Effect of exercise on the relationship between myocardial blood flow and systolic wall thickening in dogs with acute coronary stenosis.

Gallagher, Kim P.; Matsuzaki, Masunori; Osakada, Genta; Kemper, W S; Ross, John

doi:10.1161/01.res.52.6.716

Cited by 137 publications

(47 citation statements)

References 30 publications

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“…The present observation of a linear relationship between contractile performance and oxygen consumption is in qualitative agreement with previously published studies demonstrating a close correlation between the degree of blood flow impairment and the severity of contractile dysfunction during partial coronary artery obstruction (1)(2)(3)(4). However, the relative preservation of tissue high energy phosphate stores and limited lactate accumulation does not agree with the results of several previous studies demonstrating a strong correlation between the rate of coronary venous lactate and inosine production and the degree of flow and contractile impairment (1,5).…”

Section: Discussionsupporting

confidence: 92%

“…Previous studies have demonstrated that the severity of myocardial contractile dysfunction correlates with the degree of blood flow impairment during myocardial ischemia produced by partial coronary artery obstruction (1)(2)(3)(4). Based on the known effects of impaired oxygen delivery, it has been postulated that the close correlation between function and perfusion reflects corresponding abnormalities in tissue ATP content and/or oxidative ATP production (1,5,6).…”

Section: Introductionmentioning

confidence: 99%

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Correlation of contractile dysfunction with oxidative energy production and tissue high energy phosphate stores during partial coronary flow disruption in rabbit heart.

Marshall¹

1988

J. Clin. Invest.

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The relationships between contractile function, myocardial oxygen consumption, and tissue high energy phosphate and lactate content were investigated during partial coronary flow disruption. The experimental preparation was an isolated, isovolumic retrograde blood-perfused rabbit heart. Both developed pressure (r = 0.94) and dp/dt (r = 0.95) exhibited strong linear correlations with myocardial oxygen consumption that were stable for up to 45 min after blood flow reduction. In contrast, tissue high energy phosphate content exhibited nonlinear relationships with both developed pressure and oxygen consumption such that systolic mechanical function and oxidative metabolism declined to 20 and 30% of control values, respectively, before significant abnormalities in myocardial high energy phosphate stores were observed. Similarly, developed pressure and oxygen consumption decreased to 36 and 48% of control, respectively, before abnormal tissue lactate content was detected. The results of this study indicate that: (a) mechanical function is closely related to the rate of oxidative energy production during partial coronary flow disruption, and (b) despite the development of significant contractile dysfunction, tissue high energy phosphate content remains at normal levels except under the most severely flow-deprived conditions. The preservation of tissue energy stores can be explained by the apparent coupling of contractile performance to oxidative energy production, which could function to maintain myocardial energy balance during partial coronary flow restriction.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Correlation of contractile dysfunction with oxidative energy production and tissue high energy phosphate stores during partial coronary flow disruption in rabbit heart.

Marshall¹

1988

J. Clin. Invest.

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“…that animals operating at higher perfusion pressures would have exhibited different functional and metabolic responses to small reductions in coronary blood flow. However, the similarity of the functional data in this study to previously published conscious animal preparations argue against this being a significant factor (4,42).…”

Section: Myocardial Bloodflow Andfunctionsupporting

confidence: 69%

Relationship between myocardial metabolites and contractile abnormalities during graded regional ischemia. Phosphorus-31 nuclear magnetic resonance studies of porcine myocardium in vivo.

Schaefer¹,

Schwartz²,

Gober³

et al. 1990

J. Clin. Invest.

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The mechanisms responsible for changes in myocardial contractility during regional ischemia are unknown. Since changes in high-energy phosphates during ischemia are sensitive to reductions in myocardial blood flow, it was hypothesized that myocardial function under steady-state conditions of graded regional ischemia is closely related to changes in myocardial high-energy phosphates. Therefore, phosphorus-31 nuclear magnetic resonance spectroscopy was employed in an in vivo porcine model of graded coronary stenosis. Simultaneous measurements4 of regional subendocardial blood flow, high-energy phosphates, pH, and myocardial segment shortening were made during various degrees of regional ischemia in which subendocardial blood flow was reduced by 16-94%. During mild reductions in myocardial blood flow (subendocardial blood flow = 83% of nonischemic myocardium), only the ratio of phosphocreatine to inorganic phosphate (PCr/P1), Pi, and [H'I were significantly changed from control. PCr, ATP, and PCr/ATP were not significantly reduced from control with mild reductions in blood flow. Changes in myocardial segment shortening were most closely associated with changes in PCr/ Pi (r = 0.94). Pi and [H'I were negatively correlated with segment shortening (r = -0.64 and -0.58, respectively) and increased over twofold when blood flow was reduced by 62%.Thus, these data demonstrate that PCr/P; is sensitive to reductions in myocardial blood flow and closely correlates with changes in myocardial function. These data are also consistent with a role for Pi or H' as inhibitors of myocardial contractility during ischemia. (J. Clin. Invest. 1990. 85:706-713.) high-energy phosphates -magnetic resonance spectroscopy * myocardial ischemia * phosphocreatine

