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Cardiopulmonary Bypass and PVR
CORRESPONDENCE
Cardiopulmonary Bypass and PVR
tion factor is known or if the CVP is maintained constant. We were not informed whether or not this was To the Editor: done in either study. The increase in peripheral vascular resistance (PVR) The central piece of information required in these that occurs during nonpulsatile cardiopulmonary studies was the work load of the left ventricle. This is bypass is well documented. In a recent issue of The best described by the calculation of aortic input imAnnals, Landymore and colleagues [2] reported that pedance, which is defined as mean BP divided by in a series of patients, no increase occurred during mean flow in the arch of the aorta. Preferably, the nonpulsatile cardiopulmonary bypass but that there measurements should be made with high-frequency was an 80% incidence of postoperative hyperten- recording apparatus, subjected to Fourier analysis, sion. In another recent study done in Glasgow, and corrected for measurement errors. The CVP must Taylor and associates [4] found that PVR increased be maintained constant. Even then this is not necesboth during and after nonpulsatile bypass but much sarily the most important criterion, for classic physiless so during and after "pulsatile" bypass using the ology tells us that cardiac output is dependent upon Stockert roller pump for both groups of patients. the ventricular filling conditions as well as the These two groups of researchers attributed the in- ventricular afterload. crease in PVR to activation of the renin-angiotensin Hernodynamics is a relatively unexplored field in system. cardiac surgery, and the mathematical tools are powPeripheral vascular resistance was assessed by erful ones. However, for the clinician lacking the essimilar formulas of the type (BP-CVP)/Q,where BP is sential background in fluid mechanics, the pitfalls systemic arterial pressure, CVP is central venous are numerous. pressure, and Q is cardiac or pump output. Many physiologists have abandoned this technique of as- G . Wright, P h D . sessing vasomotor tone because of measurement University of Keele and problems and because of the doubtful meaning of North Staffordshire Hospital Centre, the results. During open-heart operations, additional Stoke-ow Trent, problems are introduced by relative fluid volume England shifts and changes in fluid composition. In the formula just discussed, the effects of fluid viscosity are assumed to be negligible. In many cases References this assumption is reasonable, but during open-heart 1. Barras J-P: Blood rheology-general review. In Lundsgaard-Hansen P, Hassig A, Nitschmann operations it is not. At the beginning of bypass, Hs (eds): Modified Gelatins as Plasma Substithere is generally a marked reduction in packed cell tutes. Bib1 Haematol 33:277, 1969 volume and, presumably, relative fluid viscosity, 2. Landymore RW, Murphy DA, Kinley CE, et al: due to hemodilution. This may explain the marked Does pulsatile flow influence the incidence of fall in BP that usually occurs at the onset of bypass. postoperative hypertension? Ann Thorac Surg Thereafter, the packed cell volume usually rises 28:261, 1979 slightly up to the end of bypass and then increases more rapidly. Relative viscosity varies with many 3. Lee WH, Krumhaar D, Fonkalsrud EW, et al: Denaturation of plasma proteins as a cause of morfactors including temperature and hematocrit [l], bidity and death after intracardiac operations. and is increased by plasma protein denaturation and Surgery 50:29, 1961 fluid infusions during bypass [31. It is not possible to measure blood viscosity under these conditions, but 4. Taylor KM,Bairn WH, Russell M, et al: Peripheral vascular resistance and angiotensin I1 levels durtheory tells us that PVR will vary directly and almost ing pulsatile and non-pulsatile cardiopulmonary proportionally with changes in viscosity. The actual bypass. Thorax 34:594, 1979 value of the relative viscosity is unknown throughout, and this puts the measurement of PVR into the Reply area of guesswork. A second problem is that the formula results from To the Editor: another assumption-that the relationship between Dr. Wright stated that we reported [3] a series of paBP and CVP is proportional. This is not necessarily tients who failed to demonstrate an increase in syscorrect. It may not even be linear. If the circulatory temic resistance during nonpulsatile cardiopulmosystem were purely resistive, it would be linear nary bypass but in whom significant blood pressure though not necessarily proportional, but the com- elevations were observed in the early postoperative pliance of the system inevitably introduces non- period. Dr. Wright has misinterpreted our results. linearities. This means that over the relevant range, Our data clearly demonstrated significant elevations BP increases more than proportionally to increases in of systemic resistance toward the end of bypass (p < CVP, other things being equal. This large potential 0.05). Furthermore, postoperative hypertension was error can be corrected only if the appropriate correc- observed in 80% of the control patients and was as611
612 The Annals of Thoracic Surgery Vol 30 No 6 December 1980
