Subendocardial anaerobic metabolism in experimental aortic stenosis

Dm, Griggs; Cc, Chen; Tchokoev, VV

doi:10.1152/ajplegacy.1973.224.3.607

Cited by 44 publications

(10 citation statements)

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“…The increase in myocardial tissue water percentage in Experimental Group II was unanticipated in view of our previous negative findings under somewhat similar metabolic conditions (3,4,10). However, this difference from our previous results could be due to the fact that the experimental forcing was longer in the present study.…”

Section: Methodscontrasting

confidence: 79%

“…Despite this abnormality in myocardial lactate metabolism, the coronary sinus blood oxygen tension was not significantly different from normal. This has been noted previously in the presence of subendocardial anaerobic metabolism due to experimental aortic stenosis (10), and suggests that lactate production from less than the total myocardium can raise the coronary sinus level while total myocardial oxygen extraction is unchanged or even reduced.…”

Section: Methodssupporting

confidence: 76%

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Coronary Hemodynamics and Regional Myocardial Metabolism in Experimental Aortic Insufficiency

Griggs¹,

Chen²

1974

J. Clin. Invest.

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ABSTRA CT Acute aortic valvular insufficiency was induced in open chest dogs by employing a special intravascular cannula, or by rupturing an aortic valve leaflet. Phasic and mean coronary flow were assessed in some animals, while in others data were obtained on arterial and coronary sinus blood lactate, pyruvate, Po2, Pco2, and pH, and on myocardial tissue lactate, pyruvate, and water content in the outer and inner halves of the free wall of the left ventricle. Results showed that in acute aortic insufficiency diastolic coronary flow decreased as a function of aortic diastolic pressure, but systolic coronary flow increased in such proportion that mean coronary flow did not decrease. With moderate reductions in aortic diastolic pressure due to aortic insufficiency, myocardial blood flow was judged to be nutritionally adequate in both the outer and inner regions of the left ventricle. With more severe reductions in aortic diastolic pressure, the inner region exihibited biochemical signs of anaerobic metabolism. The presence of these metabolic changes could be correlated with either of two previously described pressure indexes. These findings suggest that the reduced coronary perfusion pressure and the intramyocardial tissue pressure gradient can be compensated for by autoregulation in some cases of aortic insufficiency, but in others such compensation may be incomplete, in which case oxygen delivery to the subendocardium will be inadequate to meet local tissue oxygen needs. INTRODUCTIONIt is apparent from the high incidence of angina pectoris in patients with severe aortic insufficiency (1) December 1973. this is related to the low perfusion pressure in the coronary circulation during diastole-the time when coronary flow is normally greatest-and the greater than normal energy requirements of the hyperfunctioning left ventricle. Recently, Buckberg, Fixler, Archie, and Hoffman (2) demonstrated that when aortic diastolic pressure was lowered in the dog by opening a large arteriovenous fistula, blood flow in the wall of the left ventricle became uneven and lower in the subendocardium than the subepicardium. They correlated the regional flow changes with a special pressure index they developed to assess the balance between oxygen supply and demand in the subendocardium. It was not possible, however, to determine from the flow data or the pressure index to what extent, if any, the metabolic needs of the subendocardium were being under met when aortic diastolic pressure was reduced.In previous animal studies from our laboratory (3, 4) we showed that when pressure in the coronary circulation was independently reduced by coronary constriction, the subendocardium developed metabolic signs of inadequate oxygen delivery. This finding correlated well with a pressure index developed by us to predict the presence of uneven myocardial blood flow (5). It (Fig. 1) into the aorta via the ligated left subclavian artery and passing it retrograde across the aortic valve. This tube, henceforth referred to as an "aortic insuffi...

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Section: Methodscontrasting

confidence: 79%

Section: Methodssupporting

confidence: 76%

Coronary Hemodynamics and Regional Myocardial Metabolism in Experimental Aortic Insufficiency

Griggs¹,

Chen²

1974

J. Clin. Invest.

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“…Both studies supported the concept that the subendocardium is more vulnerable to hypoxia than is the subepicardium because of a transmural gradient in myocardial tissue pressure (5, 6) which imposes a nonuniform type of extravascular resistance on the coronary circulation. Additional studies from this (1, 3,4,8) and other laboratories (7,(20)(21)(22)(23)(24)(25) have added considerable support to the hypothesis that the greater vulnerability of the subendocardium to hypoxic injury is due to a nonuniform distribution of myocardial blood flow in the underperfused ventricle.…”

Section: Discussionmentioning

confidence: 82%

Transmural gradients in ventricular tissue metabolites produced by stopping coronary blood flow in the dog.

