Right ventricular diastolic pressure in coronary artery disease

Right Ventricular Diastolic Pressure in Coronary Artery Disease

JULIAN L. BERMAN, MD LAURENCE H. GREEN, MD WILLIAM GROSSMAN, MD, FAX’ Boston, Massachusetts

From the Departments of Medicine, Harvard Medical School and the Peter Bent Brigham Hospital, Boston, Massachusetts. This work was supported in part by Training Grant HL07049 and Grant HL19089 from the National Heart, Blood, and Lung Institute, National Institutes of Health, Bethesda, Maryland. Manuscript received March 28, 1979; revised manuscript received June 25. 1979, accepted July 1, 1979. Established Investigator of the American Heart Association, Dallas, Texas. Address for reprints: William Grossman, MD, Department of Medicine, Peter Bent Brigham Hospital, 721 Huntington Avenue, Boston, Massachusetts 02115. l

Right ventricular hemodynamics were evaluated in 179 patients with coronary artery disease to determine the effects of chronic ischemia on right ventricular diastolic pressure. Abnormal right ventricular filling pressures occurred only in patients with an abnormal right ventricular systolic pressure or an abnormal left ventricular end-diastolic pressure. Of the 63 patients whose right ventricle was stressed by an increased systolic load secondary to passive pulmonary hypertension, 44 (72 percent) had an abnormal right ventricular end-diastolic pressure. In this group obstruction of vessels serving the right ventricular free wall or septum, or both, was almost universal (43 of 44, 98 percent) and a significantly increased incidence of inferior infarction (P <0.05) was noted. Such obstruction was significantly less frequent in patients with normal filling pressures (10 of 17,59 percent;P
The contribution of the right ventricle to overall cardiac function has been controversial. Starr et al.l showed in 1943 that no change in resting right ventricular function followed extensive damage to the right ventricular free wall, and others2 confirmed this work. Although myocardial infarction was known to affect the right ventricle,3T4 this relation was widely considered a pathologic finding of no clinical relevance. However, recent work has focused attention on both the acute and chronic changes in right ventricular function that may occur with coronary artery disease. In experimental studies in which the right ventricle has been damaged by cauterizations or by ligation of its coronary suppl~,~,~ abnormal hemodynamics can be elicited by either pressure loading or volume loading. Clinical studies have demonstrated abnormalities in right ventricular function, both in acute myocardial infarctional and in chronic ischemic heart disease.14-l8 This investigation was undertaken to evaluate right ventricular hemodynamics in patients with coronary artery disease. Patients with symptomatic coronary disease both with and without obstruction of vessels serving the right ventricular free wall and septum were compared with patients having right ventricular pressure overload due to mitral or aortic stenosis. The hypothesis tested was that, in the presence of restricted myocardial blood flow, the right ventricle would exhibit evidence of diastolic dysfunction at a lower systolic pressure than it would with normal blood flow.

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Methods Patients: The cardiac catheterization data of all patients evaluated at the Peter Bent Brigham Hospital from January 1976 to September 1977 were reviewed. All patients with coronary artery disease and a right dominant coronary circulation without associated valvular or congenital heart disease who had complete right and left heart catheterization were included in the study and constituted the group with coronary artery disease (179 patients). Thirty-five patients with isolated mitral stenosis and 20 with isolated aortic stenosis were also evaluated. Potential right ventricular ischemia was defined as occurring when significant obstruction (greater than 70 percent luminal narrowing) was present in the right coronary artery proximal to the takeoff of the right ventricular marginal branches (potential free wall ischemia) or when similar ob-

struction occurred in the left main coronary artery, left anterior descending coronary artery proximal to the first septal perforating artery, or the first septal perforating vessel itself (potential septal ischemia). 179

