Acute Pressure Loading Research Articles

Role of electrocardiographic changes in discriminating acute or chronic right ventricular pressure overload

Pulmonary embolism (PE) and severe pulmonary stenosis (PS) are two distinct conditions accompanied by increased pressure load of the right ventricle (RV). Despite major advances in our understanding of the mechanisms of RV adaptation to the increased pressure, substantial gaps in our knowledge remain unsettled. One of much less known aspect of pressure overload of RV is its impact on electrocardiographic (ECG) changes. In this study, we aimed to study whether acute and chronic RV overload are accompanied by different ECG patterns. Thirty-eight patients with PE underwent ECG monitoring were compared with 20 matched patients with PS in this observational retrospective study. ECG abnormalities suggestive of RV overload were recorded and analyzed in both groups. Logistic regression analysis was used to define the predictors of chronic RV overload. Among the ECG changes studied, premature atrial contraction (OR-12.2, 95% CI, 1.3-107, p=0.008), right axis deviation (OR-20.4, 95% CI 4.2-98, p<0.001), indeterminate axis (OR-0.11, 95% CI 0.02-0.44, p=0.001 0.11), incomplete right bundle branch block (OR-4.2, 95% CI, 1.1-15.4, p=0.02), late R in aVR (OR-8.4, 95% CI 2.1-33.2, p=0.001), qR in V1 lead (OR-8.3, 95% CI 1.2-74.8, p=0.03) were found to be the independent predictors of chronic RV pressure overload. Our data indicate that the ECG changes that attributed to the acute RV pressure loading states may be more prevalent in chronic RV overload as compared with acute RV overload.

Postoperative neurodevelopmental outcome of patients with hypoplastic left heart complex: hybrid versus Norwood strategy

Besides survival, the neurological status of patients after surgical treatment of congenital heart defect constitutes the most important indicator of the outcome in the current era. Nowadays, it is well documented in the literature a state of immaturity of the brain in neonates born with congenital heart disease that makes them particularly susceptible either to newly occurring brain damage or to worsening of pre-existing brain lesions when subjected to cardiopulmonary bypass surgery [1]. This susceptibility would be further enhanced by special techniques used for the reconstruction of the aortic arch, namely the deep hypothermic circulatory arrest or the antegrade lateral cerebral perfusion [2]. This is the main explanation of the clear tendency of some centres to pursue the treatment of congenital heart disease less aggressively than in the past, by restoring traditional palliative techniques or introducing modern interventional tools, all designed to appeal to the extracorporeal circulation, whenever possible, beyond the terms of the fateful neonatal period [3]. The rationale for the hybrid procedure for treatment at the first stage of hypoplastic left heart complex should be exactly that. In spite of such rationale, literature provides controversial data regarding both survival and myocardial performance in patients undergoing hybrid procedure compared with those treated with Norwood operation. For instance, although avoiding cardiopulmonary bypass and cardioplegic arrest, the early postoperative haemodynamic profile of the hybrid procedure has been reported as not being superior to the Norwood in terms of cardiac output and pulmonary blood flow. As a matter of fact, the acute pressure load imposed by the bilateral banding to the already volume-loaded right ventricle would play a detrimental effect on myocardial performance both directly and mediated by increased circulating vasocontrictors. The resultant increase in systemic vascular resistance would be responsible for a potential for pulmonary overcirculation, with somehow elevated Qp:Qs ratios, the major benefit of the hybrid procedure residing in the avoidance of high VO2 states rather then tight control of Qp [4]. The paper by Knirsch et al .[ 5] provides further data to the evidence that deprive the hybrid procedure of the role of panacea revealing a substantial overlap of data regarding the neurodeve

Modulation of integrins and integrin signaling molecules in the pressure-loaded murine ventricle.

