Left Ventricular Peak Systolic Pressure Research Articles

Peak left ventricular pressure during percutaneous aortic balloon valvuloplasty: Clinical and echocardiographic correlations

Peak left ventricular pressure during balloon inflation was measured in 20 patients who underwent balloon valvuloplasty for severe aortic stenosis to define the determinants of ventricular pressure development in response to increased loading conditions. The peak left ventricular pressure ranged from 150 ± 5 to 386 ± 22 mm Hg (mean ± Sl), was reproducible in each patient with each balloon inflation (mean coefficient of variation 7.8%) and correlated with concurrent echocardiographic measurements of ejection fraction (r = 0.89, p = 0.0001) and mass/volume ratio in systole (r = 0.91, p = 0.0001) or diastole (r = 0.88, p = 0.0001). Thirteen patients with class II or more severe congestive heart failure had lower values for peak left ventricular pressure than did those without failure (225 ± 46 versus 305 ± 45 mm Hg, p = 0.002), whereas no difference in rest left ventricular systolic pressure was seen between the two groups. The measurement of peak left ventricular pressure was inversely related to rest mean circumferential end-systolic wall stress (r = 0.52, p = 0.046).Thus, peak left ventricular systolic pressure measured during aortic valvuloplasty in humans correlates closely with traditional measures of left ventricular function. This measurement, which previously has been obtained only in experimental animal studies, is a simple and reproducible hemodynamic index that may provide new insights in studies of ventricular function and congestive heart failure in aortic stenosis.

Reflex inhibition of plasma renin activity by increased left ventricular pressure in conscious dogs.

The purpose of the present study was to determine the effects of left ventricular (LV) outflow obstruction on plasma renin activity (PRA) and the contribution from afferent receptors located in the LV myocardium. In chronically instrumented, conscious dogs (n = 12), changes in PRA during a 15- to 20-mmHg decrease in arterial blood pressure were assessed during 1) intravenous infusions of nitroprusside (NP) alone and 2) infusions of NP while peak systolic LV pressure was elevated by acute ascending aortic occlusion (AAO + NP). Infusions of NP alone elicited significant increases in heart rate (24.9 +/- 5.1 beats/min; P less than 0.01) and in PRA [3.31 +/- 0.53 ng angiotensin I (ANG I).ml-1.h-1; P less than 0.01]. These were accompanied by decreases in both LV pressure (-13.8 +/- 3.6 mmHg; P less than 0.05) and left atrial pressure (-3.0 +/- 0.7 mmHg; P less than 0.05). During AAO + NP, LV pressure was elevated to an absolute level of 169.2 +/- 4.6 mmHg (+53.3 +/- 4.2 mmHg; P less than 0.001), whereas left atrial pressure was not changed. Both the hypotension-induced rise in PRA and tachycardia were significantly inhibited during AAO + NP (+0.59 +/- 0.29 ng ANG I.ml-1.h-1 and +6.3 +/- 4.6 beats/min, respectively; NS). The topical application of a local anesthetic in the region of the main coronary artery, sufficient to block the heart rate and arterial blood pressure responses to selective LV receptor stimulation by intracoronary veratridine (0.1-0.4 microgram/kg), resulted in significant increases in PRA and heart rate during AAO + NP.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in right ventricular relaxation during acute anterior myocardial infarction in pigs.

To determine the effect of an anteroseptal myocardial infarction on right ventricular systolic and diastolic function, we studied 12 pigs before and 1 h after left anterior descending coronary artery occlusion. Total arterial occlusion was achieved by the percutaneous, transcatheter placement of a 1 mm Teflon plug into the mid portion of the artery. The resulting infarction involved 28 (SEM 3)% of the left ventricular wall, in the anterior and septal regions. A small rim of the right ventricular free wall adjacent to the septum and the right ventricular apex were also affected. End diastolic pressures in both ventricles rose significantly: left ventricular from 12(1) to 20(2) mm Hg and right ventricular from 8(1) to 10(1) mm Hg. Right ventricular peak systolic pressure increased from 29(2) to 35(2) mm Hg while left ventricular peak systolic pressure did not change. One hour after infarction the half time of isovolumic relaxation of the right ventricle was prolonged from 6.9(0.5) to 8.7(0.4) ms. Ejection fraction in both ventricles was depressed: from 46(1) to 34(2)% in the right ventricle and from 69(3) to 49(3) in the left ventricle. There was no change in either right or left ventricular dP/dt. These data suggest that right ventricular systolic and diastolic dysfunction occurs as the result of an anteroseptal myocardial infarction in pigs.

