Effect of acute allograft rejection on exercise hemodynamics in patients who have undergone cardiac transplantation.

The effect of acute allograft rejection on exercise hemodynamics was evaluated in 8 consecutive cardiac allograft recipients (group 1) when the right ventricular endomyocardial biopsy showed evidence of allograft rejection (R), and when no evidence of rejection (NR) was present. A separate group of 10 cardiac transplant recipients (group 2) with no evidence of rejection on biopsy done at the end of the first and second year post-transplantation served as controls. The exercise hemodynamics were abnormal in both groups in both studies with a moderate increase of the pulmonary artery wedge pressure to a mean of 17.2 (NR) and 19.4 mm Hg (R) in group 1 (p = not significant [NS]) and 20.1 and 21.2 mm Hg in group 2 (p = NS), a mild increase of the mean right atrial pressure to a mean of 10 mm Hg (NR) and 10 mm Hg (R) in group 1 (p = NS), 11.9 mm Hg and 12.5 mm Hg in group 2 (p = NS), and a moderate increase of the arteriovenous oxygen content difference to a mean of 8.5 (NR) and 8.4 vol percent (R) in group 1 and 8.3 and 8.0 vol percent in group 2. No significant difference was observed between the two studies of the same group in any of the hemodynamic parameters except for the heart rate in group 1 (from 91 +/- 16 to 97 +/- 16 beats/min [p < 0.05] with and without evidence of allograft rejection, respectively). In conclusion, heart transplant recipients do not usually manifest further exercise hemodynamic deterioration during mild to moderate rejection.

Paradoxical increase of ventricular fibrillation threshold in response to coronary sinus obstruction.

We determined the ventricular fibrillation threshold (VFT) changes in response to graded coronary sinus (CS) obstruction in 13 chloralose-anesthetized dogs with fixed heart rate (150 min-1, mean systemic arterial pressure (80 mm Hg), and cardiac index (100 ml/min.kg-1 body weight). VFT in milliamperes (VFTmA) increased linearily with CS pressure (CSP) increases up to 41.2 +/- 1.4 mm Hg (VFTmA = 6.5 + 0.14 CSP mm Hg, p less than 0.01). Total coronary venous effluent (CBF) did not change significantly, suggesting compensatory coronary vasodilation. Myocardial O2 consumption also remained unchanged. At higher CSP, both CBF and VFT declined precipitously (VFTmA = 20.9 - 0.27 CSP mm Hg, p less than 0.02). With simultaneous increases of systemic arterial along with CSP, VFT increased again along with the CSP-induced reduction of gradient until it reached 42.8 +/- 3.2 mm Hg. We conclude that with coronary venous obstruction, despite coronary perfusion gradient reduction to about 40 mm Hg, CBF remains constant. This constant flow vasodilation is associated with substantial (82%) VFT increase. The mechanism may involve enhanced homogeneity of CBF distribution and increased extracellular fluid.

Comparison of Fick and dye cardiac outputs during rest and exercise in 1,022 patients.

The Fick and indicator-dilution techniques for measurement of cardiac output (CO) were compared at rest in 1,022 patients and in 786 during exercise. Duplicate measurements of dye CO at rest revealed that 92.7% fell within 10% of the line of identity and 99% within 20%. For the resting Fick and dye comparisons, 44.6% were within 10% of the identity line and 74.7% within 20%. When mean CO was less than 4.4 L/min, dye CO was higher than Fick. This relationship persisted for CO between 4.4 and 7.4 whereas for above 7.4 L/min, Fick was higher than dye. During exercise, 50.2% of the Fick and dye comparisons fell within 10% and 77.1% within 20% of the line of identity. There was a systematic difference between the two methods during exercise with dye CO higher than Fick CO. This study agrees with Fick and dye comparison studies with 74.7% and 77.1% of values within 20% of the identity line during rest and exercise, respectively. However, these results differ from others in that dye CO was higher than Fick CO for low and normal values whereas Fick was greater for the higher CO values. The overall agreement between the two methods in a large group of patients with diverse cardiac diseases over a broad spectrum of CO values supports use of either method for clinical studies.

Left main coronary artery occlusion.

