This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Karunanithi, M. K. Articles by Feneley, M. P. Search for Related Content PubMed PubMed Citation Articles by Karunanithi, M. K. Articles by Feneley, M. P. Related Collections Contractile function Animal models of human disease Coronary circulation

(Circulation. 1999;100:1562-1568.)
© 1999 American Heart Association, Inc.

Basic Science Reports

Response of the Intact Canine Left Ventricle to Increased Afterload and Increased Coronary Perfusion Pressure in the Presence of Coronary Flow Autoregulation

Mohanraj K. Karunanithi, BE, MBiomedE; Jason A. Young, BE, MBiomedE; Wally Kalnins, BE; Scott Kesteven, BSci, Grad Dip BiomedE; Michael P. Feneley, MD, FRACP

From the Victor Chang Cardiac Research Institute and Cardiology Department, St. Vincent's Hospital, Sydney, Australia.

Correspondence to Michael P. Feneley, MD, FRACP, FACC, Cardiology Department, St. Vincent's Hospital, Darlinghurst NSW 2010, Australia.

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
Background—Increased left ventricular (LV) contractile force or oxygen consumption has been documented with increased coronary arterial pressure (CAP) and flow (Gregg phenomenon). We investigated whether the increase in contractile force with increased LV afterload might be mediated by the concomitant increase in CAP when coronary autoregulation is intact.

Methods and Results—The LV of 6 autonomically blocked open-chest dogs was perfused through the left main coronary artery by a cannula with a side gate to the aortic root. With the gate open, CAP increased from 77±20 to 93±20 mm Hg (P<0.05) with aortic constriction (AC). With the gate closed, CAP was maintained at a constant level of 100 mm Hg. A small reduction in the slope of the preload recruitable stroke work (PRSW) relationship was observed with AC, but this response was not altered by the coronary perfusion gate position. The end-systolic pressure-volume (ESPV) relationship shifted upward significantly with AC (P<0.001), but this shift was not greater with open-gate perfusion than with closed-gate perfusion. Furthermore, with coronary autoregulation intact, wide changes in CAP (between 60 and 180 mm Hg, n=5) did not alter either the PRSW or ESPV relationship. In contrast, when autoregulation was abolished with intracoronary adenosine (n=6), both indexes of contractility increased progressively with increased CAP.

Conclusions—The concomitant increase in CAP with increased afterload in the intact canine LV does not contribute to the afterload-induced increase in contractile force. Coronary perfusion pressure per se does not influence LV contractile function. Coronary perfusion pressure influences contractility only when coronary flow changes.

Key Words: contractility • ventricles • perfusion • pressure • physiology

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
Increased coronary perfusion pressure has been reported to increase left ventricular (LV) oxygen consumption and contractile function in a variety of experimental preparations (Gregg phenomenon).^{1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19} In the intact circulation, coronary perfusion pressure increases concomitantly with increased LV afterload. Consequently, increases in afterload might be expected to enhance LV contractile function, consistent with observations of a leftward/upward shift of the LV end-systolic pressure-volume relationship (ESPVR) in the intact heart.^{20 21 22} Similarly, the ability of the intact heart to maintain a virtually constant relationship between LV stroke work and end-diastolic volume (the preload recruitable stroke work [PRSW] relationship), despite increments in mean ejection pressure up to 200 mm Hg,^{22 23} indicates increased force-generating capacity with increased afterload.

We have reported, however, a 45% average increase in the slope of the right ventricular ESPVR with pulmonary artery constriction sufficient to increase right ventricular mean ejection pressure 70% in conscious dogs, while the slope and volume-axis intercept of the right ventricular PRSW relationship remained constant.²⁴ Because pulmonary artery constriction does not increase coronary perfusion pressure, these observations cannot be explained by the Gregg phenomenon but are consistent with intrinsic "homeometric autoregulation" of contractility to increased afterload.²⁵ Similarly, the ESPVR of the LV may also shift leftward with increased afterload in isolated heart preparations when coronary perfusion pressure is held constant,²⁶ although this effect appeared quantitatively smaller than in the intact heart.