The effect of left ventricular wall motion during isovolumetric relaxation period in coronary artery disease.

The effect of the left ventricular (LV) regional wall motion during isovolumetric relaxation period (IRP) were studied in 9 patients with old anteroseptal myocardial infarction (OMI) and 8 normal subjects (NOR). There were no significant differences in heart rate, peak LV systolic pressure and peak (+) dP/dt between the groups. LV cavity was divided into the anterior and inferior sides by a long axis, which was equally divided with 3 perpendicular lines, creating 4 areas in each side. The sums of the 2 middle areas in each side were defined as Aa and Ab, respectively. During IRP the pattern of (-) dP/dt at the upstroke phase was convex-downward in OMI, but convex-upward in NOR. Time constant (T) was significantly prolonged in OMI compared with NOR (50 +/- 9 vs 37 +/- 6 msec; p less than 0.01). On NOR, Aa increased significantly after 33.4 msec from peak (-) dP/dt, while Ab remained unchanged. In OMI, Ab increased after 50.1 msec from peak (-) dP/dt, associated with decrease in Aa, suggesting the passive shortening of the anterior wall by the active expansion of the inferior. Such asynchronous LV wall motions during IRP might impair LV relaxation and influence the upstroke pattern of (-) dP/dt.

Left ventricular function and haemodynamics in ponies during exercise and recovery.

Myocardial and haemodynamic responses to strenuous treadmill exercise were monitored with chronically implanted instrumentation in seven physically untrained ponies. In two other ponies, haemodynamics were monitored using a conventional catheter technique. During exercise (mean +/- sem heart rate = 203 +/- 3 beats/min), left ventricular peak systolic ahd end-diastolic blood pressure significantly increased from 125 +/- 2 to 208 +/- 6 mmHg and from 29 +/- 1 to 58 +/- 3 mmHg, respectively (P less than 0.05). Peak positive first derivative of left ventricular pressure (dP/dt) was also increased significantly, (1397 +/- 144 to 6016 +/- 325 mmHg/sec), as were myocardial segment velocity of shortening during systole (dL/dtsys) and stroke work (193 and 109 per cent, respectively). Paradoxically, segment systolic shortening was reduced significantly (P less than 0.05) with respect to resting control values for 10 mins after cessation of exercise, with the maximal reduction of 22 per cent occurring at 2 mins post exercise. In addition, left ventricular segment stroke work decreased significantly to 67 per cent of resting control value at 2 mins post exercise. This study demonstrates that analysis of regional myocardial performance in conjunction with haemodynamic data permits a detailed description of cardiac events during and immediately following exercise, facilitating definition of changes which are not readily reflected by haemodynamics. Based on these findings, the authors conclude that untrained ponies may readily complete short bouts of near-maximal exercise, yet experience significantly diminished left ventricular function in the immediate post exercise period.

Ventricular premature contraction after repair of tetralogy of fallot. The influence of postoperative factors, particularly the right ventricular regional wall motion.

The presence and severity of ventricular premature contraction (VPC) in 35 patients with tetralogy of Fallot (TF) were studied, 5 to 10 years after intracardiac repair (ICR), using treadmill exercise testing and 24-hour ambulatory monitoring. VPCs were observed in 24 patients (68.6%). The patients were classified into two groups according to the types of VPCs: group A (23 patients) without VPCs or with VPCs of Lown's grade 1 and group B (12 patients) with VPCs of Lown's grade 2, 3 or 4. Group B patients were found to have significantly higher right to left ventricular peak-systolic pressure ratios and higher right ventricular peak systolic pressures than those of group A. But there were no significant differences between the two groups in operative age, the time lapse between ICR and evaluation, the duration of exercise and so on. Group B patients also showed significantly decreased right ventricular regional wall motions in the right ventricular outflow tracts (ROTs), indicating akinetic or paradoxical movements than group A patients. It is thought that postoperative right ventricular hypertension and the akinetic or paradoxical wall movement of the ROT may have some effect on the genesis of postoperative VPCs after repair of TF.