Integrins are heterodimeric cell-surface receptors that link the extracellular matrix and the intracellular cytoskeleton and function as mechanotransducers. Signaling through integrins is important for cell growth, migration, and survival. Extracellular matrix is altered in the myocardium during hypertrophic induction and the transition to heart failure. The role of integrins in this process is poorly understood. Recently, integrin subunits have been identified that are dominantly expressed in striated muscle. We tested the hypothesis that since integrins are mechanotransducers, their expression and signaling would be modulated with murine left ventricular hemodynamic loading. The acute and chronic effects of pressure overload on changes in the expression of integrins, as well as related integrin-mediated signaling events were studied. Acute pressure loading increased phosphorylation of focal adhesion kinase, p42 and p44 extracellular signal-regulated kinase. Chronic loading: (1) increased expression of alpha1, alpha5, and beta1 integrin transcripts and (2) increased protein expression of integrin subunits which are dominantly expressed in striated muscle (alpha7 and beta1D) both by western blotting and immunofluorescent microscopy. These results show that adaptive responses of the myocardium to pressure overload include acute modulation of integrin-related signaling molecules and more chronic changes effect expression of integrin subunits, including ones dominantly expressed in muscle.

Effects of gestational age on myocardial blood flow and coronary flow reserve in pressure-loaded ovine fetal hearts.

To test the hypothesis that coronary flow and coronary flow reserve are developmentally regulated, we used fluorescent microspheres to investigate the effects of acute (6 h) pulmonary artery banding (PAB) on baseline and adenosine-enhanced right (RV) and left ventricular (LV) blood flow in two groups of twin ovine fetuses (100 and 128 days of gestation, term 145 days, n = 6 fetuses/group). Within each group, one fetus underwent PAB to constrict the main pulmonary artery diameter by 50%, and the other twin served as a nonbanded control. Physiological measurements were made 6 h after the surgery was completed; tissues were then harvested for analysis of selected genes that may be involved in the early phase of coronary vascular remodeling. Within each age group, arterial blood gas values, heart rate, and mean arterial blood pressure were similar between control and PAB fetuses. Baseline endocardial blood flow in both ventricles was greater in 100 than 128-day fetuses (RV: 341 +/- 20 vs. 230 +/- 17 ml*min(-1)*100 g(-1); LV: 258 +/- 18 vs. 172 +/- 23 ml*min(-1)*100 g(-1), both P < 0.05). In both age groups, RV and LV endocardial blood flows increased significantly in control animals during adenosine infusion and were greater in PAB compared with control fetuses. After PAB, adenosine further increased RV blood flow in 128-day fetuses (from 416 +/- 30 to 598 +/- 33 ml*min(-1)*g(-1), P < 0.05) but did not enhance blood flow in 100-day animals (490 +/- 59 to 545 +/- 42 ml*min(-1)*100 g(-1), P > 0.2). RV vascular endothelial growth factor and Flk-1 mRNA levels were increased relative to controls (P < 0.05) in 128 but not 100-day PAB fetuses. We conclude that in the ovine fetus, developmentally related differences exist in 1) baseline myocardial blood flows, 2) the adaptive response of myocardial blood flow to acute systolic pressure load, and 3) the responses of selected genes involved in vasculogenesis to increased load in the fetal myocardium.

Coronary flow regulation in the fetal sheep.

