Mean Left Ventricular Systolic Pressure Research Articles

Non-invasive estimation of left ventricular systolic peak-pressure: a prerequisite to calculate of myocardial work in hypertrophic obstructive cardiomyopathy

Abstract Introduction Myocardial work (MW) is an echocardiographic parameter to estimate global and regional myocardial performance. This method utilizes pressure strain loops derived from global longitudinal strain (GLS) and left ventricular systolic pressure (LVSP) estimated by brachial blood pressure (BP). Purpose Since LVSP cannot be equated with BP in pts with HOCM, we investigated whether the LVSP can be calculated non-invasively by combining Doppler echo parameters and the BP. This estimation is mandatory to make MW applicable for HOCM-pts. Methods We studied 20 consecutive pts (8 women, 12 men; mean age 57.0±13.9 years; NYHA class 2.1±0.8) with indication for first alcohol septal ablation. 6 pts had hypertension and 2 pts unexplained syncope. 18 (90%) pts were in sinus rhythm. NTproBNP was 1431 pg/ml (1912 IQR). Echo baseline measurements showed subaortic septal (IVS) thickness of 21.0±5.0 mm and maximal IVS thickness of 24.7±6.3 mm. Pts showed high-normal left ventricular ejection fraction (70.4±10.1%). Left atrial (LA) volume was 101.2±26 ml. All measurements of pressures and gradients were performed in the catheterization laboratory after placement of a 5F Judkins JR4 in the ascending aorta and a 5.2F special pigtail catheter in the apex of LV beyond the obstruction. Simultaneous measurements of BP at left upper arm, echo intraventricular gradients (instantaneous and mean) with CW Doppler (GE Vivid E70), and invasive pressures and gradients (peak-to-peak and mean) of the LV and ascending aorta were performed. Echo and invasive gradients were averaged over 3 cardiac cycles. Finally, we tried to identify an estimation of invasively measured LV systolic pressure by combining systolic BP and echo measured gradients. Results Systolic BP was 143±21 mmHg. Max. CW Doppler gradient was 65±29 mmHg and mean gradient was 31±14 mmHg. Invasive simultaneous measurements at rest showed peak-to-peak gradient of 55±24 mmHg and mean gradient of 34±13 mmHg between apical LV and ascending aorta. Mean LVSP was 190±40 mmHg. Systolic pressure of the ascending aorta was 134±28 mmHg. Adding systolic peripheral BP and maximal echo-gradient mean value was 208±38 mmHg. Adding systolic peripheral BP and echo-mean gradient mean value was 174±26 mmHg. Correlating these values with the invasively measured systolic LV pressure we found a slightly higher correlation of the sum of systolic BP and mean-echo gradient (Pearson correlation coefficient: 0.867 p<0.001) compared with the sum of systolic BP and maximal echo-gradient (Pearson correlation coefficient: 0.851; p<0.001). Bland–Altman plots demonstrated good levels of agreements between invasively measured LVSP and both non-invasively estimated LVSP. Conclusions Non-invasive estimation of LVSP is feasible by combining conventional BP and CW Doppler measured mean LV outflow tract gradient in HOCM. Hereby estimation of MW in pts with HOCM is applicable.

Ginsenoside Rb1 pretreatment attenuates myocardial ischemia by reducing calcium/calmodulin-dependent protein kinase II-medicated calcium release

Objective: The aim of this study was to investigate the protective effects of ginsenoside Rb1 and assess whether these protective effects are related to calcium/calmodulin-dependent protein kinase II (CaMKII).Methods: A myocardial ischemia (IS) rat. model and a myocardial H9C2 cell hypoxia model were established. MI was induced by occluding the left anterior descending artery for 120 min. Ginsenoside Rb1 (10 mg/kg) was administered 30 min before ischemia induction, and the treatment continued for 7 days. Results: In the rat IS injury model, ginsenoside Rb1 reduced myocardial infarct size, mean left ventricular diastolic pressure, incidence of arrhythmia, and levels of serum creatine kinase, lactate dehydrogenase, and malondialdehyde. However, the mean left ventricular systolic pressure, and maximal rising and falling rates of ventricular pressure (±dp/dtmax) increased. In the myocardial H9C2 cell hypoxia model, ginsenoside Rb1 reduced intracellular calcium concentrations ([Ca2+ ]i) during hypoxia, and markedly reversed the hypoxia-induced decrease in cell survival. Ginsenoside Rb1 was involved in the downregulation of CaMKII and the ryanodine receptor, as well as hypoxia-induced H9C2 cell survival. Conclusion: The findings of the present study suggest that ginsenoside Rb1 attenuates MI injury in rats, partially through the downregulation of CaMKII expression.