Effects of graded intensity of oxygen deficiency on function and energy metabolism in post-ischaemic myocardium.

The effect of graded ischaemic injury on post-ischaemic myocardium was examined in rat hearts after three 4 min periods of asphyxia. Systolic function under steady state conditions and during isovolumic beats, the content of high energy phosphates and glycogen, and myocardial material properties were determined. Severity of the oxygen deficiency was varied by manipulating myocardial oxygen demand (MVO2) either by rapid atrial pacing or by vagal stimulation. After 20 min of post-asphyxial recovery, steady state haemodynamics were almost normal. In the high MVO2 group (atrial pacing) the dp/dtmax was reduced to 90%(NS). The isovolumic indices of function were decreased in all post-asphyxial groups. This was most pronounced in the high MVO2 group, with a reduction in peak left ventricular systolic pressure to 85.7 (SEM 3.4)% and a decrease in peak left ventricular systolic stress to 82.3(3.9)% (p less than 0.01). The post-asphyxial myocardial performance recovered better in the low MVO2 group (vagal stimulation). Material properties were altered only in the high MVO2 group. The decreased content of ATP and glycogen were comparable in all post-asphyxial groups. A phosphocreatine overshoot phenomenon was most marked in the high MVO2 group: 11.4(2.8) mumol.g-1 v 4.7(0.9) mumol.g-1 (control), p less than 0.01. The results indicate that post-ischaemic contractile dysfunction of reversibly injured is not closely related to the previous O2 deficit or to the functional impairment. We also obtained no correlation between ATP content and material properties in modestly injured post-ischaemic myocardium.

Cardiac function and coronary flow in chronic endotoxemic pigs.

We have reported that myocardial inotropism was depressed in acute and chronic endotoxemia. One possible mechanism for this observation is that endotoxemia reduces myocardial perfusion and indeed, we observed reduced myocardial perfusion in acute endotoxemia. This study tested the hypothesis that reduced inotropism of chronic endotoxemia was accompanied by reduced coronary artery blood flow. Fifteen pigs were equipped with left atrial and ventricular catheters, circumflex coronary and pulmonary artery flow meters, left ventricular pressure transducer, and ultrasonic crystals in the anterior-posterior axis to measure internal short axis diameter by sonomicrometry. The pigs recuperated for 3 days before basal data were collected over the next 3-5 days. After at least 7 postoperative days, an osmotic pump containing Salmonella enteriditis endotoxin was implanted in 12 pigs. Endotoxin was delivered at 10 micrograms/hr/kg for 2 days, at which time the animals were sacrificed. Osmotic pumps containing sterile saline were implanted in 3 pigs. Eight of the 12 endotoxemic pigs survived; 4 died before the morning of the second day. The survivors exhibited elevated heart rate, peak left ventricular systolic pressure, and cardiac output. Inotropism was evaluated by calculating the slope of the end-systolic pressure-diameter relationship (ESPDR) and % diameter-shortening. ESPDR was significantly depressed on the second endotoxemic day, while % diameter-shortening was depressed on both endotoxemic days. Coronary artery blood flow was significantly elevated on both endotoxemic days, while cross-sectional stroke work was unchanged. Therefore, the ratio of coronary blood flow to stroke work increased on both endotoxemic days. Nonsurvivors exhibited reduced heart rate, cardiac output, peak left ventricular systolic pressure, ESPDR, and % diameter-shortening. Neither coronary artery blood flow nor flow-to-work ratios increased in this group. Sham endotoxemic pigs demonstrated no cardiac or hemodynamic changes over 3 days. These results indicate that depressed inotropism during chronic endotoxemia was not caused by reduced coronary blood flow; rather, the myocardium was relatively overperfused.