Patients with complete occlusion of the left main coronary artery are candidates for massive myocardial infarction and sudden death and are thought to have a uniformly poor prognosis. Complete occlusion of the left main coronary artery was identified in 2 male patients among 2,546 patients undergoing cardiac catheterization over a period of 14.5 years in our institution. Both patients had angina pectoris. Left ventricular end-diastolic pressure was markedly elevated in one, and the ejection fraction was moderately to markedly reduced in both. Significant collateral flow to the left coronary system from the right coronary artery was present in both patients. Our study supports previous reports that left main coronary artery occlusion is rarely encountered during cardiac catheterization.

Recognition and diagnosis of apical hypertrophic cardiomyopathy.

Recognition and diagnosis of nonobstructive apical hypertrophic cardiomyopathy is important to begin to understand the natural history and prognosis of such patients. Our experience with three patients indicates that a clue to the recognition of apical hypertrophic cardiomyopathy lies in the striking electrocardiographic repolarization changes consistent with subendocardial ischemia often prompting admission to the coronary care unit. The diagnosis of apical hypertrophic cardiomyopathy in two patients was confirmed by two-dimensional echocardiographic apical views, but due to a technically inadequate echocardiogram, the diagnosis in the third patient was made by left ventriculography. Two of the three patients underwent right and left cardiac catheterization and their rest and exercise hemodynamic data were consistent with restrictive cardiomyopathy.

Effect of coronary vasodilation on ventricular fibrillation threshold: role of exogenous vasodilators and perfusion conditions.

Even without myocardial ischemia, coronary blood flow (CBF) constitutes a major determinant of ventricular fibrillation threshold (VFT). To clarify whether abnormal distribution of normal or increased CBF plays any additional role, 14 open-chest chloralose-anesthetized dogs with fixed-normalized heart rate, cardiac output, and systemic arterial pressure and separate servocontrolled left main coronary artery perfusion were studied as follows: VFT was determined first with coronary perfusion pressure (CPP) set at systemic level (80 mm Hg). Then CBF index was fixed at control levels (134.0 +/- 9.5 ml/min X 100 gm-1 LV) and coronary vasodilation was induced by intracoronary infusion of adenosine until CPP decreased to 49.0 +/- 2.0 mm Hg. Myocardial O2 consumption, LV pressure, LV dp/dt, and surface ECG remained unchanged. However, VFT decreased in all trials by about 45% (p less than 0.001). When CPP was reset to 80 mm Hg while maintaining vasodilation, CBF index increased by 90% to 255.4 +/- 15.4 ml/min X 100 gm-1 LV and VFT by 26% (p less than 0.005) from control. Yet these VFT increases in response to intraluminal pharmacologic vasodilation were about 19% (p less than 0.002) lower than expected for similar CBF index increases occurring physiologically. We conclude that intraluminal coronary vasodilation not matched by appropriate CBF increase results in substantial decrease of VFT. Moreover, at comparable increase of CBF, spontaneous physiologic vasodilation is more effective than intraluminal pharmacologic coronary vasodilation in increasing VFT.

Absence of clinical pulmonary edema despite elevated wedge pressures.

Pulmonary hemodynamic data were collected for 116 patients with a resting mean pulmonary artery wedge pressure of 25 mm Hg or greater who underwent exercise during cardiac catheterization without showing acute pulmonary edema. While the mechanism for the absence of evidence of pulmonary edema with pulmonary artery wedge pressure in excess of plasma oncotic pressure is unclear, presumably, it relates to compensatory changes in the structure and function of the pulmonary capillaries, alveolar wall, and lymphatic drainage capacity.

Dependence of ventricular fibrillation propensity on coronary blood flow without myocardial ischemia.