The two ventricles of the fetal sheep heart have anatomic and biochemical differences that account for their differing functional capabilities and blood flows. Coronary flows to both ventricles have been measured using radiolabeled microspheres [or left ventricular (LV) flow, by Doppler sensor on the circumflex coronary artery] during experiments of pressure loading and chronic and acute hypoxemia. Blood flow to the left ventricle with its lower wall tension is about two-thirds the flow per gram compared with the right ventricle (RV). Acute systolic pressure loading of the RV to its maximal work capability stimulates flow to double (from approximately 250 to 500 ml. min(-1). 100 g(-1)), but to a level less than stimulated by adenosine (750 ml. min(-1). 100 g(-1)). At all RV work loads, LV flow remains at two-thirds RV flow. Resting myocardial flow levels in fetuses that have been chronically hypoxemic are similar to maximal adenosine-stimulated flows of normal fetal sheep. This flow augmentation is evidently due to vascular remodeling because a normal "flow reserve" of approximately 500 ml. min(-1). 100 g(-1) during adenosine administration remains. Acute hypoxemia stimulates myocardial flow to extraordinary levels (>1.5 l. min(-1). 100 g(-1)), levels larger than can be obtained with chemical dilation alone. LV flows do not exceed adenosine-stimulated flows when nitric oxide synthase is antagonized. We conclude 1) fetal RV coronary flow increases with RV work but to levels less than during adenosine stimulation; 2) the fetal heart is designed to accommodate extremely high flows in response to acute hypoxemia, partially through large production of nitric oxide; and 3) the fetal coronary tree is dramatically remodeled in response to chronic hypoxemia.

Severe right ventricular pressure loading in fetal sheep augments global myocardial blood flow to submaximal levels.

It has previously been shown that the fetal right ventricle (RV) is sensitive to changes in arterial pressure and that its stroke volume is significantly reduced with acute increases in pulmonary arterial pressure. However, the myocardial blood flow (MBF) response to increases in pulmonary arterial pressure have not been investigated in the fetus. To assess whether the RV afterload sensitivity to arterial pressure is associated with limitation in MBF, seven fetal lambs were instrumented at 130 days of gestation with a pulmonary arterial occluder and intravascular catheters. RV stroke volume was measured by an electromagnetic flow probe and MBF by 15-microns labeled microspheres. MBF was determined at baseline and during incremental increases in pulmonary arterial pressure. Maximal MBF was determined in seven additional fetuses during adenosine infusion. The highest tolerated pressure was associated with a 50% reduction in RV stroke volume. The highest pulmonary arterial occlusion pressure resulted in a doubling of MBF to all regions of the heart (266 +/- 99 to 504 +/- 158, 193 +/- 69 to 387 +/- 100, and 171 +/- 66 to 338 +/- 134 ml/min/100 g for the RV, septum, and left ventricle, respectively). The best correlation for increases in both RV and global MBF was the RV heart rate-systolic pulmonary pressure product. Adenosine infusion was associated with a threefold increase in global MBF that was significantly greater than the MBF achieved during pulmonary arterial occlusion. The fetal RV sensitivity to acute pressure loading is not associated with limitation of MBF. The fetal myocardium has a remarkable flow reserve that allows for preservation of function during acute increases in arterial pressure.

In vivo Mechanisms of Myocardial Functional Stability during Physiological Interventions

Metabolic regulatory mechanisms are designed to maintain stable myocardial function during extremes in physiological insult; they can now be studied in vivo and may provide insight into mechanisms of altered myocardial functional decompensation during disease processes. To determine mechanisms of myocardial stability during hypoxia and acute pressure loading, creatine kinase (CK) kinetics (forward rate constant, Kf, and flux of phosphocreatine, PCr, to adenosine triphosphate, ATP), and nicotinamide adenine dinucleotide (NADH) redox state were determined with 31P nuclear magnetic resonance (NMR) and NADH fluorometry, respectively, and correlated with heart work (heart rate x systolic blood pressure, HR x SBP), cardiac output (CO) and O2 consumption (MVO2) in 15 anesthetized open chest dogs. Hypoxia (PaO2 of 30-35 mm Hg) was produced in 6 dogs with an inspired O2/N2 of 200/3,000. Cardiac loading was produced in 9 dogs by administration of norepinephrine (NE, 1 micrograms/kg/min). Each dog acted as its own control. Baseline NADH fluorometry, 31P-NMR saturation transfer and cardiac function measurements were performed simultaneously in each dog, after which the experimental interventions were made. Similar increases in HR x SBP, CO, and MVO2 which occurred during both interventions were associated with different bioenergetic responses. During NE infusion, the Kf of CK increased from control; during hypoxia, the Kf decreased from control (p less than 0.05). Flux of PCr----ATP was significantly lower during hypoxia than during NE infusion (p less than 0.05). PCr was decreased significantly during NE infusion (p less than 0.05). In addition, NADH redox state increased (from baseline of 100%) during hypoxia (140 +/- 10%) and decreased during NE infusion (78 +/- 6%).(ABSTRACT TRUNCATED AT 250 WORDS)