Investigation on the feasibility of left ventricle and coronary artery angiography through femoral artery 1in rabbits

Objective To investigate the feasibility of performing left ventricle and coronary artery angiography in rabbits through femoral artery as a method to provide accurate assessment of cardiac function in heart failure and myocardial infarction. Methods A total of 20 New Zealand rabbits were used and left ventricle and coronary artery angiography was performed through femoral artery. Peak left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP) and left ventricular ejection fraction (LVEF) were recorded. Results Left ventricle and coronary artery angiography was successfully conducted in 12 rabbits, but failed in 5 rabbits during catheterization. The other 3 rabbits died during the procedure. The mean LVEDP was (5.08±2.01)mmHg (1 mmHg=0.133 kPa), the mean LVSP was (101.04±21.12) mmHg, and the mean LVEF (68±7)%. Conclusions Left ventricle and coronary artery angiography through femoral artery in rabbits is feasible and can be used to accurately evaluate cardiac function. The method is reliable, but has strict requirements on equipment and training. Key words: Coronary angiography; Ventricular function, left

Balloon valvuloplasty in rheumatic aortic valve stenosis: immediate and long-term results.

To study the immediate and long-term results of balloon aortic valvuloplasty (BAV) in a large cohort of patients with rheumatic valvular aortic stenosis. Single tertiary care center retrospective data analysis of immediate and long-term outcomes in patients following BAV from 2000 to 2008. Ninety-two patients with rheumatic aortic stenosis (AS) were studied who underwent BAV. Mean age of patients was 21.7 years (95 % CI 14.3-28.9) with mean follow-up period of 5.7 years (±SD 1.3). Intervention resulted in successful BAV (more than 50 % reduction in baseline gradient) in 79 (85.9 %) subjects (Group A) and partially successful BPV (<50 % reduction in baseline gradient) in 8 (8.7 %) subjects (Group B). BAV failed in 5 (5.4 %) subjects (Group C). Concomitant balloon mitral valvuloplasty was done in 23/92 cases. Mean left ventricular systolic pressure decreased from 165.6 (95 % CI 142.7-196.3) to 110.9 mmHg (95 % CI 92.1-129.6), (P < 0.001) and mean aortic valve (AV) gradient from 50.7 (95 % CI 35.12-66.22) to 27.2 mmHg (95 % CI 25.83-31.23), (P < 0.001). The mean change in ejection fraction and mean AV gradient were significantly different between success (Groups A and B) and failure groups (P < 0.001). Different grades of aortic regurgitation were noted in 32 (34.78 %) patients post BAV (severe regurgitation in 2.18 %). Anova post hoc analysis showed sustained gradient reductions at 1- and 5-year follow-up (P > 0.05). The need for surgery was much lower in Group A (2.5 %) compared to Group B (50 %) and C (100 %). BAV is an effective treatment strategy in dominant AS in multi valvular rheumatic disease situations. Combined aortic and mitral valvuloplasty was performed in one-fourth of study patients.

Evaluation of NT‐Pro BNP and CT‐ANP as Markers of Concentric Hypertrophy in Dogs with a Model of Compensated Aortic Stenosis