sociated with marked elevations of systemic resistance ( p < 0.05). Also, Dr. Wright expressed the opinion that systemic resistance determinations are inaccurate when calculated from the standard resistance equation because of assumptions made about blood viscosity and central venous pressure (CVP). Resistance calculated from the standard formula assumes that viscosity is constant. If viscosity varies over a wide range of values, however, this assumption is not correct. Hematocrit is the main proponent of blood viscosity and did not differ significantly between the two patient groups throughout our study [31. Therefore, systemic resistance determinations should be valid. Furthermore, elevation of resistance during bypass would appear to be even more important since viscosity and systemic resistance decrease with hemodilution [2]. We concur with Dr. Wright’s observations that CVP and blood pressure are not proportional. However, in order to apply the standard equation for systemic resistance determination, AP is calculated as the pressure difference between the arterial and venous circulations. Dr. Wright stated that the relationship is valid only if CVP is kept constant. During cardiac operations, it is virtually impossible to do this, although CVP usually varies over a small range of values. Let us assume, however, that it is inaccurate to calculate penpheral vascular resistance utilizing CVP and therefore calculate it by dividing only systemic arterial pressure by cardiac or pump output. Computing resistance from our data without CVP results in a 6.2% difference compared with calculations carried out with the standard formula. This small percentage difference does not change the statistical significance of our observations, and they remain significant within the 95% confidence interval. Total peripheral resistance traditionally has been calculated by clinicians using Poiseuille’s law, which was designed for a steady flow system. The flow in the systemic circulation is pulsatile, and a more correct method of characterizing afterload is to measure aortic input impedance, a method introduced by McDonald [4]. Aortic input impedance is obtained from high-fidelity measurements of both the aortic blood pressure and the ascending aortic blood flow waveforms. These waveforms can be measured with a Millar PC-350 catheter and an electromagnetic or ultrasonic flowmeter. The resultant waveforms are then sampled at a frequency determined by the Nyquist criterion and digitalized, and the Fourier series [l] of each waveform is obtained using one of the standard logarithms. The input impedance is computed by dividing each harmonic term of pressure by its corresponding harmonic of flow. The resultant series of terms represents the impedance of the aorta and includes the viscous and inertial characteristics of blood as well as the compliance of the arterial vessels.
We agree with Dr. Wright that determination of aortic impedance is a more precise method of measuring vasomotor tone. However, impedance measurements require considerably more sophisticated monitoring equipment compared with resistance calculations from the standard equation. We believe that systemic resistance calculated from the standard formula is valid, especially when resistance data are used to compare two similar patient populations. Furthermore, it is difficult to discuss recent data with reference to previous reports [51 if the method of measuring vasomotor tone is dissimilar. R. W. Landymore, M . D . A . Marble, Ph.D.
Department of Surgery Dalhousie University Halifax, N S , Canada
References 1. Attinger E, Anne A, McDonald D: Use of Fourier series for the analysis of biological systems. Biophys J 6:291, 1966 2. Keliman GR: Applied Cardiovascular Physiology. Toronto, Butteworth, 1977, p 11 3. Landymore RW, Murphy DA, Kinley CE, et al: Does pulsatile flow influence the incidence of postoperative hypertension? Ann Thorac Surg 28:261, 1979 4. McDonald DA: Relation of pulsating pressure to flow in arteries. J Physiol 127:533, 1955 5. Taylor K, Morton I, Brown J, et al: Hypertension and the renin-angiotensin system following open-heart surgery. J Thorac Cardiovasc Surg 74:840, 1977
Staging Lung Cancer Patients To the Editor: On first reading the paper by Dr. Takita and colleagues (Ann Thorac Surg 28:363,1979), my immediate impulse was to consult my colleagues in chemotherapy and urge them to develop a similar treatment protocol quickly. The authors implied that chemotherapy changed the staging of 24 (18.5%) of 128 patients. If so, this is truly a remarkable achievement. More sober consideration, however, raised the following question: With 2 surgical deaths and 5 “incomplete resections,” 3 of them pneumonectomies, do these figures represent instead a 29% error rate in staging? Staging lung cancer patients according to the TNM system does not perforce define inoperability. Therefore, the information contained in the paper is difficult to process because three essential elements are missing: (1) criteria for inoperability in this group of patients; (2) definition of N2lesions; and (3) method of categorizing MI patients: tissue? gallium scan? palpation? pain? According to information in the authors’ reference 1, T2 NO MO characterizes a