Doppler evidence that true left ventricular-to-aortic pressure gradients exist in hypertrophic cardiomyopathy

The etiology of systolic left ventricular-to-aortic pressure gradients in hypertrophic cardiomyopathy is still controversial. While cavity obliteration has been proposed by some investigators as the cause for recording of a high left ventricular systolic pressure, the concept of left ventricular outflow tract obstruction has received more experimental support. To investigate further whether left ventricular pressure truly exceeds aortic pressure and implies obstruction, we studied, with imaging and Doppler echocardiographic techniques, five patients with asymmetric septal hypertrophy and systolic anterior movement of the mitral valve occasionally causing it to abut upon the septum. All had outflow tract pressure gradients (peak 85 ± 10 mm Hg) and trace to mild mitral regurgitation. Continuous wave Doppler study recorded peak flow velocities in the outflow tract (4.6 ± 0.3 m/sec), and mitral regurgitant (mean 6.6 ± 0.3 m/sec) jets. Aortic systolic and diastolic blood pressures were measured by cuff sphygmomanometry, and simultaneous carotid pulse tracings were recorded. The magnitude of systolic aortic pressure was determined at the time of peak velocity in the mitral regurgitant jet. Since the poak systolic pressure gradient across the mitral valve (left ventricular minus left atrial pressure) should equal 4 times the square of the peak velocity (V) in the mitral regurgitant jet, peak left ventricular systolic pressure should equal 4 × V 2 plus the height of left atrial pressure at the time of peak mitral regurgitant velocity. In each case, calculations were made assuming an upper normal left atrial pressure of 10 mm Hg. If actual obstruction were present, that estimate of peak systolic left ventricular pressure should equal the sum of the aortic systolic pressure and the outflow tract pressure gradient, both measured at the time of peak mitral flow velocity. By paired t tests, estimated values for left ventricular systolic pressures by both techniques were equivalent (both 187 ± 18 mm Hg). During the recording of a left ventricular-to-aortic gradient, the basal ventricular cavity was not obliterated on two-dimensional imaging, and ventricular shortening continued. Ventricular systolic dimension at the time of peak mitral regurgitant and outflow tract velocities (2.9 ± 0.4 cm) was greater in each patient than minimal systolic dimension (2.3 ± 0.4 cm, p = 0.01). The combination of marked elevation of the systolic pressure gradient across the mitral valve, relative to simultaneous aortic systolic pressure, and continued ventricular shortening indicates that true outflow obstruction can elevate left ventricular systolic pressure in hypertrophic cardiomyopathy.

Left ventricular distensibility and passive elastic stiffness in atrial septal defect

Diminished left ventricular distensibility has been postulated as a cause of left ventricular failure in atrial septal defect. To evaluate this hypothesis the indexes of left ventricular compliance and stiffness were estimated in 15 patients with atrial septal defect and the results compared with those in 10 normal subjects. Age, peak left ventricular systolic pressure, end-diastolic pressure, ejection fraction and cardiac index did not differ significantly between groups. Left ventricular end-diastolic volume for the atrial septal defect group was significantly less than that for the control group (mean ± SD, 61 ± 9 ml/m2versus 73 ± 13, p < 0.05) in keeping with previous studies. The slope of the log pressure-volume relation was significantly greater in the group with atrial septal defect than in the normal group (0.056 ± 0.010 versus 0.044 ± 0.008, p < 0.01), consistent with increased chamber stiffness.For a group of six patients with atrial septal defect and elevated left ventricular end-diastolic pressure, normalized compliance was significantly less than that in the control group (0.017 ± 0.001 versus 0.036 ± 0.007, p < 0.02). The slope k of the elastic stiffness-stress relation for the total group with atrial septal defect was significantly greater than that of the normal group (21.0 ± 2.3 versus 18.1 ± 2.3, p < 0.01). An index of muscle fiber stretch (dV/VdP × end-diastolic stress × 100) was significantly less in the atrial septal defect group than in the control group (74 ± 24 versus 106 ± 22, p < 0.01).Thus, left ventricular compliance and muscle stiffness may be adversely affected in atrial septal defect. Abnormal distensibility may exist in the presence of elevated left ventricular diastolic pressure and may have a rote in the genesis of left ventricular failure in this setting.