Patients

With

CAD

Pressure measurements: These determinations were made with the patient resting quietly at the time of the Fick cardiac output determination and prior to angiographic studies. Pressures were measured by no. 7 or 8 F fluid-filled catheters connected to Statham P23-Db pressure transducers with a 0 reference at the level of the mid chest. Right ventricular systolic and end-diastolic pressures were averaged over three respiratory cycles. End-diastolic pressures were taken at the junction of the a wave with the upstroke of the ventricular pressure wave when an a wave could be clearly defined or as the pressure 40 msec after the onset of the QRS complex of the simultaneously recorded surface electrocardiographic lead. Right and left ventricular pressures were measured within 1 to 3 minutes of each other. Pressures were considered abnormal if (1) right ventricular systolic pressure was greater than 30 mm Hg; (2) left ventricular end-diastolic pressure was greater than 12 mm Hg; and (3) right ventricular end-diastolic pressure was grea:er than 8 mm Hg. Myocardial infarction and ventriculography: Infarction involving the inferior surface of the left ventricle was taken as presumptive evidence of infarction in the right coronary arterial distribution; septal infarction was considered to involve the septal portion of the right ventricle. Inferior myocardial infarction was considered present if the conventional criteria of significant Q waves in electrocardiographic leads 11, III and aVF and conventional vectorcardiographic criteria were met. All 54 patients with inferior infarction had angiographically demonstrable wall motion abnormalities of the inferior surface of the left ventricle. Septal infarction was considered to have occurred when electrocardiographic and vectorcardiographic criteria were met. Of the 37 patients with septal infarction on electrocardiography, 19 had a left anterior oblique ventriculogram performed. All 19 of these patients had abnormalities of septal wall motion angiographically. Statistical analysis was performed using the chi-square or Fisher exact tests for percent comparisons and unpaired t tests for group means. Linear regression analysis by least squares fit was used to correlate right ventricular systolic and enddiastolic pressure.

,*_Y 143pts nl

nl

61pts 4RVSP +tLVEDP

RVSP LVEDP

nl

/\

nl

20 Patients

nl nl nl

With

Aortic

35,Patients

With

Mitral

/

i 33 Pts

28 RVEDP

15 +RVEDP

Stenosis

nl

3 a RVEDP +RVEDP

2 pt5

I

nl

tRVSP +4LVEDP

RVSP LVEDP RVEDP

nl

nl nl nl

/\

44 17 RVEDP tRVEDP

RVSP tLVEDP

nl

RVSP tLVEDP

6 RVEDP

Stenosis

+RVSP +tLVEDP

RVSP LVEDP RVEDP

/\

/\

nl

26 RVEDP

i3 ‘RVEDP

FIGURE 1. Distribution of right ventricular pressures and left ventricular end-diastolic pressure in the patients (pts) with coronary disease and comparison groups. CAD = coronary artery disease; LVEDP = left ventricular end-diastolic pressure; nl = normal; RVEDP = right ventricular end-diastolic pressure: RVSP = right ventricular systolic pressure.

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Results Right ventricular hemodynamics: Of 179 patients with coronary artery disease (Fig. l), 75 had normal right ventricular systolic pressure and normal left ventricular end-diastolic pressure. Because the right ventricle may have normal diastolic pressures even when severely ischemic if it is unstressed,6 these patients were not considered further. Sixty-one patients had elevated right ventricular systolic pressure; of these, 17 (28 percent) had a normal and 44 (72 percent) had an abnormal right ventricular end-diastolic pressure. None of the patients with aortic or mitral stenosis had an elevated right ventricular end-diastolic pressure without an elevated right ventricular systolic pressure. For any given level of right ventricular afterload, the right ventricular end-diastolic pressure was higher in patients with coronary artery disease and potential right ventricular &hernia than in those with valve disease. (Fig. 2). Fifteen patients with coronary artery disease had an elevated right ventricular end-diastolic pressure despite a normal right ventricular systolic pressure. All of these patients had an elevated left ventricular end-diastolic pressure. Finally, the remaining 28 patients had an el-

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evated left ventricular end-diastolic pressure but a normal right ventricular end-diastolic pressure. Right ventricular coronary artery disease and end-diastolic pressure: Of the patients whose right ventricle was stressed by an increased afterload (right ventricular systolic pressure greater than 30 mm Hg), anatomic obstruction to vessels supplying the right ventricle was significantly more frequent in those with an elevated right ventricular end-diastolic pressure (43 of 44, 98 percent) than in those with a normal right ventricular end-diastolic pressure (10 of 17,59 percent) (P
pe 001