Cardiopulmonary Bypass and PVR
tion factor is known or if the CVP is maintained constant. We were not informed whether or not this was To the Editor: done in either study. The increase in peripheral vascular resistance (PVR) The central piece of information required in these that occurs during nonpulsatile cardiopulmonary studies was the work load of the left ventricle. This is bypass is well documented. In a recent issue of The best described by the calculation of aortic input imAnnals, Landymore and colleagues [2] reported that pedance, which is defined as mean BP divided by in a series of patients, no increase occurred during mean flow in the arch of the aorta. Preferably, the nonpulsatile cardiopulmonary bypass but that there measurements should be made with high-frequency was an 80% incidence of postoperative hyperten- recording apparatus, subjected to Fourier analysis, sion. In another recent study done in Glasgow, and corrected for measurement errors. The CVP must Taylor and associates [4] found that PVR increased be maintained constant. Even then this is not necesboth during and after nonpulsatile bypass but much sarily the most important criterion, for classic physiless so during and after "pulsatile" bypass using the ology tells us that cardiac output is dependent upon Stockert roller pump for both groups of patients. the ventricular filling conditions as well as the These two groups of researchers attributed the in- ventricular afterload. crease in PVR to activation of the renin-angiotensin Hernodynamics is a relatively unexplored field in system. cardiac surgery, and the mathematical tools are powPeripheral vascular resistance was assessed by erful ones. However, for the clinician lacking the essimilar formulas of the type (BP-CVP)/Q,where BP is sential background in fluid mechanics, the pitfalls systemic arterial pressure, CVP is central venous are numerous. pressure, and Q is cardiac or pump output. Many physiologists have abandoned this technique of as- G . Wright, P h D . sessing vasomotor tone because of measurement University of Keele and problems and because of the doubtful meaning of North Staffordshire Hospital Centre, the results. During open-heart operations, additional Stoke-ow Trent, problems are introduced by relative fluid volume England shifts and changes in fluid composition. In the formula just discussed, the effects of fluid viscosity are assumed to be negligible. In many cases References this assumption is reasonable, but during open-heart 1. Barras J-P: Blood rheology-general review. In Lundsgaard-Hansen P, Hassig A, Nitschmann operations it is not. At the beginning of bypass, Hs (eds): Modified Gelatins as Plasma Substithere is generally a marked reduction in packed cell tutes. Bib1 Haematol 33:277, 1969 volume and, presumably, relative fluid viscosity, 2. Landymore RW, Murphy DA, Kinley CE, et al: due to hemodilution. This may explain the marked Does pulsatile flow influence the incidence of fall in BP that usually occurs at the onset of bypass. postoperative hypertension? Ann Thorac Surg Thereafter, the packed cell volume usually rises 28:261, 1979 slightly up to the end of bypass and then increases more rapidly. Relative viscosity varies with many 3. Lee WH, Krumhaar D, Fonkalsrud EW, et al: Denaturation of plasma proteins as a cause of morfactors including temperature and hematocrit [l], bidity and death after intracardiac operations. and is increased by plasma protein denaturation and Surgery 50:29, 1961 fluid infusions during bypass [31. It is not possible to measure blood viscosity under these conditions, but 4. Taylor KM,Bairn WH, Russell M, et al: Peripheral vascular resistance and angiotensin I1 levels durtheory tells us that PVR will vary directly and almost ing pulsatile and non-pulsatile cardiopulmonary proportionally with changes in viscosity. The actual bypass. Thorax 34:594, 1979 value of the relative viscosity is unknown throughout, and this puts the measurement of PVR into the Reply area of guesswork. A second problem is that the formula results from To the Editor: another assumption-that the relationship between Dr. Wright stated that we reported [3] a series of paBP and CVP is proportional. This is not necessarily tients who failed to demonstrate an increase in syscorrect. It may not even be linear. If the circulatory temic resistance during nonpulsatile cardiopulmosystem were purely resistive, it would be linear nary bypass but in whom significant blood pressure though not necessarily proportional, but the com- elevations were observed in the early postoperative pliance of the system inevitably introduces non- period. Dr. Wright has misinterpreted our results. linearities. This means that over the relevant range, Our data clearly demonstrated significant elevations BP increases more than proportionally to increases in of systemic resistance toward the end of bypass (p < CVP, other things being equal. This large potential 0.05). Furthermore, postoperative hypertension was error can be corrected only if the appropriate correc- observed in 80% of the control patients and was as611
612 The Annals of Thoracic Surgery Vol 30 No 6 December 1980