Thus, the upregulation of LV contractile force in response to increased afterload in the intact circulation might reflect both homeometric autoregulation and the Gregg phenomenon resulting from the concomitant increase in coronary perfusion pressure. It is not clear, however, that the Gregg phenomenon is due to increased coronary perfusion pressure per se. Although it has been established that increased coronary blood flow increases LV contractility even when coronary perfusion pressure is held constant,^{4 27} it remains controversial whether the converse is true.^{2 4} In most studies of the Gregg phenomenon to date, including Gregg's,¹ increases in coronary perfusion pressure have been accompanied by increases in coronary flow due to deficient coronary autoregulation.^{1 3 4 5 7 9 10 11 12 13 14 15} Recent evidence indicates that myocardial oxygen consumption does not increase with increased coronary perfusion pressure when coronary autoregulation is intact.²⁸

The primary purpose of the present investigation was to determine whether the concomitant increase in coronary perfusion pressure with increased afterload in the intact circulation contributes to the upregulation of LV contractility. For this purpose, we devised a method of perfusing the intact canine LV through a coronary cannula that could be alternately opened to receive blood from the aortic root or closed to receive blood from a pump at constant pressure while LV afterload was increased by transient aortic constriction. In a second experimental protocol, we randomly altered the fixed coronary perfusion pressure to directly examine the influence of a wider range of coronary perfusion pressures on LV contractile function. In both protocols, coronary blood flow was maintained at a constant rate by intact coronary autoregulation. We then repeated the coronary perfusion pressure protocol in additional experiments after abolishing coronary autoregulation with intracoronary adenosine.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
The experimental procedures were approved by our institutional ethics committee and conformed to the guidelines of the National Health and Medical Research Council of Australia.

Experimental Preparation
Six healthy adult dogs (weight 34 to 44 kg) were anesthetized with fentanyl (0.05 µg · kg^-1 · min^-1) and halothane (0.5%) after induction with sodium pentothal (20 mg/kg IV). A left thoracotomy was performed and the pericardium opened. Ultrasonic transducers were positioned across the base-apex major (a), anterior-posterior minor (b), and septal–free-wall minor (c) diameters of the LV, as described previously.²⁴ Pneumatic occluders were positioned around the inferior vena cava and the descending thoracic aorta. LV pressure was measured with a micromanometer (model MPC-500, Millar Instruments) introduced through the apex. Coronary blood flow was measured with flow probes (Doppler [Crystal Biotech] or Transonic [Transonic Systems Inc]) placed around the left anterior descending artery.

The tip of a coronary perfusion cannula (stainless steel, length 33 cm, flanged rubber tip with lumen diameter 3.4 mm) was inserted into the left main coronary artery via the brachiocephalic artery and secured by a ligature. The canine right coronary artery does not provide blood flow to LV myocardium.^{29 30} Left coronary perfusion was maintained through a heparinized (10 000 U) circuit from 1 of the dog's femoral arteries via a roller pump (Sarns model 5500) and a flask pressurized with oxygen to permit maintenance of a constant coronary arterial pressure. The flask was immersed in a water bath maintained at 37°C. The regulation of coronary arterial pressure was achieved by electronic feedback control of the pressure sensed from a micromanometer (Millar, model MPC-500) placed within the tip of the coronary perfusion cannula. The cannula was designed so that a gate in the wall near its distal end could be either opened to permit perfusion from the aortic root (open-gate perfusion) or closed to permit LV myocardial perfusion at a constant arterial pressure by the pressure regulation circuit (closed-gate perfusion).

Data Acquisition and Experimental Protocol
Protocol 1: LV Afterload Responses During Open-Gate and Closed-Gate Coronary Perfusion
After attenuation of autonomic reflexes with propranolol (1 mg/kg IV) and atropine (0.2 mg/kg IV), data were recorded under steady-state conditions and during transient vena caval occlusion induced by inflation of the pneumatic occluder for 10 seconds. The purpose of caval occlusion was to provide a wide range of variation in preload to permit subsequent derivation of the ESPVR and PRSW relationship. After release of the caval occlusion and restabilization, the aortic occluder was partially inflated, with careful adjustment of the inflation volume to achieve a stable constriction that increased LV systolic pressure by 30%. After stabilization of all parameters at their new levels, transient caval occlusion was repeated while the aortic constriction was maintained. The adequacy of autonomic blockade was confirmed by the absence of any increase in heart rate in response to either caval occlusion or aortic constriction in all of the dogs studied.

The same protocol of sequential caval occlusions was conducted first under open-gate coronary perfusion conditions, when coronary arterial pressure increased normally with increased aortic root pressure during aortic constriction, and then under closed-gate coronary perfusion conditions, when coronary arterial pressure was maintained at 100 mm Hg despite increased aortic pressure. We took care to ensure that the degree of aortic constriction was identical under both perfusion conditions by using the same volume to inflate the aortic occluder.