p.025

16

PC05 CAD

PC05

evated right ventricular end-diastolic pressure this group was not included for comparison. Inferior infarction was more common in patients with a systolic stress and an elevated right ventricular end-diastolic pressure (Table I) than in patients who had a normal filling pressure despite such a systolic stress (P < 0.05). Similarly, among the patients with normal right ventricular systolic pressure but an abnormal left ventricular end-diastolic pressure, those with an abnormal right ventricular end-diastolic pressure had a higher rate of inferior infarction than those with a normal right ventricular filling pressure (P <0.025). Infarction involving the septum was not significantly more frequent in either group of patients. There was a modest correlation between right ventricular systolic and end-diastolic pressures in the patients with coronary disease and potential right ventricular ischemia (r = 0.60); this correlation did not exist among patients without right ventricular ischemia (r = 0.22). Among patients with an “unstressed” right ventricle (normal right ventricular systolic and left ventricular end-diastolic pressure), potential right ventricular ischemia was present in a large proportion (76 percent) as was inferior infarction. These findings underscore the need for a stress to unmask right ventricular dysfunction. Although the number of patients studied was small, it is of interest to observe the effect of collateral vessels on the potentially ischemic regions of the right ventricle. Twenty-eight of 44 patients (64 percent) with potential right ventricular ischemia and no angiographically observable collateral vessels had an elevated right ventricular end-diastolic pressure. Similarly, 20 of 32 patients (62 percent) whose collateral vessels to the potentially ischemic regions arose from vessels with significant obstruction (greater than 70% luminal narrowing) had an elevated right ventricular end-diastolic pressure. In the small group of 10 patients with nonjeopardized collateral vessels to the potentially ischemic regions, only 2 (20 percent) had an elevated right ventricular end-diastolic pressure.

TABLE I

p-NS.

iR”l

Prevalence of Myocardial lhfarction in Patients With Coronary Artery Disease With Normal and Abnormal Right Ventricular Hemodvnamics AS n-13

Infarction

8-

Normal RVEDP

P

Elevated RVEDP

Patients With Increased Right Ventricular Systolic Pressure fi

RV S P 30-49mmHg

Septal Inferior

RVSP 250mmHg

FIGURE2. Comparison of resting right ventricular enddiastolic pressure (RVEDP) at various degrees of pulmonary hypertension in patients with coronary artery disease (CAD), mitral stenosis (MS) or aortic stenosis (AS). C RVI = with potential right ventricular ischemia; n = number of patients; N.S. = not significant: p = probability; S RVI = without potential right ventricular ischemia; RVSP = right ventricular systolic pressure.

8/17 (47%) 6117 (35%)

<::5

19144 (43%) 25144 (57 % 1

Patients With Normal Right Ventricular Systolic Pressure and Increased Left Ventricular End-Diastolic Pressure Septal Inferior

5/28 (18%) 11128 (39%)


3115 (20%) 12/15 (80%)

NS = not significant; P = probability; RVEDP = right ventricular end-diastolic pressure.

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Left ventricular end-diastolic pressure and right ventricular end-diastolic pressure: Nearly all (92 percent) of our patients with coronary artery disease had an elevated left ventricular end-diastolic pressure because this was the origin of the secondary pulmonary hypertension that produced the right ventricular systolic stress. Despite substantially increased left ventricular filling pressures, only four patients had clinical left heart failure. No patient had clinical evidence of overt right heart failure. For the 43 patients with increased right and left ventricular end-diastolic pressures but a normal right ventricular systolic pressure, the level of left ventricular end-diastolic pressure (21.0 f 1.5 mm Hg) was similar to that in patients with an elevated left ventricular end-diastolic pressure (19.5 f 0.6 mm Hg) but a normal right ventricular systolic end-diastolic pressure. Similarly, the anatomic substrate for right ventricular ischemia occurred as frequently among those with a normal right ventricular end-diastolic pressure (20 of 2671 percent) as among those with an elevated right ventricular end-diastolic pressure (13 of 15,87 percent; P = not significant [NS]). In the patients with a right ventricular systolic stress, left ventricular end-diastolic pressure was not significantly different between the patients with potential right ventricular ischemia (19.7 f 0.9 mm Hg) and those without (22.2 f 2.5 mm Hg; P = NS), despite the highly significant difference in right ventricular end-diastolic pressure.