Serum C-terminal atrial natriuretic peptide (CT-ANP) and N-terminal pro B-type natriuretic peptide (NT-pro BNP) concentrations have not been measured serially in dogs with chronic pressure overload of the heart. We investigated whether serial evaluation of CT-ANP and NT-pro BNP concentrations is a useful guide to the risk of cardiac remodeling in dogs with a model of aortic stenosis. Six male Beagles. After anesthesia, the aorta was constricted with a polyester band and mean left ventricular systolic pressure (LVPs) was 50 mmHg above baseline. Echocardiographic and intracardiac catheter examinations and blood sampling were performed before surgery and 3 and 6 months after surgery. LVP and left ventricular end-diastolic pressure (LVEDP) were significantly higher at 6 months. Compared with baseline, end-diastolic intraventricular septum thickness (IVSd), left ventricular posterior wall thickness (LVPWd), and relative wall thickness (RWT) were significantly increased 3 and 6 months after aortic constriction. Serum CT-ANP concentrations were increased significantly at 3 months and serum NT-pro BNP concentrations were significantly higher 3 and 6 months after aortic constriction. Serum NT-pro BNP concentration was significantly correlated with LVEDP and IVSd whereas serum CT-ANP concentration was not correlated with any measurement. Stepwise regression analysis showed that LVEDP, IVSd, and RWT could predict serum NT-pro BNP. This study indicated the differential regulation of NT-pro BNP and CT-ANP concentrations during pressure overload. NT-pro BNP assay may be used as an additional screening method to stratify early-stage ventricular remodeling because of aortic constriction.

Effects of a New Cardiomyoplasty Technique on Cardiac Function

Objective: The current cardiomyoplasty technique was modified to maintain the resting tension of the latissimus dorsi muscle and to prevent lateral movement of the heart during muscle stimulation. The aim of this study is to compare the short term hemodynamic effects of the new cardiomyoplasty wrap (W1) with those of the clinically applied cardiomyoplasty wrap (W2). Preliminary indications of the long-term hemodynamic effects of W1 are presented. Methods: In three acute experiments in sheep mean central venous pressure (MCVP), mean arterial pressure (MAP), mean cardiac output (MCOP), mean left ventricular systolic pressure (MLVSP). and mean left ventricular diastolic pressure (MLVDP) were measured for 30 s before and five minutes after applying each procedure with and without stimulation of the muscle graft. The same parameters were also recorded 5 min after removing each muscle wrap. Hemodynamic changes associated with unstimulated muscle wraps were compared to the baseline data. Hemodynamic effects of muscle stimulation were determined by comparing the assisted to the preceding unassisted cardiac cycle. The long-term effects of W1 on the hemodynamics of another three sheep were studied at 6–12 months after the operation. The viability of the muscles used in the chronic experiments were evaluated by morphometric analysis. Results: Unstimulated W2 significantly increased mean central venous pressure and reduced mean cardiac output. It also increased mean left ventricular diastolic pressure and reduced peak negative dP/dt. Unstimulated W1 had no deleterious effect on mean central venous pressure, mean left ventricular diastolic pressure or peak — dP/dt, but it also reduced mean cardiac output and increased mean left atrial pressure (MLAP). Synchronised muscle stimulation, in both techniques, augmented the mean arterial pressure, mean cardiac output and mean left ventricular systolic pressure. In W2, however, myostimulation was also associated with a significant increase of the mean left ventricular diastolic pressure. In two long-term experiments significant hemodynamic assistance was observed at 6 months and at 1 yr after W1. In those sheep 68% of the cross-sectional area of the muscle was well preserved. Conclusions: Unstimulated cardiomyoplasty wraps acutely impair left ventricular function in sheep. The new technique, however, may offer significant long-term hemodynamic assistance and adequate preservation of the structural and functional integrity of the muscle flap for up to 1 yr.

