Hemodynamic Determinants of Coronary Flow: Effect of Changes in Aortic Pressure and Cardiac Output on the Relationship Between Myocardial Oxygen Consumption and Coronary Flow

Braunwald, Eugene; Sarnoff, Stanley J.; Case, Robert B.; Stainsby, W. N.; Welch, G. H.

doi:10.1152/ajplegacy.1957.192.1.157

Cited by 220 publications

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“…In the present study, strict criteria were required for the diagnosis of heart failure. The elevated right ventricular end diastolic pressures might have reflected decreased compliance in the walls of the distended and obstructed ventricles (39,40), but the association with breathlessness, circulatory congestion, and elevations in systemic a-v 02 difference indicated a relationship to myocardial failure. Accurate assessment of left ventricular function in the failing hearts was difficult.…”

Section: Discussionmentioning

confidence: 99%

High Energy Phosphate Compounds in the Myocardium during Experimental Congestive Heart Failure. Purine and Pyrimidine Nucleotides, Creatine, and Creatine Phosphate in Normal and in Failing Hearts*

Fox¹,

Wikler²,

Reed³

1965

J. Clin. Invest.

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High energy phosphate compounds are generally considered essential for muscular contraction although it is not clear how their chemical energy is ultimately made available for transformation into mechanical work (1-3). According to classical concepts, hydrolysis of adenosine triphosphate (ATP) by myofibrillar .ATPase (adenosine triphosphatase) occurs at some time during repetitive cycles of muscular contraction and relaxation, and as a result adenosine diphosphate (ADP) is produced. Delivery of this ADP to mitochondria for regeneration into ATP can serve as an important regulator of the activity of mitochondrial oxidative phosphorylation (4, 5). In failing hearts, changes in oxidative phosphorylation or its products might accordingly reflect primary changes at the mitochondria or altered delivery of ADP from the failing myofibrils (6).Many studies of normal and failing hearts have examined the processes involved in the formation and utilization of high energy phosphate compounds (7). During spontaneous heart failure in man (8-10) and induced heart failure in dogs (11), there were no significant changes in uptake by the myocardium of oxygen or of the diverse substrates from which chemical energy is liberated and then conserved as nucleoside triphosphates or as creatine phosphate (CrP). However, small, long-term, or localized alterations in uptake of exogenous substrates might not have been detected by acute measurements of arteriovenous * Submitted for publication December 19, 1963; accepted October 15, 1964. Supported by grant H-3312 from the National Institutes of Health, U. S. Public Health Service. differences across intact hearts in situ (12). Concentrations of high energy phosphates have been reported to be normal in isolated, acutely failing dog hearts, guinea pig atria, and cat papillary muscles (13)(14)(15) and in chronically failing hearts from dogs with tricuspid insufficiency and pulmonary stenosis or with aortic insufficiency ( 11,16). Muscle preparations from failing canine and human hearts have shown decreased contractility (17, 18) and decreased ATPase activity (19), but myofibrillar proteins from failing canine hearts have been reported to be both normal (20) and altered (21).Recently, changes have been observed in the morphology of mitochondria from failing hearts of dogs with aortic stenosis (22) and in the metabolic responses of mitochondria from failing hearts of guinea pigs with aortic stenosis (23,24). Improved methods for isolation, separation, and specific assay of high energy phosphate compounds have made possible more precise measurements of tissue levels of these labile compounds (25)(26)(27). With the use of such improved techniques, a recent study found significant decreases in levels of ATP, CrP, and creatine (Cr) in failing hearts from guinea pigs with aortic stenosis (28). Since the status of labile phosphate compounds in the chronically failing heart did not yet seem settled, it was considered pertinent to re-examine the content of purine and pyrimidine nucleotides and CrP in h...

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Section: Discussionmentioning

confidence: 99%

High Energy Phosphate Compounds in the Myocardium during Experimental Congestive Heart Failure. Purine and Pyrimidine Nucleotides, Creatine, and Creatine Phosphate in Normal and in Failing Hearts*

Fox¹,

Wikler²,

Reed³

1965

J. Clin. Invest.

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“…left ventricle increase MVO2 more than do volume loads. 24 In one such study, Urschel et al produced acute mitral incompetence in dogs, and noted that MVO2 increased only slightly although work was significantly increased.85 Ventricular efficiency has also been measured after acute intervention. Rodbard and co-workers measured MVO2 and efficiency in dogs with different acute ventricular hemodynamic alterations and found efficiency values from 3.9 to 32.7%.""…”

Section: Methodsmentioning

confidence: 99%

Left ventricular mechanical efficiency in man with heart disease.