Discussion Right ventricular function in coronary artery disease: Because the right ventricle normally functions at an extremely low level of afterload, major myocardial dysfunction may not be manifested in overall right ventricular performance. However, when the ventricle is stressed by an increase in afterload, as occurs with pulmonary hypertension of any origin, such dysfunction may be unmasked. In the present study, we demonstrated that the right ventricle tends to show elevation of diastolic pressure at a lower level of pulmonary arterial pressure in coronary artery disease than in leftsided valve stenosis. Moreover, this response to pressure overload depends in part on the adequacy of the right ventricular coronary blood supply. When the right ventricle was stressed by pulmonary hypertension, virtually all of the patients with coronary artery disease who manifested an elevated right ventricular end-diastolic pressure had the anatomic substrate for right ventricular ischemia, whereas patients whose coronary anatomy was not consistent with right ventricular ischemia often had normal right ventricular filling pressures. Because the assumption of an inadequate myocardial blood supply is based on anatomic obstructions to the major coronary vessels to the right ventricle and not on actual measurements of regional right ventricular blood flow, it is not surprising that some patients with potential right ventricular ischemia as judged with anatomic criteria responded to pulmonary hypertension with normal right ventricular enddiastolic pressure. Infarction of the left ventricular inferior wall (which by association of a common blood

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supply may indicate involvement of the right ventricular free wall) was also more frequent in patients with abnormal right ventricular filling pressures. This association is concordant with the occurrence of right ventricular dysfunction in the acute phase of left ventricular inferior infarction.lO-l3 Effects of left ventricular dysfunction on right ventricular function: Some patients with coronary artery disease had an abnormal right ventricular enddiastolic pressure without a systolic stress, and this finding was consistently associated with elevation of left ventricular end-diastolic pressure. Several experimental studies have shown that changes in the end-diastolic pressure or volume in one ventricle affect the diastolic pressure-volume relation in the other ventricle,1s-22 presumably as a result of forces acting on the shared interventricular septum. Abnormalities occur in left ventricular volumes and pressures during diastole in patients with coronary disease who have active ischemia,23,24 but these probably did not play a role in the changes in right ventricular diastolic pressures in our study because the pressure measurements were not made during angina pectoris. The extent of elevation of right ventricular diastolic pressure may merely reflect the magnitude of the forces or changes in shape induced by the changes in left ventricular diastolic pressure. On the other hand, it is not known whether through interdependence of the ventricles, an abnormal left ventricular filling pressure may exacerbate underlying right ventricular dysfunction. Our data cannot distinguish between these two mechanisms. However, the increase in right ventricular diastolic pressure with systolic loading was greater in patients with mitral stenosis (with a normal left ventricular end-diastolic pressure) than in patients with aortic stenosis (and an abnormal left ventricular end-diastolic pressure). Among the patients wit.h coronary artery disease who had a normal right ventricular systolic pressure, there was no difference in the level of left ventricular end-diastolic pressure in those with increased and those with normal right ventricular end-diastolic pressure. Thus, the increased left ventricular end-diastolic pressure alone cannot explain entirely the concomitant changes in right ventricular diastolic pressure. Similarly, although the patients with an elevated right ventricular systolic pressure and potential right ventricular ischemia had the same level of left ventricular end-diastolic pressure recorded in similar patients without such coronary arterial anatomy, highly significant differences in right ventricular diastolic pressure existed between the two groups. These findings suggest to us that the contribution of ventricular interdependence in the absence of a limited right ventricular blood flow is small. Factors influencing right ventricular diastolic function in ischemia: Many other factors can influence the right ventricular end-diastolic pressure including right ventricular end-diastolic volume and compliance, as well as the diastolic volume and pressure in the left ventricle, viscous properties of the right ventricular myocardium, myocardial relaxation and atrial, intrapericardial and intrathoracic pressures.23 The greater