Regional myocardial volume alterations induced by brief repeated coronary occlusion in conscious dogs

The purpose of this study was to evaluate whether brief repeated coronary occlusions induce changes in regional myocardial geometry at rest. Five conscious dogs were instrumented for the measurement of subendocardial segment length and transmural wall thickness in the ischemic area, subendocardial segment length in the normally perfused area, coronary flow and left ventricular pressure. After recovery from surgery, 180 (mean) 2 min coronary occlusions were given over a period of 20 days. The heart rate at rest, left ventricular peak systolic and end-diastolic pressures and peak positive first derivative of left ventricular pressure (dP/dt) remained unchanged throughout the experiment.In the normal area, the end-diastolic segment length at rest did not change significantly. By contrast, in the ischemic area, at 14 days after the initiation of repeated coronary occlusion, the end-diastolic regional crosssectional area (product of segment length and wall thickness) at rest had increased by 9.7% (p < 0.05); thereafter it decreased to 6.5% (p < 0.05) above the value at rest before repeated occlusion despite an additional 6 days of coronary occlusions. At 10 days after the Interruption of repeated occlusion, this value had regressed to 4.3% (p = NS) above control. These findings suggest the occurrence of regional myocardial hypertrophy confined to the ischemic area in response to the periodic ischemic stimulus.

Effects of supine and lateral positions on cardiac output and intracardiac pressures

In the hospitalized patient and during cardiac catheterization, cardiac output and intracardiac pressures are almost always measured with the subject in the supine position. There are limited and sometimes conflicting data on the effects of the left and right lateral positions on these variables. In nonpregnant human beings, some studies have shown the cardiac output to be higher in the supine than in the right or left lateral positions.1,2 Others3 have reported that cardiac output is higher in the left lateral than in the supine or right lateral positions, whereas others have demonstrated no difference in output among these various positions.4 Recent studies in animals have shown that cardiac output is higher in the left and right lateral positions than when the animals are supine.5There are no published studies in man reporting the effects of the supine and lateral positions on micromanometer-measured intracardiac pressures. In experimental animals, Nakao et al5 used micromanometer-tipped catheters and demonstrated that left and right ventricular peak systolic and end-diastolic pressures are higher in the left and right lateral positions than in the supine. No previously published study has examined left and right ventricular pressures in these various positions in man. Therefore, the present study was performed to assess the influence of the 90 ° left and right lateral positions on cardiac output and intracardiac pressures (measured with micromanometer-tipped catheters) in patients referred for elective cardiac catheterization.

Beneficial effects of verapamil in diabetic cardiomyopathy.

It has been suggested that the occurrence of an intracellular Ca2+ overload may result in the development of diabetic cardiomyopathy, which is associated with depletion of high-energy phosphate stores and a derangement of ultrastructure and cardiac dysfunction. Accordingly, the effects of verapamil, a Ca2+ antagonist, on cardiac function, ultrastructure, and high-energy phosphate stores in the myocardium were evaluated in rats made diabetic by an intravenous injection of streptozocin (65 mg/kg). Four weeks after the induction of diabetes, the animals were treated with three doses (2, 4, or 8 mg.kg-1.day-1) of verapamil for 4 wk until they were used for the measurement of different parameters. Untreated diabetic animals had slower heart rates, depressed rate of contraction and rate of relaxation, lower peak left ventricular systolic pressure, and elevated left ventricular diastolic pressure. All of these changes were significantly improved in diabetic rats receiving verapamil treatment. The beneficial effects of verapamil were more evident with higher doses (8 mg.kg-1.day-1) than with the lower doses (2 mg.kg-1.day-1). The diabetic animals also showed alterations in myocardial high-energy phosphate stores and exhibited evidence of ultrastructural damage; these abnormalities were improved by verapamil treatment without affecting their hyperglycemic status. Our results demonstrate that verapamil is capable of preventing diabetes-induced myocardial changes and support the involvement of Ca2+ in the cardiac pathology during diabetes.