A nonlinear model of the arterial system incorporating a pressure-dependent compliance

The three-element modified Windkessel model has been widely used to study the characteristics of the systemic arterial system. This model provides most of the features of the systemic input impedance, but does not describe the nonlinear effect of the pressure dependence of arterial compliance. The current investigation examines the hemodynamic consequences of such an inclusion. Simultaneous aortic pressure and flow during control and brief descending aortic occlusion were measured in open chest anesthetized experimental dogs. A numerical procedure was implemented to compute constant compliance linear and nonlinear compliance model-predicted pressure waveforms with flow as the input. Results show that the nonlinear compliance model in general can more accurately predict the measured pressure waveforms during control and during acute pressure loading. The difference between the predicted waveforms is more pronounced when blood pressure is high and when the pulse pressure is large.

Hemodynamic and Neuroendocrine Adaptations of the Preterm Lamb Left Ventricle to Acutely Increased Afterload

The birth process is associated with dramatic alterations of left ventricular (LV) volume loading, pressure loading, and contractile state. The preterm LV has considerable volume loading reserve. We have assessed neuroendocrine and related hemodynamic responses of the preterm lamb LV at 0.8 gestation during acute pressure loading within the first 2-4 h after birth. We measured plasma catecholamines and hemodynamic and cineangiocardiographic parameters of LV pump performance and contractility at basal levels and during rapid LV pressure loading by partial balloon obstruction of the ascending aorta before and after propranolol. A relatively high level of propranolol (3 mg/kg) was required to produce beta-adrenoceptor blockade associated with reduction of heart rate and blood pressure, but after atrial pacing there was no detectable difference of basal LV pump performance or contractility at comparable heart rate, preload, and afterload. The LV pump performance was maintained and plasma catecholamines and LV contractility were increased when aortic systolic pressure was augmented 60% over baseline. The increased contractile state at greater afterload was minimally blunted by propranolol. Thus the preterm LV is relatively hypercontractile soon after birth and is capable of an integrated augmentation of pump performance and contractile state during pressure loading. These findings are relevant to the maintenance of adequate LV performance and successful adaptation to the acute alterations of afterload associated with the transitional circulation at birth.

In vivo myocardial bioenergetics during acute volume and/or pressure loading in a canine model: a 31P NMR study.

The effects of acute volume and/or pressure loading on myocardial metabolic and mechanical function were studied in 13 dogs. Volume loads were applied by shunting the abdominal aorta to the vena cava using polyethylene tubing (5 mm inner diameter). A plastic regulator allowed shunts to be opened or closed. Dogs were heparinized (100 units/kg) to prevent shunts from clotting. To study the effects of pressure loading, a norepinephrine infusion (1 microgram/kg/min) was administered. Mechanical function of the heart was evaluated using heart rate X systolic blood pressure (HR X SBP), cardiac output (CO), pressure X volume work (systolic blood pressure X stroke volume); (P X V), and oxygen consumption (MVO2) to estimate external myocardial work. Metabolic function was evaluated by 31P NMR. Phosphocreatine/adenosine triphosphate (PCr/ATP) ratios were used to estimate the bioenergetic regulation of oxidative phosphorylation during increased work load. HR X SBP, CO, P X V, and MVO2 were correlated with PCr/ATP. Although there was some variability, generally volume loading was associated with an increase in HR X SBP, CO, P X V, and MVO2 accompanied by no change, or small increases or small decreases in PCr/ATP throughout the loading period. These data indicate that the heart bioenergetics are quite stable during volume and/or pressure loading and that 31P spectroscopy methods can document this stability and tight metabolic regulation during in vivo loading conditions.