Effects of a new cardiomyoplasty technique on cardiac function

Objective: The current cardiomyoplasty technique was modified to maintain the resting tension of the latissimus dorsi muscle and to prevent lateral movement of the heart during muscle stimulation. The aim of this study is to compare the short term hemodynamic effects of the new cardiomyoplasty wrap (W1) with those of the clinically applied cardiomyoplasty wrap (W2). Preliminary indications of the long-term hemodynamic effects of W1 are presented. Methods: In three acute experiments in sheep mean central venous pressure (MCVP), mean arterial pressure (MAP), mean cardiac output (MCOP), mean left ventricular systolic pressure (MLVSP), and mean left ventricular diastolic pressure (MLVDP) were measured for 30 s before and five minutes after applying each procedure with and without stimulation of the muscle graft. The same parameters were also recorded 5 min after removing each muscle wrap. Hemodynamic changes associated with unstimulated muscle wraps were compared to the baseline data. Hemodynamic effects of muscle stimulation were determined by comparing the assisted to the preceding unassisted cardiac cycle. The long-term effects of W1 on the hemodynamics of another three sheep were studied at 6–12 months after the operation. The viability of the muscles used in the chronic experiments were evaluated by morphometric analysis. Results: Unstimulated W2 significantly increased mean central venous pressure and reduced mean cardiac output. It also increased mean left ventricular diastolic pressure and reduced peak negative dP/dt. Unstimulated W1 had no deleterious effect on mean central venous pressure, mean left ventricular diastolic pressure or peak −dP/dt, but it also reduced mean cardiac output and increased mean left atrial pressure (MLAP). Synchronised muscle stimulation, in both techniques, augmented the mean arterial pressure, mean cardiac output and mean left ventricular systolic pressure. In W2, however, myostimulation was also associated with a significant increase of the mean left ventricular diastolic pressure. In two long-term experiments significant hemodynamic assistance was observed at 6 months and at 1 yr after W1. In those sheep 68% of the cross-sectional area of the muscle was well preserved. Conclusions: Unstimulated cardiomyoplasty wraps acutely impair left ventricular function in sheep. The new technique, however, may offer significant long-term hemodynamic assistance and adequate preservation of the structural and functional integrity of the muscle flap for up to 1 yr.

Effects of increasing flow rate on aortic stenotic indices: evidence from percutaneous transvenous balloon dilatation of the mitral valve in patients with combined aortic and mitral stenosis.

To investigate the effects of transvalvar flow rate on aortic valve resistance and valve area after percutaneous transvenous balloon dilatation of the mitral valve in a homogeneous group of patients with rheumatic heart disease. Retrospective analysis of 12 patients with combined aortic and mitral stenosis who had undergone balloon dilatation of the mitral valve over a period of 9 years. Tertiary referral centre. Twelve (8 women, 4 men; mean (SD) age 37 (9) of 227 consecutive patients with critical mitral stenosis undergoing transvenous balloon dilation of the mitral valve in the centre also had aortic stenosis, defined as a transaortic pressure gradient of more than 25 mm Hg measured at a catheterisation study before valvuloplasty. Echocardiographic variables (mitral valve area measured by the pressure half-time method and planimetry, and the aortic valve area derived from the continuity equation) and haemodynamic measurements (cardiac output, left ventricular mean systolic pressure, aortic mean pressure, transaortic valve pressure gradient, mitral valve and aortic valve areas derived from the Gorlin formula, and aortic valve resistance) were assessed before and after transvenous balloon dilatation of the mitral valve. Follow up catheterisation to measure haemodynamic variables was performed one week after mitral valvuloplasty. Mean transaortic flow rate increased 33% after mitral valvuloplasty (from 198 (68) to 254 (41) ml/s, P = 0.002). Aortic valve areas derived from the Gorlin formula were significantly increased from 0.57 (0.12) to 0.73 (0.14) cm2 (P = 0.006) after mitral valvuloplasty. However, aortic valve area and valve resistance derived from the continuity equation were independent of the increase in flow rate after mitral valvuloplasty (from 1.29 (0.35) to 1.30 (0.29) cm2 and from 317 (65) to 259 (75) dyn.s.cm-5, both P = NS). The Gorlin-derived aortic valve area tends to be flow-dependent, and continuity equation-derived aortic valve area and catheterisation-derived valve resistance seem to be less flow-dependent. In patients with combined mitral and aortic stenosis, these flow-independent indices are important for decision-making.

Effect of ibutilide, a new class III agent, on sustained atrial fibrillation in a canine model of acute ischemia and myocardial dysfunction induced by microembolization.