Myocardial dysfunction and coronary vasoconstriction induced by platelet-activating factor in the post-infarcted rabbit isolated heart

Myocardial injury was produced in separated groups of anesthetized rabbits by occlusion of the left circumflex coronary artery for 1 h followed by reperfusion for 2, 4, or 6 h after release of the occlusive ligature. The ischemically-injured and reperfused hearts subsequently were isolated and perfused using a modified Langendorff apparatus. Platelet-activating factor in the form of AGEPC (1-0-hexadecyl-2-acetyl-sn-glyceryl-phosphorylcholine), 40 nmol in 1 ml, was infused above the coronary ostia over 15 s. Thromboxane B2 (TxB2- and peptidoleukotrienes (LT) were measured in the lymphatic effluent from the heart. Noninfarcted hearts (isolated hearts and sham-operated animals) served as procedural controls and lyso-GEPC (1-0-hexa-decyl-2-0-lyso-sn-glyceryl-phosphorylcholine), 40 nmol in 1 ml, served as the agonist control. After the infusion of AGEPC in the infarcted hearts, coronary perfusion pressure and left ventricular end-diastolic pressure increased while left ventricular peak systolic pressure decreased. The observed changes coincided with TxB2 peak release at 1 min and LT peak release at 2 min. The longer post-ischemic reperfusion time was associated with increasingly greater changes in these parameters. In hearts isolated after 6 h of reperfusion, the functional changes and the appearance of TxB2 and LT in response to the administration of AGEPC reached a significant level (ANOVA) with respect to those base-line values and the values obtained with hearts from sham-operated animals. Minimal changes occurred in noninfarcted hearts or with the administration of the biologically inactive phospholipid, lyso-GEPC. Histologic evaluation of cardiac tissue showed a progressive time-dependent migratory increase of leukocytes from the intra- and perivascular areas toward the region of infarcted myocardium. Platelet aggregates were seen in the intravascular spaces. The data are consistent with the suggestion that the infiltrating leukocytes and platelets may serve as a source for the synthesis and release of TxB2 and LT in acutely infarcted hearts upon exposure to AGEPC. If it is possible for AGEPC to be synthesized and released from vascular endothelial or inflammatory cells leading to the formation of thromboxane A2 and LT from reperfused myocardium, then these substances may participate in increasing coronary artery resistance and in the development of myocardial dysfunction during the evolution of an acute myocardial infarction and especially during the phase of perfusion.

Effects of moderate hypertension on cardiac function and metabolism in the rabbit.

To study the early effects of hypertension on the heart, we examined isolated hearts from rabbits with slowly developing hypertension of up to 64 weeks in duration after unilateral nephrectomy and renal artery stenosis. Normotensive animals kept under identical conditions served as controls. Mean arterial blood pressure rose from 83 to 155 mm Hg in the hypertensive group of longest duration, but the ratio of left ventricular weight to body weight was not different between the experimental and control groups. Although left ventricular hypertrophy was not present, left ventricular peak systolic pressure of perfused hearts was significantly higher in hypertensive than in normotensive hearts. Furthermore, while in hypertensive hearts the left ventricular end-diastolic volume was increased, the peak systolic pressure did not respond to an increase in left ventricular end-diastolic volume. Functional changes were accompanied by metabolic changes in the left ventricle. Rates of glucose utilization were increased and rates of ketone body utilization were decreased in hypertensive hearts. Activities of key enzymes of carbohydrate metabolism (phosphorylase, hexokinase, phosphofructokinase, and lactate dehydrogenase) were increased, while those of ketone body metabolism (3-oxoacid-CoA transferase, acetoacetyl-CoA synthase) were decreased and those of the citric acid cycle (citrate synthase, 2-oxoglutarate dehydrogenase) were not different between groups. In summary, moderate hypertension for a period of more than 1 year resulted in functional and metabolic changes of the left ventricle in hypertensive animals that were already manifest at 8 weeks of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of hypothermic ischemia on recovery of left ventricular function and preload reserve in the neonatal heart