The effects of coarctation hypertension upon vascular inositol phospholipid hydrolysis in Wistar rats

In order to examine the effects of imposing an acute pressure load upon vascular structure and phosphoinositide hydrolysis, aortic medial thickness, cross-sectional area, cell nuclear counts and inositol phosphate accumulation were measured in Wistar rats with experimental coarctation and sham-operated controls at 3, 9 and 20 days after surgery. Compared to sham-operated animals, rats with coarctation had significantly higher carotid artery pressures throughout the study. Below the ligature, femoral arterial pressure was significantly lower in animals with coarctation. Proximal to the coarctation, there was an increase in aortic medial cross-sectional area and medial thickness but no increase in nuclear counts, suggesting the induction of hypertrophy; statistically significant changes were present at 9 and 20 days. Distal to the ligature only small structural changes were observed indicating some atrophy had occurred. Inositol phosphate accumulation had increased slightly at 3 days in proximal aortae from ligatured rats, and was significantly raised at 9 and 20 days; no such changes were recorded below the coarctation. These data indicate that the increased load upon the proximal aorta initiates increased inositol phosphate production through local mechanisms. Whilst a causal link has not been conclusively established between phosphoinositide turnover and hypertrophy, the association between the two in these studies is consistent with the hypothesis that the induction of increased cell phosphoinositide metabolism contributes, at least in part, to the proximal aortic structural changes observed in this model.

Hysteresis of left ventricular end ejection pressure-dimension relations after acute pressure loading in the intact canine heart.

The left ventricular end systolic pressure-volume relation of the isolated canine heart is linear and independent of the loading conditions. The effects of acute pressure loading on the left ventricular end ejection pressure-length relations were studied in the intact canine heart. The lengths of two wall segments of the left ventricle parallel to the minor axis were measured with pairs of miniature piezoelectric crystals. At two levels of filling pressure, with and without control of heart rate, acute increases in left ventricular afterload were produced for six successive beats by occluding the thoracic aorta. After abrupt release of this occlusion, at left ventricular end diastolic pressure less than 10 mmHg, end ejection lengths were longer than before the occlusion for both segments despite the same or lower end ejection pressures. When heart rate was not controlled the mean(SD) difference in end ejection length was 0.46(0.21) mm (n = 100). When heart rate was controlled by atrial pacing after autonomic blockade the difference was 0.37(0.11) mm (n = 80). In contrast, at left ventricular end diastolic pressure greater than 10 mmHg there was no significant difference between end ejection lengths before and after release of the aortic occlusion. Gradual release of the aortic occlusion over 4-5 beats produced clockwise hysteresis of the left ventricular end ejection pressure-length relation when left ventricular end diastolic pressure was less than 10 mmHg. No hysteresis occurred when left ventricular end diastolic pressure was greater than 10 mmHg. Hysteresis of the end systolic pressure-dimension relation was also seen when major and minor axis dimensions of the left ventricular were measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Surgical and mechanical support of the failing heart