The effect of ibutilide, a new Class III antiarrhythmic agent, upon acute onset atrial fibrillation was investigated in a closed-chest canine model of acute left ventricular (LV) dysfunction. Twenty-four anesthetized mongrel dogs, mean weight 24.9 +/- 4 kg were subjected to coronary artery microsphere embolization and volume loading, followed by attempted induction of atrial fibrillation (AF) by rapid atrial pacing. Acute ischemic LV dysfunction was successfully induced by embolization in all dogs, and caused significant (P < 0.02) decreases in LV systolic pressure, peak + dp/dt (and -dp/dt), stroke volume, and RR interval; whereas LV end diastolic pressure and QTc significantly increased. Sustained AF (> or = 30 min) was successfully induced in 15 of 24 dogs (62%) and unsustained AF (< 30 min) was induced in the remainder (38%). At 30 minutes after induction of sustained AF, 15 dogs were randomized to intravenous ibutilide (0.15 mg/kg, given as a 0.075 mg/kg bolus, followed by 0.075 mg/kg infusion over 1 hour; n = 7) or placebo (saline; n = 8). There were no statistically significant differences between the ibutilide and the placebo groups with respect to mean LV systolic pressure, LV end diastolic pressure, LV dp/dt, RR interval, or QTc interval during AF prior to infusion. All seven dogs receiving ibutilide converted to sinus rhythm after a median of 3 minutes (range 0.5-26 min), while only three of eight placebo dogs (P < 0.03) converted to sinus rhythm after a median duration of 30 minutes (range 15-60 min) (P < 0.04 for difference in time to conversion).(ABSTRACT TRUNCATED AT 250 WORDS)

Progressive myocardial dysfunction after cardiac resuscitation.

To investigate left ventricular function by the Langendorff method after successful cardiac resuscitation in rats. Prospective, randomized, controlled animal study. University research laboratory. Adult, male Sprague-Dawley rats. Myocardial function was investigated in three subsets of isolated, perfused rat hearts that were harvested either before inducing ventricular fibrillation (controls) or at defined intervals after successful resuscitation from ventricular fibrillation. Ventricular fibrillation was induced with an electrode catheter advanced into the right ventricle of 15 mature, mechanically ventilated Sprague-Dawley rats. After an interval of 4 mins of untreated ventricular fibrillation and an additional 5 mins of precordial compression, spontaneous circulation was restored by a direct current, transthoracic countershock. The heart of each animal was then harvested at either 2 or 20 mins after successful cardiac resuscitation. The same model was utilized for harvesting the controls. Animals were randomized to each of the three subsets immediately before induction of cardiac arrest. There was a progressive decrease in myocardial contractility of the isolated, perfused hearts. Mean left ventricular systolic pressure was 128 +/- 8 mm Hg in control animals. In hearts harvested at 2 mins after successful resuscitation, the maximal generated pressure was reduced to 106 +/- 9 mm Hg. When harvested at 20 mins after successful resuscitation, it was reduced to 81 +/- 11 mm Hg. There were corresponding decreases in the mean maximal rate of left ventricular pressure increase (dP/dtmax) from 2880 +/- 110 to 2470 +/- 120 mm Hg/sec at 2 mins and to 1810 +/- 135 mm Hg/sec at 20 mins. These decreases in contractility were associated with striking decreases in myocardial relaxation and compliance. These studies, therefore, document progressive systolic and diastolic myocardial dysfunction immediately after successful cardiac resuscitation with restoration of spontaneous circulation.

Medical management of three asymptomatic infants with severe valvar aortic stenosis.

We report on the clinical course and serial hemodynamic studies of three patients with severe valvar aortic stenosis diagnosed in the neonatal period. None of the children were symptomatic in the first year of life. In each case, a conservative initial management approach was adopted. Between the time of initial study (mean age, 1.8 months) and the follow-up at 12-27 months of age (mean, 14.3 months), mean left ventricular systolic pressure decreased from 151 to 125 mmHg, the mean peak systolic pressure gradient across the aortic valve decreased from 61 to 33 mmHg, and the mean calculated aortic valve area index increased from 0.24 to 0.60 cm2/m2. One patient was operated on for symptoms that appeared at 14 months of age. The patient followed longest is now 5 years old, is growing well, has a normal electrocardiogram and an echo-predicted left ventricular systolic pressure of 128 mmHg. This experience suggests that not all asymptomatic neonates with severe valvar aortic stenosis require surgical intervention early in life. In some, the aortic valve orifice may increase in size with somatic growth and obviate the need for surgery in infancy or early childhood.