Dunn¹,

Griggs²

1975

Circulation Research

120

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To determine whether transmural metabolite gradients develop in the contracting, ischemic left ventricle due to factors other than a nonuniform distribution of myocardial blood flow, right and left coronary artery inflow was completely stopped with vessel occluders in open-chest dogs for 15 or 30 seconds before a transmural myocardial tissue sample was obtained for regional analysis of creatine phosphate, adenosine triphosphate (ATP), and lactate. Heart rate was controlled, and the decline in left ventricular systolic pressure during the period in which coronary blood flow was stopped was attenuated by aortic constriction. Studies were also performed in dogs that were (1) pretreated with propranolol, (2) subjected to ventricular fibrillation, and (3) volume loaded. Control studies revealed no transmural metabolite gradients in the normally perfused ventricle, but creatine phosphate was slightly lower in the inner region than it was in the outer and middle ventricular wall regions. With coronary blood flow stopped for 30 seconds, a significant lactate gradient, increasing from the outer to the inner region, was present. Propranolol-treated dogs with their coronary blood flow stopped for 30 seconds also exhibited a lactate gradient, but dogs with ventricular fibrillation and their coronary blood flow stopped for 30 seconds did not. Volume-loaded dogs with their coronary blood flow stopped for only 15 seconds had a significant lactate gradient. Reciprocal gradients occurred in creatine phosphate but not in ATP. The findings suggest that the contracting ventricle uses energy unevenly and that in myocardial ischemia one of the factors causing greater subendocardial vulnerability is a greater energy need in this region.• Previous studies from this laboratory have shown that metabolic changes occurring in the left ventricle because of inadequate coronary blood flow are greater in the subendocardium than they are in the subepicardium (1-4). This difference has been attributed primarily to nonuniform systolic compression of the coronary vessels (5, 6) which results in a greater impairment of subendocardial blood flow than it does of subepicardial blood flow (7,8). However, the possibility also exists that other factors, such as a higher subendocardial energy requirement (9-12), a greater capacity of subendocardial tissue cells for glycolysis (13,14), or greater subendocardial beta-adrenergic stimulation, contribute to the uneven metabolic response. The primary purpose of the present study was to investigate these possibilities in open-chest dogs by examining regional metabolite levels in the left ventricle after blood flow had been completely stopped in both the left and right coronary arteries for a brief but metabolically significant interval of time. Heart rate was controlled, and the decline in This work was supported by U. S. Public Health Service Grant HL 11876 from the National Heart and Lung Institute and by the Missouri Heart Association.Received April 7, 1975. Accepted for publication June 30, 1975. ...

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“…In another study in which /3-adrenergic stimulation in the presence of a proximal aortic stenosis caused a fall in systolic coronary perfusion pressure by 120 mm Hg below left ventricular systolic pressure, subendocardial lactate was 2.2-fold greater and ATP levels in the subendocardium were diminished by 3%. 34 It should be noted that a higher glycogen content" as well as a greater activity of glycogen phosphorylase and other glycolytic enzymes 35 - 36 are present in the subendocardium. Thus, given the same degree of ischemia, lactate formation may prevail in subendocardial layers mainly because of these transmural differences of substrate and enzyme activities.…”

Section: Transmural Gradient Of Adenosine Formationmentioning

confidence: 99%

Formation of S-adenosylhomocysteine in the heart. II: A sensitive index for regional myocardial underperfusion.

Deußen

Borst

Kroll

et al. 1988

Circulation Research

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Rate of accumulation of myocardial S-adenosylhomocysteine (SAH) was used in an open-chest dog preparation as an index of free cytosolic adenosine levels. Following 30 minutes of coronary artery ligation and infusion of L-homocysteine thiolactone (10 /umol/kg/min i.v.) SAH levels increased from 1.3 (control) to 3.3 nmoles/g in the nonischemic and to values over 100 nmoles/g in the ischemic region. Compared with regional myocardial blood flow the enhanced rate of SAH accumulation was strictly confined to the ischemic area. As long as blood flow was 0.6-1.2 ml/min/g, SAH levels remained unchanged. However, they steeply increased when regional myocardial blood flow decreased below 60% of control. Tissue levels of adenine nucleotides, adenosine, and lactate were not significantly affected in the flow range of 0.4-0.6 ml/min/g but rate of SAH accumulation was enhanced by 400%. In the nonischemic myocardium, SAH accumulation was 60% higher in the subendocardium than in the subepicardium. Decreasing coronary perfusion pressure from 110 to 60, 45, and 35 mm Hg was associated with an exponential increase in coronary venous adenosine release only when perfusion pressure was below 60 mm Hg. Transmural mapping of SAH revealed that at 110 mm Hg SAH was homogeneously distributed, while at a perfusion pressure of 60 mm Hg SAH accumulation was enhanced only in the subendocardial layers. Decreasing perfusion pressure further to 40 and 30 mm Hg not only enhanced subendocardial SAH levels to 120 and 170 nmoles/g, respectively, but also considerably steepened the transmural gradient of SAH. SAH-hydrolase exhibited a broad pH-optimum and its activity in different parts of ventricular myocardium was identical. Our findings provide evidence that 1) measurement of SAH accumulation is a sensitive metabolic index for the assessment of regional myocardial ischemia, 2) significant formation of SAH occurs only when regional myocardial blood flow is less than 0.6 ml/min/g, and 3) transmural SAH gradient, a measure of free cytosolic adenosine, and coronary venous adenosine release significantly increase only when the autoregulatory reserve is exhausted. (Circulation Research 1988;63:250-261) W hen the balance between myocardial oxygen demand and myocardial oxygen supply is upset, as during hypoxia and ischemia, cardiac adenine nucleotides are degraded, resulting in the formation of adenosine.

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Subendocardial anaerobic metabolism in experimental aortic stenosis

Cited by 44 publications

References 0 publications

Coronary Hemodynamics and Regional Myocardial Metabolism in Experimental Aortic Insufficiency

Coronary Hemodynamics and Regional Myocardial Metabolism in Experimental Aortic Insufficiency

Transmural gradients in ventricular tissue metabolites produced by stopping coronary blood flow in the dog.

Formation of S-adenosylhomocysteine in the heart. II: A sensitive index for regional myocardial underperfusion.

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