sociated with marked elevations of systemic resistance ( p < 0.05). Also, Dr. Wright expressed the opinion that systemic resistance determinations are inaccurate when calculated from the standard resistance equation because of assumptions made about blood viscosity and central venous pressure (CVP). Resistance calculated from the standard formula assumes that viscosity is constant. If viscosity varies over a wide range of values, however, this assumption is not correct. Hematocrit is the main proponent of blood viscosity and did not differ significantly between the two patient groups throughout our study [31. Therefore, systemic resistance determinations should be valid. Furthermore, elevation of resistance during bypass would appear to be even more important since viscosity and systemic resistance decrease with hemodilution [2]. We concur with Dr. Wright’s observations that CVP and blood pressure are not proportional. However, in order to apply the standard equation for systemic resistance determination, AP is calculated as the pressure difference between the arterial and venous circulations. Dr. Wright stated that the relationship is valid only if CVP is kept constant. During cardiac operations, it is virtually impossible to do this, although CVP usually varies over a small range of values. Let us assume, however, that it is inaccurate to calculate penpheral vascular resistance utilizing CVP and therefore calculate it by dividing only systemic arterial pressure by cardiac or pump output. Computing resistance from our data without CVP results in a 6.2% difference compared with calculations carried out with the standard formula. This small percentage difference does not change the statistical significance of our observations, and they remain significant within the 95% confidence interval. Total peripheral resistance traditionally has been calculated by clinicians using Poiseuille’s law, which was designed for a steady flow system. The flow in the systemic circulation is pulsatile, and a more correct method of characterizing afterload is to measure aortic input impedance, a method introduced by McDonald [4]. Aortic input impedance is obtained from high-fidelity measurements of both the aortic blood pressure and the ascending aortic blood flow waveforms. These waveforms can be measured with a Millar PC-350 catheter and an electromagnetic or ultrasonic flowmeter. The resultant waveforms are then sampled at a frequency determined by the Nyquist criterion and digitalized, and the Fourier series [l] of each waveform is obtained using one of the standard logarithms. The input impedance is computed by dividing each harmonic term of pressure by its corresponding harmonic of flow. The resultant series of terms represents the impedance of the aorta and includes the viscous and inertial characteristics of blood as well as the compliance of the arterial vessels.
We agree with Dr. Wright that determination of aortic impedance is a more precise method of measuring vasomotor tone. However, impedance measurements require considerably more sophisticated monitoring equipment compared with resistance calculations from the standard equation. We believe that systemic resistance calculated from the standard formula is valid, especially when resistance data are used to compare two similar patient populations. Furthermore, it is difficult to discuss recent data with reference to previous reports [51 if the method of measuring vasomotor tone is dissimilar. R. W. Landymore, M . D . A . Marble, Ph.D.
Department of Surgery Dalhousie University Halifax, N S , Canada
References 1. Attinger E, Anne A, McDonald D: Use of Fourier series for the analysis of biological systems. Biophys J 6:291, 1966 2. Keliman GR: Applied Cardiovascular Physiology. Toronto, Butteworth, 1977, p 11 3. Landymore RW, Murphy DA, Kinley CE, et al: Does pulsatile flow influence the incidence of postoperative hypertension? Ann Thorac Surg 28:261, 1979 4. McDonald DA: Relation of pulsating pressure to flow in arteries. J Physiol 127:533, 1955 5. Taylor K, Morton I, Brown J, et al: Hypertension and the renin-angiotensin system following open-heart surgery. J Thorac Cardiovasc Surg 74:840, 1977
Staging Lung Cancer Patients To the Editor: On first reading the paper by Dr. Takita and colleagues (Ann Thorac Surg 28:363,1979), my immediate impulse was to consult my colleagues in chemotherapy and urge them to develop a similar treatment protocol quickly. The authors implied that chemotherapy changed the staging of 24 (18.5%) of 128 patients. If so, this is truly a remarkable achievement. More sober consideration, however, raised the following question: With 2 surgical deaths and 5 “incomplete resections,” 3 of them pneumonectomies, do these figures represent instead a 29% error rate in staging? Staging lung cancer patients according to the TNM system does not perforce define inoperability. Therefore, the information contained in the paper is difficult to process because three essential elements are missing: (1) criteria for inoperability in this group of patients; (2) definition of N2lesions; and (3) method of categorizing MI patients: tissue? gallium scan? palpation? pain? According to information in the authors’ reference 1, T2 NO MO characterizes a