Protocol 2: LV Contractile Response to Various Levels of Coronary Perfusion Pressure
To examine the influence of coronary perfusion pressure per se on LV contractile performance over a broader range of pressures, caval occlusions were repeated in 5 dogs at each of various fixed levels of coronary arterial pressure ranging from 60 to 180 mm Hg. All caval occlusion data were collected after stable hemodynamic conditions were achieved at each level of coronary arterial pressure. The same protocol was repeated in 6 additional dogs (weight 28 to 41 kg) after abolition of coronary autoregulation with intracoronary adenosine (67 µg/min).

Data Analysis
Data were digitized in real time at 200 Hz. We calculated LV volume by fitting the 3 ultrasonically measured LV epicardial diameters to the formula for a general ellipsoid (/6 a · b · c) and subtracting wall volume, which was determined by postmortem displacement in water.²⁴ End-systolic pressure was defined as the time when the instantaneous pressure-volume ratio was maximal.³¹ Stroke work was calculated as the pressure-volume loop area for each beat. The PRSW relationship and ESPVR were determined by linear regression analyses, as described previously.^{23 24}

Statistical Analysis
The influence of the various interventions described above on the PRSW relationship and ESPVR was determined by multiple linear regression analyses.³² Dummy variables were used in the multiple linear regression analyses to account for the various interventions and for the interanimal variability. The general multiple linear regression model used was

(1)

where AC and Gate are dummy variables coding for aortic constriction and gate position, respectively, using effects coding,³² and D_i represents dummy variables for each dog. The effects of afterload and the mode of coronary perfusion were represented by the coefficients b₂ and b₃, respectively (a coefficient not significantly different from zero would indicate no effect of the intervention). The coefficient d_i is the individual dog coefficient. For the PRSW relationship, the dependent (y) and independent (x) variables were stroke work and end-diastolic volume, respectively. For the ESPVR, the dependent and independent variables were end-systolic pressure and end-systolic volume, respectively.

For protocol 2, the general multiple linear regression model applied was

(2)

where CAP is the coronary arterial pressure value.

Statistical analyses were performed with SPSS for Windows, version 6.1.

	Results

Top Abstract Introduction Methods Results Discussion References

 
Protocol 1: LV Afterload Responses During Open-Gate and Closed-Gate Coronary Perfusion
Representative dynamic data recordings obtained before and during aortic constriction under both open-gate and closed-gate coronary perfusion conditions are displayed in Figure 1. Steady-state hemodynamic data obtained before and during aortic constriction, under both open-gate and closed-gate coronary perfusion conditions, are summarized in Table 1. There were no significant differences in baseline steady-state hemodynamic parameters before aortic constriction between the open-gate and closed-gate perfusion states. Aortic constriction in the open-gate perfusion state increased LV mean ejection pressure from 93±22 to 116±21 mm Hg, resulting in a concomitant increase in mean coronary arterial pressure from 77±20 to 93±20 mm Hg (P<0.05). In contrast, under closed-gate coronary perfusion conditions, the increase in LV mean ejection pressure from 92±20 to 123±22 mm Hg during aortic constriction was not accompanied by any change in the mean coronary arterial pressure, which was maintained at a constant level. The coronary flowmeter failed in 1 dog, but no significant changes in left anterior descending coronary artery blood flow were found between the open-gate and closed-gate coronary perfusion conditions in the remaining 5 dogs, indicating intact coronary autoregulation over the coronary perfusion pressure range examined.

View larger version (31K): [in this window] [in a new window]   Figure 1. Representative dynamic recordings obtained before and during aortic constriction (AC) under both open-gate and closed-gate coronary perfusion conditions. Coronary arterial pressure increases with LV pressure under open-gate perfusion conditions but remains constant under closed-gate perfusion conditions. LAD indicates left anterior descending coronary artery.

View this table: [in this window] [in a new window]   Table 1. Comparison of Closed-Gate With Open-Gate Perfusion Effects on Steady-State Hemodynamic Parameters Before and During Aortic Constriction

Representative examples of pressure-volume loops obtained before and during increased LV afterload under both open-gate and closed-gate coronary perfusion conditions are shown in the upper panels of Figure 2. Superimposed on these loops are the corresponding ESPVRs. The PRSW relationships derived from the same loops are shown in the lower panels of Figure 2. The mean linear regression data for all dogs are summarized in Table 2. Under both open-gate and closed-gate perfusion conditions, there was a small but statistically significant (P<0.001) downward shift of the PRSW relationship with aortic constriction, manifested by a reduction in the slope of the relationship with little change in the volume-axis intercept, but the response of the PRSW relationship to increased afterload was not altered by the coronary perfusion gate position.

