Regional Blood Flow, Contractility and Metabolism in Early Myocardial Infarction

Weishaar, Ronald E.; Sarma, J. S. M.; Maruyama, Yukio; Fischer, Renate; Bing, Richard J.

doi:10.1159/000169836

Cited by 29 publications

(15 citation statements)

References 27 publications

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“…Decreased systolic fiber shortening (1), increased anaerobic metabolites (2,3), microvascular damage (4,5), and decreased blood flow, especially in the subendocardium (6), are all characteristics of the ischemic or infarcted region. Decreased mitochondrial respiration (7), tissue Po2 (8), and increased 02 extraction as well as decreased 02 consumption (9,10) indicate alterations in 02 availability and demand. Recent work has shown substantial variability of small artery and vein saturations as well as heterogeneous regions of 02 extraction and consumption within the center of an ischemic zone caused by coronary artery ligation (11).…”

Section: Introductionmentioning

confidence: 99%

Role of Propranolol in Improvement of the Relationship between O2 Supply and Consumption in an Ischemic Region of the Dog Heart

Conway¹,

Weiss²

1982

J. Clin. Invest.

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A B S T R A C T Several aspects of the myocardial 02 supply/consumption relationship were determined after coronary artery occlusion and subsequent /l-adrenergic blockade in 16 anesthetized open-chest dogs. Small artery and vein 02 saturations, and hence extraction, were obtained microspectrophotometrically and combined with radioactive microsphere blood flow determinations to calculate regional myocardial 02 consumption. Eight dogs remained untreated after coronary artery ligation while another group was given 2 mg/kg propranolol, 10 min after occlusion. Untreated occlusion resulted in decreased arterial and especially venous 02 saturations, indicating an increased 02 extraction. Ischemic 02 consumption was reduced and the subendocardial/subepicardial consumption ratio was reversed (1.26 vs. 0.37) due to the pattern of occluded area flow. Calculated 02 supply/ consumption also decreased. Propranolol produced no significant changes in volume or distribution of flow within the ischemic region while reducing flow, extraction, and consumption in the unoccluded region. The heterogeneity of arterial and particularly venous 02 saturations within the ischemic region decreased dramatically. Venous 02 saturations were elevated relative to the control group resulting in a reduced 02 extraction. The decrease in heterogeneity of arterial and venous 02 saturations suggest that propranolol eliminates microregions of relatively high 02 extraction, consumption, and/or a majority of vessels with extremely low flow. This leads to a significant improvement in the 02 supply/consumption ratio in the ischemic myocardium of the dog. This may be due to a reduction in the heterogeneity and level of nj-adrenergic receptor activity within the heart.

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Section: Introductionmentioning

confidence: 99%

Role of Propranolol in Improvement of the Relationship between O2 Supply and Consumption in an Ischemic Region of the Dog Heart

Conway¹,

Weiss²

1982

J. Clin. Invest.

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“…Emphasis was placed on mitochondrial function in the present study, since previous work has stressed that these organelles are sensitive indicators of myocardial damage under the conditions employed (14,(29)(30)(31)(32). The question arises whether the mitochondria isolated from the occluded region were in fact uniformly ischemic.…”

Section: Biochemical Changesmentioning

confidence: 99%

The Relationship of Regional Coronary Blood Flow to Mitoehondrial Function during Reperfusion of the Ischemic Myocardium

Weishaar¹,

Tschurtschenthaler²,

Ashikawa³

et al. 1979

Cardiology

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The relationship of changes in regional coronary flow to the nature and degree of biochemical disturbances during occlusion of branches of the left anterior descending coronary artery and following reestablishment of flow was investigated in two groups of dogs: group I, moderate ischemia before reflow, and group II, severe ischemia prior to reflow. Regional coronary blood flow was determined before ligation, after 60 min of ischemia and after 15 min of reflow using labelled microspheres. Hearts made ischemic for 60 min but not reperfused served as controls. Groups I and II were distinguished by the following features. Group II showed a marked exacerbation of biochemical damage on reperfusion of the ischemic region (reduced levels of ATP, impairment of mitoehondrial oxygen consumption and mitoehondrial calcium binding). This was accompanied by significant subendocardial hyperemia. Reperfusion in group I, on the other hand, partially reversed these changes (increased level of ATP in the ischemic-reperfused region, improved mitoehondrial oxygen consumption and calcium binding). Mitoehondrial calcium uptake and oxidative phosphorylation (ADP/O ratio) were not affected in any group. These data illustrate that the degree of biochemical damage following reperfusion of the ischemic myocardium is determined by the degree of ischemia, and suggest that interference with ATP production by the mitochondria is not responsible for the damage.