THE UNNATURAL HISTORY OF AORTIC STENOSIS

We report on the clinical course and serial hemodynamic studies of three patients with severe valvar aortic stenosis diagnosed in the neonatal period. None of the subjects was symptomatic in the first year of life. In each case, a conservative initial management approach was adopted. Between the time of initial study (mean age 1.8 months) and the follow up at 12-27 months of age (mean 14.3 months), mean left ventricular systolic pressure fell from 151 to 135 mmHg, the mean peak systolic pressure gradient across the aortic valve fell from 54 to 42 mraHg, and the mean calculated aortic valve area index increased from 0.20 to 0.39 cm2/meter2. One of the patients was operated on for symptoms which appeared at 14 months of age. The patient followed longest is now 5 years old, is growing well, has a normal electrocardiogram and an echo-predicted left ventricular systolic pressure of 128 mmHg. This experience suggests that not all asymptomatic neonates with severe valvar aortic stenosis require surgical intervention early in life. In some, the aortic valve orifice may increase in size with somatic growth and obviate the need for surgery in early childhood.

The calculation of left ventricular stroke work index.

The relation between left ventricular mean systolic pressure (LVSP) determined by planimetric integration and systolic and diastolic pressure measured in a peripheral artery (SAP and DAP) was calculated using data published by Ross & Braunwald in 1964. The relation was LVSP = SAP-0.32 +/- 0.06 (s.d.) X (SAP-DAP). The formula SAP- 0.32 (SAP-DAP) was used to calculated LVSP, and the correlation between measured and calculated LVSP was found to be 0.91 (P less than 0.001). It is concluded that LVSP can be calculated with reasonable accuracy from measurements of arterial pressure in patients without aortic stenosis. At present three different formulas are in use for the calculation of left ventricular stroke work index (LVSWI). The pressure work is defined as SAP, LVSP or mean arterial pressure minus mean pulmonary capillary wedge pressure or left ventricular end diastolic pressure. This makes comparisons between different studies with respect to LVSWI difficult or impossible.

Effects of changes in the aortic input impedance on systolic pressure-ejected volume relationships in the isolated supported canine left ventricle.

We examined the effects of aortic input impedance alteration on left ventricular pressure, aortic flow and ejected volume (integral value of aortic flow), in an isolated blood perfused ejecting canine heart, with special reference to end-systolic values. A hydraulic model which stimulates an aortic input impedance was attached to the aortic root of an excised heart. Left ventricular end-diastolic pressure was kept constant by electrical pacing. Three coronary arteries were perfused with arterial blood from support dogs. When the peripheral resistance in the hydraulic model was changed, there were inverse linear relationships between stroke volume and mean left ventricular systolic pressure and between ejected volume and pressure at end-systole. Time interval from the onset of contraction to end-systole did not change. Thus the relation between stroke volume and mean left ventricular pressure obtained by changes in peripheral resistance is governed by a source resistance, which can be considered as the contractile state of the ventricle. When the capacitance (arterial compliance) was changed, there was no inverse linear relation between stroke volume and mean systolic pressure. In many cases, there was an inverse linear relationship between ejected volume and pressure at end-systole. However, an increase in capacitance prolonged the time interval from the onset of contraction to end-systole. We conclude that the end-systolic pressure-ejected volume relationship in the ejecting heart is governed not only by contractility but also by arterial capacitance.

