end-systolic pressure-length relationship (ESPLR) area. Because the blood flow in LAD artery was diminished by approximately 70%, there was a significant decrease in O2 delivery and uptake by the ischemic myocardium. Ischemia led to a significant fall in LAD regional contractile function with %SS decreasing from 15 +/- 2 to 7 +/- 2%, PRSW slope from 82 +/- 10 to 37 +/- 5 mmHg, and ESPLR area from 121 +/- 2 to 48 +/- 14 mmHg.mm (P < 0.05). In six dogs, the intracoronary administration of NaHCO(3) resulted in a significant increase in pH in LAD arterial and venous blood. There was, however, no significant increase in %SS (6 +/- 2), PRSW slope (43 +/- 10 mmHg), or ESPLR area (60 +/- 13 mmHg.mm). Since administration of NaHCO(3) resulted in a significant increase in PCO2 in LAD arterial and venous blood, similar experiments were carried out in five dogs, but with the intracoronary infusion of the amine buffer THAM [tris(hydroxymethyl)aminomethane (Tris) buffer; 2-amino-2-hydroxyl-1,3-propandiol] instead of NaHCO3. Although administration of THAM resulted in a significant increase in pH and a significant decrease in PCO2, in both LAD arterial and venous blood, there was no significant improvement in any of the parameters used to assess myocardial contractile function. In conclusion, administration of alkali (NaHCO3 or THAM) does not enhance the contractile function of the ischemic myocardium.

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