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“…Mitochondrial dysfunction and ultrastructural subcellular damage have been previously identified as one of the first signs of cardiac ischemic injury, and this in turn affects infarcted cardiac wall motion [8,9]. Ischemic damage results in changes to mitochondrial respiration [9].…”

Section: Introductionmentioning

confidence: 99%

“…Ischemic damage results in changes to mitochondrial respiration [9]. Mitochondrial respiration can be measured in vitro from isolated mitochondria by incubating these subcellular fractions in an isotonic medium containing succinate and phosphate.…”

Section: Introductionmentioning

confidence: 99%

“…Mitochondrial respiration can be measured in vitro from isolated mitochondria by incubating these subcellular fractions in an isotonic medium containing succinate and phosphate. The addition of ADP to this medium causes a sudden burst of oxygen uptake as the ADP is converted into ATP [9]. The actively respiring state is referred to as "state 3" respiration, whereas the slower rate after all the ADP has been phosphorylated to form ATP is referred to as "state 4".…”

Section: Introductionmentioning

confidence: 99%

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Reduced cardiac output is associated with decreased mitochondrial efficiency in the non-ischemic ventricular wall of the acute myocardial-infarcted dog

et al. 2006

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Cardiogenic shock is the leading cause of death among patients hospitalized with acute myocardial infarction (MI). Understanding the mechanisms for acute pump failure is therefore important. The aim of this study is to examine in an acute MI dog model whether mitochondrial bio-energetic function within non-ischemic wall regions are associated with pump failure. Anterior MI was produced in dogs via ligation of left anterior descending (LAD) coronary artery, that resulted in an infract size of about 30% of the left ventricular wall. Measurements of hemodynamic status, mitochondrial function, free radical production and mitochondrial uncoupling protein 3 (UCP3) expression were determined over 24 h period. Hemodynamic measurements revealed a > 50% reduction in cardiac output at 24 h post infarction when compared to baseline. Biopsy samples were obtained from the posterior non-ischemic wall during acute infarction. ADP/O ratios for isolated mitochondria from non-ischemic myocardium at 6 h and 24 h were decreased when compared to the ADP/O ratios within the same samples with and without palmitic acid (PA). GTP inhibition of (PA)-stimulated state 4 respiration in isolated mitochondria from the non-ischemic wall increased by 7% and 33% at 6 h and 24 h post-infarction respectively when compared to sham and pre-infarction samples. This would suggest that the mitochondria are uncoupled and this is supported by an associated increase in UCP3 expression observed on western blots from these same biopsy samples. Blood samples from the coronary sinus measured by electron paramagnetic resonance (EPR) methods showed an increase in reactive oxygen species (ROS) over baseline at 6 h and 24 h post-infarction. In conclusion, mitochondrial bio-energetic ADP/O ratios as a result of acute infarction are abnormal within the non-ischemic wall. Mitochondria appear to be energetically uncoupled and this is associated with declining pump function. Free radical production may be associated with the induction of uncoupling proteins in the mitochondria.

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Regional Blood Flow, Contractility and Metabolism in Early Myocardial Infarction

Cited by 29 publications

References 27 publications

Role of Propranolol in Improvement of the Relationship between O2 Supply and Consumption in an Ischemic Region of the Dog Heart

Role of Propranolol in Improvement of the Relationship between O2 Supply and Consumption in an Ischemic Region of the Dog Heart

The Relationship of Regional Coronary Blood Flow to Mitoehondrial Function during Reperfusion of the Ischemic Myocardium

Reduced cardiac output is associated with decreased mitochondrial efficiency in the non-ischemic ventricular wall of the acute myocardial-infarcted dog

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