The surgical treatment of acute heart failure is limited to cases of pressure or volume overload. Acute valvular regurgitation due to active endocarditis or to prosthetic dysfunction is a classic example of failure which can be cured by restoring valvular competence. Acute pressure load is mostly caused by prosthetic dysfunction or pulmonary embolism; therapy is aimed at removal of the causative agent. Coronary heart disease can cause heart failure by volume overload: acute mitral incompetence or ventricular septal defect lend themselves to surgical correction. In the surgical treatment of acute heart failure maximal attention is devoted to optimal timing of surgery, anesthetic management and postoperative care. Careful attention to the function of the right and left ventricle and combination of catecholamines, afterload reducing agents and volume loading together with respirator support have considerably improved the surgical results. Acute pump failure due to coronary insufficiency and infarction is less amenable to surgical treatment, with rare exceptions of emergencies during coronary angiography and percutaneous dilatation. The intra-aortic balloon pump is the only method of mechanical circulatory assistance which has reached widespread clinical acceptance. The best results are achieved in conjunction with surgery: either as cardiac support in inherently reversible postoperative heart failure or as the means of circulatory stabilization prior to surgery. Ventricular assist devices are still in the experimental stage: their use has been sharply curtailed by the virtual disappearance of the postoperative low output syndrome. In selected cases of end-stage cardiomyopathy cardiac transplantation is nowadays performed with acceptable survival (70% at one year after surgery). Both orthotopic and heterotopic transplantation (transplanted heart in parallel with the natural one) give comparable results, but the procedure is still very restricted due to the lack of donors, multiple contraindications and lack of suitable heart preservation techniques.

Effects of chronic oral quinidine on left ventricular performance

We studied the effects of 10 to 14 days of oral quinidine administration (200 mg every 8 hrs) on left ventricular (LV) dP dt max and shortening fraction (%ΔD) in seve preinstrumented consclous dogs in the resting state, during atrial pacing at 120 bpm, and during an acute pressure load produced by intravenous phenylephrine. Dogs were studied before, during, and after oral quinidine administration with control measurements varying by < 10%. In the resting state, heart rate (85 ± 6 SEM vs 88 ± 7 bpm), LV end-diastolic pressure (7.2 ± 1.4 vs 6.7 ± 1.1 mm Hg), LV end-diastolic diameter (39.6 ± 3.2 vs 38.9 ± 2.7) did not differ ( p > 0.05) before or during quinidine, respectively. During atrial pacing LV dP dt increased similarly during the control and quinidine periods (+ 13 and + 11%), and %ΔD decreased equally (−26% and −21%) during phenylephrine infusion off and on quinidine. Thus chronic oral quinidine administration in clinically therapeutic doses (serum quinidine levels 2.3 to 7.5 μg/ml) produced no depression in LV performance at rest or during an acute pressure load.

Effects of oral propranolol on left ventricular size and performance during exercise and acute pressure loading.

Oral propranolol (160 mg/day) was administered to 19 normal subjects for 2 weeks. Echocardiograms were performed at rest, during graded supine bicycle exercise in 10 subjects and during acute pressure loading with intravenous phenylephrine in the remaining nine subjects. Resting heart rate on propranolol decreased compared with control (52 +/- 8 vs 63 +/- 10 beats/min; p less than 0.001), as did systolic blood pressure (99 +/- 9 vs 107 +/- 9 mm Hg; p less than 0.01). Left ventricular end-diastolic dimension was slightly enlarged (48.3 +/- 4.2 vs 47.1 +/- 3.6 mm, p = 0.05), but percent dimensional shortening was unchanged (37 +/- 4 vs 38 +/- 5%). At each stage during supine bicycle exercise, heart rate was slower, blood pressure lower, left ventricular dimensions were larger and percent dimensional shortening was reduced on propranolol by an analysis of variance. In contrast, during acute pressure loading, while the heart rate response to increased blood pressure was blocked by atropine, there was no significant difference in left ventricle size and performance compared with control. We conclude that prolonged oral propranolol therapy has little, if any, intrinsic effect on myocardial performance in normal subjects. Its major action on the heart is competitive inhibition of beta-adrenergic tone, which is most manifest during conditions associated with increased sympathetic tone, such as exercise.