Myocardial Blood Flow Distribution in Concentric Left Ventricular Hypertrophy

Regional myocardial blood flow during both control conditions and ischemia-induced vasodilatation was studied in eight chronically instrumented awake dogs. Seven of these animals had coarctation-banding of the ascending aorta performed at 6 wk of age, and the other dog had congenital subvalvular aortic stenosis. The mean left ventricular weight for the group was 157+/-7.6 g, and the left ventricular body weight ratio was 8.76+/-0.47 g/kg. None of the animals exhibited signs of congestive heart failure. During the control state, the mean left ventricular systolic pressure was 249+/-12 mm Hg and the left ventricular end-diastolic pressure was 11.5+/-0.5 mm Hg. The aortic diastolic pressure was 74+/-6 mm Hg. Mean left circumflex coronary artery blood flow was 71+/-6 cm(3)/min. In the animals with coarctation-banding, 52+/-6% of the flow occurred during systole. In the dog with congenital subvalvular aortic stenosis, 5% of the coronary flow was systolic. Mean transmural blood flow during resting conditions was 0.97+/-0.08 cm(3)/min per g, and the ratio of endocardial to epicardial flow (endo/epi) was 0.88+/-0.07. During reactive hyperemia, the mean transmural blood flow increased to 3.5+/-0.30 cm(3)/min per g; however, the endo/epi decreased to 0.52+/-0.06.THESE STUDIES DOCUMENT A DIFFERENCE IN TRANSMURAL BLOOD FLOW DISTRIBUTION BETWEEN THE NORMAL AND THE HYPERTROPHIED LEFT VENTRICLE: during resting conditions, in the normal ventricle, the highest flow occurs in the endocardial layer, whereas in the hypertrophied ventricle, the highest flow is in the middle layers with the endocardial flow less than the epicardial flow. During ischemia-induced vasodilatation, the abnormal endo/epi becomes accentuated markedly. These data demonstrate that, in situations requiring high flow, the endocardial layer of a heart with marked concentric left ventricular hypertrophy may not be perfused adequately.

Performance of an abdominal left ventricular assist device during induced tachycardias and dysrhythmias

Experiments were designed to assess the performance of an intracorporeal (abdominal) left ventricular assist device (ALVAD) in the presence of induced tachycardias, multiple premature ventricular contractions (PVC's), and ventricular fibrillation in calves. Performance criteria were the degree of left ventricular unloading and the per cent cardiac output assumed by the ALVAD. During synchronous pumping, left ventricular unloading was complete and the entire cardiac output was captured by the device. During induced tachycardias up to rates of 120 beats per minute, these degrees of performance were maintained. At rates in excess of 120 beats per minute, performance declined due to decreased biologic stroke volumes and prosthetic filling times. In the presence of induced PVC's, performance during synchronous pumping decreased because of erratic R-wave sensing. Left ventricular unloading was complete but irregular, and the total cardiac output was captured. When asynchronous pumping was utilized, mean left ventricular systolic pressures increased, but total cardiac output was still captured. During induced ventricular fibrillation, ALVAD actuation maintained cardiac outputs equal to control values for periods up to 5 1/2 hours. These experiments indicate that, during normal sinus rhythm, synchronous pumping is optimal; asynchronous pumping is optimal during complex dysrhythmias; and either can be utilized to support the circulation with varying degrees of left ventricular unloading.

Effect of uraemia upon the performance of the rat heart.

The purpose of the present experiments was to study whether the uraemic state causes any change in intrinsic cardiac function in the rat. Hearts of animals were studied 24 hr after bilateral nephrectomy (acute uraemia) or two weeks after 5/6 nephrectomy (chronic uraemia). Ventricular function curves were performed in an isolated working rat heart apparatus. Hearts from animals with acute uraemia performed the same as hearts from sham controls. Hearts from animals with chronic uraemia had enhanced performance as evidenced by increased cardiac output, peak and mean left ventricular systolic pressure, maximum rate of left ventricular pressure rise, and external work. Coronary flow, myocardial oxygen consumption, and external efficiency were also greater in hearts of rats with chronic uraemia. These studies demonstrate that short-term chronic uraemia is not associated with depressed intrinsic cardiac performance. On the contrary, isolated hearts from chronic uraemic rats, while performing external work, demonstrate enhanced dynamic and metabolic responses to increasing filling pressures.

Effect of physical training on the mechanical and metabolic response of the rat heart to hypoxia.

To study the effects of physical conditioning on cardiac function and metabolism during hypoxia, rats were conditioned by swimming. Their isolated hearts and hearts of sedentary rats were studied under isovolumic conditions and also while performing external work. During isovolumic performance only minimal improvement in hypoxic cardiac performance was observed because of conditioning. While performing external work during hypoxia cardiac output and cardiac work were approximately twice as great in hearts from conditioned rats as in those from sedentary rats. There were also slightly higher peak systolic pressures and mean left ventricular systolic pressures during hypoxia. Oxygen delivery and lactate production during hypoxia were the same in hearts from conditioned and sedentary rats as were myocardial NADH fluorescence, residual high-energy phosphate stores, and myocardial glycogen levels. External efficiency in experiments on working rat hearts was twice as great during hypoxia in hearts from conditioned rats as in those fromsedentary rats. The data suggest that hearts of conditioned rats have enhanced pumping capacity when subjected to hypoxia compared with hearts of sedentary rats. Oxygen delivery and energy formation during hypoxia are not improved in hearts of conditioned animals. The major reason for improved performance appears to be more efficient energy utilization for external cardiac work.