Neonatal and adult myocardium respond differently to ischemia. In addition, the neonatal heart possesses a limited preload reserve. The effect of uninterrupted hypothermic ischemia on recovery of left ventricular function and preload reserve was studied in two groups of isolated rabbit hearts: group 1 (neonates, n = 8), 7 to 10 days old; group 2 (adults, n = 15), 6 to 12 months old. Peak left ventricular systolic pressure, the first derivative of left ventricular systolic pressure, and heart rate were measured at left ventricular pressures of 0, 5, 10, and 15 mm Hg before and after 120 minutes of global ischemia at 27 degrees C. Before ischemia, left ventricular systolic pressure increased significantly at each increment of left ventricular end-diastolic pressure for both groups of hearts. After hypothermic ischemia, recovery of left ventricular systolic pressure was significantly reduced at each level of left ventricular end-diastolic pressure among neonatal hearts (range 75% to 79% of control values). The postischemic recovery of left ventricular systolic pressure in the adult hearts was markedly reduced from baseline values (range 43% to 53% of control values) and was significantly worse than that of neonatal hearts at each level of left ventricular end-diastolic pressure (p less than 0.001). Both groups were able to respond to increasing preload after ischemia. The slope of the curve describing the relationship between left ventricular end-diastolic pressure and percent recovery of left ventricular systolic pressure was not different from zero for neonatal hearts but was significantly greater than zero among the adults (0.22 +/- 0.21 versus 0.73 +/- 0.07, p = 0.0056). After ischemia, the first derivative of left ventricular systolic pressure fell significantly from control values among neonatal hearts (71% of control values). The reduction was considerably greater, however, among the adult hearts (54% of control values). These data indicate that the neonatal heart recovers systolic function better than the adult heart after global ischemia with moderate hypothermia.

Predictors of Operative Mortality in Critical Valvular Aortic Stenosis Presenting in Infancy

Congenital aortic stenosis presenting within the first 6 months of life is a highly lethal anomaly. Although aortic valvotomy has offered excellent palliation in many instances, the operative risk remains substantial. To better understand the factors associated with a poor operative result, the records of all patients less than 6 months of age undergoing aortic valvotomy at our institution from 1972 through 1986 were analyzed. Nineteen patients (58%) (Group I) survived operation; 14 (42%) (Group II) died. The following variables were analyzed in an attempt to define those with prognostic significance: mean pulmonary artery pressure (PAP), left ventricular (LV) peak systolic pressure, LV end-diastolic pressure, peak systolic aortic valve gradient, LV end-diastolic volume (LVEDV), LV ejection fraction, and age at operation. The only variables that were significantly different in the two groups were mean PA (Group I, 29 ± 3 mm Hg, and Group II, 54 ± 3 mm Hg; p < 0.001) and LVEDV (Group I, 50 ± 8 ml/m 2, and Group II, 20 ± 4 ml/m 2; p < 0.05). No patient with an LVEDV of 20 ml/m 2 or less survived operation. We conclude that small LV dimension and elevation of PAP may be predictive of a poor surgical result in patients with severe aortic stenosis presenting in infancy.

Impaired relaxation of the hypertrophied left ventricle in aortic stenosis: effects of aortic valvuloplasty and of postextrasystolic potentiation

Impaired left ventricular (LV) filling in aortic stenosis (AS) is explained by slow LV pressure decay, which impedes LV inflow. This slow LV pressure decay could be explained by the altered myocardial wall stress pattern of AS or by a failure of inactivation of hypertrophied myocardium. To evaluate whether altered LV loading or impaired myocardial inactivation is the predominant control of LV relaxation and filling in AS, we studied the effects of aortic valvuloplasty (PTAV) and of postextrasystolic potentiation (PESP). LV micromanometer tip pressure recordings and simultaneous LV angiograms were obtained before and after PTAV in 10 patients with AS. PTAV reduced peak-to-peak aortic valve gradient from 101 +/- 7 to 40 +/- 5 mmHg (P less than 0.01), peak LV systolic pressure from 211 +/- 8 to 169 +/- 4 mmHg (P less than 0.01) and LV end-diastolic pressure from 22 +/- 3 to 13 +/- 2 mmHg (P less than 0.01). Despite these large drops of LV loading after PTAV, the time constant, T, of LV pressure decay decreased only slightly from 47 +/- 4 to 44 +/- 4 ms (P less than 0.05) and the LV peak filling rate remained unaltered. The influence of PESP on LV relaxation and filling was investigated in patients with AS using LV micromanometer tip pressures (n = 22) and simultaneous mitral valve Doppler echocardiograms (n = 9). After PESP the time constant, T, of isovolumic LV pressure decay increased from 43 +/- 4 to 54 +/- 4 ms (P less than 0.01).2+ 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of the Novel Calcium Channel Blocker, McN-5691, on Cardiocirculatory Dynamics and Cardiac Output Distribution in Conscious Spontaneously Hypertensive Rat