View larger version (48K): [in this window] [in a new window]   Figure 2. Top, Representative examples of pressure-volume loops obtained before (Control) and during aortic constriction (AC) under both open-gate and closed-gate coronary perfusion conditions. ESPVR is shown by line joining left uppermost corners of pressure-volume loops. Broken loops and lines indicate control. Solid loops and lines indicate AC. There is higher end-systolic pressure for any given end-systolic volume during AC under both open-gate and closed-gate conditions. Bottom, PRSW relationships derived from pressure-volume loops in top panels. There is a small depression of the PRSW relationship with AC during both open-gate and closed-gate conditions.

View this table: [in this window] [in a new window]   Table 2. Comparison of Closed-Gate With Open-Gate Perfusion Effects on Linear Regression Data for Control State and Aortic Constriction

The ESPVR shifted upward significantly (P<0.001) with aortic constriction under both open-gate and closed-gate coronary perfusion conditions, equivalent to an average 25.4±4.0 mm Hg increase in end-systolic pressure for a given end-systolic volume, but this was manifested by a flattening of the slope of the relationship accompanied by a marked leftward shift of the volume-axis intercept. The upward shift of the ESPVR with aortic constriction was not greater when coronary perfusion pressure was permitted to increase with increased afterload. In fact, the upward shift was somewhat smaller in the open-gate position, equivalent to 7.8±5.1 mm Hg less of an increase in end-systolic pressure for a given end-systolic volume (P<0.001).

Protocol 2: LV Contractile Response to Various Levels of Coronary Perfusion Pressure
Figure 3 shows the relationship between coronary blood flow and coronary arterial pressure in 5 dogs not administered adenosine and 6 dogs after intracoronary administration of adenosine. It can be seen that there was no relationship between coronary arterial pressure and coronary blood flow in the first group, indicating intact coronary autoregulation. In contrast, coronary blood flow increased with coronary arterial pressure in the second group, confirming that coronary autoregulation was abolished by adenosine administration.

View larger version (14K): [in this window] [in a new window]   Figure 3. Relationship between mean coronary blood flow and coronary arterial pressure in presence (left) and absence (right) of intact coronary autoregulation. Coronary blood flow data are normalized to baseline flow (autoregulation present) or flow at a coronary arterial pressure of 80 mm Hg (autoregulation absent). The different symbols represent different dogs.

Representative examples of the PRSW relationship and ESPVR obtained in these 2 groups of dogs at various levels of mean coronary arterial pressure, ranging from 60 to 180 mm Hg, are shown in Figure 4. As these examples demonstrate, under conditions of constant coronary blood flow, increasing coronary arterial pressure did not change either the ESPVR or the PRSW relationship significantly (the coefficient b₂ in Equation 2 was not significantly different from zero for either relationship). This lack of effect of coronary arterial pressure on contractility remained when the data were reanalyzed with a simpler statistical analysis that did not include the term for interaction between coronary arterial pressure and LV volume (CAP · x in Equation 2). In contrast, when coronary autoregulation was absent, so that coronary blood flow increased in parallel with coronary arterial pressure, there was a progressive upward/leftward shift of both the ESPVR and PRSW relationship with increasing perfusion pressure (the coefficient b₂ in Equation 2 was significantly greater than zero; P<0.001).

View larger version (34K): [in this window] [in a new window]   Figure 4. Representative examples of ESPVRs (top) and corresponding PRSW relationships (bottom) obtained at various fixed levels of coronary arterial pressure, ranging between 60 and 180 mm Hg, in presence (left) and absence (right) of intact coronary autoregulation.

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
This study demonstrates that the concomitant increase in coronary perfusion pressure with increased afterload in the intact circulation with intact coronary autoregulation does not contribute to the upregulation of LV contractile performance. Thus, the normal upregulation of LV contractility in response to increased afterload^{20 21 22 23} is not a manifestation of the Gregg phenomenon.¹ Moreover, this study demonstrates that provided coronary autoregulation is intact so that coronary blood flow does not vary with coronary perfusion pressure, coronary perfusion pressure does not influence LV contractile function. Thus, the Gregg phenomenon is not due to an increase in coronary perfusion pressure per se. We observed increased LV contractile function with increased coronary perfusion pressure only when coronary blood flow also increased.