Ventricular fibrillation threshold (VFT) changes have been linked to coronary blood flow (CBF) in the context of CBF reduction and subsequent myocardial hypoxia. To clarify the effect of CBF on VFT in the absence of myocardial hypoxia, 18 open-chest pentobarbital-anesthetized dogs with uniformly controlled heart rate, cardiac output, and mean systemic arterial pressure (SAP) were studied as follows: CBF, coronary sinus O2 content (CcsO2), and thereby myocardial O2 consumption were continuously monitored. Baseline VFT determined by the single stimulus scanning technique was 33.0 +/- 3.9 mA. Initial values of CBF index (I) and VFT (n = 18) were positively correlated (VFTmA = 0.8 +/- 0.245 . CBFI ml/min . 100g-1LV; r = 0.60, p less than 0.01). Stepwise CBFI increments up to five times in excess of initial 131.5 +/- 9.7 ml/min . 100g-1LV were then induced by changing in random order. SAP (n = 10), left coronary perfusion pressure (n = 7), and arterial O2 content (n = 10) with VFT determined at each step; CcsO2 remained above 5.5 vol% while CBFI and VFT changes were positively correlated, and mean weighted slope of VFTmA = 16.6 +/- 0.103 . CBFI ml/min . 100 g-1Lv (r = 0.82, p less than 0.05). Systemic or coronary perfusion pressure and arterial or coronary sinus O2 content did not appear to affect VFT independently. It is concluded that even in the absence of myocardial hypoxia, CBF itself is a major determinant of VFT and thereby of innate arrhythmogenic propensity.

Effect of arterial pressure on left ventricular O2 consumption, coronary blood flow, and reserve capacity following coronary occlusion.

The effect of mean systemic arterial pressure (SAP) on myocardial O2 consumption (MVO2) coronary blood flow (CBF) and the reduction of left ventricular (LV) reserve capacity resulting from coronary artery occlusion was studied in 25 open-chest pentobarbital anesthetized dogs with fixed cardiac output and controlled heart rate (HR) and SAP. In all animals, baseline MVO2 and CBF were obtained and LV reserve capacity was determined by identifying the HR and SAP level which raised mean left atrial pressure to 12 mm. Hg. After uniform placement of a pericoronary snare, the dogs were randomized to five equal groups, and SAP was set at 40, 70 (two groups), 100, and 130 mm. Hg. MVO2 and CBF were redetermined and the coronary artery was ligated in all except one group (70 mm. Hg) which served as sham control. thirty minutes after coronary occlusion, MVO2, CBF, and LV reserve capacity were determined again. Percent of nonperfused myocardium did not differ among groups (27.6 +/- 1%). MVO2 bore a linear relationship to SAP setting wheras CBF bore a curvilinear relationship. Coronary occlusion did not modify these relationships. Significant, but similar decreases in tolerated HR (23.1 +/- 4.7 min.-1) and SAP (41.9 +/- 6.2 mm. Hg) from control values were observed in all four groups regardless of SAP setting. We concluded that the impact of coronary ligation on MVO2, CBF, the loss of functional reserve capacity, and possibly the extent of ischemic injury of the left ventricle, is not modified by afterload changes. However, optimal O2 supply-to-demand ratio appears at SAP of about 100 mm. Hg.

Hemodynamic and clinical comparison of the Hancock modified orifice and standard orifice bioprostheses in the aortic position.

Bioprosthetic aortic valve replacement in patients with a small aortic root has been associated with postoperative transvalvular gradients. A modified orifice Hancock xenograft bioprosthesis has been developed and is purported to increase significantly the effective orifice area (as evaluated by in vitro testing) compared to the standard orifice Hancock bioprosthesis. To assess the in vivo differences, we compared 481 patients with standard orifice prostheses with 156 patients with modified orifice prostheses. Postoperative catheterization was performed in 24 patients with modified orifice (valve diameters 19 to 25 mm) with 14 with standard orifice valves (valve diameters 21 to 25 mm). Actuarial rates of survival, valve failure, endocarditis, and thromboembolism did not differ significantly between the two subgroups. Peak aortic valve gradients on the whole were less in the modified orifice subgroup than in the standard origice subgroup (12 +/- 1 torr versus 20 +/- 6 torr [mean +/- SEM]), but the difference was not statistically significant (p greather than 0.05). The calculated in vivo aortic valve areas were slightly, but insignificantly, greater in the modified orifice subgroup than in the standard orifice subgroup (p greater than 0.05). These in vivo data partially corroborate the in vitro findings of increased effective orifice area and internal-to-external diameter ratio for the modified orifice bioprosthesis. The hemodynamic differences between the two valve types are small, however, and the putative clinical advantages inherent in the use of the modified orifice bioprosthesis remain to be completely defined.