The purpose of this study was to characterize the cardiocirculatory effects of McN-5691 in the conscious spontaneously hypertensive rat (SHR) and in age matched Wistar-Kyoto (WKY) control rats. Animals were instrumented under halothane anesthesia for right atrial, left ventricular arterial, and venous pressure recordings. The radioactive microsphere technique was used to estimate regional blood flow and cardiac output before (control) and during intravenous (i.v.) infusion of either McN-5691 at three dosage levels (0.3, 1.0, 3.0 mg/kg), or vehicle (VH) at an infusion rate of 0.0408 ml/min. The predominant hemodynamic effect of McN-5691 (cumulative dose = 0.3-4.3 mg/kg i.v.) in conscious SHR was dose-related reduction in mean arterial pressure with normalization occurring at a cumulative dose of 1.3 mg/kg i.v. The antihypertensive effect of McN-5691 was accompanied by reductions in left ventricular peak systolic pressure (cumulative dose = 1.0-4.3 mg/kg i.v.), arterial pressure-rate product (1.3-4.3 mg/kg i.v.), and systemic vascular resistance (4.3 mg/kg i.v.). McN-5691 had no statistically significant effect on heart rate or cardiac contractility as measured by dP/dt/peak left ventricular pressure. The predominant peripheral vascular effects of McN-5691 were increases in skeletal muscle blood flow (4.3 mg/kg i.v.) and reductions in skeletal muscle (1.3-4.3 mg/kg i.v.), renal (1.3-4.3 mg/kg i.v.), gastrointestinal (4.3 mg/kg i.v.), and coronary (1.3-4.3 mg/kg i.v.) vascular resistances. Despite the fall in renal vascular resistance, renal blood flow was not changed by McN-5691. McN-5691 did not have major effects on other regions of the peripheral circulation. Thus, McN-5691 is an antihypertensive agent as defined by its ability to normalize blood pressure in the SHR, and the hemodynamic mechanism leading to this effect is reduction in peripheral vascular resistance. This antihypertensive effect is not accompanied by reflex tachycardia and is not associated with negative inotropic activity or detrimental peripheral circulatory changes in the conscious SHR.

Intrinsic left ventricular contractility in normal subjects

The influence of autonomictone on left ventricular (LV) contractility, along with the range of normal values and the effects of exercise on contractile state, were studied in 12 normal volunteers. Serial reproducibility was examined in a subgroup of 6. LV contractility was estimated by the LV peak-systolic pressure to end-systolic volume relation (pressure-volume relation), and the ratio of peak-systolic pressure to end-systolic volume (pressure/volume ratio). The cuff blood pressure and radionuclide ventriculogram were recorded at rest, during exercise and during pharmacologic pressure-afterloading with phenylephrine, before and after vagal and β-adrenergic “blockade.” Both the pressure/volume ratio and ejection fraction increased during the stimulus of exercise (both p ≤ 0.008). After blockade, the pressure-volume relations were highly linear (r = 0.95 ± 0.05 [standard deviation], n = 12), and there was no systematic difference in their slopes induced by blockade. The serial studies of pressure-volume relations showed no significant differences. The results demonstrated that vagal and sympathetic tone were not important in the support of LV contractility in normal subjects at rest, and that the pressure-volume relation and pressure/volume ratio are reproducible between studies. Also, the findings confirmed that both the pressure/volume ratio and the ejection fraction were sensitive to exercise-induced changes in contractility. This demonstration of intrinsic LV contractility in normal subjects, plus the reproducibility of the measurements, supports the feasibility of serial study of LV contractility.