Since Gregg's original observation that increased coronary perfusion pressure in open-chest dogs increased myocardial oxygen consumption,¹ many studies have demonstrated increased myocardial contractile function and/or oxygen consumption with increased coronary perfusion pressure and flow.^{1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19} Most of these studies have been conducted in isolated heart or isolated cardiac muscle preparations. Factors confounding the interpretation of many of these studies included the possibility that enhanced contractility with increased perfusion pressure and flow reflected correction of baseline ischemia,⁶ particularly in studies in which the control measurements were recorded with coronary perfusion pressures below 60 mm Hg,^{2 9 17 18 19} and the use of nonblood coronary perfusion solutions^{2 3 5 7 14 15 33} that may result in LV wall edema. In addition, some coronary perfusates contained calcium or induced increased intracellular calcium,^{3 14 15 34} thus further confounding the interpretation of contractility changes.

The most important confounding factor, however, in nearly all previous studies of the Gregg phenomenon, including that by Gregg,¹ was that both coronary perfusion pressure and coronary flow increased simultaneously.^{1 2 3 4 5 6 7 8 9 10 11 12 13 14 15} Consequently, the effect of increased coronary perfusion pressure per se could not be separated from that of increased coronary flow.

Arnold and colleagues² observed, in isolated guinea pig hearts, that increased coronary blood flow induced by hypoxia at constant perfusion pressure did not increase LV oxygen consumption or systolic pressure, but increasing the perfusion pressure of coronary dextran infusion at a constant flow rate increased both. The depression of contractile function by hypoxia, however, might have masked any increase in contractile function and oxygen consumption during increased coronary flow,²⁷ whereas the infusion of hypertonic dextran may have enhanced contractility by inducing increased intracellular calcium.³⁴

In support of coronary blood flow as the major determinant of contractile function, Abel and Reis⁴ demonstrated, in isovolumically beating canine hearts, increased oxygen consumption and maximal velocity of fiber shortening with increased coronary blood flow induced by nitroglycerin at constant perfusion pressure, whereas neither parameter changed with decreased perfusion pressure at a constant blood flow rate. Goto and colleagues²⁷ demonstrated that the ESPVR slope and unloaded oxygen consumption increased with increased coronary blood flow induced by adenosine at constant perfusion pressure in isovolumically beating rabbit hearts. Sunagawa and colleagues³⁵ demonstrated, in isovolumically beating canine hearts, that the ESPVR was not dependent on coronary perfusion pressure provided that the pressure exceeded 67±22 mm Hg, below which coronary autoregulation was lost, but the highest pressure examined was only 120 mm Hg. Abel and Reis⁴ observed progressive increments in isovolumic peak pressure with step increases in coronary perfusion pressure from 45 to 175 mm Hg only when coronary blood flow also increased with each step in pressure.

From our findings and those discussed above, it appears that increased coronary blood flow is a necessary condition for the Gregg phenomenon, but this will occur with an increase in coronary perfusion pressure only when coronary autoregulation is deficient. This conclusion is supported by the recent finding of Bai and colleagues²⁸ that effective coronary autoregulation in dogs minimizes increases in coronary vascular volume in response to increases in perfusion pressure, so that increased myocardial oxygen consumption in response to increased coronary perfusion pressure was seen only when coronary autoregulation was poor and coronary vascular volume increased significantly.

This nexus between the Gregg phenomenon, increased coronary blood flow, and increased coronary vascular volume is consistent with the view that the mechanism of the Gregg phenomenon is an increase in end-diastolic sarcomere length due to stretching by the engorged vasculature ("garden-hose" effect),² but this is not the only possible interpretation. One study in an isovolumically contracting heart preparation¹⁵ and another in an isolated cardiac muscle preparation¹⁴ demonstrated large increases in force generation with increased perfusion pressure and flow that were not associated with significant increments in end-diastolic fiber length but were associated in 1 of the studies¹⁵ with an increased intracellular calcium transient. Both studies were subject to the limitations of nonblood perfusates and absent flow autoregulation summarized above. In 1 of the studies,¹⁵ flow rates were unphysiologically high, and force generation was much higher than that observed in blood-perfused preparations.²⁷ Nevertheless, these studies raise the possibility that coronary vascular engorgement and increased wall volume are simply markers of the increased flow rate that is more directly responsible for the inotropic effect, possibly by increased washout of negatively inotropic agents or increased delivery or stimulated production of positively inotropic agents from the endothelium or myocytes.^{14 15 36 37}