Left atrial booster function in valvular heart disease.

This study was designed to assess atrial booster pump action in valvular heart disease and to dissect booster pump from reservoir-conduit functions. In five patients with aortic stenosis and six with mitral stenosis, sequential atrioventricular (A-V) pacing was instituted during the course of diagnostic cardiac catheterization. Continuous recording of valvular gradient allowed estimation of flow for each cardiac cycle by transposition of the Gorlin formula. Left ventricular ejection time and left ventricular stroke work in aortic stenosis or left ventricular mean systolic pressure in mitral stenosis were also determined. Control observations were recorded during sequential A-V pacing with well-timed atrial systole. Cardiac cycles were then produced with no atrial contraction but undisturbed atrial reservoir function by intermittently interrupting the atrial pacing stimulus during sequential A-V pacing. This intervention significantly reduced valvular gradient, flow, left ventricular ejection time, and left ventricular mean systolic pressure or stroke work. Cardiac cycles were then produced with atrial booster action eliminated by instituting synchronous A-V pacing. The resultant simultaneous contraction of the atrium and ventricle not only eliminated effective atrial systole but also placed atrial systole during the normal period of atrial reservoir function. This also significantly reduced all the hemodynamic measurements. However, comparison of the magnitude of change from these two different pacing interventions showed no greater impairment of hemodynamic state when both booster pump action and reservoir function were impaired than when booster pump action alone was impaired. The study confirms the potential benefit of well placed atrial booster pump action in valvular heart disease in man.

Beta adrenergic blockade: Hemodynamics and myocardial energy metabolism in patients with ischemic heart disease

Systemic and coronary hemodynamics and myocardial intermediary metabolism were studied before and after beta adrenergic blockade with propranolol in 9 patients with ischemic heart disease. A significant reduction was produced in heart rate, left ventricular isometric tension development (dp/dt) and pressure-time per minute, whereas left ventricular end-diastolic pressure rose. Cardiac output and left ventricular mean systolic pressure and mechanical work did not change consistently. Myocardial oxygen consumption was influenced by left ventricular external work and pressure-time per min., the latter having the predominant effect. Myocardial oxygen consumption was not closely related to the consistent reduction of dp/dt, presumably because of wide variations in stroke volume. Coronary blood flow was reduced in 5 of 8 patients, changes in coronary diastolic vascular resistance in most cases favoring the preservation of an autoregulatory mechanism. A constant or reduced coronary arteriovenous oxygen extraction in 6 of 9 patients suggested that changes in perfusion rather than in extraction accommodated the altered myocardial oxygen needs. Propranolol appeared to have no direct action on vasomotor tone but probably reduced extravascular compression resistance. Myocardial efficiency did not change consistently. External efficiency was generally reduced, but internal efficiency rose in 3 patients. When a reduction in efficiency indexes resulted from decreased cardiac work but increased coronary flow and myocardial oxygen consumption, the overstressed myocardium may have benefited. Total myocardial substrate oxygen extraction ratios exceeded 100 per cent under control conditions and after beta blockade; therefore the respective energy contributions of carbohydrates and fatty acids were obscure, and conversion and storage seemed likely. The NAD +/NADH redox potential gradient was consistently changed to a more positive value. Arterial levels of inorganic phosphate and creatine phosphokinase activity rose, and the myocardial balance of creatine phosphokinase became positive after propranolol. The antianginal action of propranolol may be related to the following mechanisms: (1) myocardial work is reduced, thus lessening the disparity between oxygen demand and supply; (2) a relative or absolute improvement in coronary perfusion and myocardial oxygen delivery may result, subject to arteriolosclerotic limitations; (3) changes in myocardial intermediary metabolism and enzyme systems favor lessened cellular hypoxia and enhanced aerobiosis.