Baxley¹,

Dodge²,

Rackley³

et al. 1977

Circulation

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SUMMARY Thirty-eight adults with valvular and/or myocardial disease had heart catheterization with coronary blood flow and myocardial 02 consumption (MVO2) per 100 g measured by the nitrous oxide washout technique. Quantitative biplane angiocardiography was performed to assess left ventricular volume, mass, ejection fraction and work. Left ventricular efficiency was calculated from work, MVO2/100 g and mass. Efficiency ranged from 4 to 40% and was normal in some patients with severe ventricular pressure-volume work MECHANICAL EFFICIENCY is a performance parameter of energy-transfer systems, most commonly used in an engineering context. Expressed as a percent, it is the dimensionless ratio of mechanical work performed to energy utilized over a given time period. In terms of human left ventricular dynamics, energy utilized has been shown to result relatively exclusively from aerobic metabolism in the absence of ischemic coronary disease.1 2 Thus left ventricular efficiency can be calculated from its rate of performing work and the rate of energy consumption (oxygen consumption or MVO2) over the same time interval.' In this way ventricular efficiency has been calculated in animals.4 In man, methods utilized for coronary blood flow determination have included the nitrous oxide washout,3' 68 helium washout9 and other techniques.'0 MVO2 is then computed as the product of coronary blood flow and coronary arterialvenous oxygen difference. The values of MVO2 obtained by these methods are expressed in MVO2/min/100 g of myocardium. Thus, knowledge of the left ventricular weight or mass is also necessary to calculate total left ventricular MVO2 and hence left ventricular efficiency. Left ventricular mass in normal humans has been estimated for this purpose, and ventricular efficiency calculated.3 However, the variable degrees of ventricular hypertrophy associated with chronic left ventricular hemodynamic abnormalities make ventricular mass measurements necessary for determination of efficiency in patients with long-standing disease. Materials and Methods The subjects of this investigation were 38 adult male patients, age range 25-65 years, studied by right and left heart catheterization and biplane angiocardiography at the University of Alabama Hospital, the University of Washington Hospital or the Seattle Veterans Administration Hospital. The patients all had valvular or myocardial disease with symptoms of heart failure, at least NYHA class III. None had evidence of coronary artery disease by history or electrocardiogram. All were studied as part of a diagnostic evaluation. Initially coronary sinus and systemic arterial catheterization were performed. Coronary blood flow per 100 g of left ventricular myocardium was measured by the N20 desaturation curves following a 15 minute period of 15% N20 inhalation.7 The desaturation curves were constructed from N20 analysis data from multiple arterial and coronary sinus blood samples drawn simultaneously over a 10 minute period immediately following cessation of the N20 inhalation. ...

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“…In spite of the maintenance of ATP at a relatively constant level in the hearts perfused with a coronary flow of 4 ml/min, even at maximum right ventricular pressures, the lactate production increased. Hence, it was entirely possible that the increased oxygen requirement at these pressures (12)(13)(14) in the presence of right ventricular hypoxia left little available for protein synthesis. The latter might explain the drop in protein synthesis at the high afterload pressures.…”

Section: Progressive Right Ventricular Hypoxiamentioning

confidence: 99%

The effect of pressure or flow stress on right ventricular protein synthesis in the face of constant and restricted coronary perfusion.

Schreiber¹,

Rothschild²,

Evans³

et al. 1975

J. Clin. Invest.

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A B S T R A C T Cardiac stress produced by hypertension or excess volume loading results in different types of hypertrophy. Elevated left ventricular pressure rapidly results in increased myocardial protein synthesis in vivo and in vitro, but such rapid alterations are not consistently seen in volume loading. The difference in response is difficult to clarify since it is not possible to effect alterations in left ventricular pressure or perfusion without profoundly affecting coronary perfusion. The present study describes cardiac protein synthesis in the right ventricle of the young guinea pig heart in vitro by utilizing a perfusion model in which the right ventricle could be stressed by elevations of pressure or volume loading in the presence of constant and restricted coronary perfusion. With coronary flow maintained at 4 ml/min per heart equivalent to 25 ml/min/g dry wt, an increase in right ventricular pressure from normal levels of 3 mm Hg to 11 mm Hg resulted in a 60% increase of myocardial incorporation of [14C] INTRODUCTIONCardiac stress produced by experimental hypertension or excess volume loading eventually results in hypertrophy (1-3) though the mechanisms and types of hypertrophy may be different in each stress, e.g., concentric hypertrophy with little increase in ventricular volume is described in hypertension or valvular stenosis while hypertrophy with dilatation is most often seen in valvular insufficiency or volume stress (4, 5). Acute aortic hypertension or volume loading is also accompanied by increased coronary flow which has been shown to enhance protein synthesis (6-8), and few data are available on the effects of such loading in the face of controlled or restricted coronary perfusion.The present report presents data obtained with an in vitro perfusion modal which was designed to separate pressure and volume stresses in the right ventricle from alterations in coronary perfusion and which permits study of protein synthesis in this ventricle in the presence of controlled as well as restricted coronary flow. Two patterns are indicated with this model of the young guinea pig heart. First, protein synthesis is stimulated by acute pressure stress but not by acute volume loading. Second, with maximum stresses right ventricular protein synthesis returns to control levels. A preliminary description of this model was previously reported (9). METHODS Received for publication 8 October 1973 and in revised Young male guinea pigs, 260-320 g, approximately 4-6 wk form 16 September 1974.after weaning, were used in all the studies. The diet beforeThe Journal of Clinical Investigation Volume 55 January 1975 -1-11 1 the operation and anesthesia were as described previously (6, 7). After anesthesia, the chest cage was opened and the proximal aorta cannulated and perfused with oxygenated Krebs-Henseleit solution containing amino acids in concentrations previously described (6, 10). The pulmonary artery was then cannulated with a no. 240 nondistensible polyethylene catheter which was gently passed through the p...

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Hemodynamic Determinants of Coronary Flow: Effect of Changes in Aortic Pressure and Cardiac Output on the Relationship Between Myocardial Oxygen Consumption and Coronary Flow

Cited by 220 publications

References 0 publications

High Energy Phosphate Compounds in the Myocardium during Experimental Congestive Heart Failure. Purine and Pyrimidine Nucleotides, Creatine, and Creatine Phosphate in Normal and in Failing Hearts*

High Energy Phosphate Compounds in the Myocardium during Experimental Congestive Heart Failure. Purine and Pyrimidine Nucleotides, Creatine, and Creatine Phosphate in Normal and in Failing Hearts*

Left ventricular mechanical efficiency in man with heart disease.

The effect of pressure or flow stress on right ventricular protein synthesis in the face of constant and restricted coronary perfusion.

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