Blood perfusion at 37°C and the presence of intact coronary autoregulation were 2 important advantages of our experimental preparation relative to most previous investigations of the Gregg phenomenon. The fact that the canine right coronary artery, unlike its human counterpart, does not supply any LV myocardium^{29 30} allowed control of LV myocardial perfusion pressure by cannulation of the left main coronary artery. In addition, the coronary perfusion cannula allowed us to switch rapidly between the open-gate and closed-gate perfusion conditions, thus minimizing any temporal variability in the baseline contractile state between the 2 perfusion conditions. Nevertheless, our experiments were conducted with the chest open under general anesthesia. These experimental conditions may have produced some depression of baseline contractility. The baseline slope of the ESPVR was indeed somewhat lower than reported values in conscious dogs after autonomic blockade.²¹ This may explain the small depression of the PRSW relationship with aortic constriction in the present study compared with the previously reported insensitivity of the relationship to larger increments in afterload in conscious animals.^{23 24} Presumably for the same reason, the relatively modest increments in LV mean ejection pressure with aortic constriction were the highest stable levels we could maintain in this preparation for the several minutes necessary to acquire the contractility data. It was for this reason, in part, that we used the second experimental protocol to achieve a much higher level of coronary perfusion pressure than could be achieved during aortic constriction.

In summary, in the intact canine circulation with intact coronary autoregulation, the concomitant increase in coronary perfusion pressure with increased afterload did not contribute to the upregulation of contractile force. Moreover, in the absence of any significant changes in blood flow, due to intact coronary autoregulation, wide variations in coronary perfusion pressure did not influence LV contractile function.

	Acknowledgments

 
This study was supported by a project grant from the National Health and Medical Research Council of Australia.

Received December 7, 1998; revision received May 27, 1999; accepted June 2, 1999.

	References

Top Abstract Introduction Methods Results Discussion References

 
1. Gregg DE. Effect of coronary perfusion pressure and coronary flow on oxygen usage of the myocardium. Circ Res. 1963;13:497–500.[Free Full Text]

2. Arnold G, Kosche F, Miessner A, Neitzert A, Lochner W. The importance of the perfusion pressure in coronary arteries for the contractility and oxygen consumption of the heart. Pflugers Arch. 1968;299:339–356.

3. Opie LH. Coronary flow rate and perfusion pressure as determinants of mechanical function and oxidative metabolism of isolated perfused rat heart. J Physiol (Lond). 1965;180:529–541.[Free Full Text]

4. Abel RM, Reis RL. Effects of coronary blood flow and perfusion pressure on left ventricular contractility in dogs. Circ Res. 1970;27:961–971.[Abstract/Free Full Text]

5. Rubanyi G, Kovach GB. The role of coronary perfusion pressure in the control of mechanical performance and oxygen consumption in the isolated rat heart. Acta Physiol Hung. 1980;53:189–196.

6. Feigl EO. Coronary physiology. Physiol Rev. 1983;63:13–18.

7. Schipke JD, Stocks I, Sunderdeik U, Arnold G. Effect of changes in aortic pressure and in coronary arterial pressure on left ventricular geometry and function: Anrep vs. gardenhose effect. Basic Res Cardiol. 1993;88:621–637.[Medline] [Order article via Infotrieve]

8. Fukui A, Yamaguchi S, Tamada Y, Miyawaki H, Shirakabe M, Baniya G, Tomoike H. Increasing coronary perfusion pressure on diastolic and systolic performance is less pronounced in right ventricle than in left ventricle. Cardiovasc Res. 1996;31:899–906.[Medline] [Order article via Infotrieve]

9. Arnold G, Morgenstern C, Lochner W. The autoregulation of the heart work by the coronary perfusion pressure. Pflugers Arch. 1970;321:34–55.[Medline] [Order article via Infotrieve]

10. Miller WP, Nellis SH, Liedtke AJ, Whitesell L, Effron BA. Coronary hyperperfusion and ventricular function in intact and isovolumic pig hearts. Am J Physiol. 1990;258(Heart Circ Physiol 27):H500–H507.