Effects of oral quinidine on left ventricular performance in normal subjects and patients with congestive cardiomyopathy

To evaluate the effects of oral quinidine therapy on left ventricular performance, 10 normal subjects and 8 patients with Cardiomyopathy were studied with echocardiography at rest, after intravenous injection of atropine and during infusion with phenylephrine. The echocardiographic studies were performed during oral quinidine therapy and during placebo administration. In the normal subjects heart rate was significantly faster with quinidine than with placebo (74 ± 8 (standard deviation) versus 68 ± 9 beats/min, P < 0.01), but there was no significant change in blood pressure or left ventricular size and performance. After administration of atropine, heart rate was identical with and without quinidine but the mean normalized velocity of left ventricular dimension shortening was significantly less with quinidine than with placebo (1.28 ± 0.19 versus 1.44 ± 0.21, P < 0.01). During acute pressure loading with phenylephrine there was no difference in left ventricular size or performance during quinidine therapy. In the patients with Cardiomyopathy, no significant differences in left ventricular function were detected with this protocol during quinidine therapy. It is concluded that oral quinidine therapy appears to have little adverse effect on left ventricular performance at rest or during acute pressure loading.

Favorable effects of oral maintenance digoxin therapy on left ventricular performance in normal subjects: Echocardiographic study

Left ventricular performance was assessed with echocardiography in 10 normal subjects before and during maintenance therapy with digoxin (0.5 mg/day orally) in the basal state and after acute pressure loading with intravenously administered phenylephrine. During digoxin therapy, despite a decrease in mean heart rate of 5 beats/min in the basal state, mean left ventricular ejection fraction increased from 74 ± 2 to 79 ± 1 percent (standard error, P < 0.03); percent shortening of a left ventricular minor dimension increased from 37 ± 2 to 41 ± 1 percent ( P < 0.04) and the mean rate of left ventricular dimension shortening increased from 5.66 ± 0.22 to 6.31 ± 0.23 cm/sec ( P = 0.05). During acute pressure loading with phenylephrine there was no change in mean heart rate after digoxin and mean ejection fraction increased from 69 ± 3 to 75 ± 2 percent; mean percent shortening increased from 33 ± 2 to 38 ± 2 percent; mean rate of shortening increased from 5.46 ± 0.32 to 6.48 ± 0.33 cm/sec and mean normalized rate of shortening increased from 1.11 ± 0.06 to 1.29 ± 0.05 sec −1 (all P < 0.01). In a few subjects the response to digoxin did not coincide with the mean data for the whole group. This variability was largely due to difficulties in exactly matching heart rate between the control and digoxin studies. These data (1) support the concept that long-term oral digoxin therapy exerts a positive inotropic effect on the normal left ventricle, and (2) demonstrate the usefulness of echocardiography in noninvasive assessment of the effects of drugs on left ventricular performance.

Left ventricle contractile function in trained dogs with cardial hypertrophy.

Eight mongrel dogs exercised for 8 weeks by treadmill running at 20 per cent incline 20 to 25 minutes twice daily, 4-5 days/week. Another eight dogs which were kept in the cages for a similar period served as controls. The exercise program was effective in inducing myocardial hypertrophy since the ratio left ventricular weight/body weight was significantly (P less than 0.001) higher in the trained dogs (5.04 g/kg) than in the sedentary animals (3.83 g/kg). In morphine-chloralose anesthesia the dogs were studied by left heart catherization and cineangiography at spontaneous heart rate (run I), at paced heart rate (run II), at paced heart rate following cardiac autonomic nervous blockade by bilateral vagotomy and the administration of propranolol (run III) and during acute pressure loading with methoxzmine at constant heart rate (run IV). Intergroup comparison yielded no significant difference in any hemodynamic or volumetric parameter throughout the entire study. However, with intragroup comparisons between run III and run IV a less significant increase in left ventricular end-diastolic pressure (from 5 to 15 mm Hg; P less than 0.05) was observed in the trained animals than in the control dogs (from 6 to 25 mm Hg; P less than 0.001). Left ventricular end-diastolic volume increased significantly only in the control dogs during acute pressure loading. Mean aortic pressure and left ventricular peak dP/dt increased to a similar extent in both groups. Since in the trained dogs the left ventricle encroaches less on the Frank-Starling mechanism than in normal animals for overcoming an acute pressure burden it is concluded that the development of hypertrophy concomitant with chronic exercise represents an adaptive mechanism with evidence of beneficial consequences for the intrinsic contractile function of the myocardium.