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elevations of right ventricular end-diastolic pressures seen in our patients with coronary artery disease by comparison with findings in patients whose right ventricle had an equivalent pressure load from other causes represent the sum total of the influence of all these variables. Myocardial ischemia causes changes in contractility and relaxation of the left ventricle, and infarction also causes changes in its elasticity.23,25J6 Although these properties have not been studied in the ischemic right ventricle, they are likely to cause similar directional changes in its diastolic properties that would tend to increase right ventricular end-diastolic pressure. Viscous properties of the ventricle, the time-dependent changes in resting tension and myocardial fiber length with prolonged stretch, are of unknown consequence in right ventricular diastolic function. To the extent that they are active, they might be expected to decrease end-diastolic pressure and minimize the elevations seen in our patients. Erectile properties-those related to increased stiffness of the ventricular wall when coronary pressure or blood volume increases-are probably of lesser importance in patients with diminished coronary arterial flow to the right ventricle. Factors extrinsic to the ventricles, such as intrapericardial and intrathoracic pressures, could not be evaluated in our study. However, the lack of any tendency toward equalization of the diastolic pressures in the ventricles and the lack of any typical diastolic pressure features of constrictive or restrictive physiology argue against an important role for these factors in our patients. ‘Despite the multitude of influences on right ventricular diastolic function, in our study the degree of right ventricular dysfunction was proportionate to the right ventricular afterload only in patients with right ventricular ischemia, a finding that implies that ischemia played a major role in the abnormalities of right ventricular end-diastolic pressure. Role of right ventricular infarction: In the acute phase of inferior myocardial infarction, changes in right ventricular hemodynamics,s-10 chamber sizell and wall motion1°J2 may occur in up to 30 percent of patients. Lore11 and co-workerslo have recently pointed out that right ventricular infarction may lead to such marked increases in right ventricular diastolic pressure at relatively normal right ventricular afterload as to suggest cardiac tamponade or pericardial constriction. In rare

cases, right ventricular infarction may be severe enough to produce cardiogenic shock because of the inability of the right ventricle to deliver an adequate preload to the left ventricle.gJO Documentation of right ventricular dysfunction in the chronic phase of coronary artery disease is uncommon,gJ7 although abnormalities in right ventricular ejection fractioni and wall motion15 have been demonstrated in patients with coronary disease who had normal right-sided pressures. Two studies have demonstrated abnormalities in right ventricular hemodynamics in chronic coronary artery disease. One studyI showed a high rate (67 percent) of abnormal right ventricular end-diastolic pressure at rest in a consecutive series of patients with coronary artery disease; in 20 percent the abnormality coexisted with normal left ventricular end-diastolic pressure. Experimental evidence supports the concept of an increased need for free wall and septal blood flow in the right ventricle with increased work loads27J8 and a deleterious change in the function of this chamber with ischemia.6~7~2g,s0 Subtle changes in right ventricular contractile function are seen in otherwise normal animals after selective ligation of the blood supply to the right ventricle, but only pressure loading causes elevation of the right ventricular end-diastolic pressure6*2g and this abnormality is proportionate to the severity of the ischemia.2g Implications: We suggest that a mechanism of decreased right ventricular contractile function unmasked by increased afterload is present in our patients with coronary artery disease. That our patients without an abnormal right ventricular systolic pressure or abnormal left ventricular end-diastolic pressure did not have an elevated filling pressure to the right ventricle supports the experimental data indicating that abnormalities in right ventricular function may not be manifested without right ventricular stress. The presence of potential right ventricular ischemia in our patients with an abnormal right ventricular end-diastolic pressure and the lower systolic pressures at which these patients manifested elevated right ventricular end-diastolic pressure compared with patients with passive pulmonary hypertension from other causes lead us to conclude that abnormalities in right ventricular function occur when the appropriate substrate of right ventricular coronary artery disease is present.

References 1. Starr I, Jeffers WA, Meads RH Jr: Absence of conspicuous increments of venous pressure after severe damage to the right ventricle of the dog, with a discussion of the relation between clinical congestive failure and heart disease. Am Heart J 26: 291-301, 1943 2. Kagan A: Dynamic response of the right ventricle following extensive damage by cauterization. Circulation 5:816-823, 1952 3. Wartman WB, yellerstein HK: The incidence of heart disease in 2000 consecutive autopsies. Ann Intern Med 28:41-65, 1948 4. Wade WG; The pathogenesis of infarction of the right ventricle. Br Heart J 21545-554, 1959 5. Guiha NH, Limas CJ, Cohn JN: Predominant right ventricular dysfunction after right ventricular destruction in the dog. Am J

Cardiol 33:254-258, 1974 Brooks, H, Kirk ES, Vokonas PS, Urschel CW, Sonnenblick EH: Performance of the rioht ventricle under stress: relationshio to riaht coronary flow. J Clin-lnvest 50:2176-2183, 1971 ’ Peter RH, Ftamo BW. Ratliff N. Morris JJ Jr: Collateral vessel development after right ventricular infarction in the pig. Am J Cardiol 29:56-60, 1972 Rackley CE, Russell RO: Right ventricular function in acute myocardial infarction. Am J Cardiol 33:927-929, 1974 Cohn JN, Guiha NH, Broder Mt, Limas CJ: Right ventricular infarction, clinical and hemodynamic features. Am J Cardiol 33: 209-214, 1974 10. Lorell B, Leinbach, RC, Pohost GM, Gold HK, Dinsmore RE, Hutter

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11.