11. Goto Y, Slinker BK, LeWinter MM. Effects of amrinone and isoproterenol on mechanoenergetics of blood-perfused rabbit heart. Am J Physiol. 1992;262:H719–H727.[Abstract/Free Full Text]

12. Miller WP, Shimamoto N, Nellis SH, Liedtke JA. Coronary hyperperfusion and myocardial metabolism in isolated and intact hearts. Am J Physiol. 1987;253(Heart Circ Physiol 22):H1271–H1278.

13. Miller WP, Flygenring BP, Nellis SH. Effects of load alteration and coronary perfusion pressure on regional end-systolic relations. Circulation. 1988;78:1299–1309.[Abstract/Free Full Text]

14. Schouten VAJ, Allart CP, Westerhof N. Effect of perfusion pressure on force of contraction in thin papillary muscles and trabeculae from rat heart. J Physiol. 1992;451:585–604.[Abstract/Free Full Text]

15. Kitakaze M, Marban E. Cellular mechanism of the modulation of contractile function by coronary perfusion pressure in ferret hearts. J Physiol. 1989;414:455–472.[Abstract/Free Full Text]

16. Cross CE, Reiben PA, Salisbury PF. Influence of coronary perfusion and myocardial edema on pressure-volume diagram of left ventricle. Am J Physiol. 1961;201:102–108.

17. Weisfeldt ML, Shock NW. Effect of perfusion pressure on coronary flow and oxygen usage of non-working heart. Am J Physiol. 1970;218:95–101.

18. Salisbury PF, Cross CE, Reiben PA. Influence of coronary arterial pressure upon myocardial elasticity. Circ Res. 1960;8:794–800.[Abstract/Free Full Text]

19. Templeton GH, Wildenthal K, Mitchell JH. Influence of coronary blood flow on left ventricular contractility and stiffness. Am J Physiol. 1972;223:1216–1220.

20. Sodums MT, Badke FR, Starling MR, Little WC, O'Rourke RA. Evaluation of left ventricular contractile performance utilizing end-systolic pressure-volume relationships in conscious dogs. Circ Res. 1984;54:731–739.[Abstract/Free Full Text]

21. Spratt JA, Tyson GS, Glower DD, Davis JW, Muhlbaier LH, Olsen CO, Rankin JS. The end-systolic pressure-volume relationship in conscious dogs. Circulation. 1987;75:1295–1309.[Abstract/Free Full Text]

22. Little WC, Cheng C-P, Mumma M, Igarashi Y, Vinten-Johansen J, Johnston WE. Comparison of measures of left ventricle contractile performance derived from pressure-volume loops in conscious dogs. Circulation. 1989;80:1378–1387.[Abstract/Free Full Text]

23. Glower DD, Spratt JA, Snow ND, Kabas JS, Davis JW, Olsen CO, Tyson GS, Sabiston DC Jr, Rankin JS. Linearity of the Frank-Starling relationship in the intact heart: the concept of preload recruitable stroke work. Circulation. 1985;71:994–1009.[Abstract/Free Full Text]

24. Karunanithi MK, Michniewicz J, Copeland SE, Feneley MP. Right ventricular preload recruitable stroke work, end-systolic pressure-volume, and dP/dt_max-end-diastolic volume relations compared as indexes of right ventricular contractile performance in conscious dogs. Circ Res. 1992;70:1169–1179.[Abstract/Free Full Text]

25. Sarnoff SJ, Mitchell JH, Gilmore JP, Remensnyder JP. Homeometric autoregulation in the heart. Circ Res. 1960;8:1077–1091.[Abstract/Free Full Text]

26. Maughan WL, Sunagawa K, Burkhoff D, Sagawa K. Effect of arterial impedance changes on the end-systolic pressure-volume relation. Circ Res. 1984;54:595–602.[Abstract/Free Full Text]

27. Goto Y, Slinker BK, LeWinter MM. Effect of coronary hyperemia on Emax and oxygen consumption in blood-perfused rabbit hearts: energetic consequences of Gregg's phenomenon. Circ Res. 1991;68:482–492.[Abstract/Free Full Text]

28. Bai X-J, Iwamoto T, Williams AG, Fan W-L, Downey HR. Coronary pressure-flow autoregulation protects myocardium from pressure-induced changes in oxygen consumption. Am J Physiol. 1994;266:H2359–H2368.[Abstract/Free Full Text]

29. Kazzaz D, Shanklin WM. The coronary vessels of the dog demonstrated by colored plastic (vinyl acetate) injection and corrosion. Anat Rec. 1950;107:43–59.[Medline] [Order article via Infotrieve]

30. Scheel KW, Ingram LA, Gordey RL. Relationship of coronary flow and perfusion territory in dogs. Am J Physiol. 1982;243:H738–H747.