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“…During exercise-induced ischemia, the heart rate is also a major determinant of the amount of blood flow (and hence oxygen) available per beat, which, in turn, largely determines the level of regional contractile dysfunction in the steady state. 5,27 No attempt was made to measure regional MVo2 per minute in these experiments because practical methods for assessing inner and outer wall MVo2 are not available. Although bradycardia is generally stated to reduce MVo2 during ischemia, this assump- low impedance to the left ventricular ejection may cause an increase in the extent of shortening.…”

Section: Potential Mechanisms Of Improved Contractionmentioning

confidence: 99%

Mechanisms of improved ischemic regional dysfunction by bradycardia. Studies on UL-FS 49 in swine.

et al. 1989

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In anesthetized swine, the left anterior descending coronary artery was cannulated and perfused at constant blood flow levels during two grades of ischemia. In one group (n = 10), moderate ischemia reduced percent systolic wall thickening (by sonomicrometry) from 25+±7% to 6±2%, whereas in the other group (n =7), severe ischemia reduced percent wall thickening from 24+6% to -0.5+4%. Heart rate was paced in both groups at 91 beats/min. After reperfusion and complete return to control conditions, administration of the bradycardic agent UL-FS 49 (0.37 mg/kg i.v.) decreased the heart rate to 55±5 beats/min. During subsequent ischemia at the same coronary inflow as before bradycardia, percent wall thickening in the ischemic zone during moderate ischemia was increased from 6+2% to 25 ±6% (p<0.01) (not significantly different from control without ischemia), and during severe ischemia, percent wall thickening increased from -0.5±4% to 13 ±7% (p <0.01). During moderate ischemia, bradycardia caused an increase in the subendocardial blood flow from 0.24+±0.60 to 0.42+±0.17 (ml/min)/g (p<0.009) and during severe ischemia, bradycardia caused an increase from 0.14±0.08 to 0.2+0.1 (ml/min)/g (p<0.001). At each level of ischemia, a more marked improvement occurred in subendocardial blood flow per beat ([(ml/min)/g]/heart rate). The relation between myocardial blood flow and wall function at a heart rate of 55 beats/min (n = 14) was plotted and compared with that studied at a heart rate of 122 beats/min in another group of pigs (n = 14). The increase in subendocardial blood flow per minute during bradycardia was not sufflicient to explain the striking increase in function; thus, an independent relation (p<0.05) between blood flow per minute and contractile function (percent wall thickening) was found for each heart rate. In contrast, when myocardial blood flow was normalized for heart rate and expressed per beat, data from both heart rate groups could be described by a single relation. Thus, the subendocardial blood flow per beat predicted wall function independently of heart rate and accounted for changes in both oxygen supply and demand. (Circulation 1989;80:983-993) I ncreased heart rate aggravates myocardial ischemia,1-4 and pharmacologic reduction of heart rate by ,B-adrenergic blockade has been an important form of therapy in patients with coronary artery disease. Mechanisms involved in the

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Effect of exercise on the relationship between myocardial blood flow and systolic wall thickening in dogs with acute coronary stenosis.

Cited by 137 publications

References 30 publications

Correlation of contractile dysfunction with oxidative energy production and tissue high energy phosphate stores during partial coronary flow disruption in rabbit heart.

Correlation of contractile dysfunction with oxidative energy production and tissue high energy phosphate stores during partial coronary flow disruption in rabbit heart.

Relationship between myocardial metabolites and contractile abnormalities during graded regional ischemia. Phosphorus-31 nuclear magnetic resonance studies of porcine myocardium in vivo.

Mechanisms of improved ischemic regional dysfunction by bradycardia. Studies on UL-FS 49 in swine.

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