The concept of afterload mismatch and its implications in the clinical assessment of cardiac contractility.

The characteristics of left ventricular ejection (velocity and extent of wall shortening) can be analysed in relation to the appropriateness of the matching between afterload and the level of inotropic state (contractility), as modified by the preload (Frank-Starling) reserve. In the normal left ventricle if the preload is not allowed to compensate for an acute increase in afterload, or if the limit of preload reserve is reached, velocity (V CF) and stroke volume will diminish; that is an afterload mismatch occurs. This acute mismatch can be corrected by administration of a positive inotropic agent. In normal conscious animals and in man the ejection phase measures in the basal state (such as ejection fraction, and VCF corrected for heart size) encompass a relatively narrow range, and when the normal heart adapts successfully to a chronic pressure or volume overload such measures remain normal per unit of muscle. These findings provide the basis for their use in detecting a depressed basal level of inotropic state, even in the presence of certain valvular lesions. When there is mild depression of the basal inotropic state, enhanced preload and dilatation can allow full compensation of VCF, but acute pressure loading can allow detection of the the reduced preload reserve by inducing a substantial fall in stroke volume and VCF. When the basal inotropic state is greatly reduced, a mismatch between afterload and contractility, expressed as reduced VCF or ejection function, will become evident in the basal state even if the afterload is normal. Any increase in aortic pressure will then cause a sharp reduction in stroke volume or VCF. Also, under these circumstances therapeutic afterload reduction with agents such as nitroprusside can increase velocity and extent of wall shortening, and the cardiac output, providing the preload is maintained. The concept of afterload mismatch with limited preload reserve provides a framework for understanding the behavior of the normal or depressed ventrile and how it can operate on a "descending limb" of function. It helps to explain why measures of the ejecting phase (which are sensitive to afterload) appear to be more reliable than isovolumic phase indices (which are relatively insensitive to afterload) for detecting depressed basal inotropic state. Finally, the concept allows for interpretation of the responses observed in the clinical setting to acute and chronic increases and decreases in loading conditions on the left ventricle.

Afterload mismatch and preload reserve: A conceptual framework for the analysis of ventricular function

A two-dimensional framework can be used for considering the characteristics of left ventricular ejection in terms of the appropriateness of the matching between afterload and the level of inotropic state, as modulated by the preload reserve. An afterload mismatch (reduced velocity and extent of shortening) can be induced acutely in the normal heart under controlled conditions if the preload is not allowed to compensate for an increased afterload, or if the limit of preload (Frank-Starling) reserve has been reached. In the intact circulation the normal heart is sensitive to some degree to acute changes in afterload, perhaps due to impaired venous return; but under basal resting conditions the ejection phase measures (such as the ejection fraction and the mean velocity of circumferential fiber shortening or V CF, corrected for heart size) encompass a relatively narrow range. This finding, and the lack of change in ejection phase measures after the normal heart has adapted to a chronic pressure or volume overload, provides justification for the use of ejection phase indices for detecting depressed inotropic state under basal conditions. When there is mild depression of myocardial inotropic state, with or without accompanying mechanical overload, enhanced preload may allow full compensation, but acute pressure loading may allow early detection of a less than normal preload reserve. When the inotropic state is substantially reduced, however, a mismatch between afterload and contractility (a reduction in mean V CF) will become evident even in the basal state (venous return being presumed to be adequate under these conditions). The concept of afterload mismatch with limited preload reserve provides an explanation for the value of ejection phase indices compared to isovolumic phase measures in assessing the basal level of inotropic state: the former may be more reliable because they are sensitive to afterload. The effects and implications of therapeutic afterload reduction as modulated by the preload also are understood within this framework.