31. Sagawa K, Suga H, Shoukas AA, Bakalar KM. End-systolic pressure/volume ratio: a new index of ventricular contractility. Am J Cardiol. 1977;40:748–753.[Medline] [Order article via Infotrieve]

32. Glantz SA, Slinker BK. Primer of Applied Regression and Analysis of Variance. New York, NY: McGraw-Hill; 1990:316–463.

33. Lukas VD, Krams R, Sipkema P, Westerhof N. Changes in coronary pressure-flow relation after transition from blood to Tyrode perfusion. Am J Physiol. 1988;255:H476–H482.[Abstract/Free Full Text]

34. Allen DG, Smith GL. The effects of hypertonicity on tension and intracellular calcium concentration in ferret ventricular muscle. J Physiol (Lond). 1987;383:425–439.[Abstract/Free Full Text]

35. Sunagawa K, Maughan WL, Firesinger G, Guzman P, Chang M-S, Sagawa K. Effects of coronary arterial pressure on left ventricular end-systolic pressure-volume relation of isolated canine heart. Circ Res. 1982;50:727–734.[Abstract/Free Full Text]

36. Mohan P, Brutsaert DL. Mechanisms of endothelial modulation of myocardial performance. Adv Exp Med Biol. 1995;382:249–260.[Medline] [Order article via Infotrieve]

37. Brutsaert DL, Fransen P, Andries LJ, DeKeulenaer GW, Sys SU. Cardiac endothelium and myocardial function. Cardiovasc Res. 1998;38:281–290.[Abstract/Free Full Text]

This article has been cited by other articles:

				N. Westerhof, C. Boer, R. R. Lamberts, and P. Sipkema Cross-talk between cardiac muscle and coronary vasculature. Physiol Rev, October 1, 2006; 86(4): 1263 - 1308. [Abstract] [Full Text] [PDF]

				E. I. Tikh, R. A. Fenton, and J. G. Dobson Jr. Contractile effects of adenosine A1 and A2A receptors in isolated murine hearts Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H348 - H356. [Abstract] [Full Text] [PDF]

				S. Schenk, Z. B. Popovic, Y. Ochiai, F. Casas, P. M. McCarthy, R. C. Starling, M. W. Kopcak Jr., R. Dessoffy, J. L. Navia, N. L. Greenberg, et al. Preload-adjusted right ventricular maximal power: concept and validation Am J Physiol Heart Circ Physiol, October 1, 2004; 287(4): H1632 - H1640. [Abstract] [Full Text] [PDF]

				G. Cotter, Y. Moshkovitz, E. Kaluski, O. Milo, Y. Nobikov, A. Schneeweiss, R. Krakover, and Z. Vered The role of cardiac power and systemic vascular resistance in the pathophysiology and diagnosis of patients with acute congestive heart failure Eur J Heart Fail, August 1, 2003; 5(4): 443 - 451. [Abstract] [Full Text] [PDF]

				G. Cotter, E. Kaluski, O. Milo, A. Blatt, A. Salah, A. Hendler, R. Krakover, A. Golick, and Z. Vered LINCS: L-NAME (a NO synthase inhibitor) In the treatment of refractory Cardiogenic Shock: A prospective randomized study Eur. Heart J., July 2, 2003; 24(14): 1287 - 1295. [Abstract] [Full Text] [PDF]

				M. K. Karunanithi, J. Michniewicz, J. A. Young, and M. P. Feneley Effect of acutely increased left ventricular afterload on work output from the right ventricle in conscious dogs J. Thorac. Cardiovasc. Surg., January 1, 2001; 121(1): 0116 - 124. [Abstract] [Full Text] [PDF]

				F. Lin, W. A. Owens, S. Chen, M. E. Stevens, S. Kesteven, J. F. Arthur, E. A. Woodcock, M. P. Feneley, and R. M. Graham Targeted {alpha}1A-Adrenergic Receptor Overexpression Induces Enhanced Cardiac Contractility but not Hypertrophy Circ. Res., August 17, 2001; 89(4): 343 - 350. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Karunanithi, M. K. Articles by Feneley, M. P. Search for Related Content PubMed PubMed Citation Articles by Karunanithi, M. K. Articles by Feneley, M. P. Related Collections Contractile function Animal models of human disease Coronary circulation