12.

13.

14.

15.

16. 17.

18.

19.

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ET AL.

AM Jr, Pastore JO, DeSanctis RW: Right ventricular infarction. Clinical diagnosis and differentiation from cardiac tamponade and pericardial constriction. Am J Cardiol 43:465-471, 1979 Rigo P, Murray M, Taylor DR. Weisfeldt ML, Kelly DT, Strauss HW, Pitt B: Right ventricular dysfunction detected by gated scintiphotography in patients with acute inferior myocardial infarction. Circulation 52:268-274, 1975 Sharpe N, Botvinick E, Shames D, Chatterjee K, Massie B, Schiller N, Parmley W: Noninvasive diagnosis of right ventricular infarction: a common clinical entity (abstr). Circulation 54:Suppl ll:ll-76, 1976 lsner JM, Roberts WC: Right ventricular infarction complicating left ventricular infarction secondary to coronary heart disease. Frequency, location, associated findings and significance from analysis of 238 necropsv patients with acute or healed myocardial infarction. Am J Cardioi 42:885-894, 1978 Ferlinz J, Gorlin R. Cohn PF. Herman MV: Riqht ventricular performance in patients with coronary artery disease. Circulation 52:608-615, 1975 Ferlinz J, Delvicario M, Gorlin R: Incidence of right ventricular asynergy in patients with coronary artery disease. Am J Cardiol 381557-563, 1976 Wells DE, Befeler B: Dysfunction of the right ventricle in coronary artery disease. Chest 66:230-235, 1974 Zone DD, Botti RE: Right ventricular infarction with tricuspid insufficiency and chronic right heart failure. Am J Cardiol 37: 445-448, 1976 Roy PR, Sowton GE, DiLurio V: Hemodynamic events in the right and left ventricle during angina induced by atrial pacing. Br Heart J 37:520-524, 1975 Taylor RR, Covell JW, Sonnenblick EH, Ross J Jr: Dependence of ventricular distensibility on filling of the opposite ventricle. Am J Physiol 213:711-718, 1967

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20. Bemis CE, Serur JR, Borkenhagan D, Sonnenblick EH, Urschel CW: Influence of right ventricular filling pressure on left ventricular pressure and dimension. Circ Res 34:498-504, 1974 21. Glantz SA, Parmley WW: Factors that affect the diastolic pressure-volume curve. Circ Res 42:171-180, 1978 22. Armour JA, Lippincott DB, Randall WC: Regional dynamic behavior of the total right ventricle. Proc Sot Exp Biol Med 142:703-711, 1973 23. Grossman W, McLaurin LP: Diastolic properties of the left ventricle. Ann Intern Med 84:316-326, 1976 24. Mann T, Brodie BR, Grossman W, McLaurin LP: Effect of angina on the left ventricular diastolic pressure-volume relationship. Circulation 55:761-766, 1977 25. McLaurin LP, Rolett EL, Grossman W: Impaired left ventricular relaxation during pacing-induced ischemia. Am J Cardiol 32: 751-757, 1973 26. Grossman W, Mann JT: Evidence for impaired left ventricular relaxation during acute ischemia in man. Eur J Cardiol 7:Suppl I: 239-249, 1978 27. Fixler DE, Archie JP Jr, Ullyot DJ, Hoffman JIE: Regional coronary flow with increased right ventricular output in anesthetized dogs. Am Heart J 86:788-799, 1973 28. Fixler DE, Archie JP Jr, Ullyot DJ, Buckberg GD, Hoffman JIE: Effects of acute right ventricular systolic hypertension on regional myocardial blood flow in anesthetized dogs. Am Heart J 85: 491-500, 1973 29. Brooks H, Holland R, Al-Sadir J: Right ventricular performance during ischemia: an anatomic and hemodynamic analysis. Am J Physiol 233:H505-H513, 1977 30. Fixler DE, Monroe GA, Wheeler JM: Hemodynamic alterations during septal or right ventricular ischemia in dogs. Am Heart J 93:210-215.1977

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