Rest and exercise hemodynamic studies in patients with isolated aortic stenosis.

Hemodynamic data obtained during rest and exercise in 22 patients with aortic stenosis were analyzed. Mean aortic valve gradient for the group did not change significantly during exercise but there was large individual variability. Aortic valve flow increased during exercise in all but 2 patients. There was no correlation between change in gradient and change in flow during exercise. Although the mean calculated aortic valve area for the group did not change significantly during exercise, the calculated area was larger during exercise in most patients. Change in the calculated valve area correlated best with changes in aortic valve flow, left ventricular stroke work index, and the product of left ventricular systolic pressure and stroke volume. This suggests that in some patients there may be a dynamic component to aortic valve obstruction that may vary with changing hemodynamics.

Comparative effect of counterpulsation and bypass on left ventricular myocardial oxygen consumption and dynamics before and after coronary occlusion.

In this preparation counterpulsation effect was found equivalent to 42 +/- 7% of complete left ventricular bypass before, and 46 +/- 9% post-coronary occlusion. We conclude that counterpulsation is effective mainly by reducing a major determinant of myocardial oxygen consumption, i.e., afterload, whereas left ventricular bypass by reducing primarily preload results in secondary afterload reduction when peripheral resistance is unchanged. At the higher left ventricular bypass levels, reduction of myocardial oxygen consumption is far greater than during balloon counterpulsation. Acute functional loss of myocardium does not alter the effect of these assist methods regarding the reduction of myocardial oxygen consumption. Whether selection of either method for clinical application should be made only on the basis of its capability for reduction of myocardial oxygen consumption remains to be justified by conclusive demonstration of beneficial effect of reduction of myocardial oxygen consumption in the specific circulatory disorders.

Intermittent severe mitral regurgitation.

The findings in two patients with hemodynamic evidence of intermittent severe mitral regurgitation with cyclic variation in right and left ventricular pressures are presented. Both patients had aortic and mitral valvular regurgitation of unknown etiology without definite evidence of papillary muscle dysfunction. The basis for the variation in the degree of mitral regurgitation is unclear.

Effect of activation sequence on MVO2 before and after coronary ligation.

In pentobarbital-anesthetized, open-chest dogs with fixed heart rate, cardiac output, and systemic arterial pressure, ectopic ventricular activation originating from apical as compared to basilar regions of either ventricle was associated with small (3--5%) but significantly (P less than 0.005) lower myocardial O2 consumption (MVO2) and thus higher left ventricular (LV) efficiency without change in LV end-diastolic pressure (LVEDP), work index (LVWI), and LV dP/dt. Data obtained during epicardial and corresponding endocardial activation did not differ. During normal ventricular activation, MVO2 remained unchanged but LVEDP was significantly (P less than 0.005) lower, thus yielding higher LVWI and efficiency. MVO2 differences among ectopic sites were abolished after coronary artery occlusion, whereas data obtained during endocardial and epicardial on normal and ectopic activation were not affected. Thus, normal activation resulting in lower LVEDP is most efficient; apical ventricular activation is less efficient at the same MVO2P basilar is the least efficient, because both MVO2 and LVEDP are higher. Ventricular activation sequence changes do not constitute a substantial determinant of MVO2.

A comparison of hemodynamic and angiographic indices of left ventricular performance in patients with coronary artery disease.

We compared ejection fraction, left ventricular end-diastolic pressure, cardiac index and the relation of left ventricular stroke work index to left ventricular end-diastolic pressure during rest and exercise in 60 patients with coronary artery disease. Left ventricular end-diastolic pressure was usually normal at rest (48/60) and abnormal during exercise (46/60) and did not correlate with ejection fraction. Cardiac index was insensitive, usually remaining normal until ejection fraction was less than 0.40. Patients with a normal left ventricular stroke work index response to exercise had higher ejection fractions than those with an abnormal response (p is less than 0.05). However, 9 patients with normal ejection fractions had an abnormal exercise response. This may reflect loss of left ventricular reserve, abnormal compliance or clinically silent ischemia during exercise. Different indices of left ventricular performance may be widely disparate in coronary artery disease, and abnormalities are frequently apparent only during exercise.